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0000000000000000000000000000000000000000..70f0e3b58da33e8c4385c1225e3badebe60ea250 --- /dev/null +++ b/data/pubmed_abstract/11-100/108_108.jsonl @@ -0,0 +1,4599 @@ +{"meta":{"pmid":24744421,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Evidence for vocal learning in juvenile male killer whales, Orcinus orca, from an adventitious cross-socializing experiment.\nKiller whales (Orcinus orca) are thought to learn their vocal dialect. Dispersal in the species is rare, but effects of shifts in social association on the dialect can be studied under controlled conditions. Individual call repertoires and social association were measured in three adult female killer whales and three males (two juveniles and an adult) during two periods, 2001-2003 and 2005-2006. Three distinct dialect repertoires were represented among the subjects. An adventitious experiment in social change resulted from the birth of a calf and the transfer of two non-focal subjects in 2004. Across the two periods, 1691 calls were collected, categorized and attributed to individuals. Repertoire overlap for each subject dyad was compared with an index of association. During 2005-2006, the two juvenile males increased association with the unrelated adult male. By the end of the period, both had begun producing novel calls and call features characteristic of his repertoire. However, there was little or no reciprocal change and the adult females did not acquire his calls. Repertoire overlap and association were significantly correlated in the first period. In the second, median association time and repertoire similarity increased, but the relationship was only marginally significant. The results provided evidence that juvenile male killer whales are capable of learning new call types, possibly stimulated by a change in social association. The pattern of learning was consistent with a selective convergence of male repertoires.","subset":"pubmed_abstract"} +{"meta":{"pmid":31258062,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Circulating Factors and Ultrasono-findings are Linked to Previous Atherosclerotic Burden and Recurrent Risk.\nIn the progression of atherosclerosis, platelet activation and the interaction of platelets with leukocytes play a crucial role in arterial thrombus formation and are associated with the pathophysiology of carotid and cerebrovascular disease (CVD), including ischemic stroke. With aged participants, we evaluated and followed up the change in circulating factor and platelet-leukocyte aggregate levels in participants with or without CVD history. This study investigated whether circulating factor changes and ultrasonographic characteristics link to CVD risk and other relating long-term outcomes. Two hundred fifteen participants who enrolled in the study were divided into two groups with CVD and without CVD history. We evaluated and analyzed the correlation between ultrasonography-based morphological characteristics and circulating factor-based functional changes in both groups. There was no difference in p-selectin level between both groups. However, activated monocyte and platelet-monocyte aggregate levels were higher in patients with previous CVD than without previous CVD. Circulating factor and ultrasonographical characteristics were correlated in the group with CVD, whereas these factors were not correlated in the group without CVD. We found that circulating blood factor levels showed a different tendency in participants with and without CVD history. The results depict that atherosclerotic severity might depend on the history of CVD and progression of atherosclerosis. We suggest that the circulating factor levels, atherosclerotic severity, and history of CVD are considered in the observation of pathologic progression to manage the development of CVD risks and CVD relating outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29772016,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-43":1,"2021-04":1,"2020-34":1,"2020-29":1,"2020-24":2,"2020-10":1,"2020-05":1,"2019-47":1,"2019-43":2,"2019-39":1,"2022-33":1}}},"text":"Development of a duplex droplet digital PCR assay for absolute quantitative detection of \"Candidatus Liberibacter asiaticus\".\nHuanglongbing (HLB, citrus greening) is a devastating citrus disease affecting citrus production worldwide. It is associated with the bacterium \"Candidatus Liberibacter asiaticus\" (CLas) and is vectored by the Asian citrus psyllid (ACP). Currently, diagnosis of CLas in regulatory samples is based on real-time quantitative polymerase chain reaction (qPCR) using 16S rRNA gene specific primers\/probe. The detection of CLas using qPCR is challenging due to low pathogen titer and uneven distribution in infected plants and exacerbated by sampling issues and presence of inhibitors. This study evaluated a duplex droplet digital polymerase chain reaction (ddPCR) using multi-copy gene targets, 16S and RNR, to simultaneously detect CLas DNA targets in the same sample for unambiguous detection of the HLB pathogen in DNA extracts from citrus leaves and ACP. Standard curve analyses on tenfold dilution series with plasmid, citrus leaf and ACP DNA showed that both ddPCR and qPCR exhibited good linearity and efficiency in the duplex assay. CLas-infected low titer samples were used to validate the duplex ddPCR and qPCR performance and demonstrated that detection rate is higher when both 16S and RNR primers were used in duplex assay. However, the receiver operating characteristic analysis indicated that area under the curve for RNR primer was significantly broader, compared to 16S primers for CLas detection at low target titer. The absolute quantification of CLas at variable titers was reproducible and repeatable for both primer sets and the ddPCR showed higher resilience to PCR inhibitors with citrus leaf and ACP extracts. Hence, the resultant duplex ddPCR assay resulted in a significantly improved detection platform for diagnosis of CLas in samples with low pathogen titer.","subset":"pubmed_abstract"} +{"meta":{"pmid":27039377,"dup_signals":{"dup_doc_count":11}},"text":"Work environment, volume of activity and staffing in neonatal intensive care units in Italy: results of the SONAR-nurse study.\nNeonatal units' volume of activity, and other quantitative and qualitative variables, such as staffing, workload, work environment, care organization and geographical location, may influence the outcome of high risk newborns. Data about the distribution of these variables and their relationships among Italian neonatal units are lacking. Between March 2010-April 2011, 63 neonatal intensive care units adhering to the Italian Neonatal Network participated in the SONAR Nurse study. Their main features and work environment were investigated by questionnaires compiled by the chief and by physicians and nurses of each unit. Twelve cross-sectional monthly-repeated surveys on different shifts were performed, collecting data on number of nurses on duty and number and acuity of hospitalized infants. Six hundred forty five physicians and 1601 nurses compiled the questionnaires. In the cross-sectional surveys 702 reports were collected, with 11082 infant and 3226 nurse data points. A high variability was found for units' size (4-50 total beds), daily number of patients (median 14.5, range 3.4-48.7), number of nurses per shift (median 4.2, range 0.7-10.8) and number of team meetings per month. Northern regions performed better than Central and Southern regions for frequency of training meetings, qualitative assessment of performance, motivation within the unit and nursing work environment; mean physicians' and nurses' age increased moving from North to South. After stratification by terciles of the mean daily number of patients, the median number of nurses per shift increased at increasing volume of activity, while the opposite was found for the nurse-to-patient ratio adjusted by patients' acuity. On average, in units belonging to the lower tercile there was 1 nurse every 2.5 patients, while in those belonging to the higher tercile the ratio was 1 nurse every 5 patients. In Italy, there is a high variability in organizational characteristics and work environment among neonatal units and an uneven distribution of human resources in relation to volume of activity, suggesting that the larger the unit the greater the workload for each nurse. Urgent modifications in planning and organization of services are needed in order to pursue more efficient, homogeneous and integrated regionalized neonatal care systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":20460479,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Efficacy, biodistribution, and pharmacokinetics of CD22-targeted pegylated liposomal doxorubicin in a B-cell non-Hodgkin's lymphoma xenograft mouse model.\nNon-Hodgkin's lymphoma (NHL) is the sixth most common cause of cancer death in the U.S. Pegylated liposomal doxorubicin (PLD) is a liposomal form of doxorubicin (DXR) that causes less toxicity than does free DXR. To further enhance efficacy and decrease toxicity, we conjugated HB22.7, an anti-CD22 monoclonal antibody to PLD, thus creating CD22-targeted immunoliposomal PLD (IL-PLD). In vitro cytotoxicity of IL-PLD and PLD was assessed in CD22-positive and CD22-negative cell lines. Biodistribution, myelotoxicity, and plasma pharmacokinetics were measured in NHL xenograft-bearing mice treated with IL-PLD or PLD. Survival, tumor volume, and toxicity (WBC counts, body weights) were assessed in mice receiving a single dose (8, 12, or 16 mg DXR\/kg) or three doses (8 mg DXR\/kg\/dose) of IL-PLD; controls were PLD, free DXR, PLD plus unconjugated HB22.7, IL-null (HB22.7-conjugated empty liposome), and nontreated mice. IL-PLD improved cytotoxicity over PLD only in CD22-positive cells. IL-PLD displayed similar pharmacokinetics and toxicities as PLD. Tumor DXR accumulation was greater and tumor\/normal tissue ratios were similar (spleen) or greater (kidney, lung, and liver) in mice treated with IL-PLD versus PLD. IL-PLD reduced tumor volume more effectively than PLD at all doses; the three-dose regimen was superior. The three-dose regimen was used in confirmatory studies, which showed that IL-PLD produced significantly greater tumor volume reduction and enhanced survival versus PLD. IL-PLD has increased efficacy without increased toxicity compared with PLD. This suggests that IL-PLD may be an improved form of DXR-based therapy of NHL.","subset":"pubmed_abstract"} +{"meta":{"pmid":2160627,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-27":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-10":1,"2019-47":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2023-23":1,"2024-10":1,"2024-30":1}}},"text":"Dopaminergic transmission and the sleep-wakefulness continuum in man.\nModulation of dopaminergic transmission on daytime alertness and performance and on nocturnal sleep were studied in man using 30, 60 and 90 mg pemoline, a dopamimetic drug, and 2, 4 and 6 mg pimozide, a dopamine receptor antagonist. Pemoline lengthened daytime sleep latencies and improved attention, and increased wakefulness during nocturnal sleep. Rapid eye movement (REM) sleep was reduced with 90 mg pemoline, but this was due entirely to increased wakefulness. Pimozide had little effect on overnight sleep, but increased the tendency to fall asleep and impaired performance during the day. These studies suggest that the effects of certain drugs which modulate the activity of neurotransmitters, involved in the control of sleep and wakefulness, may be related to the inherent level of activity of the central nervous system. Modulation of the dopaminergic system can have a profound influence on the manifestation of wakefulness and vigilance, but is unlikely to modify directly the elaboration of REM sleep in man.","subset":"pubmed_abstract"} +{"meta":{"pmid":21999740,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Dialysis vascular access management by interventional nephrology programs at University Medical Centers in the United States.\nThe development of interventional nephrology has undoubtedly led to an improvement in patient care at many facilities across the United States. However, these services have traditionally been offered by interventional nephrologists in the private practice arena. While interventional nephrology was born in the private practice setting, several academic medical centers across the United States have now developed interventional nephrology programs. University Medical Centers (UMCs) that offer interventional nephrology face challenges, such as smaller dialysis populations, limited financial resources, and real or perceived political \"turf\" issues.\" Despite these hurdles, several UMCs have successfully established interventional nephrology as an intricate part of a larger nephrology program. This has largely been accomplished by consolidating available resources and collaborating with other specialties irrespective of the size of the dialysis population. The collaboration with other specialties also offers an opportunity to perform advanced procedures, such as application of excimer laser and endovascular ultrasound. As more UMCs establish interventional nephrology programs, opportunities for developing standardized training centers will improve, resulting in better quality and availability of nephrology-related procedures, and providing an impetus for research activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":11564133,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-29":1,"2020-16":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2023-14":1,"2024-30":1}}},"text":"Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia Jack.\nThe aphrodisiac effect of Eurycoma longifolia Jack (0.5 g\/kg) was evaluated in noncopulator male rats using an electrical cage. Fractions of E. longifolia Jack decreased the hesitation time of noncopulator male rats, throughout the investigation period. Furthermore, it possessed a transient increase in the percentage of the male rats responding to the right choice, more than 50% of the male rats scored \"right choice\" after 3 weeks post-treatment and the effect became more prominent after 8 weeks post-treatment (only 40-50% of the control male rats responded to the right choice) using the electrical copulation cage. Hence, this study lends further support to the use of the plant by indigenous populations as a traditional medicine for its aphrodisiac property.","subset":"pubmed_abstract"} +{"meta":{"pmid":34258603,"dup_signals":{"dup_doc_count":58,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":4,"2023-23":3,"2023-14":2,"2023-06":1,"2022-49":3,"2022-40":9,"2022-33":4,"2022-27":2,"2022-21":2,"2022-05":2,"2021-49":1,"2021-43":4,"2021-39":4,"2024-30":3,"2024-26":4,"2024-22":3,"2024-18":2,"2024-10":1}}},"text":"Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.\nMutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1\/28 and P.1\/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2\/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17-38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134-230 days after the second dose). Antibody neutralisation of P.1\/28, P.1\/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8\u00b76 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR <20-45] for P.1\/28 and 30 [<20-40] for P.1\/30) than against the lineage B isolate (260 [160-400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p\u22640\u00b70001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20-23 days earlier (VNT50s below the limit of detection [<20] for most plasma samples), a second dose 17-38 days earlier (median VNT50 24 [IQR <20-25] for P.1\/28 and 28 [<20-25] for P.1\/30), or a second dose 134-260 days earlier (all VNT50s below limit of detection). Median VNT50s against the lineage B isolate were 20 (IQR 20-30) after a first dose of CoronaVac 20-23 days earlier, 75 (<20-263) after a second dose 17-38 days earlier, and 20 (<20-30) after a second dose 134-260 days earlier. In plasma collected 17-38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0\u00b70051 for P.1\/28 and p=0\u00b70336 for P.1\/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. S\u00e3o Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. For the Portuguese translation of the abstract see Supplementary Materials section.","subset":"pubmed_abstract"} +{"meta":{"pmid":24480486,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2015-18":1,"unknown":6}}},"text":"Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson's disease with hallucinations.\nVisual hallucinations are frequent, disabling complications of advanced Parkinson's disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson's disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson's disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson's disease hallucinators to Parkinson's disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson's disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (\u00b1 3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson's disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson's disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred predominantly in brain regions responsible for processing visuoperceptual information including the ventral 'what' and dorsal 'where' pathways, which are important in object and facial recognition and identification of spatial locations of objects, respectively. Furthermore, the structural brain changes seen on magnetic resonance imaging occurred independently of cognitive function and age. Our findings suggest that when hallucinators and non-hallucinators are similar in their cognitive performance, the neural networks involving visuoperceptual pathways, rather than the mesial temporal lobe regions, distinctively contribute to the pathophysiology of visual hallucinations and may explain their predominantly visual nature in Parkinson's disease. Identification of distinct structural MRI differences associated with hallucinations in Parkinson's disease may permit earlier detection of at-risk patients and ultimately, development of therapies specifically targeting hallucinations and visuoperceptive functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":7670946,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Longitudinal study of associations of microalbuminuria with the insulin resistance syndrome and sodium-lithium countertransport in nondiabetic subjects.\nMicroalbuminuria in diabetic patients is associated with ischemic heart disease and insulin resistance. We previously found a 9% prevalence of microalbuminuria in a nondiabetic population that we have reassessed, investigating associations of microalbuminuria with hypertension, dyslipidemia, hyperinsulinemia, and sodium-lithium countertransport. Of 125 subjects reexamined, 42 had been microalbuminuric 3 years previously. Twelve of these (29%) were microalbuminuric on at least one sample at follow-up, and 30 (76%) were normoalbuminuric on two. Of the 79 previously normoalbuminuric subjects, 12 (15%) became microalbuminuric on one sample, while 67 (85%) remained normoalbuminuric. Subjects who were microalbuminuric at both screening and recall were older (mean +\/- SD, 65.9 +\/- 11 versus 59.1 +\/- 10.2 years, P = .04), with a higher waist-to-hip ratio (0.93 +\/- 0.09 versus 0.86 +\/- 0.08, P = .008) and at recall, on univariate analysis, had higher specific insulin (44.2 [range, 16.9 to 157.0] versus 28.4 [7.4 to 129.0] pmol\/L, P = .005), intact proinsulin (5.1 [1.5 to 11.0] versus 3.0 [0.8 to 14.6] pmol\/L, P = .003), and des-31,32-proinsulin (5.0 [0.5 to 9.8] versus 1.0 [0.5 to 12.2] pmol\/L, P = .004) concentrations. There was also a significant difference in des-31,32-proinsulin concentration, after adjustment for covariates (P = .013), between subjects classified either as microalbuminuric or as normoalbuminuric at screening. There was no difference in body mass index; fasting blood glucose; systolic or diastolic blood pressure; total, HDL, or LDL cholesterol; triglycerides; plasminogen activator inhibitor-1; or sodium-lithium countertransport activity between consistently normoalbuminuric and persistently microalbuminuric subjects.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":28083044,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Serum C-reactive protein level in COPD patients stratified according to GOLD 2011 grading classification.\nThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 grading classification has been used to evaluate the severity of patients with chronic obstructive pulmonary disease (COPD). However, little is known about the relationship between the systemic inflammation and this classification. We aimed to study the relationship between serum CRP and the components of the GOLD 2011 grading classification. C-reactive protein (CRP) levels were measured in 391 clinically stable COPD patients and in 50 controls from June 2, 2015 to October 31, 2015 in the First Affiliated Hospital of Xiamen University. The association between CRP levels and the components of the GOLD 2011 grading classification were assessed. Correlation was found with the following variables: GOLD 2011 group (0.240), age (0.227), pack year (0.136), forced expiratory volume in one second % predicted (FEV1%; -0.267), forced vital capacity % predicted (-0.210), number of acute exacerbations in the past year (0.265), number of hospitalized exacerbations in the past year (0.165), British medical Research Council dyspnoea scale (0.121), COPD assessment test score (CAT, 0.233). Using multivariate analysis, FEV1% and CAT score manifested the strongest negative association with CRP levels. CRP levels differ in COPD patients among groups A-D based on GOLD 2011 grading classification. CRP levels are associated with several important clinical variables, of which FEV1% and CAT score manifested the strongest negative correlation.","subset":"pubmed_abstract"} +{"meta":{"pmid":12420577,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Comparison of impact strength of acrylic resin reinforced with kevlar and polyethylene fibres.\nThe present study was done to evaluate the impact strengths of heat-activated acrylic resins reinforced with Kevlar fibres, polyethylene fibres and unreinforced heat activated acrylic resin. Each of three groups had 25 specimens. Brass rods of uniform length of 40 mm and diameter of 8 mm were used to prepare the moulds. A combination of long fibres (40 mm length) and short fibres (6 mm length) were used. The total amount of fibres incorporated was limited to 2% by weight of the resin matrix. Short and long fibres of equal weight were incorporated. The short fibres were mixed with polymer and monomer and packed into the mould, while, the long axis of the specimen, perpendicular to the applied force. The specimens were then processed. Impact strength testing was done on Hounsfield's impact testing machine. Kevlar fibre reinforced heat activated acrylic resin specimens recorded higher mean impact strength of 0.8464 Joules, while polyethylene fibres reinforced heat activated acrylic resin recorded mean impact strength of 0.7596 joules. The unreinforced heat activated acrylic resin recorded mean impact strength of 0.3440 Joules.","subset":"pubmed_abstract"} +{"meta":{"pmid":12466962,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells.\nThe development of nontoxic natural agents with chemopreventive activity against colon cancer is the focus of investigation in many laboratories. Curcumin (feruylmethane), a natural plant product, possesses such chemopreventive activity, but the mechanisms by which it prevents cancer growth are not well understood. In the present study, we examined the mechanisms by which curcumin treatment affects the growth of colon cancer cells in vitro. Results showed that curcumin treatment causes p53- and p21-independent G(2)\/M phase arrest and apoptosis in HCT-116(p53(+\/+)), HCT-116(p53(-\/-)) and HCT-116(p21(-\/-)) cell lines. We further investigated the association of the beta-catenin-mediated c-Myc expression and the cell-cell adhesion pathways in curcumin-induced G(2)\/M arrest and apoptosis in HCT-116 cells. Results described a caspase-3-mediated cleavage of beta-catenin, decreased transactivation of beta-catenin\/Tcf-Lef, decreased promoter DNA binding activity of the beta-catenin\/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2\/cyclin B1 kinase activity, a function of the G(2)\/M phase arrest. The decreased transactivation of beta-catenin in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor Z-DEVD-fmk, even though the curcumin-induced cleavage of beta-catenin was blocked in Z-DEVD-fmk pretreated cells. The curcumin treatment also induced caspase-3-mediated degradation of cell-cell adhesion proteins beta-catenin, E-cadherin and APC, which were linked with apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our results suggest that curcumin treatment impairs both Wnt signaling and cell-cell adhesion pathways, resulting in G(2)\/M phase arrest and apoptosis in HCT-116 cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":22298705,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":14}}},"text":"Genetic analysis of complex interactions among components of the mitochondrial import motor and translocon in Saccharomyces cerevisiae.\nA highly conserved, Hsp70-based, import motor, which is associated with the translocase on the matrix side of the inner mitochondrial membrane, is critical for protein translocation into the matrix. Hsp70 is tethered to the translocon via interaction with Tim44. Pam18, the J-protein co-chaperone, and Pam16, a structurally related protein with which Pam18 forms a heterodimer, are also critical components of the motor. Their N termini are important for the heterodimer's translocon association, with Pam18's and Pam16's N termini interacting in the intermembrane space and the matrix, respectively. Here, using the model organism Saccharomyces cerevisiae, we report the identification of an N-terminal segment of Tim44, important for association of Pam16 with the translocon. We also report that higher amounts of Pam17, a nonessential motor component, are found associated with the translocon in both PAM16 and TIM44 mutants that affect their interaction with one another. These TIM44 and PAM16 mutations are also synthetically lethal with a deletion of PAM17. In contrast, a deletion of PAM17 has little, or no genetic interaction with a PAM18 mutation that affects translocon association of the Pam16:Pam18 heterodimer, suggesting a second role for the Pam16:Tim44 interaction. A similar pattern of genetic interactions and enhanced Pam17 translocon association was observed in the absence of the C terminus of Tim17, a core component of the translocon. We suggest the Pam16:Tim44 interaction may play two roles: (1) tethering the Pam16:Pam18 heterodimer to the translocon and (2) positioning the import motor for efficient engagement with the translocating polypeptide along with Tim17 and Pam17.","subset":"pubmed_abstract"} +{"meta":{"pmid":17623732,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"Antidepressant use in multiple sclerosis: epidemiologic study of a large community sample.\nDepressive symptoms and disorders among individuals with multiple sclerosis (MS) are more common when compared to other chronic illnesses and the general population, but relatively little is known about the use of antidepressant medication in this population. In this cross-sectional study of 542 community-dwelling adults with MS, we examined the prevalence of antidepressant use and employed multivariate logistic regression modeling to identify factors significantly associated with antidepressant use. Thirty-five percent of the sample reported currently using at least one antidepressant medication. Gender, marital status, insurance status, fatigue, and use of disease modifying therapies were all significantly associated with antidepressant use. Just over half of the sample endorsed a clinically significant level of depressive symptoms, and the majority of this group was not currently taking an antidepressant. Conversely, 41% of those with depressive symptoms reported taking at least one antidepressant medication. More research is needed to better understand why people with MS and depressive symptoms use or do not use antidepressant medications and to further explore the possibility of an under-treatment of depressive disorder in this population. Rigorous studies testing the feasibility, acceptability, and efficacy of currently available therapies for depression in the MS population should also be conducted.","subset":"pubmed_abstract"} +{"meta":{"pmid":9125550,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evidence for a methyl-accepting chemotaxis protein gene (mcp1) that encodes a putative sensory transducer in virulent Treponema pallidum.\nThe clinical and histopathological manifestations of syphilis and the invasive behavior of Treponema pallidum in tissue culture systems reflect the propensity for treponemes to migrate through skin, hematogenously disseminate, and invade targeted tissues. Treponemal motility is believed to be essential to this process and thereby an important facet of syphilis pathogenesis. By analogy with other bacterial pathogens, it is plausible that treponemal motility and tissue invasion are modulated by sensory transduction events associated with chemotactic responses. Recent studies have demonstrated the existence in T. pallidum of accessory molecules typically associated with sensory transduction events involving methyl-accepting chemotaxis proteins (MCPs). Intrinsic radiolabeling of T. pallidum in vitro with L-[methyl-3H] methionine revealed one methylated treponemal polypeptide with an apparent molecular mass of 64 kDa. A degenerate oligonucleotide probe corresponding to a highly conserved C-terminal domain within Bacillus subtilis and Escherichia coli MCPs was used in Southern blotting of T. pallidum DNA to identify and subsequently clone a putative T. pallidum MCP gene (mcp1). Computer analyses predicted a near-consensus promoter upstream of mcp1, and primer extension analysis employing T. pallidum RNA revealed a transcriptional initiation site. T. pallidum mcp1 encoded a 579-amino-acid (64.6-kDa) polypeptide which was highly homologous to at least 69 other known or putative sensory transducer proteins, with the highest degrees of homology existing between the C terminus of mcp1 and the C-terminal (signaling) domains of the other bacterial MCPs. Other salient features of Mcp1 included (i) six potential membrane-spanning domains at the N terminus, (ii) two predicted alpha-helical coiled coil regions containing at least three putative methylation sites, and (iii) homologies with two ligand-binding domains (LI-1 and LI-2) of the E. coli MCPs Trg and Tar. This study is the first to provide both metabolic and genetic evidence for an MCP sensory transducer in T. pallidum. The combined findings prompt key questions regarding the relationship(s) among sensory transduction, regulation of endoflagellar rotation, and chemotactic responses (in particular, the role of glucose) during virulence expression by T. pallidum.","subset":"pubmed_abstract"} +{"meta":{"pmid":23372824,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":9}}},"text":"Effectiveness of efavirenz-based regimens in young HIV-infected children treated for tuberculosis: a treatment option for resource-limited settings.\nAntiretroviral treatment (ART) options for young children co-infected with HIV and tuberculosis are limited in resource-poor settings due to limited data on the use of efavirenz (EFV). Using available pharmacokinetic data, an EFV dosing schedule was developed for young co-infected children and implemented as the standard of care at Macha Hospital in Southern Province, Zambia. Treatment outcomes in children younger than 3 years of age or weighing less than 10 kg receiving either EFV-based ART plus anti-tuberculous treatment or nevirapine-based (NVP) ART were compared. Treatment outcomes were measured in a cohort of HIV-infected children seeking care at Macha Hospital in rural Zambia from 2007 to 2010. Information on the diagnosis and treatment of tuberculosis was abstracted from medical records. Forty-five children treated for tuberculosis initiated an EFV-based regimen and 69 children initiated a NVP-based regimen, 7 of whom also were treated for tuberculosis. Children receiving both regimens were comparable in age, but children receiving EFV started ART with a lower CD4(+) T-cell percentage and weight-for-age z-score. Children receiving EFV experienced increases in both CD4(+) T-cell percentage and weight-for-age z-score during follow-up, such that levels were comparable to children receiving NVP after two years of ART. Cumulative survival after 12 months of ART did not differ between groups (NVP:87%;EFV:80%;p = 0.25). Eleven children experienced virologic failure during follow-up.The adjusted hazard ratio of virologic failure comparing EFV to NVP was 0.25 (95% CI:0.05,1.24) and 0.13 (95% CI:0.03,0.62) using thresholds of 5000 and 400 copies\/mL, respectively.Five children receiving EFV were reported to have had convulsions after ART initiation compared to only one child receiving NVP (p = 0.04). Despite poorer health at ART initiation, children treated for tuberculosis and receiving EFV-based regimens showed significant improvements comparable to children receiving NVP-based regimens. EFV-based regimens should be considered for young HIV-infected children co-infected with tuberculosis in resource-limited settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":22935101,"dup_signals":{"dup_doc_count":22,"dup_details":{"curated_sources":2,"unknown":20}}},"text":"ncDNA and drift drive binding site accumulation.\nThe amount of transcription factor binding sites (TFBS) in an organism's genome positively correlates with the complexity of the regulatory network of the organism. However, the manner by which TFBS arise and accumulate in genomes and the effects of regulatory network complexity on the organism's fitness are far from being known. The availability of TFBS data from many organisms provides an opportunity to explore these issues, particularly from an evolutionary perspective. We analyzed TFBS data from five model organisms - E. coli K12, S. cerevisiae, C. elegans, D. melanogaster, A. thaliana - and found a positive correlation between the amount of non-coding DNA (ncDNA) in the organism's genome and regulatory complexity. Based on this finding, we hypothesize that the amount of ncDNA, combined with the population size, can explain the patterns of regulatory complexity across organisms. To test this hypothesis, we devised a genome-based regulatory pathway model and subjected it to the forces of evolution through population genetic simulations. The results support our hypothesis, showing neutral evolutionary forces alone can explain TFBS patterns, and that selection on the regulatory network function does not alter this finding. The cis-regulome is not a clean functional network crafted by adaptive forces alone, but instead a data source filled with the noise of non-adaptive forces. From a regulatory perspective, this evolutionary noise manifests as complexity on both the binding site and pathway level, which has significant implications on many directions in microbiology, genetics, and synthetic biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":24759978,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2014-41":1,"2023-50":1,"2024-22":1}}},"text":"Automated mosaicing of feature-poor optical coherence tomography volumes with an integrated white light imaging system.\nWe demonstrate the first automated, volumetric mosaicing algorithm for optical coherence tomography (OCT) that both accommodates 6-degree-of-freedom rigid transformations and implements a bundle adjustment step amenable to generating large fields of view with endoscopic and freehand imaging systems. Our mosaicing algorithm exploits the known, rigid connection between a combined white light and OCT imaging system to reduce the computational complexity of traditional volumetric mosaicing pipelines. Specifically, the search for 3-D point correspondences is replaced by two, 2-D processing steps: We first coregister a pair of white light images in 2-D and then generate a surface map based on the volumetric OCT data, which is used to convert 2-D image homographies into 3-D volumetric transformations. A significant benefit of our dual-modality approach is its tolerance for feature-poor datasets such as bladder tissue; in contrast, approaches to mosaic feature-rich volumes with significant variations in the local intensity gradient (e.g., retinal data containing prolific vasculature) are not suitable for such feature-poor datasets. We demonstrate the performance of our algorithm using ex vivo bladder tissue and a custom tissue-mimicking phantom. The algorithm shows excellent performance over the range of volume-to-volume transformations expected during endoscopic examination and comparable accuracy with several orders of magnitude superior run times than an open-source gold-standard algorithm (N-SIFT). We anticipate the proposed algorithm can benefit bladder surveillance and surgical planning. Furthermore, its generality gives it broad applicability and potential to extend the use of OCT to clinical applications relevant to large organs typically imaged with freehand, forward-viewing endoscopes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29250278,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"The Nonvitamin K Antagonist Oral Anticoagulants and Atrial Fibrillation: Challenges and Considerations.\nThe nonvitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are used for the reduction of the risk of stroke or systemic embolism (SEE) in patients with nonvalvular atrial fibrillation (NVAF). The purpose of this review is to highlight the safety and efficacy results of the pivotal NOAC clinical trials for use in NVAF, discuss some of the unique management challenges in the use of NOACs in special populations, summarize data on emerging and novel indications, and address potential future directions. A literature search was conducted and to identify relevant clinical trials and studies regarding the use of NOACs for the prevention of stroke or SEE in patients with atrial fibrillation. Relative to warfarin, NOACs are as effective or superior in the prevention of stroke or SEE, and are associated with similar or lower rates of major bleeding and significantly decreased rates of intracranial bleeding, but may be associated with a slightly increased risk of gastrointestinal bleeding in patients with AF. The NOACs are not indicated for use and have not been widely tested in AF patients with other cardiovascular conditions. Additional ongoing and planned clinical trials will provide additional information regarding the use of NOACs in these patients. In situations requiring rapid reversal of anticoagulation, the availability of specific antidotes will improve safety and facilitate NOAC use. Use of NOACs in clinical practice requires consideration of patient characteristics as well as potentially required procedures.","subset":"pubmed_abstract"} +{"meta":{"pmid":6203997,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Immunochemical analysis of the released Leu-2 (T8) molecule.\nWe recently have found that the human T cell antigen Leu-2 was specifically released from Leu-2-bearing cells. The preliminary study showed that the released Leu-2 (RLeu-2) from HPB-ALL cells was composed of a single polypeptide chain of 27,000 molecular weight (mol wt), which was smaller than the subunit of the homodimeric molecule found on the cell surface. In the present study, RLeu-2 was further characterized and compared with cellular Leu-2 (CLeu-2). Metabolically radiolabeled Leu-2 was released from HPB-ALL cells and this released Leu-2 molecule had a mol wt of 27,000. Cell surface radioiodinated HPB-ALL cells were found to release radioactive Leu-2 molecules and this antigen also had the same mol wt of 27,000. In both experiments, the CLeu-2 was reconfirmed to be composed of a 33,000-mol wt subunit under reducing conditions. These experiments establish that the 27,000-mol wt single polypeptide chain of Leu-2 released from the cell is derived directly from the homodimeric Leu-2 molecule on the cell surface, presumably by a specific proteolytic cleavage. Two-dimensional gel analysis showed that CLeu-2 exhibited extensive charge heterogeneity with predominantly basic isoelectric points, whereas RLeu-2 was a group of more acidic proteins with less charge heterogeneity. Although CLeu-2 and RLeu-2 showed several different immunochemical characteristics, the homology between these two antigens was confirmed by the following results: CLeu-2 and RLeu-2 were found to share at least three different antigenic determinants, Leu-2a and Leu-2b, and those which were detected by a polyvalent rabbit antiserum. Significant similarities between CLeu-2 and RLeu-2 were demonstrated by peptide mapping analysis of these antigens. Therefore, RLeu-2 appears to be the specific, physiological product of the CLeu-2 protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":31363756,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950 000 adults.\nSubarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)\/100 000 person-years] in men and 13.8 [(11.4-16.2)\/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.","subset":"pubmed_abstract"} +{"meta":{"pmid":19381342,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":13}}},"text":"Telephone triage service data for detection of influenza-like illness.\nSurveillance for influenza and influenza-like illness (ILI) is important for guiding public health prevention programs to mitigate the morbidity and mortality caused by influenza, including pandemic influenza. Nontraditional sources of data for influenza and ILI surveillance are of interest to public health authorities if their validity can be established. National telephone triage call data were collected through automated means for purposes of syndromic surveillance. For the 17 states with at least 500,000 inhabitants eligible to use the telephone triage services, call volume for respiratory syndrome was compared to CDC weekly number of influenza isolates and percentage of visits to sentinel providers for ILI. The degree to which the call data were correlated with either CDC viral isolates or sentinel provider percentage ILI data was highly variable among states. Telephone triage data in the U.S. are patchy in coverage and therefore not a reliable source of ILI surveillance data on a national scale. However, in states displaying a higher correlation between the call data and the CDC data, call data may be useful as an adjunct to state-level surveillance data, for example at times when sentinel surveillance is not in operation or in areas where sentinel provider coverage is considered insufficient. Sufficient population coverage, a specific ILI syndrome definition, and the use of a threshold of percentage of calls that are for ILI would likely improve the utility of such data for ILI surveillance purposes.","subset":"pubmed_abstract"} +{"meta":{"pmid":18049575,"dup_signals":{"dup_doc_count":15,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2016-44":2,"2016-40":1,"2016-36":2,"2016-30":1,"2015-48":2,"2015-35":1,"2015-32":1,"2015-27":1}}},"text":"Optical pattern recognition by use of a segmented semiconductor optical amplifier.\nA technique for high-speed, all-optical pattern recognition based on cross correlation in a segmented semiconductor optical amplifier (SSOA) is presented. A counterpropagating pump-probe setup is used to perform cross correlation of the spatial gain-loss pattern in the SSOA with the optical data pattern (pump), and the result is read out with a counterpropagating probe. Cross correlation of 4-bit patterns at 85 Gbits\/s is experimentally demonstrated. Simulations show reasonable agreement with experimental measurements and are used to address scalability to higher bit rates and longer data patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":11454241,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"The rise and fall of malarial sporozoite rates in Anopheles gambiae s.l. and An. funestus in north-eastern Tanzania, between 1934 and 1999.\nThe proportion of Anopheles mosquitoes found to be carrying Plasmodium sporozoites, usually called the 'malarial sporozoite rate', has often been used as a measure of mosquito infectivity. Although the sporozoite rates found in Anopheles gambiae and An. funestus in Muheza, north-eastern Tanzania, showed a marked decline between the mid-1930s and the mid-1970s, they then began to rise again. This fall and rise in mosquito infectivity is attributed to the widespread use of antimalarial drugs, which initially tended to reduce the infectivity of patients for mosquitoes, and the subsequent development of resistance to these drugs in the malarial parasites. The rise observed in the sporozoite rates in Muheza in the 1980s-1990s may be attributed to widespread resistance of P. falciparum to chloroquine, until recently the drug of choice for the treatment of malaria in Tanzania. Changes in the survival rates, abundance, or predominant species of the mosquito vectors are unlikely to have influenced the pattern observed. The role of antimalarial drugs in malaria transmission risk is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":20849297,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Navigating the challenges of global reproductive health research.\nReproductive health research in low-resource settings poses unique and complex challenges that must be addressed to ensure that global research is conducted with strict adherence to ethical principles, offers direct benefit to the research subjects, and has the potential for adoption of positive findings to the target population. This article addresses challenges to conducting reproductive health research in low-resource settings in the following areas: (1) establishment and maintenance of global collaboration, (2) community partnerships, (3) ethical issues, including informed consent and the role of incentives, (4) staff training and development, (5) data collection and management, and (6) infrastructure and logistics. Particular attention to these challenges is important to ensure that research is culturally appropriate and methodologically sound and enhances the adoption of health-promoting behaviors. Rigorous evaluation of interventions in low-resource settings may be a cost-effective and time-efficient way to identify interventions for large-scale program replication to improve women's health.","subset":"pubmed_abstract"} +{"meta":{"pmid":33200655,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":12}}},"text":"Development of cancer prognostic signature based on pan-cancer proteomics.\nUtilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. And the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has generated extensive proteomics data of the vast majority of tumors. Based on CPTAC, we can perform a proteomic pan-carcinoma analysis. We collected the proteomics data and clinical features of cancer patients from CPTAC. Then, we screened 69 differentially expressed proteins (DEPs) with R software in five cancers: hepatocellular carcinoma (HCC), children's brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). GO and KEGG analysis were performed to clarify the function of these proteins. We also identified their interactions. The DEPs-based prognostic model for predicting over survival was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model in training cohort. Then, we used the time-dependent receiver operating characteristics analysis to evaluate the ability of the prognostic model to predict overall survival and validated it in validation cohort. The results showed that the DEPs-based prognostic model could accurately and effectively predict the survival rate of most cancers.","subset":"pubmed_abstract"} +{"meta":{"pmid":31070747,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-43":1,"2021-17":1,"2020-40":1,"2020-10":1,"2023-50":1}}},"text":"Return to the Sea, Get Huge, Beat Cancer: An Analysis of Cetacean Genomes Including an Assembly for the Humpback Whale (Megaptera novaeangliae).\nCetaceans are a clade of highly specialized aquatic mammals that include the largest animals that have ever lived. The largest whales can have \u223c1,000\u00d7 more cells than a human, with long lifespans, leaving them theoretically susceptible to cancer. However, large-bodied and long-lived animals do not suffer higher risks of cancer mortality than humans-an observation known as Peto's Paradox. To investigate the genomic bases of gigantism and other cetacean adaptations, we generated a de novo genome assembly for the humpback whale (Megaptera novaeangliae) and incorporated the genomes of ten cetacean species in a comparative analysis. We found further evidence that rorquals (family Balaenopteridae) radiated during the Miocene or earlier, and inferred that perturbations in abundance and\/or the interocean connectivity of North Atlantic humpback whale populations likely occurred throughout the Pleistocene. Our comparative genomic results suggest that the evolution of cetacean gigantism was accompanied by strong selection on pathways that are directly linked to cancer. Large segmental duplications in whale genomes contained genes controlling the apoptotic pathway, and genes inferred to be under accelerated evolution and positive selection in cetaceans were enriched for biological processes such as cell cycle checkpoint, cell signaling, and proliferation. We also inferred positive selection on genes controlling the mammalian appendicular and cranial skeletal elements in the cetacean lineage, which are relevant to extensive anatomical changes during cetacean evolution. Genomic analyses shed light on the molecular mechanisms underlying cetacean traits, including gigantism, and will contribute to the development of future targets for human cancer therapies.","subset":"pubmed_abstract"} +{"meta":{"pmid":17106245,"dup_signals":{"dup_doc_count":27,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":2,"2014-10":1,"2024-26":1,"unknown":21}}},"text":"The cell-adhesion and signaling molecule PECAM-1 is a molecular mediator of resistance to genotoxic chemotherapy.\nDefects in the regulation of apoptotic pathways have been implicated in the emergence of cancers resistant to chemotherapy-induced cell death. Identification of novel signaling molecules that influence cell survival has the potential to facilitate the development of new cancer therapies. The cell adhesion and signaling molecule, PECAM-1, is expressed in many hematopoietic and endothelial cell malignancies, and has previously been shown to suppress mitochondrial-dependent, Bax-mediated apoptosis. The ability of PECAM-1 to influence tumor cell survival following exposure to chemotherapeutic agents, however, is not known. Here we show that, when overexpressed in HEK293 and REN mesothelioma cells, PECAM-1 confers resistance to apoptosis induced by the DNA-damaging chemotherapeutic agent, etoposide. Surprisingly, PECAM-1-mediated cytoprotection was found to be largely independent of its ability to form a signaling complex with the protein-tyrosine phosphatase SHP-2, as virtually no tyrosine phosphorylation of, or SHP-2 association with, PECAM-1 could be detected after etoposide treatment. Furthermore, PECAM-1 retained its ability to protect against chemotherapy-induced apoptosis in cells with SHP-2 levels significantly reduced using SHP-2-specific siRNA, and in cells in which Erk1\/2--a downstream effector of SHP-2--had been inhibited. Finally, to determine whether endogenous PECAM-1 confers resistance to chemotherapy-induced apoptosis in lymphoid malignancies and endothelial cells, we used a lentiviral vector to stably express PECAM-1-specific siRNA in the Jurkat leukemia cell line and human umbilical vein endothelial cells (HUVECs). siRNA-expressing Jurkat cells with a 70% reduction of PECAM-1 expression were significantly more sensitive to chemotherapy-induced apoptosis. HUVECs with PECAM-1 expression reduced 75% were also markedly more sensitive to chemotherapy-induced cell death. Taken together, these data demonstrate that endogenous PECAM-1 expression on lymphoid cancers confers resistance to apoptosis, and that lowering PECAM-1 expression in lymphoid malignancies can render them more susceptible to chemotherapy-induced apoptosis. In addition, reducing PECAM-1 levels in the tumor endothelium may aid in low-dose, anti-angiogenic therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":26585100,"dup_signals":{"dup_doc_count":30,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-21":3,"2021-49":2,"2021-21":1,"2021-04":2,"2020-34":3,"2020-24":1,"2020-10":1,"2018-26":3,"2018-09":2,"2017-47":2,"2017-39":3,"2023-23":1,"2024-26":2,"2024-22":1,"2024-10":1}}},"text":"Cognitive ability in childhood and the chronicity and suicidality of depression.\nThere is inconsistent evidence regarding the influence of general cognitive abilities on the long-term course of depression. To investigate the association between general childhood cognitive abilities and adult depression outcomes. We conducted a cohort study using data from 633 participants in the New England Family Study with lifetime depression. Cognitive abilities at age 7 were measured using the Wechsler Intelligence Scale for Children. Depression outcomes were assessed using structured diagnostic interviews administered up to four times in adulthood between ages 17 and 49. In analyses adjusting for demographic factors and parental psychiatric illness, low general cognitive ability (i.e. IQ<85 v. IQ>115) was associated with recurrent depressive episodes (odds ratio (OR) = 2.19, 95% CI 1.20-4.00), longer episode duration (rate ratio 4.21, 95% CI 2.24-7.94), admission to hospital for depression (OR = 3.65, 95% CI 1.34-9.93) and suicide ideation (OR = 3.79, 95% CI 1.79-8.02) and attempt (OR = 4.94, 95% CI 1.67-14.55). Variation in cognitive abilities, predominantly within the normal range and established early in childhood, may confer long-term vulnerability for prolonged and severe depression. The mechanisms underlying this vulnerability need to be established to improve the prognosis of depression among individuals with lower cognitive abilities.","subset":"pubmed_abstract"} +{"meta":{"pmid":21750650,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":14}}},"text":"A new trick of an old molecule: androgen receptor splice variants taking the stage?!\nProstate cancer is the second leading cause of cancer-related death in American men. Although most prostate cancers are initially androgen-dependent and respond to androgen ablation therapy, majority of them eventually relapse and progress into incurable castration-resistant (or hormone refractory) prostate cancer. The underlying mechanisms are the focus of intensive investigation for development of more effective treatment. Mounting evidence from both clinical and basic research has demonstrated that the activity of the androgen receptor (AR) is still required for castration-resistant prostate cancer. Multiple mechanisms by which AR is re-activated under androgen-depleted conditions may be involved in the development of castration resistance. The recent identification of AR splicing variants may add another layer of complexity in AR biology. The present review summarizes recent progress in study of AR splicing variants in prostate cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":33727689,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":2,"2024-10":2,"unknown":11}}},"text":"Impact of g force and timing on the characteristics of platelet-rich fibrin matrices.\nRecently, new centrifugation protocols for the preparation of platelet-rich fibrin (PRF) have been introduced in an attempt to further improve the beneficial impact of these 2nd generation platelet concentrate membranes. This in-vitro study aimed to compare the biological and physical characteristics of three types of PRF membranes using two different centrifuges with adapted relative centrifugal forces (RCF): leucocyte- and platelet-rich fibrin, advanced platelet-rich fibrin, and advanced platelet-rich fibrin+. Release of growth factors, macroscopic dimensions, cellular content and mechanical properties of the respective membranes, prepared from blood of the same individual were explored. Furthermore, the impact of timing (blood draw-centrifugation and centrifugation-membrane preparation) was assessed morphologically as well as by electron microscopy scanning. No statistically significant differences amongst the three PRF modifications could be observed, neither in their release of growth factors or the cellular content, nor in clot\/membrane dimensions. The difference between both centrifuges were negligible when the same g-force was used. A lower g-force, however, reduced membrane tensile strength. Timing in the preparation process had a significant impact. Adaptation of RCF only had a minimal impact on the final characteristics of PRF membranes.","subset":"pubmed_abstract"} +{"meta":{"pmid":10889617,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":14}}},"text":"Cancer patients' experiences of nurses' behaviour and health promotion activities: a critical incident analysis.\nPatients with head and neck cancer report several disease- and health-related problems before, during and a long time after completed treatment. Nurses have an important role in educating\/supporting these patients about\/through the disease and treatment so that they can attain well-being. This study describes the cancer patients' experiences of nurses' behaviour in terms of critical incidents after nurses had given them care to promote health. The study had a qualitative, descriptive design and the method used was the critical incident technique. Twenty-one informants from the Nordic countries diagnosed with head and neck cancer were strategically selected. It was explained to the informants what a critical incident implies before the interviews took place; this was defined as a major event of great importance, an incident, which the informants still remember, due to its great importance for the outcome of their health and well-being. The nurses' behaviour was examined, and critical incidents were involved in 208 cases-150 positive and 58 negative ones-the number of incidents varying between three and 20 per informant. The nurses' health promotion activities or lack of such activities based on the patients' disease, treatment and symptoms, consisted of informing and instructing the patients as well as enabling their participation. Personal consideration and the nurses' cognisance, knowledge, competence, solicitude, demeanour and statements of understanding were found to be important. Continuous health promotion nursing interventions were of considerable value for the majority of this group of cancer patients. Oncology nurses could reconfirm and update the care of head and neck cancer patients by including health promotion activities in individual care plans. By more frequent use of health promotion models, such as the empowerment model, the nurses could identify and focus on those individuals who needed to alter their life-style as well as tailor their approach towards these patient by setting goals for well-being and a healthy life-style.","subset":"pubmed_abstract"} +{"meta":{"pmid":16946082,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve.\nCentral nervous system neurons process information converging from the uterus, colon, and bladder, partly via the hypogastric nerve. This processing is influenced by the estrous cycle, suggesting the existence of an estrous-modifiable central nervous system substrate by which input from one pelvic organ can influence functioning of other pelvic organs. Here, we tested predictions from this hypothesis that acute inflammation of colon, uterine horn, or bladder would produce signs of inflammation in the other uninflamed organs (increase vascular permeability) and that cross-organ effects would vary with estrous and be eliminated by hypogastric neurectomy (HYPX). Under urethane anesthesia, the colon, uterine horn, or bladder of rats in proestrus or metestrus, with or without prior HYPX, was treated with mustard oil or saline. Two hours later, Evans Blue dye extravasation was measured to assess vascular permeability. Extravasation was increased in all inflamed organs, regardless of estrous stage. For rats in proestrus, but not metestrus, either colon or uterine horn inflammation significantly increased extravasation in the uninflamed bladder. Much smaller cross-organ effects were seen in colon and uterine horn. HYPX reduced extravasation in the inflamed colon and inflamed uterine horn, but not the inflamed bladder. HYPX eliminated the colon-to-bladder and uterine horn-to-bladder effects. These results demonstrate that inflaming one pelvic organ can produce estrous-modifiable signs of inflammation in other pelvic organs, particularly bladder, and suggest that the cross-organ effects involve the hypogastric nerve and are at least partly centrally mediated. Such effects could contribute to co-occurrence and cyclicity of distressing pelvic disorders in women.","subset":"pubmed_abstract"} +{"meta":{"pmid":23956055,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2023-50":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2020-45":1,"2020-16":1}}},"text":"Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group.\nThis phase 2 study was designed to assess the efficacy of single agent cixutumumab (IMC-A12) and gain further information about associated toxicities and pharmacodynamics in children, adolescents, and young adults with recurrent or refractory solid tumors. Patients with relapsed or refractory solid tumors were treated with 9 mg\/kg of cixutumumab as a 1-hour IV infusion once weekly. Strata included: osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma (evaluable disease), neuroblastoma (measurable disease), Wilms tumor, adrenocortical carcinoma, synovial sarcoma, hepatoblastoma, and retinoblastoma. Correlative studies in consenting patients included an assessment of c-peptide, IGFBP-3, IGF-1, IGF-2, hGH, and insulin in consenting patients. One hundred sixteen patients with 114 eligible having a median age of 12 years (range, 2-30) were enrolled. Five patients achieved a partial response: 4\/20 with neuroblastoma (evaluable only) and 1\/20 with rhabdomyosarcoma. Fourteen patients had stable disease for a median of 10 cycles. Hematologic and non-hematologic toxicities were generally mild and infrequent. Serum IGF-1 and IGFBP-3 increased in response to therapy with cixutumumab. Cixutumumab is well tolerated in children with refractory solid tumors. Limited objective single-agent activity of cixutumumab was observed; however, prolonged stable disease was observed in 15% of patients. Ongoing studies are evaluating the toxicity and benefit of cixutumumab in combination with other agents that inhibit the IGF pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":26940101,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Regulation of bovine oviductal NO synthesis by follicular steroids and prostaglandins.\nNitric oxide (NO) is a regulator of sperm motility, oocyte\/embryo survival, and waves of contraction\/relaxation in mammalian oviducts. As follicles control oviductal functions by two routes at least, (1) a systemic way via blood vessels before ovulation, (2) a direct way by entering of follicular fluid through fimbria at ovulation, we hypothesized that NO synthesis in the bovine oviduct is regulated by follicular steroids and prostaglandins (PGs). Quantification of mRNA expressions in the ampullary tissues showed that inducible NO synthase (NOS2) mRNA expression was highest on the day of ovulation (day 0). By contrast, NOS2 mRNA expression in the isthmus was highest on days 5-6 and lowest on days 19-21. Endothelial NOS (NOS3) mRNA expressions in either the ampulla or the isthmus did not change during the estrous cycle. PGE2 and PGF2\u03b1 increased NOS2 mRNA expressions in cultured ampullary oviductal epithelial cells after 1-h incubation. These increases were suppressed by an antagonist of E-prostanoid receptor type 2, one of the PGE2 receptor. Estradiol-17\u03b2 decreased the expression of NOS2 mRNA expression in cultured isthmic epithelial cells 24h after treatment. This effect was suppressed by an antagonist of estrogen receptor\u03b1(ESR1). Expression of ESR1 was highest on days 19-21 in the isthmic tissues. The overall findings indicate region-specific difference of NO synthesis in the oviduct. PGs flowed from ruptured follicle may up-regulate NO synthesis in the oviductal epithelium, whereas circulating E2 seems to inhibit NO synthesis via ESR1 in the isthmus at the follicular stage.","subset":"pubmed_abstract"} +{"meta":{"pmid":24787174,"dup_signals":{"dup_doc_count":43,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2019-43":1,"2018-22":2,"2018-13":2,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":2,"2017-04":2,"2016-44":2,"2016-40":1,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-32":2,"2015-27":2,"2015-22":2,"2021-39":1}}},"text":"Plasmonic metal-dielectric-metal stack structure with subwavelength metallic gratings for improving sensor sensitivity and signal quality.\nIn this study, we investigated the performance improvement of a localized surface plasmon resonance (LSPR) biosensor by incorporating a metal-dielectric-metal (MDM) stack structure and subwavelength metallic nanograting. The numerical results showed that the LSPR substrate with a MDM stack can provide not only a better sensitivity by more than five times but also a notably improved signal quality. While the gold nanogratings on a gold film inevitably lead to a broad and shallow reflectance curve, the presence of a MDM stack can prevent propagating surface plasmons from interference by locally enhanced fields excited at the gold nanogratings, finally resulting in a strong and deep absorption band at resonance. Therefore, the proposed LSPR structure could potentially open a new possibility of enhanced detection for monitoring biomolecular interactions of very low molecular weights.","subset":"pubmed_abstract"} +{"meta":{"pmid":17251080,"dup_signals":{"dup_doc_count":12}},"text":"Epidemiology and burden of malaria in pregnancy.\nWe reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100,000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.","subset":"pubmed_abstract"} +{"meta":{"pmid":32843882,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":18}}},"text":"Medical Library Association Diversity and Inclusion Task Force 2019 Survey Report.\nThe goal of this survey by the Medical Library Association (MLA) Diversity and Inclusion Task Force was to have a better understanding of the demographics of the association as well as ascertain how the membership feels about MLA's diversity efforts. A survey was created with the input of both task force members as well as MLA professional staff. It was administered via SurveyMonkey and distributed through email over the course of two weeks in October 2019. The demographics portion of the survey-beyond asking the usual questions about race or ethnicity (72% white), age (65% between 30 and 59), and so on-also asked questions that were more specific to diversity including, but not limited to, gender representation (79% female), sexuality (67% heterosexual), military service (97% have never served), ability (26% have anxiety sometimes or in certain situations), and college financial aid (49% used federal student loans). Diversity-specific questions asked about diversity, equity, and inclusion (DEI) in the association: 59% strongly agreed or agreed that MLA has a strong commitment to DEI; 54% felt that the amount of time that association was spending on DEI issues was just about right; and 56% were very satisfied or satisfied with the DEI environment at MLA. Members also reported feeling like they belonged in MLA (59%), they were treated with respect (77%), and they were valued by MLA (59%). The survey paints a picture of the membership that is much deeper than any previously conducted membership survey. It shows the diversity of membership, especially in terms of ability and religion. Generally, the membership feels that MLA is right on target with the level of focus that MLA is giving issues of diversity. This survey reinforces the diversity work that has been done and supports diversity work in MLA in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":21630274,"dup_signals":{"dup_doc_count":19,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":5,"2024-26":2,"2024-22":1,"2024-18":4,"2024-10":2,"unknown":3}}},"text":"Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.\nGermline mutations in the FH gene encoding the Krebs cycle enzyme fumarate hydratase predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. FH-deficient cells and tissues accumulate high levels of fumarate, which may act as an oncometabolite and contribute to tumourigenesis. A recently proposed role for fumarate in the covalent modification of cysteine residues to S-(2-succinyl) cysteine (2SC) (termed protein succination) prompted us to assess 2SC levels in our existing models of HLRCC. Herein, using a previously characterized antibody against 2SC, we show that genetic ablation of FH causes high levels of protein succination. We next hypothesized that immunohistochemistry for 2SC would serve as a metabolic biomarker for the in situ detection of FH-deficient tissues. Robust detection of 2SC was observed in Fh1 (murine FH)-deficient renal cysts and in a retrospective series of HLRCC tumours (n = 16) with established FH mutations. Importantly, 2SC was undetectable in normal tissues (n = 200) and tumour types not associated with HLRCC (n = 1342). In a prospective evaluation of cases referred for genetic testing for HLRCC, the presence of 2SC-modified proteins (2SCP) correctly predicted genetic alterations in FH in every case. In two series of unselected type II papillary renal cancer (PRCC), prospectively analysed by 2SCP staining followed by genetic analysis, the biomarker accurately identified previously unsuspected FH mutations (2\/33 and 1\/36). The investigation of whether metabolites in other tumour types produce protein modification signature(s) that can be assayed using similar strategies will be of interest in future studies of cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":23958155,"dup_signals":{"dup_doc_count":20,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":1,"2014-15":2,"2019-13":1}}},"text":"Production of 2,3-butanediol from cellulose and Jatropha hulls after ionic liquid pretreatment and dilute-acid hydrolysis.\nAbundant Jatropha waste is a promising renewable feedstock for the production of sugars and 2,3-butanediol fermentation. To obtain high yield of water-soluble products and high concentration of reducing-sugars, ionic liquid (IL) pretreatment and dilute acid hydrolysis at 150\u00b0C were combined in this work. The destruction of crystalline structure and increase surface area of biomasses after IL-pretreatment, made their hydrolysis more efficient. Compared with original cellulose, after IL-pretreatment, both the yield and concentration of reducing-sugars increased by 139%, and the water-soluble products yield increased by 128% after hydrolysis. Compared with water-washed Jatropha hulls, after IL-pretreatment, the yield and concentration of reducing-sugars increased by 80% and 76%, respectively, and the water-soluble products yield increased by 70% after hydrolysis. IL-pretreatment benefited the fermentation of Jatropha hull hydrolysate with 66.58% diol yield and its productivity increased from 0.35 to 0.40 g\/(L \u00b7 h).","subset":"pubmed_abstract"} +{"meta":{"pmid":30287417,"dup_signals":{"dup_doc_count":23,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-40":2,"2019-47":1,"2019-39":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-18":1,"2023-50":1,"2024-10":1,"2024-22":1}}},"text":"Identifying the Underlying Factors Associated With Patients' Attitudes Toward Antidepressants: Qualitative and Quantitative Analysis of Patient Drug Reviews.\nNonadherence to antidepressants is a major obstacle to deriving antidepressants' therapeutic benefits, resulting in significant burdens on the individuals and the health care system. Several studies have shown that nonadherence is weakly associated with personal and clinical variables but strongly associated with patients' beliefs and attitudes toward medications. Patients' drug review posts in online health care communities might provide a significant insight into patients' attitude toward antidepressants and could be used to address the challenges of self-report methods such as patients' recruitment. The aim of this study was to use patient-generated data to identify factors affecting the patient's attitude toward 4 antidepressants drugs (sertraline [Zoloft], escitalopram [Lexapro], duloxetine [Cymbalta], and venlafaxine [Effexor XR]), which in turn, is a strong determinant of treatment nonadherence. We hypothesized that clinical variables (drug effectiveness; adverse drug reactions, ADRs; perceived distress from ADRs, ADR-PD; and duration of treatment) and personal variables (age, gender, and patients' knowledge about medications) are associated with patients' attitude toward antidepressants, and experience of ADRs and drug ineffectiveness are strongly associated with negative attitude. We used both qualitative and quantitative methods to analyze the dataset. Patients' drug reviews were randomly selected from a health care forum called askapatient. The Framework method was used to build the analytical framework containing the themes for developing structured data from the qualitative drug reviews. Then, 4 annotators coded the drug reviews at the sentence level using the analytical framework. After managing missing values, we used chi-square and ordinal logistic regression to test and model the association between variables and attitude. A total of 892 reviews posted between February 2001 and September 2016 were analyzed. Most of the patients were females (680\/892, 76.2%) and aged less than 40 years (540\/892, 60.5%). Patient attitude was significantly (P<.001) associated with experience of ADRs, ADR-PD, drug effectiveness, perceived lack of knowledge, experience of withdrawal, and duration of usage, whereas oth age (F4,874=0.72, P=.58) and gender (\u03c724=2.7, P=.21) were not found to be associated with patient attitudes. Moreover, modeling the relationship between variables and attitudes showed that drug effectiveness and perceived distress from adverse drug reactions were the 2 most significant factors affecting patients' attitude toward antidepressants. Patients' self-report experiences of medications in online health care communities can provide a direct insight into the underlying factors associated with patients' perceptions and attitudes toward antidepressants. However, it cannot be used as a replacement for self-report methods because of the lack of information for some of the variables, colloquial language, and the unstructured format of the reports.","subset":"pubmed_abstract"} +{"meta":{"pmid":15817689,"dup_signals":{"dup_doc_count":26,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2020-40":1,"2019-39":1,"2019-35":1,"2019-30":3,"2019-22":1,"2019-18":3,"2019-13":1,"2019-04":1,"2018-26":1,"2018-09":1,"2017-39":1,"2017-30":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2021-17":1,"2017-13":1}}},"text":"Rapid and selective surveillance of Arabidopsis thaliana genome annotations with Centrifuge.\nCentrifuge is a user-friendly system to simultaneously access Arabidopsis gene annotations and intra- and inter-organism sequence comparison data. The tool allows rapid retrieval of user-selected data for each annotated Arabidopsis gene providing, in any combination, data on the following features: predicted protein properties such as mass, pI, cellular location and transmembrane domains; SWISS-PROT annotations; Interpro domains; Gene Ontology records; verified transcription; BLAST matches to the proteomes of A.thaliana, Oryza sativa (rice), Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens. The tool lends itself particularly well to the rapid analysis of contigs or of tens or hundreds of genes identified by high-throughput gene expression experiments. In these cases, a summary table of principal predicted protein features for all genes is given followed by more detailed reports for each individual gene. Centrifuge can also be used for single gene analysis or in a word search mode. http:\/\/centrifuge.unil.ch\/ firstname.lastname@example.com.","subset":"pubmed_abstract"} +{"meta":{"pmid":19958966,"dup_signals":{"dup_doc_count":13}},"text":"Improving global vascular risk prediction with behavioral and anthropometric factors. The multiethnic NOMAS (Northern Manhattan Cohort Study).\nThis study sought to improve global vascular risk prediction with behavioral and anthropometric factors. Few cardiovascular risk models are designed to predict the global vascular risk of myocardial infarction, stroke, or vascular death in multiethnic individuals, and existing schemes do not fully include behavioral risk factors. A randomly derived, population-based, prospective cohort of 2,737 community participants free of stroke and coronary artery disease was followed up annually for a median of 9.0 years in the NOMAS (Northern Manhattan Study) (mean age 69 years, 63.2% women, 52.7% Hispanic, 24.9% African American, and 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criteria. Model utility was assessed through receiver-operating characteristics, calibration, and effect on reclassification of subjects. Variables that significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten-year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10-year event rates compared with a model restricted to the traditional variables. A GVRS that combines traditional, behavioral, and anthropometric risk factors; uses continuous variables for physiological parameters; and is applicable to nonwhite subjects could improve primary prevention strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":21544615,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-29":2,"2019-47":1,"2019-26":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-39":1,"2017-26":1,"2023-50":1,"2024-18":1}}},"text":"H2 inhibits TNF-\u03b1-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor \u03baB activation in endothelial cells.\nH(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-\u03b1. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) in endothelial cells. H(2) significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-\u03b1, at the protein and mRNA levels. The TNF-\u03b1-induced upregulation of LOX-1 was also attenuated by the NF-\u03baB inhibitor N-acetyl-L-cysteine. H(2) inhibited the TNF-\u03b1-induced activation of NF-\u03baB and the phosphorylation of I\u03baB-\u03b1. Furthermore, H(2) inhibited the expression of LOX-1 and the activation of NF-\u03baB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-\u03baB activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":18350096,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Two-Dimensional Electric-Field Vector Measurement by a LiTaO(3) electro-optic probe tip.\nAn electro-optic probe tip that is made from LiTaO crystal to make tangentially two-dimensional electric-field (E-field) vector measurements is presented. We combine a new electro-optic modulation technique and a conventional one to resolve the two E-field components. The new modulation effect on the optical probing beam is caused by rotation of the principal axis the electro-optic crystal, which is proportional to the E-field. Inasmuch as there is no free charge involved in the axis rotation, rotation modulation of the axis can be as fast as conventional modulation. The principles are carefully derived, and an experimental system constructed, to measure two-dimensional E-field vectors on a test pattern. The results are in good agreement with those obtained with commercial software for electromagnetic simulation. The sensitivities of two tangential E-field components are 76 (mV\/cm)\/ radicalHz and 0.8 (V\/cm)\/ radicalHz, respectively. The root-mean-square error of an E-field directional measurement is 1.5 degrees .","subset":"pubmed_abstract"} +{"meta":{"pmid":20173777,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2021-49":1,"2020-50":1,"2019-47":1,"2018-51":1,"2018-30":1,"2018-09":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2022-49":1,"2017-13":1}}},"text":"Blockade of interleukin 1 in type 1 diabetes mellitus.\nInterleukin 1 (IL-1) is a 17 kDa protein highly conserved through evolution and is a key mediator of inflammation, fever and the acute-phase response. IL-1 has important functions in the innate immune defense against microbes, trauma and stress, and is also an effector molecule involved in tissue destruction and fibrosis. The inhibition of IL-1 action has clinical efficacy in many inflammatory diseases, such as hereditary autoinflammatory disorders, familial hereditary fever, gout, rheumatoid arthritis and type 2 diabetes mellitus (T2DM). The latter is a common metabolic condition caused by insulin resistance and pancreatic beta-cell failure, the causes of both of which have inflammatory components. IL-1 signaling has roles in beta-cell dysfunction and destruction via the NFkappaB and mitogen-activated-protein-kinase pathways, leading to endoplasmic reticulum and mitochondrial stress and eventually activating the apoptotic machinery. In addition, IL-1 acts on T-lymphocyte regulation. The modulating effect of IL-1 on the interaction between the innate and adaptive immune systems and the effects of IL-1 on the beta-cell point to this molecule being a potential interventional target in autoimmune diabetes mellitus. Genetic or pharmacological abrogation of IL-1 action reduces disease incidence in animal models of type 1 diabetes mellitus (T1DM) and clinical trials have been started to study the feasibility, safety and efficacy of IL-1 therapy in patients with T1DM. Here, we review the rationale for blocking IL-1 in patients with T1DM.","subset":"pubmed_abstract"} +{"meta":{"pmid":25904877,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"It's all in the past: temporal-context effects modulate subjective evaluations of emotional visual stimuli, regardless of presentation sequence.\nThe aim of this study was to investigate if and how temporal context influences subjective affective responses to emotional images. To do so, we examined whether the subjective evaluation of a target image is influenced by the valence of its preceding image, and\/or its overall position in a sequence of images. Furthermore, we assessed if these potentially confounding contextual effects can be moderated by a common procedural control: randomized stimulus presentation. Four groups of participants evaluated the same set of 120 pictures from the International Affective System (IAPS) presented in four different sequences. Our data reveal strong effects of both aspects of temporal context in all presentation sequences, modified only slightly in their nature and magnitude. Furthermore, this was true for both valence and arousal ratings. Subjective ratings of negative target images were influenced by temporal context most strongly across all sequences. We also observed important gender differences: females expressed greater sensitivity to temporal-context effects and design manipulations relative to males, especially for negative images. Our results have important implications for future emotion research that employs normative picture stimuli, and contributes to our understanding of context effects in general.","subset":"pubmed_abstract"} +{"meta":{"pmid":21303925,"dup_signals":{"dup_doc_count":22,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2021-49":1,"2020-50":1,"2019-47":1,"2019-43":1,"2018-43":1,"2018-22":2,"2018-09":1,"2017-51":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-44":1,"2022-05":1,"2017-13":2}}},"text":"Electron tomography reveals a flared morphology on growing microtubule ends.\nMicrotubules (MTs) exhibit dynamic instability, alternating between phases of growth and shortening, mostly at their uncapped plus ends. Based on results from cryo-electron microscopy it was proposed that growing MTs display mainly curved sheets and blunt ends; during depolymerisation curled 'ramshorns' predominate. Observations of MTs in mitotic cells have suggested that the situation in vivo differs from that in vitro, but so far, a clear comparison between in vivo and in vitro results has not been possible because MT end structures could not be correlated directly with the dynamic state of that particular MT. Here we combine light microscopy and electron tomography (ET) to show that growing MT plus ends in the fission yeast Schizosaccharomyces pombe display predominantly a flared morphology. This indicates that MT polymerisation in vivo and in vitro can follow different paths.","subset":"pubmed_abstract"} +{"meta":{"pmid":28003017,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":3,"unknown":11}}},"text":"Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host.\nEnterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from re-infection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157:H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed. Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157:H7 (Stx-) due to an upregulation of immune suppressive effects (7\/12 genes) or a downregulation of immunostimulatory effects (69\/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function.","subset":"pubmed_abstract"} +{"meta":{"pmid":32296264,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"Resonant Ta Doping for Enhanced Mobility in Transparent Conducting SnO2.\nTransparent conducting oxides (TCOs) are ubiquitous in modern consumer electronics. SnO2 is an earth abundant, cheaper alternative to In2O3 as a TCO. However, its performance in terms of mobilities and conductivities lags behind that of In2O3. On the basis of the recent discovery of mobility and conductivity enhancements in In2O3 from resonant dopants, we use a combination of state-of-the-art hybrid density functional theory calculations, high resolution photoelectron spectroscopy, and semiconductor statistics modeling to understand what is the optimal dopant to maximize performance of SnO2-based TCOs. We demonstrate that Ta is the optimal dopant for high performance SnO2, as it is a resonant dopant which is readily incorporated into SnO2 with the Ta 5d states sitting \u223c1.4 eV above the conduction band minimum. Experimentally, the band edge electron effective mass of Ta doped SnO2 was shown to be 0.23m 0, compared to 0.29m 0 seen with conventional Sb doping, explaining its ability to yield higher mobilities and conductivities.","subset":"pubmed_abstract"} +{"meta":{"pmid":7892297,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats.\nExposure to naturally occurring estrogens during critical periods of development can alter morphologic and physiologic markers of sexual differentiation. The current experiment characterizes the effects of in utero treatment with genistein, an isoflavonoid phytoestrogen, on birth weight, anogenital distance (AGD) at birth. GnRH stimulated luteinizing hormone (LH) secretion, volume of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA), puberty onset, and vaginal cyclicity. Pregnant Charles River CD rats were injected sc daily on gestation day 16-20 with either 25,000 micrograms genistein (G25), 5,000 micrograms genistein (G5), 5 micrograms diethylstillbestrol (DES), 50 micrograms estradiol benzoate (E), or corn oil alone for controls. Birth weights and anogenital distance was taken and exposed progeny were subsequently used in two experiments. In Experiment 1 intra-atrial catheters were placed in adult castrated rats, GnRH was given iv, serial blood samples were drawn and sera were assayed for LH by radioimmunoassay (RIA). Brains obtained by subsequent decapitation were saved for histology. In Experiment 2, females were monitored for timing of vaginal opening as a marker of puberty onset, and vaginal smears were taken to monitor cyclicity. G25-treated females and DES- and E-treated animals of both sexes had decreased weights at birth compared with controls. G5- and E-treated animals of both sexes and DES males had smaller AGD than controls. No significant differences in pituitary responsiveness to GnRH were found among treatment groups. There was a nonsignificant decrease in SDN-POA volume in G5-treated females while DES- and E-treated females had increased SDN-POA volume compared with controls. G5-treated females had delayed puberty onset, and DES-treated females had atypical vaginal cycles in comparison with controls. The results confirm that prenatal exposure to estrogens in the environment can influence sexual differentiation. Our previous experiments have demonstrated that castrate female rats exposed as neonates to genistein have decreased pituitary responsiveness to GnRH challenge and enlarged SDN-POA volume in comparison with controls. Prenatal genistein at these dosages did not significantly alter these markers. However, genistein did mimic other estrogens' effects on AGD and birth weight and had a unique influence on puberty onset. Not only are genistein's effects different from other estrogens, but dosage and timing of exposure during development appear to be important factors in genistein's ability to modify these end points.","subset":"pubmed_abstract"} +{"meta":{"pmid":20463022,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Pro-tumorigenic effects of miR-31 loss in mesothelioma.\nThe human genome encodes several hundred microRNA (miRNA) genes that produce small (21-23n) single strand regulatory RNA molecules. Although abnormal expression of miRNAs has been linked to cancer progression, the mechanisms of this dysregulation are poorly understood. Malignant mesothelioma (MM) of pleura is an aggressive and highly lethal cancer resistant to conventional therapies. We and others previously linked loss of the 9p21.3 chromosome in MM with short time to tumor recurrence. In this study, we report that MM cell lines derived from patients with more aggressive disease fail to express miR-31, a microRNA recently linked with suppression of breast cancer metastases. We further demonstrate that this loss is due to homozygous deletion of the miR-31-encoding gene that resides in 9p21.3. Functional assessment of miR-31 activity revealed its ability to inhibit proliferation, migration, invasion, and clonogenicity of MM cells. Re-introduction of miR-31 suppressed the cell cycle and inhibited expression of multiple factors involved in cooperative maintenance of DNA replication and cell cycle progression, including pro-survival phosphatase PPP6C, which was previously associated with chemotherapy and radiation therapy resistance, and maintenance of chromosomal stability. PPP6C, whose mRNA is distinguished with three miR-31-binding sites in its 3'-untranslated region, was consistently down-regulated by miR-31 introduction and up-regulated in clinical MM specimens as compared with matched normal tissues. Taken together, our data suggest that tumor-suppressive propensity of miR-31 can be used for development of new therapies against mesothelioma and other cancers that show loss of the 9p21.3 chromosome.","subset":"pubmed_abstract"} +{"meta":{"pmid":31601772,"dup_signals":{"dup_doc_count":23,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":2,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2020-40":1,"2020-34":2,"2020-24":1,"2020-16":1,"2020-10":2,"2019-51":1,"2019-47":2,"2023-40":1,"2024-10":1}}},"text":"Global modeling of nature's contributions to people.\nThe magnitude and pace of global change demand rapid assessment of nature and its contributions to people. We present a fine-scale global modeling of current status and future scenarios for several contributions: water quality regulation, coastal risk reduction, and crop pollination. We find that where people's needs for nature are now greatest, nature's ability to meet those needs is declining. Up to 5 billion people face higher water pollution and insufficient pollination for nutrition under future scenarios of land use and climate change, particularly in Africa and South Asia. Hundreds of millions of people face heightened coastal risk across Africa, Eurasia, and the Americas. Continued loss of nature poses severe threats, yet these can be reduced 3- to 10-fold under a sustainable development scenario.","subset":"pubmed_abstract"} +{"meta":{"pmid":30316958,"dup_signals":{"dup_doc_count":12}},"text":"Predicting Outcome After Hand Orthosis and Hand Therapy for Thumb Carpometacarpal Osteoarthritis: A Prospective Study.\n(1) To identify predictive factors for outcome after splinting and hand therapy for carpometacarpal (CMC) osteoarthritis (OA) and to identify predictive factors for conversion to surgical treatment; and (2) to determine how many patients who have not improved in outcome within 6 weeks after start of treatment will eventually improve after 3 months. Observational prospective multicenter cohort study. Xpert Clinic in the Netherlands. This clinic comprises 15 locations in the Netherlands, with 16 European Board certified (FESSH) hand surgeons and over 50 hand therapists. Between 2011 and 2014, patients with CMC OA (N=809) received splinting and weekly hand therapy for 3 months. Not applicable. Satisfaction and pain were measured with a visual analog scale and function with the Michigan Hand Questionnaire at baseline, 6 weeks, and 3 months posttreatment. Using regression analysis, patient demographics and pretreatment baseline scores were considered as predictors for the outcome of conservative treatment after 3 months and for conversion to surgery. Multivariable regression model explained 34%-42% of the variance in outcome (P<.001) with baseline satisfaction, pain, and function as significant predictors. Cox regression analysis showed that baseline pain and function were significant predictors for receiving surgery. Of patients with no clinically relevant improvement in pain and function after 6 weeks, 73%-83% also had no clinically relevant improvement after 3 months. This study showed that patients with either high pain or low function may benefit most from conservative treatment. We therefore recommend to always start with conservative treatment, regardless of symptom severity of functional loss at start of treatment. Furthermore, it seems valuable to discuss the possibility of surgery with patients after 6 weeks of therapy, when levels of improvement are still mainly unsatisfactory.","subset":"pubmed_abstract"} +{"meta":{"pmid":27641140,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Magnetic resonance cholangiopancreatography (MRCP) using new negative per-oral contrast agent based on superparamagnetic iron oxide nanoparticles for extrahepatic biliary duct visualization in liver cirrhosis.\nMagnetic resonance cholangiopancreatography (MRCP) is often used for imaging of the biliary tree and is required by surgeons before liver transplantation. Advanced liver cirrhosis and ascites in patients however present diagnostic problems for MRCP. The aim of this study was to find out if the use of our negative per-oral contrast agent containing superparamagnetic iron oxide nanoparticles (SPIO) in MRCP is helpful for imaging of hepatobiliary tree in patients with liver cirrhosis. Forty patients with liver cirrhosis were examined on a 1.5 T MR unit using standard MRCP protocol. Twenty patients (group A) underwent MRCP after administration of per-oral SPIO contrast agent 30 min before examination. In group B, twenty patients were examined without per-oral bowel preparation. Ascites was present in eleven patients from group A and in thirteen patients in group B. Four radiologists analyzed MR images for visibility and delineation of the biliary tree. \u03c72 tests were used for comparison of the visibility of intrahepatic and extrahepatic biliary ducts in patients with and without ascites. Better extrahepatic biliary duct visualization and visibility of extraluminal pathologies in patients with ascites was proved after administration of SPIO contrast agent. No statistically significant difference between group A and B was found for visualization of extrahepatic biliary ducts in patients without ascites. Delineation of intrahepatic biliary ducts was independent on bowel preparation. Application of our negative per-oral SPIO contrast agent before MRCP improves the visualization of extrahepatic biliary ducts in patients with ascites which is helpful during the liver surgery, mainly in liver transplantation.","subset":"pubmed_abstract"} +{"meta":{"pmid":26941402,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"PLZF mutation alters mouse hematopoietic stem cell function and cell cycle progression.\nHematopoietic stem cells (HSCs) give rise to all blood populations due to their long-term self-renewal and multipotent differentiation capacities. Because they have to persist throughout an organism's life span, HSCs tightly regulate the balance between proliferation and quiescence. Here, we investigated the role of the transcription factor promyelocytic leukemia zinc finger (plzf) in HSC fate using the Zbtb16(lu\/lu)mouse model, which harbors a natural spontaneous mutation that inactivates plzf. Regenerative stress revealed that Zbtb16(lu\/lu)HSCs had a lineage-skewing potential from lymphopoiesis toward myelopoiesis, an increase in the long-term-HSC pool, and a decreased repopulation potential. Furthermore, oldplzf-mutant HSCs present an amplified aging phenotype, suggesting that plzf controls age-related pathway. We found that Zbtb16(lu\/lu)HSCs harbor a transcriptional signature associated with a loss of stemness and cell cycle deregulation. Lastly, cell cycle analyses revealed an important role for plzf in the regulation of the G1-S transition of HSCs. Our study reveals a new role for plzf in regulating HSC function that is linked to cell cycle regulation, and positions plzf as a key player in controlling HSC homeostasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":11872835,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Micro\/nano encapsulation via electrified coaxial liquid jets.\nWe report a method to generate steady coaxial jets of immiscible liquids with diameters in the range of micrometer\/nanometer size. This compound jet is generated by the action of electro-hydrodynamic (EHD) forces with a diameter that ranges from tens of nanometers to tens of micrometers. The eventual jet breakup results in an aerosol of monodisperse compound droplets with the outer liquid surrounding or encapsulating the inner one. Following this approach, we have produced monodisperse capsules with diameters varying between 10 and 0.15 micrometers, depending on the running parameters.","subset":"pubmed_abstract"} +{"meta":{"pmid":1735584,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"The effect of upright tilt on nifedipine-induced natriuresis.\nCalcium channel blockers are antihypertensive agents with diuretic actions. Yet edema occurs in some patients receiving long-term treatment with these drugs. As with other vasodilators, stimulation for fluid retention could result from systemic vasodilation. We speculated that the upright posture could enhance sodium retention. To test this hypothesis, we studied the effect of upright tilt in 10 patients before and after the oral administration of 20 mg nifedipine. Before nifedipine upright tilt caused a 41% drop in the sodium excretion rate, from 0.27 +\/- 0.04 to 0.16 +\/- 0.03 meq\/min (p less than 0.05). Fractional sodium excretion decreased by 46%, from 2.4 +\/- 0.5 to 1.3 +\/- 0.3% (p less than 0.01). Urinary volume and renal plasma flow also decreased (p less than 0.05). Plasma renin activity (PRA) rose by 46% (p less than 0.005). With the patients in the supine posture nifedipine increased the sodium excretion rate to 0.49 +\/- 0.09 meq\/min (p less than 0.05). Fractional sodium excretion was 3.1 +\/- 0.6 meq\/min (p = 0.2). The natriuresis took place despite a fall in mean blood pressure and a significant rise in PRA (up 115% from prenifedipine supine values, p less than 0.005). Renal plasma flow also increased (p less than 0.01). The upright tilt caused a reversal of the nifedipine-induced natriuresis. The sodium excretion rate dropped to 0.23 +\/- 0.05 meq\/min and fractional sodium excretion to 1.3 +\/- 0.2% (both not different from control). This drop in natriuresis occurred while mean blood pressure was at its lowest and PRA was 254% above the initial levels (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":30464314,"dup_signals":{"dup_doc_count":26,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":24}}},"text":"Machine learning based classification of cells into chronological stages using single-cell transcriptomics.\nAge-associated deterioration of cellular physiology leads to pathological conditions. The ability to detect premature aging could provide a window for preventive therapies against age-related diseases. However, the techniques for determining cellular age are limited, as they rely on a limited set of histological markers and lack predictive power. Here, we implement GERAS (GEnetic Reference for Age of Single-cell), a machine learning based framework capable of assigning individual cells to chronological stages based on their transcriptomes. GERAS displays greater than 90% accuracy in classifying the chronological stage of zebrafish and human pancreatic cells. The framework demonstrates robustness against biological and technical noise, as evaluated by its performance on independent samplings of single-cells. Additionally, GERAS determines the impact of differences in calorie intake and BMI on the aging of zebrafish and human pancreatic cells, respectively. We further harness the classification ability of GERAS to identify molecular factors that are potentially associated with the aging of beta-cells. We show that one of these factors, junba, is necessary to maintain the proliferative state of juvenile beta-cells. Our results showcase the applicability of a machine learning framework to classify the chronological stage of heterogeneous cell populations, while enabling detection of candidate genes associated with aging.","subset":"pubmed_abstract"} +{"meta":{"pmid":25901623,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Fifty most-cited articles in anterior cruciate ligament research.\nThe number of times an article has been cited in the peer-reviewed literature is indicative of its impact on its respective medical specialty. No study has used citation analysis to determine the most influential studies pertaining to the anterior cruciate ligament (ACL). The primary aims of this study were to identify the classic works in ACL research using citation analysis and to characterize these articles to determine which types of studies have had the most influence on the field. A systematic query of ISI Web of Science (Thomson Reuters, Philadelphia, Pennsylvania) was performed for articles pertaining to the ACL, and the 50 most-cited articles were selected for evaluation. The following characteristics were determined for each article: number of citations, citation density, journal, publication year, country of origin, language, article type, article subtype, and level of evidence. The number of citations ranged from 219 to 1073 (mean, 326), and the citation densities ranged from 4.9 to 55.6 citations per year (mean, 18.2). All articles were published in 1 of 11 journals, with the most being published in The American Journal of Sports Medicine (46%) and The Journal of Bone and Joint Surgery American (30%). The most common decades of publication were the 1990s (34%), 1980s (28%), and 2000s (26%). The majority (68%) of articles originated from the United States, and all were written in English. By article type, 42% were basic science, and 58% were clinical. Of the clinical articles, 3% were Level I, 17% were Level II, 28% were Level III, and 52% were Level IV. The articles were heterogeneous with regard to article type, article subtype, and level of evidence and tended to have the following characteristics: high-impact journal of publication, recent publication year, US origin, English language, and low level of evidence. These works represent some of the most popular scientific contributions to ACL research. This list may aid residency and fellowship programs in the compilation of articles for trainee reading curriculums.","subset":"pubmed_abstract"} +{"meta":{"pmid":22456912,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2015-18":1,"unknown":9}}},"text":"Household income and spiritual well-being but not body mass index as determinants of poor self-rated health among African American adolescents.\nVery little is known about predictors of subjective health status among African American adolescents. This study was designed to determine whether selected anthropometric, psychological, lifestyle behavioral, and structural variables predicted poor self-rated general health in a cross-sectional nonclinical sample of 310 female African American adolescents, 14-18 years old. The odds of reporting poor self-rated health were 2-3 times greater for African American teens from lower socioeconomic households when compared to teens residing in higher socioeconomic households and for those reporting infrequent participation in activities that promote spiritual well-being compared to those who participate more frequently in activities that enhance spiritual health. Findings indicate that socioeconomic level and engagement in behaviors that enhance healthy spirituality appear to be the most salient predictors of self-rated health. In addition to biodiversity considerations that influence perceptions of health status, culturally focused interventions should integrate variables shown to influence self-rated health among African American teens. These inclusions may inform a more integrated understanding of health, health outcomes, and health disparities in this vulnerable population.","subset":"pubmed_abstract"} +{"meta":{"pmid":16707374,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Usefulness (or lack thereof) of immunophenotyping in atypical cutaneous T-cell infiltrates.\nOur purpose was to evaluate the interobserver concordance for the diagnoses of mycosis fungoides (MF), atypical dermatoses (AD), and benign dermatoses (BD) and the impact of T-cell immunophenotyping on the diagnoses MF, AD, and BD. Specimens of MF (n = 57), AD (n = 27), BD and normal skin (n = 54) were reviewed by 2 hematopathologists and 1 dermatopathologist to establish diagnostic interobserver concordance by routine morphologic examination. Immunophenotyping was performed to evaluate expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and MIB-1. The interobserver concordance was fair to moderate compared with the original diagnosis. Partial deletion of CD2 alone was associated significantly with MF. Epidermal deletions of 2 or 3 T-cell antigens or 2 T-cell antigens not including CD7 were associated significantly with MF. An elevated CD4\/CD8 ratio correlated with MF. Morphologic features were most diagnostic of MF. Immunophenotyping generally resulted in downgrading of the reaction pattern but was helpful in distinguishing MF from benign dermatoses.","subset":"pubmed_abstract"} +{"meta":{"pmid":12228714,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"Deformation on nearby faults induced by the 1999 Hector Mine earthquake.\nInterferometric Synthetic Aperture Radar observations of surface deformation due to the 1999 Hector Mine earthquake reveal motion on several nearby faults of the eastern California shear zone. We document both vertical and horizontal displacements of several millimeters to several centimeters across kilometer-wide zones centered on pre-existing faults. Portions of some faults experienced retrograde (that is, opposite to their long-term geologic slip) motion during or shortly after the earthquake. The observed deformation likely represents elastic response of compliant fault zones to the permanent co-seismic stress changes. The induced fault displacements imply decreases in the effective shear modulus within the kilometer-wide fault zones, indicating that the latter are mechanically distinct from the ambient crustal rocks.","subset":"pubmed_abstract"} +{"meta":{"pmid":16661432,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"A proposed role of zein and glutelin as N sinks in maize.\nZea mays grown with high levels of N fertilizer transports more sucrose into kernels than with low N. Sucrose translocation was greatest in genotypes with the highest capacity to deposit nitrogenous compounds as zein and glutelin in the kernel. These two proteins combined contain about 80% of the total N in the kernel and about 60% of the total N in the plant at maturity. They appear to serve as a functional N sink for the deposition of nitrogenous compounds. As the N sink capacity increases with additional available N fertilizer, more sucrose is transported into the kernel, resulting in increased kernel weight and grain yield. Zein functions as a more dynamic N sink than glutelin because the synthesis of zein is readily manipulated by N fertilization and genetic means. Increases in N deposition in the normal endosperm induced by N fertilizer are confined primarily to zein. Early termination of zein accumulation in the opaque-2 mutant results in a reduction of sucrose movement into kernels. By using plants heterozygous for normal and opaque-2 in these studies, interplant variability was eliminated and the hypothesis relating the kernel N sink capacity to productivity was strengthened.","subset":"pubmed_abstract"} +{"meta":{"pmid":32028680,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Genome Assembly and Annotation of the Southern Elephant Seal Mirounga leonina.\nThe southern elephant seal Mirounga leonina is the largest phocid seal and one of the two species of elephant seals. They are listed as 'least concern' by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species 2015. Here, we have assembled the reference genome for M. leonina using the 10\u00d7 chromium sequencing platform. The final genome assembly of M. leonina was 2.42 Gb long, with a contig N50 length of 54 Mb and a maximum length of 111.6 Mb. The M. leonina genome contained 20,457 predicted protein-coding genes and possessed 41.51% repeated sequences. The completeness of the M. leonina genome was evaluated using benchmarking universal single-copy orthologous genes (BUSCOs): the assembly was highly complete, containing 95.6% of the core set of mammalian genes. The high-quality genomic information on M. leonina will be essential for further understanding of adaptive metabolism upon repeated breath-hold dives and the exploration of molecular mechanisms contributing to its unique biochemical and physiological characteristics. The southern elephant seal genome project was deposited at NCBI (National Center for Biotechnology Information) under BioProject number PRJNA587380.","subset":"pubmed_abstract"} +{"meta":{"pmid":1281502,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Acetylcholine activates non-selective cation and chloride conductances in canine and guinea-pig tracheal myocytes.\n1. Membrane currents activated by acetylcholine (ACh) were investigated in isolated canine and guinea-pig tracheal myocytes using the nystatin perforated patch configuration of whole-cell recording. ACh caused depolarization accompanied by a membrane conductance increase. 2. When cells were held under voltage clamp (holding potential, Vh = -60 mV), ACh elicited inward current (IACh) of up to 3900 pA, with a reversal potential (Erev) of approximately -20 mV. 3. Removal of extracellular Na+ (Na+o) reduced but did not eliminate IACh. IACh remaining in the absence of Na+ reversed direction close to the predicted equilibrium potential for Cl-. Erev shifted 32 +\/- 4 mV per 10-fold change of [Cl-]i. Increasing external [K+] caused Erev to shift in the positive direction. These results suggest that ACh activated chloride and non-selective cation conductances. 4. In the absence of Na+o, the Cl- channel blockers SITS or niflumic acid reversibly antagonized IACh. 5. Caffeine and ryanodine elicited currents both in the presence and absence of Na+o; these currents had a reversal potential similar to that of IACh. Caffeine applied before ACh occluded the response to ACh. 6. We also observed two types of spontaneous membrane currents. Spontaneous transient outward currents (STOCs) may represent Ca(2+)-activated K+ currents. Spontaneous inward currents were also observed which were reduced in magnitude (but not eliminated) by removal of Na+o and reversed direction at approximately the Cl- equilibrium potential. The spontaneous inward currents and STOCs were coincident and were reversibly suppressed by ACh. 7. ACh elicited contractions of cells under voltage clamp at -60 mV, an effect also observed in the absence of extracellular Ca2+ or when IACh was reduced by omission of Na+o and exposure to Cl- channel blockers. The number of cells which did contract in response to ACh decreased, however, when the concentration of internal Cl- decreased. 8. All effects of ACh on contraction and membrane currents were antagonized by atropine. 9. We conclude that activation of muscarinic receptors in mammalian tracheal myocytes causes release of Ca2+ from intracellular stores and subsequent activation of Cl- and non-selective cation conductances. This is the first direct demonstration of these conductances in tracheal smooth muscle cells. Activation of these conductances does not appear to be required for contraction. However, regulation of cytosolic Cl- levels may be important for release and uptake of Ca2+ from internal stores.","subset":"pubmed_abstract"} +{"meta":{"pmid":27573792,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.\nCo-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg\/kg s.c.\u00d77 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.","subset":"pubmed_abstract"} +{"meta":{"pmid":2370043,"dup_signals":{"dup_doc_count":60,"dup_dump_count":28,"dup_details":{"curated_sources":1,"2018-13":1,"2017-43":1,"2017-30":1,"2017-22":2,"2017-17":2,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":2,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":2,"2014-42":5,"2014-41":5,"2014-35":3,"2014-23":4,"2014-15":4,"2018-22":1}}},"text":"Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics.\nDNA libraries from sorted human gonosomes were used selectively to stain the X and Y chromosomes in normal and aberrant cultured human cells by chromosomal in situ suppression (CISS-) hybridization. The entire X chromosome was stained in metaphase spreads. Interphase chromosome domains of both the active and inactive X were clearly delineated. CISS-hybridization of the Y chromosome resulted in the specific decoration of the euchromatic part (Ypter-q11), whereas the heterochromatic part (Yq12) remained unlabeled. The stained part of the Y chromosome formed a compact domain in interphase nuclei. This approach was applied to amniotic fluid cells containing a ring chromosome of unknown origin (47,XY: +r). The ring chromosome was not stained by library probes from the gonosomes, thereby suggesting its autosomal origin. The sensitivity of CISS-hybridization was demonstrated by the detection of small translocations and fragments in human lymphocyte metaphase spreads after irradiation with 60Co-gamma-rays. Lymphocyte cultures from two XX-males were investigated by CISS-hybridization with Y-library probes. In both cases, metaphase spreads demonstrated a translocation of Yp-material to the short arm of an X chromosome. The translocated Y-material could also be demonstrated directly in interphase nuclei. CISS-hybridization of autosomes 7 and 13 was used for prenatal diagnosis in a case with a known balanced translocation t(7:13) in the father. The same translocation was observed in amniotic fluid cells from the fetus. Specific staining of the chromosomes involved in such translocations will be particularly important, in the future, in cases that cannot be solved reliably by conventional chromosome banding alone.","subset":"pubmed_abstract"} +{"meta":{"pmid":17604496,"dup_signals":{"dup_doc_count":20,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2024-18":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"unknown":9}}},"text":"A novel perspective on natural therapeutic approaches in glaucoma therapy.\nGlaucoma is becoming recognised as a condition for which not only elevated intraocular pressure (IOP), but also non-pressure-dependent risk factors, are responsible. Better knowledge of the pathogenesis has opened up new therapeutic approaches that are often referred to as non-IOP-lowering treatment. These new avenues of treatment, some of which are still under investigation, include agents that can improve vascular regulation and blood flow to the eye and reduce oxidative stress. Vascular regulation can be improved systemically with magnesium. Dark chocolate and omega-3-fatty acids can also improve blood flow regulation. Oxidative stress at mitochondrial level can be reduced by gingko. Polyphenolic flavonoids (tea, coffee and red wine), anthocyanosides, ubiquinone and melatonin have antioxidant properties, and heat-shock proteins can be induced naturally by the use of sauna baths. Future intensive studies on the effect of these compounds may open up a new therapeutic era in glaucoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":15527670,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2017-13":1,"unknown":15}}},"text":"Acupuncture of chronic headache disorders in primary care: randomised controlled trial and economic analysis.\nTo determine the effects of a policy of using acupuncture, compared with a policy of avoiding acupuncture, on headache in primary care patients with chronic headache disorders. The effects of acupuncture on medication use, quality of life, resource use and days off sick in this population and the cost-effectiveness of acupuncture were also examined. Randomised, controlled trial. General practices in England and Wales. The study included 401 patients with chronic headache disorder, predominantly migraine. Patients were randomly allocated to receive up to 12 acupuncture treatments over 3 months or to a control intervention offering usual care. Outcome measures included headache score; assessment of Short Form 36 (SF-36) health status and use of medication at baseline, 3 months and 12 months; assessment of use of resources every 3 months; and assessment of incremental cost per quality-adjusted life-year (QALY) gained. Headache score at 12 months, the primary end-point, was lower in the acupuncture group than in controls. The adjusted difference between means was 4.6. This result was robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year. SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication, made 25% fewer visits to GPs and took 15% fewer days off sick. Total costs during the 1-year period of the study were on average higher for the acupuncture group than for controls because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the year of the trial was 0.021 QALYs, leading to a base-case estimate of GBP9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial. The study suggests that acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. It is relatively cost-effective compared with a number of other interventions provided by the NHS. Further studies could examine the duration of acupuncture effects beyond 1 year and the relative benefit to patients with migraine with compared to tension-type headache. Trials are also warranted examining the effectiveness and cost-effectiveness of acupuncture in patients with headache receiving more aggressive pharmacological management.","subset":"pubmed_abstract"} +{"meta":{"pmid":22649741,"dup_signals":{"dup_doc_count":18,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":1,"2017-13":1,"2024-30":1,"unknown":11}}},"text":"Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer.\nPurpose. To evaluate the results and quality of life of patients with resistant of castration-resistant tumors previously treated with Insulin-potentiation therapy (IPT) combined with hormone therapy. Materials and methods. Sixteen patients with metastasis prostate tumors after bilateral castration, androgenic blockade, and progression of the disease were observed during the study. The patients were divided into two groups: group A consisting of 8 patients treated with low-dose chemotherapy Epirubicin, Vinblastine, and Cyclophosphamide combined with LHRH agonist and group B consisting of another 8 patients treated with low-dose chemotherapy Docetaxel combined with LHRH agonist. Results. The overall (groups A and B) results concerning PSA after the sixth IPT show partial effect in 8 out of 16 (50%) patients, stabilization in 4 out of 16 (25%), and progression in 4 out of 16 (25%). The median survival for all treated patients is 11,7 months (range 3-30 months). During the treatment no significant side effects were observed, and no lethal cases occurred. Conclusion. In spite of the small number of the treated patients with castration-resistant prostate tumors, the preliminary results are promising and this gives us hope and expectations for future serious multicenter research over the possibilities for routine implementation of IPTLD.","subset":"pubmed_abstract"} +{"meta":{"pmid":19817286,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2014-10":1,"2015-06":1,"unknown":7}}},"text":"[In situ suture repair procedure of knee dislocation with multiple-ligament injury at acute stage].\nTo investigate the method and the short term clinical effectiveness of in situ suture repair procedure of knee dislocation with multiple-ligament injury at acute stage. From February 2006 to November 2007, 9 patients suffering from single knee closed dislocation with multiple-ligament injury underwent open in situ suture repair procedure with non-absorbable thread and managements of other combined injuries simultaneously. Nine patients included 6 males and 3 females, aged 34-52 years old. The injured knees were left side in 4 cases and right side in 5 cases. Injuries were caused by traffic accident in 8 cases and heavy-weight crushing in 1 case. EMRI and arthroscopic examination showed that all patients suffered from the avulsion injuries of anterior cruciate ligament and posterior cruciate ligament. The time from injury to operation was 4 to 7 days with an average of 5.1 days. No bacterial arthritis occurred after operation. Subcutaneous ligated fat occurred and cured after symptomatic treatment in 2 cases, other incisions healed by first intension. All patients were followed up 12 months. At 12 months postoperatively, 2 patients' flexion range of the suffering knees lost 10 degrees when to compared with normal knees, and the range of motion was from 0 to 125 degrees. The Lysholm knee scores were 83-92 (average 86.3), the results were excellent in 3 cases and good in 6 cases. The posterior drawer test and anterior drawer test were one-degree positive in 3 cases respectively; the Lachman tests were one-degree positive in 5 cases, lateral stress tests were negative in all cases. In situ suture repair procedure of knee dislocation with multiple-ligament injury at acute stage has the advantages such as reliable fixation, simultaneous management of other combined injuries and satisfactory short term effect.","subset":"pubmed_abstract"} +{"meta":{"pmid":21517110,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Quantitative measurement of Ca(2+)-dependent calmodulin-target binding by Fura-2 and CFP and YFP FRET imaging in living cells.\nCalcium dynamics and its linked molecular interactions cause a variety of biological responses; thus, exploiting techniques for detecting both concurrently is essential. Here we describe a method for measuring the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and protein-protein interactions within the same cell, using Fura-2 and superenhanced cyan and yellow fluorescence protein (seCFP and seYFP, respectively) FRET imaging techniques. Concentration-independent corrections for bleed-through of Fura-2 into FRET cubes across different time points and [Ca(2+)](i) values allowed for an effective separation of Fura-2 cross-talk signals and seCFP and seYFP cross-talk signals, permitting calculation of [Ca(2+)](i) and FRET with high fidelity. This correction approach was particularly effective at lower [Ca(2+)](i) levels, eliminating bleed-through signals that resulted in an artificial enhancement of FRET. By adopting this correction approach combined with stepwise [Ca(2+)](i) increases produced in living cells, we successfully elucidated steady-state relationships between [Ca(2+)](i) and FRET derived from the interaction of seCFP-tagged calmodulin (CaM) and the seYFP-fused CaM binding domain of myosin light chain kinase. The [Ca(2+)](i) versus FRET relationship for voltage-gated sodium, calcium, and TRPC6 channel CaM binding domains (IQ domain or CBD) revealed distinct sensitivities for [Ca(2+)](i). Moreover, the CaM binding strength at basal or subbasal [Ca(2+)](i) levels provided evidence of CaM tethering or apoCaM binding in living cells. Of the ion channel studies, apoCaM binding was weakest for the TRPC6 channel, suggesting that more global Ca(2+) and CaM changes rather than the local CaM-channel interface domain may be involved in Ca(2+)CaM-mediated regulation of this channel. This simultaneous Fura-2 and CFP- and YFP-based FRET imaging system will thus serve as a simple but powerful means of quantitatively elucidating cellular events associated with Ca(2+)-dependent functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":22361711,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":8}}},"text":"Association of blood pressure and metabolic syndrome components with magnesium levels in drinking water in some Serbian municipalities.\nChronic exposure to insufficient levels of magnesium (Mg) in drinking water increases the risk of magnesium deficiency and its association with hypertension, dyslipidemia and type 2 diabetes mellitus. The aim of the study was to assess the potential association of mineral contents in drinking water with blood pressure and other components of metabolic syndrome (MetS) (BMI as measure of obesity, triglycerides, glucose, and insulin resistance, index-HOMA IR), in a healthy population. This study was conducted in three randomly selected municipalities (Pozarevac, Grocka and Banovci), and recruited 90 healthy blood donors, aged 20-50 years. The Pozarevac area had a four times higher mean Mg level in drinking water (42 mg L(-1)) than Grocka (11 mg L(-1)). Diastolic blood pressure was lowest in subjects from Pozarevac. Serum Mg (sMg) was highest, and serum Ca(2+)\/Mg (sCa\/Mg) lowest in subjects from Pozarevac, and after adjustment for confounders (age, gender, BMI), only total cholesterol and sMg levels were independent predictors of diastolic blood pressure, sMg levels were independent predictors of triglycerides, and sCa\/Mg predicted glucose levels. These results suggest that Mg supplementation in areas of lower magnesium levels in drinking water may be an important measure in the prevention of hypertension and MetS in general.","subset":"pubmed_abstract"} +{"meta":{"pmid":18065666,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A hospital-wide study of the impact of introducing a personal data assistant-augmented blood culture round.\nBlood culture is the cornerstone of an established aetiological diagnosis of septicaemia. The automated blood culture systems used for this purpose have changed little in the last decade, and the clinical value of results depends on a variety of factors, including pre- and post-analytical variables. Growing scepticism over the value of blood culture results and pressure for the introduction of molecular detection systems have prompted a critical path analysis of pre-, peri- and post-analytical stages in the generation of positive blood culture results. The impact of a positive blood culture was studied in a teaching hospital for 12 months before and 12 months after the introduction of a microbiologist's blood culture round. Active culture reporting via a blood culture ward round was supported by a personal data assistant database of contemporaneous laboratory and clinical data. Hospital occupancy and death register records were subsequently obtained through the State Government data linkage project. There was no evidence that faster laboratory generation of positive blood culture results, faster reporting of results or direct clinical interaction with the patient's primary medical team reduced the risk of death in hospital. However, there was a threefold increase in the rate of death in hospital following a 1 day delay in collection of blood cultures after hospital admission (P=0.0010). The overall duration of hospital stay for patients with a positive blood culture fell by 2.5 days compared with the previous 12 month period (P=0.0003). The interval between the initial positive culture result and patient discharge fell by 2 days (P=0.0010). This difference was attributed to shorter overall admissions and shorter intervals between positive cultures containing Gram-positive cocci and subsequent patient discharge (P=0.0018). An increased mortality rate from community-acquired bacteraemic infections was associated with delayed culture collection, but not with a prolonged laboratory processing interval. Thus, the speed of conventional blood culture analysis and the form of clinical reporting have little direct effect on the clinical outcome of bacteraemia, but may contribute to a reduction in the length of hospital admission. Introduction of molecular identification tests, such as multiplex PCR methods, at the Gram-stain stage of blood culture is unlikely to affect the rate of death in hospital, but may reduce the length of hospital admission.","subset":"pubmed_abstract"} +{"meta":{"pmid":33087734,"dup_signals":{"dup_doc_count":20,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":4,"2024-22":2,"2024-10":2,"2024-30":1,"unknown":10}}},"text":"Influence of plasmon excitations on atomic-resolution quantitative 4D scanning transmission electron microscopy.\nScanning transmission electron microscopy (STEM) allows to gain quantitative information on the atomic-scale structure and composition of materials, satisfying one of todays major needs in the development of novel nanoscale devices. The aim of this study is to quantify the impact of inelastic, i.e. plasmon excitations (PE), on the angular dependence of STEM intensities and answer the question whether these excitations are responsible for a drastic mismatch between experiments and contemporary image simulations observed at scattering angles below [Formula: see text] 40 mrad. For the two materials silicon and platinum, the angular dependencies of elastic and inelastic scattering are investigated. We utilize energy filtering in two complementary microscopes, which are representative for the systems used for quantitative STEM, to form position-averaged diffraction patterns as well as atomically resolved 4D STEM data sets for different energy ranges. The resulting five-dimensional data are used to elucidate the distinct features in real and momentum space for different energy losses. We find different angular distributions for the elastic and inelastic scattering, resulting in an increased low-angle intensity ([Formula: see text] 10-40 mrad). The ratio of inelastic\/elastic scattering increases with rising sample thickness, while the general shape of the angular dependency is maintained. Moreover, the ratio increases with the distance to an atomic column in the low-angle regime. Since PE are usually neglected in image simulations, consequently the experimental intensity is underestimated at these angles, which especially affects bright field or low-angle annular dark field imaging. The high-angle regime, however, is unaffected. In addition, we find negligible impact of inelastic scattering on first-moment imaging in momentum-resolved STEM, which is important for STEM techniques to measure internal electric fields in functional nanostructures. To resolve the discrepancies between experiment and simulation, we present an adopted simulation scheme including PE. This study highlights the necessity to take into account PE to achieve quantitative agreement between simulation and experiment. Besides solving the fundamental question of missing physics in established simulations, this finally allows for the quantitative evaluation of low-angle scattering, which contains valuable information about the material investigated.","subset":"pubmed_abstract"} +{"meta":{"pmid":27493569,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2021-17":1,"2020-50":1,"2020-40":1,"2018-51":1,"2018-39":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2021-25":1,"2024-26":2,"2024-30":1}}},"text":"Loose powder detection and surface characterization in selective laser sintering via optical coherence tomography.\nDefects produced during selective laser sintering (SLS) are difficult to non-destructively detect after build completion without the use of X-ray-based methods. Overcoming this issue by assessing integrity on a layer-by-layer basis has become an area of significant interest for users of SLS apparatus. Optical coherence tomography (OCT) is used in this study to detect surface texture and sub-surface powder, which is un-melted\/insufficiently sintered, is known to be a common cause of poor part integrity and would prevent the use of SLS where applications dictate assurance of defect-free parts. To demonstrate the capability of the instrument and associated data-processing algorithms, samples were built with graduated porosities which were embedded in fully dense regions in order to simulate defective regions. Simulated in situ measurements were then correlated with the process parameters used to generate variable density regions. Using this method, it is possible to detect loose powder and differentiate between densities of \u00b15% at a sub-surface depth of approximately 300 \u03bcm. In order to demonstrate the value of OCT as a surface-profiling technique, surface texture datasets are compared with focus variation microscopy. Comparable results are achieved after a spatial bandwidth- matching procedure.","subset":"pubmed_abstract"} +{"meta":{"pmid":28756449,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Unplanned Returns to Hospital Care: A Linked Data Study.\nThe linkage of data across facilities and settings of care provides a holistic view of the patient journey through the healthcare system. This study, through data linkage, reviews alternative approaches to the measurement of unplanned returns to care in NSW public hospital emergency departments and admitted patient care settings. The study shows that existing measures of unplanned returns do not identify the true extent of these events and highlight the need to develop new approaches to measurement using the increasing availability of integrated patient information.","subset":"pubmed_abstract"} +{"meta":{"pmid":18213366,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Identification of novel pro-migratory, cancer-associated genes using quantitative, microscopy-based screening.\nCell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion.","subset":"pubmed_abstract"} +{"meta":{"pmid":27626808,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Blue-Emitting Arylalkynyl Naphthalene Derivatives via a Hexadehydro-Diels-Alder Cascade Reaction.\nWe describe here three alkynyl substituted naphthalenes that display promising luminescence characteristics. Each compound is easily and efficiently synthesized in three steps by capitalizing on the hexadehydro-Diels-Alder (HDDA) cycloisomerization reaction in which an intermediate benzyne is captured by tetraphenylcyclopentadienone, a classical trap for benzyne itself. These compounds luminesce in the deep blue when stimulated either optically (i.e., photoluminescence in both solution and solid films) or electrically [in a light-emitting diode (LED)]. The photophysical properties are relatively insensitive to the electronic nature of the substituents (H, OMe, CO2Me) that define these otherwise identical compounds. Overall, our observations suggest that the twisted nature of the five adjacent aryl groups serves to minimize the intermolecular interaction between core naphthalene units in different sample morphologies. These compounds represent promising leads for the identification of others of value as the emissive component of organic LEDs (OLEDs).","subset":"pubmed_abstract"} +{"meta":{"pmid":15466849,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Reliability of self-reported neighborhood characteristics.\nThe majority of studies examining the relation between neighborhood environments and health have used census-based indicators to characterize neighborhoods. These studies have shown that neighborhood socioeconomic characteristics are associated with a range of health outcomes. Establishing if these associations reflect causal relations requires testing hypotheses regarding how specific features of neighborhoods are related to specific health outcomes. However, there is little information on the reliability of neighborhood measures. The purpose of this study was to estimate the reliability of a questionnaire measuring various self-reported measures of the neighborhood environment of possible relevance to cardiovascular disease. The study consisted of a face-to-face and telephone interview administered twice to 48 participants over a 2-week period. The face-to-face and telephone portions of the interview lasted an average of 5 and 11 minutes, respectively. The questionnaire was piloted among a largely Latino and African American study sample recruited from a public hospital setting in New York City. Scales were used to assess six neighborhood domains: aesthetic quality, walking\/exercise environment, safety from crime, violence, access to healthy foods, and social cohesion. Cronbach's alpha's ranged from .77 to .94 for the scales corresponding to these domains, with test-retest correlations ranging from 0.78 to 0.91. In addition, neighborhood indices for presence of recreational facilities, quality of recreational facilities, neighborhood participation, and neighborhood problems were examined. Test-retest reliability measures for these indices ranged from 0.73 to 0.91. The results from this study suggested that self-reported neighborhood characteristics can be reliably measured.","subset":"pubmed_abstract"} +{"meta":{"pmid":24362380,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"The Teamwork Mini-Clinical Evaluation Exercise (T-MEX): a workplace-based assessment focusing on collaborative competencies in health care.\nTeamwork is an important and challenging area of learning during the transition from medical graduate to intern. This preliminary investigation examined the psychometric and logistic properties of the Teamwork Mini-Clinical Evaluation Exercise (T-MEX) for the workplace-based assessment of key competencies in working with health care teams. The authors designed the T-MEX for direct observation and assessment of six collaborative behaviors in seven clinical situations important for teamwork, feedback, and reflection. In 2010, they tested it on University of New South Wales senior medical students during their last six-week clinical term to investigate its overall utility, including validity and reliability. Assessors rated students in different situations on the extent to which they met expectations for interns for each collaborative behavior. Both assessors and students rated the tool's usefulness and feasibility. Assessment forms for 88 observed encounters were submitted by 25 students. The T-MEX was suited to a broad range of collaborative clinical practice situations, as evidenced by the encounter types and the behaviors assessed by health care team members. The internal structure of the behavior ratings indicated construct validity. A generalizability study found that eight encounters were adequate for high-stakes measurement purposes. The mean times for observation and feedback and the participants' perceptions suggested usefulness for feedback and feasibility in busy clinical settings. Findings suggest that the T-MEX has good utility for assessing trainee competence in working with health care teams. It fills a gap within the suite of existing tools for workplace-based assessment of professional attributes.","subset":"pubmed_abstract"} +{"meta":{"pmid":24349111,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Metarhizium anisopliae pathogenesis of mosquito larvae: a verdict of accidental death.\nMetarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host.","subset":"pubmed_abstract"} +{"meta":{"pmid":24176729,"dup_signals":{"dup_doc_count":37,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":2,"2022-49":3,"2022-40":1,"2022-27":3,"2021-21":1,"2021-04":2,"2020-45":2,"2020-40":2,"2020-24":1,"2019-18":1,"2019-09":1,"2018-34":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2024-18":3,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey.\nTo determine whether exposure to angiotensin-converting enzyme (ACE) inhibitors prior to the onset of scleroderma renal crisis (SRC) leads to worse outcomes of SRC. Prospective cohort study of incident SRC subjects. The exposure of interest was ACE inhibitors prior to the onset of SRC. The outcomes of interest were death or dialysis during the first year after the onset of SRC. A total of 87 subjects with incident SRC were identified and 1-year follow-up data were obtained in 75 (86%) subjects. Overall, 27 (36%) subjects died within the first year and an additional 19 (25%) remained on dialysis 1 year after the onset of SRC. In adjusted analyses, exposure to ACE inhibitors prior to the onset of SRC was associated with an increased risk of death (hazard ratio 2.42, 95% CI 1.02, 5.75, p < 0.05 in the primary analysis and 2.17, 95% CI 0.88, 5.33, p = 0.09 after post-hoc adjustment for pre-existing hypertension). Overall, the 1-year outcomes of SRC were poor. Prior exposure to ACE inhibitors was associated with an increased risk of death after the onset of SRC, although there was uncertainty around the magnitude of the risk and the possibility of residual confounding could not be ruled out. Further studies will be needed to confirm these findings.","subset":"pubmed_abstract"} +{"meta":{"pmid":28265884,"dup_signals":{"dup_doc_count":14}},"text":"D\u00e9bridement and Reconstruction Improve Postoperative Sagittal Alignment in Kyphotic Cervical Spinal Tuberculosis.\nCervical spinal tuberculosis is relatively common in some developing countries. It erodes vertebrae and discs, which sometimes results in cervical kyphosis and myelopathy. However, to our knowledge, no studies have evaluated improvements to patient-reported outcomes among patients who undergo surgical cervical sagittal realignment after kyphotic cervical spinal tuberculosis has been treated by d\u00e9bridement and reconstruction. (1) Can a spine with kyphotic cervical spinal tuberculosis be returned to normal alignment and fused successfully? (2) Will patient-reported outcomes be improved with this intervention? (3) Are patient-reported outcomes correlated with realignment? Forty-six patients with kyphotic cervical spinal tuberculosis were evaluated in this retrospective study. We generally performed surgery on patients with this condition when patients with cervical spinal tuberculosis presented with cervical kyphosis with or without neurologic deficits. Patients who did not meet these criteria were treated with other surgical procedures during the study period. Study patients were evaluated with cervical imaging, patient-reported outcomes questionnaires (Neck Disability Index [NDI], and the Japanese Orthopaedic Association [JOA] score), and physical examinations. Scores were collected by fellows preoperatively and at followup. No patient died during the followup. The mean followup was 26.8 months (range, 20-35 months). Preoperative and 2-year followup radiologic parameters were measured, including C0-2 Cobb angle, C2-7 Cobb angle, C2-7 sagittal vertical axis, center of gravity (CG) to C7 sagittal vertical axis (CG-C7 sagittal vertical axis), thoracic inlet angle, T1 slope, and neck tilt. The correlations between cervical alignment and the NDI and JOA score were analyzed. Factors correlated with the NDI and JOA score improvements were identified by multiple stepwise regression analysis. CT was used to assess bone fusion after surgery. All 46 patients showed bone fusion on CT scans. The preoperative C0-2 Cobb angle improved after surgery (mean difference, 5.0\u00b0; 95% CI, 2.3\u00b0-7.7\u00b0; p = 0.0068), as did C2-7 Cobb angle (mean difference, -33\u00b0; 95% CI, -35\u00b0 to -31\u00b0; p = 0.0074), C2-7 sagittal vertical axis (mean difference, -28 mm; 95% CI, -30 mm to -26 mm; p = 0.0036), CG-7 sagittal vertical axis (mean difference, -26 mm; 95% CI, -28 mm to -24 mm; p = 0.0049), T1 slope (mean difference, 6.0\u00b0; 95% CI, 3.7\u00b0-8.3\u00b0; p = 0.0053) and the thoracic inlet angle (mean difference, 8.0\u00b0; 95% CI, 3.7\u00b0-12\u00b0; p = 0.0072). With the numbers available, the neck tilt angle did not improve (mean difference, -0.2\u00b0; 95% CI, -1.0\u00b0 to 0.6\u00b0; p = 0.079). The preoperative NDI of 34 \u00b1 5.1 decreased to 17 \u00b1 4.6 (p = 0.0096) at followup. Improvements in NDI were correlated with the magnitude of correction of the cervical deformities, including C0-2 Cobb angle (r = -0.357, p = 0.007), C2-7 Cobb angle (r = 0.410, p = 0.002), T1 slope (r = -0.366, p = 0.006, thoracic inlet angle (r = -0.376, p = 0.005), C2-7 sagittal vertical axis (r = 0.450, p = 0.001), and CG-C7 sagittal vertical axis (r = 0.361, p = 0.007). The JOA score improved to 13 \u00b1 2.6 from 7.2 \u00b1 1.9, which did not correlate with postoperative cervical realignment. After controlling for potential confounding variables like Cobb angles and T1 slope, we found C2-7 sagittal vertical axis was the most influential factor correlated with NDI improvement (r = 0.450, p = 0.002). When treating kyphotic cervical spinal tuberculosis by d\u00e9bridement, decompression, and reconstruction, more attention should be drawn to realigning the cervical spine, in particular to restoring the C2-7 sagittal vertical axis. However, how best to restore the C2-7 sagittal vertical axis and cervical alignment in a kyphotic cervical spine needs further study. Level III, therapeutic study.","subset":"pubmed_abstract"} +{"meta":{"pmid":34259891,"dup_signals":{"dup_doc_count":32,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":2,"2022-49":2,"2022-27":2,"2022-21":2,"2022-05":1,"2021-49":2,"2021-43":1,"2021-39":2,"2021-31":2,"2024-30":6,"2024-26":2,"2024-18":1,"2024-10":1}}},"text":"Metagenomics: a path to understanding the gut microbiome.\nThe gut microbiome is a major determinant of host health, yet it is only in the last 2 decades that the advent of next-generation sequencing has enabled it to be studied at a genomic level. Shotgun sequencing is beginning to provide insight into the prokaryotic as well as eukaryotic and viral components of the gut community, revealing not just their taxonomy, but also the functions encoded by their collective metagenome. This revolution in understanding is being driven by continued development of sequencing technologies and in consequence necessitates reciprocal development of computational approaches that can adapt to the evolving nature of sequence datasets. In this review, we provide an overview of current bioinformatic strategies for handling metagenomic sequence data and discuss their strengths and limitations. We then go on to discuss key technological developments that have the potential to once again revolutionise the way we are able to view and hence understand the microbiome.","subset":"pubmed_abstract"} +{"meta":{"pmid":22712007,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits.\nDeep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule\/ventral striatum (VC\/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and\/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.","subset":"pubmed_abstract"} +{"meta":{"pmid":10535972,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Evidence for the recent horizontal transfer of long terminal repeat retrotransposon.\nThe evolutionary dynamics existing between transposable elements (TEs) and their host genomes have been likened to an \"arms race.\" The selfish drive of TEs to replicate, in turn, elicits the evolution of host-mediated regulatory mechanisms aimed at repressing transpositional activity. It has been postulated that horizontal (cross-species) transfer may be one effective strategy by which TEs and other selfish genes can escape host-mediated silencing mechanisms over evolutionary time; however, to date, the most definitive evidence that TEs horizontally transfer between species has been limited to class II or DNA-type elements. Evidence that the more numerous and widely distributed retroelements may also be horizontally transferred between species has been more ambiguous. In this paper, we report definitive evidence for a recent horizontal transfer of the copia long terminal repeat retrotransposon between Drosophila melanogaster and Drosophila willistoni.","subset":"pubmed_abstract"} +{"meta":{"pmid":27134311,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":15}}},"text":"A Robust Cross-Linking Strategy for Block Copolymer Worms Prepared via Polymerization-Induced Self-Assembly.\nA poly(glycerol monomethacrylate) (PGMA) chain transfer agent is chain-extended by reversible addition-fragmentation chain transfer (RAFT) statistical copolymerization of 2-hydroxypropyl methacrylate (HPMA) with glycidyl methacrylate (GlyMA) in concentrated aqueous solution via polymerization-induced self-assembly (PISA). A series of five free-standing worm gels is prepared by fixing the overall degree of polymerization of the core-forming block at 144 while varying its GlyMA content from 0 to 20 mol %. 1H NMR kinetics indicated that GlyMA is consumed much faster than HPMA, producing a GlyMA-rich sequence close to the PGMA stabilizer block. Temperature-dependent oscillatory rheological studies indicate that increasing the GlyMA content leads to progressively less thermoresponsive worm gels, with no degelation on cooling being observed for worms containing 20 mol % GlyMA. The epoxy groups in the GlyMA residues can be ring-opened using 3-aminopropyltriethoxysilane (APTES) in order to prepare core cross-linked worms via hydrolysis-condensation with the siloxane groups and\/or hydroxyl groups on the HPMA residues. Perhaps surprisingly, 1H NMR analysis indicates that the epoxy-amine reaction and the intermolecular cross-linking occur on similar time scales. Cross-linking leads to stiffer worm gels that do not undergo degelation upon cooling. Dynamic light scattering studies and TEM analyses conducted on linear worms exposed to either methanol (a good solvent for both blocks) or anionic surfactant result in immediate worm dissociation. In contrast, cross-linked worms remain intact under such conditions, provided that the worm cores comprise at least 10 mol % GlyMA.","subset":"pubmed_abstract"} +{"meta":{"pmid":11950116,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2017-47":1,"2017-39":1,"2017-22":1,"2017-17":1,"2019-26":1}}},"text":"Clinical outcome of invasive pneumococcal infection in children: a 10-year retrospective analysis.\nA retrospective study was conducted on 72 children admitted to a medical center in Taiwan due to invasive pneumococcal infections diagnosed between January 1990 and April 2000. Of these patients, 28 had meningitis and 44 had other invasive diseases. Forty-one (56.9%) strains of Streptococcus pneumoniae showed reduced susceptibility to penicillin by the oxacillin disc diffusion method. The total mortality was 20.8%, 32.1% for meningitis, and 13.6% for other invasive diseases. Ten (52.6%) of the patients survived from meningitis had long-term sequelae. Statistical analysis showed that initial presentation of coma, shock, respiratory distress requiring mechanical ventilation, and leukopenia (leukocyte <4,000 \/mm3) were associated with mortality of invasive pneumococcal infections. Low cerebrospinal fluid leukocyte count (<50 \/mm3) and high cerebrospinal fluid protein level (> or = 660 mg\/dL) were also associated with mortality of meningitis. The presence of underlying diseases and high alanine aminotransferase level (> or = 100 U\/L) were associated with fatal non-meningitic invasive diseases. Patients with shock and high alanine aminotransferase level but without high C-reactive protein level (> or = 20 mg\/dL) were associated with rapidly fatal outcome. The outcome of invasive pneumococcal diseases was not associated with penicillin susceptibility.","subset":"pubmed_abstract"} +{"meta":{"pmid":24114076,"dup_signals":{"dup_doc_count":13,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":2,"2017-04":1,"2016-50":1,"2017-43":1}}},"text":"Emergence of the white-collar sign after coil embolization of cerebral aneurysms.\nThe white-collar sign (WCS) is represented by the formation of neointimal tissue at the level of the aneurysm neck as the successful outcome on follow-up angiography after coil embolization. WCS has been reported only in aneurysms treated with Matrix\u00ae coils. This is the first study to report WCS emergence in aneurysms treated with bare platinum coils, and potential factors associated with WCS emergence were evaluated. Total 130 unruptured (female: male ratio, 100: 30; mean age, 60 years) cerebral aneurysms were treated with coil embolization. Embolization status was assessed immediately and 1 year after treatment, and emergence of WCS in follow-up angiography was assessed. We evaluated the association between WCS emergence and aneurysm location, dome diameter, neck diameter, dome-neck ratio, and type of coil used (bare platinum or bioactive). WCS appeared in nine aneurysms (6.9%), of which six were treated only with bare platinum coils. Neck diameter was significantly smaller in the WCS-positive group than in the WCS-negative group. The proportion of aneurysms treated with bioactive coils was not significantly different between the groups. Immediate embolization status in the WCS-positive group tended to be slightly better than that in the WCS-negative group. No aneurysmal morphological characteristics other than small neck diameter were associated with WCS emergence. WCS is not specific to bioactive coil usage. Small neck diameter was significantly associated with WCS emergence in our series. Further investigations to clarify the predictors of WCS will contribute to progress of aneurysmal embolization.","subset":"pubmed_abstract"} +{"meta":{"pmid":8246250,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Evaluation of the polymerase chain reaction for detecting the urease C gene of Helicobacter pylori in gastric biopsy samples and dental plaque.\nA polymerase chain reaction (PCR) assay with oligonucleotide primers homologous to a portion of the urease C gene of Helicobacter pylori was evaluated for specificity with pure DNA and biopsy material. The assay was used to test for the presence of the organism in dental plaque. The species specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from H. cinaedi, H. felis, H. fennelliae, H. mustelae and H. nemestrinae. Sixty-two gastric biopsy samples collected from 14 patients (antrum, body and duodenal sites) were cultured and PCR was performed on the samples after culture. Primer sites were conserved in genomically diverse strains. Samples prepared by single-step heat lysis of bacterial cells and biopsy material did not inhibit PCR. The overall specificity was 96% irrespective of genotype. H. pylori was not cultured from dental plaque (15 patients), neither was H. pylori DNA detected by PCR in either urea breath test-positive or -negative individuals. The results showed that primer pair sequences within the urease C gene are conserved in most strains and provide an accurate basis for detecting H. pylori. As the PCR assay was not inhibited and did not yield false positive results with crude extracts from organisms or in the presence of biopsy material, its value as a diagnostic test was confirmed.","subset":"pubmed_abstract"} +{"meta":{"pmid":1945608,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Long-bone radiographic abnormalities as a sign of active congenital syphilis in asymptomatic newborns.\nMetaphyseal abnormalities are present in greater than 90% of infants with symptomatic congenital syphilis. The incidence of these lesions in asymptomatic newborns in the present epidemic is not known. To determine the incidence of bone lesions at birth in asymptomatic congenital syphilis, long-bone films were obtained for all babies born during a 9-month period with a positive perinatal serology. Of 2544 newborns, 61 had a positive maternal serology and 40 also had a positive cord serology. Two symptomatic babies had abnormal radiographs and 12 of 59 asymptomatic newborns had metaphyseal changes consistent with congenital syphilis. It is concluded that long-bone radiographs are abnormal in approximately 20% of asymptomatic newborns with positive perinatal treponemal serology. With the increasing incidence of congenital syphilis, radiologic studies should be included in the assessment of all newborns with a positive serology. Indeed, those patients with any sign of active disease should be carefully followed because even treated infants remain at some risk for developing the late sequelae of congenital syphilis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24194825,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Best of both worlds: simultaneous high-light and shade-tolerance adaptations within individual leaves of the living stone Lithops aucampiae.\n\"Living stones\" (Lithops spp.) display some of the most extreme morphological and physiological adaptations in the plant kingdom to tolerate the xeric environments in which they grow. The physiological mechanisms that optimise the photosynthetic processes of Lithops spp. while minimising transpirational water loss in both above- and below-ground tissues remain unclear. Our experiments have shown unique simultaneous high-light and shade-tolerant adaptations within individual leaves of Lithops aucampiae. Leaf windows on the upper surfaces of the plant allow sunlight to penetrate to photosynthetic tissues within while sunlight-blocking flavonoid accumulation limits incoming solar radiation and aids screening of harmful UV radiation. Increased concentration of chlorophyll a and greater chlorophyll a:b in above-ground regions of leaves enable maximum photosynthetic use of incoming light, while inverted conical epidermal cells, increased chlorophyll b, and reduced chlorophyll a:b ensure maximum absorption and use of low light levels within the below-ground region of the leaf. High NPQ capacity affords physiological flexibility under variable natural light conditions. Our findings demonstrate unprecedented physiological flexibility in a xerophyte and further our understanding of plant responses and adaptations to extreme environments.","subset":"pubmed_abstract"} +{"meta":{"pmid":9036320,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure.\nNeonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure. Infants born after a gestation of > or =34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas. The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The nitric oxide group had significantly greater improvement in PaO2 (increase, 58.2+\/-85.2 mm Hg, vs. 9.7+\/-51.7 mm Hg in the controls; P<0.001) and in the oxygenation index (a decrease of 14.1+\/-21.1, vs. an increase of 0.8+\/-21.1 in the controls; P<0.001). The study gas was not discontinued in any infant because of toxicity. Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality in critically ill infants with hypoxic respiratory failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":26334633,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Enhanced Expression of Integrin \u03b1v\u03b23 Induced by TGF-\u03b2 Is Required for the Enhancing Effect of Fibroblast Growth Factor 1 (FGF1) in TGF-\u03b2-Induced Epithelial-Mesenchymal Transition (EMT) in Mammary Epithelial Cells.\nEpithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis, and is regulated by growth factors such as transforming growth factor \u03b2 (TGF-\u03b2) and fibroblast growth factors (FGF) secreted from the stromal and tumor cells. However, the role of growth factors in EMT has not been fully established. Several integrins are upregulated by TGF-\u03b21 during EMT. Integrins are involved in growth factor signaling through integrin-growth factor receptor crosstalk. We previously reported that FGF1 directly binds to integrin \u03b1v\u03b23 and the interaction was required for FGF1 functions such as cell proliferation and migration. We studied the role of \u03b1v\u03b23 induced by TGF-\u03b2 on TGF-\u03b2-induced EMT. Here, we describe that FGF1 augmented EMT induced by TGF-\u03b21 in MCF10A and MCF12A mammary epithelial cells. TGF-\u03b21 markedly amplified integrin \u03b1v\u03b23 and FGFR1 (but not FGFR2). We studied if the enhancing effect of FGF1 on TGF-\u03b21-induced EMT requires enhanced levels of both integrin \u03b1v\u03b23 expression and FGFR1. Knockdown of \u03b23 suppressed the enhancement by FGF1 of TGF-\u03b21-induced EMT in MCF10A cells. Antagonists to FGFR suppressed the enhancing effect of FGF1 on EMT. Integrin-binding defective FGF1 mutant did not augment TGF-\u03b21-induced EMT in MCF10A cells. These findings suggest that enhanced integrin \u03b1v\u03b23 expression in addition to enhanced FGFR1 expression is critical for FGF1 to augment TGF-\u03b21-induced EMT in mammary epithelial cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":24576608,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-27":1,"2020-34":2,"2020-10":1,"2018-47":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2023-23":1,"2024-10":1,"2024-22":1}}},"text":"Development of surface imprinted core-shell nanoparticles and their application in a solid-phase dispersion extraction matrix for methyl parathion.\nApplying molecular imprinting techniques to the surface of functionalized SiO2 allows the preparation of molecularly imprinted polymers (MIPs) with accessible, high affinity and surface exposed binding sites. This paper demonstrates a new strategy for producing such hybrid organic-inorganic surface imprinted silica nanoparticles for specific recognition of methyl parathion. The technique provides surface grafting imprinting in chloroform using amino modified silica nanoparticles as supports, acrylamide as the functional monomer, \u03b3-methacryloxypropyl trimethoxy silane as the grafting agent, and methyl parathion as a template. The amino propyl functional monomer layer directs the selective occurrence of imprinting polymerization at the silica surface through copolymerization of grafting agents with functional monomers, but also acts as an assistive monomer to drive the template into the formed polymer shells to create effective recognition sites. The resulting MIPs-SiO2 nanoparticles display three-dimensional core-shell architectures and large surface areas. The molecularly imprinted shell provides recognition sites for methyl parathion, with the materials exhibiting excellent performance for selecting the template. Using MIPs-SiO2 nanoparticles as a matrix of solid-phase dispersion extraction sorbents, trace amounts of methyl parathion are selectivity extracted from pear and green vegetable samples while simultaneously eliminating matrix interferences, attaining recoveries of 84.7-94.4% for the samples.","subset":"pubmed_abstract"} +{"meta":{"pmid":22690898,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-10":2,"2024-30":1,"unknown":9}}},"text":"Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys.\nThyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)\/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg\/dL. TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.","subset":"pubmed_abstract"} +{"meta":{"pmid":32801657,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Characteristics of \"Hard-to-Use\" Press-Through-Package Sheets: An Analysis of Information Collected by Marketing Specialists of a Japanese Medical Wholesaler.\nPress-through-package (PTP) sheets are common forms of packaging for medicines in Japan. However, patients and\/or pharmacists have reported difficulty in extracting tablets or capsules from some PTP sheets. We used postmarketing surveillance data to identify the characteristics of PTP sheets that patients and pharmacists feel are \"hard to use\". Marketing specialists of Toho Pharmaceutical Co., Ltd. canvassed patients and medical workers during November 2014-April 2016. Among 1,129 anonymous reports of products being \"hard to use\", we identified 39 products with 5 or more reports (Problem group). We compared the sizes of the drugs and PTP pockets, the size ratio, the material used for the front of PTPs, the shape of the pockets, the thickness of the pocket wall, and the force needed to release the drug from the PTP (press-out force: POF) in this Problem group with those in a Control group of 97 problem-free products. Logistic regression analyses revealed that a bigger pocket, a smaller drug size and a smaller drug-pocket size ratio increase the risk of being \"hard to use\". Regarding the material, aluminum, PCTFE and PE increase the risk, while PP and PVC decrease the risk. Other factors had no significant influence. Pockets in PTP sheets should be designed so as to minimize the gap between the drug and the pocket, and PP or PVC should be used as the front material instead of aluminum, PCTFE or PE. Our results suggest that marketing specialists can play effective roles in postmarketing surveillance.","subset":"pubmed_abstract"} +{"meta":{"pmid":24993530,"dup_signals":{"dup_doc_count":12}},"text":"Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency.\nLysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Sebelipase alfa (1mg\/kg or 3mg\/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. 216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184).","subset":"pubmed_abstract"} +{"meta":{"pmid":16371578,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Mitral regurgitation: quantification with 16-detector row CT--initial experience.\nTo prospectively determine if retrospectively electrocardiographic (ECG)-gated multi-detector row computed tomography (CT) with a 16-detector row CT scanner can depict mitral regurgitation and enable quantification of the severity of the disease. The study had institutional review board approval, and patients gave informed consent. Nineteen patients with mitral regurgitation (10 men, nine women; mean age, 66 years +\/- 9 [standard deviation]; range, 41-83 years) and 25 patients without mitral regurgitation (14 men, 11 women; mean age, 68 years +\/- 9; range, 43-83 years) as determined with transesophageal color Doppler echocardiography and ventriculography underwent retrospectively ECG-gated 16-detector row CT. Twenty CT data sets covering the entire mitral valve apparatus were reconstructed in 5% steps of the R-R interval for each patient, and data analysis was performed with four-dimensional software. Using planimetry, two readers measured in consensus the area of the regurgitant orifice during systole. These measurements were compared with semiquantitative data from transesophageal echocardiography and ventriculography by using Spearman rank order correlation coefficients. In the 25 patients without mitral regurgitation, no regurgitant orifice during systole could be detected with multi-detector row CT. In the 19 patients with mitral regurgitation, a regurgitant orifice could be visualized in all cases. The mean regurgitant orifice area at CT-45 mm(2) +\/- 34 (range, 10-148 mm(2))-correlated significantly with the results at transesophageal echocardiography (r = 0.807, P < .001) and ventriculography (r = 0.922, P < .001). Planimetric measurements of the regurgitant orifice area at retrospectively ECG-gated 16-detector row CT enable quantification of mitral regurgitation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21533241,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2019-35":1,"2019-18":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2021-04":1}}},"text":"Shift work in nurses: contribution of phenotypes and genotypes to adaptation.\nDaily cycles of sleep\/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular\/metabolic\/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work. Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses. Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (\u223c25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol\/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work). Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and\/or irregularly between different schedules of the light-dark cycle and social\/workplace time. This study of shift work nurses illustrates how an environmental \"stress\" to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy.","subset":"pubmed_abstract"} +{"meta":{"pmid":35035243,"dup_signals":{"dup_doc_count":21,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-40":2,"2023-06":1,"2022-49":2,"2022-21":2,"2021-39":4,"2021-31":2,"2021-25":1,"2023-50":1,"2024-26":2,"2024-18":1,"2024-10":1}}},"text":"The effects of Korean Red Ginseng-derived components on oligodendrocyte lineage cells: Distinct facilitatory roles of the non-saponin and saponin fractions, and Rb1, in proliferation, differentiation and myelination.\nAbnormalities of myelin, which increases the efficiency of action potential conduction, are found in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy against some of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, we examined the effects of KRG-derived components on development and protection of OL-lineage cells. Primary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. The protective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adult male mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. The non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Both processes were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, the saponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponin significantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested, Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelin formation in adult mouse brain. All KRG components prevented OPC deaths under oxidative stress. While non-saponin promoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size and significantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 for myelin-related disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":28764185,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Kikuchi-Fujimoto Disease Masquerading as Acute Appendicitis.\nKikuchi-Fujimoto Disease (KFD) is a self-limiting necrotizing lymphadenitis that usually presents with fever and cervical lymphadenopathy. Recognition of this condition is crucial, because it can be mistaken for tuberculosis, lymphoma and connective tissue disorders. When present at an unusual location the diagnosis can be challenging. We present an unusual case of Kikuchi-Fujimoto disease involving mesenteric lymph node masquerading as acute appendicitis along with its differential diagnosis. A 30-year-old female presented with complaints of acute abdominal pain, vomiting and fever. Physical examination revealed rebound tenderness in the right iliac fossa. The abdominal sonography was suspicious of acute appendicitis. The patient underwent appendectomy with excision of an enlarged mesenteric lymph node. On histopathology mesenteric node showed features of KFD which was confirmed on immunohistochemistry. Appendix was unremarkable. Although rare KFD should be added to the differential diagnosis of acute appendicitis in patients with enlarged mesenteric lymph nodes, Awareness of this disorder helps to prevent misdiagnosis and inappropriate treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":26200194,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"Ginger (Zingiber officinale) as an Analgesic and Ergogenic Aid in Sport: A Systemic Review.\nGinger is a popular spice used to treat a variety of maladies, including pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used by athletes to manage and prevent pain; unfortunately, NSAIDs contribute to substantial adverse effects, including gastrointestinal (GI) dysfunction, exercise-induced bronchoconstriction, hyponatremia, impairment of connective tissue remodeling, endurance competition withdrawal, and cardiovascular disease. Ginger, however, may act as a promoter of GI integrity and as a bronchodilator. Given these potentially positive effects of ginger, a systematic review of randomized trials was performed to assess the evidence for ginger as an analgesic and ergogenic aid for exercise training and sport. Among 7 studies examining ginger as an analgesic, the evidence indicates that roughly 2 g\u00b7d(-1) of ginger may modestly reduce muscle pain stemming from eccentric resistance exercise and prolonged running, particularly if taken for a minimum of 5 days. Among 9 studies examining ginger as an ergogenic aid, no discernable effects on body composition, metabolic rate, oxygen consumption, isometric force generation, or perceived exertion were observed. Limited data suggest that ginger may accelerate recovery of maximal strength after eccentric resistance exercise and reduce the inflammatory response to cardiorespiratory exercise. Major limitations to the research include the use of untrained individuals, insufficient reporting on adverse events, and no direct comparisons with NSAID ingestion. While ginger taken over 1-2 weeks may reduce pain from eccentric resistance exercise and prolonged running, more research is needed to evaluate its safety and efficacy as an analgesic for a wide range of athletic endeavors.","subset":"pubmed_abstract"} +{"meta":{"pmid":28085961,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review.\nHIV infection is associated with an increased risk of cardiovascular disease (CVD). Chronic low-grade immune activation is likely one of the driving mechanisms. This systematic review provides an overview of the evidence addressing the relation between immune markers and surrogate markers of CVD (except CIMT) in HIV infection. A systematic search was performed in PubMed, Embase and Cochrane Library identifying all articles from 1996 to April 2015. It addressed the relation between immune markers and surrogate markers of CVD (except Carotid Intima-media Thickness) in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis focused on immune markers that were assessed most frequently. The review was conducted according to the PRISMA guideline and performed as part of an overarching review registered with PROSPERO (CRD42014010516). Twenty-nine articles were selected, describing 34 immune markers and nine different CVD surrogate outcomes: coronary calcium score (13 times) and flow-mediated dilation (10 times) were used most frequently. Twenty-seven studies had a cross-sectional design. CRP, IL-6 and sVCAM-1 were assessed most frequently. None of the immune markers were clearly associated with any of the surrogate CVD outcomes. No effect estimate could be calculated due to marked heterogeneity in study populations, immune markers, outcomes and statistical approaches. This review could not identify a clear association between any of the immune markers and surrogate CVD outcomes. This may reflect a true lack of association, or may be explained by heterogeneity across studies and lack of follow-up data. Future research should focus on longitudinal studies measuring a select set of immune markers and surrogate CVD outcomes awaiting the primary outcome of clinical cardiovascular events.","subset":"pubmed_abstract"} +{"meta":{"pmid":11869449,"dup_signals":{"dup_doc_count":23,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-14":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Career destinations and views in 1998 of the doctors who qualified in the United Kingdom in 1993.\nTo report career destinations and views in 1998 of doctors who qualified in the United Kingdom (UK) in 1993. Postal questionnaire survey. This study took place in the United Kingdom. All doctors who qualified in the UK in 1993. The percentage of doctors in each branch of medicine five years after qualification, and their views on their training and career opportunities. The NHS and universities in the UK employed 88% of respondents (men 90%, women 86%). UK general practice employed 24% of respondents (men 19%, women 28%). There were significant differences (P < 0.01) between the percentages of men and women working in the surgical specialties (men 28%, women 10%), paediatrics (men 8%, women 15%) and obstetrics and gynaecology (men 5%, women 10%). Respondents not in paid employment comprised 1.4% of men and 6.6% of women. 45% of respondents agreed that their postgraduate training was of a high standard, with 26% disagreeing and 29% unsure. 47% of specialist registrars felt their training was too short and 78% were concerned about the availability of consultant posts on completion. Although loss of doctors from the British workforce through emigration or unemployment is not increasing, our findings confirm a substantial shift away from careers in general practice. The number of home-trained GPs from this generation of doctors will be inadequate to meet service needs. GPs and hospital specialist doctors expressed concerns about quality of training, lack of careers advice, the shortness of specialist registrar training and availability of consultant posts on completion of training.","subset":"pubmed_abstract"} +{"meta":{"pmid":12688589,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":1,"2017-13":1,"unknown":8}}},"text":"Correlation of NK cell activation and inhibition markers with NK cytoxicity among women experiencing immunologic implantation failure after in vitro fertilization and embryo transfer.\nThe pivotal event in determining successful from unsuccessful cycles after in vitro fertilization is implantation. The purpose of this study was to compare the percentage of circulating NK cells expressing activation and inhibition markers between infertile and fertile control women and to determine the correlation between these markers and those of the NK cytotoxicity activation assay. Lastly, we wish to determine the ability of each of these markers to predict pregnancy outcome after IVF\/ET (in vitro fertilization\/embryo transfer). Blood samples from 22 infertile women undergoing IVF\/ET during the November 2001 cycle were drawn on cycle Day 9 and analyzed for expression of CD69+, HLA-DR, CD161+, CD94+, and CD158a+ as well as NK cytotoxicity using immunofluorescent labeling and flow cytometry. Results were compared with those from 26 fertile control women and correlated to pregnancy outcome that of cycle. Infertile women had significantly higher expression of NK cell activation markers of CD69+ and CD161+ than fertile women. NK cytotoxicity correlated inversely with expression of NK cells bearing the inhibition marker of CD94+. None of the successfully pregnant women of that cycle had elevated levels of NK cytotoxicity whereas 50% of those experiencing a chemical pregnancy loss and those not becoming pregnant had elevated levels of NK cytotoxicity. Immunologic markers can identify mechanisms involved in implantation failure. Activation markers of CD69+ and CD161+ expressed on NK cells as well as NK cytotoxicity can be added to the previously reported risk factors for immunologic implantation failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":18175773,"dup_signals":{"dup_doc_count":75,"dup_dump_count":45,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-14":2,"2023-06":1,"2022-49":2,"2022-40":1,"2022-33":2,"2022-27":3,"2022-21":2,"2022-05":1,"2021-43":2,"2021-39":1,"2021-31":2,"2021-25":1,"2021-21":2,"2021-17":3,"2021-04":3,"2020-45":2,"2020-40":3,"2019-13":2,"2018-51":2,"2018-43":2,"2018-34":2,"2018-26":2,"2018-17":2,"2018-09":1,"2017-51":2,"2017-43":2,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2023-50":1,"2024-30":2,"2024-22":1,"2024-18":2,"2024-10":2,"2017-13":1}}},"text":"The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure.\nTo determine the cardiovascular benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-2.2 years after closure of the lipid-lowering arm of the trial (ASCOT-LLA). The Blood Pressure Lowering Arm of the ASCOT trial (ASCOT-BPLA) compared two different antihypertensive treatment strategies on cardiovascular outcomes. ASCOT-LLA was a double-blind placebo-controlled trial of atorvastatin in those enrolled into ASCOT-BPLA with total cholesterol concentrations at baseline of < or =6.5 mmol\/L. A total of 19 342 hypertensive patients were enrolled in ASCOT-BPLA and 10 305 were further assigned either atorvastatin, 10 mg, or placebo. ASCOT-LLA was stopped prematurely after a median 3.3 years follow-up because of substantial cardiovascular benefits in those assigned atorvastatin. Trial physicians were invited to offer atorvastatin to all ASCOT-LLA patients until the end of ASCOT-BPLA. The primary outcome of ASCOT-LLA was combined fatal coronary heart disease (CHD) or non-fatal myocardial infarction. Secondary outcomes included all coronary events, all cardiovascular events and procedures, fatal and non-fatal stroke, cardiovascular mortality, all cause mortality, development of chronic stable angina, heart failure, and peripheral arterial disease. By the end of ASCOT-LLA, there was a 36% relative risk reduction in primary events (n = 254) in favour of atorvastatin [hazard ratio (HR) 0.64, 95% CI: 0.50-0.83, P = 0.0005]. At the end of ASCOT-BPLA, 2.2 years later, despite extensive crossovers from and to statin usage, the relative risk reduction in primary events (n = 412) among those originally assigned atorvastatin remained at 36% (HR 0.64, 95% CI: 0.53-0.78, P = 0.0001). For almost all other endpoints, risk reductions also remained essentially unchanged and in the case of all cause mortality, the risk reduction of 15% now achieved borderline statistical significance (P = 0.02). Carry-over benefits from those originally assigned atorvastatin but no longer taking the drug may account for unchanged relative risk reductions in most cardiovascular endpoints observed 2 years after ASCOT-LLA closed.","subset":"pubmed_abstract"} +{"meta":{"pmid":12717631,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":1,"2013-20":2,"unknown":4}}},"text":"Serotyping of Toxoplasma gondii infections in humans using synthetic peptides.\nTo determine whether the characteristics of disease due to Toxoplasma gondii (toxoplasmosis) are dependent on the infecting strain, we have developed an enzyme-linked immunosorbent assay for typing strains that uses infection serum reacted against polymorphic peptides derived from Toxoplasma antigens SAG2A, GRA3, GRA6, and GRA7. Pilot studies with infected mice established the validity of the approach, which was then tested with human serum. In 8 patients who had Sabin-Feldman dye test titers >64 and for whom the infecting strain type was known, the peptides correctly distinguished type II from non-type II infections. ELISA analysis of a second group of 10 infected pregnant women from whom the parasite strain had not been isolated gave a clear prediction of the strain type causing infection. This method should allow statistically significant data to be obtained about whether different strain types cause disease with different characteristics.","subset":"pubmed_abstract"} +{"meta":{"pmid":28866620,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":12}}},"text":"Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma.\nHippo signalling is a recently identified major oncosuppressive pathway that plays critical roles in inhibiting hepatocyte proliferation, survival and hepatocellular carcinoma (HCC) formation. Hippo kinase (Mst1 and Mst2) inhibits HCC proliferation by suppressing Yap\/Taz transcription activities. As human HCC is mainly driven by chronic liver inflammation, it is not clear whether Hippo signalling inhibits HCC by shaping its inflammatory microenvironment. We have established a genetic HCC model by deleting Mst1 and Mst2 in hepatocytes. Functions of inflammatory responses in this model were characterised by molecular, cellular and FACS analysis, immunohistochemistry and genetic deletion of monocyte chemoattractant protein-1 (Mcp1) or Yap. Human HCC databases and human HCC samples were analysed by immunohistochemistry. Genetic deletion of Mst1 and Mst2 in hepatocytes (DKO) led to HCC development, highly upregulated Mcp1 expression and massive infiltration of macrophages with mixed M1 and M2 phenotypes. Macrophage ablation or deletion of Mcp1 in DKO mice markedly reduced hepatic inflammation and HCC development. Moreover, Yap removal abolished induction of Mcp1 expression and restored normal liver growth in the Mst1\/Mst2 DKO mice. Finally, we showed that MCP1 is a direct transcription target of YAP in hepatocytes and identified a strong gene expression correlation between YAP targets and MCP-1 in human HCCs. Hippo signalling in hepatocytes maintains normal liver growth by suppressing macrophage infiltration during protumoural microenvironment formation through the inhibition of Yap-dependent Mcp1 expression, providing new targets and strategies to treat HCCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":22275080,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":2,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2018-22":1,"2017-13":1}}},"text":"Refocusing on nature: holistic assessment of ecosystem services.\nThe benefits people obtain from ecosystems vary from direct benefits that are easily monetized (e.g., timber) to indirect benefits that are not easily monetized (e.g., maintenance of water quality). Commonly, there is wide variation among individuals in the values placed on ecosystem benefits or services. The lack of consensus both in identifying ecosystem services and in valuing them with respect to other services poses a great challenge to those charged with evaluating changes in the provision of ecosystem service after, for example, a natural disaster. Natural resource economics provides some tools, but economics alone will not ensure a balanced, holistic assessment. An inherent complexity in valuing services is often associated with the interrelationships between services and the background and expertise of those leading the assessment. We argue that a holistic evaluation of ecosystems founded on solid expertise in ecosystem dynamics is essential for the accurate assessment of ecosystem services. A reductionist approach to ecosystem service valuation often fails to capture ecological dynamics that are vital to the functioning and ultimate provision of services. In this article, we present case studies of ecosystem services valuation for forest fires, dam removal, and chemical contamination of sediment to explore the complexity of ecosystem service valuation. Additionally, we offer assessment strategies for recognizing the importance of holistic assessment of ecosystem services.","subset":"pubmed_abstract"} +{"meta":{"pmid":24979015,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"High-efficiency dual-absorption InGaAs\/InP photodetector incorporating GaAs\/AlGaAs Bragg reflectors.\nA reflection-enhanced dual-absorption InP-PIN\/GaAs-DBR photodetector was fabricated and characterized. The photodetector is monolithically integrated using a heteroepitaxy growth of an InGaAs\/InP dual-absorption \"PINIP\" structure on the GaAs\/AlGaAs Bragg reflectors. These features lead to an increase in quantum efficiency over a wide wavelength range while maintaining a high speed. The measured quantum efficiency was increased by 48.8% in comparison with that without reflectors. A quantum efficiency of 64% at a wavelength of 1522 nm and a 3 dB bandwidth of 26 GHz at a reverse bias of 3 V were simultaneously obtained in the device.","subset":"pubmed_abstract"} +{"meta":{"pmid":21986185,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2013-20":1,"2024-30":1,"unknown":11}}},"text":"The relationships between eating habits, smoking and alcohol consumption, and body mass index among baby boomers.\nThe study was to examine the eating habits of baby boomers and to investigate the relationship of these and other lifestyle habits on their reported body mass indices (BMI). A questionnaire was administered by mail to a random sample of people aged 40 years and above, drawn from the Electoral Rolls in Victoria, Australia. Part of the questionnaire contained questions about the respondents' eating habits, smoking status and alcohol use, as well as self reported heights and weights and demographic characteristics. Eight hundred and forty-four people (out of 1470) returned usable questionnaires. Statistically significant differences were found between the eating habits of men and women. Generally, more women snacked on high energy dense foods (e.g., confectionery). More men took larger mouthfuls than women. The eating habits of women appeared to be more formal than men's. Four constructs named: unconstrained eating, traditional eating style, gulping, and chocolate and junk food were derived from the eating behaviour literature. Structural equation modelling showed that eating behaviour was associated with BMI along with current smoking, ex-smoking status, alcohol consumption, and demographics. Eating habits and other lifestyle behaviours appear to be associated with BMI though in different pathways for men and women.","subset":"pubmed_abstract"} +{"meta":{"pmid":17052344,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":8}}},"text":"Analysis and functional annotation of expressed sequence tags from the fall armyworm Spodoptera frugiperda.\nLittle is known about the genome sequences of lepidopteran insects, although this group of insects has been studied extensively in the fields of endocrinology, development, immunity, and pathogen-host interactions. In addition, cell lines derived from Spodoptera frugiperda and other lepidopteran insects are routinely used for baculovirus foreign gene expression. This study reports the results of an expressed sequence tag (EST) sequencing project in cells from the lepidopteran insect S. frugiperda, the fall armyworm. We have constructed an EST database using two cDNA libraries from the S. frugiperda-derived cell line, SF-21. The database consists of 2,367 ESTs which were assembled into 244 contigs and 951 singlets for a total of 1,195 unique sequences. S. frugiperda is an agriculturally important pest insect and genomic information will be instrumental for establishing initial transcriptional profiling and gene function studies, and for obtaining information about genes manipulated during infections by insect pathogens such as baculoviruses.","subset":"pubmed_abstract"} +{"meta":{"pmid":27766323,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Development of a functional point-of-need diagnostic for myeloperoxidase detection to identify neutrophilic bronchitis.\nWith over 4.8 million Canadians suffering from chronic airway diseases, respiratory exacerbations are currently the leading cause of hospitalization in Canada. In cases of bacterial infection, neutrophil cell density increases from \u223c10 million cells per gram to over 15 million cells per gram. As sputum is a direct discharge from the primarily affected areas of respiratory diseases, quantification of granulocytes (including neutrophils) can be used to effectively determine a course of patient treatment. Unfortunately this quantification is currently limited to labour-intensive and time-consuming cell counts. In the present study, we describe a simple one-step lateral flow test (LFT) that can semi-quantitatively determine myeloperoxidase (MPO), a biomarker found in neutrophils, in minimally-processed sputum samples. This point-of-need (PON) diagnostic device provides positive results observable to the naked eye after 15 minutes. 37 human sputum samples were quantified for MPO using the developed LFT and compared to neutrophil levels quantified through traditional cell counting. A trend between sputum MPO concentration and total neutrophils was observed, suggesting that the LFT has the potential to replace cell counting for neutrophil approximation to aid in directing therapies quickly at the point of need.","subset":"pubmed_abstract"} +{"meta":{"pmid":8118024,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"The SCL\/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.\nActivation of the SCL (or TAL-1) gene as a result of chromosomal translocation or deletion is a frequent molecular lesion in acute T-cell leukemia. By virtue of its membership in the basic helix-loop-helix family of transcription factors, the SCL gene is a candidate to regulate events in hematopoietic differentiation. We have used polyclonal antibody raised against a bacterial expressed malE-SCL fusion protein to characterize SCL protein expression in postimplantation embryos and in neonatal and adult mice. SCL protein was detected at day 7.5 post coitum at both embryonic and extraembryonic sites, approximately 24 hours before the formation of recognizable hematopoietic elements. Expression then localized to blood islands of the yolk sac followed by localization to fetal liver and spleen, paralleling the hematopoietic activity of these tissues during development. SCL protein was detected in erythroblasts in fetal and adult spleen, myeloid cells and megakaryocytes in spleen and bone marrow, mast cells in skin, and in rare cells in fetal and adult thymus. In addition, SCL protein was noted in endothelial progenitors in blood islands and in endothelial cells and angioblasts in a number of organs at times coincident with their vascularization. SCL expression was also observed in other nonhematopoietic cell types in the developing skeletal and nervous systems. These results show that SCL expression is one of the earliest markers of mammalian hematopoietic development and are compatible with a role for this transcription factor in terminal differentiation of the erythroid and megakaryocytic lineages. SCL expression by cells in the thymus suggests that the gene may be active at some stage of T-cell differentiation and may be relevant to its involvement by chromosomal rearrangements in T-lymphoid leukemias. Finally, expression of the gene in developing brain, cartilage, and vascular endothelium indicates SCL may have actions in neural development, osteogenesis, and vasculogenesis, as well as in hematopoietic differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":37824290,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Effectiveness of suicide prevention gatekeeper training: 12-month follow-up of SafeTALK training to community members.\nLong-term assessments of gatekeeper training (GKT) with multiple follow-ups are rare. Therefore, the aim of the current analysis is to examine 12-month follow-up outcomes of SafeTALK training in addition to the earlier analysis of pre-, post-, and 6-month follow-up. Two hundred and sixty two community volunteers participated in half-day (4-h) gatekeeper training sessions. Before, after, and 6- and 12-month follow-up surveys were used to assess participants' knowledge, efficacy, and reluctance to intervene. Linear mixed effects regression was used in statistical analysis. Fifty six participants (21.4%) completed the 12-month follow-up, representing an attrition rate of 78.6% from pre-test. Linear mixed model analysis revealed a significant, consistent effect for time for knowledge, efficacy, and reluctance. Post-hoc testing revealed significant differences between scores at pre-test and 12-month follow-up for GK knowledge and efficacy; however, no significant difference was seen between these time points for reluctance to intervene. No significant change was measured between the 6 and 12 months for any outcomes. GK knowledge and efficacy remained significantly above pre-test scores. The evaluation of the GKT demonstrated the long-term effectiveness of community-based suicide prevention training programs to improve and maintain GK knowledge and efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":7033435,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.\nThe membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.","subset":"pubmed_abstract"} +{"meta":{"pmid":22344759,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Elevated plasma homocysteine in association with decreased vitamin B(12), folate, serotonin, lipids and lipoproteins in depressed patients.\nIncreased plasma homocysteine, decreased vitamin B(12) and folic acid levels have been implicated in depressive mood. Plasma homocystine, vitamin B(12), folic acid tryptophan, lipids and lipoproteins were determined in depressed patients and controls. Sixty subjects consisting of 30 depressed patients and 30 apparently healthy volunteers, who served as controls, were selected for this study. Anthropometric indices and biochemical parameters were determined using standard procedures. The results showed a significantly higher plasma homocysteine level amongst depressed patients when compared with the corresponding controls (p < 0.001), the percentage increase was 116%, while the plasma vitamin B(12) (p < 0.01), total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol levels (p < 0.001) were markedly lower when amongst depressed patients when compared with the corresponding controls; the percentage differences were 21%, 42% and 42% respectively. Plasma triglyceride, folic acid and tryptophan levels amongst depressed patients were not significantly different from the controls. The male subjects had significantly higher plasma tHcy levels than the female counterparts ( p < 0.001). This study showed a significant increase in plasma tHcy coexisting with a decrease in plasma vitamin B(12) TC, LDLC and HDLC, in depressed patients. Increased plasma homocysteine could be a sensitive indicator of plasma B vitamin deficiency.","subset":"pubmed_abstract"} +{"meta":{"pmid":11459379,"dup_signals":{"dup_doc_count":27,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":3,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":2,"2022-27":1,"2022-21":2,"2022-05":2,"2021-39":2,"2021-25":2,"2024-26":2,"2024-22":2}}},"text":"Cultural influences on the prevalence of common mental disorder, general practitioners' assessments and help-seeking among Punjabi and English people visiting their general practitioner.\nCulture influences symptom presentation and help-seeking and may influence the general practitioner's assessment. We recruited Punjabi and English GP attenders to a two-phase survey in London (UK) using the Amritsar Depression Inventory and the General Health Questionnaire as screening instruments. The Clinical Interview Schedule was the criterion measure. General practitioners completed Likert assessments. The second phase was completed by 209 Punjabi and 180 English subjects. The prevalence of common mental disorders was not influenced by culture. Punjabi cases more often had 'poor concentration and memory' and 'depressive ideas' but were not more likely to have somatic symptoms. General practitioners were more likely to assess Punjabis with common mental disorder as having 'physical and somatic' symptoms or 'sub-clinical disorders'. Punjabi cases with depressive ideas were less likely to be detected compared with English ones. In comparison to English men, English women were under-detected by Asian general practitioners. Help-seeking English subjects were more likely to be correctly identified as cases. The prevalence of common mental disorders and somatic symptoms does not differ across cultures. Among English subjects, general practitioners were more likely to identify correctly pure psychiatric illness and mixed pathology; but Punjabi subjects with common mental disorders were more often assessed as having 'sub-clinical disorders' and 'physical and somatic' disorders. English women were less well detected than English men. English help-seeking cases were more likely to be detected.","subset":"pubmed_abstract"} +{"meta":{"pmid":23615548,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Prenatal stress alters noradrenergic modulation of LTP in hippocampal slices.\nLong-term effects of stress during pregnancy on brain and behavior have been analyzed extensively in recent years. These effects include changes in emotional behavior, a reduction in learning capacity, and ability to generate long-term potentiation (LTP) in the offspring. In earlier studies, we and others have described a difference in ability to express LTP in dorsal and ventral sectors of the hippocampus (DH and VH, respectively) and its modification by prior stress. We now found that norepinephrine (NE) facilitated conversion of short-term potentiation to LTP in the normal DH but not in VH. Prenatal stress (PS) switched the locus of the facilitating action of NE from the DH to the VH. The effects of NE are likely to be mediated by activation of calcium stores. PS also facilitated (S)-3,5-dihydroxyphenylglycine hydrate (DHPG)-induced LTD in the VH, assumed to be mediated by release of calcium from stores. These observations have important implications for the role of the hippocampus in cognitive and emotional memories.","subset":"pubmed_abstract"} +{"meta":{"pmid":17310494,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2015-18":1,"2015-06":1,"2024-10":1,"unknown":8}}},"text":"Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.\nMentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism.","subset":"pubmed_abstract"} +{"meta":{"pmid":31386686,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Networks of face-to-face social contacts in Niakhar, Senegal.\nWe present the first analysis of face-to-face contact network data from Niakhar, Senegal. Participants in a cluster-randomized influenza vaccine trial were interviewed about their contact patterns when they reported symptoms during their weekly household surveillance visit. We employ a negative binomial model to estimate effects of covariates on contact degree. We estimate the mean contact degree for asymptomatic Niakhar residents to be 16.5 (95% C.I. 14.3, 18.7) in the morning and 14.8 in the afternoon (95% C.I. 12.7, 16.9). We estimate that symptomatic people make 10% fewer contacts than asymptomatic people (95% C.I. 5%, 16%; p = 0.006), and those aged 0-5 make 33% fewer contacts than adults (95% C.I. 29%, 37%; p < 0.001). By explicitly modelling the partial rounding pattern observed in our data, we make inference for both the underlying (true) distribution of contacts as well as for the reported distribution. We created an estimator for homophily by compound (household) membership and estimate that 48% of contacts by symptomatic people are made to their own compound members in the morning (95% CI, 45%, 52%) and 60% in the afternoon\/evening (95% CI, 56%, 64%). We did not find a significant effect of symptom status on compound homophily. We compare our findings to those from other countries and make design recommendations for future surveys.","subset":"pubmed_abstract"} +{"meta":{"pmid":16212563,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Assessment of chronic neuropsychological effects of mercury vapour poisoning in chloral-alkali plant workers.\nA prospective case study was conducted in the Department of Occupational Medicine, Tuzla. The purpose of this study was to indicate negative effects from occupational exposure to mercury on behavioural and mental health, memory and psychomotor function that was tested in 46 chloral-alkali plant workers (mean age was 38. 8+\/- 5. 7 years; mean age of occupational history 16. 5+\/- 6. 0 years). Data on toxicological monitoring on atomic absorption spectrometer, and data on mental health were collected, psychiatric and other subjective symptoms, and behavioural, psychomotor and memory function tested. The data were compared to control group, 32 healthy non exposed workers. The study was designed to assess blood and urine mercury levels and length of occupational exposure and investigate its relationships to effects on the mental health. The mean air mercury levels were 0.23 mg\/m3, the mean blood mercury concentrations was 3. 6 mg\/ dl and the mean urine mercury concentrations were 151.7 +\/- 180.4 mg\/l. In 25 (53%) workers exposed to mercury vapour was identified Depression-Hypochondrias Syndrome (p trend < 0. 001) with higher scores for scales: Hysteria (p trend <0. 001), Schizoid and Psychoastenia (MMPI). All psychological parameters were in highly significantly correlations with mercury levels and length of occupational exposure. Pathological parameters were possible general identified if the concentration of blood mercury levels are >2. 9 mg\/ dl, or urine mercury levels > 87 mg\/l workers exposed to mercury vapour knew that toxic effects in body resulted in loosing some of intellectual abilities, and that people who handle chemicals had an increased health risk (ESW questionnaire). The occupational mercury exposed workers had introvert behaviour (EPQ). Aggressiveness was found in 71.7% workers. The cognitive disturbances: short-term memory loss, difficult to concentrate on tasks which require attention and thinking, were significantly differed compared to those of controls (p trend < 0. 001). In 24 (52%) exposed to mercury workers we have determined ego strength loss and regressive defensive mechanisms (LB). Handwriting disturbances-micrography we have identified in 27 (58.7%) workers.","subset":"pubmed_abstract"} +{"meta":{"pmid":29075452,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Survival of a specialist natural enemy experiencing resource competition with an omnivorous predator when sharing the invasive prey Tuta absoluta.\nCan specialist natural enemies persist in ecosystems when competing with omnivorous natural enemies for their shared prey? The consequences of omnivory have been studied theoretically, but empirical studies are still lacking. Omnivory is nevertheless common in nature and omnivorous predators coexist with specialists in many ecosystems, even when they are intraguild predators. This type of association is also common in agroecosystems in which biological control strategies are used. Our study provides an example of the outcome of such an association in the context of biological control of the invasive pest Tuta absoluta (Lepidoptera) in a tomato agroecosystem. The two natural enemies involved, that is, a specialist (Stenomesius japonicus (Hymenoptera) parasitoid) and an omnivore (Macrolophus pygmaeus (Hemiptera) predator), were able to coexist for 3 months in our experimental cages in the absence of metacommunity mechanisms (i.e., emigration and recolonization), contrary to theoretical expectations. However, they negatively affected each other's population dynamics. We found that spatial resource segregation was not a mechanism that promoted their coexistence. Regarding pest control, the specialist and omnivorous natural enemies were found to exhibit complementary functional traits, leading to the best control when together. Mechanisms that may have promoted the coexistence of the two species as well as consequences with regard to the inoculative biological control program are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8730757,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":10}}},"text":"Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice.\n1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.","subset":"pubmed_abstract"} +{"meta":{"pmid":3612557,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2021-43":1,"2017-13":1}}},"text":"Transport of benzylpenicillin by the rat choroid plexus in vitro.\nTo characterize the transport system by which benzylpenicillin, an organic anion, is accumulated by the isolated rat choroid plexus, kinetic analysis of benzylpenicillin transport was performed. Accumulation of benzylpenicillin was against an electrochemical potential gradient via a saturable process (Km = 58 microM and Vmax = 84 nmol\/ml of tissue per min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate and N-ethylmaleimide), metabolic inhibitors (KCN and 2,4-dinitrophenol) and anion exchange inhibitors (4-acetamide-4'-isothiocyanatostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), but is major transport system did not require the inward Na+ gradient. Organic anions, such as 5-hydroxyindoleacetic acid, homovanillic acid, p-aminohippuric acid and probenecid inhibited the accumulation of benzylpenicillin, whereas dipeptides did not affect it. Kinetic analysis of the accumulation of benzylpenicillin suggests that both phenoxymethylpenicillin and cefpiramide are also transported via the benzylpenicillin transport system. Other penicillin and cephalosporin derivatives inhibited the accumulation of benzylpenicillin with different affinities. Penicillin derivatives without dissociating groups in the side chain had the higher affinity for the benzylpenicillin transport system than other beta-lactam antibiotics did. Among penicillin derivatives examined, a good correlation (r = 0.92) was observed between the lipophilicity and the affinity for the benzylpenicillin transport system, whereas no correlation was observed among the cephalosporin derivatives. These findings suggest that the major transport system of benzylpenicillin in the rat choroid plexus is via a carrier-mediated active anion transport process which is distinct from that of dipeptides, and does not require the inward Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":30865198,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":14}}},"text":"Nanotopography-based engineering of retroviral DNA integration patterns.\nControlling the interactions between cells and viruses is critical for treating infected patients, preventing viral infections, and improving virus-based therapeutics. Chemical methods using small molecules and biological methods using proteins and nucleic acids are employed for achieving this control, albeit with limitations. We found, for the first time, that retroviral DNA integration patterns in the human genome, the result of complicated interactions between cells and viruses, can be engineered by adapting cells to the defined nanotopography of silica bead monolayers. Compared with cells on a flat glass surface, cells on beads with the highest curvature harbored retroviral DNAs at genomic sites near transcriptional start sites and CpG islands during infections at more than 50% higher frequencies. Furthermore, cells on the same type of bead layers contained retroviral DNAs in the genomic regions near cis-regulatory elements at frequencies that were 2.6-fold higher than that of cells on flat glass surfaces. Systems-level genetic network analysis showed that for cells on nanobeads with the highest curvature, the genes that would be affected by cis-regulatory elements near the retroviral integration sites perform biological functions related to chromatin structure and antiviral activities. Our unexpected observations suggest that novel engineering approaches based on materials with specific nanotopography can improve control over viral events.","subset":"pubmed_abstract"} +{"meta":{"pmid":19008281,"dup_signals":{"dup_doc_count":39,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-42":2,"2014-41":2,"2014-35":1,"2014-23":2,"2014-15":2,"2017-17":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-10":1}}},"text":"A content analysis of mass media sources in relation to the MMR vaccine scare.\nIn light of the mass media coverage that the MMR (measles, mumps and rubella) vaccine received as a result of questions raised about its safety, a content analysis of mass media articles about the MMR vaccine was undertaken. The analysis examined 227 articles published in five different information sources in a 2 month period. The analysis looked at 94 content-based variables and the key attributes of these articles including word count and date of publication. Descriptive and analytical statistics relating to both article content and format were produced. The analysis showed that the content and format of articles between different information sources varied widely. These differences can be attributed to the information source in which they are published, but the variability in the content of these information sources provides a challenge to parents who were shown to be using the mass media as an information source.","subset":"pubmed_abstract"} +{"meta":{"pmid":20826420,"dup_signals":{"dup_doc_count":16,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2021-04":2,"2020-40":2,"2020-29":2,"2020-16":2,"2020-10":2,"2019-51":2,"2021-25":1}}},"text":"The role of kinesiotaping combined with botulinum toxin to reduce plantar flexors spasticity after stroke.\nTo evaluate the effect of kinesiotaping as an adjuvant therapy to botulinum toxin A (BTX-A) injection in lower extremity spasticity. This is a single-center, randomized, and double-blind study. Twenty hemiplegic patients with spastic equinus foot were enrolled into the study and randomized into 2 groups. The first group (n=10) received BTX-A injection and kinesiotaping, and the second group (n=10) received BTX-A injection and sham-taping. Clinical assessment was done before injection and at 2 weeks and 1, 3, and 6 months. Outcome measures were modified Ashworth scale (MAS), passive ankle dorsiflexion, gait velocity, and step length. Improvement was recorded in both kinesiotaping and sham groups for all outcome variables. No significant difference was found between groups other than passive range of motion (ROM), which was found to have increased more in the kinesiotaping group at 2 weeks. There is no clear benefit in adjuvant kinesiotaping application with botulinum toxin for correction of spastic equinus in stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":28766206,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2023-40":1,"2022-33":2,"2021-49":1,"2021-43":1,"2021-21":1,"2021-17":1,"2020-45":1,"2020-40":1,"2020-16":1,"2018-05":1,"2023-50":1}}},"text":"The American Society of Breast Surgeons and Quality Payment Programs: Ranking, Defining, and Benchmarking More Than 1 Million Patient Quality Measure Encounters.\nTo identify and remediate gaps in the quality of surgical care, the American Society of Breast Surgeons (ASBrS) developed surgeon-specific quality measures (QMs), built a patient registry, and nominated itself to become a Center for Medicare and Medicaid Services (CMS) Qualified Clinical Data Registry (QCDR), thereby linking surgical performance to potential reimbursement and public reporting. This report provides a summary of the program development. Using a modified Delphi process, more than 100 measures of care quality were ranked. In compliance with CMS rules, selected QMs were specified with inclusion, exclusion, and exception criteria, then incorporated into an electronic patient registry. After surgeons entered QM data into the registry, the ASBrS provided real-time peer performance comparisons. After ranking, 9 of 144 measures of quality were chosen, submitted, and subsequently accepted by CMS as a QCDR in 2014. The measures selected were diagnosis of cancer by needle biopsy, surgical-site infection, mastectomy reoperation rate, and appropriateness of specimen imaging, intraoperative specimen orientation, sentinel node use, hereditary assessment, antibiotic choice, and antibiotic duration. More than 1 million patient-measure encounters were captured from 2010 to 2015. Benchmarking functionality with peer performance comparison was successful. In 2016, the ASBrS provided public transparency on its website for the 2015 performance reported by our surgeon participants. In an effort to improve quality of care and to participate in CMS quality payment programs, the ASBrS defined QMs, tracked compliance, provided benchmarking, and reported breast-specific QMs to the public.","subset":"pubmed_abstract"} +{"meta":{"pmid":25867964,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Topcoat-Assisted Perpendicular and Straightly Parallel Coexisting Orientations of Block Copolymer Films.\nHighly ordered perpendicular orientation and straightly parallel orientation coexisting polystyrene-block-polydimethylsiloxane (PS-b-PDMS) cylindrical microdomains with 10 nm width can be realized by using polyvinyl acetate as a partially dewetted topcoat and solvent annealing with acetone vapor. During solvent annealing, the swelled topcoat begins to dewet and the dewetting rim sweeps the surface of the block copolymer films to align the cylindrical microdomains with the direction of dewetting propagation. However, the wetted region of the topcoat\/PS-b-PDMS film forms with a perpendicular orientation due to reduced surface tension and sufficient concentration gradient in the solvent evaporation step. The orientational changes (perpendicular\/straightly parallel orientation) in the dewetted\/wetted area are also investigated according to the vapor pressure of solvent annealing. The degree of directionality of the swept PS-b-PDMS films according to the distance from the dewetting front, which is equivalent with time after sweeping, is examined. To control the direction of dewetting and complex structures within a specific area, an imprinting process is introduced to form topographical line-space patterns in the topcoat and perpendicular\/parallel orientation of BCP patterns in the line-space patterns, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":28427211,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome.\nBrahma (BRM) is a critical catalytic subunit of the SWI\/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk\/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients. Of 270 patients, 37% were stage IV. Minor allele frequencies were 47-49%; 15% were double-homozygotes. When compared to the wild-type genotype, the homozygous variant of BRM-741 carried an adjusted OS hazard ratio (aHR) of 1.64 (95% CI:1.1-2.4); for BRM-1321, the aHR was 2.09 (95% CI:1.4-3.0). Compared to the double wild-type, carrying homozygous variants of both promoter polymorphisms (double-homozygote) yielded an aHR of 2.21 (95% CI:1.4-3.6). Directions\/magnitudes of associations were similar in subsets by age, gender, smoking status, use of platinum agents, and disease stage, and for progression-free survival. In a cohort of EAC patients of all stages (84% male; median age of 64 years), two BRM polymorphisms were genotyped. Cox proportional hazards models, adjusted for known prognostic variables, estimated the association of polymorphisms with OS. BRM polymorphisms were associated with OS in EAC in this study. Validation studies are warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":7928178,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Image analysis of the tapetal-like reflex in carriers of X-linked retinitis pigmentosa.\nTo increase understanding of the tapetal-like reflex (TLR), a unique retinal feature in carriers of X-linked retinitis pigmentosa (XLRP). Color fundus photographs of XLRP carriers were digitized at high resolution. A mathematical model of the imaging system was used to restore the digital retinal images. TLR was separated from the retinal background with an automated segmentation method. Mathematical morphology was used to estimate directional properties. Images from serial photos were registered and compared to study temporal progression. Quantitative analysis of well-focused funduscopic images show point-like unit reflexes forming the TLR. The average unit reflex is circularly symmetric with a diameter of approximately 8.5 microns and has a maximum reflectance 40% higher than that of the neighboring nonreflex retina. Two or more unit reflexes form small elongate patches that can cluster together into larger patches. Both smaller and larger patches have a strong preferential direction toward the fovea. Comparison of images taken 23 years apart in one patient and 3 years apart in another patient show no detectable changes in the size and location of the reflexes. The pattern of reflexes at high and low resolution suggests that the TLR represents an X-inactivation mosaic. Based on the size of the unit reflexes, the authors speculate that the cone photoreceptors participate in the TLR. The stability of the reflex over more than two decades questions the longstanding assumption that the TLR is a stage of the retinal degeneration.","subset":"pubmed_abstract"} +{"meta":{"pmid":19283997,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"[Psychotherapy with physically challenged children and young people: implications of a change of paradigm].\nIn the light of newer scientific developments the biopsychosocial approach in psychotherapy appears to be in need of a revision. In neurosciences a paradigm change from a linear to a dynamic outlook on development as a self-organizing process guided by interactions with the environment took place under the heading of Neural Plasticity during the last ten years. This implies that the conditions of development for challenged children are not comparable with those of healthy children as the case-examples of children with Spina Bifida indicate. On this background, a pilot project was launched with the goal of determining which forms of psychotherapy are helpful for challenged children. A practically oriented, eclectic approach was developed applying empiric-regulative cycles which promotes the dynamics of self-organizing psychic and physical processes as shown in a presented example of a child experiencing post-lesional plasticity. Thus, psychotherapy is understood as a co-constructive process of reciprocal shaping of relationship; it fosters beneficial organization processes of psychic and physical impact.","subset":"pubmed_abstract"} +{"meta":{"pmid":28157750,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Management of Unruptured Intracranial Aneurysms and Cerebrovascular Malformations.\nUnruptured intracranial aneurysms and vascular malformations are detected more frequently because of the increased use and availability of brain imaging. Management of these entities requires knowledge of which patients are at high risk for hemorrhage and what treatment options are available. This article summarizes the epidemiology, natural history, and management strategies for unruptured intracranial aneurysms, arteriovenous malformations, cavernous malformations, developmental venous anomalies, and capillary telangiectasias. Pooled cohort studies and meta-analyses have improved the ability to predict hemorrhage for each vascular abnormality. Scores and tools have been developed to aid the practitioner in predicting hemorrhage risk for unruptured intracranial aneurysms. Advances in endovascular techniques for unruptured intracranial aneurysms have improved the ability to treat difficult wide-necked aneurysms. Unruptured intracranial aneurysms are a common incidental finding. The PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) score and Unruptured Intracranial Aneurysm Treatment Score may be useful tools for predicting natural history and treatment recommendations. The overall risk of hemorrhage for both arteriovenous malformations and cavernous malformations is about 2% to 4% per year. With both of these entities, prior hemorrhage predicts future hemorrhage. In addition, other select patient and radiologic factors influence risk of hemorrhage. The risk of future hemorrhage should be compared to the risk of treatment. Developmental venous anomalies and capillary telangiectasias are largely benign entities and rarely symptomatic.","subset":"pubmed_abstract"} +{"meta":{"pmid":30569438,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Social-ecological timelines to explore human adaptation to coastal change.\nThrough the construction of a socio-ecological timeline for the Porsanger fjord ecosystem, this article illustrates the different ways in which environmental and social-ecological changes have influenced the adaptations of rural households in coastal Sami communities in Finnmark, north Norway. The main finding is that, although environmental change in the form of seal invasions and dwindling fish stocks directly impacted the fisheries, the introduction of a new vessel quota system decisively changed adaptive capacity and coastal Sami household adaptation strategies. These changes represented a tipping point for the social-ecological system in the period between 1986 and 1990. It is thus important to discuss the ways in which governance systems may facilitate actions to adapt to climate and biodiversity change and foster sustainable rural livelihood systems in coastal Norway. Based on traditional and local ecological knowledge on the state of the ecosystem prior to the tipping point, two relevant actions to increase the resilience of the system were identified: ensuring the possibility of re-entry into fisheries as part of rural livelihood combinations, and ecological restoration of kelp beds. Flexible diversification of livelihoods allows exploitation of a range of adjacent species without large investments in a fossile fuel-driven fisheries economy. Investing in regrowth of macroalgae to foster cod nursery areas and increase carbon sequestration can be a relevant alternative for communities that are interested in contributing to climate change mitigation on a larger scale.","subset":"pubmed_abstract"} +{"meta":{"pmid":25771121,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-05":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-30":1,"2017-17":1,"2023-40":1,"2017-13":2,"2024-10":1}}},"text":"Isoxanthohumol--Biologically active hop flavonoid.\nIsoxanthohumol (IXN), apart from xanthohumol (XN) and 8-prenylnaringenin (8PN), is one of the most important prenylflavonoids found in hops. Another natural source of this compound is a shrub Sophora flavescens, used in traditional Chinese medicine. Main dietary source of IXN is beer, and the compound is produced from XN during wort boiling. In the human body, the compound is O-demethylated to 8PN, the strongest known phytoestrogen. This process takes place in the liver and in the intestine, where it is mediated by local microflora. It has been reported in some studies that even though beer contains small amounts of hops and its preparations, these compounds may affect the functioning of the human body. IXN exhibits an antiproliferative activity against human cell lines typical for breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer (DU145 and PC-3), and colon cancer (HT-29 and SW620) cells. It strongly inhibits the activation of the following carcinogens: 2-amino-3-methylimidazol-[4,5-f]quinoline and aflatoxin B1 (AFB1) via human cytochrome P450 (CYP1A2). It also inhibits the production of prostate specific antigen (PSA). IXN significantly reduces the expression of transforming growth factor-\u03b2 (TGF-\u03b2) in the case of invasive breast cancer MDA-MB-231. It interferes with JAK\/STAT signaling pathway and inhibits the expression of pro1inflammatory genes in the monoblastic leukemia cell line (MonoMac6). It activates apoptosis in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMCs). In addition, IXN shows an antiviral activity towards herpes viruses (HSV1 and HSV2) and bovine viral diarrhea virus (BVDV).","subset":"pubmed_abstract"} +{"meta":{"pmid":24580697,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Non-Abelian gauge fields in photonic cavities and photonic superfluids.\nWe show that the TE-TM modes splitting and the structure anisotropy of a semiconductor microcavity combine into a non-Abelian gauge field for exciton-polaritons or cavity photons. The field texture can be tuned simply by rotating the sample and ranges continuously from a Rashba to a monopolar field. In the noninteracting regime, the latter leads to remarkable focusing and conical diffraction effects. In the interacting regime, the spin-orbit coupling induces a breakdown of superfluidity. The spatially homogeneous flows become unstable and dynamically evolve into spin textured states, such as stripes or domain walls.","subset":"pubmed_abstract"} +{"meta":{"pmid":7071583,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Impulse-coded and analog signaling in single mechanoreceptor neurons.\nAlthough most sensory neurons convey temporally coded impulses to the central nervous system, certain nonspiking receptors use only graded afferent signals. Each of three large nerve fibers from the lobster oval organ, a mechanoreceptor subserving ventilation, carry both impulses and graded potentials. Thus, both impulse frequency and receptor potential amplitude are available for information transfer.","subset":"pubmed_abstract"} +{"meta":{"pmid":28557551,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"MAP-IT: A Practical Tool for Planning Complex Behavior Modification Interventions.\nHealth research often aims to prevent noncommunicable diseases and to improve individual and public health by discovering intervention strategies that are effective in changing behavior and\/or environments that are detrimental to one's health. Ideally, findings from original research support practitioners in planning and implementing effective interventions. Unfortunately, interventions often fail to overcome the translational block between science and practice. They often ignore theoretical knowledge, overlook empirical evidence, and underrate the impact of the environment. Accordingly, sustainable changes in individual behavior and\/or the environment are difficult to achieve. Developing theory-driven and evidence-based interventions in the real world is a complex task. Existing implementation frameworks and theories often do not meet the needs of health practitioners. The purpose of this article is to synthesize existing frameworks and to provide a tool, the Matrix Assisting Practitioner's Intervention Planning Tool (MAP-IT), that links research to practice and helps practitioners to design multicomponent interventions. In this article, we use physical activity of older adults as an example to explain the rationale of MAP-IT. In MAP-IT, individual as well as environmental mechanisms are listed and behavior change techniques are linked to these mechanisms and to intervention components. MAP-IT is theory-driven and evidence-based. It is time-saving and helpful for practitioners when planning complex interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":2320391,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":7}}},"text":"Molecular forms of lactoferrin in stool and urine from infants fed human milk.\nThe molecular forms of lactoferrin (LF) were examined in stools and urine collected at 2.5 or 5 wk of age from very low birth wt infants fed either a cow's milk formula or a fortified human milk preparation. LF was not found by Western blotting in excreta from infants fed cow's milk. In contrast, intact and fragmented forms of LF were detected in stools and concentrated urine of each infant who received human milk. Only intact LF was detected in the fortified human milk preparation, whereas many types of LF fragments were present in the stools and urine. The approximate molecular wt of the most prominent fragments were 44, 38, 34, and 32 kD. However, the stools also displayed lower molecular wt fragments that were not found in urines of those infants. The LF fragments in those excreta were similar in size to those produced in vitro by limited digestion of apo-LF with trypsin. Furthermore, fragments produced by in vitro proteolysis were immunoreactive in an ELISA for LF. Thus, the fragments of LF in stools of very low birth wt infants fed human milk appeared to be produced by in vivo proteolysis, and the close resemblance between the LF fragments in the stools and urine suggests that the urinary LF fragments originated in the gastrointestinal tract. It remains unclear, however, whether the whole LF molecules that were fragmented were derived solely from ingested LF in human milk or in part from LF produced by the infant in response to human milk feedings.","subset":"pubmed_abstract"} +{"meta":{"pmid":9657576,"dup_signals":{"dup_doc_count":17,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-23":2,"2022-49":1,"2022-27":1,"2021-43":1,"2021-17":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-05":1,"2017-34":1,"2023-40":1,"2024-30":1}}},"text":"Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD.\nWe examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":19401035,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Up-regulation of heparanase in the ethmoid sinus mucosa of patients with chronic sinusitis.\nHeparanase (HPA) is known to be involved in tissue remodeling of various organs with inflammatory diseases. The aim of this study was to investigate the level of expression and the pattern of distribution of HPA in normal human sinus mucosa, inflammatory sinus mucosa, and nasal polyps to evaluate the possible effect of HPA on the tissue remodeling of chronic inflammatory sinus mucosa and nasal polyps. Normal sinus mucosa was obtained from the ethmoid sinus during endoscopic reduction in 25 patients with blowout fractures. Inflammatory sinus mucosa and nasal polyps were obtained from 25 patients undergoing endoscopic sinus surgery for chronic sinusitis with nasal polyps. The levels of expression and the pattern of distribution of HPA were evaluated in normal human sinus mucosa, inflammatory sinus mucosa, and nasal polyps, using reverse transcriptase-polymerase chain reaction, immunohistochemical analysis, and Western blot analysis. HPA mRNA and protein were detected in inflammatory sinus mucosa and nasal polyps but not in normal sinus mucosa. HPA was mainly localized in the vascular endothelium, epithelium, submucosal glands, and inflammatory cells of inflammatory sinus mucosa. In nasal polyps, inflammatory cells and vascular endothelium showed immunopositivity in the entire portion, whereas glands and epithelial cells did not show positivity. Our results indicate that HPA is not constitutively expressed in normal sinus mucosa and is upregulated in chronic inflammatory sinus mucosa and nasal polyps, suggesting that HPA may play an important role in the tissue remodeling in chronic sinusitis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29670004,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":8}}},"text":"Analogs of the Scorpion Venom Peptide Stigmurin: Structural Assessment, Toxicity, and Increased Antimicrobial Activity.\nScorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the \u03b1-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":19920810,"dup_signals":{"dup_doc_count":17,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-10":1,"2014-10":1,"2013-48":1,"2013-20":2,"2024-26":1,"unknown":10}}},"text":"Information processing and signal integration in bacterial quorum sensing.\nBacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum-sensing network of the marine bacterium Vibrio harveyi uses three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within these three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration on the basis of information theory and use it to analyze quorum sensing in V. harveyi. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input-output relation of the V. harveyi quorum-sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal-integration networks, and that bacteria probably have evolved active strategies for minimizing this interference. Here, we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.","subset":"pubmed_abstract"} +{"meta":{"pmid":19903330,"dup_signals":{"dup_doc_count":11}},"text":"Comparative analysis of Panicum streak virus and Maize streak virus diversity, recombination patterns and phylogeography.\nPanicum streak virus (PanSV; Family Geminiviridae; Genus Mastrevirus) is a close relative of Maize streak virus (MSV), the most serious viral threat to maize production in Africa. PanSV and MSV have the same leafhopper vector species, largely overlapping natural host ranges and similar geographical distributions across Africa and its associated Indian Ocean Islands. Unlike MSV, however, PanSV has no known economic relevance. Here we report on 16 new PanSV full genome sequences sampled throughout Africa and use these together with others in public databases to reveal that PanSV and MSV populations in general share very similar patterns of genetic exchange and geographically structured diversity. A potentially important difference between the species, however, is that the movement of MSV strains throughout Africa is apparently less constrained than that of PanSV strains. Interestingly the MSV-A strain which causes maize streak disease is apparently the most mobile of all the PanSV and MSV strains investigated. We therefore hypothesize that the generally increased mobility of MSV relative to other closely related species such as PanSV, may have been an important evolutionary step in the eventual emergence of MSV-A as a serious agricultural pathogen.The GenBank accession numbers for the sequences reported in this paper are GQ415386-GQ415401.","subset":"pubmed_abstract"} +{"meta":{"pmid":3291114,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-05":1,"2019-51":1,"2018-47":1,"2018-26":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2020-16":1}}},"text":"The expert witness in psychology and psychiatry.\nThe involvement of psychologists and psychiatrists within the legal arena continues to grow rapidly but remains highly controversial. Extensive research on clinical judgement provides a scientific basis for clarifying the growing disputes about the values of such professional activities. Studies show that professionals often fail to reach reliable or valid conclusions and that the accuracy of their judgements does not necessarily surpass that of laypersons, thus raising substantial doubt that psychologists or psychiatrists meet legal standards for expertise. Factors that underlie the research findings and implications for courtroom testimony are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8366195,"dup_signals":{"dup_doc_count":45,"dup_dump_count":39,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":2,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":3,"2021-10":1,"2021-04":1,"2020-45":1,"2020-40":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2024-10":1,"2017-13":1,"2024-22":1}}},"text":"Neuronal morphology and efferent projections of the dorsal nucleus of the lateral lemniscus in the rat.\nThe dorsal nucleus of the lateral lemniscus (DLL) is the main source of inhibitory influence in the auditory brainstem of mammals. The cytoarchitecture and connectional properties of DLL were established in the cat in contrast to the rat. The goal of the present study was to establish to what extent the anatomical properties of the rat DLL compare to those of the cat, thus providing a basis of interpretation for future functional studies in the rat, an animal model used more and more in the auditory system. DLL of the rat contains four well-differentiated neuronal types, as seen in Nissl-stained material. Type I neurons are large and multipolar with abundant cytoplasm and darkly stained Nissl substance. Type II neurons are large, bipolar and darkly stained in Nissl material. Type III neurons are medium in size and their soma is round or ovoid. Type IV neurons are small and round with scant cytoplasm; they seem to be also the least common neuronal type of the DLL. After Phaseolus vulgaris-leucoagglutinin or biocytin injections in the DLL, fibers and terminals labeled by orthograde transport were observed in the corresponding region of the contralateral DLL and in the inferior colliculus, bilaterally. A few labeled fibers and terminal fields were seen in the deep layers of the superior colliculus bilaterally, as well as in the medial division of the medial geniculate body and, even more rostrally, in the posterior nucleus of the thalamus. Descending projections from DLL terminated in the periolivary regions of the ipsilateral superior olivary complex. Retrograde tracing based on injections of horseradish peroxidase in the various targets of the DLL confirmed the connections established with orthograde labeling.","subset":"pubmed_abstract"} +{"meta":{"pmid":23330994,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Training to acquire psychomotor skills for endoscopic endonasal surgery using a personal webcam trainer.\nExisting training methods for neuroendoscopic surgery have mainly emphasized the acquisition of anatomical knowledge and procedures for operating an endoscope and instruments. For laparoscopic surgery, various training systems have been developed to teach handling of an endoscope as well as the manipulation of instruments for speedy and precise endoscopic performance using both hands. In endoscopic endonasal surgery (EES), especially using a binostril approach to the skull base and intradural lesions, the learning of more meticulous manipulation of instruments is mandatory, and it may be necessary to develop another type of training method for acquiring psychomotor skills for EES. Authors of the present study developed an inexpensive, portable personal trainer using a webcam and objectively evaluated its utility. Twenty-five neurosurgeons volunteered for this study and were divided into 2 groups, a novice group (19 neurosurgeons) and an experienced group (6 neurosurgeons). Before and after the exercises of set tasks with a webcam box trainer, the basic endoscopic skills of each participant were objectively assessed using the virtual reality simulator (LapSim) while executing 2 virtual tasks: grasping and instrument navigation. Scores for the following 11 performance variables were recorded: instrument time, instrument misses, instrument path length, and instrument angular path (all of which were measured in both hands), as well as tissue damage, max damage, and finally overall score. Instrument time was indicated as movement speed; instrument path length and instrument angular path as movement efficiency; and instrument misses, tissue damage, and max damage as movement precision. In the novice group, movement speed and efficiency were significantly improved after the training. In the experienced group, significant improvement was not shown in the majority of virtual tasks. Before the training, significantly greater movement speed and efficiency were demonstrated in the experienced group, but no difference in movement precision was shown between the 2 groups. After the training, no significant differences were shown between the 2 groups in the majority of the virtual tasks. Analysis revealed that the webcam trainer improved the basic skills of the novices, increasing movement speed and efficiency without sacrificing movement precision. Novices using this unique webcam trainer showed improvement in psychomotor skills for EES. The authors believe that training in terms of basic endoscopic skills is meaningful and that the webcam training system can play a role in daily off-the-job training for EES.","subset":"pubmed_abstract"} +{"meta":{"pmid":21309971,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Drought advances spring growth phenology of the Mediterranean shrub Erica multiflora.\nCurrent climate projections predict drier and warmer conditions in the Mediterranean basin over the next century. While advanced spring growth due to warming has been described in the literature, few data are available on the effects of drought on phenology. Hence, the phenology and growth of two Mediterranean shrubs, Erica multiflora and Globularia alypum, was studied in a rainfall exclusion field experiment to simulate spring drought in a natural shrubland. We estimated the onset of growth in spring by monitoring the appearance of new stems, and the end of growth in summer by following the elongation of stems. Drought treatment caused earlier onset of the spring growing season in E. multiflora, whereas no advance was observed in G. alypum. However, growth cessation was not affected in E. multiflora. Drought reduced the growth of both shrubs, as reflected in less stem elongation. The results show that a drier climate might affect not only growth but also spring phenology of some Mediterranean species. We suggest that a reduction in the cooling effect of transpiration may have analogous effects to warming and might advance the start of growth in E. multiflora, a species whose phenology has been described as warming-sensitive. The lengthening of the growing season resulting from advanced growth did not imply higher productivity, as growth was restricted by drought.","subset":"pubmed_abstract"} +{"meta":{"pmid":2543640,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Molecular characteristics and physical state of human papillomavirus DNA change with progressing malignancy: studies in a patient with epidermodysplasia verruciformis.\nIn order to establish the role of human papillomavirus (HPV) in carcinogenesis of epidermodysplasia verruciformis (EV), the presence, the molecular characteristics and the physical state of HPV DNA in a benign lesion, a primary carcinoma and a metastatic carcinoma developing in the same EV patient were studied and compared. Of the 2 HPV DNAs isolated from benign macular lesions, only one (a subtype of HPV 5) was detected in both primary and metastatic tumors. Only one normal species of viral DNA molecule was detected in the benign lesion, whereas most, if not all, viral DNA molecules present in the carcinoma (both primary and metastatic) were aberrant ones. The major viral DNA molecule in the primary carcinoma was a large HPV DNA with duplicated 40% subgenomic segments, and was present as free episomes. The major viral DNA molecule in the metastatic carcinoma was the 40% subgenomic segment itself, lacking the remaining 60% segment of the viral genome, and was integrated within cellular DNA. Thus, HPV DNA was present in tumors at any stage of malignancy, and its molecular characteristics and physical state changed not only with the development but also with the enhancement of malignancy, consistently conserving its defined 40% subgenomic segment as the predominant viral sequences. Our results suggest that HPV 5 may be actually involved in carcinogenesis in EV patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":21215264,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Two-color in vivo imaging of photoreceptor apoptosis and development in Drosophila.\nWe report a new two-color fluorescent imaging system to visualize the mosaic adult photoreceptor neurons (PRs) in real-time. Using this method, we examined a collection of 434 mutants and identified genes required for PR survival, planar cell polarity (PCP), patterning and differentiation. We could track the progression of PR degeneration in living flies. By introducing the expression of p35, a caspase inhibitor, we found mutations that specifically activate caspase-dependent death. Moreover, we showed that grh is required in R3 for correct PCP establishment. The \"Tomato\/GFP-FLP\/FRT\" method allows high-throughput, rapid and precise identification of survival and developmental pathways in living adult PRs at single-cell resolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":15908786,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":15}}},"text":"Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.\nAberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3sigma and ERM protein expression. Expression of 14-3-3sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":18371985,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-26":1}}},"text":"Natural selection of altruism in inelastic viscous homogeneous populations.\nBiological explanations are given of three main uninterpreted theoretical results on the selection of altruism in inelastic viscous homogeneous populations, namely that non-overlapping generations hinder the evolution of altruism, fecundity effects are more conducive to altruism than survival effects, and one demographic regime (so-called death-birth) permits altruism whereas another (so-called birth-death) does not. The central idea is 'circles of compensation', which measure how far the effects of density dependence extend from a focal individual. Relatednesses can then be calculated that compensate for density dependence. There is very generally a 'balancing circle of compensation', at which the viscosity of the population slows up selection of altruism, but does not affect its direction, and this holds for altruism towards any individual, not just immediate neighbours. These explanations are possible because of recent advances in the theory of inclusive fitness on graphs. The assumption of node bitransitivity in that recent theory is relaxed to node transitivity and symmetry of the dispersal matrix, and new formulae show how to calculate relatedness from dispersal and vice versa.","subset":"pubmed_abstract"} +{"meta":{"pmid":28289411,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Immunogenicity of a Bivalent Adjuvanted Glycoconjugate Vaccine against Salmonella Typhimurium and Salmonella Enteritidis.\nSalmonella enterica serovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidal Salmonella (iNTS) disease. Considering the co-endemicity of S. Typhimurium and S. Enteritidis, a bivalent vaccine formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced by S. Typhimurium and S. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG). Humoral and cellular, systemic and local, immune responses were characterized in two different mouse strains. All conjugate vaccines elicited high levels of serum IgG against the respective O-antigens (OAg) with bactericidal activity. The bivalent conjugate vaccine induced systemic production of antibodies against both S. Typhimurium and S. Enteritidis OAg. The presence of alum or alum + CpG adjuvants in vaccine formulations significantly increased the serum antigen-specific antibody production. The alum + CpG bivalent vaccine formulation triggered the highest systemic anti-OAg antibodies and also a significant increase of anti-OAg IgG in intestinal washes and fecal samples, with a positive correlation with serum levels. These data demonstrate the ability of monovalent and bivalent conjugate vaccines against S. Typhimurium and S. Enteritidis to induce systemic and local immune responses in different mouse strains, and highlight the suitability of a bivalent glycoconjugate formulation, especially when adjuvanted with alum + CpG, as a promising candidate vaccine against iNTS disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":17599422,"dup_signals":{"dup_doc_count":54,"dup_dump_count":31,"dup_details":{"curated_sources":2,"2023-40":4,"2023-14":1,"2023-06":1,"2022-49":4,"2022-40":2,"2022-33":1,"2022-27":1,"2022-21":2,"2022-05":1,"2021-49":2,"2021-43":1,"2021-39":2,"2021-31":2,"2021-25":3,"2021-21":1,"2021-17":2,"2021-10":3,"2021-04":1,"2020-50":2,"2020-45":1,"2020-40":2,"2020-34":1,"2020-29":1,"2020-16":2,"2019-43":1,"2019-35":1,"2019-22":1,"2024-22":1,"2024-18":3,"2024-10":1,"2024-26":1}}},"text":"Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods.\nMost patients with type 2 diabetes mellitus develop cardiovascular disease (CVD), with substantial loss of life expectancy. Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes. The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge. Despite the importance of this health problem, there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors. ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality. All participants are in the glycemia trial, which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin (HbA1c) level of <6.0% will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9%. The lipid trial includes 5,518 of the participants, who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether, in the context of good glycemic control, a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo. The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of <120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of <140 mm Hg. The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Upon the expected completion of participant follow-up in 2009, the ACCORD trial should document for the first time the benefits and risks of intensive glucose control, intensive blood pressure control, and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":21533657,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"A multicentered, randomized, controlled trial comparing radioguided seed localization to standard wire localization for nonpalpable, invasive and in situ breast carcinomas.\nStudies suggest radioguided seed localization (RSL) yields fewer positive margins than wire-guided localization (WL). The goal of this study is to determine whether RSL is superior to WL. Women with confirmed invasive or ductal carcinoma in situ (DCIS) undergoing localization and breast conserving surgery were enrolled. Outcomes measured include positive margin and reoperation rates, specimen weight, operative and localization times, and surgeon and radiologist ranking of procedural difficulty. Randomization was centralized, concealed, and stratified by surgeon with 153 patients in the WL group and 152 in RSL group. Localizations were performed using either ultrasound (70%) or mammographic guidance (30%). Pathology was either DCIS (18%) or invasive carcinoma (82%). Procedures were performed at 3 sites, by 7 surgeons. Only difference found for patient and tumor characteristics was more multifocal disease in RSL group. Using intention-to-treat analysis, there were no differences in positive margins rates for RSL (10.5%) and WL (11.8%), (P=.99) or for positive or close margins (<1 mm) (RSL 19% and WL 22%; P=.61). Mean operative time (minutes) was shorter for RSL (RSL 19.4 vs WL 22.2; P<.001). Specimen volume, weight, reoperation and localization times were similar. Surgeons ranked the seed technique as easier (P=.008), while radiologists ranked them similarly. Patient's pain rankings during wire localization were higher (P=.038). In contrast to other trials positive margin and reoperation rates were similar for RSL and WL. However, for RSL operative times were shorter, and the technique was preferred by surgeons, making it an acceptable method for localization.","subset":"pubmed_abstract"} +{"meta":{"pmid":2372641,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":1,"unknown":14}}},"text":"Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s.\nTo assess the magnitude of the problem of interval cancers of the cervix (those that are diagnosed within a short time after negative screening test results) in the 1980s, to compare the nature of interval cancers in younger women with that in older women, and, by reviewing negative cervical smears, to determine the proportion of interval cancers that might represent the development of malignancy anew compared with the proportion that might be associated with difficulties in sampling or errors in reporting. An audit of the interval cases of cervical cancer that had been diagnosed within 36 months of a smear having been reported as negative by the Victorian Cytology Gynaecological Service among women registered with cervical cancer during 1982-6. The Victorian Cytology Gynaecological Service, a free public sector cytology laboratory in Victoria, Australia. 138 Women, all of whom had had cervical cancer diagnosed during the 36 months after having had a negative cervical smear. Subjects were divided into two age groups: younger women, aged less than 35; older women, aged 35-69. Negative slides were reviewed for evidence of optimal sampling and for the presence of cellular abnormalities that had been missed at the time of the original reporting. The number of interval cases of cancer of the cervix registered during 1982-6. The proportion of interval cases occurring in younger women and the proportion occurring in older women. Division of women into three risk categories based on clinical history and screening history that broadly corresponded to the probability that a diagnosis of cervical cancer might be expected during the 36 months after the issuing of a negative smear report. 138 Of 1044 (13.2%) women who had been registered with cervical cancer during 1982-6 had had one or more negative smears during the 36 months preceding the diagnosis of cancer. Interval cancers comprised a larger proportion of registrations of cervical cancer in women aged less than 35 years than in women aged 35-69 (21.1% v 11.0%, p less than 0.01). Women with interval cancer who had had at least three negative smears during the 10 years before the diagnosis of cancer were commoner in the younger age group than in the older age group (7.0% v 2.5%, p less than 0.01). When, however, the number of observed cases of squamous cell carcinoma was related to the number of expected cases in the absence of screening, no significant difference was found between the two age groups (6.8% v 4.8%, p greater than 0.10). The rate of diagnosis of interval cancer per 100,000 negative tests was lower among younger women than among older women (10\/100,000 v 16\/100,000). Review of the negative slides showed that 11.9% were again considered to be negative with an optimal sample having been obtained as evidenced by the presence of endocervical cells or metaplastic cells, or both. Interval cancers might comprise a larger proportion of all registered cases of cervical cancer among younger women owing to the larger proportion of such cancers being prevented in this age group. Among women with interval cancer review of the negative slides showed that most were accounted for by suboptimal sampling or by errors of reporting.","subset":"pubmed_abstract"} +{"meta":{"pmid":26981311,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis-NHANES 2009-2012.\nObjective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists. Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units\/liter, and periodontitis was dichotomized to the presence or absence of periodontitis. Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated (p = 0.0360) and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]). Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24918220,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin.\nSafety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence\/absence of cartilage injury. Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report. Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were \"possibly related\" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as \"likely related\" to study drug. With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.","subset":"pubmed_abstract"} +{"meta":{"pmid":27212244,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":12}}},"text":"Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis.\nThere have been many studies of the effects of non-alcoholic fatty liver disease (NAFLD) and the risk of cardiovascular disease (CVD), but these have produced conflicting results. We performed a meta-analysis of these studies to quantify the magnitude of the association between NAFLD (and NAFLD severity) and risk of CVD events. We searched PubMed, Google scholar, and Web of Science databases using terms \"NAFLD\", \"cardiovascular events\", \"cardiovascular mortality\", \"prognosis\" and their combinations to identify observational studies published through January 2016. We included only observational studies conducted in adults >18years and in which NAFLD was diagnosed on imaging or histology. Data from selected studies were extracted and meta-analysis was then performed using random effects modelling. A total of 16 unique, observational prospective and retrospective studies with 34,043 adult individuals (36.3% with NAFLD) and approximately 2,600 CVD outcomes (>70% CVD deaths) over a median period of 6.9years were included in the final analysis. Patients with NAFLD had a higher risk of fatal and\/or non-fatal CVD events than those without NAFLD (random effect odds ratio [OR] 1.64, 95% CI 1.26-2.13). Patients with more 'severe' NAFLD were also more likely to develop fatal and non-fatal CVD events (OR 2.58; 1.78-3.75). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias. NAFLD is associated with an increased risk of fatal and non-fatal CVD events. However, the observational design of the studies included does not allow to draw definitive causal inferences. The data on whether NAFLD by itself is associated with increased cardiovascular events and death remains an issue of debate. The findings of this updated and large meta-analysis of observational studies indicate that NAFLD is significantly associated with an increased risk of fatal and non-fatal cardiovascular events. However, the observational design of the studies included does not allow us to prove that NAFLD causes cardiovascular disease. Clinicians who manage patients with NAFLD should not focus only on liver disease but should also consider the increased risk of cardiovascular disease and undertake early, aggressive risk factor modification.","subset":"pubmed_abstract"} +{"meta":{"pmid":11884693,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Data and models determine treatment proposals--an illustration from meta-analysis.\nA relevant problem in meta-analysis concerns the possible heterogeneity between trial results. If a test of heterogeneity is not significant the trials are often considered to be \"homogeneous\" and the individual trial results are replaced by an overall mean effect size and its confidence interval (\"equal effects model\"). If the trials are heterogeneous the individual trial effect sizes are conserved (\"fixed effects model\"). In a more flexible approach (\"random effects model\"), each trial makes use of knowledge from the other trials so individual effect sizes are \"shrunken\" towards an overall mean effect size. The more flexible tool may be useful for doctors involved in a trial when the outcome of their individual trial differs markedly from the overall mean effect size. Where a particular trial result is opposite in direction to the overall mean result, a conflict may arise: should a new patient be treated with the new method or not? The more flexible position and a graphical comparison of the three approaches are likely to be helpful in guiding the decision. Applying different models to the same data may lead to apparently paradoxical results: an individual trial result may be interpreted to be beneficial or harmful depending on the choice of model.","subset":"pubmed_abstract"} +{"meta":{"pmid":18288231,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2015-18":1,"unknown":8}}},"text":"Application of the correlation coefficient method for determination of the focal plane to digital particle holography.\nThe correlation coefficient (CC) method, which was proposed by our research group, is applied to digital particle holography to locate the focal plane of particles. It uses the fact that the CC is maximum at the focal plane. The factors influencing this method are discussed with a numerical simulation of holograms. For real holograms, the Wiener filter was proposed to process both recorded holograms and reconstructed images. The application results using the dot array target showed that the Wiener filter is a very effective tool for processing holography-related images. The effects of the dot size and the object distance on the errors in the determination of the focal plane by the CC method were investigated by using the calibration target.","subset":"pubmed_abstract"} +{"meta":{"pmid":27635059,"dup_signals":{"dup_doc_count":40,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":1,"2023-23":2,"2023-06":2,"2022-40":2,"2022-21":2,"2021-43":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":3,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-30":2,"2024-18":1,"2024-10":1}}},"text":"Paired suicide in a young refugee couple on the Thai-Myanmar border.\nA young refugee woman attended antenatal clinic on the Thai-Myanmar border at 9 weeks' gestation. As part of an ongoing study of perinatal mental health, she underwent a structured psychiatric interview during which she described occasional depressed mood, anhedonia and passive suicidal ideation. Her husband was a young refugee known to use alcohol and drugs. 2 days later, the couple committed suicide together by herbicide ingestion. Refugee populations are at risk of developing mental disorders as a result of their marginalised status, socioeconomic disadvantage and exposures to trauma. Pregnancy may have exacerbated feelings of hopelessness in this couple. The prevalence of mental disorders such as depression is increased in the perinatal period and suicide is the second leading cause of death in young women globally. Prevention programmes and early recognition of mental disorders may improve detection and lead to better support for vulnerable individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":22959563,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2021-31":1,"2019-09":1,"2018-51":1,"2018-34":1,"2018-13":1,"2017-47":2,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-40":1,"2017-13":1}}},"text":"Incidence of sternal wound infection after reexploration in the intensive care unit and the use of local gentamycin.\nReoperation for bleeding is a known emergency complication after cardiac operations. When performed in the intensive care unit (ICU), sterility issues arise. Our aim was to examine the incidence of sternal wound infection (SWI) after reexploration in the ICU for bleeding with routine use of local gentamycin. From January 2003 until December 2009, 4,863 patients underwent cardiac operations through a median sternotomy at our institution. We conducted a retrospective database review identifying all patients who required reoperations. The occurrence of SWI in this group was compared with the general cardiac surgical population. Reoperations for bleeding during this period were conducted routinely in the ICU with prophylactic application of a gentamycin sponge between the sternal halves before closure in all cases. Reexploration for bleeding was necessary in 302 patients (6.2%), and SWI occurred in 11, for a rate of 3.6%. SWI occurred in 174 of the 4,561 non-reexplored patients, for a similar rate of 3.8% (p>0.9). These values are similar to our overall rate of SWI of 3.8% (n=185) in the total cohort of 4,863 patients. The incidence of SWI was not increased in our study group after emergency reoperation for bleeding in the ICU after the local use of gentamycin. Our data suggest that reexploration in an ICU setting for bleeding does not pose a sterility challenge and that life-threatening delays due to transfer to the operating theater may be avoided.","subset":"pubmed_abstract"} +{"meta":{"pmid":29648440,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-33":1,"2020-34":2,"2020-29":1,"2020-05":2,"2019-51":2,"2019-39":1,"2023-50":1}}},"text":"Spontaneous Transport of Single-Stranded DNA through Graphene-MoS2 Heterostructure Nanopores.\nThe effective transport of a single-stranded DNA (ssDNA) molecule through a solid-state nanopore is essential to the future success of high-throughput and low-cost DNA sequencing. Compatible with current electric sensing technologies, here, we propose and demonstrate by molecular dynamics simulations the ssDNA transport through a quasi-two-dimensional nanopore in a heterostructure stacked together with different 2D materials, such as graphene and molybdenum disulfide (MoS2). Due to different chemical potentials, U, of DNA bases on different 2D materials, it is energetically favorable for a ssDNA molecule to move from the low- U MoS2 surface to the high- U graphene surface through a nanopore. With the proper attraction between the negatively charged phosphate group in each nucleotide and the positively charged Mo atoms exposed on the pore surface, the ssDNA molecule can be temporarily seized and released thereafter through a thermal activation, that is, a slow and possible nucleotide-by-nucleotide transport. A theoretical formulation is then developed for the free energy of the ssDNA transiting a heterostructure nanopore to properly characterize the non-equilibrium stick-slip-like motion of a ssDNA molecule.","subset":"pubmed_abstract"} +{"meta":{"pmid":9234732,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain.\nSimian virus 40 (SV40) encodes two proteins, large T antigen and small t antigen that contribute to virus-induced tumorigenesis. Both proteins act by targeting key cellular regulatory proteins and altering their function. Known targets of the 708-amino-acid large T antigen include the three members of the retinoblastoma protein family (pRb, p107, and p130), members of the CBP family of transcriptional adapter proteins (cap-binding protein [CBP], p300, and p400), and the tumor suppressor p53. Small t antigen alters the activity of phosphatase pp2A and transactivates the cyclin A promoter. The first 82 amino acids of large T antigen and small t antigen are identical, and genetic experiments suggest that an additional target(s) important for transformation interacts with these sequences. This region contains a motif similar to the J domain, a conserved sequence found in the DnaJ family of molecular chaperones. We show here that mutations within the J domain abrogate the ability of large T antigen to transform mammalian cells. To examine whether a purified 136-amino-acid fragment from the T antigen amino terminus acts as a DnaJ-like chaperone, we investigated whether this fragment stimulates the ATPase activity of two hsc70s and discovered that ATP hydrolysis is stimulated four- to ninefold. In addition, ATPase-defective mutants of full-length T antigen, as well as wild-type small t antigen, stimulated the ATPase activity of hsc70. T antigen derivatives were also able to release an unfolded polypeptide substrate from an hsc70, an activity common to DnaJ chaperones. Because the J domain of T antigen plays essential roles in viral DNA replication, transcriptional control, virion assembly, and tumorigenesis, we conclude that this region may chaperone the rearrangement of multiprotein complexes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27785263,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Abnormal Anatomical Variations of Extra-Hepatic Biliary Tract, and Their Relation to Biliary Tract Injuries and Stones Formation.\nTo determine the most common abnormal anatomical variations of extra-hepatic biliary tract (EHBT), and their relation to biliary tract injuries and stones formation. This is a retrospective review of 120 patients, who underwent endoscopic retrograde cholangiopancreaticography (ERCP) and\/or magnetic resonance cholangiopancreaticography (MRCP), between July 2011 and June 2013. The patients' ERCP and MRCP images were reviewed and evaluated for the anatomy of EHBT; the medical records were reviewed for demographic data, biliary tracts injuries and stones formation. Out of 120 patients, 50 were males (41.7%) and 70 were females (58.3%). The mean age was 54 years old (range 20 - 88). Abnormal anatomy was reported in 30% (n = 36). Short cystic duct (CD) was found in 20% (n = 24), left CD insertion in 5% (n = 6), CD inserted into the right hepatic duct (RHD) in 1.7% (n = 2), duct of Luschka in 3.33% (n = 4) and accessory hepatic duct in also 3.33% (n = 4). Biliary tract injuries were reported in 15% (n = 18) and stones in 71.7% (n = 86). Biliary tract injuries were higher in abnormal anatomy (P = 0.04), but there was no relation between abnormal anatomy and stones formation. Abnormal anatomy of EHBT was found to be 30%. The most common abnormality is short CD followed by left CD insertion. Surgeons should be aware of these common abnormalities in our patients, hence avoiding injuries to the biliary tract during surgery. The abnormal anatomy was associated with high incidence of biliary tract injury but has no relation to biliary stone formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":7821392,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Increased nerve growth factor level in the distal stump of transected sciatic nerve in relation to aging and its application for neural grafting.\nThe nerve growth factor (NGF) level in the distal stump of mouse sciatic nerve transected 24 h before increased significantly compared with that in the nontransected contralateral side. This level was higher in aged (24-month-old) mice than in aging (12-month-old) or in young (1-month-old) mice. Adrenal medullary tissue mixed with the pretransected (24 h before) distal stump of the sciatic nerve of aged mice was cografted into the ipsilateral striatum of aged mice with a unilateral 6-hydroxydopamine lesion of dopaminergic system. Two and 4 weeks after transplantation, cografted mice showed partial functional compensation in amphetamine-induced motor asymmetry while mice with adrenal grafts alone did not show the functional recovery. The immunocytochemical staining of tyrosine hydroxylase revealed large numbers of chromaffin cells surviving in cografted animals. It is concluded that NGF level in the distal stump of pretransected peripheral nerve is increased even in aged animals and cografting of this nerve stump with adrenal medulla can be effectively utilized in aged animals with nigrostriatal insufficiency.","subset":"pubmed_abstract"} +{"meta":{"pmid":30542664,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-22":1,"unknown":13}}},"text":"Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis.\nBackground: Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines. However, our understanding of these models remains fragmentary. Although the immune response to Leishmania donovani infection in mice has been extensively characterized, transcriptomic analysis capturing the tissue-specific evolution of disease has yet to be reported. Methods: We provide an analysis of the transcriptome of spleen, liver and peripheral blood of BALB\/c mice infected with L. donovani. Where possible, we compare our data in murine experimental visceral leishmaniasis with transcriptomic data in the public domain obtained from the study of L. donovani-infected hamsters and patients with human visceral leishmaniasis. Digitised whole slide images showing the histopathology in spleen and liver are made available via a dedicated website, www.leishpathnet.org. Results: Our analysis confirms marked tissue-specific alterations in the transcriptome of infected mice over time and identifies previously unrecognized parallels and differences between murine, hamster and human responses to infection. We show commonality of interferon-regulated genes whilst confirming a greater activation of type 2 immune pathways in infected hamsters compared to mice. Cytokine genes and genes encoding immune checkpoints were markedly tissue specific and dynamic in their expression, and pathways focused on non-immune cells reflected tissue specific immunopathology. Our data also addresses the value of measuring peripheral blood transcriptomics as a potential window into underlying systemic disease. Conclusions: Our transcriptomic data, coupled with histopathologic analysis of the tissue response, provide an additional resource to underpin future mechanistic studies and to guide clinical research.","subset":"pubmed_abstract"} +{"meta":{"pmid":30333273,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Evaluation of Iron Overload Between Age Groups Using Magnetic Resonance Imaging and Its Correlation with Iron Profile in Transfusion-dependent Thalassemia.\nroutine blood transfusion in transfusion-dependent-thalassemia (TDT) causes iron accumulation in various organ. Serum markers of iron overload, serum ferritin and transferrin saturation, are sensitive but not specific. MRI T2-star (T2*) is valuable for detecting iron level in organs. This study aimed to explore the degree of iron overload in various organs, iron deposition difference between children and adults, also its correlation with serum marker of iron overload. this was a cross-sectional study of TDT patients who had been evaluated by MRI T2* examination in Cipto Mangunkusumo Hospital from 2014 to 2018. a total of 546 subjects was included in this study. The number of subjects between children and adults was almost equal. Most of subjects had normal cardiac iron deposition. The difference of cardiac iron overload between children and adults was significant (p=0.009). Liver evaluation showed that most of subjects had moderate to severe iron overload. This difference between children and adults was significant (p=0.017). Pancreas evaluation showed that either children or adults mostly had mild pancreatic iron overload. Analysis of T2* showed that pancreatic iron deposition progressed with increasing age. Serum ferritin had weak correlation with heart T2* MRI, moderate correlation with pancreas and liver T2* MRI. Relationship between transferrin saturation and T2* MRI was extremely weak. cardiac and hepatic iron deposition between children and adults differ significantly. Liver has the greatest iron overload, followed by pancreas and heart. Iron deposition in liver and pancreas has been started from earlier age. Pancreatic iron deposition rises with increasing age. Serum ferritin and transferrin saturation should not be used solely to predict iron overload in various organs. We suggest that MRI evaluation must be conducted at least once to assess iron deposition in organs.","subset":"pubmed_abstract"} +{"meta":{"pmid":29072245,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Impact of oral antibiotics on health-related quality of life after mandibular third molar surgery: An observational study.\nTo compare the impact of antibiotics on health-related quality of life (QoL) outcomes following third molar surgery. The study population consisted of 135 subjects that required surgical extraction of mandibular third molar under local anesthesia and met the inclusion criteria. The subjects were randomized into three study groups of 45 subjects each: Group A - extended amoxicillin\/clavulanic acid (GlaxoSmithKline Beecham England), 1 gram pre-operatively and then 625 mg BD for 5 days Group B - prophylactic amoxicillin\/clavulanic acid (GlaxoSmithKline Beecham England) 1 gram pre-operatively only, and Group C - prophylactic levofloxacin 1 gram pre-operatively only. Patients were assessed pre- and post-operatively on days 1, 3, 5, 7, and 14 using the United Kingdom oral health-related QoL (OHRQoL) questionnaire. This study showed that surgical removal of impacted teeth exerted a negative influence on patient's QoL across various physical, social, and psychological aspects of life. Comparing the three groups, Group A showed a slightly better QoL score; although, there was no statistically significant difference among them. Studies have shown better clinical recovery following administration of antibiotics after third molar surgery. There was a significant deterioration in OHRQoL in the immediate postoperative period, particularly postoperative days 1 and 3 following third molar surgery. QoL was also observed to be slightly better in Group A than Groups B and C, although this was not statistically significant.","subset":"pubmed_abstract"} +{"meta":{"pmid":24125731,"dup_signals":{"dup_doc_count":11}},"text":"Comparative metabolomics of estrogen receptor positive and estrogen receptor negative breast cancer: alterations in glutamine and beta-alanine metabolism.\nMolecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER-) breast cancer tissues were investigated using GC-TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2\/3 of tumors) and could be validated in a predefined validation set (1\/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER- subtype. Beta-alanine demonstrated the strongest change between ER- and ER+ breast cancer (fold change=2.4, p=1.5E-20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R=-0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER- breast cancer. In a Kaplan-Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR=0.6, p=3.2E-15). It is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER- breast as different diseases requiring different treatment strategies. Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER- breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER- subtype as a preferential target for glutaminase inhibitors. For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER- breast cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":29384534,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Direct monitoring of spin transitions in a dinuclear triple-stranded helicate iron(ii) complex through X-ray photoelectron spectroscopy.\nA dinuclear helical iron(ii) complex of a new ditopic thiazolylimine ligand (L) has been synthesised via supramolecular assembly. The resulting dinuclear helical cylinder [Fe2L3]\u00b74BF4 was investigated by variable temperature X-ray crystallography, ESI high resolution mass spectrometry, CHN analysis, FT-IR and UV-Vis spectroscopy. The nature of the spin transition was investigated by magnetic susceptibility measurements, and confirmed by VT-SCXRD and X-ray photoelectron spectroscopy. [Fe2L3]\u00b74BF4 displays a complete spin transition with a gradual-abrupt character at T1\/2 = 348 K and represents a new example of a dinuclear iron(ii) complex exhibiting a spin transition at high temperature. Both VT-SCXRD and XPS measurements show excellent correlation with the magnetic susceptibility experiments, demonstrating the power of XPS not just to confirm, but also to clearly follow the spin-state transition in Fe(ii) SCO complexes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19002237,"dup_signals":{"dup_doc_count":23,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2016-44":2,"2016-40":1,"2016-36":2,"2016-30":2,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":2,"2015-40":1,"2015-22":1,"2019-22":1,"2013-20":1}}},"text":"Theoretical evaluation of measurement uncertainties of two-color pyrometry applied to optical diagnostics.\nWe present a theoretical analysis of two-color pyrometry applied to optical diagnostics. A two-color pyrometer built with a single CCD is advantageous due to the simple system design. We evaluate the possibility and degree of ill-conditionness on the basis of measurement uncertainties for different measurement approaches of this two-color system. We classify measurement approaches. The corresponding ill-conditionness criterion is established. The greater the criterion value is, the worse the ill-conditioned degree of solution is. So, the optimum choice of measurement approach for the two-color system is achieved through intercomparison of the criterion values. Numerical examples are also given to illustrate this point. The theoretical analysis not only provides an effective way of evaluating different measurement approaches, but also may help us to better understand the influences that determine the choices between wavelength\/waveband measurements and calibration\/noncalibration modes for temperature and soot distribution.","subset":"pubmed_abstract"} +{"meta":{"pmid":27199223,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Putting Meaning into Meaningful Use: A Roadmap to Successful Integration of Evidence at the Point of Care.\nPressures to contain health care costs, personalize patient care, use big data, and to enhance health care quality have highlighted the need for integration of evidence at the point of care. The application of evidence-based medicine (EBM) has great promise in the era of electronic health records (EHRs) and health technology. The most successful integration of evidence into EHRs has been complex decision tools that trigger at a critical point of the clinical visit and include patient specific recommendations. The objective of this viewpoint paper is to investigate why the incorporation of complex CDS tools into the EMR is equally complex and continues to challenge health service researchers and implementation scientists. Poor adoption and sustainability of EBM guidelines and CDS tools at the point of care have persisted and continue to document low rates of usage. The barriers cited by physicians include efficiency, perception of usefulness, information content, user interface, and over-triggering. Building on the traditional EHR implementation frameworks, we review keys strategies for successful CDSs: (1) the quality of the evidence, (2) the potential to reduce unnecessary care, (3) ease of integrating evidence at the point of care, (4) the evidence's consistency with clinician perceptions and preferences, (5) incorporating bundled sets or automated documentation, and (6) shared decision making tools. As EHRs become commonplace and insurers demand higher quality and evidence-based care, better methods for integrating evidence into everyday care are warranted. We have outlined basic criteria that should be considered before attempting to integrate evidenced-based decision support tools into the EHR.","subset":"pubmed_abstract"} +{"meta":{"pmid":17256551,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Structural aspects of surfactant selection for the design of vegetable oil semi-synthetic metalworking fluids.\nThis paper presents a set of surfactant-selection guidelines that can be used to design bio-based semi-synthetic metalworking fluid (MWF) microemulsions as a renewable alternative to conventional petroleum formulations. Ten surfactant classes (six anionic and four nonionic) with different head and tail structures and three vegetable base oils (canola oil, soybean oil, and a fatty acid trimethylolpropane ester) were investigated as representatives of oil and surfactant options currently under consideration in the MWF industry. All combinations of these surfactants and oils were formulated at the full range of oil to surfactant ratios and surfactant concentrations. The stability of each formulation was evaluated based on visual transparency, light transmittance, and droplet diameter. The experimental results yield the following guidelines that produce stable bio-based MWF microemulsions with minimum necessary concentrations of surfactants: (1) a combination of two surfactants, one nonionic and one water soluble co-surfactant (either nonionic or anionic) is preferred over a single surfactant; (2) the nonionic surfactant should have a carbon tail length greater than or equal to the nominal carbon chain length of the fatty acids in the oil as well as a head group that is not excessively small or large (e.g., 10-20 ethylene oxide groups for a polysorbitan ester, ethoxylated alcohol, or ethoxylated glyceryl ester); (3) the difference in tail lengths between the surfactant and the co-surfactant should be less than 6 to maximize the feasible range of oil to surfactant ratios yielding stable emulsions. These guidelines are consistent with general results of micelle solubilization theory and evidence is provided to suggest that common semi-synthetic MWF systems can be thought of as swollen micelle systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":24179223,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"One-dimensional electrical contact to a two-dimensional material.\nHeterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the 1D edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":10781620,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":11}}},"text":"Ceftriaxone-resistant salmonella infection acquired by a child from cattle.\nThe emergence of resistance to antimicrobial agents within the salmonellae is a worldwide problem that has been associated with the use of antibiotics in livestock. Resistance to ceftriaxone and the fluoroquinolones, which are used to treat invasive salmonella infections, is rare in the United States. We analyzed the molecular characteristics of a ceftriaxone-resistant strain of Salmonella enterica serotype typhimurium isolated from a 12-year-old boy with fever, abdominal pain, and diarrhea. We used pulsed-field gel electrophoresis and analysis of plasmids and beta-lactamases to compare the ceftriaxone-resistant S. enterica serotype typhimurium from the child with four isolates of this strain obtained from cattle during a local outbreak of salmonellosis. The ceftriaxone-resistant isolate from the child was indistinguishable from one of the isolates from cattle, which was also resistant to ceftriaxone. Both ceftriaxone-resistant isolates were resistant to 13 antimicrobial agents; all but one of the resistance determinants were on a conjugative plasmid of 160 kb that encoded the functional group 1 beta-lactamase CMY-2. Both ceftriaxone-resistant isolates were closely related to the three other salmonella isolates obtained from cattle, all of which were susceptible to ceftriaxone. This study provides additional evidence that antibiotic-resistant strains of salmonella in the United States evolve primarily in livestock. Resistance to ceftriaxone, the drug of choice for invasive salmonella disease, is a public health concern, especially with respect to children, since fluoroquinolones, which can also be used to treat this disease, are not approved for use in children.","subset":"pubmed_abstract"} +{"meta":{"pmid":30626089,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Avocado Oil Extract Modulates Auditory Hair Cell Function through the Regulation of Amino Acid Biosynthesis Genes.\nSensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":19108592,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":2,"2024-10":1,"unknown":10}}},"text":"Reproductive health of bass in the Potomac, U.S.A., drainage: part 2. Seasonal occurrence of persistent and emerging organic contaminants.\nThe seasonal occurrence of organic contaminants, many of which are potential endocrine disruptors, entering the Potomac River, USA, watershed was investigated using a two-pronged approach during the fall of 2005 and spring of 2006. Passive samplers (semipermeable membrane device and polar organic chemical integrative sampler [POCIS]) were deployed in tandem at sites above and below wastewater treatment plant discharges within the watershed. Analysis of the samplers resulted in detection of 84 of 138 targeted chemicals. The agricultural pesticides atrazine and metolachlor had the greatest seasonal changes in water concentrations, with a 3.1- to 91-fold increase in the spring compared with the level in the previous fall. Coinciding with the elevated concentrations of atrazine in the spring were increasing concentrations of the atrazine degradation products desethylatrazine and desisopropylatrazine in the fall following spring and summer application of the parent compound. Other targeted chemicals (organochlorine pesticides, polycyclic aromatic hydrocarbons, and organic wastewater chemicals) did not indicate seasonal changes in occurrence or concentration; however, the overall concentrations and number of chemicals present were greater at the sites downstream of wastewater treatment plant discharges. Several fragrances and flame retardants were identified in these downstream sites, which are characteristic of wastewater effluent and human activities. The bioluminescent yeast estrogen screen in vitro assay of the POCIS extracts indicated the presence of chemicals that were capable of producing an estrogenic response at all sampling sites.","subset":"pubmed_abstract"} +{"meta":{"pmid":9648830,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells.\nThe incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase-activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive, Ca2+-dependent nonselective cation current in pancreatic beta-cells and insulinoma cells. This MTX-sensitive current is present in human beta-cells as well as in mouse and rat beta-cells, and is accompanied by a rise in cytosolic Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+ channels is prevented. Activation of the nonselective cation current is inhibited by reduction of disulfide bonds with intracellular, but not extracellular, dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The nonselective cation channels that carry this current have a conductance of about 30 pS, with Na+ as the major extracellular cation. We estimate that these cation channels are expressed on beta-cells at a density similar to that of ATP-sensitive potassium channels (K(ATP) channels) and exhibit spontaneous activity at basal glucose concentrations. We propose that this spontaneous cation channel activity constitutes at least part of the depolarizing background conductance that permits changes in the activity of K(ATP) channels to regulate the resting potential of beta-cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":7463097,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The pathogenesis of primary internodal demyelination produced by acetyl ethyl tetramethyl tetralin: evidence for preserved Schwann cell somal function.\nThe pathogenesis of primary internodal PNS demyelination produced by acetyl ethyl tetramethyl tetralin (AETT) has been studied using subchronically intoxicated rats with intact sciatic nerves (right side), and with focally traumatized nerves (left side) undergoing myelin breakdown and repair. Sixteen Sprague-Dawley rats were given approximately 50 mg\/kg\/d of AETT, dissolved in ethanol and placed in food. Six age-matched control animals received daily an equivalent amount of food treated with the same volume of alcohol. After six weeks and prior to the onset of demyelination, AETT treatment had increased the number of visible Schmidt-Lanterman incisures per internode of large-diameter fibers in tibial nerves. By ten weeks, the same group of fibers had begun to develop juxtanodal and internodal myelin bubbles. Subsequently, intramyelinic phagocytes of hematogenous derivation removed entire internodes of edematous myelin. Schwann cell response to injury was studied in control and AETT-intoxicated animals which had undergone left hindlimb surgery 1 to 2 days after beginning toxin treatment: (a) a perineurial window was placed in the peroneal nerve to induce focal demyelination and remyelination, (b) the tibial nerve was transected between ligatures to study Wallerian degeneration of the distal stump, and (c) the sural nerve was focally crushed to induce axonal regeneration and myelination. Qualitatively similar responses to nerve injury were seen 1 to 16 weeks later in AETT-treated and control animals. These results are compatible with the view that AETT damages myelin directly, that Schwann cell somal functions are not seriously affected by AETT, and that Schmidt-Lanterman incisures undergo changes prior to demyelination, which may represent a physiological response of the Schwann cell to toxic attack on its myelin sheath. Taken in concern, these observations challenge the long-held view that primary internodal demyelination is necessarily indicative of metabolic dysfunction of the Schwann cell soma.","subset":"pubmed_abstract"} +{"meta":{"pmid":33706257,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Healthcare Utilization and End-of-Life Outcomes in Patients Receiving CAR T-Cell Therapy.\nCAR T-cell therapy has revolutionized the treatment of patients with hematologic malignancies, but it can result in prolonged hospitalizations and serious toxicities. However, data on the impact of CAR T-cell therapy on healthcare utilization and end-of-life (EoL) outcomes are lacking. We conducted a retrospective analysis of 236 patients who received CAR T-cell therapy at 2 tertiary care centers from February 2016 through December 2019. We abstracted healthcare utilization and EoL outcomes from the electronic health record, including hospitalizations, receipt of ICU care, hospitalization and receipt of systemic therapy in the last 30 days of life, palliative care, and hospice referrals. Most patients (81.4%; n=192) received axicabtagene ciloleucel. Overall, 28.1% of patients experienced a hospital readmission and 15.5% required admission to the ICU within 3 months of CAR T-cell therapy. Among the deceased cohort, 58.3% (49\/84) were hospitalized and 32.5% (26\/80) received systemic therapy in the last 30 days of life. Rates of palliative care and hospice referrals were 47.6% and 30.9%, respectively. In multivariable logistic regression, receipt of bridging therapy (odds ratio [OR], 3.15; P=.041), index CAR-T hospitalization length of stay >14 days (OR, 4.76; P=.009), hospital admission within 3 months of CAR T-cell infusion (OR, 4.29; P=.013), and indolent lymphoma transformed to diffuse large B-cell lymphoma (OR, 9.83; P=.012) were associated with likelihood of hospitalization in the last 30 days of life. A substantial minority of patients receiving CAR T-cell therapy experienced hospital readmission or ICU utilization in the first 3 months after CAR T-cell therapy, and most deceased recipients of CAR T-cell therapy received intensive EoL care. These findings underscore the need for interventions to optimize healthcare delivery and EoL care for this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":21983008,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative.\nThe aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor\/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":7930045,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Reward fails to alter response bias in depression.\nSeveral different models postulate that depression is associated with decreased approach-related behavior. Relatively little has been done to date to specifically investigate this issue. In the present study, a signal-detection analysis was used to examine the response biases of dysphoric and nondysphoric female undergraduates during 3 payoff conditions: neutral, reward, and punishment. As predicted, the dysphoric subjects had a smaller change in bias from the neutral to the reward condition compared with the nondysphoric group. The 2 groups did not differ during the neutral and punishment conditions. These findings are consistent with the hypothesis that the left frontal hypoactivation observed in depression reflects a deficit in approach-related behavior.","subset":"pubmed_abstract"} +{"meta":{"pmid":22544026,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":8}}},"text":"[Clinicopathologic characteristics of patients who underwent curative additional gastrectomy after endoscopic submucosal dissection for early gastric cancer or adenoma].\nEndoscopic submucosal dissection (ESD) has been widely performed. However, procedure related-complications and the risk of tumor recurrence are limitations. We analyzed the clinicopathological characteristics of patients who underwent curative additional gastrectomy (gastrectomy) after ESD. The clinical characteristics of cases underwent gastrectomy after ESD were retrospectively analyzed. Between January 2002 and August 2010, 1,512 cases underwent ESD for early gastric cancer (n=511) or adenoma (n=1,001). Thirty-two cases (2.1%) underwent gastrectomy after ESD. Thirty cases (2.0%) were EGC and 2 cases (0.1%) were adenoma. Extended indication, larger tumor size and piecemeal resection were risk factors for gastrectomy after ESD. According to the causes of gastrectomy, 13 cases underwent gastrectomy due to complications (40.6%; bleeding in 9, perforation in 4), and 19 cases based on pathological results (incomplete resection in 13, lymphatic invasion in 6). In cases with incomplete resection, the rate of residual tumor and lymph node metastasis after gastrectomy was 69.2% (75% lateral margin, 60% deep and 75% both) and 7.7%, respectively. Three (50%) of the 6 cases with lymphatic invasion had lymph node metatstasis. The causes of gastrectomy after ESD were the procedure-related complications, the incomplete resection and lymphatic invasion. For complete and curative ESD, endoscopists should try to minimize complications and determine the depth of invasion accurately before ESD.","subset":"pubmed_abstract"} +{"meta":{"pmid":16649909,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Serum concentrations and analgesic effects of liposome-encapsulated and standard butorphanol tartrate in parrots.\nTo compare serum concentrations of liposome-encapsulated butorphanol tartrate (LEBT) and standard butorphanol tartrate (STDBT) following SC and IM administration, respectively, and to evaluate analgesic effects of LEBT and STDBT after parenteral administration to Hispaniolan parrots. 11 adult Hispaniolan parrots. The ability of LEBT to prolong the duration of analgesia in an avian species was tested. Blood samples were collected at serial time points after SC administration of LEBT (10 mg\/kg or 15 mg\/kg) or IM administration of STDBT (5 mg\/kg). Serum concentrations of butorphanol tartrate were determined by use of a commercial immunoassay that measured parent drug and metabolites. Analgesic efficacy was evaluated in parrots exposed to electrical and thermal stimuli. Foot withdrawal thresholds were recorded at baseline and at serial time points after LEBT (15 mg\/kg), liposome vehicle, STDBT (2 mg\/kg), or physiologic saline (0.9% NaCl) solution administration. LEBT had a prolonged in vivo release for up to 5 days. Negligible serum butorphanol and butorphanol metabolite concentrations were obtained at 24 hours after IM administration of STDBT. Analgesic efficacy of LEBT as measured by foot withdrawal threshold to noxious thermal and electrical stimuli persisted for 3 to 5 days following SC administration of LEBT. SC administration of LEBT provided analgesia and detectable serum butorphanol concentrations in Hispaniolan parrots for up to 5 days. The use of LEBT may allow for substantial improvement in long-term pain relief without subjecting birds to the stress of handling and multiple daily injections.","subset":"pubmed_abstract"} +{"meta":{"pmid":28640907,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":15}}},"text":"Accelerometer measured levels of moderate-to-vigorous intensity physical activity and sedentary time in children and adolescents with chronic disease: A systematic review and meta-analysis.\nModerate-to-vigorous physical activity (MVPA) and sedentary time (ST) are important for child and adolescent health. To examine habitual levels of accelerometer measured MVPA and ST in children and adolescents with chronic disease, and how these levels compare with healthy peers. Data sources: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus and CINAHL from 2000-2017. Study selection: Studies with accelerometer-measured MVPA and\/or ST (at least 3 days and 6 hours\/day to provide estimates of habitual levels) in children 0-19 years of age with chronic diseases but without co-morbidities that would present major impediments to physical activity. In all cases patients were studied while well and clinically stable. Out of 1592 records, 25 studies were eligible, in four chronic disease categories: cardiovascular disease (7 studies), respiratory disease (7 studies), diabetes (8 studies), and malignancy (3 studies). Patient MVPA was generally below the recommended 60 min\/day and ST generally high regardless of the disease condition. Comparison with healthy controls suggested no marked differences in MVPA between controls and patients with cardiovascular disease (1 study, n = 42) and type 1 diabetes (5 studies, n = 400; SMD -0.70, 95% CI -1.89 to 0.48, p = 0.25). In patients with respiratory disease, MVPA was lower in patients than controls (4 studies, n = 470; SMD -0.39, 95% CI -0.80, 0.02, p = 0.06). Meta-analysis indicated significantly lower MVPA in patients with malignancies than in the controls (2 studies, n = 90; SMD -2.2, 95% CI -4.08 to -0.26, p = 0.03). Time spent sedentary was significantly higher in patients in 4\/10 studies compared with healthy control groups, significantly lower in 1 study, while 5 studies showed no significant group difference. MVPA in children\/adolescents with chronic disease appear to be well below guideline recommendations, although comparable with activity levels of their healthy peers except for children with malignancies. Tailored and disease appropriate intervention strategies may be needed to increase MVPA and reduce ST in children and adolescents with chronic disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":28394951,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-22":1,"unknown":7}}},"text":"Dietary Patterns and 10-year (2002-2012) Incidence of Type 2 Diabetes: Results from the ATTICA Cohort Study.\nTo identify dietary patterns among apparently healthy individuals and to determine their long-term effect on diabetes incidence. During 2001-2002, a random sample of 3,042 men and women (18-89 years old), living in greater Athens, was randomly selected to participate in the study. During 2011-2012, the 10-year follow-up was performed in 2,583 participants (15% drop-out rate). After excluding participants with diabetes at baseline and those for whom no information on diabetes status was available at follow-up, the working sample consisted of 1,485 participants. Dietary habits were assessed by means of a validated semi-quantitative, food frequency questionnaire. Factor analysis was performed to extract dietary patterns from 18 food groups. Diabetes diagnosis at follow-up was made in 191 participants, yielding an incidence rate of 12.9%. Six factors (i.e. dietary patterns) were identified that explained 54% of the variation in consumption. After adjusting for major confounders, and stratification by age-group, logistic regression revealed that the most healthful pattern consisted of the consumption of fruits, vegetables, legumes, bread, rusk, and pasta which reduced the 10-year diabetes risk by 40%, among participants aged 45-55 years. The association reached marginal statistical significance (95% CI: 0.34, 1.07), while no significant association was observed for the other age-groups. When the analysis was additionally adjusted for carbohydrate percentage, statistical significance was lost completely, suggesting a possibly mediating effect of this macronutrient. The results confirm the potentially protective effect of a plant-based dietary pattern in the primary prevention of diabetes, in particular among middle-aged people. Carbohydrate content may be a specific factor in this relationship; other micronutrients found in plant-based food groups may also play a role.","subset":"pubmed_abstract"} +{"meta":{"pmid":32618731,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Metabolic and cardiovascular outcomes of bariatric surgery.\nBariatric surgery is an effective therapy for morbid obesity that also improves weight-related metabolic parameters and reduces morbidity and mortality. The purpose of this review is to consolidate our current understanding of metabolic, macrovascular and microvascular benefits of bariatric surgery and to provide an update. Early resolution of insulin resistance and type 2 diabetes mellitus (T2DM) varies by type of bariatric surgery and appears to be mediated by changes in secretion of gut hormones, metabolism of bile acids, expression of glucose transporters and the gut microbiome. Dyslipidaemia, atherosclerosis, microvascular complications of obesity and diabetes, systemic and tissue-level inflammation show evidence of regression and hypertension improves significantly after bariatric surgery. Bariatric surgery leads to improvements in obesity-related metabolic comorbidities such as dyslipidaemia, HDL functionality, hypertension, T2DM, insulin resistance and inflammation. It slows the atherosclerotic process and reduces cardiovascular and all-cause mortality. Recent data have demonstrated regression of the microvascular complications of obesity and diabetes including the regeneration of small nerve fibres. The magnitude of change in short-term metabolic effects depends on the surgical procedure whilst longer term effects are related to the amount of sustained excess weight loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":1954671,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Force-pCa relation and troponin T isoforms of rabbit myocardium.\nWe have previously reported the existence of at least four troponin T isoforms in rabbit ventricular muscle and described the changes in their distribution with development. In this report we test whether the proportions of the troponin T isoforms are related to the sensitivity of the myofilaments to calcium. We measured the force-pCa relations in 12 detergent-skinned ventricular strands of cardiac muscle from newborn (2-5-day-old) rabbits. We determined from each strand the amount of each troponin T isoform relative to the total amount of troponin T by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and densitometric scans of Western blots probed with a cardiac-specific troponin T monoclonal antibody, MAb 13-11. To assess the presence of different relative amounts of cardiac and slow skeletal troponin I among the strands, we determined the amount of cardiac troponin I relative to tropomyosin. We determined the Hill coefficient and the pCa for half-maximal force, pCa50, for each strand. pCa50 was related directly to the relative amount of troponin T2 (pslope = 0.037). Our results do not indicate a relation between the Hill coefficient and troponin T2. We also did not find a relation between pCa50 and the cardiac troponin I\/tropomyosin ratio, which suggests that the correlation between pCa50 and troponin T2 was not a result of changes in the relative amounts of cardiac and slow skeletal muscle troponin I. Our findings indicate that a relation exists between the force-pCa characteristics of rabbit myocardium and the troponin T isoforms that it expresses, suggesting a role for troponin T in modulating the sensitivity of cardiac myofilaments to calcium.","subset":"pubmed_abstract"} +{"meta":{"pmid":17603504,"dup_signals":{"dup_doc_count":15,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1}}},"text":"Irreversible cell-cycle transitions are due to systems-level feedback.\nThe irreversibility of cell-cycle transitions is commonly thought to derive from the irreversible degradation of certain regulatory proteins. We argue that irreversible transitions in the cell cycle (or in any other molecular control system) cannot be attributed to a single molecule or reaction, but that they derive from feedback signals in reaction networks. This systems-level view of irreversibility is supported by many experimental observations.","subset":"pubmed_abstract"} +{"meta":{"pmid":28861524,"dup_signals":{"dup_doc_count":27,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-40":5,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2020-45":1,"2020-34":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-35":1,"2024-30":3,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":2}}},"text":"Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut.\nIn this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.","subset":"pubmed_abstract"} +{"meta":{"pmid":24209839,"dup_signals":{"dup_doc_count":11}},"text":"Modeling the synergy of cofilin and Arp2\/3 in lamellipodial protrusive activity.\nRapid polymerization of actin filament barbed ends generates protrusive forces at the cell edge, leading to cell migration. Two important regulators of free barbed ends, cofilin and Arp2\/3, have been shown to work in synergy (net effect greater than additive). To explore this synergy, we model the dynamics of F-actin at the leading edge, motivated by data from EGF-stimulated mammary carcinoma cells. We study how synergy depends on the localized rates and relative timing of cofilin and Arp2\/3 activation at the cell edge. The model incorporates diffusion of cofilin, membrane protrusion, F-actin capping, aging, and severing by cofilin and branch nucleation by Arp2\/3 (but not G-actin recycling). In a well-mixed system, cofilin and Arp2\/3 can each generate a large pulse of barbed ends on their own, but have little synergy; high synergy occurs only at low activation rates, when few barbed ends are produced. In the full spatially distributed model, both synergy and barbed-end production are significant over a range of activation rates. Furthermore, barbed-end production is greatest when Arp2\/3 activation is delayed relative to cofilin. Our model supports a direct role for cofilin-mediated actin polymerization in stimulated cell migration, including chemotaxis and cancer invasion.","subset":"pubmed_abstract"} +{"meta":{"pmid":22711050,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A rare coronary artery anomaly: duplication of right coronary artery with separate ostium on 64-row multidetector computed tomography.\nCoronary artery anomalies are rare, and their incidence varies from 0.6% to 1.3%. Conventional angiography is a commonly used modality for the assessment of coronary artery anomalies, but it may not identify and define the anatomy of anomalous arteries due to the complexity of the course and three-dimensional orientation of the arteries. We present a rare case of duplicated right coronary artery (RCA) with separate ostium on 64-row multidetector computed tomography (MDCT). MDCT is better than conventional angiography in cases where selective catheterisation of either a single artery or ostium during catheter angiography has resulted in missing an important vessel. So far, 13 cases of duplicated RCA have been reported in the literature, and the features on MDCT were described only in three cases.","subset":"pubmed_abstract"} +{"meta":{"pmid":28333685,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":20}}},"text":"A spatially resolved network spike in model neuronal cultures reveals nucleation centers, circular traveling waves and drifting spiral waves.\nWe show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks. In contrast, if the probability of interneuronal connection formation is independent of the distance between neurons, then the nucleation centers do not arise and the synchronization of spiking activity during a network spike occurs spatially uniform throughout the network. Therefore one can conclude that spatial proximity of connections between neurons is important for the formation of nucleation centers. It is also shown that fluctuations of the spatial density of neurons at their random homogeneous distribution typical for the experiments in vitro do not determine the locations of the nucleation centers. The simulation results are qualitatively consistent with the experimental observations.","subset":"pubmed_abstract"} +{"meta":{"pmid":22241045,"dup_signals":{"dup_doc_count":22,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":4,"2024-22":2,"2024-18":3,"2024-10":8,"2024-30":1,"unknown":2}}},"text":"The effect of iron availability on transcription of the Neisseria meningitidis fHbp gene varies among clonal complexes.\nFactor H binding protein (fHbp) is a major antigenic component of novel vaccines designed to protect against meningococcal disease. Prediction of the potential coverage of these vaccines is difficult, as fHbp is antigenically variable and levels of expression differ among isolates. Transcriptional regulation of the fHbp gene is poorly understood, although evidence suggests that oxygen availability is involved. In this study iron accessibility was found to affect fHbp transcription. However, regulation differed among meningococcal clonal complexes (ccs). For the majority of isolates, increased iron concentrations upregulated transcription. This effect was enhanced by the presence of a 181 bp insertion element upstream of fHbp, associated with isolates belonging to cc4 and cc5. Conversely, meningococci belonging to cc32 showed iron-repressed control of fHbp, as regulation was dominated by cotranscription with the iron-repressed upstream gene cbbA. These results highlight the complexity of fHbp regulation and demonstrate that control of transcription can vary among genetic lineages.","subset":"pubmed_abstract"} +{"meta":{"pmid":24584081,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Seroprevalences of Toxoplasma gondii and Neospora caninum in pet rabbits in Japan.\nThe potential contamination of Toxoplasma gondii and Neospora caninum oocysts in the human environment is a concern from the public health viewpoint. However, estimation of their seroprevalences in humans cannot be performed in a manner that distinguishes between oocysts and tissue cysts as a source of infection. Rabbits are considered popular pet animals in Japan that can acquire natural infections by the aforementioned parasites only through the ingestion of oocysts. Therefore, this study was conducted to estimate the seroprevalences of T. gondii and N. caninum in pet rabbits in Japan as an indicator of the possible oocyst contamination in the environment surrounding human beings. Serum samples of 337 rabbits were examined by different serological methods. Enzyme-linked immunosorbent assays were performed to measure the titer of IgG and IgM antibodies. Samples revealed to be seropositive by ELISA were further analyzed by a latex agglutination test, Western blotting and an indirect immunofluorescence assay. The rates of seropositivity for T. gondii were 0.89% (3\/337) and 0.29% (1\/337) in IgG and IgM ELISA, respectively. SAG1 and SAG2 were detected as major antigens by the positive rabbit sera in Western blotting associated with strong staining observed by IFA in T. gondii tachyzoites. Regarding N. caninum, none of the serum samples showed a specific reaction in both Western blotting and the IFA. The results of this study indicate low seroprevalences of toxoplasmosis and neosporosis in pet rabbits in Japan, suggesting low oocyst contamination in the human environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":22236771,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":13}}},"text":"Delineation and diagnostic criteria of Oral-Facial-Digital Syndrome type VI.\nOral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip\/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and\/or additional frenula and\/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":18470746,"dup_signals":{"dup_doc_count":48,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":2,"2022-27":1,"2022-21":1,"2022-05":2,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":2,"2020-45":1,"2020-40":1,"2020-34":1,"2019-47":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-26":1,"2024-18":1,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"Changes produced by external radiation in parameters influencing intestinal permeability and microparticle uptake in vitro.\nTo determine the interaction between X-irradiation and in vitro intestinal microparticle uptake through Caco-2 epithelial cells. Caco-2 cells were cultured on 3 microm porous membranes for 21 days, X-irradiated with 2 Gy or sham-irradiated, then incubated for 5 or 30 min and exposed apically for 30 min to 2 microm latex microparticles. Measurements included cell dimensions, from confocal microscope 'optical slices'; transepithelial resistance (TER) for tight junction (TJ) permeability; particle aggregation; and particle numbers on (adsorbed), in (intraepithelial) and through (submembranous) the epithelium. Irradiation alone reduced TJ permeability more than sham-treatment, more so 5 min than 30 min after treatment. Irradiated epithelia were more permeable to particles than the equivalent sham-irradiated or previously untreated (particle only) groups: the latter two were similar. Irradiation altered adsorbed particle numbers and increased submembranous counts: particle uptake correlated best with cell height. 2 Gy X-irradiation increased particle uptake and translocation through the epithelium. This correlated well with the TJ opening seen after particle exposure in irradiated samples and changes in cell morphology. New data on cell dimensions underlined the similarity in particle uptake between this in vitro epithelium and that in an in vivo model, highlighting the translational significance of the work.","subset":"pubmed_abstract"} +{"meta":{"pmid":23613869,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Combined MRI and \u00b3\u00b9P-MRS investigations of the ACTA1(H40Y) mouse model of nemaline myopathy show impaired muscle function and altered energy metabolism.\nNemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle \u03b1-actin gene (ACTA1) account for \u223c25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and (31)Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (-40%) and specific (-25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.","subset":"pubmed_abstract"} +{"meta":{"pmid":3002660,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure.\nAlthough past reports have identified a variety of prognostic factors in patients with severe chronic heart failure, previous studies have not evaluated the interaction of prognostic variables and drug treatment. We analyzed the association of 30 clinical, hemodynamic, and biochemical variables with survival in 203 consecutive patients with severe heart failure; all variables were assessed just before initiation of treatment with a variety of vasodilator drugs, and all patients were subsequently followed for 6 to 94 months. By regression analysis, pretreatment serum sodium concentration was the most powerful predictor of cardiovascular mortality, with hyponatremic patients having a substantially shorter median survival than did patients with a normal serum sodium concentration (164 vs 373 days, p = .006). The unfavorable prognosis for hyponatremic patients appeared to be related to the marked elevation of plasma renin activity that we noted in these individuals (10.0 +\/- 2.0 ng\/ml\/hr), since hyponatremic patients fared significantly better when treated with angiotensin converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II biosynthesis (median survival 232 vs 108 days, p = .003). In contrast, there was no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low (1.9 +\/- 0.3 ng\/ml\/hr). This interaction between serum sodium concentration, drug treatment, and long-term outcome suggests that the renin-angiotensin system may exert a deleterious effect on the survival of some patients with chronic heart failure, which can be antagonized by converting enzyme inhibition, and provides a clinical counterpart for the similar prognostic role that has been postulated for angiotensin II in experimental preparations of heart failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":12445590,"dup_signals":{"dup_doc_count":14}},"text":"The Tripartite Influence model of body image and eating disturbance: a covariance structure modeling investigation testing the mediational role of appearance comparison.\nRecent theoretical approaches to the etiology of eating disorders and body image disturbances have begun to focus on multifactorial models. In the current study, the Tripartite Influence model was examined in a large sample of college females (ages 18-22). This model proposes that three primary core sources of influence--parents, peers and media--contribute to the development of body image and eating disturbances. Additionally, the model suggests that at least two factors mediate the relationship between influences and disturbance-appearance comparison and internalization of media information. In this study, appearance comparison was examined as a mediational link between peer, family and media influence variables and the outcome disturbance measures of eating dysfunction and body image dissatisfaction. Covariance structure modeling (CSM) was used to test the proposed pathways. The results indicated that appearance comparison mediated the effects of family and media influences on body dissatisfaction, which in turn influenced restrictive and bulimic behaviors. In addition, peer influences had a direct influence on restriction. Perfectionism was hypothesized to relate to body dissatisfaction, but was in fact found to influence appearance comparison. The findings were limited by the necessity of several modifications to the originally proposed models, yet offer replication and extension of previous work with appearance comparison and support for further testing of the Tripartite Influence model.","subset":"pubmed_abstract"} +{"meta":{"pmid":21356737,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":15}}},"text":"The Dogfish Scyliorhinus canicula: A Reference in Jawed Vertebrates.\nINTRODUCTIONDue to their large size and long generation times, chondrichthyans have been largely ignored by geneticists. However, their key phylogenetic position makes them ideal subjects to study the molecular bases of the important morphological and physiological innovations that characterize jawed vertebrates. Such analyses are crucial to understanding the origin of the complex genetic mechanisms unraveled in osteichthyans. The small spotted dogfish Scyliorhinus canicula, a representative of the largest order of extant sharks, presents a number of advantages in this context. Due to its relatively small size among sharks, its abundance, and easy maintenance, the dogfish has been an important model in comparative anatomy and physiology for more than a century. Recently, revived interest has occurred with the development of large-scale transcriptomic and genomic resources, together with the establishment of facilities allowing massive egg and embryo production. These new tools open the way to molecular analyses of the elaborate physiological and sensory systems used by sharks. They also make it possible to take advantage of unique characteristics of these species, such as organ zonation, in analyses of cell proliferation and differentiation. Finally, they offer important perspectives to evolutionary developmental biology that will provide a better understanding of the origin and diversifications of jawed vertebrates. The dogfish whole-genome sequence, which may shortly become accessible, should establish this species as an essential shark reference, complementary to other chondrichthyan models. These analyses are likely to reveal an organism of an underestimated complexity, far from the primitive prototypical gnathostome anticipated in gradistic views.","subset":"pubmed_abstract"} +{"meta":{"pmid":11293908,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Interdigitating dendritic cell sarcoma. A report of four cases and review of the literature.\nTo better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included 1 case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node. Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally, the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months.","subset":"pubmed_abstract"} +{"meta":{"pmid":32187191,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":13}}},"text":"Revision of the sixgill sawsharks, genus Pliotrema (Chondrichthyes, Pristiophoriformes), with descriptions of two new species and a redescription of P. warreni Regan.\nRecent sampling efforts in Madagascar and Zanzibar, as well as examinations of six-gilled sawsharks in several museum collections provided evidence for a complex of species within Pliotrema warreni Regan. The present manuscript contains a redescription of P. warreni involving the syntypes and additional material, as well as formal descriptions of two new species of Pliotrema Regan. All specimens of both new species were found in the western Indian Ocean. Individuals of the first new species, hereafter referred to as P. kajae sp. nov., were identified originating from Madagascar and the Mascarene Ridge. Specimens of the second new species, hereafter referred to as P. annae sp. nov., were only found off Zanzibar. Pliotrema kajae sp. nov. appears to inhabit upper insular slopes and submarine ridges at depths of 214-320 m, P. annae sp. nov. so far is only known from shallow waters (20-35 m). Both new species differ from P. warreni in a number of characteristics including the known distribution range and fresh coloration. Taxonomical differences include barbels that are situated approximately half way from rostral tip to mouth, with prebarbel length equidistant from barbel origin to symphysis of the upper jaw in P. kajae sp. nov. and P. annae sp. nov. (vs. about two thirds way from rostral tip to mouth, with prebarbel length about twice the distance from barbel origin to symphysis of upper jaw in P. warreni) and rostra that are clearly and slightly constricted between barbel origin and nostrils, respectively (vs. rostrum not constricted). Pliotrema kajae sp. nov. differs from P. annae sp. nov. in a longer snout, more numerous large lateral rostral teeth and upper jaw tooth rows, jaw teeth with (vs. without) sharp basal folds, and coloration, particularly pale to light brown (vs. medium to dark brown) dorsal coloration with (vs. without) two indistinct yellowish stripes. A revised diagnosis of Pliotrema and a key to the species are provided.","subset":"pubmed_abstract"} +{"meta":{"pmid":35107832,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":9}}},"text":"On the role of phase separation in the biogenesis of membraneless compartments.\nMolecular mechanistic biology has ushered us into the world of life's building blocks, revealing their interactions in macromolecular complexes and inspiring strategies for detailed functional interrogations. The biogenesis of membraneless cellular compartments, functional mesoscale subcellular locales devoid of strong internal order and delimiting membranes, is among mechanistic biology's most demanding current challenges. A developing paradigm, biomolecular phase separation, emphasizes solvation of the building blocks through low-affinity, weakly adhesive unspecific interactions as the driver of biogenesis of membraneless compartments. Here, I discuss the molecular underpinnings of the phase separation paradigm and demonstrate that validating its assumptions is much more challenging than hitherto appreciated. I also discuss that highly specific interactions, rather than unspecific ones, appear to be the main driver of biogenesis of subcellular compartments, while phase separation may be harnessed locally in selected instances to generate material properties tailored for specific functions, as exemplified by nucleocytoplasmic transport.","subset":"pubmed_abstract"} +{"meta":{"pmid":22294733,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Microfluidic amplification as a tool for massive parallel sequencing of the familial hypercholesterolemia genes.\nFamilial hypercholesterolemia (FH) is an autosomal dominant disorder that affects cholesterol metabolism and is an important risk factor for heart disease. Three different genes were causally linked to this disorder: LDLR (low density lipoprotein receptor), APOB [apolipoprotein B (including Ag(x) antigen)], and PCSK9 (proprotein convertase subtilisin\/kexin type 9). We evaluated a new amplicon preparation tool for resequencing these genes on next generation sequencing (NGS) platforms. For the 3 genes, 38 primer pairs were designed and loaded on the Fluidigm Access Array, a microfluidic array in which a PCR was performed. We amplified 144 DNA samples (73 positive controls and 71 patient samples) and performed 3 sequencing runs on a GS FLX Titanium system from Roche 454, using pyrosequencing. Data were analyzed with the SeqNext module of the Sequence Pilot software. From the 38 amplicons, 37 were amplified successfully, without any further optimization. Sequencing resulted in a mean coverage of the individual amplicons of 71-fold, 74-fold, and 117-fold for the 3 runs, respectively. In the positive controls, all known mutations were identified. In 29% of the patient samples, a pathogenic point mutation or small deletion\/insertion was found. Large rearrangements were not detectable with NGS, but were picked up by multiplex ligation-dependent probe amplification. Combining a microfluidic amplification system with massive parallel sequencing is an effective method for mutation scanning in FH patients, which can be implemented in diagnostics. For data analysis, we propose a minimum variant frequency threshold of 20% and a minimum coverage of 25-fold.","subset":"pubmed_abstract"} +{"meta":{"pmid":20454674,"dup_signals":{"dup_doc_count":46,"dup_dump_count":32,"dup_details":{"curated_sources":4,"2023-50":2,"2022-49":1,"2022-33":1,"2021-25":1,"2021-21":1,"2020-24":1,"2019-30":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-26":2,"2018-17":1,"2018-09":2,"2017-47":2,"2017-39":2,"2017-30":2,"2017-17":1,"2017-09":2,"2017-04":1,"2016-50":2,"2016-44":2,"2016-40":2,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1}}},"text":"Feeding ecology of Coryphaenoides rupestris from the mid-Atlantic Ridge.\nThe Macrourid fish roundnose grenadier, Coryphaenoides rupestris, is one of the most common benthopelagic fishes on the northern mid-Atlantic Ridge. The ecology of the species is comparatively well studied in continental slope waters of the North Atlantic, but not on the mid-Atlantic Ridge, which is a central mid-ocean area of its distribution. In total, 166 specimens from the RV G.O. Sars cruise in July 2004 were examined. The diet mainly comprised cephalopods, pelagic shrimps and fish. Pelagic and benthopelagic copepods were the most numerous prey, but did not contribute much on a weight basis. Cephalopods were by far the most important prey of the small grenadiers, while shrimps and fish became increasingly significant with increasing size. Previous studies from other areas have also found pelagic prey to be important, but in contrast to this study, cephalopods were generally of less importance. The study was an element of more wide-ranging food-web studies of the mid-Atlantic Ridge macro- and megafauna communities within the international MAR-ECO project.","subset":"pubmed_abstract"} +{"meta":{"pmid":18351910,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2021-04":1,"2020-40":1,"2020-10":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2021-17":1}}},"text":"Consensus formation on adaptive networks.\nThe structure of a network can significantly influence the properties of the dynamical processes that take place on them. While many studies have been paid to this influence, much less attention has been devoted to the interplay and feedback mechanisms between dynamical processes and network topology on adaptive networks. Adaptive rewiring of links can happen in real life systems such as acquaintance networks, where people are more likely to maintain a social connection if their views and values are similar. In our study, we consider different variants of a model for consensus formation. Our investigations reveal that the adaptation of the network topology fosters cluster formation by enhancing communication between agents of similar opinion, although it also promotes the division of these clusters. The temporal behavior is also strongly affected by adaptivity: while, on static networks, it is influenced by percolation properties, on adaptive networks, both the early and late time evolutions of the system are determined by the rewiring process. The investigation of a variant of the model reveals that the scenarios of transitions between consensus and polarized states are more robust on adaptive networks.","subset":"pubmed_abstract"} +{"meta":{"pmid":15157692,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":2,"unknown":16}}},"text":"Nicotine differentially activates inhibitory and excitatory neurons in the dorsal spinal cord.\nNicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation of the large family of differentially expressed nicotinic receptors (nAChRs). In order to elucidate the action of nicotinic agonists on spinal local circuits, we have investigated the expression and function of nAChRs in functionally identified neurons of neonate mice spinal cord. Molecular markers, amplified at the single-cell level by RT-PCR, distinguished two neuronal populations in the dorsal horn of the spinal cord: GABAergic\/glycinergic inhibitory interneurons, and calbindin (CA) or NK1 receptor (NK1-R) expressing, excitatory interneurons and projection neurons. The nicotinic response to acetylcholine of single cells was examined, as well as the pattern of expression of nAChR subunit transcripts in the same neuron. Beside the most expressed subunits alpha4, beta2 and alpha7, the alpha2 subunit transcript was found in 19% of neurons, suggesting that agonists targeting alpha2* nAChRs may have specific actions at a spinal level without major supra-spinal effects. Both inhibitory and excitatory neurons responded to nicotinic stimulation, however, the nAChRs involved were markedly different. Whereas GABA\/glycine interneurons preferentially expressed alpha4alpha6beta2* nAChRs, alpha3beta2alpha7* nAChRs were preferentially expressed by CA or NK1-R expressing neurons. Recorded neurons were also classified by firing pattern, for comparison to results from single-cell RT-PCR studies. Altogether, our results identify distinct sites of action of nicotinic agonists in circuits of the dorsal horn, and lead us closer to an understanding of mechanisms of nicotinic spinal analgesia.","subset":"pubmed_abstract"} +{"meta":{"pmid":22552005,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2021-25":2,"2021-04":1,"2020-40":2,"2020-16":1,"2020-05":1,"2019-43":1,"2019-39":1,"2019-30":1,"2019-22":1,"2021-39":1,"2024-26":1,"2024-30":1}}},"text":"Quantitative determination of atenolol in dried blood spot samples by LC-HRMS: a potential method for assessing medication adherence.\nThe use of blood spot collection cards was investigated as a means of obtaining small volume samples for the quantification of therapeutic drugs for assessing medication adherence. A liquid chromatography-high resolution TOF mass spectrometry (LC-HRMS) method, based on the measurement at the accurate mass to charge ratio of the target analyte, was used to ensure specificity for atenolol in the dried blood spot (DBS) samples. A working method was developed and validated. For the preparation of DBS samples whole blood spiked with analyte was used to produce 30 \u03bcl blood spots on specimen collection cards. A 5mm disc was cut from the dried blood spot and extracted using methanol:water (60:40, v\/v) containing the internal standard, atenolol-d(7). Extracts were vortexed, sonicated and then centrifuged. Gradient chromatographic elution was achieved using an Ascentis Express C18 100mm\u00d72.1mm column and a mobile phase flow rate of 0.2 ml\/min and the column oven temperature at 30 \u00b0C. MS detection was carried out in electrospray positive ion mode for target ions at accurate mass m\/z 267.1703 for atenolol and 274.2143 for the IS. Drug extraction efficiency from spiked blood spots was demonstrated to be 96\u00b15% and the drug was stable in DBS for at least 10 weeks. The developed LC-HRMS method was linear within the tested calibration range of 25-1500 ng\/ml and validation showed the accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of \u2264 5% at all concentrations with a limit of quantification of 25 ng\/ml. Factors with potential to affect drug quantification measurements such as the matrix effects, volume of blood applied onto the collection card and effect of different sampling cards were investigated. The developed LC-HRMS method was applied to blood spots on sampling card taken from adult healthy volunteers previously administered a 50mg atenolol tablet and a DBS concentration-time profile was obtained for atenolol. Requiring only a micro volume (30 \u03bcl) blood sample for analysis, the developed DBS based assay has the potential to assess patient adherence to atenolol.","subset":"pubmed_abstract"} +{"meta":{"pmid":24880493,"dup_signals":{"dup_doc_count":23,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2019-30":2,"2019-22":2,"2019-13":2,"2019-04":2,"2018-47":2,"2018-39":2,"2018-30":2,"2018-22":2,"2018-13":2,"2017-43":1,"2017-34":1,"2017-26":1,"2021-17":1}}},"text":"Sulforaphane reduces vascular inflammation in mice and prevents TNF-\u03b1-induced monocyte adhesion to primary endothelial cells through interfering with the NF-\u03baB pathway.\nSulforaphane, a naturally occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 \u03bcM significantly inhibited tumor necrosis factor-\u03b1 (TNF-\u03b1)-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-\u03b1-induced production of monocyte chemotactic protein-1 and adhesion molecules including soluble vascular adhesion molecule-1 and soluble E-selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-\u03b1-induced nuclear factor (NF)-\u03baB transcriptional activity, Inhibitor of NF-\u03baB alpha (I\u03baB\u03b1) degradation and subsequent NF-\u03baB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-\u03baB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-\u03b1-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL\/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced vascular adhesion molecule-1 and monocyte-derived F4\/80-positive macrophages in the aorta of TNF-\u03b1-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-\u03b1-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be, at least in part, associated with interfering with the NF-\u03baB pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":35018034,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Clinical Profile and Comorbidities Associated with Rheumatoid Arthritis Patients in Sudair, Saudi Arabia.\nRheumatoid arthritis (RA) is a chronic, debilitating condition that has a significant effect on the lives of patients, their families, and society at large. The aim is to determine the clinical profile and any comorbidities associated with RA patients in the Sudair region of Saudi Arabia. Sixty patients were included in this cross-sectional observational study, both newly or already diagnosed with RA, fulfilling the 2010 American College of Rheumatology\/European League Against Rheumatism Classification Criteria for RA. They were followed up in the rheumatology clinic in King Khalid Majmaah Hospital in the Majmaah province from January 2017 to December 2020. The subjects' mean age was 47.87 \u00b1 11.55 years, 52 female and 8 male (female-to-male ratio 6.5:1). About 23.3% of patients with RA had positive family history. The main comorbidities and associated diseases were hypertension (18.3%) and hypothyroidism (15%). The most frequently involved joints were the wrist, metacarpophalangeal, proximal interphalangeal, elbow, and knee joints. Subjects were positive in 66.7% for rheumatoid factor and 78.3% for anti-cyclic citrullinated peptide. Both markers were positive in 60% of the patients. Approximately one-quarter of the studied group had a family history of RA. Hypertension followed by hypothyroidism was the most common comorbidities reported in our study.","subset":"pubmed_abstract"} +{"meta":{"pmid":10374318,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[Study on p53, mdm-2 and p21WAF1 protein expression in ER-positive and ER-negative human breast cancer cell lines and its relation to biological features].\nTo study p53, mdm-2 and p21WAF1 protein expression levels in ER-positive and ER-negative human breast cancer cell lines and their relations to biological features. Using cell culture, DNA stable transfection and immunohistochemical methods, the protein expression levels of p53, mdm-2 and WAF1 genes in ER-positive expressing wtp53 MCF-7 cells, ER-negative expressing mtp53 MDA-MB-231 cells and ER-transfected MDA-MB-231 cells were determined, and then, their relation to biological features were compared. (1) The function and expression of p53 protein of MCF-7 and MDA-MB-231 cells were obviously different. The expression levels of mdm-2 and p21WAF1 proteins in MCF-7 cells were higher than those of MDA-MB-231 cells (P < 0.05), The biological features of the former were more favorable than those of the latter. (2) The ER-transfected MDA-MB-231 cells showed lower expression of mtp53 and higher expression of mdm-2 protein (P < 0.05), but no significant difference from that of p21WAF1 protein (P > 0.05). Meanwhile, biological features leading to favorable prognosis were manifested. The ER status of breast cancer cell lines is related to the expression level of p53 and mdm-2 proteins and the biological features.","subset":"pubmed_abstract"} +{"meta":{"pmid":31070578,"dup_signals":{"dup_doc_count":20,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-21":1,"2021-25":1,"2020-29":2,"2020-16":1,"2019-43":2,"2019-39":1,"2019-35":2,"2019-30":2,"2019-22":1,"2022-49":1,"2024-10":1,"2024-26":1}}},"text":"Serological screening for celiac disease in children with systemic lupus erythematosus.\nThe aim of the present study was to investigate the frequency of celiac disease (CD) in patients with juvenile systemic lupus erythematosus (JSLE) and the potential association of JSLE and CD. This was a cross-sectional study performed from October 2015 to October 2017. A total of 50 patients with JSLE were included in the study. The levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all patients. Subjects with increased tTG were further evaluated for anti-endomysial antibodies (EMAs). Gastroduodenoscopy and intestinal biopsy were performed in those with increased EMA levels to confirm the diagnosis of CD. The study included 44 (88.0%) female and 6 (12.0%) male patients. Of the 50 patients, 30 (60.0%) received corticosteroids, and only 4 (8.0%) received no therapy at the time of the study. Only 3 (6.0%) patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies, and none of them had a positive result. We did not find CD in children with systemic lupus erythematosus. Studies with more patients with JSLE are needed to conclude a more precise result.","subset":"pubmed_abstract"} +{"meta":{"pmid":26817924,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":14}}},"text":"Demographically Corrected Normative Standards for the Spanish Language Version of the NIH Toolbox Cognition Battery.\nHispanics are the fastest growing ethnicity in the United States, yet there are limited well-validated neuropsychological tools in Spanish, and an even greater paucity of normative standards representing this population. The Spanish NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neurocognitive screener; however, the original norms were developed combining Spanish- and English-versions of the battery. We developed normative standards for the Spanish NIHTB-CB, fully adjusting for demographic variables and based entirely on a Spanish-speaking sample. A total of 408 Spanish-speaking neurologically healthy adults (ages 18-85 years) and 496 children (ages 3-7 years) completed the NIH Toolbox norming project. We developed three types of scores: uncorrected based on the entire Spanish-speaking cohort, age-corrected, and fully demographically corrected (age, education, sex) scores for each of the seven NIHTB-CB tests and three composites (Fluid, Crystallized, Total Composites). Corrected scores were developed using polynomial regression models. Demographic factors demonstrated medium-to-large effects on uncorrected NIHTB-CB scores in a pattern that differed from that observed on the English NIHTB-CB. For example, in Spanish-speaking adults, education was more strongly associated with Fluid scores, but showed the strongest association with Crystallized scores among English-speaking adults. Demographic factors were no longer associated with fully corrected scores. The original norms were not successful in eliminating demographic effects, overestimating children's performances, and underestimating adults' performances on the Spanish NIHTB-CB. The disparate pattern of demographic associations on the Spanish versus English NIHTB-CB supports the need for distinct normative standards developed separately for each population. Fully adjusted scores presented here will aid in more accurately characterizing acquired brain dysfunction among U.S. Spanish-speakers.","subset":"pubmed_abstract"} +{"meta":{"pmid":17848109,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Developing a telepresence robot for interpersonal communication with the elderly in a home environment.\n\"Telepresence\" is an interesting field that includes virtual reality implementations with human-system interfaces, communication technologies, and robotics. This paper describes the development of a telepresence robot called Telepresence Robot for Interpersonal Communication (TRIC) for the purpose of interpersonal communication with the elderly in a home environment. The main aim behind TRIC's development is to allow elderly populations to remain in their home environments, while loved ones and caregivers are able to maintain a higher level of communication and monitoring than via traditional methods. TRIC aims to be a low-cost, lightweight robot, which can be easily implemented in the home environment. Under this goal, decisions on the design elements included are discussed. In particular, the implementation of key autonomous behaviors in TRIC to increase the user's capability of projection of self and operation of the telepresence robot, in addition to increasing the interactive capability of the participant as a dialogist are emphasized. The technical development and integration of the modules in TRIC, as well as human factors considerations are then described. Preliminary functional tests show that new users were able to effectively navigate TRIC and easily locate visual targets. Finally the future developments of TRIC, especially the possibility of using TRIC for home tele-health monitoring and tele-homecare visits are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":1901706,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Biolistic transformation of a procaryote, Bacillus megaterium.\nWe present a simple and rapid method for introducing exogenous DNA into a bacterium, Bacillus megaterium, utilizing the recently developed biolistic process. A suspension of B. megaterium was spread onto the surface of nonselective medium. Plasmid pUB110 DNA, which contains a gene that confers kanamycin resistance, was precipitated onto tungsten particles. Using a biolistic propulsion system, the coated particles were accelerated at high velocities into the B. megaterium recipient cells. Selection was done by use of an agar overlay containing 50 micrograms of kanamycin per ml. Antibiotic-resistant transformants were recovered from the medium interface after 72 h of incubation, and the recipient strain was shown to contain the delivered plasmid by agarose gel electrophoresis of isolated plasmid DNA. All strains of B. megaterium tested were successfully transformed by this method, although transformation efficiency varied among strains. Physical variables of the biolistic process and biological variables associated with the target cells were optimized, yielding greater than 10(4) transformants per treated plate. This is the first report of the biolistic transformation of a procaryote.","subset":"pubmed_abstract"} +{"meta":{"pmid":28830497,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-06":2,"2022-40":1,"2022-21":1,"2022-05":1,"2021-49":2,"2021-31":1,"2021-21":1,"2021-17":1,"2020-45":2,"2020-16":1}}},"text":"Combining quantitative and qualitative breast density measures to assess breast cancer risk.\nAccurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race\/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk. We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. We calculated ORs and 95% CIs for the effect of BI-RADS breast density and Volpara\u2122 automated dense breast volume on invasive cancer risk, adjusting for other BCSC risk model factors plus body mass index (BMI), and we compared C-statistics between models. We calculated BCSC 5-year breast cancer risk, incorporating the adjusted ORs associated with dense breast volume. Compared with women with BI-RADS scattered fibroglandular densities and second-quartile dense breast volume, women with BI-RADS extremely dense breasts and third- or fourth-quartile dense breast volume (75% of women with extremely dense breasts) had high breast cancer risk (OR 2.87, 95% CI 1.84-4.47, and OR 2.56, 95% CI 1.87-3.52, respectively), whereas women with extremely dense breasts and first- or second-quartile dense breast volume were not at significantly increased breast cancer risk (OR 1.53, 95% CI 0.75-3.09, and OR 1.50, 95% CI 0.82-2.73, respectively). Adding continuous dense breast volume to a model with BCSC risk model factors and BMI increased discriminatory accuracy compared with a model with only BCSC risk model factors (C-statistic 0.639, 95% CI 0.623-0.654, vs. C-statistic 0.614, 95% CI 0.598-0.630, respectively; P < 0.001). Women with dense breasts and fourth-quartile dense breast volume had a BCSC 5-year risk of 2.5%, whereas women with dense breasts and first-quartile dense breast volume had a 5-year risk \u2264 1.8%. Risk models with automated dense breast volume combined with BI-RADS breast density may better identify women with dense breasts at high breast cancer risk than risk models with either measure alone.","subset":"pubmed_abstract"} +{"meta":{"pmid":16829779,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder.\nA series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetamine psychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P=0.018, odds ratio=1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.","subset":"pubmed_abstract"} +{"meta":{"pmid":28808101,"dup_signals":{"dup_doc_count":32,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2020-34":3,"2020-29":2,"2020-24":1,"2019-51":1,"2019-47":2,"2019-43":2,"2019-39":1,"2019-35":1,"2019-26":1,"2018-51":3,"2018-47":1,"2018-43":3,"2018-39":1,"2018-34":3,"2018-30":1,"2018-26":2}}},"text":"Increased SBPase activity improves photosynthesis and grain yield in wheat grown in greenhouse conditions.\nTo meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin-Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of a Brachypodium distachyon SBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regard to future strategies for further improvement of photosynthesis in wheat.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'.","subset":"pubmed_abstract"} +{"meta":{"pmid":8641799,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-45":1,"2020-40":1,"2020-34":2,"2020-29":1,"2020-24":1,"2020-10":2,"2020-05":2,"2019-43":1,"2019-39":1,"2019-35":1,"2021-04":1}}},"text":"Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis.\nHelicobacter pylori is a gram-negative bacterium which causes chronic gastritis and is associated with peptic ulcer disease, gastric carcinoma, and gastric lymphoma. The bacterium is characterized by potent urease activity, thought to be located on the outer membrane, which is essential for survival at low pH. The purpose of the present study was to investigate mechanisms whereby urease and HspB, a GroEL homolog, become surface associated in vitro. Urease, HspB, and catalase were located almost exclusively within the cytoplasm in fresh log-phase cultures assessed by cryo- immunoelectron microscopy. In contrast, significant amounts of surface-associated antigen were observed in older or subcultured preparations concomitantly with the appearance of significant amounts of extracellular antigen, amorphous debris, and membrane fragments. By use of a variety of biochemical methods, a significant fraction of urease and HspB was associated with the outer membrane in subcultured preparations of H. pylori. Taken together, these results strongly suggest that H. pylori cells undergo spontaneous autolysis during culture and that urease and HspB become surface associated only concomitant with bacterial autolysis. By comparing enzyme sensitivity to flurofamide (a potent, poorly diffusible urease inhibitor) in whole cells with that in deliberately lysed cells, we show that both extracellular and intracellular urease molecules are active enzymatically. Autolysis of H. pylori is an important phenomenon to recognize since it likely exerts significant effects on the behavior of H. pylori. Furthermore, the surface properties of H. pylori must be unique in promoting adsorption of cytoplasmic proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":21448103,"dup_signals":{"dup_doc_count":15,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2018-51":1,"2018-43":1,"2018-34":2,"2018-22":1,"2018-13":1,"2017-51":2,"2017-43":2,"2019-13":1}}},"text":"Myths and realities of continuous dopaminergic stimulation.\nMotor fluctuations and dyskinesia in later stages of Parkinson's disease (PD) are caused by pharmacokinetic as well as pharmacodynamic factors, intermittent dopaminergic stimulation being one of the most important. In the healthy brain, dopamine neurons in the substantia nigra pars compacta fire tonically at a steady rate of about 4 cycles\/second. In later stages of PD, steady firing is replaced by pulsatile stimulation which causes molecular and physiologic changes in the basal ganglia. Continuous dopaminergic stimulation has been shown to dramatically improve motor fluctuations and dyskinesia by modifications of oral treatment (dopamine agonists, smaller, more frequent levodopa doses, controlled-release formulation of levodopa, addition of agents that slow down the catabolism of dopamine, such as inhibitors of catechol-O-methyl transferase and monoamine oxidase), transdermal delivery (rotigotine), infusion therapies (intravenous levodopa, subcutaneous application of apomorphine and lisuride, duodenal infusion of levodopa) and deep brain stimulation of the subthalamic nucleus.","subset":"pubmed_abstract"} +{"meta":{"pmid":31651633,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-16":1,"2023-23":1,"2024-10":1,"2024-26":1}}},"text":"Pharmaceutical Care in NICUs in Australia and Poland: Attitudes and Perspectives of Doctors and Nurses.\nA multidisciplinary and collaborative team network is essential in ensuring positive health outcomes for critically ill neonatal patients. The objective of this study was to investigate the perceptions of neonatal intensive care unit (NICU) doctors and nurses in Australia and Poland toward pharmaceutical care services in the NICU. A cross-sectional, anonymous, electronic-based survey was distributed between January and April 2017 among a sample of NICU doctors, nurses, and midwives. A total of 77 participants from Australia and 93 from Poland completed the survey. Overall, from the perspectives of medical and nursing staff, it is apparent that clinical pharmacy practice on the NICU is more established in Australia than in Poland. Only 8.6% of Polish participants reported that a pharmacist worked directly on the NICU in comparison with 87% of Australian participants (P < .001). The main roles performed by pharmacists in Polish NICUs related to the provision of medicines, whereas Australian pharmacists were highly involved in all aspects of pharmacotherapy, particularly in the clinical and education domains. Future efforts should focus on how practice is structured in each country and what support can be implemented from educational, cultural, and legislative levels to enable better pharmacist integration into the NICU therapeutic team.","subset":"pubmed_abstract"} +{"meta":{"pmid":32260599,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"One-dimensional metal oxide-carbon hybrid nanostructures for electrochemical energy storage.\nNumerous metal oxides (MOs) have been considered as promising electrode materials for electrochemical energy storage devices, including lithium-ion batteries (LIBs) and electrochemical capacitors (ECs), because of their outstanding features such as high capacity\/capacitance, low cost, as well as environmental friendliness. However, one major challenge for MO-based electrodes is the poor cycling stability derived from the large volume variation and intense mechanic strain, which are inevitably generated during repeated charge\/discharge processes. Nanostructure engineering has proven to be one of the most effective strategies to improve the electrochemical performance of MO-based electrode materials. Among various nanostructures, one-dimensional (1D) metal oxide-carbon hybrid nanostructures might offer some solution for the challenging issues involved in bulk MO-based electrode materials for energy storage devices. Herein, we give an overview of the rational design, synthesis strategies and electrochemical properties of such 1D MO-carbon structures and highlight some of the latest advances in this niche area. It starts with a brief introduction to the development of nanostructured MO-based electrodes. We will then focus on the advanced synthesis and improved electrochemical performance of 1D MO-carbon nanostructures with different configurations, including MO-carbon composite nanowires, core-shell nanowires and hierarchical nanostructures. Lastly, we give some perspective on the current challenges and possible future research directions in this area.","subset":"pubmed_abstract"} +{"meta":{"pmid":26096909,"dup_signals":{"dup_doc_count":15,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2018-43":1,"2018-26":2,"2018-09":2,"2017-43":2,"2016-40":2,"2019-09":1,"2024-18":1}}},"text":"Dimensionality of stress experiences: Factorial structure of the Perceived Stress Questionnaire (PSQ) in a population-based Swedish sample.\nWe investigated the factorial structure of the Perceived Stress Questionnaire (PSQ-recent; Levenstein, Prantera, Varvo et al., 1993) in a large (N = 1516; 35-95 years) population-based Swedish sample (Nilsson, Adolfsson, B\u00e4ckman et al., 2004; Nilsson, B\u00e4ckman, Erngrund et al., 1997). Exploratory principal components analysis (PCA) was conducted on a first, randomly drawn subsample (n = 506). Next, the model based on the PCA was tested in a second sample (n = 505). Finally, a third sample (n = 505) was used to cross-validate the model. Five components were extracted in the PCA (eigenvalue > 1) and labeled \"Demands,\" \"Worries\/Tension,\" \"Lack of joy,\" \"Conflict,\" and \"Fatigue,\" respectively. Twenty-one out of the 30 original PSQ items were retained in a confirmatory factor analysis (CFA) model that included the five (first-order) factors and, additionally, a general (second-order) stress factor, not considered in prior models. The model showed reasonable goodness of fit [\u03c7(2)(184) = 511.2, p < 0.001; CFI = 0.904; RMSEA = 0.059; and SRMR = 0.063]. Multigroup confirmatory factor analyses supported the validity of the established model. The results are discussed in relation to prior investigations of the factorial structure of the PSQ.","subset":"pubmed_abstract"} +{"meta":{"pmid":37348497,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":2,"2024-18":4,"2024-26":1,"unknown":5}}},"text":"Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.\nAged hematopoietic stem cells (HSCs) display diminished self-renewal and a myeloid differentiation bias. However, the drivers and mechanisms that underpin this fundamental switch are not understood. HSCs produce genotoxic formaldehyde that requires protection by the detoxification enzymes ALDH2 and ADH5 and the Fanconi anemia (FA) DNA repair pathway. We find that the HSCs in young Aldh2-\/-Fancd2-\/- mice harbor a transcriptomic signature equivalent to aged wild-type HSCs, along with increased epigenetic age, telomere attrition, and myeloid-biased differentiation quantified by single HSC transplantation. In addition, the p53 response is vigorously activated in Aldh2-\/-Fancd2-\/- HSCs, while p53 deletion rescued this aged HSC phenotype. To further define the origins of the myeloid differentiation bias, we use a GFP genetic reporter to find a striking enrichment of Vwf+ myeloid and megakaryocyte-lineage-biased HSCs. These results indicate that metabolism-derived formaldehyde-DNA damage stimulates the p53 response in HSCs to drive accelerated aging.","subset":"pubmed_abstract"} +{"meta":{"pmid":9452478,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"Loss of cellular K+ mimics ribotoxic stress. Inhibition of protein synthesis and activation of the stress kinases SEK1\/MKK4, stress-activated protein kinase\/c-Jun NH2-terminal kinase 1, and p38\/HOG1 by palytoxin.\nThe tumor promoter palytoxin has been found to activate the stress-activated protein kinase\/c-Jun NH2-terminal kinase 1 (SAPK\/JNK1), and it also potentiates, as demonstrated here, the p38\/HOG1 mitogen-activated protein kinase and the upstream activator of SAPK\/JNK1, SEK1\/MKK4. In search of possible mechanisms for both the cytotoxicity and the activation of stress kinases by palytoxin, we found that palytoxin is a potent inhibitor of cellular protein synthesis. The inhibition of translation by palytoxin does not result from its direct binding to the translational apparatus. We have previously demonstrated that ribotoxic stressors (Iordanov, M. S., Pribnow, D., Magun, J. L., Dinh, T.-H., Pearson, J. A., Chen, S. L.-Y., and Magun, B. E. (1997) Mol. Cell. Biol. 17, 3373-3381) signal the activation of SAPK\/JNK1 by binding to or covalently modifying 28 S rRNA in ribosomes that are active at the time of exposure to the stressor. Palytoxin acted as a ribotoxic stressor, inasmuch as it required actively translating ribosomes at the time of exposure to activate SAPK\/JNK1. Palytoxin has been shown to augment ion fluxes by binding to the Na+\/K+-ATPase in the plasma membrane of cells. To determine whether altered fluxes of either Na+ or K+ could be responsible for the effects of palytoxin on translation and on activation of SAPK\/JNK1, cells were exposed to palytoxin in modified culture medium in which a major portion of the Na+ was replaced by either K+ or by choline+. The substitution of Na+ by K+ strongly inhibited the ability of palytoxin both to inhibit protein translation and to activate SAPK\/JNK1, whereas the substitution of Na+ by choline+ did not. These results suggest that palytoxin-induced efflux of cellular K+ mimics ribotoxic stress by provoking both translational inhibition and activation of protein kinases associated with cellular defense against stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":22918174,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":2,"unknown":8}}},"text":"Understanding how consumers categorise nutritional labels: a consumer derived typology for front-of-pack nutrition labelling.\nSignificant ongoing debate exists amongst stakeholders as to the best front-of-pack labelling approach and emerging evidence suggests that the plethora of schemes may cause confusion for the consumer. To gain a better understanding of the relevant psychological phenomena and consumer perspectives surrounding FoP labelling schemes and their optimal development a Multiple Sort Procedure study involving free sorting of a range of nutritional labels presented on cards was performed in four countries (n=60). The underlying structure of the qualitative data generated was explored using Multiple Scalogram Analysis. Elicitation of categorisations from consumers has the potential to provide a very important perspective in this arena and results demonstrated that the amount of information contained within a nutrition label has high salience for consumers, as does the health utility of the label although a dichotomy exists in the affective evaluation of the labels containing varying degrees of information aggregation. Classification of exiting front-of-pack labelling systems on a proposed dimension of 'directiveness' leads to a better understanding of why some schemes may be more effective than others in particular situations or for particular consumers. Based on this research an enhanced hypothetical front-of-pack labelling scheme which combines both directive and non-directive elements is proposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":32542336,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Diagnosis of a primary pericardial mesothelioma by the combination of conventional echocardiography and contrast echocardiography.\nPrimary malignancies arising from the pericardium are rare, even more unusual for primary pericardial mesothelioma. The diagnosis is difficult and has no standard treatment. We herein present a case of a 65-year-old woman with primary pericardial mesothelioma associated with dyspnoea and palpitations. Transthoracic conventional echocardiography revealed mild pericardial effusion and a hypo-echogenic mass in the pericardium. Contrast echocardiography showed that the mass was hyper-enhanced with a radial enhancement pattern. The patient underwent open chest exploration and was diagnosed by pathological examination. She had no further treatment and died 2 years later. In conclusion, the combination of conventional echocardiography and contrast echocardiography plays a significant role in diagnosing primary pericardial mesothelioma. Comprehensive evaluation and accurately preoperative diagnosis are important to exclude certain tumours that do not require surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":30671038,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":4,"2022-27":2,"2022-05":2,"2021-31":2,"2021-17":3,"2022-33":1}}},"text":"AgNPs Change Microbial Community Structures of Wastewater.\nDue to their strong antimicrobial activity, silver nanoparticles (AgNPs) are massively produced, applied, consumed and, as a negative consequence, released into wastewater treatment plants. Most AgNPs are assumed to be bound by sludge, and thus bear potential risk for microbial performance and stability. In this lab-scale study, flow cytometry as a high-throughput method and 16S rRNA gene amplicon Illumina MiSeq sequencing were used to track microbial community structure changes when being exposed to AgNPs. Both methods allowed deeper investigation of the toxic impact of chemicals on microbial communities than classical EC50 determination. In addition, ecological metrics were used to quantify microbial community variations depending on AgNP types (10 and 30 nm) and concentrations. Only low changes in \u03b1- and intra-community \u03b2-diversity values were found both in successive negative and positive control batches and batches that were run with AgNPs below the EC50 value. Instead, AgNPs at EC50 concentrations caused upcoming of certain and disappearance of formerly dominant subcommunities. Flavobacteriia were among those that almost disappeared, while phylotypes affiliated with Gammaproteobacteria (3.6-fold) and Bacilli (8.4-fold) increased in cell abundance in comparison to the negative control. Thus, silver amounts at the EC50 value affected community structure suggesting a potential negative impact on functions in wastewater treatment systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":22262219,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2019-26":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2019-39":1}}},"text":"The endothelial safety of using a gentian violet dry-ink \"S\" stamp for precut corneal tissue.\nTo determine the endothelium damage resulting from the application of \"dry\" gentian violet (GV) stromal markings on corneas precut for Descemet stripping automated endothelial keratoplasty (DSAEK) using a Moria \"S\" Stamp. Five precut corneas had the stromal graft bed marked with GV using the Moria \"S\" stamp and 6 precut corneas were left unmarked as controls. After applying the ink to the stamp, care was taken to allow the alcohol carrier to dry for 10 seconds before applying the dry dye to the stromal surface. Tissue was then trephinated and stained with calcein AM to assess endothelial viability. Grafts were photographed and digital pixel planometry, using an established analysis technique, was used to compare the damage between the control and experimental groups. The mean percent cell damage of corneas treated with GV \"S\" stamp (n = 5) was 8.6% (range 4.4-12.9), and it was 8.1% (range 3.9-15.1) in the DSAEK control set (n = 6). Median percent cell damage was 6.7% among GV-treated corneas and 7.4% among control corneas. The distributions were not significantly different between groups (Mann-Whitney U test = 15.0, two-tailed P = 1.0). Moreover, no \"S\" pattern of damage was seen in any study eye. There were no significant differences in endothelial damage between the 2 groups. GV stromal markings may be applied without undue damage to the endothelium using the dry-ink technique described.","subset":"pubmed_abstract"} +{"meta":{"pmid":23517524,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Association between preoperative diuretic use and in-hospital outcomes after cardiac surgery.\nThere is a paucity of evidence on the association between preoperative diuretics use and outcomes following cardiac surgery. We hypothesized that diuretic use prior to cardiac surgery will be associated with adverse in-hospital clinical outcomes. We evaluated patients undergoing cardiac surgery at a single institution between January 1, 2000, and December 31, 2011. Patients were grouped as follows: isolated coronary artery bypass grafting (CABG) (n = 8759), CABG plus valve surgery (n = 1188), and valve surgery only (n = 2646). A fourth group \"All cardiac surgery\" is comprised of patients from all three groups. Preoperative diuretic use was defined as patient on any diuretic till the day of surgery. Primary outcome was the incidence of major adverse events (MAEs) defined as the composite of mortality, postoperative renal dysfunction, myocardial infarction, stroke, and new-onset atrial fibrillation (AF). Logistic regression analysis and propensity score matching were performed. We included 12,593 patients [3546 on diuretic (28%)]. After logistic regression analyses, preoperative diuretic use was associated with an increased risk of the following: (1) MAE among all groups except the concomitant CABG and valve surgery group, (2) AF in \"All cardiac surgery\" and isolated CABG groups, (3) postoperative renal dysfunction in all groups. After propensity score matching (n = 3050 in each group), preoperative diuretic use was significantly associated with MAE (48% vs. 43%; P < 0.0001), postoperative renal dysfunction (19% vs. 14%; P < 0.0001), and AF (34% vs. 32%; P = 0.03) in the \"All cardiac surgery\" group. Preoperative diuretics use is associated with an increased incidence of MAEs after cardiac surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":15599055,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Unusual distribution of mitochondrial large subunit rRNA in the cytosol during conjugation in Tetrahymena thermophila.\nThe distribution of mitochondria during conjugation of the ciliated protozoan Tetrahymena thermophila was surveyed using a mitochondrial stain and fluorescence in situ hybridization (FISH). When the mitochondria-specific stain, Mito-Tracker, was used, the majority of mitochondria were detected in the cortex; their distribution was not changed during conjugation. On the other hand, FISH using mitochondrial large subunit (LSU) rRNA as a probe showed an unusual distribution of signals during conjugation. Unexpectedly, the signals were detected throughout the cytoplasm of conjugating cells. These signals were not observed in pre-mating cells and in exconjugants. The cytosolic localization of mitochondrial rRNA was supported by northern blot analysis using post-mitochondrial RNA fraction at the later stages of conjugation. These observations suggest selective mitochondrial breakdown or transport of LSU rRNA into cytosol. The biological significance of the conjugation-specific appearance of the cytosolic mitochondrial rRNA is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":22476815,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2021-49":1,"2019-26":1,"2019-18":1,"2018-47":1,"2018-30":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2023-40":1,"2017-13":1,"2024-26":1}}},"text":"Quality-score refinement of SSU rRNA gene pyrosequencing differs across gene region for environmental samples.\nDue to potential sequencing errors in pyrosequencing data, species richness and diversity indices of microbial systems can be miscalculated. The \"traditional\" sequence refinement method is not sufficient to account for overestimations (e.g., length, primer errors, ambiguous nucleotides). Recent in silico and single-organism studies have revealed the importance of sequence quality scores in the estimation of ecological indices; however, this is the first study to compare quality-score stringencies across four regions of the SSU rRNA gene sequence (V1V2, V3, V4, and V6) with actual environmental samples compared directly to corresponding clone libraries produced from the same primer sets. The nucleic acid sequences determined via pyrosequencing were subjected to varying quality-score cutoffs that ranged from 25 to 32, and at each quality-score cutoff, either 10 or 15 % of the nucleotides were allowed to be below the cutoff. When species richness estimates were compared for the tested samples, the cutoff values of Q27(15%), Q30(10%), and Q32(15%) for V1V2, V4, and V6, respectively, estimated similar values as obtained with clone libraries and Sanger sequencing. The most stringent Q tested (Q32(10%)) was not enough to account for species richness inflation of the V3 region pyrosequence data. Results indicated that quality-score assessment greatly improved estimates of ecological indices for environmental samples (species richness and \u03b1-diversity) and that the effect of quality-score filtering was region-dependent.","subset":"pubmed_abstract"} +{"meta":{"pmid":17349018,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Melatonin induces neuritogenesis at early stages in N1E-115 cells through actin rearrangements via activation of protein kinase C and Rho-associated kinase.\nMelatonin increases neurite formation in N1E-115 cells through microtubule enlargement elicited by calmodulin antagonism and vimentin intermediate filament reorganization caused by protein kinase C (PKC) activation. Microfilament rearrangement is also a necessary process in growth cone formation during neurite outgrowth. In this work, we studied the effect of melatonin on microfilament rearrangements present at early stages of neurite formation and the possible participation of PKC and the Rho-associated kinase (ROCK), which is a downstream kinase in the PKC signaling pathway. The results showed that 1 nm melatonin increased both the number of cells with filopodia and with long neurites. Similar results were obtained with the PKC activator phorbol 12-myristate 13-acetate (PMA). Both melatonin and PMA increased the quantity of filamentous actin. In contrast, the PKC inhibitor bisindolylmaleimide abolished microfilament organization elicited by either melatonin or PMA, while the Rho inhibitor C3, or the ROCK inhibitor Y27632, abolished the bipolar neurite morphology of N1E-115 cells. Instead, these inhibitors prompted neurite ramification. ROCK activity measured in whole cell extracts and in N1E-115 cells was increased in the presence of melatonin and PMA. The results indicate that melatonin increases the number of cells with immature neurites and suggest that these neurites can be susceptible to differentiation by incoming extracellular signals. Data also indicate that PKC and ROCK are involved at initial stages of neurite formation in the mechanism by which melatonin recruits cells for later differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":8558425,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.\n(-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol\/kg s.c. and 0.54 mumol\/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol\/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which selectively stimulates the D1 receptor, may represent a novel mechanism for Parkinson's disease therapy with the potential for an improved side-effect profile and, consequently, improved patient compliance.","subset":"pubmed_abstract"} +{"meta":{"pmid":6331338,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A search for cytomegalovirus and herpes viral antigen in brains of schizophrenic patients.\nThe peroxidase-antiperoxidase method was employed to search for evidence of cytomegalovirus (CMV) or herpes simplex virus (HSV) antigen in the brains of 25 patients with a diagnosis of schizophrenia, 25 nonschizophrenic neuropsychiatric patients, and 16 nonpsychiatric control subjects. Brain specimens from patients with acute CMV and herpes encephalitis served as positive controls. Although early results with low-titer CMV antisera suggested immunoreactivity in specific brain regions of a small number of schizophrenic and control cases, the present studies with high-titer anti-CMV IgG did not give a positive immunoperoxidase reaction in sections from the basal forebrain, hypothalamus, or midbrain. Scattered neurons in the lateral vestibular nucleus and hippocampus showed questionable staining with CMV IgG in one schizophrenic patient and none in control subjects. No schizophrenic or control cases demonstrated an immune reaction to HSV antisera.","subset":"pubmed_abstract"} +{"meta":{"pmid":25885447,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Extending life for people with a terminal illness: a moral right and an expensive death? Exploring societal perspectives.\nMany publicly-funded health systems apply cost-benefit frameworks in response to the moral dilemma of how best to allocate scarce healthcare resources. However, implementation of recommendations based on costs and benefit calculations and subsequent challenges have led to 'special cases' with certain types of health benefits considered more valuable than others. Recent debate and research has focused on the relative value of life extensions for people with terminal illnesses. This research investigates societal perspectives in relation to this issue, in the UK. Q methodology was used to elicit societal perspectives from a purposively selected sample of data-rich respondents. Participants ranked 49 statements of opinion (developed for this study), onto a grid, according to level of agreement. These 'Q sorts' were followed by brief interviews. Factor analysis was used to identify shared points of view (patterns of similarity between individuals' Q sorts). Analysis produced a three factor solution. These rich, shared accounts can be broadly summarised as: i) 'A population perspective - value for money, no special cases', ii) 'Life is precious - valuing life-extension and patient choice', iii) 'Valuing wider benefits and opportunity cost - the quality of life and death'. From the factor descriptions it is clear that the main philosophical positions that have long dominated debates on the just allocation of resources have a basis in public opinion. The existence of certain moral positions in the views of society does not ethically imply, and pragmatically cannot mean, that all are translated into policy. Our findings highlight normative tensions and the importance of critically engaging with these normative issues (in addition to the current focus on a procedural justice approach to health policy). Future research should focus on i) the extent to which these perspectives are supported in society, ii) how respondents' perspectives relate to specific resource allocation questions, and iii) the characteristics of respondents associated with each perspective.","subset":"pubmed_abstract"} +{"meta":{"pmid":32015065,"dup_signals":{"dup_doc_count":21,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-50":2,"2021-43":2,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":3,"2020-40":1,"2020-34":3,"2020-24":1,"2020-16":1,"2020-10":1,"2024-18":1,"2024-30":1}}},"text":"A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities.\nWe present a technological advancement for the estimation of the affinities of Protein-Protein Interactions (PPIs) in living cells. A novel set of vectors is introduced that enables a quantitative yeast two-hybrid system based on fluorescent fusion proteins. The vectors allow simultaneous quantification of the reaction partners (Bait and Prey) and the reporter at the single-cell level by flow cytometry. We validate the applicability of this system on a small but diverse set of PPIs (eleven protein families from six organisms) with different affinities; the dissociation constants range from 117 pm to 17 \u03bcm After only two hours of reaction, expression of the reporter can be detected even for the weakest PPI. Through a simple gating analysis, it is possible to select only cells with identical expression levels of the reaction partners. As a result of this standardization of expression levels, the mean reporter levels directly reflect the affinities of the studied PPIs. With a set of PPIs with known affinities, it is straightforward to construct an affinity ladder that permits rapid classification of PPIs with thus far unknown affinities. Conventional software can be used for this analysis. To permit automated analysis, we provide a graphical user interface for the Python-based FlowCytometryTools package.","subset":"pubmed_abstract"} +{"meta":{"pmid":16951379,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.\nIL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-\/-)) fibroblasts as compared with wild-type Stat6(+\/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-\/-) fibroblasts as compared with Stat1(+\/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-\/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-\/-) fibroblasts and yet enhanced Egr-1 mRNA and protein levels in Stat1(-\/-) fibroblasts. Our findings support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory effects on Egr-1 and PDGF ligand mRNA transcription, respectively. This novel mechanism could aid in identifying molecular targets for the treatment of chronic airway remodeling and fibrosis in asthma.","subset":"pubmed_abstract"} +{"meta":{"pmid":21448971,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Stressful life events predict eating disorder relapse following remission: six-year prospective outcomes.\nTo examine prospectively the natural course of bulimia nervosa (BN) and eating disorder not-otherwise-specified (EDNOS) and test for the effects of stressful life events (SLE) on relapse after remission from these eating disorders. 117 female patients with BN (N = 35) or EDNOS (N = 82) were prospectively followed for 72 months using structured interviews performed at baseline, 6- and 12-months, and then yearly thereafter. ED were assessed with the structured clinical interview for DSM-IV, and monitored over time with the longitudinal interval follow-up evaluation. Personality disorders were assessed with the diagnostic interview for DSM-IV-personality-disorders, and monitored over time with the follow-along-version. The occurrence and specific timing of SLE were assessed with the life events assessment interview. Cox proportional-hazard-regression-analyses tested associations between time-varying levels of SLE and ED relapse, controlling for comorbid psychiatric disorders, ED duration, and time-varying personality-disorder status. ED relapse probability was 43%; BN and EDNOS did not differ in time to relapse. Negative SLE significantly predicted ED relapse; elevated work and social stressors were significant predictors. Psychiatric comorbidity, ED duration, and time-varying personality-disorder status were not significant predictors. Higher work and social stress represent significant warning signs for triggering relapse for women with remitted BN and EDNOS.","subset":"pubmed_abstract"} +{"meta":{"pmid":30391627,"dup_signals":{"dup_doc_count":33,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-21":2,"2021-49":2,"2021-43":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":3,"2020-45":1,"2020-40":1,"2019-30":1,"2019-13":1,"2019-04":1,"2023-50":1,"2024-18":1,"2024-10":3,"2024-26":1}}},"text":"Multisensory processing in event-based prospective memory.\nFailures in prospective memory (PM) - that is, the failure to remember intended future actions - can have adverse consequences. It is therefore important to study those processes that may help to minimize such cognitive failures. Although multisensory integration has been shown to enhance a wide variety of behaviors, including perception, learning, and memory, its effect on prospective memory, in particular, is largely unknown. In the present study, we investigated the effects of multisensory processing on two simultaneously-performed memory tasks: An ongoing 2- or 3-back working memory (WM) task (20% target ratio), and a PM task in which the participants had to respond to a rare predefined letter (8% target ratio). For PM trials, multisensory enhancement was observed for congruent multisensory signals; however, this effect did not generalize to the ongoing WM task. Participants were less likely to make errors for PM than for WM trials, thus suggesting that they may have biased their attention toward the PM task. Multisensory advantages on memory tasks, such as PM and WM, may be dependent on how attention resources are allocated across dual tasks.","subset":"pubmed_abstract"} +{"meta":{"pmid":33708076,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Neuroserpin Is Strongly Expressed in the Developing and Adult Mouse Neocortex but Its Absence Does Not Perturb Cortical Lamination and Synaptic Proteome.\nNeuroserpin is a serine protease inhibitor that regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin is strongly expressed during nervous system development as well as during adulthood, when it is predominantly found in regions eliciting synaptic plasticity. In the hippocampus, neuroserpin regulates developmental neurogenesis, synaptic maturation and in adult mice it modulates synaptic plasticity and controls cognitive and social behavior. High expression levels of neuroserpin in the neocortex starting from prenatal stage and persisting during adulthood suggest an important role for the serpin in the formation of this brain region and in the maintenance of cortical functions. In order to uncover neuroserpin function in the murine neocortex, in this work we performed a comprehensive investigation of its expression pattern during development and in the adulthood. Moreover, we assessed the role of neuroserpin in cortex formation by comparing cortical lamination and neuronal maturation between neuroserpin-deficient and control mice. Finally, we evaluated a possible regulatory role of neuroserpin at cortical synapses in neuroserpin-deficient mice. We observed that neuroserpin is expressed starting from the beginning of corticogenesis until adulthood throughout the neocortex in several classes of glutamatergic projection neurons and GABA-ergic interneurons. However, in the absence of neuroserpin we did not detect any alteration either in cortical layer formation, or in neuronal soma size and dendritic length. Furthermore, no significant quantitative changes were observed in the proteome of cortical synapses upon neuroserpin deficiency. We conclude that, although strongly expressed in the neocortex, absence of neuroserpin does not lead to gross developmental abnormalities, and does not perturb the composition of the cortical synaptic proteome.","subset":"pubmed_abstract"} +{"meta":{"pmid":20299815,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Radiofrequency coblation decreases blood loss during endoscopic sinonasal and skull base tumor removal.\nMinimizing bleeding during transnasal resections of sinonasal tumors is imperative for optimizing visualization and decreasing complications. The purpose of the present study was to determine whether radiofrequency coblation decreases blood loss during endoscopic tumor removal. Sinonasal\/skull base tumors treated in 2008 with endoscopic techniques were reviewed. The data collected included demographics, histopathology, technique, duration, complications and estimated blood loss (EBL). Full operative videoendoscopy was available in all cases and scored by the authors using the 11-point Wormald surgical field grading scale. Twenty-three patients (average age: 46 years) with sinonasal or skull base tumors treated with transnasal endoscopic techniques were identified. Coblation was used in 10 cases. The sinus\/skull base tumors included were esthesioneuroblastoma (n = 6), melanoma (n = 3), squamous cell carcinoma (n = 3), inverted papilloma (n = 3), adenocarcinoma (n = 2), intracranial dermoid cyst (n = 2), adenoid cystic carcinoma (n = 1), craniopharyngioma (n = 1), fibromyxosarcoma (n = 1) and undifferentiated carcinoma (n = 1). The use of the coblation device was associated with a significant decrease in all categories including EBL (350 vs. 1,000 ml; p = 0.0001), EBL per operative time (66 vs. 166 ml\/h; p = 0.0001) and Wormald grade (3.3 vs. 6.4; p = 0.0001). Radiofrequency coblation significantly decreased blood loss during endoscopic tumor removal and is a useful tool in the armamentarium of the endoscopic skull base surgeon.","subset":"pubmed_abstract"} +{"meta":{"pmid":22191311,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2022-49":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-13":1,"2023-14":1,"2024-18":1}}},"text":"[Quality of life in women with pelvic floor dysfunction].\nPelvic floor dysfunction is a frequent problem affecting more than 50% of women in peri- and postmenopause. Considering that ageing and menopause befall in the significant factors causing this issue, as well as the expected longevity of women in the world and in our country, pelvic floor dysfunction prevelence is foreseen to be even higher. The aim of the study was to evaluate impact of the symptoms of pelvic dysfunction on quality of life and examine body image satisfaction in adult women with pelvic organ prolapse presenting to tertiary care clinic for surgical treatment. This prospective case-control study included 50 patients who presented to tertiary care gynecology clinic for surgical treatment and 50 controls with normal pelvic floor support and without urinary incontinence who presented tertiary care gynecology clinic for other reasons. Both, patients and controls, completed two quastionnaires recommended for the evaluation of symptoms (Pelvic floor distress inventory - short forms) and quality of life impact (Pelvic floor impact questionnaire - short form) of pelvic organ prolapse, and Body Image Scale. The patients scored significantly worse on the prolapse, urinary, colorectal scales and overall score of Pelvic floor distress inventory--20 than controls subjects (134.91 vs 78.08; p < 0.01). The patients also measured significant decrease in condition-specific quality of life (89.23 vs 3.1; p < 0.01). They were more likely to feel self-conscious (78% vs 42%; p < 0.01), less likely to feel physically attractive (78% vs 22%; p < 0.01), more likely to have difficulty looking at themselves naked (70% vs 42%; p < 0.01), less likely to feel sexually attractive (64% vs 32%; p < 0.01), and less likely to feel feminine (56% vs 16%; p < 0.05), than controls. There were no differencies in their feeling of dissatisfaction with appearance when dressed, avoiding people because of appereance and overall dissatisfaction with their body. There was a positive correlation between decreased quality of life and body image in women with pelvic dysfunction. Women with pelvic floor dysfunction have decreased quality of life and body image.","subset":"pubmed_abstract"} +{"meta":{"pmid":8316841,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2020-50":2,"2020-34":1,"2020-24":1,"2020-10":2,"2019-47":1,"2018-43":1,"2018-17":1,"2016-50":1,"2021-17":1}}},"text":"Commitment of cell fate in the early zebrafish embryo.\nWhen do single cells in the early zebrafish embryo become irreversibly committed to a specific fate? Work with lineage tracing and fate mapping has shown that the marginal cells of the blastoderm give rise to hypoblast-derived fates (mesoderm and endoderm). However, experiments described here show that these marginal blastoderm cells remain pluripotent and uncommitted throughout the late blastula and early gastrula stages. Embryonic cells become committed to a hypoblast-derived fate at mid-gastrulation. Time-lapse photographic analysis reveals that committed cells, when transplanted heterotopically and heterochronically, can migrate along atypical pathways to reposition themselves within a more correct environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":30682109,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"Social representation of palliative care in the Spanish printed media: A qualitative analysis.\nLack of social awareness is a major barrier to the development of palliative care. Mass media influences public opinion, and frequently deal with palliative care contributing to its image and public understanding. To analyse how palliative care is portrayed in Spanish newspapers, as well as the contribution made by the press to its social representation. Based on criteria of scope and editorial plurality, four print newspapers were selected. Using the newspaper archive MyNews (www.mynews.es), articles published between 2009 and 2014 containing the words \"palliative care\" or \"palliative medicine\" were identified. Sociological discourse analysis was performed on the identified texts on two levels: a) contextual analysis, focusing on the message as a statement; b) interpretative analysis, considering the discourse as a social product. We examined 262 articles. Politician and healthcare professionals were the main representatives transmitting messages on palliative care. The discourses identified were characterised by: strong ideological and moral content focusing on social debate, strong ties linking palliative care and death and, to a lesser degree, as a healthcare service. The messages transmitted by representatives with direct experience in palliative care (professionals, patients and families) contributed the most to building a positive image of this healthcare practice. Overall, media reflect different interests in framing public understanding about palliative care. The knowledge generated about how palliative care is reflected in the printed media may help to understand better one of the main barriers to its development not only in Spain, but also in other contexts.","subset":"pubmed_abstract"} +{"meta":{"pmid":30950175,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Total and added sugars consumption in Argentina: Their contribution to daily energy intake. Results from Latin American Study of Nutrition and Health (ELANS).\nThe aim of the present study is to determine the intake of total sugars (TS) and added sugars (AS) in Argentina based on the local data of the Latin American Study of Nutrition and Health (ELANS). This is a cross-sectional study of a representative sample of the urban Argentine population (n = 1266). The sample was stratified by age group (15-65 years), gender, geographic region and socioeconomic level (SEL). TS and AS intake were obtained by two 24-hour recalls (R24) and analysed using the Nutrition Data System for Research Software 2013. On average, TS consumption in Argentina was 114.3 g\/day, accounting for 39.8% of the total carbohydrate intake and 20.6% total energy (TE) intake. Overall, 77.2% of the TS intake consisted of AS (90.4 g\/day), contributing to 30.4% of total carbohydrate intake and 15.9%TE. Men consume more TS and AS (in g\/day), with no difference in the AS %TE between men and women. The consumption of sugars decreased with age, with adolescents consuming more AS and older adults more intrinsic sugars. The intake of AS was higher in low SEL. In Argentina, the intake of AS was 50% above the recommendations. Younger and socially vulnerable people are at higher risk of excessive intake.","subset":"pubmed_abstract"} +{"meta":{"pmid":29651848,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mass-Spectrometry-Based Identification of Cross-Links in Proteins Exposed to Photo-Oxidation and Peroxyl Radicals Using 18O Labeling and Optimized Tandem Mass Spectrometry Fragmentation.\nProtein cross-links are formed in regulated biochemical processes in many biological systems, but they are also generated inadvertently via the reactions of exogenous or endogenous oxidants. Site-specific identification and characterization of such cross-links is challenging, and the goal was, therefore, to develop mass-spectrometry-based approaches tailored for proteins subjected to oxidative challenges that also are applicable for the analysis of complex samples. Using trypsin-mediated 18O isotopic labeling, different types of data acquisition workflows, and designated database software tools, we successfully identified tyrosine-tyrosine, tyrosine-tryptophan, tyrosine-lysine, and histidine-lysine cross-links in proteins subjected to sensitizer-mediated photo-oxidation with rose bengal or chemical oxidation with peroxyl radicals generated from the water-soluble compound 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Subsequently, AAPH was also applied to a protein extract from the Gram-positive bacterium Lactococcus lactis, demonstrating the feasibility to identify tyrosine-tyrosine, tyrosine-tryptophan, and tryptophan-tryptophan cross-linked peptides in a complex system. Different fragmentation techniques were evaluated, and it was observed that higher-energy collisional dissociation (HCD) resulted in a higher number of identified cross-link peptides, while electron-transfer dissociation supplemented with HCD (EThcD) generally provides higher fragment ion coverage of the cross-linked peptides.","subset":"pubmed_abstract"} +{"meta":{"pmid":27017331,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":12}}},"text":"Long term effects of olfactory training in patients with post-infectious olfactory loss.\nThere is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.","subset":"pubmed_abstract"} +{"meta":{"pmid":11459290,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":15}}},"text":"Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.\nThe mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK\/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":16122702,"dup_signals":{"dup_doc_count":13}},"text":"ISG15 modification of ubiquitin E2 Ubc13 disrupts its ability to form thioester bond with ubiquitin.\nISG15 was the first ubiquitin-like modifier to be identified. However, the function of ISG15 modification has been an enigma for many years. At present, no data are available about the function of ISGylation for any target. In this paper, we report the identification of Ubc13, which forms a unique ubiquitin-conjugating enzyme (Ubc) complex with ubiquitin enzyme variant Mms2 and generates atypical Lys63-linked ubiquitin conjugates, as one of the targets of ISG15 modification. Furthermore, we identify Lys92 as the only ISG15 modification site in Ubc13, which is the first report about the ISG15 modification site. Using the \"covalent affinity\" purification assay, we found that unmodified Ubc13 can bind to the ubiquitin-agarose, whereas ISGylated Ubc13 cannot. This result indicates that ISGylation of Ubc13 disrupts its ability to form thioester bond with ubiquitin.","subset":"pubmed_abstract"} +{"meta":{"pmid":20826898,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The biological effectiveness of targeted radionuclide therapy based on a whole-body pharmacokinetic model.\nBiologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumour response relationships. By taking into account the dose rate and tissue-specific parameters such as repair and radiosensitivity, it is possible to compare the relative biological effects of different targeted radionuclide therapy (TRT) agents. The aim of this work was to develop an analytical tumour BED calculation for TRT that could predict a relative biological effect based on normal body and tumour pharmacokinetics. This work represents a step in the direction of establishing relative pharmacokinetic criteria of when the BED formalism is more applicable than absorbed dose for TRT. A previously established pharmacokinetic (PK) model for TRT was used and adapted into the BED formalism. An analytical equation for the protraction factor, which incorporates dose rate and repair rate, was derived. Dose rates within the normal body and tumour were related to the slopes of their time-activity curves which were determined by the ratios of their respective PK parameters. The relationships between the tumour influx-to-efflux ratio (k(34):k(43)), central compartment efflux-to-influx ratio (k(12):k(21)), central elimination (k(el)), and tumour repair rate (\u03bc), and tumour BED were investigated. As the k(34):k(43) ratio increases and the k(12):k(21) ratio decreases, the difference between tumour BED and D increases. In contrast, as the k(34):k(43) ratios decrease and the k(12):k(21) ratios increase, the tumour BED approaches D. At large k(34):k(43) ratios, the difference between tumour BED and D increases to a maximum as k(el) increases. At small k(34):k(43) ratios, the tumour BED approaches D at very small k(el). At small \u03bc and small k(34):k(43) ratios, the tumour BED approaches D. For large k(34):k(43) ratios, large \u03bc values cause tumour BED to approach D. This work represents a step in the direction of establishing relative PK criteria of when the BED formalism is more applicable than absorbed dose for TRT. It also provides a framework by which the biological effects of different TRT agents can be compared in order to predict efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":8370118,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":9}}},"text":"Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle.\nThe influence of Ca2+ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 mumol\/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (ktr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which ktr increases almost 10-fold from low to maximal activation levels, ktr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, ktr never increased with length. Data presented here are consistent with a model of myocardial Ca2+ activation in which Ca2+ modulates the number of crossbridges interacting with the thin filament and are inconsistent with a model in which Ca2+ modulates the kinetics of transitions to force producing states within the actomyosin cycle. Differences in the activation dependence of the force redevelopment rate between cardiac and skeletal muscle suggest that there are fundamental differences in the mechanism of Ca2+ activation between these two muscle types.","subset":"pubmed_abstract"} +{"meta":{"pmid":10773859,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Modalities of fatigue in multiple sclerosis: correlation with clinical and biological factors.\nAlthough different factors are probably involved in the etiology of fatigue in multiple sclerosis patients, no definite mechanism has been proposed. We have proposed that fatigue is a complex symptom that includes three clinical different entities (asthenia, fatigability and worsening of symptoms with effort). The goal of this study is to demonstrate if there is a peculiar mechanism for each of the different varieties of fatigue. A control sample of 155 patients (105 women, 50 men) with clinically definite MS was studied. Fatigue was measured using the Fatigue Descriptive Scale (FDS) and the Fatigue Severity Scale (FSS). Treatment, depression, anxiety, sleep and cellular immune status were studied too. Fatigue was a symptom in 118 patients (76.13%); 26 patients (22.03%) described it as asthenia (fatigue at rest); 85 patients (72.03%) as fatigability (fatigue with exercise), and seven patients (5.9%) as worsening of symptoms. The severity of pyramidal involvement was significantly more severe in patients suffering from fatigue; some immunological parameters were associated with fatigue as well. The discriminant analysis of the data shows that some of the immunoactivation parameters are associated with asthenia (F=21.5, P<0.001), and pyramidal tract involvement is associated with fatigability (F=10.5, P<0.001). Sleep disorders, anxiety and depression were linked with fatigue in a few patients. No relationship with treatment was proven. In conclusion, fatigue in MS seems to be a heterogeneous entity. Asthenia and fatigability may be different clinical entities. Certain immunoactivation parameters correlate with the presence of asthenia while pyramidal involvement is associated with fatigability.","subset":"pubmed_abstract"} +{"meta":{"pmid":25981959,"dup_signals":{"dup_doc_count":85,"dup_dump_count":46,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-23":3,"2023-14":1,"2023-06":2,"2022-49":2,"2022-40":2,"2022-27":3,"2022-21":3,"2022-05":1,"2021-43":3,"2021-39":2,"2021-31":4,"2021-21":3,"2021-17":2,"2021-10":2,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":2,"2019-13":1,"2018-51":1,"2018-43":1,"2018-39":1,"2018-30":2,"2018-26":1,"2018-13":2,"2018-09":1,"2018-05":2,"2017-51":1,"2017-47":1,"2017-43":3,"2017-39":1,"2017-34":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-30":2,"2024-26":4,"2024-22":1,"2024-18":1,"2024-10":4,"2017-13":1}}},"text":"De novo point mutations in patients diagnosed with ataxic cerebral palsy.\nCerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies.","subset":"pubmed_abstract"} +{"meta":{"pmid":28173609,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The effect of tapered toothbrush filaments compared to end-rounded filaments on dental plaque, gingivitis and gingival abrasion: a systematic review and meta-analysis.\nThis systematic review was performed to establish the effect of a manual toothbrush with tapered toothbrush filaments (TFTBs) compared to a manual toothbrush with end-rounded toothbrush filaments (ERTB) on clinical parameters of dental plaque, gingivitis and gingival abrasion. MEDLINE-PubMed and Cochrane-CENTRAL databases were searched. The inclusion criteria were (randomized) controlled clinical trials, participants \u226518 years and papers evaluating the effect of a TFTB compared to an ERTB. Data were extracted for dental plaque index (PI), bleeding scores (BS), gingival index scores (GI) and gingival abrasion scores (GA). A descriptive analysis and a meta-analysis were performed when appropriate. An independent screening of 33 unique papers resulted in seven eligible publications, which included eight comparisons. Meta-analysis did not show a significant difference between TFTB and ERTB with respect to PI scores. The meta-analysis of the GI scores showed a significant mean difference in favour of the TFTB (DiffM=-0.12 [95% CI: -0.17; -0.07]). Of the three comparisons evaluating GA, no differences were found. With respect to plaque removal, evidence that supports the recommendation for usage of a TFTB over an ERTB is lacking. Regarding GI, there is minimal evidence favouring a TFTB over an ERTB and the clinical relevance of this difference is probably negligible. Therefore, based on the collective evidence emerging from this systematic review, the strength and direction of the recommendation, there appears to be no firm evidence for a dental healthcare professional to advise the use of a TFTB over the use of an ERTB.","subset":"pubmed_abstract"} +{"meta":{"pmid":17541997,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Using relative distributions to investigate the body mass index in England and Canada.\nIn this paper we use relative distributions to examine changes in the distribution of the body mass index (BMI) in England and Canada during the period 1994\/5-2000\/1. The use of relative distributions allows us to describe changes in the whole distribution of the BMI in a non-parametric fashion. While statistics analogous to the Gini index can be constructed based on the relative distribution, important characteristics of changes in the distribution of the BMI such as changes in the proportions overweight and obese are more naturally handled using measures of relative polarization. Our results show that while BMI has increased in both countries, BMI in England has increased at a much faster rate than in Canada. Both groups show polarization over time towards both tails of the weight distribution, with the English polarizing towards the upper tail at a faster rate than Canadians.","subset":"pubmed_abstract"} +{"meta":{"pmid":22191732,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Ozone-initiated particle formation, particle aging, and precursors in a laser printer.\nAn increasing number of researchers have hypothesized that ozone may be involved in the particle formation processes that occur during printing, however no studies have investigated this further. In the current study, this hypothesis was tested in a chamber study by adding supplemental ozone to the chamber after a print job without measurable ozone emissions. Subsequent particle number concentration and size distribution measurements showed that new particles were formed minutes after the addition of ozone. The results demonstrated that ozone did react with printer-generated volatile organic compounds (VOCs) to form secondary organic aerosols (SOAs). The hypothesis was further confirmed by the observation of correlations among VOCs, ozone, and particles concentrations during a print job with measurable ozone emissions. The potential particle precursors were identified by a number of furnace tests, which suggested that squalene and styrene were the most likely SOA precursors with respect to ozone. Overall, this study significantly improved scientific understanding of the formation mechanisms of printer-generated particles, and highlighted the possible SOA formation potential of unsaturated nonterpene organic compounds by ozone-initiated reactions in the indoor environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":20462412,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice.\nAntibodies generated against West Nile virus (WNV) during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E) are targets for neutralizing antibodies, with determinants in domain III (DIII) eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene) were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM\/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT80 titer >1\/40). Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines.","subset":"pubmed_abstract"} +{"meta":{"pmid":8601581,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":3,"unknown":13}}},"text":"Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes.\nWe have followed the transfer of EGF-EGF receptor (EGFR) complexes from endosomal vacuoles that contain transferrin receptors (TfR) to lysosome vacuoles identified by their content of HRP loaded as a 15-min pulse 4 h previously. We show that the HRP-loaded lysosomes are lysosomal-associated membrane protein-1 (LAMP-1) positive, mannose-6-phosphate receptor (M6PR) negative. and contain active acid hydrolase. EGF-EGFR complexes are delivered to these lysosomes intact and are then rapidly degraded. Preactivating the HRP contained within the preloaded lysosomes inhibits the delivery of EGFR and degradation of EGF, and results in the accumulation of EGFR-containing multivesicular bodies (MVB). With time these accumulating MVB undergo a series of maturation changes that include the loss of TfR, the continued recruitment of EGFR, and the accumulation of internal vesicles, but they remain LAMP-1 and M6PR negative. The mature MVB are often seen to make direct contact with lysosomes containing preactivated HRP, but their perimeter membranes remain intact. Together our observations suggest that the transfer of EGF-EGFR complexes from the TfR-containing endosome compartment to the lysosomes that degrade them employs a single vacuolar intermediate, the maturing MVB, and can be achieved by a single heterotypic fusion step.","subset":"pubmed_abstract"} +{"meta":{"pmid":2556109,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Phosphoinositide hydrolysis in mitogen-stimulated human peripheral-blood T lymphocytes.\nBoth phytohaemagglutinin and antibodies to the CD3 molecule induced proliferation and phosphoinositide hydrolysis in human peripheral-blood T lymphocytes, but the magnitude of the inositol phosphate response was small and the rate of accumulation slow [significant increases in Ins(1,4,5)P3 were observed only after 10 min]. Hence this response differs from the well-characterized Ins(1,4,5)P3 responses of many other systems. This slow response, its abrogation in Ca2+-depleted medium, the slow and maintained increase in Ca2+ as measured by Quin-2, and the ability of the Ca2+ ionophore A23187 to stimulate Ins(1,4,5)P3 accumulation all suggest that the increase in Ins(1,4,5)P3 occurs, at least in part, as a result of receptor-mediated Ca2+ influx in mitogen-stimulated T lymphocytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":24176981,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease.\nHigh amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimer's disease, and the detection of decline in non-memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":34795308,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Comparative analysis of loop-mediated isothermal amplification (LAMP)-based assays for rapid detection of SARS-CoV-2 genes.\nThe COVID-19 pandemic caused by SARS-CoV-2 has infected millions worldwide, therefore there is an urgent need to increase our diagnostic capacity to identify infected cases. Although RT-qPCR remains the gold standard for SARS-CoV-2 detection, this method requires specialised equipment in a diagnostic laboratory and has a long turn-around time to process the samples. To address this, several groups have recently reported the development of loop-mediated isothermal amplification (LAMP) as a simple, low cost and rapid method for SARS-CoV-2 detection. Herein we present a comparative analysis of three LAMP-based assays that target different regions of the SARS-CoV-2: ORF1ab RdRP, ORF1ab nsp3 and Gene N. We perform a detailed assessment of their sensitivity, kinetics and false positive rates for SARS-CoV-2 diagnostics in LAMP or RT-LAMP reactions, using colorimetric or fluorescent detection. Our results independently validate that all three assays can detect SARS-CoV-2 in 30 min, with robust accuracy at detecting as little as 1000 RNA copies and the results can be visualised simply by color changes. Incorporation of RT-LAMP with fluorescent detection further increases the detection sensitivity to as little as 100 RNA copies. We also note the shortcomings of some LAMP-based assays, including variable results with shorter reaction time or lower load of SARS-CoV-2, and false positive results in some experimental conditions and clinical saliva samples. Overall for RT-LAMP detection, the ORF1ab RdRP and ORF1ab nsp3 assays have faster kinetics for detection but varying degrees of false positives detection, whereas the Gene N assay exhibits no false positives in 30 min reaction time, which highlights the importance of optimal primer design to minimise false-positives in RT-LAMP. This study provides validation of the performance of LAMP-based assays as a rapid, highly sensitive detection method for SARS-CoV-2, which have important implications in development of point-of-care diagnostics for SARS-CoV-2.","subset":"pubmed_abstract"} +{"meta":{"pmid":11710177,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Blocking adhesion to cell and tissue surfaces by the chemisorption of a poly-L-lysine-graft-(poly(ethylene glycol); phenylboronic acid) copolymer.\nA family of graft copolymers that can sterically inhibit interactions between biological surfaces was developed. These copolymers contained phenylboronic acid (PBA) groups as saccharide-binding moieties on a poly-(L-lysine) backbone and poly(ethylene glycol) (PEG) grafted as adhesion-resisting side chains. These copolymers spontaneously chemisorbed to a saccharide-containing resin, and this binding was sterically controlled by the PEG grafting ratio. Copolymers with optimal grafting ratios spontaneously assembled on red blood cell surfaces and sterically prevented their agglutination by lectins and by antibodies to blood groups. The simple conjugation scheme created a PBA moiety with a pKa ca. 6, which can bind cis-diols much more strongly at physiological pH than typical PBA moieties, whose pKas are typically greater than 8. These surfactant copolymers can be employed to PEGylate cell or tissue surfaces by simply incubating the surfaces with an aqueous polymer solution, and have many potential applications such as preventing antibody binding to transplanted cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":8239440,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-40":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2023-50":1,"2017-13":1}}},"text":"Scrotal construction by expansion of labia majora in biological female transsexuals.\nConstruction of male genitalia in biological female transsexual patients is problematic. We report 3 transsexuals with scrotal construction by tissue expansion of the labia majora. In each patient, tissue expanders were inserted into the labia majora several months before free flap phalloplasty. In 2 patients, the tissue expanders were removed, and testicular implants were placed into the labial pockets. In the other patient, the tissue expanders were left in place. Because of the close embryological relationship between the labia majora and the scrotum, the neoscrotum appears natural in color match, hair pattern, and skin texture. The anatomical position of the labia majora produces a scrotum properly located in relation to surrounding anatomical structures. Excellent aesthetic results can be achieved with this procedure. Based on our experience, we advocate this procedure for scrotal construction in biological female transsexual patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":10748198,"dup_signals":{"dup_doc_count":11}},"text":"Transducin-like enhancer of split proteins, the human homologs of Drosophila groucho, interact with hepatic nuclear factor 3beta.\nMembers of the hepatic nuclear factor 3 (HNF3) family, including HNF3alpha, HNF3beta, and HNF3gamma, play important roles in embryonic development, the establishment of tissue-specific gene expression, and the regulation of gene expression in differentiated tissues. We found, using the glutathione S-transferase pull-down method, that the transducin-like Enhancer of split (TLE) proteins, which are the human homologs of Drosophila Groucho, directly associate with HNF3beta. Conserved region II of HNF3beta (amino acids 361-388) is responsible for the interaction with TLE1. A mammalian two-hybrid assay was used to confirm that this interaction occurs in vivo. Overexpression of TLE1 in HepG2 and HeLa cells decreases transactivation mediated through the C-terminal domain of HNF3beta, and Grg5, a naturally occurring dominant negative form of Groucho\/TLE, also increases the transcriptional activity of this region of HNF3. These results lead us to suggest that TLE proteins could influence the expression of mammalian genes regulated by HNF3.","subset":"pubmed_abstract"} +{"meta":{"pmid":29205244,"dup_signals":{"dup_doc_count":18,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2018-43":2,"2018-30":2,"2018-22":1,"2018-17":2,"2018-13":1,"2018-05":3,"2017-51":3}}},"text":"Synchronous magnetic control of water droplets in bulk ferrofluid.\nWe present a microfluidic platform for magnetic manipulation of water droplets immersed in bulk oil-based ferrofluid. Although non-magnetic, the droplets are exclusively controlled by magnetic fields without any pressure-driven flow. The fluids are dispensed in a sub-millimeter Hele-Shaw chamber that includes permalloy tracks on its substrate. An in-plane rotating magnetic field magnetizes the permalloy tracks, producing local magnetic gradients, while an orthogonal magnetic field magnetizes the bulk ferrofluid. To minimize the magnetostatic energy of the system, the water droplets are attracted towards the locations on the tracks where the bulk ferrofluid is repelled. Using this technique, we demonstrate synchronous generation and propagation of water droplets, study the kinematics of propagation, and analyze the flow of the bulk ferrofluid. In addition, we show controlled break-up of droplets and droplet-to-droplet interactions. Finally, we discuss future applications owing to the potential biocompatibility of the droplets.","subset":"pubmed_abstract"} +{"meta":{"pmid":10980696,"dup_signals":{"dup_doc_count":13}},"text":"The MDM2 RING-finger domain is required to promote p53 nuclear export.\nMDM2 can bind to p53 and promote its ubiquitination and subsequent degradation by the proteasome. Current models propose that nuclear export of p53 is required for MDM2-mediated degradation, although the function of MDM2 in p53 nuclear export has not been clarified. Here we show that MDM2 can promote the nuclear export of p53 in transiently transfected cells. This activity requires the nuclear-export signal (NES) of p53, but not the NES of MDM2. A mutation within the MDM2 RING-finger domain that inhibits p53 ubiquitination also inhibits the ability of MDM2 to promote p53 nuclear export. Finally, inhibition of nuclear export stabilizes wild-type p53 and leads to accumulation of ubiquitinated p53 in the nucleus. Our results indicate that MDM2-mediated ubiquitination, or other activities associated with the RING-finger domain, can stimulate the export of p53 to the cytoplasm through the activity of the p53 NES.","subset":"pubmed_abstract"} +{"meta":{"pmid":11866008,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Clinical significance of histological classification of idiopathic interstitial pneumonia.\nPatients with idiopathic interstitial pneumonias (IIPs) can be subdivided into groups based on the histological appearance of lung tissue obtained by surgical biopsy. The quantitative impact of histological diagnosis, baseline factors and response to therapy on survival has not been evaluated. Surgical lung biopsy specimens from 168 patients with suspected IIP were reviewed according to the latest diagnostic criteria. The impact of baseline clinical, physiological, radiographic and histological features on survival was evaluated using Cox regression analysis. The predictive value of honeycombing on high-resolution computed tomography (HRCT) as a surrogate marker for usual interstitial pneumonia (UIP) was examined. The response to therapy and survival of 39 patients treated prospectively with high-dose prednisone was evaluated. The presence of UIP was the most important factor influencing mortality. The risk ratio of mortality when UIP was present was 28.46 (95% confidence interval (CI) 5.5-148.0; p=0.0001) after controlling for patient age, duration of symptoms, radiographic appearance, pulmonary physiology, smoking history and sex. Honeycombing on HRCT indicated the presence of UIP with a sensitivity of 90% and specificity of 86%. Patients with nonspecific interstitial pneumonia were more likely to respond or remain stable (9 of 10) compared to patients with UIP (14 of 29) after treatment with prednisone. Patients remaining stable had the best prognosis. The risk ratio of mortality for stable patients compared to nonresponders was 0.32 (95% CI 0.11-0.93; p=0.04) in all patients and 0.33 (95% CI 0.12-0.96; p=0.04) in patients with UIP. The histological diagnosis of usual interstitial pneumonia is the most important factor determining survival in patients with suspected idiopathic interstitial pneumonia. The presence of honeycombing on high-resolution computed tomography is a good surrogate for usual interstitial pneumonia and could be utilized in patients unable to undergo surgical lung biopsy. Patients with nonspecific interstitial pneumonia are more likely to respond or remain stable following a course of prednisone. Patients remaining stable following prednisone therapy have the best prognosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":28273407,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2024-26":1,"unknown":14}}},"text":"Use of the PARIHS Framework for Retrospective and Prospective Implementation Evaluations.\nThe Promoting Action on Research Implementation in Health Services (PARIHS) framework has been used by implementation researchers to assess factors impacting implementation and to use that information to identify optimal interventions and implementation strategies. In this paper, two studies are presented demonstrating the utility of PARIHS as a tool for retrospective and prospective evaluation of implementation in the health care setting. Descriptive case study. A qualitative consensus process was used to evaluate provider perceptions of PARIHS constructs of evidence, context, and facilitation and their subelements which were scored on a continuum of low to high. The first example demonstrates retrospective use of PARIHS which provided insight into the factors contributing to variations in implementation across sites in an ongoing program. Evidence was strong (high), whereas context noted some challenges in culture and measurement (mixed), and the presence of dedicated program facilitators was positive but dual roles limited their ability to fully support implementation (mixed). The second example demonstrates prospective use of PARIHS for evaluation which gathered information about intervention sites for the purposes of selecting implementation strategies responsive to site needs. Evidence supporting the intervention was limited (low), context noted that limited awareness of the intervention was a challenge (low), and that a strong internal facilitator supported implementation (high). The descriptive case study presented here underscores the value of a theory-guided approach to implementation and highlights that PARIHS can help implementers understand factors impacting implementation, identify areas for future intervention, and inform selection of strategies to support or enhance implementation efforts.","subset":"pubmed_abstract"} +{"meta":{"pmid":21343873,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Morphologic differences, according to etiology, in pigment epithelial detachments by means of en face optical coherence tomography.\nTo assess morphologic differences in pigment epithelial detachment (PED) with en face optical coherence tomography in central serous chorioretinopathy (CSC) and age-related macular degeneration (AMD). We recruited 30 eyes of 22 patients with PED. Nine eyes had a clinical diagnosis of CSC and 21 had AMD. All patients were assessed with en face optical coherence tomography. Morphologic PED aspects were estimated on C-scans and classified according to shape, inner silhouette, content, wall aspects, wall thickness, and size. Pigment epithelial detachment shape was predominantly circular (88.8%) in CSC and irregular or with multilobular features in AMD (76.2%). The PED inner silhouette had a smooth aspect (88.9%) in CSC and a slightly granular aspect or granular profile in AMD (100%). Clear PED content was the most characteristic feature of CSC (88.9%) but not of AMD. In CSC, PED morphologic wall aspect was uniform or slightly irregular (100%), while in AMD, it was slightly irregular (52.4%) or irregular (47.6%). Pigment epithelial detachment wall thickness and dimensions were larger in AMD than in CSC. Statistically significant differences were observed between CSC and AMD concerning PED inner silhouette, contents, wall aspects, and wall thickness measurements. En face optical coherence tomography scanning is a valuable tool for showing important morphologic differences between CSC and AMD.","subset":"pubmed_abstract"} +{"meta":{"pmid":18626265,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-05":1,"2021-49":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2023-23":1}}},"text":"Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study.\nThe objective of this study was to assess the dose-response relationship of standard and higher doses of olanzapine in a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg\/d (n = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal response to current treatment. Patients meeting criteria for antipsychotic treatment resistance were excluded. Dose-response relationship was assessed by linear regression analysis with log-transformed dose (independent variable) and Positive and Negative Syndrome Scale (PANSS) total score (dependent variable). There were no significant dose group differences in patients completing the study (overall, 67.8%). All dose groups showed statistically significant improvement in PANSS total scores from baseline to end point without significant dose-response relationship (P = 0.295). Post hoc analysis of response showed significant interaction between baseline PANSS and dose (P = 0.023), indicating better response at higher doses for patients with higher baseline PANSS. There was a significant dose response for mean change in weight (P = 0.003) with significant difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg\/d], 2.3 [20 mg\/d], and 3.0 kg [40 mg\/d]). There was a significant dose response for change in prolactin (P < 0.001) with a significant difference between each group (-10.5 [10 mg\/d], -1.7 [20 mg\/d], and 4.9 ng\/mL [40 mg\/d]; P < or = 0.018). Over 8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective disorder responded to all 3 doses of olanzapine, without a statistically significant dose-response relationship, suggesting that for many patients with schizophrenia or schizoaffective disorder, particularly those who are mildly or moderately ill, 10 mg\/d should be the initial dose of choice.","subset":"pubmed_abstract"} +{"meta":{"pmid":30977744,"dup_signals":{"dup_doc_count":28,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":6,"2024-22":3,"2024-10":1,"unknown":14}}},"text":"Inter-Professionalism in Health Care Post-graduate specialization: an innovative Laboratory.\nInter- professional Collaboration (IPC) is an important component of a well-functioning healthcare system. It is linked to improvements in patient safety and case management, optimal use of the skills of each healthcare team member and provision of better health services. Inter- professional Education (IPE), is one key factor in the development of positive behaviors useful for IPC: the basic and post-basic training are key moments to raise awareness, train and help implement the IPC. Aim of this paper is to present and evaluate the use of an innovative laboratory of Consensus Conference implemented in the Nursing Post-graduate specialization at the University of Parma to train students to IPC. An Innovative Laboratory inspired by of the Consensus Conference (CC) methodology on the \"Integrated Narrative Nursing Assessment\" was designed. Three Post-graduate specialization courses were involved and assigned to different tasks in the CC, according to the characteristics of the specializations. Strengths and weaknesses of the methodology were analyzed. Strengths: students' engagement in their competencies building, and the acquisition inter-professional collaboration skills. Weaknesses: the lack of time to develop the whole process, and the need of a deeper guidance in the scientific production. Although the methodology have to be continuously improved through practice, this experimental Laboratory reached the aim of offering a real experience of IPC to the students. They really collaborated with different professionals to reach a common goal and being already considered an expert.","subset":"pubmed_abstract"} +{"meta":{"pmid":7635809,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2020-45":2,"2020-40":1,"2020-34":1,"2020-24":1,"2019-51":1,"2019-47":1,"2019-30":1,"2019-22":2,"2019-09":1}}},"text":"Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate (ppGpp) and penicillin tolerance in Escherichia coli.\nThe penicillin tolerance exhibited by amino acid-deprived Escherichia coli has been previously proposed to be a consequence of the stringent response. Evidence indicating that penicillin tolerance is directly attributable to guanosine 3',5'-bispyrophosphate (ppGpp) overproduction and not to some other effect of amino acid deprivation is now presented. Accumulation of ppGpp in the absence of amino acid deprivation was achieved by the controlled overexpression of the cloned relA gene, which encodes ppGpp synthetase I. The overproduction of ppGpp resulted in the inhibition of both peptidoglycan and phospholipid synthesis and in penicillin tolerance. The minimum concentration of ppGpp required to establish these phenomena was determined to be 870 pmol per mg (dry weight) of cells. This represented about 70% of the maximum level of ppGpp accumulated during the stringent response. Penicillin tolerance and the inhibition of peptidoglycan synthesis were both suppressed when ppGpp accumulation was prevented by treatment with chloramphenicol, an inhibitor of ppGpp synthetase I activation. Glycerol-3-phosphate acyltransferase, the product of plsB, was recently identified as the main site of ppGpp inhibition in phospholipid synthesis (R. J. Health, S. Jackowski, and C. O. Rock, J. Biol. Chem. 269:26584-26590, 1994). The overexpression of the cloned plsB gene reversed the penicillin tolerance conferred by ppGpp accumulation. This result supports previous observations indicating that the membrane-associated events in peptidoglycan metabolism were dependent on ongoing phospholipid synthesis. Interestingly, treatment with beta-lactam antibiotics by itself induced ppGpp accumulation, but the maximum levels attained were insufficient to confer penicillin tolerance.","subset":"pubmed_abstract"} +{"meta":{"pmid":16382152,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":15}}},"text":"Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast.\nSelf-perpetuating protein aggregates transmit prion diseases in mammals and heritable traits in yeast. De novo prion formation can be induced by transient overproduction of the corresponding prion-forming protein or its prion domain. Here, we demonstrate that the yeast prion protein Sup35 interacts with various proteins of the actin cortical cytoskeleton that are involved in endocytosis. Sup35-derived aggregates, generated in the process of prion induction, are associated with the components of the endocytic\/vacuolar pathway. Mutational alterations of the cortical actin cytoskeleton decrease aggregation of overproduced Sup35 and de novo prion induction and increase prion-related toxicity in yeast. Deletion of the gene coding for the actin assembly protein Sla2 is lethal in cells containing the prion isoforms of both Sup35 and Rnq1 proteins simultaneously. Our data are consistent with a model in which cytoskeletal structures provide a scaffold for generation of large aggregates, resembling mammalian aggresomes. These aggregates promote prion formation. Moreover, it appears that the actin cytoskeleton also plays a certain role in counteracting the toxicity of the overproduced potentially aggregating proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":27281371,"dup_signals":{"dup_doc_count":25,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2023-50":3,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-21":2,"2021-17":1,"2021-04":1,"2020-45":1,"2018-47":1,"2024-30":2,"2024-22":3,"2024-18":1}}},"text":"Brief mindfulness training reduces salivary IL-6 and TNF-\u03b1 in young women with depressive symptomatology.\nPro-inflammatory cytokines have been implicated in the pathophysiology and maintenance of depression. This study investigated the effects of a brief mindfulness intervention on salivary pro-inflammatory correlates of depression (IL-6, TNF-\u03b1) and self-reported symptoms of depression in college women. Sixty-four females with a cut score of \u226516 on the Center for Epidemiological Studies for Depression Scale (CES-D) were assigned to a 4-week mindfulness-based intervention (MBI; N = 31) or a contact-control group (N = 33). For both groups, salivary cytokines and depressive symptoms were assessed at baseline and posttreatment. For the mindfulness group only, salivary cytokines were also assessed at a 3-month follow-up. Both groups showed similar reductions in depression. However, MBI (vs. control) predicted greater reductions in IL-6 and TNF-\u03b1; changes in IL-6 were sustained at 3-month follow-up. Higher baseline depressive symptoms predicted greater reductions in inflammation in the mindfulness group. MBIs may reduce inflammatory immune markers commonly implicated in depression. Individuals with greater depressive symptoms may benefit more from mindfulness training. Although reductions in salivary cytokines in the mindfulness condition were not attributable to changes in depressive symptoms, future work should examine the possibility that such reductions are protective against the development of future depressive episodes. (PsycINFO Database Record","subset":"pubmed_abstract"} +{"meta":{"pmid":23998171,"dup_signals":{"dup_doc_count":24,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-40":1,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":2,"2021-31":2,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":1,"2020-40":1,"2023-50":1,"2024-30":2,"2024-18":1,"2024-10":1}}},"text":"Patient and family perceptions of hospice services: 'I knew they weren't like hospitals'.\nThe vision for palliative care service provision in New Zealand is for all people who are dying and their families to have timely access to culturally appropriate, quality palliative care services. An Auckland hospice's records show that the ethnically diverse population statistics were not reflected in the referrals for hospice services. The aim of this research was to gain a patient-and-their-family perspective on the hospice, including exploration of components of service care that could be improved for various cultural groups. Patients currently under the care of the hospice and family members were recruited from hospice records. Semi-structured interviews were conducted to explore the emerging issues. The study collected data from a purposive sample of 18 palliative care patients or carer family members, ranging in age from 39 to 81 years, who reflected the ethnic diversity of the population of the region. Interviewing was carried out by an experienced research assistant and continued until data saturation was reached. Four key themes emerged-hospice personnel's approach to patients, quality of service, cultural barriers, and strategies for future improvement. It was determined that the latter two were the most significant to address in this article. The study revealed the need for information-giving and education, including public profiling of the hospice to strengthen community involvement. Strategies to reduce ethnic disparities include strengthening the awareness of, and access to, services by connecting with cultural groups through churches, community and specific cultural media.","subset":"pubmed_abstract"} +{"meta":{"pmid":23755828,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2019-51":2,"2019-47":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-09":1,"2018-43":2,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1}}},"text":"Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study.\nVKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged \u226518 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G\u2192A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5\u00d710(-8) in the discovery cohort and p<0\u00b70038 in the replication cohort. The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1\u00b751\u00d710(-8)). This association was confirmed in the replication cohort (p=5\u00b704\u00d710(-5)); analysis of the two cohorts together produced a p value of 4\u00b75\u00d710(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6\u00b792 mg\/week and those homozygous 9\u00b734 mg\/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population. National Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust.","subset":"pubmed_abstract"} +{"meta":{"pmid":33636869,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Severe Isotype-Matched Immunosuppression (IMI) as a Potential Risk Factor for Progression of MGUS Patients.\nMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma in virtually every case. However, only a small percentage will progress and at very different rates. In addition, recent data have suggested that MGUS is associated with other comorbidities including infections, suggesting impaired immune function in some MGUS patients. Therefore, we aimed at assessing the value of isotype-matched immunosuppression (IMI; e.g., suppression of an IgA\u03ba in an IgA\u03bb patient), a type of immunosuppression more specific than classical immunoparesis (IP; e.g., IgG and\/or IgM suppression in an IgA patient), as a prognostic marker for MGUS progression. The Hevylite assay was used to assess IMI and immunoglobulin ratios in 307 serum samples from a cohort of 248 MGUS patients. Follow-up clinical records were available for 154 individuals. A greater incidence of IMI (51%) over classical IP (37%) was observed, although both show a progressive increase with higher risk groups. Survival analysis of 154 patients showed that severe IMI (>50% suppression) differentiates 2 groups with significantly different time to progression (P = 0.024) while severe IP does not (P = 0.48). Also, a combination of severe IMI and involved monoclonal immunoglobulin >1.5g\/dL by Hevylite (both variables found to be independent prognostic markers in multivariate analysis) identified a group of patients with a median time to progression 6-fold shorter than the remaining group (P < 0.0001). These findings indicate a possible role for IMI in the malignant transformation of MGUS patients and a potential utility as a new risk factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":27914153,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"[Pulmonary Embolism in Portugal: Epidemiology and In-Hospital Mortality].\nIn Portugal, the epidemiology of acute pulmonary embolism is poorly understood. In this study, we sought to characterize the pulmonary embolism from the hospital data and evaluate its in-hospital mortality and respective prognostic factors. The study used diagnostic related groups data from National Health System hospitals from 2003 to 2013 and National Statistics Institute population data to establish the evolution of admissions with the diagnosis of pulmonary embolism, their inhospital mortality rates and the population incidence rates. Diagnosis-related group microdata were used in a logit regression modeling in-hospital mortality as a function of individual characteristics and context variables. Between 2003 and 2013 there were 35,200 episodes of hospitalization in patients with 18 or more years in which one of the diagnoses was pulmonary embolism (primary diagnosis in 67% of cases). The estimated incidence rate in 2013 was 35\/100,000 population (\u2265 18 years). Between 2003 and 2013, the annual number of episodes kept increasing, but the in-hospital mortality rate decreased (from 31.8% to 17% for all cases and from 25% to 11.2% when pulmonary embolism was the main diagnosis). The probability of death decreases when there is a computerized tomography scan registry or when patients are females and increases with age and the presence of co-morbidities. In the last decade there was an increased incidence of pulmonary embolism likely related to an increased number of dependents and bedridden. However, there was a in-hospital mortality reduction of such size that the actual mortality in the general population was reduced. One possible explanation is that there has been an increase in episodes of pulmonary embolism with incrementally lower levels of severity, due to the greater capacity of diagnosis of less severe cases. Another possible explanation is greater effectiveness of hospital care. According to the logistic regression analysis, improvements in hospital care effectiveness in recent years are primarily responsible for the mortality reduction. About 79% of the reduction of in-hospital mortality of pulmonary embolism between 2003 and 2013 can be attributed to greater effectiveness of hospital care and the rest to the favorable change in patient characteristics associated with risk of death.","subset":"pubmed_abstract"} +{"meta":{"pmid":32571398,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-14":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-39":1,"2021-31":1,"2020-40":1,"2020-34":1,"2020-29":1}}},"text":"Modifiable environmental exposure and risk of rheumatoid arthritis-current evidence from genetic studies.\nRheumatoid arthritis (RA) is a multifactorial chronic autoimmune disease, which involves a complex interplay of environmental triggers and genetic components in its etiology. It has been shown that genetics only explain about half of the liability to develop RA, leaving a large room for non-genetic factors. Indeed, several environmental exposures including smoking, drinking, obesity, and dietary patterns (and more) have been identified to be associated with RA risk, yet the observational nature of conventional epidemiological investigation hampers causal inference, as the validity of results could be plagued by measurement error, confounding, and\/or reverse causality. Mendelian randomization (MR) is a novel statistical approach that uses genetic variants as instrumental variables (IV) to make causal inferences from observational data. The current genetic discoveries in the many heritable and modifiable human complex traits have provided an exceptional opportunity to evaluate a putative causal relationship between exposure and outcome in the absence of high-quality experimental or intervention studies, through a MR design. In the current review, we detail the contribution of MR studies hitherto conducted for modifiable environmental exposures with the risk of RA to understand the role of these factors in RA pathogenesis. We start with a brief introduction of each study, follow by a summarization of shortcomings and conclude by highlighting future directions. The application of MR design in the field of rheumatology remains limited. Only a few MR studies have examined the causal roles of vitamin D, cigarette smoking, alcohol consumption, coffee consumption, and levels of education in RA, where, no consistent evidence for a causal relationship has been found. Most studies lacked sensitivity analyses to verify MR model assumptions and to guarantee the validity of results. Almost all studies are likely to bias the strength of association towards a null value, since they used IVs from earlier GWAS(s) of exposures with a small sample size (i.e., few genetic markers). As the magnitudes of GWAS expand rapidly, additional trait-associated loci have been discovered. Incorporating these loci would greatly improve the strength of genetic instruments, as well as both the accuracy and precision of MR estimates. To conclude, there is a need for an update and a huge space for improvement of future MR studies in RA.","subset":"pubmed_abstract"} +{"meta":{"pmid":14646786,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Aspects of social support associated with depression at hospitalization and follow-up assessment among cardiac patients.\nHigh levels of depressive symptoms have been shown to affect the morbidity, mortality, and functioning of patients with myocardial infarction (MI). Findings have shown that social support is associated with depression in both patient and community samples. This study examined various aspects of social support as they relate to depressive symptoms in patients with MI, both in the hospital and 2 weeks later. As part of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) pilot study, measures of perceived social support, social networks, social support received, and social conflict were administered to 196 patients with MI. These patients also were administered the Beck Depression Inventory and the Hamilton Rating Scale for Depression. Depression was reassessed 2 weeks later. Relations between social support indicators and the depression measures were examined. The prevalence of depression symptoms was high, especially among poorer and younger patients. There was modest improvement across time. Patients with high social support scores, particularly those reflecting perceived support, had lower scores on depression measures at baseline. High levels of perceived support and low social conflict at baseline were associated with less follow-up depression, as measured by the Beck cognitive scale, but not the Beck somatic scale nor the Hamilton scale. There were few associations with measures of social networks and received support. Social support indicators were differentially related to depression among patients with MI while in the hospital and 2 weeks later. The pattern of associations also depended on the measure of depression. A broad assessment strategy of both social support and depression is needed for a full understanding of their interrelations.","subset":"pubmed_abstract"} +{"meta":{"pmid":29669555,"dup_signals":{"dup_doc_count":12}},"text":"The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin.\nMultiple population based analyses have demonstrated a high incidence of cardiovascular disease (CVD) and cardiovascular (CV) mortality in subjects with T2DM that reduces life expectancy by as much as 15 years. Importantly, the CV system is particularly sensitive to the metabolic and immune derangements present in obese pre-diabetic and diabetic individuals; consequently, CV dysfunction is often the initial CV derangement to occur and promotes the progression to end organ\/tissue damage in T2DM. Specifically, diabetic CVD can manifest as microvascular complications, such as nephropathy, retinopathy, and neuropathy, as well as, macrovascular impairments, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease. Despite some progress in prevention and treatment of CVD, mainly via blood pressure and dyslipidemia control strategies, the impact of metabolic disease on CV outcomes is still a major challenge and persists in proportion to the epidemics of obesity and diabetes. There is abundant pre-clinical and clinical evidence implicating the DPP-4-incretin axis in CVD. In this regard, linagliptin is a unique DPP-4 inhibitor with both CV and renal safety profiles. Moreover, it exerts beneficial CV effects beyond glycemic control and beyond class effects. Linagliptin is protective for both macrovascular and microvascular complications of diabetes in preclinical models, as well as clinical models. Given the role of endothelial-immune cell interactions as one of the key events in the initiation and progression of CVD, linagliptin modulates these cell-cell interactions by affecting two important pathways involving stimulation of NO signaling and potent inhibition of a key immunoregulatory molecule.","subset":"pubmed_abstract"} +{"meta":{"pmid":19390164,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2020-40":2,"2020-34":1,"2019-51":1,"2019-43":2,"2019-35":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1}}},"text":"Secretion of fibrinolytic enzymes facilitates human mesenchymal stem cell invasion into fibrin clots.\nAdult human mesenchymal stem cells (hMSC) are involved in wound healing and regeneration of mesodermal tissue, but the underlying homing mechanisms are not well understood. Fibrin clot formation is associated with most wound healing processes and potentially guides the recruitment of hMSC. The objective of this study is the investigation of a fibrinolytic capacity, which is required for hMSC to migrate into a wounded tissue and thus to contribute to tissue regeneration. Using RT-PCR, semiquantitative real-time PCR and ELISA, we detected key components of the fibrinolytic cascade, including the urokinase plasminogen activator (uPA) and its receptor (uPAR), the tissue plasminogen activator (tPA) and the plasminogen activator inhibitor (PAI), suggesting a strong fibrinolytic activity of hMSC. To test this activity in a functional assay, we cultured fibrin-embedded hMSC in vitro for 7 days. The cells efficiently dissolved the surrounding fibrin mesh into the fibrin degradation products, the fibrinopeptides. The fibrinolytic activity of hMSC and human dermal fibroblasts, known to be critically involved in skin wound extracellular matrix remodeling, was similar. Our results suggest that a high intrinsic fibrinolytic capacity of hMSC mediates the invasion into a fibrin clot of a wounded tissue.","subset":"pubmed_abstract"} +{"meta":{"pmid":16119886,"dup_signals":{"dup_doc_count":23,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2023-14":1,"2022-40":1,"2022-05":1,"2021-43":1,"2021-25":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-10":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-22":1,"2019-13":1,"2018-26":1,"2018-09":1,"2017-47":1,"2023-23":1,"2024-18":1}}},"text":"Possible modes of dissemination of the amphibian chytrid Batrachochytrium dendrobatidis in the environment.\nAmphibian chytridiomycosis caused by Batrachochytrium dendrobatidis has spread at an alarming rate over large distances throughout sensitive frog populations in eastern Australia, Central America and New Zealand. Infected amphibians and contaminated water are implicated in translocation, but other vectors are unknown. Through in vitro studies we show that potential means of translocation may be moist soil and bird feathers. B. dendrobatidis survived for up to 3 mo in sterile, moist river sand with no other nutrients added. B. dendrobatidis attached to and grew on sterile feathers and were able to be transported by feathers to establish new cultures in media, surviving between 1 and 3 h of drying between transfers. If these in vitro results are valid in the natural environment, the findings raise the possibilities that B. dendrobatidis may be translocated by movement of moist river sand and that birds may carry the amphibian chytrid between frog habitats. However, further studies using sand and feathers containing normal microflora are essential.","subset":"pubmed_abstract"} +{"meta":{"pmid":16055183,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties.\nOne of the main issues in tissue engineering is the fabrication of scaffolds that closely mimic the biomechanical properties of the tissues to be regenerated. Conventional fabrication techniques are not sufficiently suitable to control scaffold structure to modulate mechanical properties. Within novel scaffold fabrication processes 3D fiber deposition (3DF) showed great potential for tissue engineering applications because of the precision in making reproducible 3D scaffolds, characterized by 100% interconnected pores with different shapes and sizes. Evidently, these features also affect mechanical properties. Therefore, in this study we considered the influence of different structures on dynamic mechanical properties of 3DF scaffolds. Pores were varied in size and shape, by changing fibre diameter, spacing and orientation, and layer thickness. With increasing porosity, dynamic mechanical analysis (DMA) revealed a decrease in elastic properties such as dynamic stiffness and equilibrium modulus, and an increase of the viscous parameters like damping factor and creep unrecovered strain. Furthermore, the Poisson's ratio was measured, and the shear modulus computed from it. Scaffolds showed an adaptable degree of compressibility between sponges and incompressible materials. As comparison, bovine cartilage was tested and its properties fell in the fabricated scaffolds range. This investigation showed that viscoelastic properties of 3DF scaffolds could be modulated to accomplish mechanical requirements for tailored tissue engineered applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":14972059,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-11":1,"unknown":9}}},"text":"Diet, nutrition and the prevention of hypertension and cardiovascular diseases.\nCardiovascular diseases (CVD) are growing contributors to global disease burdens, with epidemics of CVD advancing across many regions of the world which are experiencing a rapid health transition. Diet and nutrition have been extensively investigated as risk factors for major cardiovascular diseases like coronary heart disease (CHD) and stroke and are also linked to other cardiovascular risk factors like diabetes, high blood pressure and obesity. The interpretation of evidence needs to involve a critical appraisal of methodological issues related to measurement of exposures, nature of outcome variables, types of research design and careful separation of cause, consequence and confounding as the basis for observed associations. Adequate evidence is available, from studies conducted within and across populations, to link several nutrients, minerals, food groups and dietary patterns with an increased or decreased risk of CVD. Dietary fats associated with an increased risk of CHD include trans-fats and saturated fats, while polyunsaturated fats are known to be protective. Dietary sodium is associated with elevation of blood pressure, while dietary potassium lowers the risk of hypertension and stroke. Regular frequent intake of fruits and vegetables is protective against hypertension, CHD and stroke. Composite diets (such as DASH diets, Mediterranean diet, 'prudent' diet) have been demonstrated to reduce the risk of hypertension and CHD. Sufficient knowledge exists to recommend nutritional interventions, at both population and individual levels, to reduce cardiovascular risk. That knowledge should now be translated into policies which promote healthy diets and discourage unhealthy diets. This requires coordinated action at the level of governments, international organizations, civil society and responsible sections of the food industry.","subset":"pubmed_abstract"} +{"meta":{"pmid":24872547,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum.\nOf the two members of the \u03b4 subfamily of ionotropic glutamate receptors, GluD2 is exclusively expressed at parallel fiber-Purkinje cell (PF-PC) synapses in the cerebellum and regulates their structural and functional connectivity. However, little is known to date regarding cellular and synaptic expression of GluD1 and its role in synaptic circuit formation. In the present study, we investigated this issue by producing specific and sensitive histochemical probes for GluD1 and analyzing cerebellar synaptic circuits in GluD1-knock-out mice. GluD1 was widely expressed in the adult mouse brain, with high levels in higher brain regions, including the cerebral cortex, striatum, limbic regions (hippocampus, nucleus accumbens, lateral septum, bed nucleus stria terminalis, lateral habenula, and central nucleus of the amygdala), and cerebellar cortex. In the cerebellar cortex, GluD1 mRNA was expressed at the highest level in molecular layer interneurons and its immunoreactivity was concentrated at PF synapses on interneuron somata. In GluD1-knock-out mice, the density of PF synapses on interneuron somata was significantly reduced and the size and number of interneurons were significantly diminished. Therefore, GluD1 is common to GluD2 in expression at PF synapses, but distinct from GluD2 in neuronal expression in the cerebellar cortex; that is, GluD1 in interneurons and GluD2 in PCs. Furthermore, GluD1 regulates the connectivity of PF-interneuron synapses and promotes the differentiation and\/or survival of molecular layer interneurons. These results suggest that GluD1 works in concert with GluD2 for the construction of cerebellar synaptic wiring through distinct neuronal and synaptic expressions and also their shared synapse-connecting function.","subset":"pubmed_abstract"} +{"meta":{"pmid":30746802,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Investing in antibiotics to alleviate future catastrophic outcomes: What is the value of having an effective antibiotic to mitigate pandemic influenza?\nOver 95% of post-mortem samples from the 1918 pandemic, which caused 50 to 100 million deaths, showed bacterial infection complications. The introduction of antibiotics in the 1940s has since reduced the risk of bacterial infections, but growing resistance to antibiotics could increase the toll from future influenza pandemics if secondary bacterial infections are as serious as in 1918, or even if they are less severe. We develop a valuation model of the option to withhold wide use of an antibiotic until significant outbreaks such as pandemic influenza or foodborne diseases are identified. Using real options theory, we derive conditions under which withholding wide use is beneficial, and calculate the option value for influenza pandemic scenarios that lead to secondary infections with a resistant Staphylococcus aureus strain. We find that the value of withholding an effective novel oral antibiotic can be positive and significant unless the pandemic is mild and causes few secondary infections with the resistant strain or if most patients can be treated intravenously. Although the option value is sensitive to parameter uncertainty, our results suggest that further analysis on a case-by-case basis could guide investment in novel agents as well as strategies on how to use them.","subset":"pubmed_abstract"} +{"meta":{"pmid":27614387,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"CRISPR\/Cas9-mediated knockout of p22phox leads to loss of Nox1 and Nox4, but not Nox5 activity.\nThe NADPH oxidases are important transmembrane proteins producing reactive oxygen species (ROS). Within the Nox family, different modes of activation can be discriminated. Nox1-3 are dependent on different cytosolic subunits, Nox4 seems to be constitutively active and Nox5 is directly activated by calcium. With the exception of Nox5, all Nox family members are thought to depend on the small transmembrane protein p22phox. With the discovery of the CRISPR\/Cas9-system, a tool to alter genomic DNA sequences has become available. So far, this method has not been widely used in the redox community. On such basis, we decided to study the requirement of p22phox in the Nox complex using CRISPR\/Cas9-mediated knockout. Knockout of the gene of p22phox, CYBA, led to an ablation of activity of Nox4 and Nox1 but not of Nox5. Production of hydrogen peroxide or superoxide after knockout could be rescued with either human or rat p22phox, but not with the DUOX-maturation factors DUOXA1\/A2. Furthermore, different mutations of p22phox were studied regarding the influence on Nox4-dependent H2O2 production. P22phox Q130* and Y121H affected maturation and activity of Nox4. Hence, Nox5-dependent O2\u2022- production is independent of p22phox, but native p22phox is needed for maturation of Nox4 and production of H2O2.","subset":"pubmed_abstract"} +{"meta":{"pmid":17002482,"dup_signals":{"dup_doc_count":57,"dup_dump_count":19,"dup_details":{"curated_sources":1,"2022-27":1,"2022-21":1,"2022-05":3,"2021-49":4,"2021-43":1,"2021-31":1,"2021-21":1,"2021-04":4,"2020-50":1,"2020-40":3,"2020-34":5,"2020-29":1,"2020-24":5,"2020-16":7,"2020-10":2,"2020-05":9,"2019-51":2,"2019-47":4,"2022-33":1}}},"text":"Hospitalisation costs of cystic fibrosis.\nTo calculate per-case hospital costs for patients with cystic fibrosis under routine conditions from a healthcare provider's perspective; identify the impact of different cost categories; investigate whether cases with cystic fibrosis can be grouped into homogenous cost groups according to defined severity levels; and determine the value of specific factors as predictors of hospital cost variations. All data were collected from cases (n = 131) admitted to an inpatient cystic fibrosis unit under routine conditions during a period of 6 months in 2004. All costs were calculated for the year 2004 and divided into categories with high and low impact on variation in hospitalisation costs between patients. Staff costs for patient care, laboratory costs and drug costs were defined as categories with high impact, thus the individual resource utilisation for each case was measured. Cost categories that were classified as having a low impact were measured as overhead costs. Cases were classified according to two different severity models; within each model, patients were classified according to three severity levels. The diagnosis-related model classifies patients with pulmonary hypertension and global respiratory insufficiency as having severe disease, patients with Pseudomonas aeruginosa as having moderate disease, and patients with no colonisation of the lungs as having mild disease. The lung-function-related model differentiates patients as having mild, moderate and severe disease when patients have forced expiratory volumes in 1 second (FEV(1)) that are > or =70%, between > or =40% and <70%, and <40%, respectively. Analysis of variance tests were performed to investigate the differences of mean costs between the groups. Ordinary least squares regression analysis was used to determine predictors for cost variation. The mean total costs per case were 7326 euro. Almost one-third of the total mean costs were attributable to drug costs (28% of total costs), while shares of staff costs for patient care and laboratory costs (both 9% of total costs) were relatively small. Most of the difference in costs between severity levels was attributable to the variation in overhead costs and drug costs. For both severity models differences in mean total costs of mild and severe cases were statistically significant (p < 0.01 and p < 0.05, respectively) when compared with the mean costs of non-mild and non-severe cases. However, in moderate cases, significant differences compared with cases that were not of moderate severity were only seen for certain cost categories. In the multiple regression model the variables 'diagnosis-related severity' and 'FEV(1)' explained 31% of the variance of 'Ln (total costs per case)' between severity levels (p < or = 0.01). This study shows that to a large extent hospitalisation costs for patients with cystic fibrosis vary according to the severity of their disease; drug costs play a major role in these differences. In the light of this variation it seems plausible to create separate reimbursement rates for two or three severity groups. Diagnoses as well as FEV(1) seem suitable criteria for such a classification.","subset":"pubmed_abstract"} +{"meta":{"pmid":22465825,"dup_signals":{"dup_doc_count":11}},"text":"Immunohistopathologic demonstration of deleterious effects on growing rat testes of radiofrequency waves emitted from conventional Wi-Fi devices.\nTo investigate effects on rat testes of radiofrequency radiation emitted from indoor Wi-Fi Internet access devices using 802.11.g wireless standards. Ten Wistar albino male rats were divided into experimental and control groups, with five rats per group. Standard wireless gateways communicating at 2.437 GHz were used as radiofrequency wave sources. The experimental group was exposed to radiofrequency energy for 24 h a day for 20 weeks. The rats were sacrificed at the end of the study. Intracardiac blood was sampled for serum 8-hydroxy-2'-deoxyguanosine levels. Testes were removed and examined histologically and immunohistochemically. Testis tissues were analyzed for malondialdehyde levels and prooxidant-antioxidant enzyme activities. We observed significant increases in serum 8-hydroxy-2'-deoxyguanosine levels and 8-hydroxyguanosine staining in the testes of the experimental group indicating DNA damage due to exposure (p < 0.05). We also found decreased levels of catalase and glutathione peroxidase activity in the experimental group, which may have been due to radiofrequency effects on enzyme activity (p < 0.05). These findings raise questions about the safety of radiofrequency exposure from Wi-Fi Internet access devices for growing organisms of reproductive age, with a potential effect on both fertility and the integrity of germ cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":26337695,"dup_signals":{"dup_doc_count":11}},"text":"rs4771122 Predicts Multiple Measures of Long-Term Weight Loss After Bariatric Surgery.\nWe examined the association of 34 single nucleotide polymorphisms with weight loss up to 9.5 years after Roux-en-Y surgery. Participants were enrollees in the NUgene biobank with stored DNA and linked electronic health records. Ninety-five self-identified white participants underwent surgery and had follow-up weights obtained between 1 and 9.5 years after surgery. SNP rs4771122 was the variant most significantly associated with long-term weight loss after surgery in a repeated linear mixed model (p = .004) of long-term weight loss. In this model, each additional copy of the minor allele was associated with nearly 5 % greater percentage weight loss. This same SNP was also nominally significantly (p < .05) associated with weight loss trajectories, weight loss nadir, and weight loss 2 years after surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":22017646,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Using a time-geographical diary method in order to facilitate reflections on changes in patterns of daily occupations.\nTime-use methodologies have been proposed to be established research techniques when exploring aspects of daily occupations. In this study, two graphs illustrating the time arrangement of occupations as they appear in a continuous sequence were used in order to encourage individuals to reflect on their everyday life. The aim was to investigate the usefulness of a time-geographical diary method (using illustrative graphs) in combination with stimulated-recall interviews, to facilitate reflections on how patterns of daily occupations change over time and the causes that lie behind these changes. The study had a qualitative design. The participants were two working, married mothers, i.e. individuals considered to have highly complex patterns of daily occupations. The data analysis was performed by using thematic content analysis. The results showed that the stimulated-recall interviews, based on the graphs, facilitated new insights that came to light concerning the scope of the participants' daily life. The method enabled the participants to reflect on their patterns of daily occupations and become aware of changes relevant to explain the causes for engaging in occupations the way they did. The method thus seems useful in research and practice for occupational therapists working with individuals with a need to change lifestyle.","subset":"pubmed_abstract"} +{"meta":{"pmid":30285851,"dup_signals":{"dup_doc_count":18}},"text":"Hidden in plain sight-highly abundant and diverse planktonic freshwater Chloroflexi.\nRepresentatives of the phylum Chloroflexi, though reportedly highly abundant in the extensive deep water habitats of both marine (SAR202 up to 30% of total prokaryotes) and freshwater (CL500-11 up to 26% of total prokaryotes), remain uncultivated and uncharacterized. There are few metagenomic studies on marine Chloroflexi representatives, while the pelagic freshwater Chloroflexi community is largely unknown except for a single metagenome-assembled genome of CL500-11. Here, we provide the first extensive examination of the community composition of this cosmopolitan phylum in a range of pelagic habitats (176 datasets) and highlight the impact of salinity and depth on their phylogenomic composition. Reconstructed genomes (53 in total) provide a perspective on the phylogeny, metabolism, and distribution of three novel classes and two family-level taxa within the phylum Chloroflexi. We unraveled a remarkable genomic diversity of pelagic freshwater Chloroflexi representatives that thrive not only in the hypolimnion as previously suspected, but also in the epilimnion. Our results suggest that the lake hypolimnion provides a globally stable habitat reflected in lower species diversity among hypolimnion-specific CL500-11 and TK10 clusters in distantly related lakes compared to a higher species diversity of the epilimnion-specific SL56 cluster. Cell volume analyses show that the CL500-11 are among the largest prokaryotic cells in the water column of deep lakes and with a biomass to abundance ratio of two they significantly contribute to the deep lake carbon flow. Metabolic insights indicate participation of JG30-KF-CM66 representatives in the global cobalamin production via cobinamide to cobalamin salvage pathway. Extending phylogenomic comparisons to brackish and marine habitats suggests salinity as the major influencer of the community composition of the deep-dwelling Chloroflexi in marine (SAR202) and freshwater (CL500-11) habitats as both counterparts thrive in intermediate brackish salinity; however, freshwater habitats harbor the most phylogenetically diverse community of pelagic Chloroflexi representatives that reside both in epi- and hypolimnion.","subset":"pubmed_abstract"} +{"meta":{"pmid":29030372,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.\nOmecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. The effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment (Pdf), and a slowed rate of XB detachment (krel) at submaximal Ca2+ activations. Ca2+ sensitivity of force generation (pCa50) was higher in HF myocardium when compared with donor myocardium, both prior to and after OM incubations. OM incubation (0.5 and 1.0 \u03bcmol\/L) enhanced force generation at submaximal Ca2+ activations in a dose-dependent manner. Notably, OM induced a slowing in krel with 1.0 \u03bcmol\/L OM but not with 0.5 \u03bcmol\/L OM in HF myocardium. Additionally, OM exerted other differential effects on XB behavior in HF myocardium as evidenced by a greater enhancement in Pdf and slowing in the time course of cooperative XB recruitment (Trec), which collectively prolonged achievement of peak force development (Tpk), compared with donor myocardium. Our findings demonstrate that OM augments force generation but also prolongs the time course of XB transitions to force-bearing states in remodeled HF myocardium, which may extend the systolic ejection time in vivo. Optimal OM dosing is critical for eliciting enhanced systolic function without excessive prolongation of systolic ejection time, which may compromise diastolic filling.","subset":"pubmed_abstract"} +{"meta":{"pmid":32028257,"dup_signals":{"dup_doc_count":20,"dup_dump_count":8,"dup_details":{"curated_sources":3,"2022-40":4,"2022-27":3,"2022-21":5,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2024-22":1}}},"text":"Predicting Lower Quarter Y-Balance Test Performance From Foot Characteristics.\nThe lower quarter Y-Balance Test (YBT-LQ) is associated with injury risk; however, ankle range of motion impacts YBT-LQ. Arch height and foot sensation impact static balance, but these characteristics have not yet been evaluated relative to YBT-LQ. Determine if arch height index (AHI), forefoot sensation (SEN), and ankle dorsiflexion predict YBT-LQ composite score (CS). Descriptive cohort. Athletic training laboratory. Twenty general population (14 females and 6 males; mean [SD]: age 35 [18] y, weight 70.02 [16.76] kg, height 1.68 [0.12] m) participated in this study. AHI measurement system assessed arch height in 10% (AHI10) and 90% (AHI90) weight-bearing. Two-point discrim-a-gon discs assessed sensation (SEN) at the plantar great toe, third and fifth metatarsal heads. Biplane goniometer and weight-bearing lunge tests were used to measure static and weight-bearing dorsiflexion, respectively. The YBT-LQ assessed dynamic single-leg balance. For right-limb dynamic single-leg balance, AHI90 and SEN were included in the final sequential prediction equation; however, neither model significantly (P = .052 and .074) predicted variance in YBT-LQ CS. For left-limb dynamic single-leg balance, both SEN and weight-bearing lunge test were included in the final sequential prediction equation. The regression model (SEN and weight-bearing lunge test) significantly (P = .047) predicted 22% of the variance in YBT-LQ CS. This study demonstrates that foot characteristics may play a role in YBT-LQ CS. The authors did not assess limb dominance in this study; therefore, the authors are unable to determine which limb would be the stance versus kicking limb. However, altered SEN and weight-bearing dorsiflexion appear to be contributing factors to YBT-LQ CS.","subset":"pubmed_abstract"} +{"meta":{"pmid":14593178,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Origin and migration of the Alpine Iceman.\nThe Alpine Iceman provides a unique window into the Neolithic-Copper Age of Europe. We compared the radiogenic (strontium and lead) and stable (oxygen and carbon) isotope composition of the Iceman's teeth and bones, as well as 40Ar\/39Ar mica ages from his intestine, to local geology and hydrology, and we inferred his habitat and range from childhood to adult life. The Iceman's origin can be restricted to a few valleys within approximately 60 kilometers south(east) of the discovery site. His migration during adulthood is indicated by contrasting isotopic compositions of enamel, bones, and intestinal content. This demonstrates that the Alpine valleys of central Europe were permanently inhabited during the terminal Neolithic.","subset":"pubmed_abstract"} +{"meta":{"pmid":30400334,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Inhibitory Effects of Helianthus tuberosus Ethanol Extract on Dermatophagoides farina body-induced Atopic Dermatitis Mouse Model and Human Keratinocytes.\nAtopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex symptoms. To treat AD without adverse effects, alternative therapeutic agents are required. The tubers of Helianthus tuberosus L. (Jerusalem artichoke) have been used in folk remedies for diabetes and rheumatism. However, its effect on AD development remains unknown. Therefore, this study examined the inhibitory effect of H. tuberosus (HT) on AD skin symptoms using an NC\/Nga mouse model and HaCaT keratinocytes. The effect of HT and associated molecular mechanisms were evaluated in Dermatophagoides farina body (Dfb)-induced AD mice and tumor necrosis factor (TNF)-\u03b1\/interferon (IFN)-\u03b3-stimulated HaCaT keratinocytes by ELISA, western blot, and histological analysis. Topical HT administration attenuated AD skin symptoms in Dfb-induced AD mice, with a significant reduction in the dermatitis score and production of inflammatory mediators. HT also decreased epidermal thickness and mast cell infiltration. Moreover, HT restored filaggrin expression and inhibited adhesion molecules in the mice. These effects were confirmed in vitro. Furthermore, HT suppressed the activation of NF-\u03baB, Akt, and mitogen-activated protein kinase (MAPK) signaling pathways induced by TNF-\u03b1\/IFN-\u03b3. These results suggest that HT is a potential therapeutic agent or supplement for skin allergic inflammatory diseases such as AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":34048087,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Lifelong chronic psychosocial stress induces a proteomic signature of Alzheimer's disease in wildtype mice.\nLate onset, sporadic Alzheimer's disease (AD) accounts for the vast majority of cases. Unlike familial AD, the factors that drive the onset of sporadic AD are poorly understood, although aging and stress play a role. The early onset\/severity of neuropathology observed in most genetic mouse models of AD hampers the study of the role of aging and environmental factors; thus alternate strategies are necessary to understand the contributions of these factors to sporadic AD. We demonstrate that mice acquiring a low social status (subordinate) in a lifelong chronic psychosocial stress (CPS) model, accrue widespread proteomic changes in the frontal\/temporal cortex during aging. To better understand the significance of these stress-induced changes, we compared the differentially expressed proteins (DEPs) of subordinate mice to those of patients at varying stages of dementia. Sixteen and fifteen DEPs upregulated in subordinate mice were also upregulated in patients with mild cognitive impairment (MCI) and AD, respectively. Six of those upregulated proteins (CPE, ERC2, GRIN2B, SLC6A1, SYN1, WFS1) were shared by subordinate mice and patients with MCI or AD. Finally, comparison with a spatially detailed transcriptomic database revealed that the superior frontal gyrus and hippocampus had the greatest overlap between mice subjected to lifelong CPS and AD patients. Overall, most of the overlapping proteins were functionally associated with enhanced NMDA receptor mediated glutamatergic signaling, an excitotoxicity mechanism known to affect neurodegeneration. These findings support the association between stress and AD progression and provide valuable insight into potential early biomarkers and protein mediators of this relationship.","subset":"pubmed_abstract"} +{"meta":{"pmid":8099577,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Treating anxiety while minimizing abuse and dependence.\nAnxiety is common and often disabling. Although effective treatments are available, the use of antianxiety medication remains controversial. Some of the controversy involves the relative benefits of psychological versus pharmacologic interventions. Much of the expressed concern, however, relates to the risks of abuse and dependence associated with standard antianxiety drugs. In some instances, concern about these risks prevents patients from receiving potentially effective treatment. In other instances, failure to recognize possible abuse and dependence results in a clinical dilemma. This presentation will address the factors involved in anxiolytic drug dependence and abuse, including patient characteristics and the pharmacologic profiles of anxiolytic drugs. Specific recommendations about how to minimize abuse and dependence through such measures as diagnostic assessment, patient education, drug selection, and treatment planning will be offered.","subset":"pubmed_abstract"} +{"meta":{"pmid":27923048,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Contribution of Wastewater Irrigation to Soil Transmitted Helminths Infection among Vegetable Farmers in Kumasi, Ghana.\nWastewater irrigation is associated with several benefits but can also lead to significant health risks. The health risk for contracting infections from Soil Transmitted Helminths (STHs) among farmers has mainly been assessed indirectly through measured quantities in the wastewater or on the crops alone and only on a limited scale through epidemiological assessments. In this study we broadened the concept of infection risks in the exposure assessments by measurements of the concentration of STHs both in wastewater used for irrigation and the soil, as well as the actual load of STHs ova in the stool of farmers and their family members (165 and 127 in the wet and dry seasons respectively) and a control group of non-farmers (100 and 52 in the wet and dry seasons, respectively). Odds ratios were calculated for exposure and non-exposure to wastewater irrigation. The results obtained indicate positive correlation between STH concentrations in irrigation water\/soil and STHs ova as measured in the stool of the exposed farmer population. The correlations are based on reinfection during a 3 months period after prior confirmed deworming. Farmers and family members exposed to irrigation water were three times more likely as compared to the control group of non-farmers to be infected with Ascaris (OR = 3.9, 95% CI, 1.15-13.86) and hookworm (OR = 3.07, 95% CI, 0.87-10.82). This study therefore contributes to the evidence-based conclusion that wastewater irrigation contributes to a higher incidence of STHs infection for farmers exposed annually, with higher odds of infection in the wet season.","subset":"pubmed_abstract"} +{"meta":{"pmid":28813557,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Facial Erosive Pustular Dermatosis After Cosmetic Resurfacing.\nErosive pustular dermatosis (EPD) is a rare condition that typically affects actinically damaged skin of the scalp. Characterized by sterile pustules, erosions, and crusts, EPD is difficult to treat and heals slowly. The exact cause of EPD is unknown, although trauma is an inciting factor. To describe 3 women who presented with prolonged facial erosions after cosmetic resurfacing procedures, specifically fully ablative carbon dioxide laser or medium-depth chemical peel. This case series describes the clinical features, histopathological findings, laboratory results, and treatment of 3 patients with an ultimate diagnosis most consistent with facial EPD. Patients were evaluated between September 10, 2010, and May 6, 2016, in a dermatology clinic in an academic medical center. The patients were 3 women seeking diagnostic evaluation and therapeutic options for nonhealing facial erosions occurring after ablative procedures (carbon dioxide laser resurfacing or Jessner solution\/trichloroacetic acid chemical peel). Histologic examination and wound culture from initial presentation as well as clinical follow-up documenting improvement with therapeutic interventions. All 3 patients were women in their 50s or 60s for whom EPD was deemed to be the best diagnosis, after infection, immunobullous disorders, and other pustular dermatoses were considered. Histologic features were nonspecific. Treatment included a combination of topical and systemic therapies, such as corticosteroids, dapsone, isotretinoin, and\/or antibiotics. Watchful waiting (tincture of time) appeared to be central to the healing process. After cosmetic resurfacing, patients may develop EPD isolated to the face. As a diagnosis of exclusion that should be considered in patients who have nonhealing wounds following ablative procedures, EPD is challenging to treat and may require the use of anti-inflammatory agents. Recognizing this condition is important, especially as cosmetic procedures become more widespread.","subset":"pubmed_abstract"} +{"meta":{"pmid":26322220,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"A comprehensive meta-analysis of common genetic variants in autism spectrum conditions.\nAutism spectrum conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity and performed stratified analyses for a subset of these variants. We identified 15 variants nominally significant for the mean effect size, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.","subset":"pubmed_abstract"} +{"meta":{"pmid":7951774,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"unknown":10}}},"text":"Exposure of iron foundry workers to polycyclic aromatic hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as biomarkers for exposure.\nExposure to polycyclic aromatic hydrocarbons (PAHs) in foundry workers has been evaluated by determination of benzo(a)pyrene-serum albumin adducts and urinary 1-hydroxypyrene. Benzo(a)pyrene binding to albumin and 1-hydroxypyrene were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and reverse phase high performance liquid chromatography (HPLC), respectively. 70 male foundry workers and 68 matched controls were investigated. High and low exposure groups were defined from breathing zone hygienic samples, consisting of 16 PAH compounds in particulate and gaseous phase. Mean total PAH was 10.40 micrograms\/m3 in the breathing zone, and mean dust adsorbed PAH was 0.15 microgram\/m. All carcinogenic PAH was adsorbed to dust. Median benzo(a)pyrene-albumin adduct concentrations (10-90% percentiles) were similar in foundry workers (smokers 0.55 (0.27-1.00) and non-smokers 0.58 (0.17-1.15)) pmol\/mg albumin and age matched controls (smokers 0.57 (0.16-1.45) and non-smokers 0.70 (0.19-1.55) pmol\/mg albumin). Median 1-hydroxypyrene concentrations were significantly higher (P < 0.0001) in smoking and non-smoking foundry workers (0.022 (0.006-0.075) and 0.027 (0.006-0.164)) mumol\/mol creatinine than in smoking and non-smoking controls (0 (0-0.022) and 0 (0-0.010) mumol\/mol creatinine). Dose-response relations between total PAH, pyrene, carcinogenic PAHs, and 1-hydroxypyrene for smokers, and polycyclic aromatic hydrocarbons adsorbed to dust for non-smokers are suggested. Exposure to PAHs adsorbed to dust showed an additive effect. There was no correlation between the concentrations of 1-hydroxypyrene and benzo(a)pyrene-albumin adducts. The change in 1-hydroxypyrene over a weekend was also studied. Friday morning median 1-hydroxypyrene concentrations were significantly higher in both smokers and non-smokers (0.021 (0-0.075) and 0.027 (0.06-0.164)) mumol\/mol creatinine than Monday morning median concentrations (0.007 (0-0.021) and 0.008 (0-0.021) mumol\/mol creatinine). Smoking did not affect the concentrations of 1-hydroxypyrene or benzo(a)pyrene-albumin adducts. These data suggest that 1-hydroxypyrene is a sensitive biomarker for low dose PAH exposure. Exposure to PAHs may be aetiologically related to increased risk of lung cancer in foundry workers.","subset":"pubmed_abstract"} +{"meta":{"pmid":30195736,"dup_signals":{"dup_doc_count":15}},"text":"Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide.\nGlioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor due, at least in part, to its poor response to current anticancer treatments. These features could be explained, at least partially, by the presence within the tumor mass of a small population of cells termed Glioma Initiating Cells (GICs) that has been proposed to be responsible for the relapses occurring in this disease. Thus, the development of novel therapeutic approaches (and specifically those targeting the population of GICs) is urgently needed to improve the survival of the patients suffering this devastating disease. Previous observations by our group and others have shown that \u03949-Tetrahydrocannabinol (THC, the main active ingredient of marijuana) and other cannabinoids including cannabidiol (CBD) exert antitumoral actions in several animal models of cancer, including gliomas. We also found that the administration of THC (or of THC + CBD at a 1:1 ratio) in combination with temozolomide (TMZ), the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts. In this work we investigated the effect of the combination of TMZ and THC:CBD mixtures containing different ratios of the two cannabinoids in preclinical glioma models, including those derived from GICs. Our findings show that TMZ + THC:CBD combinations containing a higher proportion of CDB (but not TMZ + CBD alone) produce a similar antitumoral effect as the administration of TMZ together with THC and CBD at a 1:1 ratio in xenografts generated with glioma cell lines. In addition, we also found that the administration of TMZ + THC:CBD at a 1:1 ratio reduced the growth of orthotopic xenografts generated with GICs derived from GBM patients and enhanced the survival of the animals bearing these intracranial xenografts. Remarkably, the antitumoral effect observed in GICs-derived xenografts was stronger when TMZ was administered together with cannabinoid combinations containing a higher proportion of CBD. These findings support the notion that the administration of TMZ together with THC:CBD combinations - and specifically those containing a higher proportion of CBD - may be therapeutically explored to target the population of GICs in GBM.","subset":"pubmed_abstract"} +{"meta":{"pmid":17005020,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":7}}},"text":"Enhancing tissue integration in cartilage repair procedures.\nArguably, the gold standard of biological repair of articular cartilage lesions is autologous chondrocyte transplantation. Although the clinical outcomes appear to range between good and excellent in most cases, there are, nevertheless, both clinical and biological challenges that remain to improve rehabilitation and clinical outcome. One of the major biological problems relates to tissue integration of the reparative tissue into the host tissue at a predictable level. Often within a single lesion, varying degrees of integration can be observed from total integration through to non-integration as one passes through the defect. Here we briefly review some of the literature relating to this problem and include some of our own data drawn from questions we have posed about the biological nature of cartilage\/cartilage integration. The nature and status of the tissue that comprises the wound lesion edge is central to tissue integration, and controlling aspects of trauma and free-radical-induced cell death together with matrix synthesis are identified as two components that require further investigation. Interestingly, there appears to be a limited ability of chondrocytes to be able to infiltrate existing cartilage matrices and even to occupy empty chondrocyte lacunae. Proliferation as a result of blunt and sharp trauma shows differential responses. As expected, blunt trauma induces a greater proliferative burst than sharp trauma and is more widespread from the lesion edge. However, in the case of sharp trauma, the basal cells enter proliferation before surface zone chondrocytes, which is not the case in blunt wounds. Regulation of these and associated processes will be necessary in order to devise strategies that can predict successful integration in biological repair procedures.","subset":"pubmed_abstract"} +{"meta":{"pmid":19912113,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Clinical significance of the KRAS mutation.\nThe challenge of translational medicine is to translate very complex scientific data into the clinical setting so that medical management can be better guided towards the ultimate goal of better patient outcome. Physicians now have the opportunity to use specific biomarkers to personalize therapeutic options in various settings. Recent research has demonstrated that presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation may directly influence medical decisions in patients with colon and lung cancer. Use of KRAS oncogene as a selection marker for specific treatment is a good example of individualized medicine approach to cancer treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":22675435,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":3,"2013-48":3,"2013-20":2,"unknown":2}}},"text":"Priority medicines for maternal and child health: a global survey of national essential medicines lists.\nIn April 2011, the World Health Organization (WHO) published a list of \"priority medicines\" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84\/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83\/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7\/89); artesunate injection was on 16% (14\/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32\/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45\/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13\/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23\/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45\/89) of the lists. The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health.","subset":"pubmed_abstract"} +{"meta":{"pmid":27144276,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets.\nHere we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro \u03b2-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the \u03b2-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9\u00c5 crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore \u03b2-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":26076062,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Juvenile granulosa cell tumors of the testis: a clinicopathologic study of 70 cases with emphasis on its wide morphologic spectrum.\nThe clinical and pathologic features of 70 juvenile granulosa cell tumors (JGCTs) of the testis are presented. The patients were from 30 weeks gestational age to 10 years old; 60 of 67 (90%) whose ages are known to us were 6 months old or younger. Sixty-two underwent gonadectomy, 6 wedge excision, and 2 only biopsy. Twenty-six tumors were left sided and 22 right sided. Six occurred in an undescended testis and 2 in dysgenetic gonads. The most common presentation was a testicular mass (65%), followed by an \"enlarging testis\" (25%). Six of 14 patients in whom it was measured had \"elevated\" serum \u03b1-fetoprotein (AFP), likely physiologically, and 1 had gynecomastia. The tumors measured 0.5 to 5 cm (mean, 1.7 cm; median, 1.5 cm) and were most commonly well circumscribed and typically yellow-tan; approximately 2\/3 had a cystic component, whereas 1\/3 were entirely solid. Microscopic examination typically showed a lobular growth, punctuated in 67 cases by variably sized and shaped follicles containing material that was basophilic (21%), eosinophilic (44%), or of both characters (35%); 3 lacked follicles. In nonfollicular areas, the tumor cells typically grew diffusely but occasionally had a corded arrangement (26%) or reticular appearance (29%). The stroma was either fibrous or fibromyxoid; hemorrhage associated with hemosiderin-laden macrophages was focally seen in 16%. The tumor cells were mostly small to medium sized with round to oval nuclei containing inconspicuous nucleoli and moderate to abundant, but occasionally scant, pale to lightly eosinophilic, sometimes vacuolated, cytoplasm; nuclear grooves were infrequent (6%). Focal columnar morphology was seen in 27% of the tumors. Mitoses were plentiful in 37%, and apoptosis was prominent in 46%. Intratubular tumor was seen in 43% and entrapped seminiferous tubules in 70%. Lymphovascular invasion was present in 2 cases, rete testis involvement in 4, and necrosis in 1. Rare features\/patterns included: regressed tumor with hyalinization and prominent blood vessels (13%), papillary growth (4%), basaloid morphology (1%), spindle cell predominance (1%), microcystic foci (1%), adult granulosa cell-like (1%) patterns, and hyaline globules (1%). Inhibin (16\/18), calretinin (8\/9), WT1 (6\/7), FOXL2 (12\/12), SF-1 (12\/12), and SOX9 (6\/11) were positive, whereas SALL4 and glypican-3 were consistently negative in the neoplastic granulosa cells. Only 1 of 10 tumors was focally positive for \u03b1-fetoprotein. JGCT is a rare neoplasm with a wide morphologic spectrum that also occurs rarely in undescended testes and dysgenetic gonads. The solid and reticular patterns may pose diagnostic challenges, but the lobular appearance and follicular differentiation are characteristic. Immunohistochemical stains may aid in its distinction from other tumors of young male individuals, particularly yolk sac tumor, a neoplasm that peaks at a somewhat later age. Twenty-four patients with follow-up, including 4 of 6 patients treated with wedge resection\/biopsy, had no evidence of disease (2 to 348 mo; mean, 83 mo; median, 61 mo). One additional patient was alive at 260 months, but the disease status is unknown. The benign clinical course of all cases of JGCT with follow-up, despite often frequent mitotic activity, supports testis sparing surgery when technically feasible.","subset":"pubmed_abstract"} +{"meta":{"pmid":6177404,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Use of aminoglutethimide as second-line endocrine therapy in metastatic breast cancer.\nSixty-five patients with advanced breast cancer, progressive despite prior endocrine therapy in all cases and prior chemotherapy in most cases, were treated with aminoglutethimide, 250 mg four times a day. At present, 52 are evaluable for response assessment, and of these 10 (19%) showed an overall objective response, major sites of response being soft tissue and lung. A further 12 patients (23%) had stable disease during aminoglutethimide therapy, while a total of 9 patients with bone metastases reported marked relief of pain without objective evidence of response. Forty-nine patients had received prior treatment with tamoxifen, and of the 10 tamoxifen responders 4 (40%) responded to subsequent aminoglutethimide, while of the 20 tamoxifen failures only 2 (10%) responded to subsequent aminoglutethimide. Aminoglutethimide was reasonably well tolerated, although 6 patients (0%) discontinued treatment because of intolerable side effects. Six of the 10 responding patients have subsequently relapsed, with a mean duration of response of 17 weeks, but 4 continued to respond at 24, 32, 55, and 111 weeks, respectively. The median survival from the start of aminoglutethimide therapy is in excess of 41 weeks for responders and 11 weeks for nonresponders, while the median survival from first relapse is 48 months for aminoglutethimide responders and 28 months for aminoglutethimide nonresponders. These results confirm that aminoglutethimide can offer a useful alternative form of endocrine therapy for advanced breast cancer, but the response rates obtained in heavily pretreated patients are inferior to those obtained when aminoglutethimide is used earlier in sequential treatment. For optimal results, particularly in terms of quality of life, aminoglutethimide should generally be used prior to chemotherapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28399870,"dup_signals":{"dup_doc_count":19}},"text":"The role of traditional healers in the diagnosis and management of Burkitt lymphoma in Cameroon: understanding the challenges and moving forward.\nBurkittlymphoma(BL) is the most common childhood cancer in Cameroon with a reported incidence of 3 per 100,000 children under 15 years in the Northwest region. Treatment at three Baptist mission hospitals has a recorded cure rate of over 50%. Traditional medicine(TM) is recognized by the national health system, but its scope is undefined and entraps children with BL. The aim of this study was to investigate the attitudes and practices of parents and traditional healers (TH) towards TM in children with BL in order to develop recommendations for an integrative approach and improved access to life-saving treatment for children with BL. This is a descriptive case series of children diagnosed with BL treated at Banso, Mbingo, and Mutengene Baptist Hospitals between 2003 and 2014. A questionnaire was used to obtain the following information: demographic information, religion, the rate of use of TM, reasons why guardians chose to use TM, the diagnoses made by the TH, treatment offered, and the type of payment requested, based on the accounts of patient caregivers. Data was analyzed using Center for Disease Control Epi Info 7. Three hundred eighty-seven questionnaires were completed by parents\/guardians. 55% had consulted a TH, of whom 76.1% consulted the TH as first choice. Common diagnoses provided by TH included liver problem, abscess, witchcraft, poison, hernia, side pain, mushroom in the belly and toothache. Methods of management included massage, cuts, concoctions, and incantations. The fee for these services included chickens, farm tools, and cash ranging from 200FCFA (0.4USD) to 100,000FCFA(200USD). The choice of TM was based on accessibility, failed clinic\/hospital attendance, recommendation of relatives, and belief in TM. TH are involved in BL management in Cameroon. TH are ignorant about BL, resulting in non-referral, and thus delay in diagnosis and treatment. Collaboration with TH could reduce late diagnosis and improve cure rates of BL and other childhood cancers.","subset":"pubmed_abstract"} +{"meta":{"pmid":11467940,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Membrane interactions of mutated forms of the influenza fusion peptide.\nWe have studied a group of fusion peptides of influenza hemagglutinin in which the N-terminal amino acid, Gly (found in the wild-type peptide), has been systematically substituted with Ala, Ser, Val, or Glu. The activity of the intact hemagglutinin protein with these same substitutions has already been reported. As a measure of the extent of modulation of intrinsic membrane curvature by these peptides, we determined their effects on the polymorphic phase transition of dipalmitoleoylphosphatidylethanolamine. The wild-type peptide is the only one that, at pH 5, can substantially decrease the temperature of this transition. This is also the only form in which the intact protein promotes contents mixing in cells. The Ala and Ser mutant hemagglutinins exhibit a hemifusion phenotype, and their fusion peptides have little effect on lipid polymorphism at low pH. The two mutant proteins that are completely fusion inactive are the Val and Glu mutant hemagglutinins. The fusion peptides from these forms significantly increase the polymorphic phase transition temperature at low pH. We find that the effect of the fusion peptides on membrane curvature, as monitored by a shift in the temperature of this polymorphic phase transition, correlates better with the fusogenic activities of the corresponding protein than do measurements of the isotropic (31)P NMR signals or the ability to induce the fusion of liposomes. The inactivity of the hemagglutinin protein with the hydrophobic Val mutation can be explained by the change in the angle of membrane insertion of the helical fusion peptide as measured by polarized FTIR. Thus, the nature of the interactions of the fusion peptides with membranes can, in large part, explain the differences in the fusogenic activity of the intact protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":27636464,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-33":1,"2020-45":1,"2020-10":1,"2020-05":1,"2019-35":1,"2018-26":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2022-49":1,"2024-10":1,"2024-22":1}}},"text":"Demonstration of a Coherent Electronic Spin Cluster in Diamond.\nAn obstacle for spin-based quantum sensors is magnetic noise due to proximal spins. However, a cluster of such spins can become an asset, if it can be controlled. Here, we polarize and readout a cluster of three nitrogen electron spins coupled to a single nitrogen-vacancy spin in diamond. We further achieve sub-nm localization of the cluster spins. Finally, we demonstrate coherent spin exchange between the species by simultaneous dressing of the nitrogen-vacancy and the nitrogen states. These results establish the feasibility of environment-assisted sensing and quantum simulations with diamond spins.","subset":"pubmed_abstract"} +{"meta":{"pmid":22463733,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":9}}},"text":"Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial.\nDespite continual improvements in the management of acute coronary syndromes, adherence to guideline-based medications remains suboptimal. We aim to improve adherence with guideline-based therapy following acute coronary syndrome using an existing service that is provided by specifically trained pharmacists, called a Home Medicines Review. We have made two minor adjustments to target the focus of the existing service including an acute coronary syndrome specific referral letter and a training package for the pharmacists providing the service. We will be conducting a randomized controlled trial to compare the directed home medicines review service to usual care following acute coronary syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute coronary syndrome, who are admitted to two public, acute care hospitals, will be screened for enrolment into the trial. Exclusion criteria will include: not being discharged home, documented cognitive decline, non-Medicare eligibility, and presence of a terminal malignancy. Randomization concealment and sequence generation will occur through a centrally-monitored computer program. Patients randomized to the control group will receive usual post-discharge care. Patients randomized to receive the intervention will be offered usual post-discharge care and a directed home medicines review at two months post-discharge. The study endpoints will be six and twelve months post-discharge. The primary outcome will be the proportion of patients who are adherent to a complete, guideline-based medication regimen. Secondary outcomes will include hospital readmission rates, length of hospital stays, changes in quality of life, smoking cessation rates, cardiac rehabilitation completion rates, and mortality. As the trial is closely based on an existing service, any improvements observed should be highly translatable into regular practice. Possible limitations to the success of the trial intervention include general practitioner approval of the intervention, general practitioner acceptance of pharmacists' recommendations, and pharmacists' ability to make appropriate recommendations. A detailed monitoring process will detect any barriers to the success of the trial. Given that poor medication persistence following acute coronary syndrome is a worldwide problem, the findings of our study may have international implications for the care of this patient group. Australian New Zealand Clinical Trials Registry ACTRN12611000452998.","subset":"pubmed_abstract"} +{"meta":{"pmid":17101916,"dup_signals":{"dup_doc_count":84,"dup_dump_count":41,"dup_details":{"curated_sources":4,"2023-50":4,"2023-40":1,"2023-23":7,"2023-14":4,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":2,"2022-21":4,"2022-05":3,"2021-39":4,"2021-31":1,"2021-25":2,"2021-17":2,"2021-10":1,"2021-04":2,"2020-45":3,"2020-40":2,"2019-22":1,"2019-18":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-30":2,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":3,"2017-43":3,"2017-34":3,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2024-22":3,"2024-18":2,"2017-13":1,"2013-20":1,"2024-30":1}}},"text":"Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene.\nWe screened 100 patients with inherited and sporadic lower motor neuron degeneration and identified three novel missense mutations in the glycyl-tRNA synthetase (GARS) gene. One mutation was in the anticodon binding domain and associated with onset in early childhood and predominant involvement of the lower limbs, thus extending the phenotype associated with GARS mutations.","subset":"pubmed_abstract"} +{"meta":{"pmid":7678799,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mechanisms of thyroid hormone action on the insulin-like growth factor system: all thyroid hormone effects are not growth hormone mediated.\nNormal somatic growth requires that both the thyroid hormone axis and GH axis be intact. Thyroid hormone stimulates GH secretion, and many thyroid hormone actions on the insulin-like growth factor (IGF) system can be explained by this mechanism. We have previously described distinct changes in IGF binding protein (IGFBP) expression in experimental hypothyroidism in the rat; these changes could be completely corrected by thyroid hormone replacement. To see if the effects of thyroid hormone on IGFBP expression are, in fact, indirect GH effects, we rendered both newborn and adult rats hypothyroid with methimazole treatment, and investigated whether we could correct the resulting IGF and IGFBP changes with GH replacement. The prolonged high expression of serum IGFBP-2 and liver IGFBP-2 messenger RNA (mRNA) during the perinatal period in hypothyroid rat pups could not be normalized by GH therapy, although serum IGF-I values (reduced to 54% of control levels in the hypothyroid animals) were brought up to control level. In adult hypothyroid rats, serum IGF-I concentrations (51% of control levels), were increased up to 79% of control levels, but not totally corrected, by GH therapy. Reduced IGFBP-3 expression (80% of control serum and 50% of control liver mRNA levels) in adult hypothyroid animals was normalized by GH, but there was no correction of the reduced IGFBP-4 serum levels (50% of control levels). Hepatic mRNA levels for the type 1 and 2 IGF receptors were not altered by hypothyroidism, or by thyroid or GH replacement. Somatic growth in hypothyroid pups and adults was only partially corrected by GH therapy. We conclude that GH treatment of hypothyroid animals normalized serum IGF-I levels in the hypothyroid rat pup, but did not correct their prolonged IGFBP-2 expression. In the mature animal, serum IGF-I levels were partially corrected and IGFBP-3 levels were normalized by GH, but no change could be induced in the reduced serum IGFBP-4 levels. All the above changes were normalized by thyroid hormone replacement. Thus, the effects of thyroid hormone on serum IGF levels and IGFBP-3 expression seem to be mediated indirectly via GH. The effects on IGFBP-2 ontogeny, and IGFBP-4 expression in the mature animal, however, are either direct thyroid hormone effects, or mediated by some other route, independent of GH, IGFs, or IGF receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":30095567,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Nonmedical Use of Stimulants Is Associated With Riskier Sexual Practices and Other Forms of Impulsivity.\nThis study sought to examine the occurrence of the nonmedical use of prescription stimulants (amphetamines and methylphenidate) in a university sample and their associated physical and mental health correlates, including potential relationships with risky sexual practices. A 156-item anonymous online survey was distributed via e-mail to a sample of 9449 university students. Current use of alcohol and drugs, psychological and physical status, and academic performance were assessed, along with questionnaire-based measures of impulsivity and compulsivity. A total of 3421 participants (59.7% female) were included in the analysis. 6.7% of the sample reported current\/recent nonmedical use of prescription stimulants, while an additional 5.8% reported misuse in the past. Nonmedical use of prescription stimulants was associated with lower grade point averages, and with taking a broad range of other drugs (including alcohol, nicotine, illicit substances, and consumption of caffeinated soft drinks). Nonmedical use of stimulants was also significantly associated with impulsivity (Barratt scale), prior treatment for substance use problems, and elevated occurrence of disordered gambling, post-traumatic stress disorder, and anxiety; but not depression symptoms or binge-eating disorder (though it was associated with using drugs to lose weight). The relationship with probable attention-deficit\/hyperactivity disorder (ADHD) on screening was not significant but was numerically elevated. Finally, those using nonmedical prescribed stimulants were significantly more sexually active (including at a younger age), and were less likely to use barrier contraception. Nonmedical use of prescription stimulants is common in young adults and has profound public health associations including with a profundity of other drug use (licit and illicit), certain mental health diagnoses (especially gambling, anxiety, and post-traumatic stress disorder ), worse scholastic performance, and riskier sexual practices. The majority of people with nonmedical use of prescription stimulants do not have ADHD, and its link with current ADHD symptoms was less marked than for certain other disorders. Clinicians should screen for the misuse of prescription stimulants as they may be associated with a range of problematic behaviors. Risk of diversion (which may be higher for those living in shared accommodation and those with substance use disorder history) merits careful assessment before prescribing stimulant medication.","subset":"pubmed_abstract"} +{"meta":{"pmid":17355257,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":7}}},"text":"The unique pharmacology of the scorpion alpha-like toxin Lqh3 is associated with its flexible C-tail.\nThe affinity of scorpion alpha-toxins for various voltage-gated sodium channels (Na(v)s) differs considerably despite similar structures and activities. It has been proposed that key bioactive residues of the five-residue-turn (residues 8-12) and the C-tail form the NC domain, whose topology is dictated by a cis or trans peptide-bond conformation between residues 9 and 10, which correlates with the potency on insect or mammalian Na(v)s. We examined this hypothesis using Lqh3, an alpha-like toxin from Leiurus quinquestriatus hebraeus that is highly active in insects and mammalian brain. Lqh3 exhibits slower association kinetics to Na(v)s compared with other alpha-toxins and its binding to insect Na(v)s is pH-dependent. Mutagenesis of Lqh3 revealed a bi-partite bioactive surface, composed of the Core and NC domains, as found in other alpha-toxins. Yet, substitutions at the five-residue turn and stabilization of the 9-10 bond in the cis conformation did not affect the activity. However, substitution of hydrogen-bond donors\/acceptors at the NC domain reduced the pH-dependency of toxin binding, while retaining its high potency at Drosophila Na(v)s expressed in Xenopus oocytes. Based on these results and the conformational flexibility and rearrangement of intramolecular hydrogen-bonds at the NC domain, evident from the known solution structure, we suggest that acidic pH or specific mutations at the NC domain favor toxin conformations with high affinity for the receptor by stabilizing the bound toxin-receptor complex. Moreover, the C-tail flexibility may account for the slower association rates and suggests a novel mechanism of dynamic conformer selection during toxin binding, enabling alpha-like toxins to affect a broad range of Na(v)s.","subset":"pubmed_abstract"} +{"meta":{"pmid":28547881,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":14}}},"text":"Prevalence and clinical correlates of insomnia in adults with attention-deficit hyperactivity disorder.\nTo investigate the prevalence of insomnia in adults with Attention-deficit hyperactivity disorder (ADHD) and its association with clinical subtypes, current ADHD symptoms, and stimulant treatment. We obtained diagnostic information, symptom rating scales and treatment history from clinically ascertained adult ADHD patients diagnosed according to DSM-IV criteria (n = 268, mean age 38.1 years) and randomly selected population controls (n = 202, mean age 36.5 years). The Bergen Insomnia Scale (BIS) was used to measure insomnia. ADHD symptom domains were self-rated using the Adult ADHD Self-Rating Scale. Insomnia was far more frequent among adults with ADHD (66.8%) than in the population controls (28.8%) (P < 0.001). Insomnia was more common in adults with the combined subtype than in those with the inattentive subtype (79.7% and 55.6%, respectively) (P = 0.003). For self-reported current ADHD symptoms, inattention was strongly correlated to insomnia. Patients currently using stimulant treatment for ADHD reported a lower total insomnia score compared to patients without medication (P < 0.05). Insomnia was highly prevalent among adults with ADHD. The lower insomnia score in patients on current stimulant treatment suggests that stimulant treatment is not associated with worsening of insomnia symptoms in adult ADHD patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":24993697,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":14}}},"text":"Human telomeres and telomere biology disorders.\nTelomeres consist of long nucleotide repeats and a protein complex at chromosome ends essential for chromosome stability. Telomeres shorten with each cell division and thus are markers of cellular age. Dyskeratosis congenita (DC) is a cancer-prone inherited bone marrow failure syndrome caused by germ-line mutations in key telomere biology genes that result in extremely short telomeres. The triad of nail dysplasia, abnormal skin pigmentation, and oral leukoplakia is diagnostic of DC but highly variable. Patients with DC may also have but numerous other medical problems, including pulmonary fibrosis, liver abnormalities, avascular necrosis of the hips, and stenosis of the esophagus, lacrimal ducts, and\/or urethra. All modes of inheritance have been reported in DC and de novo mutations are common. Broad phenotypic heterogeneity occurs within DC. Clinically severe variants of DC are Hoyeraal-Hreidarsson syndrome and Revesz syndrome. Coats plus syndrome joined the spectrum of DC with the discovery that it is caused by mutations in a telomere-capping gene. Less clinically severe variants, such as subsets of apparently isolated aplastic anemia or pulmonary fibrosis, have also been recognized. These patients may not have the DC-associated mucocutaneous triad or complicated medical features, but they do have the same underlying genetic etiology. This has led to the use of the descriptive term telomere biology disorder (TBD). This chapter will review the connection between telomere biology and human disease through the examples of DC and its related TBDs.","subset":"pubmed_abstract"} +{"meta":{"pmid":32404092,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2021-21":13,"2021-17":1}}},"text":"Complementary and alternative medicine use among outpatients during the 2015 MERS outbreak in South Korea: a cross-sectional study.\nThe 2015 MERS outbreak in South Korea was the largest event outside of the Middle East. Under such circumstances, individuals tend to resort to non-conventional solutions such as complementary and alternative medicine (CAM) to manage health. Thus, this study aims to examine characteristics of CAM use among outpatients in a community hospital setting during the 2015 MERS outbreak and to assess potential predictors of CAM use during the epidemic. A cross-sectional study was conducted among 331 patients (response rate: 82.75%) at a community hospital located in Seoul, South Korea. The survey instrument included 36 questions on the use of CAM, demographic characteristics, health status, and respondents' perceptions and concerns about MERS infection. Chi-square test and logistic regression were conducted for data analysis using SPSS ver. 21.0., and a p-value of less than 0.05 was considered statistically significant for all analyses. 76.1% of respondents used one or more types of CAM modalities during the MERS outbreak. Consumption of easily accessible modalities such as multivitamin (51.2%) and food products (32.1%) was most popular, and the majority of CAM users relied on mass media (52.4%) and the internet (27.4%) to obtain information on CAM. The use of CAM was associated with age between 40 and 49, age over 50, prior CAM use, and dissatisfaction with the government response to the MERS outbreak. CAM was commonly used by outpatients during the 2015 MERS outbreak in Korea, and mass media was the main source of information. Establishing a media platform is of paramount importance to provide reliable information and ensure the safety of its use.","subset":"pubmed_abstract"} +{"meta":{"pmid":26201876,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Multi-sensor super-resolution for hybrid range imaging with application to 3-D endoscopy and open surgery.\nIn this paper, we propose a multi-sensor super-resolution framework for hybrid imaging to super-resolve data from one modality by taking advantage of additional guidance images of a complementary modality. This concept is applied to hybrid 3-D range imaging in image-guided surgery, where high-quality photometric data is exploited to enhance range images of low spatial resolution. We formulate super-resolution based on the maximum a-posteriori (MAP) principle and reconstruct high-resolution range data from multiple low-resolution frames and complementary photometric information. Robust motion estimation as required for super-resolution is performed on photometric data to derive displacement fields of subpixel accuracy for the associated range images. For improved reconstruction of depth discontinuities, a novel adaptive regularizer exploiting correlations between both modalities is embedded to MAP estimation. We evaluated our method on synthetic data as well as ex-vivo images in open surgery and endoscopy. The proposed multi-sensor framework improves the peak signal-to-noise ratio by 2 dB and structural similarity by 0.03 on average compared to conventional single-sensor approaches. In ex-vivo experiments on porcine organs, our method achieves substantial improvements in terms of depth discontinuity reconstruction.","subset":"pubmed_abstract"} +{"meta":{"pmid":9729865,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2019-04":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2016-44":1,"2016-40":1,"2016-36":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2020-10":1}}},"text":"Optical isolation of portions of a wave front.\nA criterion is established for determining when portions of a wave front can be said to be optically isolated from the rest of the wave front in the sense that they can subsequently be treated separately when one is considering the formation of images. The subarea of the wave front is treated as a separate aperture, and it is said to be isolated if diffraction maxima for the majority of the wave front fall at or beyond the first minima for the subarea. An illustrative example employing two circular unequal-diameter apertures is presented. A method is given for identifying portions of wave front that may be optically isolated; the method uses the technique of fitting a reference surface to the actual wave front and then finding what is defined as the differential deflection of the actual surface with respect to the reference surface at all locations. Subpopulations of locations with similar differential deflection values, sufficient numbers, and sufficient differential deflection are candidates for area of optical isolation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22978553,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":9}}},"text":"Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling.\nThe complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1\u03b1 activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and\/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein-protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1\u03b1. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":11956349,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"In vivo muscle fibre behaviour during counter-movement exercise in humans reveals a significant role for tendon elasticity.\nSix men performed a single ankle plantar flexion exercise in the supine position with the maximal effort with counter movement (CM, plantar flexion preceded by dorsiflexion) and without counter movement (NoCM, plantar flexion only) produced by a sliding table that controlled applied load to the ankle (40 % of the maximal voluntary force). The reaction force at the foot and ankle joint angle were measured using a force plate and a goniometer, respectively. From real-time ultrasonography of the gastrocnemius medialis muscle during the movement, the fascicle length was determined. The estimated peak force, average power, and work at the Achilles' tendon during the plantar flexion phase in CM were significantly greater than those in NoCM. In CM, in the dorsiflexion phase, fascicle length initially increased with little electromyographic activity, then remained constant while the whole muscle-tendon unit lengthened, before decreasing in the final plantar flexion phase. In NoCM, fascicle length decreased throughout the movement and the fascicle length at the onset of movement was longer than that of the corresponding phase in CM. It was concluded that during CM muscle fibres optimally work almost isometrically, by leaving the task of storing and releasing elastic energy for enhancing exercise performance to the tendon.","subset":"pubmed_abstract"} +{"meta":{"pmid":26079170,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":3,"2020-29":1,"2020-05":3,"2019-51":1,"2019-35":2,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2020-34":1}}},"text":"Chemically Functionalized Conjugated Oligoelectrolyte Nanoparticles for Enhancement of Current Generation in Microbial Fuel Cells.\nWater-soluble conjugated oligoelectrolyte nanoparticles (COE NPs), consisting of a cage-like polyhedral oligomeric silsesquioxanes (POSS) core equipped at each end with pendant groups (oligo(p-phenylenevinylene) electrolyte, OPVE), have been designed and demonstrated as an efficient strategy in increasing the current generation in Escherichia coli microbial fuel cells (MFCs). The as-prepared COE NPs take advantage of the structure of POSS and the optical properties of the pendant groups, OPVE. Confocal laser scanning microscopy showed strong photoluminescence of the stained cells, indicating spontaneous accumulation of COE NPs within cell membranes. Moreover, the electrochemical performance of the COE NPs is superior to that of an established membrane intercommunicating COE, DSSN+ in increasing current generation, suggesting that these COE NPs thus hold great potential to boost the performance of MFCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26994483,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2021-10":1,"2019-26":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":1,"2023-40":1,"2024-30":2,"2024-26":1,"2024-18":1,"2024-10":1}}},"text":"Testosterone reduces functional connectivity during the 'Reading the Mind in the Eyes' Test.\nWomen on average outperform men in cognitive-empathic abilities, such as the capacity to infer motives from the bodily cues of others, which is vital for effective social interaction. The steroid hormone testosterone is thought to play a role in this sexual dimorphism. Strikingly, a previous study shows that a single administration of testosterone in women impairs performance on the 'Reading the Mind in Eyes' Test (RMET), a task in which emotions have to be inferred from the eye-region of a face. This effect was mediated by the 2D:4D ratio, the ratio between the length of the index and ring finger, a proxy for fetal testosterone. Research in typical individuals, in individuals with autism spectrum conditions (ASC), and in individuals with brain lesions has established that performance on the RMET depends on the left inferior frontal gyrus (IFG). Using functional magnetic resonance imaging (fMRI), we found that a single administration of testosterone in 16 young women significantly altered connectivity of the left IFG with the anterior cingulate cortex (ACC) and the supplementary motor area (SMA) during RMET performance, independent of 2D:4D ratio. This IFG-ACC-SMA network underlies the integration and selection of sensory information, and for action preparation during cognitive empathic behavior. Our findings thus reveal a neural mechanism by which testosterone can impair emotion-recognition ability, and may link to the symptomatology of ASC, in which the same neural network is implicated.","subset":"pubmed_abstract"} +{"meta":{"pmid":25783156,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Focus issue: noncoding RNAs in cancer.\nThrough various means, noncoding RNAs regulate the expression of genes, many of which are associated with cellular homeostasis. Noncoding RNAs--especially microRNAs--are critical regulators of the mechanisms underlying numerous processes in cell biology, particularly those involved in the development and progression of cancer. This special issue of Science Signaling sheds light on the physiological and pathophysiological functions of this distinct class of molecules.","subset":"pubmed_abstract"} +{"meta":{"pmid":29665881,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Seeking out SARI: an automated search of electronic health records.\nThe definition of severe acute respiratory infection (SARI) - a respiratory illness with fever and cough, occurring within the past 10 days and requiring hospital admission - has not been evaluated for critically ill patients. Using integrated electronic health records data, we developed an automated search algorithm to identify SARI cases in a large cohort of critical care patients and evaluate patient outcomes. We conducted a retrospective cohort study of all admissions to a medical intensive care unit from August 2009 through March 2016. Subsets were randomly selected for deriving and validating a search algorithm, which was compared with temporal trends in laboratory-confirmed influenza to ensure that SARI was correlated with influenza. The algorithm was applied to the cohort to identify clinical differences for patients with and without SARI. For identifying SARI, the algorithm (sensitivity, 86.9%; specificity, 95.6%) outperformed billing-based searching (sensitivity, 73.8%; specificity, 78.8%). Automated searching correlated with peaks in laboratory-confirmed influenza. Adjusted for severity of illness, SARI was associated with more hospital, intensive care unit and ventilator days but not with death or dismissal to home. The search algorithm accurately identified SARI for epidemiologic study and surveillance.","subset":"pubmed_abstract"} +{"meta":{"pmid":21303538,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"Seasonal and geographic differences in treatment-seeking and household cost of febrile illness among children in Malawi.\nHouseholds in malaria endemic countries experience considerable costs in accessing formal health facilities because of childhood malaria. The Ministry of Health in Malawi has defined certain villages as hard-to-reach on the basis of either their distance from health facilities or inaccessibility. Some of these villages have been assigned a community health worker, responsible for referring febrile children to a health facility. Health facility utilization and household costs of attending a health facility were compared between individuals living near the district hospital and those in hard-to-reach villages. Two cross-sectional household surveys were conducted in the Chikhwawa district of Malawi; one during each of the wet and dry seasons. Half the participating villages were located near the hospital, the others were in areas defined as hard-to-reach. Data were collected on attendance to formal health facilities and economic costs incurred due to recent childhood febrile illness. Those living in hard-to-reach villages were less likely to attend a formal health facility compared to those living near the hospital (Dry season: OR 0.35, 95%CI0.18-0.67; Wet season: OR 0.46, 95%CI0.27-0.80). Analyses including community health workers (CHW) as a source of formal health-care decreased the strength of this relationship, and suggested that consulting a CHW may reduce attendance at health facilities, even if indicated. Although those in hard-to-reach villages were still less likely to attend in both the dry (OR 0.53, 95%CI 0.25-1.11) and wet (OR 0.60, 95%CI 0.37-0.98) seasons. Household costs for those who attended a health facility were greater for those in HTR villages (Dry: USD5.24; Wet: USD5.60) than for those living near the district hospital (Dry: USD3.45; Wet: USD4.46). Those living in hard-to-reach areas were less likely to attend a health facility for a childhood febrile event and experienced greater associated household costs. Consulting CHWs was infrequent, but appeared to reduce attendance at a health facility, even when indicated. Health service planners must consider geographic and financial barriers to accessing public health facilities in designing appropriate interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":11827325,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-40":1,"2023-14":1,"2022-27":1,"2021-31":1,"2021-17":1,"2020-50":1,"2020-34":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2023-50":1,"2024-18":1}}},"text":"A method for treating wastewater containing formaldehyde.\nMany industrial activities utilise formaldehyde as a key chemical in organic synthesis including: synthesis of special chemicals such as pentaerythritol and ethylene glycol, synthetic resins, paper products, medicinal products and drugs and others, too numerous to mention. Therefore, effluents arising from these applications may contain significant amounts of formaldehyde. In a biodegradation experiments of a wastewater sample containing formaldehyde ranging from 31.5 to 125 mg\/l, residual formalin (a solution of formaldehyde gas in water) ranging from 40% to 85%, respectively, was found at the end of the run (16 d) showing the inhibition effect of formalin which increased with the increase in formalin concentration. The biodegradation of formalin decreased significantly at concentrations higher than 300 mg\/l. A method to convert formaldehyde to an easily biodegradable substance is herein described. In the commercial manufacture of resins from phenol and formalin the reaction is never completely quantitative. As a result during the dehydration stage phenol and formalin are distilled from the wastewater. Phenol is toxic to several biochemical reactions. However, biological transformation of phenol to a non-toxic entity is possible through specialized microbes. Transformation of phenol is inhibited by the presence of formaldehyde. Biotransformation of phenol in a wastewater containing high concentrations of formaldehyde started shortly after treating the wastewater with calculated amounts of sodium sulphite. Sodium sulphite is believed to react with formaldehyde forming sodium formaldehyde bisulphite, which is not only non-toxic to microorganisms but also a biodegradable substance. From the DO measurements before and after the addition of sodium sulphite, the authors noticed that the dissolved oxygen in a wastewater containing formaldehyde is not affected by the addition of the calculated amount of sodium sulphite, which is just enough to consume the measured amount of formaldehyde in that wastewater.","subset":"pubmed_abstract"} +{"meta":{"pmid":20967364,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2013-48":1,"unknown":11}}},"text":"Effect of dibenzopyrene measurement on assessing air quality in Beijing air and possible implications for human health.\nSize fractionated particulate matter (PM) was collected in summer and winter from Beijing, China for the characterization of an expanded list of PAHs and evaluation of air pollution metrics. Summertime \u03a3PAHs on PM was 14.6 \u00b1 29(PM 1.5), 0.88 \u00b1 0.49(PM 1.5-7.2) and 0.29 \u00b1 0.076(PM 7.2) ng m(-3) air while wintertime concentrations were 493 \u00b1 206(PM 1.5), 26.7 \u00b1 14(PM 1.5-7.2) and 5.3 \u00b1 2.5(PM 7.2) ng m(-3) air. Greater than 90% of the carcinogenic PAHs were concentrated on PM(1.5). Dibenzopyrene isomers made up a significant portion (\u223c30%) of the total carcinogenic PAH load during the winter. To our knowledge, this is the first report of dibenzopyrenes in the Beijing atmosphere and among the few studies that report these highly potent PAHs in ambient particulate matter. Lifetime risk calculations indicated that 1 out of 10,000 to over 6 out of 100 Beijing residents may have an increased risk of lung cancer due to PAH concentration. Over half of the lifetime risk was attributed to \u03a3dibenzopyrenes. The World Health Organization and Chinese daily PM(10) standard was exceeded on each day of the study, however, PAH limits were only exceeded during the winter. The outcomes of the air pollution metrics were highly dependent on the individual PAHs measured and seasonal variation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22523067,"dup_signals":{"dup_doc_count":25,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":22}}},"text":"Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells.\nAllergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.","subset":"pubmed_abstract"} +{"meta":{"pmid":19378669,"dup_signals":{"dup_doc_count":25,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":17}}},"text":"A decision framework for coordinating bioterrorism planning: lessons from the BioNet program.\nEffective disaster preparedness requires coordination across multiple organizations. This article describes a detailed framework developed through the BioNet program to facilitate coordination of bioterrorism preparedness planning among military and civilian decision makers. The authors and colleagues conducted a series of semistructured interviews with civilian and military decision makers from public health, emergency management, hazardous material response, law enforcement, and military health in the San Diego area. Decision makers used a software tool that simulated a hypothetical anthrax attack, which allowed them to assess the effects of a variety of response actions (eg, issuing warnings to the public, establishing prophylaxis distribution centers) on performance metrics. From these interviews, the authors characterized the information sources, technologies, plans, and communication channels that would be used for bioterrorism planning and responses. The authors used influence diagram notation to describe the key bioterrorism response decisions, the probabilistic factors affecting these decisions, and the response outcomes. The authors present an overview of the response framework and provide a detailed assessment of two key phases of the decision-making process: (1) pre-event planning and investment and (2) incident characterization and initial responsive measures. The framework enables planners to articulate current conditions; identify gaps in existing policies, technologies, information resources, and relationships with other response organizations; and explore the implications of potential system enhancements. Use of this framework could help decision makers execute a locally coordinated response by identifying the critical cues of a potential bioterrorism event, the information needed to make effective response decisions, and the potential effects of various decision alternatives.","subset":"pubmed_abstract"} +{"meta":{"pmid":24722339,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Histone deacetylase 1 and p300 can directly associate with chromatin and compete for binding in a mutually exclusive manner.\nLysine acetyltransferases (KATs) and histone deacetylases (HDACs) are important epigenetic modifiers and dynamically cycled on active gene promoters to regulate transcription. Although HDACs are recruited to gene promoters and DNA hypersensitive sites through interactions with DNA binding factors, HDAC activities are also found globally in intergenic regions where DNA binding factors are not present. It is suggested that HDACs are recruited to those regions through other distinct, yet undefined mechanisms. Here we show that HDACs can be directly recruited to chromatin in the absence of other factors through direct interactions with both DNA and core histone subunits. HDACs interact with DNA in a non-sequence specific manner. HDAC1 and p300 directly bind to the overlapping regions of the histone H3 tail and compete for histone binding. Previously we show that p300 can acetylate HDAC1 to attenuate deacetylase activity. Here we have further mapped two distinct regions of HDAC1 that interact with p300. Interestingly, these regions of HDAC1 also associate with histone H3. More importantly, p300 and HDAC1 compete for chromatin binding both in vitro and in vivo. Therefore, the mutually exclusive associations of HDAC1\/p300, p300\/histone, and HDAC1\/histone on chromatin contribute to the dynamic regulation of histone acetylation by balancing HDAC or KAT activity present at histones to reorganize chromatin structure and regulate transcription.","subset":"pubmed_abstract"} +{"meta":{"pmid":8913756,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-50":1,"2020-29":1,"2019-51":1,"2019-47":1,"2019-43":1,"2019-22":2,"2019-18":1,"2018-26":1,"2017-47":1,"2017-26":1,"2021-04":1}}},"text":"Genes regulating the remote wing margin enhancer in the Drosophila cut locus.\nThe mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the suppressor of Hairy-wing protein (SUHW) of Drosophila. SUHW binds a DNA sequence in the gypsy retrotransposon and prevents enhancers promoter-distal to a gypsy insertion in a gene from activating without affecting promoter-proximal enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions between scalloped, mastermind and Chip mutations indicate that mastermind and Chip act synergistically with scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of SUHW enhancer-blocking activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":11222517,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Psychometric properties of the 25-item NEI-VFQ in a Hispanic population: Proyecto VER.\nTo assess the psychometric properties of the NEI-VFQ-25 in a population-based study of older Hispanic persons living in the United States, explore other demographic factors that affect participant response, and observe the comparability of the Spanish and English versions of the instrument. A sample of randomly selected block groups in Tucson and Nogales, Arizona, were selected for study. Participants were interviewed at home; a majority of the interviews were conducted in Spanish. The home interview included questions from the NEI-VFQ-25 and HHANES: Presenting acuity was done using ETDRS methodology, followed by a standardized eye examination by an ophthalmologist. The authors analyzed the internal consistency of the NEI-VFQ-25 responses using Cronbach's alpha coefficient and the construct validity by assessing the relationship between presenting acuity and scale scores, adjusting for age and gender. A second model was also explored to determine whether other demographic variables affected scale scores; differences in reporting between the Spanish and English versions was observed in this model, used in a subset of the population that minimized interviewer effect. Of the 4774 participants in the study, 99.7% had completed questionnaires, not completed by proxy. The highest nonresponse rate occurred in the Driving scale, with 25% of participants not driving for reasons other than problems with vision. Internal consistency was high, with Cronbach alpha ranging between 0.65 and 0.86 for scales with multiple items. Adjusting for age and gender, those with presenting acuity worse than 20\/40 scored significantly lower than those with presenting acuity 20\/40 or better, for all scales. The demographic variables with the most consistent association across the NEI-VFQ-25 scales were presenting acuity, income, and gender. No significant differences in reporting were found between the Spanish and English versions of the questionnaire in the subset of the population. In this study of Hispanic people age 40 years or older, the NEI-VFQ-25 was sensitive to presenting acuity and other demographic variables, such as age, gender, and income. The findings from this psychometric analysis provide evidence of the reliability and validity of some of the scales in the 25-item NEI-VFQ when used among people with a range of visual acuity level, providing other explanatory variables are also considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":29775507,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"\"Coming from a different place\": Partnerships between consumers and health services for system change.\nThe aim of the current study is to explore whether and how the expectations of consumers to be \"representative\" influences consumers' ability to contribute to health services partnerships. Health standards call for services to partner with consumers in service development and governance. While existing research criticises the assumption that individual mental health consumers working with mental health services must be representative of consumers more broadly, research has yet to explore whether this requirement exists for consumers of other health services. Requiring individual consumers to be representative of consumers more broadly marginalises and limits consumer involvement. A qualitative, exploratory design was employed. Consumers (n = 6), clinicians (n = 7) and health managers (n = 5) were interviewed about consumer participation in health services. Data analysis was conducted through the lens of social exchange theory and informed by discursive psychological principles. The current study extends the existing literature within mental health, finding that consumers of other health services are also held responsible for representing broader communities. Data also suggested that a requirement to be representative would marginalise consumers with a passion to bring about change in health systems. The findings suggest that organisations might need a culture change so that individual consumers are not expected to be representative of consumers more broadly and that participation be made more accessible for diverse groups of consumers. Given the role that nurses might play as allies to consumers within health services, the findings of this study contribute to knowledge about the expectations placed on consumers and the ways that nurses might advocate for better partnerships.","subset":"pubmed_abstract"} +{"meta":{"pmid":33793979,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Breast cancer patients' insurance status and residence zip code correlate with early discontinuation of endocrine therapy: An analysis of the ECOG-ACRIN TAILORx trial.\nEarly discontinuation is a substantial barrier to the delivery of endocrine therapies (ETs) and may influence recurrence and survival. The authors investigated the association between early discontinuation of ET and social determinants of health, including insurance coverage and the neighborhood deprivation index (NDI), which was measured on the basis of patients' zip codes, in breast cancer. In this retrospective analysis of a prospective randomized clinical trial (Trial Assigning Individualized Options for Treatment), women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who started ET within a year of study entry were included. Early discontinuation was calculated as stopping ET within 4 years of its start for reasons other than distant recurrence or death via Kaplan-Meier estimates. A Cox proportional hazards joint model was used to analyze the association between early discontinuation of ET and factors such as the study-entry insurance and NDI, with adjustments made for other variables. Of the included 9475 women (mean age, 55.6 years; White race, 84%), 58.0% had private insurance, whereas 11.7% had Medicare, 5.8% had Medicaid, 3.8% were self-pay, and 19.1% were treated at international sites. The early discontinuation rate was 12.3%. Compared with those with private insurance, patients with Medicaid (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.23-1.92) and self-pay patients (HR, 1.65; 95% CI, 1.25-2.17) had higher early discontinuation. Participants with a first-quartile NDI (highest deprivation) had a higher probability of discontinuation than those with a fourth-quartile NDI (lowest deprivation; HR, 1.34; 95% CI, 1.11-1.62). Patients' insurance and zip code at study entry play roles in adherence to ET, with uninsured and underinsured patients having a high rate of treatment nonadherence. Early identification of patients at risk may improve adherence to therapy. In this retrospective analysis of 9475 women with breast cancer participating in a clinical trial (Trial Assigning Individualized Options for Treatment), Medicaid and self-pay patients (compared with those with private insurance) and those in the highest quartile of neighborhood deprivation scores (compared with those in the lowest quartile) had a higher probability of early discontinuation of endocrine therapy. These social determinants of health assume larger importance with the expected increase in unemployment rates and loss of insurance coverage in the aftermath of the coronavirus disease 2019 pandemic. Early identification of patients at risk and enrollment in insurance optimization programs may improve the persistence of therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":12198839,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":1,"2014-10":1,"unknown":12}}},"text":"Retention of alkali, alkaline earth and transition metals on an itaconic acid cation-exchange column. Eluent pH, ionic strength and temperature effects upon selectivity.\nThe unusual selectivity of a methylene succinic (itaconic) acid modified polymeric column was investigated for the separation of alkali, alkaline earth, transition and heavy metals employing non-chelating inorganic eluents. The retention of selected metal ions on the column was investigated with simple HNO3 eluents and eluents prepared from KNO3 and KCl salts of varying pH (adjusted using HNO3). From these studies both the effect of eluent ionic strength and pH upon retention was evaluated for the itaconic acid stationary phase. The results obtained showed that despite slow exchange kinetics causing poor efficiencies, acceptable baseline separations of selected alkaline earth and transitions could be obtained under optimum conditions (the baseline separation of Mg(II), Ca(II), Mn(II), Cd(II), Zn(II) and Co(II) was possible using a 15 mM KNO3-5 mM KCl eluent at pH 3.50 in under 25 min). The use of an simple ionic strength step gradient was shown that facilitated the addition of Pb(II) to the above group of metal ions. An investigation into the effect of temperature upon peak efficiency and retention showed increased column temperature could be used to improve the resolution of closely eluting metal ions such as Ca(II) and Sr(II) and Ca(II) and Mn(II).","subset":"pubmed_abstract"} +{"meta":{"pmid":12465429,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":11}}},"text":"Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.\nThis prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg\/kg\/day, MMF dose was 1 g\/day, azathioprine was administered at 1-2 mg\/day. Steroids were tapered from 20 mg\/day to 5 mg\/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol\/L. Study duration was 6 months. Patient survival at month 6 was 98.3% (Tac\/MMF\/S) and 98.4% (Tac\/Aza\/S), graft survival at 6 month was 95.0% (Tac\/MMF\/S) and 93.5% (Tac\/Aza\/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac\/MMF\/S) compared with 26.8% (Tac\/Aza\/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac\/MMF\/S) and 4.9% (Tac\/Aza\/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac\/MMF\/S) and 48.8% (Tac\/Aza\/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac\/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac\/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac\/MMF\/S) and 7.1% (Tac\/Aza\/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol\/L (Tac\/MMF) and 115.1 mumol\/L (Tac\/Aza); the median serum creatinine of the total study group was 130.5 mumol\/L (Tac\/MMF\/S) and 132.8 mumol\/L (Tac\/Aza\/S). Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.","subset":"pubmed_abstract"} +{"meta":{"pmid":18456715,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Double outlet right ventricle: aetiologies and associations.\nDouble outlet right ventricle (DORV), a clinically significant congenital heart defect, occurs in 1-3% of individuals with congenital heart defects. In contrast to other major congenital heart defects, there are no systematic or comprehensive data regarding associations, aetiologies, and pathogenesis of DORV. We analysed reported cases in the medical literature to address these issues. We queried the PubMed database using key words \"double outlet right ventricle\" and \"DORV\" for case reports, epidemiologic analyses and animal studies with this cardiac anomaly. The anatomic subtype of DORV was classified according to criteria of Van Praagh. Chromosomal abnormalities were present in 61 of the 149 cases of DORV. Trisomies 13 and 18, and del 22q11 were the most commonly associated cytogenetic lesions; different anatomic subtypes of DORV were noted in trisomies 13 and 18 versus del 22q11. DORV was reported in many uncommon or rare non-chromosomal syndromes. Mutations and non-synonymous sequence variants in the CFC1 and CSX genes were the most commonly reported monogenic loci associated with DORV in humans; numerous genes are reported in murine models of DORV. Animal studies implicate maternal diabetes and prenatal exposure to ethanol, retinoids, theophylline, and valproate in DORV teratogenesis. The large number of genes associated with DORV in both humans and animal models and the different anatomic subtypes seen in specific aetiologies indicate the likelihood of several distinct pathogenetic mechanisms for DORV, including impairment of neural crest derivative migration and impairment of normal cardiac situs and looping.","subset":"pubmed_abstract"} +{"meta":{"pmid":22560091,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-20":1,"2024-18":1,"unknown":9}}},"text":"A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome.\nAuriculocondylar syndrome (ACS) is a rare, autosomal-dominant craniofacial malformation syndrome characterized by variable micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic \"question-mark\" ear malformation. Careful phenotypic characterization of severely affected probands in our cohort suggested the presence of a mandibular patterning defect resulting in a maxillary phenotype (i.e., homeotic transformation). We used exome sequencing of five probands and identified two novel (exclusive to the patient and\/or family studied) missense mutations in PLCB4 and a shared mutation in GNAI3 in two unrelated probands. In confirmatory studies, three additional novel PLCB4 mutations were found in multigenerational ACS pedigrees. All mutations were confirmed by Sanger sequencing, were not present in more than 10,000 control chromosomes, and resulted in amino-acid substitutions located in highly conserved protein domains. Additionally, protein-structure modeling demonstrated that all ACS substitutions disrupt the catalytic sites of PLCB4 and GNAI3. We suggest that PLCB4 and GNAI3 are core signaling molecules of the endothelin-1-distal-less homeobox 5 and 6 (EDN1-DLX5\/DLX6) pathway. Functional studies demonstrated a significant reduction in downstream DLX5 and DLX6 expression in ACS cases in assays using cultured osteoblasts from probands and controls. These results support the role of the previously implicated EDN1-DLX5\/6 pathway in regulating mandibular specification in other species, which, when disrupted, results in a maxillary phenotype. This work defines the molecular basis of ACS as a homeotic transformation (mandible to maxilla) in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":19381841,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mechanistic approaches to predicting oral drug absorption.\nModeling and simulation of oral drug absorption have been widely used in drug discovery, development, and regulation. Predictive absorption models are used to determine the rate and extent of oral drug absorption, facilitate lead drug candidate selection, establish formulation development strategy, and support the development of regulatory policies. This review highlights the development of recent drug absorption models including dispersion and compartmental models. The compartmental models include the compartmental absorption and transit model; Grass model; gastrointestinal transit absorption model; advanced compartmental absorption and transit model; and advanced dissolution, absorption, and metabolism model. Compared to the early absorption models, the above models developed or extended since the mid-1990s have demonstrated greatly improved predictive performance by accounting for multiple factors such as drug degradation, gastric emptying, intestinal transit, first-pass metabolism, and intestinal transport. For future model development, more heterogeneous features of the gastrointestinal tract (villous blood flow, metabolizing enzymes, and transporters), food effects, and drug-drug interactions should be fully characterized and taken into consideration. Moreover, predicting population inter- and intravariability in oral drug absorption can be useful and important for the evaluation of clinical safety and efficacy of drugs. Establishing databases and libraries that contain accurate pharmaceutical and pharmacokinetic information for commercialized and uncommercialized drugs may also be helpful for model development and validation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29757618,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Does Size Matter? An Experimental Evaluation of the Relative Abundance and Decay Rates of Aquatic Environmental DNA.\nEnvironmental DNA (eDNA) is increasingly used to monitor aquatic macrofauna. Typically, short mitochondrial DNA fragments are targeted because these should be relatively more abundant in the environment as longer fragments will break into smaller fragments over time. However, longer fragments may permit more flexible primer design and increase taxonomic resolution for eDNA metabarcoding analyses, and recent studies have shown that long mitochondrial eDNA fragments can be extracted from environmental water samples. Nuclear eDNA fragments have also been proposed as targets, but little is known about their persistence in the aquatic environment. Here we measure the abundance of mitochondrial eDNA fragments of different lengths and of short nuclear eDNA fragments, originating from captive fish in experimental tanks, and we test whether longer mitochondrial and short nuclear fragments decay faster than short mitochondrial fragments following fish removal. We show that when fish are present, shorter mitochondrial fragments are more abundant in water samples than both longer mitochondrial fragments and short nuclear eDNA fragments. However, the rate of decay following fish removal was similar for all fragment types, suggesting that the differences in abundance resulted from differences in the rates at which different fragment types were produced rather than differences in their decay rates.","subset":"pubmed_abstract"} +{"meta":{"pmid":6840846,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Correlation of host immune response with quantitative recovery of Chlamydia trachomatis from the human endocervix.\nWe studied 95 women with uncomplicated Chlamydia trachomatis cervical infection. Quantitative isolation of C. trachomatis was performed in HeLa 229 cells, and the results were correlated with serum immunoglobulin M and immunoglobulin G antibody to the organism. We found that quantitative cultures for C. trachomatis can provide a meaningful measurement by which to evaluate the effect of the acquired immune response. In particular, secretory immunoglobulin A antibody to C. trachomatis in cervical secretion demonstrated a striking and inverse correlation with recovery of the organism from the cervix. It is suggested that this component of the immune response may regulate shedding of the organism.","subset":"pubmed_abstract"} +{"meta":{"pmid":7490263,"dup_signals":{"dup_doc_count":25,"dup_dump_count":22,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2023-50":1,"2024-22":1}}},"text":"An improved phage display antibody cloning system using newly designed PCR primers optimized for Pfu DNA polymerase.\nAn improved combinatorial library system to raise mouse monoclonal antibodies was constructed. PCR primers have been newly designed to optimize the reaction for Pfu DNA polymerase, which has proofreading activity. The phagemid vector (pPDS) is designed to accommodate VH and Vk cDNAs, which had previously been assembled by PCR either in single chain fragment of variable regions (scFv) or Fab form. Antibody cloned in scFv form can be converted to Fab form by substituting the scFv linker of (Gly4Ser)3 with a fragment containing murine CH1 cDNA. This vector will produce soluble Fab in non-amber suppressor cells and allow the shuffling of light chains against a heavy chain. Hybridoma cell lines producing anti-human procollagenase monoclonal antibodies were used as the source of antibody mRNA. Antigen-binding ability of both scFv- and Fab-displaying phage was confirmed by ELISA against human procollagenase. They were also analyzed by DNA sequencing to verify the fidelity of Pfu DNA polymerase and to identify the primer incorporated. The mutation rate was considerably reduced compared to the mutation rate achieved by Taq DNA polymerase. Primers are incorporated into target sequences in most cases.","subset":"pubmed_abstract"} +{"meta":{"pmid":28274883,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-05":1,"2021-49":1,"2021-43":2,"2021-39":1,"2021-25":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-16":1,"2022-33":1}}},"text":"Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis.\nComplex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy, is common after conservatively or surgically treated wrist fractures. Several studies support the efficacy of vitamin C in preventing CRPS-I, although the data are somewhat conflicting. The primary objective of this systematic literature review and meta-analysis was to assess the efficacy of vitamin C therapy in preventing CRPS-I after a wrist fracture. Randomised, placebo-controlled trials of vitamin C to prevent CRPS-I after wrist fractures were sought in the three main databases: PubMed (1980 to December 2015), CENTRAL (Central 2015, number 12), and Embase (1980 to December 2015). Two authors worked independently to select articles. Data from selected articles were collected independently. Three randomised placebo-controlled trials in a total of 875 patients were included. Treatment was non-operative in 758\/890 (85.1%) fractures and operative in 132 (14.9%) fractures. Vitamin C supplementation was started on the day of the injury and continued for 50 days. In the group given 500mg of vitamin C daily, the risk ratio for CRPS-I was 0.54 (95%CI, 0.33-0.91; P=0.02). Thus, the risk of developing CRPS-I was significantly decreased by prophylactic treatment with 500mg of vitamin C per day. The heterogeneity rate was 65% (non-significant). Daily supplementation with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I after wrist fracture. II, systematic review of level I and II studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":11783007,"dup_signals":{"dup_doc_count":24,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2022-33":2,"2022-21":1,"2022-05":2,"2021-49":2,"2021-43":1,"2020-45":2,"2020-40":1,"2020-10":1,"2019-47":1,"2019-43":2,"2019-39":1,"2022-49":1,"2024-18":2,"2024-10":1,"2024-26":1}}},"text":"Toucan protein is essential for the assembly of syncytial mitotic spindles in Drosophila melanogaster.\nThe toc gene of Drosophila melanogaster encodes a 235-kD polypeptide with a coiled-coil domain, which is highly expressed during oogenesis (Grammont et al., 1997, 2000). We now report the localization of the Toucan protein during early embryonic development. The Toucan protein is present only during the syncytial stages and is associated with the nuclear envelope and the cytoskeletal structures of the syncytial embryo. In anaphase A, Toucan is concentrated at the spindle poles near the minus end of microtubules. This microtubule association is very dynamic during the nuclear cell cycle. Mutant embryos lacking the Toucan protein are blocked in a metaphase-like state. They display abnormal and nonfunctional spindles, characterized by broad poles, detachment of the centrosomes, and failure of migration of the chromosomes. These results strongly suggest that Toucan represents a factor essential for the assembly and the function of the syncytial mitotic spindles.","subset":"pubmed_abstract"} +{"meta":{"pmid":33680145,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Heuristics in Judgment Tasks with Unrecognized Elements.\nAccording to published studies in the field, random choice and random estimation are the only options for tackling judgment and decision-making tasks where the elements from which to infer a required criteria are not recognized. In Campitelli and Labollita (2010), participants were asked to estimate the nationality and Elo rating of chess players based on their surnames. In the present study I re-analyze those 123 participants from Campitelli and Labollita (2010) who declared not to have recognized any player. Even in this scenario of null recognition, they managed to correctly infer the Russian players' nationality and Elo ratings; it is likely that successful and ecologically rational heuristics were used. I found evidence of new structured probabilistic environments external to the lab, likely to have generated a number of undirected and involuntary associations in the memories of the participants, who may have used them in their heuristics to infer the criteria requested. The results support the models of limited rationality: despite the scarcity of available information, the fact that the heuristics did not guarantee success, and the risk of overestimating the heuristics' effectiveness while underestimating their own biases, participants still favored them over random guesswork, thus suggesting an adaptive use. I invite a revision of what is considered \"good reasoning\" when applied to problems in environments of uncertainty that call for satisfactory, rather than optimal, solutions. This research provides the basis for new studies in the field of heuristics under previously unexplored conditions, and a new perspective for the analysis of prior works, towards a better understanding of the relationship between cognition and the environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":31222106,"dup_signals":{"dup_doc_count":11}},"text":"Neuropeptide precursors and neuropeptides in the sea cucumber Apostichopus japonicus: a genomic, transcriptomic and proteomic analysis.\nThe sea cucumber Apostichopus japonicus is a foodstuff with very high economic value in China, Japan and other countries in south-east Asia. It is at the heart of a multibillion-dollar industry and to meet demand for this product, aquaculture methods and facilities have been established. However, there are challenges associated with optimization of reproduction, feeding and growth in non-natural environments. Therefore, we need to learn more about the biology of A. japonicus, including processes such as aestivation, evisceration, regeneration and albinism. One of the major classes of molecules that regulate physiology and behaviour in animals are neuropeptides, and a few bioactive peptides have already been identified in A. japonicus. To facilitate more comprehensive investigations of neuropeptide function in A. japonicus, here we have analysed genomic and transcriptomic sequence data and proteomic data to identify neuropeptide precursors and neuropeptides in this species. We identified 44 transcripts encoding neuropeptide precursors or putative neuropeptide precursors, and in some instances neuropeptides derived from these precursors were confirmed by mass spectrometry. Furthermore, analysis of genomic sequence data enabled identification of the location of neuropeptide precursor genes on genomic scaffolds and linkage groups (chromosomes) and determination of gene structure. Many of the precursors identified contain homologs of neuropeptides that have been identified in other bilaterian animals. Precursors of neuropeptides that have thus far only been identified in echinoderms were identified, including L- and F-type SALMFamides, AN peptides and others. Precursors of several peptides that act as modulators of neuromuscular activity in A. japonicus were also identified. The discovery of a large repertoire of neuropeptide precursors and neuropeptides provides a basis for experimental studies that investigate the physiological roles of neuropeptide signaling systems in A. japonicus. Looking ahead, some of these neuropeptides may have effects that could be harnessed to enable improvements in the aquaculture of this economically important species.","subset":"pubmed_abstract"} +{"meta":{"pmid":28801210,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-10":4,"2024-30":1,"unknown":9}}},"text":"The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study.\nIn this population-based cohort study, we examined the association between the presence of symptomatic osteoarthritis (OA) and risk for cardiovascular (CV) events. A cohort aged \u226555 years recruited from 1996 to 98 was followed through provincial health administrative data to 2014. Demographics, joint complaints and functional limitations were collected. Hip, knee and hand OA were defined using a validated definition. Using Cox-regressions, the relationship between OA and a composite CV outcome (myocardial infarction (MI), stroke, angina, heart failure, revascularization) was assessed controlling for age, body mass index (BMI), sex, pre-existing metabolic factors, comorbidities, income status, primary care exposure and functional limitations. 18,490 participants were included: median age was 68 years, 60.3% were female; 24.4% met criteria for OA (10.0% hip, 15.3% knee, 16.0% hand), 16.3% self-reported limitation in grip and 25.4% in walking. Over a median 13.4 years, 31.9% experienced a CV event. Controlling for all but walking limitation, a dose-response relationship was observed between number of joints affected by knee\/hip OA and CV risk (HR 2 hips\/knees vs none: 1.13, 95% CI 1.03-1.23; 3+ hips\/knees: 1.22, 95% CI 1.09-1.36). This relationship became non-significant additionally controlling for difficulty walking. Self-reported difficulty walking was associated with a 30% increased hazard for CV events. The effect of hand OA was not significant. In a large population cohort, a greater burden of hip\/knee OA was associated with higher CV risk; the relationship was explained by OA-related difficulty walking. Increased attention to management of OA with a view to improving mobility has potential to reduce CV events.","subset":"pubmed_abstract"} +{"meta":{"pmid":21787390,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2019-18":1,"2018-51":1,"2018-43":1,"2018-30":1,"2018-09":1,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2015-22":1,"2015-14":1,"2014-35":1,"2023-06":1}}},"text":"Strength and tempo of selection revealed in viral gene genealogies.\nRNA viruses evolve extremely quickly, allowing them to rapidly adapt to new environmental conditions. Viral pathogens, such as influenza virus, exploit this capacity for evolutionary change to persist within the human population despite substantial immune pressure. Understanding the process of adaptation in these viral systems is essential to our efforts to combat infectious disease. Through analysis of simulated populations and sequence data from influenza A (H3N2) and measles virus, we show how phylogenetic and population genetic techniques can be used to assess the strength and temporal pattern of adaptive evolution. The action of natural selection affects the shape of the genealogical tree connecting members of an evolving population, causing deviations from the neutral expectation. The magnitude and distribution of these deviations lends insight into the historical pattern of evolution and adaptation in the viral population. We quantify the degree of ongoing adaptation in influenza and measles virus through comparison of census population size and effective population size inferred from genealogical patterns, finding a 60-fold greater deviation in influenza than in measles. We also examine the tempo of adaptation in influenza, finding evidence for both continuous and episodic change. Our results have important consequences for understanding the epidemiological and evolutionary dynamics of the influenza virus. Additionally, these general techniques may prove useful to assess the strength and pattern of adaptive evolution in a variety of evolving systems. They are especially powerful when assessing selection in fast-evolving populations, where temporal patterns become highly visible.","subset":"pubmed_abstract"} +{"meta":{"pmid":17579047,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis.\nExperimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. This study explores a novel use of sodium benzoate (NaB), a commonly used food additive and a Food and Drug Administration-approved nontoxic drug for urea cycle disorders, in treating the disease process of relapsing-remitting EAE in female SJL\/J mice. NaB, administered through drinking water at physiologically tolerable doses, ameliorated clinical symptoms and disease progression of EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. Histological studies reveal that NaB effectively inhibited infiltration of mononuclear cells and demyelination in the spinal cord of EAE mice. Consequently, NaB also suppressed the expression of proinflammatory molecules and normalized myelin gene expression in the CNS of EAE mice. Furthermore, we observed that NaB switched the differentiation of myelin basic protein-primed T cells from Th1 to Th2 mode, enriched regulatory T cell population, and down-regulated the expression of various contact molecules in T cells. Taken together, our results suggest that NaB modifies encephalitogenic T cells at multiple steps and that NaB may have therapeutic importance in multiple sclerosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29364683,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Programmable Assembly of Hybrid Nanoclusters.\nHybrid nanoparticle clusters (often metallic) are interesting plasmonic materials with tunable resonances and a near-field electromagnetic enhancement at interparticle junctions. Therefore, in recent years, we have witnessed a surge in both the interest in these materials and the efforts to obtain them. However, a versatile fabrication of hybrid nanoclusters, that is, combining more than one material, still remains an open challenge. Current lithographical or self-assembly methods are limited to the preparation of hybrid clusters with up to two different materials and typically to the fabrication of hybrid dimers. Here, we provide a novel strategy to deposit and align not only hybrid dimers but also hybrid nanoclusters possessing more complex shapes and compositions. Our strategy is based on the downscaling of sequential capillarity-assisted particle assembly over topographical templates. As a proof of concept, we demonstrate dimers, linear trimers, and 2D nanoclusters with programmable compositions from a range of metallic nanoparticles. Our process does not rely on any specific chemistry and can be extended to a large variety of particles and shapes. The template also simultaneously aligns the hybrid (often anisotropic) nanoclusters, which could facilitate device integration, for example, for optical readout after transfer to other substrates by a printing step. We envisage that this new fabrication route will enable the assembly and positioning of complex hybrid nanoclusters of different functional nanoparticles to study coupling effects not only locally but also at larger scales for new nanoscale optical devices.","subset":"pubmed_abstract"} +{"meta":{"pmid":2382121,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2018-47":1,"2018-34":1,"2018-26":1,"2018-22":2,"2018-13":1,"2018-09":1,"2017-51":1,"2017-39":1,"2016-44":1,"2019-09":1}}},"text":"Otoneurological findings in workers exposed to styrene.\nAn otoneurological test battery was administered to 18 workers with long-term exposure (6-15 years) to styrene at levels well below the current Swedish limit (110 mg\/m3). The results were compared with those of a reference group. Disturbances were found in the central auditory pathways of seven workers. Tests reflecting central processing of impulses from different sensory equilibrium organs were abnormal for 16 workers. The most relevant tests seemed to be static posturography and the rotatory visual suppression test. In the posturography the styrene group had a significantly larger sway area than the reference group. In the visual suppression test, the styrene workers displayed a significantly poorer ability to suppress vestibular nystagmus than the reference group. It was concluded that styrene exposure in industrial environments at moderate or low levels causes central nervous system disturbances which are not always diagnosable with psychometric tests but can be apparent in special otoneurological tests.","subset":"pubmed_abstract"} +{"meta":{"pmid":22371492,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-27":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-41":1,"2014-35":1,"2016-18":1}}},"text":"Structural characterization and oligomerization of the TssL protein, a component shared by bacterial type VI and type IVb secretion systems.\nThe Type VI secretion system (T6SS) is a macromolecular system distributed in Gram-negative bacteria, responsible for the secretion of effector proteins into target cells. The T6SS has a broad versatility as it can target both eukaryotic and prokaryotic cells. It is therefore involved in host pathogenesis or killing neighboring bacterial cells to colonize a new niche. At the architecture level, the T6SS core apparatus is composed of 13 proteins, which assemble in two subcomplexes. One of these subcomplexes, composed of subunits that share structural similarities with bacteriophage tail and baseplate components, is anchored to the cell envelope by the membrane subcomplex. This latter is constituted of at least three proteins, TssL, TssM, and TssJ. The crystal structure of the TssJ outer membrane lipoprotein and its interaction with the inner membrane TssM protein have been recently reported. TssL and TssM share sequence homology and characteristics with two components of the Type IVb secretion system (T4bSS), IcmH\/DotU and IcmF, respectively. In this study, we report the crystal structure of the cytoplasmic domain of the TssL inner membrane protein from the enteroaggregative Escherichia coli Sci-1 T6SS. It folds as a hook-like structure composed of two three-helix bundles. Two TssL molecules associate to form a functional complex. Although the TssL trans-membrane segment is the main determinant of self-interaction, contacts between the cytoplasmic domains are required for TssL function. Based on sequence homology and secondary structure prediction, we propose that the TssL structure is the prototype for the members of the TssL and IcmH\/DotU families.","subset":"pubmed_abstract"} +{"meta":{"pmid":23580802,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Outcomes and characteristics of intermittent hemodialysis for acute kidney injury in an intensive care unit.\nRenal replacement therapy in intensive care units (ICUs) varies globally and is dependent on medical and non-medical factors. We performed a retrospective analysis of patients initiated on dialysis in an ICU. Patient and clinical characteristics, cause of kidney injury, laboratory parameters, hemodialysis characteristics, and survival were reviewed. Acute physiological and chronic health (APACHE II) score was use to study the sickness profile. A total of 92 patients underwent 525 hemodialysis sessions. There were 60 male and 32 female patients. The mean age of the patients was 56.5 \u00b1 16 years. The cause of acute kidney injury included sepsis 64, cardiac 7, malaria 7, postoperative 4, trauma 3, poisoning 2, and others 4. Vasopressors were used in 75% and mechanical ventilation was used in 74 (82%) of the cases. APACHE II score was 22.3 + 7.4. The mean creatinine level was 3.6 + 3.7 mg\/dl. The duration of dialysis was less than 4 h in 324 (61.2%) sessions and greater than 6 h in 118 (22.5%) sessions. The percentage of 30-day survival was 30%. Intermittent hemodialysis customized to renal support needs of ICU patients is an appropriate option in resource-limited settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":24023024,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Neuraxial anesthesia decreases postoperative systemic infection risk compared with general anesthesia in knee arthroplasty.\nSurgical stress has been shown to result in immune disturbance. Neuraxial anesthesia (NA) has long been hypothesized to blunt undesired surgical insults and thus limit immune compromise and improve surgical outcomes. We hypothesized that NA would decrease postoperative infectious complications compared with general anesthesia (GA) among knee arthroplasty patients. We studied the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2010. There were 16,555 patients included in our final cohort, with 9167 patients receiving GA and 7388 patients receiving spinal or epidural anesthesia.. Outcomes of interest included infection-related 30-day postoperative complications, including surgical site-related infections, pneumonia, urinary tract infection, sepsis, septic shock, and a composite end point of any systemic infection. Multivariable logistic regression was performed to test for effect of anesthesia type while adjusting for the influence of preexisting comorbidities. The overall mortality was 0.24% and 0.15% among NA and GA subjects, respectively (P = 0.214). NA subjects had fewer unadjusted incidences of pneumonia (P = 0.035) and composite systemic infection (P = 0.006). After risk adjustment for preexisting comorbidities, NA was associated with lower odds of pneumonia (odds ratio = 0.51 [95% confidence interval, 0.29-0.90]) and lower odds of composite systemic infection (odds ratio = 0.77 [95% confidence interval, 0.64-0.92]). Our study suggested that NA was associated with lower adjusted odds of both pneumonia and a composite outcome of any systemic infectious complication within 30 days of surgery compared with GA.","subset":"pubmed_abstract"} +{"meta":{"pmid":28410023,"dup_signals":{"dup_doc_count":25,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2018-30":3,"2018-13":1,"2018-09":2,"2018-05":1,"2017-47":3,"2017-39":3,"2017-30":1,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":1,"2017-13":1}}},"text":"Timing of Breeding in an Ecologically Trapped Bird.\nIn human-modified environments, organisms may prefer to use habitats where their reproductive performance is lower compared to alternative options. Many such ecological traps occur in seasonally changing environments. Although the timing of breeding has been shown to impact reproductive performance in a variety of organisms, it has never been considered as a potential mechanism underlying ecological traps. We address this issue with a migratory bird, the red-backed shrike, breeding in a human-modified, farmland-forest landscape. Shrikes prefer breeding in forest clear-cuts where their reproductive performance is lower than in less attractive farmland. We compared brood size and quality of early (first broods) and delayed breeders (replacement broods) between the two habitats. We found a stronger seasonal decrease in reproductive performance in preferred forest clear-cuts than in farmland. Food resources were slightly more abundant in forest than in farmland at the beginning of the season but depleted more steeply in forest by the end of the breeding season. By contrast, the phenotypic quality of breeders did not decline over the course of the season in either habitat. This is the first report that the timing of breeding relative to the seasonal change in key resources may play a significant role in explaining low reproductive performance in ecological traps.","subset":"pubmed_abstract"} +{"meta":{"pmid":21304913,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Lysine residue 185 of Rad1 is a topological but not a functional counterpart of lysine residue 164 of PCNA.\nMonoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164)) is a highly conserved, DNA damage-inducible process that is mediated by the E2\/E3 complex Rad6\/Rad18. This ubiquitylation event recruits translesion synthesis (TLS) polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6\/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185)) was identified as the only topological equivalent of PCNA(K164). To investigate a potential role of posttranslational modifications of Rad1(K185) in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R) allele. The Rad1(K185) residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185) is not a functional counterpart of PCNA(K164).","subset":"pubmed_abstract"} +{"meta":{"pmid":28392984,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Non-native molluscan colonizers on deliberately placed shipwrecks in the Florida Keys, with description of a new species of potentially invasive worm-snail (Gastropoda: Vermetidae).\nArtificial reefs created by deliberately sinking ships off the coast of the Florida Keys island chain are providing new habitat for marine invertebrates. This newly developing fouling community includes the previously reported invasive orange tube coral Tubastraea coccinea and the non-native giant foam oyster Hyotissa hyotis. New SCUBA-based surveys involving five shipwrecks spanning the upper, middle, and lower Florida Keys, show T. coccinea now also established in the lower Keys and H. hyotis likewise extending to new sites. Two additional mollusks found on the artificial reefs, the amathinid gastropod Cyclothyca pacei and gryphaeid oyster Hyotissa mcgintyi, the latter also common in the natural reef areas, are discussed as potentially non-native. A new species of sessile, suspension-feeding, worm-snail, Thylacodes vandyensis Bieler, Rawlings & Collins n. sp. (Vermetidae), is described from the wreck of the USNS Vandenberg off Key West and discussed as potentially invasive. This new species is compared morphologically and by DNA barcode markers to other known members of the genus, and may be a recent arrival from the Pacific Ocean. Thylacodes vandyensis is polychromatic, with individuals varying in both overall head-foot coloration and mantle margin color pattern. Females brood stalked egg capsules attached to their shell within the confines of their mantle cavity, and give rise to crawl-away juveniles. Such direct-developing species have the demonstrated capacity for colonizing habitats isolated far from their native ranges and establishing rapidly growing founder populations. Vermetid gastropods are common components of the marine fouling community in warm temperate and tropical waters and, as such, have been tagged as potentially invasive or with a high potential to be invasive in the Pacific Ocean. As vermetids can influence coral growth\/composition in the Pacific and have been reported serving as intermediate hosts for blood flukes of loggerhead turtles, such new arrivals in the Florida Keys National Marine Sanctuary are of concern. Growing evidence indicates that artificial reefs can act as permanent way-stations for arriving non-natives, providing nurseries within which populations may grow in an environment with reduced competition compared to native habitats. Consequently, artificial reefs can act as sentinels for the appearance of new species. Ongoing monitoring of the developing molluscan fauna on the artificial reefs of the Florida Keys is necessary to recognize new invasions and identify potential eradication targets, thereby assuring the health of the nearby natural barrier reef.","subset":"pubmed_abstract"} +{"meta":{"pmid":23279566,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-16":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-30":1,"2017-17":1,"2023-40":1,"2017-13":2,"2024-10":1}}},"text":"Blockade of p-selectin is sufficient to reduce MHC I antibody-elicited monocyte recruitment in vitro and in vivo.\nDonor-specific HLA antibodies significantly lower allograft survival, but as yet there are no satisfactory therapies for prevention of antibody-mediated rejection. Intracapillary macrophage infiltration is a hallmark of antibody-mediated rejection, and macrophages are important in both acute and chronic rejection. The purpose of this study was to investigate the Fc-independent effect of HLA I antibodies on endothelial cell activation, leading to monocyte recruitment. We used an in vitro model to assess monocyte binding to endothelial cells in response to HLA I antibodies. We confirmed our results in a mouse model of antibody-mediated rejection, in which B6.RAG1(-\/-) recipients of BALB\/c cardiac allografts were passively transferred with donor-specific MHC I antibodies. Our findings demonstrate that HLA I antibodies rapidly increase intracellular calcium and endothelial presentation of P-selectin, which supports monocyte binding. In the experimental model, donor-specific MHC I antibodies significantly increased macrophage accumulation in the allograft. Concurrent administration of rPSGL-1-Ig abolished antibody-induced monocyte infiltration in the allograft, but had little effect on antibody-induced endothelial injury. Our data suggest that antagonism of P-selectin may ameliorate accumulation of macrophages in the allograft during antibody-mediated rejection.","subset":"pubmed_abstract"} +{"meta":{"pmid":33730330,"dup_signals":{"dup_doc_count":32,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-14":2,"2023-06":1,"2022-49":2,"2022-33":2,"2022-27":3,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2023-50":1,"2024-26":3,"2024-22":5,"2024-18":1}}},"text":"Obesity in the absence of comorbidities is not related to clinically meaningful left ventricular hypertrophy.\nObesity is associated with the development of left ventricular (LV) hypertrophy. Whether obesity in in the absence of comorbidities can cause LV hypertrophy to an extent which could create diagnostic uncertainty with pathological states (such as hypertrophic cardiomyopathy) is unknown. We used cine cardiovascular magnetic resonance imaging to precisely measure LV wall thickness in the septum and lateral wall in 764 people with body mass indices ranging from 18.5 kg\/m2 to 59.2 kg\/m2 in the absence of major comorbidities. Obesity was related to LV wall thickness across the cohort (basal septum r 0.30, P < 0.001 and basal lateral wall r 0.18, P < 0.001). Although no participant had hypertension, these associations remained highly significant after controlling for systolic blood pressure (all P < 0.01). Each 10 kg\/m2 increase in BMI was associated with an increase in basal septal wall thickness of 1.0 mm males and 0.8 mm in females, with no statistically significant difference between genders (P = 0.1). Even in class 3 obesity (BMI > 40 kg\/m2), no LV wall thickness > 13.4 mm in males or > 12.7 mm in females was observed in this cohort. We confirm that obesity in the absence of comorbidities is associated with LV hypertrophy, and establish that the magnitude of this change is modest even in severe obesity. LV hypertrophy > 14 mm cannot safely be attributed to obesity alone and alternative diagnoses should be considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":9010428,"dup_signals":{"dup_doc_count":20,"dup_dump_count":8,"dup_details":{"curated_sources":6,"2022-27":1,"2022-21":4,"2022-05":2,"2021-49":3,"2021-43":1,"2019-51":1,"2019-13":1,"2022-33":1}}},"text":"Progressive loss of glutamic acid decarboxylase, parvalbumin, and calbindin D28K immunoreactive neurons in the cerebral cortex and hippocampus of adult rat with experimental hydrocephalus.\nThe authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus. Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event in hydrocephalic brain injury. Although the mechanism of this impairment is still speculative, these findings emphasize the importance of investigating the neuronal pathophysiology in hydrocephalus.","subset":"pubmed_abstract"} +{"meta":{"pmid":34045447,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":2,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"FORTIS: a live-cell assay to monitor AMPA receptors using pH-sensitive fluorescence tags.\nThe real-time live fluorescent monitoring of surface AMPA receptors (AMPARs) could open new opportunities for drug discovery and phenotypic screening concerning neuropsychiatric disorders. We have developed FORTIS, a tool based on pH sensitivity capable of detecting subtle changes in surface AMPARs at a neuronal population level. The expression of SEP-GluA1 or pHuji-GluA1 recombinant AMPAR subunits in mammalian neurons cultured in 96-well plates enables surface AMPARs to be monitored with a microplate reader. Thus, FORTIS can register rapid changes in surface AMPARs induced by drugs or genetic modifications without having to rely on conventional electrophysiology or imaging. By combining FORTIS with pharmacological manipulations, basal surface AMPARs, and plasticity-like changes can be monitored. We expect that employing FORTIS to screen for changes in surface AMPARs will accelerate both neuroscience research and drug discovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":11700268,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"unknown":15}}},"text":"Smoking and lung cancer risk in American and Japanese men: an international case-control study.\nRates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.","subset":"pubmed_abstract"} +{"meta":{"pmid":19697327,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":9}}},"text":"CCK2 receptor expression transforms non-tumorigenic human NCM356 colonic epithelial cells into tumor forming cells.\nExpression of gastrin and cholecystokinin 2 (CCK(2)) receptor splice variants (CCK(2)R and CCK(2i4sv)R) are upregulated in human colonic adenomas where they are thought to contribute to tumor growth and progression. To determine the effects of ectopic CCK(2) receptor variant expression on colonic epithelial cell growth in vitro and in vivo, we employed the non-tumorigenic colonic epithelial cell line, NCM356. Receptor expression was induced using a retroviral expression vector containing cDNAs for either CCK(2i4sv)R or CCK(2)R. RT-PCR and intracellular Ca(2+) ([Ca(2+)](i)) imaging of RIE\/CCK(2)R cells treated with conditioned media (CM) from NCM356 revealed that NCM356 cells express gastrin mRNA and secrete endogenous, biologically active peptide. NCM356 cells expressing either CCK(2)R or CCK(2i4sv)R (71 and 81 fmol\/mg, respectively) grew faster in vitro, and exhibited an increase in basal levels of phosphorylated ERK (pERK), compared with vector. CCK(2) receptor selective antagonist, YM022, partially inhibited the growth of both receptor-expressing NCM356 cells, but not the control cells. Inhibitors of mitogen activated protein kinase pathway (MEK\/ERK) or protein kinase C (PKC) isozymes partially inhibited the elevated levels of basal pERK and in vitro growth of receptor-expressing cells. Vector-NCM356 cells did not form tumors in nude mice, whereas, either CCK(2) receptor-expressing cells formed large tumors. Autocrine activation CCK(2) receptor variants are sufficient to increase in vitro growth and tumorigenicity of non-transformed NCM356 colon epithelial cells through a pathway involving PKC and the MEK\/ERK axis. These findings support the hypothesis that expression of gastrin and its receptors in human colonic adenomas contributes to tumor growth and progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":23320030,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":2,"2024-18":1,"unknown":14}}},"text":"Bridelia ferruginea Produces Antineuroinflammatory Activity through Inhibition of Nuclear Factor-kappa B and p38 MAPK Signalling.\nBridelia ferruginea is commonly used in traditional African medicine (TAM) for treating various inflammatory conditions. Extracts from the plant have been shown to exhibit anti-inflammatory property in a number of in vivo models. In this study the influence of B. ferruginea (BFE) on the production of PGE(2), nitrite, and proinflammatory cytokines from LPS-stimulated BV-2 microglia was investigated. The effects of BFE on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expressions were evaluated in LPS-activated rat primary microglia. The roles of NF-\u03baB and MAPK signalling in the actions of BFE were also investigated. BFE (25-200 \u03bcg) inhibited the production of PGE(2), nitrite, tumour necrosis factor-\u03b1 (TNF\u03b1), and interleukin-6 (IL-6) as well as COX-2 and iNOS protein expressions in LPS-activated microglial cells. Further studies to elucidate the mechanism of anti-inflammatory action of BFE revealed interference with nuclear translocation of NF-\u03baBp65 through mechanisms involving inhibition of I\u03baB degradation. BFE prevented phosphorylation of p38, but not p42\/44 or JNK MAPK. It is suggested that Bridelia ferruginea produces anti-inflammatory action through mechanisms involving p38 MAPK and NF-\u03baB signalling.","subset":"pubmed_abstract"} +{"meta":{"pmid":27923466,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-22":1,"unknown":7}}},"text":"Predicting lethal entanglements as a consequence of drag from fishing gear.\nLarge whales are frequently entangled in fishing gear and sometimes swim while carrying gear for days to years. Entangled whales are subject to additional drag forces requiring increased thrust power and energy expenditure over time. To classify entanglement cases and aid potential disentanglement efforts, it is useful to know how long an entangled whale might survive, given the unique configurations of the gear they are towing. This study establishes an approach to predict drag forces on fishing gear that entangles whales, and applies this method to ten North Atlantic right whale cases to estimate the resulting increase in energy expenditure and the critical entanglement duration that could lead to death. Estimated gear drag ranged 11-275N. Most entanglements were resolved before critical entanglement durations (mean\u00b1SD 216\u00b1260days) were reached. These estimates can assist real-time development of disentanglement action plans and U.S. Federal Serious Injury assessments required for protected species.","subset":"pubmed_abstract"} +{"meta":{"pmid":17898300,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Retinal nerve fiber layer defects in RP patients.\nTo determine, with the use of optical coherence tomography (OCT), the peripapillary retinal nerve fiber layer (RNFL) thickness among patients with retinitis pigmentosa (RP) of different degrees of disease severity. One eye in each of 25 RP patients was included. All patients underwent complete ocular examination, including the measurement of intraocular pressure, corneal thickness, and detailed fundus examination. Visual fields were evaluated by Goldmann perimetry. An RNFL thickness protocol was used to acquire circular scans of 3.46 mm in diameter around the optic nerve. For each eye, RNFL thickness was studied in the temporal (316 degrees -45 degrees ), superior (46 degrees -135 degrees ), nasal (136 degrees -225 degrees ), and inferior (226 degrees -315 degrees ) quadrants. Three smaller segments were also measured within each quadrant, all automatically calculated by the existing OCT software. The severity of damage to the peripapillary nerve fiber layer was compared with the clinical appearance of the optic disc, severity of field loss, and mode of inheritance for RP. The mean age of patients included in the study was 48.6 years (range, 23-73 years). Of the 25 patients examined, 10 had abnormal thinning of the peripapillary RNFL in 2 or more segments, and 7 of those had abnormal thinning in at least 1 quadrant. The number of patients with abnormal thinning of the RNFL was considerably greater in those with clinically observed moderately severe or severe pallor of the optic disc than in those with normal appearance or mild pallor of the optic disc. No consistent association was noted between the remaining visual field and the presence of a RNFL defect (P > 0.05). Patients with retinitis pigmentosa may have a measurable degree of RNFL thinning as determined by OCT. These observations could have an impact on future treatment strategies and imply that patients considered for various treatment options would benefit by an evaluation of nerve fiber layer thickness.","subset":"pubmed_abstract"} +{"meta":{"pmid":27262333,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Polyketide Natural Products, Acetogenins from Graviola (Annona muricata L), its Biochemical, Cytotoxic Activity and Various Analyses Through Computational and Bio-Programming Methods.\nPlants became the basis of traditional medicine system throughout the world for thousands of years and continue to provide mankind with new remedies. Annona muricata, the plant of Annonaceae family, is also known as sour sop or Graviola. In recent years, many compounds have been reported and have gained organic chemist's and biochemist's attention because of their novel structure and wide range of bioactivity. Local populations have used the bark, leaves, roots, fruit, seeds and flowers for thousands of years to treat everything from arthritis to liver problems. Annonaceous acetogenins found only in the Annonaceae family kill malignant cells of 12 different types of cancer including Breast, Ovarian, Colon, Prostate, Liver, Lung, Pancreatic and Lymphoma. Hence, the study was initiated to identify, fractionate and validate compounds of pharmaceutical importance from the leaf extract. Research was made for the phytochemical screening using different solvents and the metabolites were screened using TLC. The presence of acetogenins was confirmed using PMA 5% spray. The anti-cancer activity studies were done for Breast Cancer cell lines, MCF-7 and the cell inhibition activity was 98%. We were curious to study the computational part of the aetogenins; hence, apart from the experimental studies, various computational studies were progressed using Schr\u00f6dinger and other computational tools to validate the key target protein and the potent molecule \"Coronin\" and Annonaine. To predict and decipher the activity of various acetogenins in Annona muricata and its potent activity towards the inhibition of cancer cell lines, it is interesting to look out for the potent lead compound against the disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":1967648,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Pharmacological properties of the N-methyl-D-aspartate receptor system coupled to the evoked release of gamma-[3H] aminobutyric acid from striatal neurons in primary culture.\nThe actions of a series of endogenous excitatory amino acid (EAA) agonists and synthetic antagonists at the N-methyl-D-aspartate (NMDA) receptor system coupled to the evoked release of gamma-[3H]aminobutyric acid (GABA) from purified populations of striatal neurons in primary culture were examined. EAA agonists displayed the following rank order of potency in evoking [3H]GABA release: glutamate greater than homocysteate greater than aspartate, NMDA greater than cysteine sulfinate. Glutamate, homocysteate and cysteine sulfinate were equieffective, whereas at saturating concentrations, aspartate and NMDA reached 75 and 65%, respectively, of the maximum efficacy of the former three agonists. The release of [3H]GABA evoked by 100 microM NMDA was attenuated in a dose-dependent manner by the following antagonists (IC50, micromolar): MK-801 (0.067), phencyclidine (0.151), CGS-19755 (3.31), 2-aminophosphonovalerate (18.8), kynurenate (100) and gamma-D-glutamylglycine (100). The antagonist properties of MK-801 and phencyclidine were not competitive with NMDA, whereas NMDA dose-response curves performed in the absence and presence of increasing concentrations of CGS-19755 resulted in parallel rightward shifts (pA2 = 5.95). CGS-19755 produced similar rightward shifts of the homocysteate dose-response curve (pA2 = 5.89). At glutamate concentrations less than 100 microM, CGS-19755 and 2-aminophosphonovalerate were potent antagonists of glutamate-evoked release; however, at glutamate concentrations greater than 100 microM these agents were ineffective blockers. The blockade of NMDA-evoked release of [3H]GABA by kynurenate was not competitive in nature.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":23960137,"dup_signals":{"dup_doc_count":25,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":21}}},"text":"From data to function: functional modeling of poultry genomics data.\nOne of the challenges of functional genomics is to create a better understanding of the biological system being studied so that the data produced are leveraged to provide gains for agriculture, human health, and the environment. Functional modeling enables researchers to make sense of these data as it reframes a long list of genes or gene products (mRNA, ncRNA, and proteins) by grouping based upon function, be it individual molecular functions or interactions between these molecules or broader biological processes, including metabolic and signaling pathways. However, poultry researchers have been hampered by a lack of functional annotation data, tools, and training to use these data and tools. Moreover, this lack is becoming more critical as new sequencing technologies enable us to generate data not only for an increasingly diverse range of species but also individual genomes and populations of individuals. We discuss the impact of these new sequencing technologies on poultry research, with a specific focus on what functional modeling resources are available for poultry researchers. We also describe key strategies for researchers who wish to functionally model their own data, providing background information about functional modeling approaches, the data and tools to support these approaches, and the strengths and limitations of each. Specifically, we describe methods for functional analysis using Gene Ontology (GO) functional summaries, functional enrichment analysis, and pathways and network modeling. As annotation efforts begin to provide the fundamental data that underpin poultry functional modeling (such as improved gene identification, standardized gene nomenclature, temporal and spatial expression data and gene product function), tool developers are incorporating these data into new and existing tools that are used for functional modeling, and cyberinfrastructure is being developed to provide the necessary extendibility and scalability for storing and analyzing these data. This process will support the efforts of poultry researchers to make sense of their functional genomics data sets, and we provide here a starting point for researchers who wish to take advantage of these tools.","subset":"pubmed_abstract"} +{"meta":{"pmid":26602523,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats.\nThis study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg\/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg\/kg and Nigella sativa oil at a dose of 2.5 mg\/kg for 8 weeks, respectively, concomitantly with L-NAME administration. Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.","subset":"pubmed_abstract"} +{"meta":{"pmid":21307249,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":8}}},"text":"Akt suppresses retrograde degeneration of dopaminergic axons by inhibition of macroautophagy.\nAxon degeneration is a hallmark of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Such degeneration is not a passive event but rather an active process mediated by mechanisms that are distinct from the canonical pathways of programmed cell death that mediate destruction of the cell soma. Little is known of the diverse mechanisms involved, particularly those of retrograde axon degeneration. We have previously observed in living animal models of degeneration in the nigrostriatal projection that a constitutively active form of the kinase, myristoylated Akt (Myr-Akt), demonstrates an ability to suppress programmed cell death and preserve the soma of dopamine neurons. Here, we show in both neurotoxin and physical injury (axotomy) models that Myr-Akt is also able to preserve dopaminergic axons due to suppression of acute retrograde axon degeneration. This cellular phenotype is associated with increased mammalian target of rapamycin (mTor) activity and can be recapitulated by a constitutively active form of the small GTPase Rheb, an upstream activator of mTor. Axon degeneration in these models is accompanied by the occurrence of macroautophagy, which is suppressed by Myr-Akt. Conditional deletion of the essential autophagy mediator Atg7 in adult mice also achieves striking axon protection in these acute models of retrograde degeneration. The protection afforded by both Myr-Akt and Atg7 deletion is robust and lasting, because it is still observed as protection of both axons and dopaminergic striatal innervation weeks after injury. We conclude that acute retrograde axon degeneration is regulated by Akt\/Rheb\/mTor signaling pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":30564735,"dup_signals":{"dup_doc_count":34,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-06":1,"2022-40":1,"2022-27":2,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-25":2,"2021-21":3,"2021-17":2,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-47":1,"2019-39":1,"2023-23":1,"2024-10":1,"2024-30":1}}},"text":"Non-vitamin k antagonist oral anticoagulants in a European primary care physician survey.\nFamiliarity and competency in the options for stroke prevention in atrial fibrillation (AF) and the role of non-vitamin K antagonist oral anticoagulants (NOACs) may vary among primary care physicians (PCPs) from different European countries. To investigate PCP views on prescribing and managing NOACs across Europe and identify perceived unmet needs. Web-based survey including PCPs with particular interest in cardiovascular medicine. A questionnaire was drawn up, containing 10 questions on initiation and ongoing management of NOACs; use of AF stroke guidelines on NOACs and anticoagulant switching; and perceived information needs. The overall response rate was 42%. The majority of PCPs declared they are responsible for and confident in both initiating and managing NOAC therapy. In some countries, PCPs are not able to initiate NOAC therapy due to administrative barriers (namely, Italy and Slovakia). No single set of guidelines is referred to across all countries and over a fifth of responders indicate they do not follow specific guidelines. The main learning needs reported were more related to initiation than to ongoing management of anticoagulant therapy. According to this self-assessment survey, the experience of most PCPs in management of different aspects of AF appears good and only some felt the need for further training. However, in the light of the importance of this topic as public health issue, intensified efforts aiming at better equipping PCPs to meet their key roles in an integrated service across Europe are overdue.","subset":"pubmed_abstract"} +{"meta":{"pmid":17087385,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Sludge production and management processes: case study in China.\nIn 2010, the sewage sludge production rate will be 178,500 t dried solids (ds) for Beijing and 294,000 t-ds for Shanghai, respectively. Beijing adopts a centralized system to stabilize 78% of her sludge in three rural Stabilization Centres. Aerated composting technique will be used. Shanghai on the contrary decentralizes the management plan to treat the sludge on site. Diverse treatment trains, such as aerobic\/anaerobic digestion, drying, incineration, and composting will be applied. Production rate, treatment plan, and the associated costs, energy consumption, carbon dioxide emission, and risk assessment for heavy metals and pathogens on human health were evaluated in this report for sludges yielded in Beijing and Shanghai, China.","subset":"pubmed_abstract"} +{"meta":{"pmid":19930589,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-18":1,"2014-10":1,"2013-48":3,"2024-30":1,"unknown":9}}},"text":"Household exposure to violence and human rights violations in western Bangladesh (I): prevalence, risk factors and consequences.\nThe ruling parties in Bangladesh have systematically used violence against political opponents and criminals. It is essential to 1) determine the magnitude and burden of organised crime and political violence (OPV) and human rights violations in the affected community, and to 2) identify the risk factors and key indicators for developing effective health intervention and prevention measures. The population-based study consisted of two parts: a household survey and OPV screening at mobile clinics (presented in Part II). A cross-sectional, multistage cluster household survey was conducted in the Meherpur district in February-March 2008; 22 clusters with a sample size of 1,101 households (population of 4,870) were selected. Around 83% of households reported being exposed to at least two categories of OPV or human rights violations: 29% reported that the family members had been arrested or detained; 31% reported torture or other cruel, inhuman or degrading treatment or punishment. Crude mortality rate was 17.9\/1,000 and under 5 mortality rate was 75\/1,000. The annual injury rate was 36%, lifetime experience of violence-related injury was 50%, and pain experience within 2 weeks was reported by 57%. Over 80% of the population over 35 years old complained of pain. High prevalence of injury, lifetime experience of OPV-related injury and pain complaints are related to the level of exposure to OPV and human rights violations. A financial burden was imposed on families with an injured person. A geographical variation was revealed regarding reports of torture and lifetime experience of violence-related injury. A combination of individual, relational, community and societal factors, including variables such as political party affiliation, conflict with other families, household income and residential area, affected the risk of victimisation in the household. The odds ratio for reporting extrajudicial execution of a family member was 9.22 for Awami League supporters, 9.15 for Bangladesh Nationalist Party supporters; and 3.97 for Jamaat-e-Islami Party supporters compared with families with no political involvement. The level of violence and human rights violations is high. The affected population suffers from violence-related injuries and traumas, which could be a factor contributing to poverty. Victimisation is not random.","subset":"pubmed_abstract"} +{"meta":{"pmid":24865870,"dup_signals":{"dup_doc_count":97,"dup_dump_count":36,"dup_details":{"curated_sources":4,"2020-50":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-26":1,"2019-22":3,"2019-18":1,"2019-13":3,"2019-09":1,"2019-04":2,"2018-47":4,"2018-39":3,"2018-30":3,"2018-17":4,"2018-09":2,"2018-05":2,"2017-47":7,"2017-43":2,"2017-39":4,"2017-34":4,"2017-30":4,"2017-26":4,"2017-22":4,"2017-17":3,"2017-09":3,"2017-04":4,"2016-50":4,"2016-44":4,"2016-40":4,"2014-49":1,"2021-17":1,"2017-13":3,"2024-18":1}}},"text":"The effects of written emotional disclosure and coping skills training in rheumatoid arthritis: a randomized clinical trial.\nTwo psychological interventions for rheumatoid arthritis (RA) are cognitive-behavioral coping skills training (CST) and written emotional disclosure (WED). These approaches have developed independently, and their combination may be more effective than either one alone. Furthermore, most studies of each intervention have methodological limitations, and each needs further testing. We randomized 264 adults with RA in a 2 \u00d7 2 factorial design to 1 of 2 writing conditions (WED vs. control writing) followed by 1 of 2 training conditions (CST vs. arthritis education control training). Patient-reported pain and functioning, blinded evaluations of disease activity and walking speed, and an inflammatory marker (C-reactive protein) were assessed at baseline and 1-, 4-, and 12-month follow-ups. Completion of each intervention was high (>90% of patients), and attrition was low (10.2% at 12-month follow-up). Hierarchical linear modeling of treatment effects over the follow-up period, and analyses of covariance at each assessment point, revealed no interactions between writing and training; however, both interventions had main effects on outcomes, with small effect sizes. Compared with control training, CST decreased pain and psychological symptoms through 12 months. The effects of WED were mixed: Compared with control writing, WED reduced disease activity and physical disability at 1 month only, but WED had more pain than control writing on 1 of 2 measures at 4 and 12 months. The combination of WED and CST does not improve outcomes, perhaps because each intervention has unique effects at different time points. CST improves health status in RA and is recommended for patients, whereas WED has limited benefits and needs strengthening or better targeting to appropriate patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":20446266,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Ovarian abscess as a complication of assisted reproduction techniques: a case report.\nAMP makes true great strides these last decades. Logically some complications were noticed even due to ovarian puncture such as hemorrhage, perforation or infection. The aim of this report is to try, through a review of literature, to draw the attention of physicians to a rare entity, ovarian abscess after follicle aspiration for in-vitro fertilization, and to means of prevention. We report a 38-year-old woman who was plainting from lower abdominal pain located in the left iliac fossa one month after failed IVF trial. The pain was associated with fever and vomiting. The patient's past medical history involves 2 myomectomys (2003-2007). On admission, her temperature was 38.9 degrees C and her blood pressure was 90\/60 mm Hg. Physical examination found nondistended abdomen. Tenderness to deep palpation in the left lower quadrant, without peritoneal signs, was detected. No masses were palpated. Mild tenderness in the left cul-de-sac was found. A full blood count showed a white cell count of 17,500 cells\/mm3 with 84.5% polymorph nuclear cells, CRP 173 mg\/dl. Pelvic ultrasound shows a left latero uterine mass; right ovary and the uterus are unremarkable; there was no free abdominal fluid. The laparotomy was performed 24 hours later and a left ovarian abscess was found. The treatment was conservative. Antibiotics were associated during 15 days. The clinical evolution was satisfying. The ovarian puncture might be technically difficult, incomplete, and even impossible which exposes to a greater infection risk. An ultrasound evaluation of ovarian accessibility is necessary before starting an IVF attempt, especially in case of overweight or history of abdominal or pelvic surgery, endometriosis, tubal abnormalities or myomas. The treatment is based on surgery and antibiotics.","subset":"pubmed_abstract"} +{"meta":{"pmid":18473669,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2022-21":1,"2024-18":1}}},"text":"Distinct and combined roles of the MAP kinases of Cochliobolus heterostrophus in virulence and stress responses.\nPathogenicity mitogen-activated protein kinases (MAPKs), related to yeast FUS3\/KSS1, are essential for virulence in fungi, including Cochliobolus heterostrophus, a necrotrophic pathogen causing Southern corn leaf blight. We compared the phenotypes of mutants in three MAPK genes: HOG1, MPS1, and CHK1. The chk1 and mps1 mutants show autolytic appearance, light pigmentation, and dramatic reduction in virulence and conidiation. Similarity of mps1 and chk1 mutants is reflected by coregulation by these two MAPKs of several genes. Unlike chk1, mps1 mutants are female-fertile and form normal-looking appressoria. HOG1 mediates resistance to hyperosmotic and, to a lesser extent, oxidative stress, and is required for stress upregulation of glycerol-3-phosphate phosphatase, transaldolase, and a monosaccharide transporter. Hog1, but not Mps1 or Chk1, was rapidly phosphorylated in response to increased osmolarity. The hog1 mutants have smaller appressoria and cause decreased disease symptoms on maize leaves. Surprisingly, loss of MPS1 in a wild-type or hog1 background improved resistance to some stresses. All three MAPKs contribute to the regulation of central developmental functions under normal and stress conditions, and full virulence cannot be achieved without appropriate input from all three pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":19715118,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Initial study on fibers and coatings for the fabrication of bioscaffolds.\nScaffolds composed of a mixture of poly (L-lactic) acid (PLLA) and polyethylene glycol (PEG) biodegradable polymers were prepared by electrospinning. Three-dimensional scaffolds of highly porous non-woven fibers were produced for biomedical applications and coated with calcium phosphate for bone tissue engineering. A mixture (80\/20) of PLLA\/PEG was dissolved at 5.7%, 7%, 8% and 9% blend solution concentrations. The structure and morphology of the scaffolds were investigated by scanning electron microscopy. Average fiber diameters ranging from 600 nm to 800 nm were obtained as result of the change in viscosity. The low polymer concentration fibers were found to be flat with fused junctions between fibers. For high polymer concentrations fibers they were cylindrical with fibers overlaying each other. For samples deposited at 9% concentration, individual fibers contained pores on their surface with nanometric dimensions. In addition, thin films of calcium deficient hydroxyapatite were prepared by rf magnetron sputtering on silicon substrates heated to temperatures between 300-6000C. These results suggest that it is feasible to fabricate biopolymer scaffolds using methods combining electrospinning and sputtering techniques.","subset":"pubmed_abstract"} +{"meta":{"pmid":27530325,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Water Concentration Analysis by Raman Spectroscopy to Determine the Location of the Tumor Border in Oral Cancer Surgery.\nAdequate resection of oral cavity squamous cell carcinoma (OCSCC) means complete tumor removal with a clear margin of more than 5 mm. For OCSCC, 85% of the surgical resections appear inadequate. Raman spectroscopy is an objective and fast tool that can provide real-time information about the molecular composition of tissue and has the potential to provide an objective and fast intraoperative assessment of the entire resection surface. A previous study demonstrated that OCSCC can be discriminated from healthy surrounding tissue based on the higher water concentration in tumor. In this study, we investigated how the water concentration changes across the tumor border toward the healthy surrounding tissue on freshly excised specimens from the oral cavity. Experiments were performed on tissue sections from 20 patients undergoing surgery for OCSCC. A transition from a high to a lower water concentration, from tumor (76% \u00b1 8% of water) toward healthy surrounding tissue (54% \u00b1 24% of water), takes place over a distance of about 4 to 6 mm across the tumor border. This was accompanied by an increase of the heterogeneity of the water concentration in the surrounding healthy tissue. The water concentration distributions between the regions were significantly different (P < 0.0001). This new finding highlights the potential of Raman spectroscopy for objective intraoperative assessment of the resection margins. Cancer Res; 76(20); 5945-53. \u00a92016 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":28410086,"dup_signals":{"dup_doc_count":14}},"text":"Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study.\nTo determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs. A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists. We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants). Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":28645914,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.\nThe interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg\/kg\/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats.","subset":"pubmed_abstract"} +{"meta":{"pmid":11354611,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A test of processing efficiency theory in a team sport context.\nIn this study, we tested some key postulates of Eysenck and Calvo's processing efficiency theory in a team sport. The participants were 12 elite male volleyball players who were followed throughout the course of a competitive season. Self-report measures of pre-match and in-game cognitive anxiety and mental effort were collected in groups of players high and low in dispositional anxiety. Player performance was determined from the statistical analysis of match-play. Sets were classified according to the point spread separating the two teams into one of three levels of criticality. Game momentum was also analysed to determine its influence on in-game state anxiety. Significant differences in in-game cognitive anxiety were apparent between high and low trait anxiety groups. An interaction between anxiety grouping and momentum condition was also evident in cognitive anxiety. Differences in set criticality were reflected in significant elevations in mental effort, an effect more pronounced in dispositionally high anxious performers. Consistent with the predictions of processing efficiency theory, mental effort ratings were higher in high trait-anxious players in settings where their performance was equivalent to that of low trait-anxious performers. The usefulness of processing efficiency theory as an explanatory framework in sport anxiety research is discussed in the light of these findings.","subset":"pubmed_abstract"} +{"meta":{"pmid":24777536,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":14}}},"text":"A synthesis of methane emissions from 71 northern, temperate, and subtropical wetlands.\nWetlands are the largest natural source of atmospheric methane. Here, we assess controls on methane flux using a database of approximately 19 000 instantaneous measurements from 71 wetland sites located across subtropical, temperate, and northern high latitude regions. Our analyses confirm general controls on wetland methane emissions from soil temperature, water table, and vegetation, but also show that these relationships are modified depending on wetland type (bog, fen, or swamp), region (subarctic to temperate), and disturbance. Fen methane flux was more sensitive to vegetation and less sensitive to temperature than bog or swamp fluxes. The optimal water table for methane flux was consistently below the peat surface in bogs, close to the peat surface in poor fens, and above the peat surface in rich fens. However, the largest flux in bogs occurred when dry 30-day averaged antecedent conditions were followed by wet conditions, while in fens and swamps, the largest flux occurred when both 30-day averaged antecedent and current conditions were wet. Drained wetlands exhibited distinct characteristics, e.g. the absence of large flux following wet and warm conditions, suggesting that the same functional relationships between methane flux and environmental conditions cannot be used across pristine and disturbed wetlands. Together, our results suggest that water table and temperature are dominant controls on methane flux in pristine bogs and swamps, while other processes, such as vascular transport in pristine fens, have the potential to partially override the effect of these controls in other wetland types. Because wetland types vary in methane emissions and have distinct controls, these ecosystems need to be considered separately to yield reliable estimates of global wetland methane release.","subset":"pubmed_abstract"} +{"meta":{"pmid":31230452,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Sequence analysis and biological characterization of virulent Avian avulavirus 1 isolated from asymptomatic migratory fowl.\nContinuous monitoring and surveillance of avian avulaviruses (AAvVs) in water\/migratory fowl is imperative to ascertain the evolutionary dynamics of these viruses. Here, we report genomic and amino acid characteristics of two AAvVs strains isolated from asymptomatic waterfowl (Anas carolinensis). Sequence characteristics including the presence of virulent motif (112RRQKR\u2193F117) and biological assessment confirmed the virulent nature of study isolates. Phylogenetic analysis of complete fusion (F) and hemagglutinin-neuraminidase (HN), and hyper-variable region of F gene revealed clustering of both strains within genotype VII and sub-genotype VIIi. The inferred residue analysis of complete F and HN genes revealed a number of substitutions in functionally and structurally important motif\/s compared to reference strains of each genotype (I-XI). This study concludes an evolutionary nature of avian avulavaris 1 (AAvV-1), ascertaining continuous surveillance of migratory fowl to better elucidate their infection, epidemiology and subsequent impacts on commercial and backyard poultry. Keywords: virulent AAvV-1; migratory fowl; genetic characterization; evolutionary analysis; Pakistan.","subset":"pubmed_abstract"} +{"meta":{"pmid":11015147,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":8}}},"text":"Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team.\nTo prospectively examine differences in baseline characteristics and study outcomes between HIV-infected women and men during a clinical trial of nucleoside analogue therapy. ACTG 175 randomized HIV-infected patients with CD4+ counts between 200 and 500 cells\/mm3 to one of four nucleoside analogue regimens: zidovudine (ZDV), didanosine (ddI), ZDV + ddI, or ZDV + zalcitabine (ddC). Differences in time to first dose modification, voluntary withdrawal, development of toxicity and symptomatology, and AIDS progression were compared by gender. The study included 438 women and 2029 men. Baseline values of HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4+ count. Women reported reducing dosage and discontinue ddI-containing regimens more frequently than men did; adjustment for weight did not completely explain this difference. Women were at lower risk than men for progression to a study endpoint (19% of women versus 24% of men; p <.0001). Among those antiretroviral-naive study subjects receiving ZDV, men were four times more likely to progress to a study endpoint than women. Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral-naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":22031155,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":3}}},"text":"[Social representations on the diet of nursing mothers].\nThis is a qualitative study that sought to establish the significance attributed by women to adequate eating habits with respect to prohibited, permitted and breastmilk-enhancing products during breastfeeding. It was based on the Theory of Social Representations described by Moscovici (2003) and Minayo (2006). 58 mothers of children up to 2 years of age living in the city of Coimbra in Minas Gerais state participated in the survey. Comprehensive analysis of feeding revealed that the new mothers interviewed understood the need for a special diet during postpartum based on healthy, fortified and lactose-rich food, as well as the need for ingesting liquids. Breatfeeding mothers appreciated the need to avoid hot, creamy and fatty food. In this perspective, feeding during this physiological phase implies an understanding of cultural, social and historical aspects which dictate eating habits. This assists in understanding customs and beliefs in order to provide professional assistance geared to the group being assisted in its proper context.","subset":"pubmed_abstract"} +{"meta":{"pmid":18204806,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":13}}},"text":"Testing the SF-36 in Parkinson's disease. Implications for reporting rating scale data.\nRating scales are increasingly the primary outcome measures in clinical trials. However, clinically meaningful interpretation of such outcomes requires that the scales used satisfy basic requirements (scaling assumptions) within the data. These are rarely tested. The SF-36 is the most widely used patient-reported rating scale. Its scaling assumptions have been challenged in neurological disorders but remain untested in Parkinson's disease (PD). We therefore tested these by analyzing SF-36 data from 202 PD patients (54% men; mean age 70) to determine if it was legitimate to report scores for the eight SF-36 scales and its two summary measures of physical and mental health, and if those scores were reliable and valid. Results supported generation of the eight SF-36 scale scores and their reliabilities were generally good (> or = 0.74 in all but one instance). However, we found limitations that question the meaningfulness of four scales and other limitations that restrict the ability of four scales to detect change in clinical trials (floor\/ceiling effects, 19.6-46.2 %). The two SF-36 summary measures were not found to be valid indicators of physical and mental health. This study demonstrates important limitations of the SF-36 and provides the first evidence-based guidelines for its use in PD. The limitations of the SF-36 demonstrated here may explain some unexpected findings in previous studies. However, the main implication is a general one for the clinical research community regarding requirements for reporting rating scale endpoints. Specifically, investigators should routinely provide scale evaluations based on data from within major clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":10754503,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns.\nVasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel columns. It is proposed that the differential morphology of neurons with different locations as stated above parallels to some extent the divergence of input streaming into the corresponding layer-defined areas. As a possible consequence of this, VIP-IR neurons may be capable of adapting the excitability and metabolism of cortical compartments either in a spatially limited or more extensive way.","subset":"pubmed_abstract"} +{"meta":{"pmid":9046624,"dup_signals":{"dup_doc_count":40,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":4,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2018-17":1}}},"text":"Transverse dentofacial structure of young men who have undergone surgical correction of unilateral cleft lip and palate: a posteroanterior cephalometric study.\nThe transverse dentofacial structure of 34 young adult males with unilateral cleft lip and palate, studied by means of posteroanterior cephalograms, was compared to that of a normal sample of 102 young adult males. All cleft patients had been treated surgically and orthodontically in accordance with a standardized protocol. Orthognathic surgical treatment was carried out when growth had ended in a few subjects. In studying the posteroanterior cephalograms, eight lengths, 10 ratios, and three angular variables were used. Comparison of the cephalometric values of the subjects with cleft palate and the normal sample of young adult males indicated (1) the absence of any significant differences in angular variables describing the transverse dentoalveolar relationships in the maxillary and mandibular incisal regions as well as the mandibular position; (2) the absence of any significant differences in the ratios of the nasal, maxillary, and mandibular widths to the interorbital width; (3) the presence, in the cleft group of significantly decreased ratios of maxillary intermolar width to interorbital width, mandibular intermolar width to interorbital width, maxillary intermolar width to mandibular intermolar width, and maxillary intermolar width to maxillary width; (4) the presence, in the cleft group, of a significantly increased ratio of innerorbital width to interorbital width; and (5) significant correlations between the maxillary and mandibular molar widths in the cleft group.","subset":"pubmed_abstract"} +{"meta":{"pmid":19389456,"dup_signals":{"dup_doc_count":44,"dup_dump_count":37,"dup_details":{"curated_sources":2,"2020-40":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2021-17":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Decreased density of serotonin 2A receptors in the superior temporal gyrus in schizophrenia--a postmortem study.\nThe superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, using in situ quantitative autoradiography in postmortem tissue, we investigated the binding of the [3H]ketanserin to 5-HT(2A) receptors and [3H]mesulergine to 5-HT(2C) receptors in the left STG of 8 male schizophrenic patients compared to 8 control subjects. A strong [3H]ketanserin binding was observed in the STG, however there was a very weak [3H]mesulergine binding in the STG. A significant decrease in binding of [(3)H]ketanserin was clearly observed in schizophrenia patients in comparison with control subjects. There were no significant correlations between 5-HT(2A) binding density and age, postmortem intervals, or brain pH. These results suggest that the alterations of the 5-HT(2A) receptors contribute to the pathophysiology of the STG in schizophrenia. Furthermore, there is a clear tendency for a positive correlation between 5-HT(2A) and muscarinic M1 receptor bindings, and for negative correlations between 5-HT(2A) and GABA(A) receptor bindings and between muscarinic M1 and GABA(A) receptor bindings. This provides a possible mechanism of auditory hallucinations through interactions between 5-HT(2A), acetylcholine muscarinic and GABA transmissions in the STG in schizophrenia.","subset":"pubmed_abstract"} +{"meta":{"pmid":33413051,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":9}}},"text":"A comparison of COVID-19 epidemiological indicators in Sweden, Norway, Denmark, and Finland.\nAims: To compare the early impact of COVID-19 infections and mortality from February to July 2020 across the Nordic nations of Sweden, Norway, Denmark, and Finland through available public data sources and conduct a descriptive analysis of the potential factors that drove different epidemiological outcomes, with a focus on Sweden's response. Methods: COVID-19 cases, deaths, tests, case age distribution, and the difference between 2020 all-cause mortality and the average mortality of the previous 5 years were compared across nations. Patterns in cell phone mobility data, testing strategies, and seniors' care home deaths were also compared. Data for each nation were based on publicly available sources as of July 31, 2020. Results: Compared with its Nordic peers, Sweden had a higher incidence rate across all ages, a higher COVID-19-related death rate only partially explained by population demographics, a higher death rate in seniors' care, and higher all-cause mortality. Sweden had approximately half as much mobility change as its Nordic neighbours until April and followed similar rates as its neighbours from April to July. Denmark led its Nordic peers in testing rates, while Sweden had the highest cumulative test-positivity rate continuously from mid-March. Conclusions: COVID-19 pushed Sweden's health system to its capacity, exposed systemic weaknesses in the seniors' care system, and revealed challenges with implementing effective contact tracing and testing strategies while experiencing a high case burden. Looser government restrictions at the beginning of the outbreak are likely to have played a role in the impact of COVID-19 in Sweden. In an effort to improve epidemic control, Sweden has increased testing rates, implemented more restrictive prevention measures, and increased their intensive care unit bed capacity.","subset":"pubmed_abstract"} +{"meta":{"pmid":31378494,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Immunometabolic status and productive performance differences between periparturient Simmental and Holstein dairy cows in response to pegbovigrastim.\nIn the present study, we aimed to investigate the side effects of pegbovigrastim, injected approximately 7 d before parturition and on the day of calving, on a panel of plasma biomarkers to evaluate energy, inflammatory, oxidative, and liver function status. We also addressed treatment responses in different breeds during the transition period. Holstein and Simmental cows were randomly assigned into 2 groups based on expected calving date and according to parity: the treated group (PEG; 14 Holstein and 12 Simmental cows) received pegylated recombinant bovine granulocyte colony stimulating factor (pegbovigrastim, Imrestor; Elanco Animal Health, Greenfield, IN), and the control group (CTR; 14 Holstein and 14 Simmental cows) received saline solution. The PEG or CTR treatments were administered via subcutaneous injection in the scapular region at approximately 7 d (mean 7.80 \u00b1 5.50 d) before expected parturition and within 24 h after calving. Blood samples were collected at -21, -7 (before injection), 1, 3, and 28 d relative to calving. Milk production was recorded at 7, 15, 21, 30, and 42 d. A mixed model with repeated measures was fitted to the normalized data using Proc MIXED of SAS (SAS Institute Inc., Cary, NC). Simmental PEG cows showed higher plasma protein concentrations at 1 and 3 d after calving compared with Simmental CTR and Holstein PEG cows, whereas no differences were detected between Holstein PEG and CTR cows. Albumin was greater at 1 d in Simmental PEG compared with Simmental CTR cows. In contrast, \u03b3-glutamyl transferase was higher overall (across breed) in PEG than in CTR. The PEG group had higher values throughout the postcalving period compared with CTR. Cows treated with pegbovigrastim had also higher alkaline phosphatase (ALP) activity at 1 and 3 d after calving. The Holstein PEG group had higher ALP activity at 3 d compared with the Holstein CTR and Simmental PEG groups, and higher ALP at 1 d compared with the Simmental CTR group. The PEG group had higher levels of IL-6 at 3 and 28 d but higher IL-1\u03b2 only at 28 d after calving compared with the CTR group. Overall, Holstein cows were characterized by a greater response in the production of inflammation biomarkers (cytokines, haptoglobin, and ceruloplasmin). In addition, PEG cows had higher values of zinc at 1 and 3 d after calving compared with CTR cows. The response observed in plasma biomarkers for energy metabolism and liver functionality after pegbovigrastim treatment in Simmental and Holstein cows was not different from that in control cows. However, our data shed light on the different metabolic adaptations during the transition period between Simmental and Holstein cows, characterized by different energy, inflammatory, and oxidative pattern responses. For the first time, we have highlighted the effect of pegbovigrastim in maintaining stable cytokine levels during the first month after parturition, reflecting greater regulation of neutrophil recruitment, trafficking, and maturation during the inflammatory response. These results provide evidence of the immunomodulatory action of pegbovigrastim around parturition, when dairy cows are highly immunosuppressed. At the same time, these data demonstrate that increasing release of cytokines after parturition is not linked to exacerbation of a systemic inflammation evaluated based on haptoglobin and ceruloplasmin levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":16549011,"dup_signals":{"dup_doc_count":15}},"text":"Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host.\nThe ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV\/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":18065730,"dup_signals":{"dup_doc_count":18,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2024-10":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2024-26":1,"unknown":8}}},"text":"Panel of serum biomarkers for the diagnosis of lung cancer.\nCurrently, a blood test for lung cancer does not exist. Serum biomarkers that could aid clinicians in making case management decisions would be enormously valuable. We used two proteomic platforms and a literature search to select candidate serum markers for the diagnosis of lung cancer. We initially assayed six serum proteins, four discovered by proteomics and two previously known to be cancer associated, on a training set of sera from 100 patients (50 with a new diagnosis of lung cancer and 50 age- and sex-matched controls). Classification and Regression Tree (CART) analysis selected a panel of four markers that most efficiently predicted which patients had lung cancer. An independent, blinded validation set of sera from 97 patients (49 lung cancer patients and 48 matched controls) determined the accuracy of the four markers to predict which patients had lung cancer. Four serum proteins-carcinoembryonic antigen, retinol binding protein, alpha1-antitrypsin, and squamous cell carcinoma antigen-were collectively found to correctly classify the majority of lung cancer and control patients in the training set (sensitivity, 89.3%; specificity, 84.7%). These markers also accurately classified patients in the independent validation set (sensitivity, 77.8%; specificity, 75.4%). Remarkably, 90% of patients who fell into any one of three groupings in the CART analysis had lung cancer. This panel of four serum proteins is valuable in suggesting the diagnosis of lung cancer. These data may be useful for treating patients with an indeterminate pulmonary lesion, and potentially in predicting individuals at high risk for lung cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":9006312,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":2,"unknown":21}}},"text":"Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children.\nThis study investigated whether a child's first infection with Cryptosporidium parvum had an acute effect on weight gain. Specifically, the authors compared monthly rates of weight gain between C. parvum-infected and noninfected children. Over a 2-year period (1989-1991), a cohort of Peruvian children aged 0-3 months at recruitment were followed twice weekly for assessment of daily diarrheal status, weekly for C. parvum stool examinations, and monthly for anthropometric measurements. Data on 207 children permitted the authors to examine the effect of C. parvum infection on weight gain. During the 2-year study period, 45% (94\/207) of the children became infected with C. parvum for the first time. Weight gain intervals in 57 of the 94 infected children met criteria for analysis. Of these, 63 percent (36\/57) were asymptomatic (i.e., had no diarrhea). On average, children with symptomatic cryptosporidiosis gained (i.e., grew) 342 g less (95% confidence interval 167-517) during the first month of infection than did children without diarrhea who were not yet infected. The effect of asymptomatic cryptosporidiosis was less severe: On average, children with asymptomatic infection gained 162 g less (95% confidence interval 27-297) during the first month of infection than did children without diarrhea who were not yet infected. Symptomatic cryptosporidiosis retarded weight gain more than did asymptomatic cryptosporidiosis, but the latter was twice as common. Since asymptomatic cryptosporidiosis is more prevalent, it may have more of an overall adverse effect on child growth in the community than symptomatic cryptosporidiosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":19940574,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":7}}},"text":"Improving the provision of language services at an academic medical center: ensuring high-quality health communication for limited-English-proficient patients.\nTo evaluate and improve the provision of language services at an academic medicine center caring for a diverse population including many limited-English-proficient (LEP) patients. The authors performed a prospective observational study between November 2006 and December 2008 evaluating the provision of language services at the University of Michigan Health System. The primary performance measures were (1) screening patients for their preferred language for health care, (2) assessing the proportion of LEP patients receiving language services from a qualified language services provider, and (3) assessing whether there were any disparities in diabetes care for LEP patients compared with English-speaking patients. The proportion of patients screened for preferred language increased from 59% to 96% with targeted inventions, such as training staff to capture preferred language for health care and correcting prior inaccurate primary language data entry. The proportion of LEP outpatients with a qualified language services provider increased from 19% to 83% through the use of staff and contract interpreters, over-the-phone interpreting and bilingual providers. There were no systematic differences in diabetes quality performance measures between LEP and English-proficient patients. Academic medical centers should measure their provision of language services and compare quality and safety data (e.g., performance measures and adverse events) between LEP and English-speaking patients to identify disparities in care. Leadership support and ongoing training are needed to ensure language-specific services are embedded into clinical care to meet the needs of our diverse patient populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":14576049,"dup_signals":{"dup_doc_count":23,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-34":1,"2020-29":1,"2023-50":1,"2024-26":2,"2024-22":1}}},"text":"DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation.\nDendritic cells (DCs) facilitate HIV-1 spread in the host by capturing virions and transferring them to permissive lymphocytes in lymphoid organs. Lectins such as DC-specific ICAM-grabbing non-integrin (DC-SIGN) are involved in HIV-1 uptake by DCs, through high-affinity binding to viral envelope glycoproteins. We examined the role of DC-SIGN on the fate of incoming virions and on major histocompatibility complex class I (MHC-I)-restricted HIV-1 antigen presentation. We show that DC-SIGN expression in B-cell lines dramatically enhances viral internalization. In these cells, and also in primary DCs, most of the captured virions are rapidly degraded, likely in a lysosomal compartment. In addition, a fraction of incoming viral material is processed by the proteasome, leading to activation of anti-HIV-specific cytotoxic T lymphocytes (CTLs) by DC-SIGN-expressing cells. In DCs, DC-SIGN is not the only receptor involved, and redundant pathways of virus capture leading to antigen presentation likely coexist. Altogether, our results highlight new aspects of DC-SIGN interactions with HIV-1. The lectin does not significantly protect captured virions against degradation and promotes MHC-I exogenous presentation of HIV-1 antigens.","subset":"pubmed_abstract"} +{"meta":{"pmid":19735809,"dup_signals":{"dup_doc_count":37,"dup_dump_count":31,"dup_details":{"curated_sources":2,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2017-43":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"A prospective comparative evaluation of persistent respiratory morbidity in esophageal atresia and congenital diaphragmatic hernia survivors.\nThe aim of the study was to compare long-term respiratory morbidity in children after repair of esophageal atresia (EA) or congenital diaphragmatic hernia (CDH). Children were seen at 6, 12, and 24 months and 5 years within a prospective longitudinal follow-up program in a tertiary children's hospital. Respiratory morbidity and physical condition were evaluated at all moments. At age 5 years, pulmonary function and maximal exercise performance were tested. In 3 of 23 atresia patients and 10 of 20 hernia patients, bronchopulmonary dysplasia was developed. Seventeen atresia and 11 hernia patients had recurrent respiratory tract infections mainly in the first years of life. At age 5, 25% of EA and CDH patients measured showed reduced forced expiratory volume in 1 second (z-score < -2). Both atresia and hernia patients showed impaired growth, with catch-up growth at 5 years in patients with EA but not in those with hernia. Maximal exercise performance was significantly below normal for both groups. Esophageal atresia and CDH are associated with equal risk of long-term respiratory morbidity, growth impairment, and disturbed maximal exercise performance. Prospective follow-up of EA patients aimed at identifying respiratory problems other than tracheomalacia should be an integral part of interdisciplinary follow-up programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":28670841,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-23":1,"2024-10":1,"2024-18":1}}},"text":"The sensitivity of 38 heart rate variability measures to the addition of artifact in human and artificial 24-hr cardiac recordings.\nArtifact is common in cardiac RR interval data derived from 24-hr recordings and has a significant impact on heart rate variability (HRV) measures. However, the relative impact of progressively added artifact on a large group of commonly used HRV measures has not been assessed. This study compared the relative sensitivity of 38 commonly used HRV measures to artifact to determine which measures show the most change with increasing increments of artifact. A secondary aim was to ascertain whether short-term and long-term HRV measures, as groups, share similarities in their sensitivity to artifact. Up to 10% of artifact was added to 20 artificial RR (ARR) files and 20 human cardiac recordings, which had been assessed for artifact by a cardiac technician. The added artifact simulated deletion of RR intervals and insertion of individual short RR intervals. Thirty-eight HRV measures were calculated for each file. Regression analysis was used to rank the HRV measures according to their sensitivity to artifact as determined by the magnitude of slope. RMSSD, SDANN, SDNN, RR triangular index and TINN, normalized power and relative power linear measures, and most nonlinear methods examined are most robust to artifact. Short-term time domain HRV measures are more sensitive to added artifact than long-term measures. Absolute power frequency domain measures across all frequency bands are more sensitive than normalized and relative frequency domain measures. Most nonlinear HRV measures assessed were relatively robust to added artifact, with Poincare plot SD1 being most sensitive.","subset":"pubmed_abstract"} +{"meta":{"pmid":22363008,"dup_signals":{"dup_doc_count":22,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2017-39":2,"2017-30":1,"2017-22":2,"2017-17":1,"2017-09":1,"2017-04":2,"2016-40":2,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":2,"2017-13":1}}},"text":"Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a polyglutamine-repeat protein.\nDeath is a vital developmental cell fate. In Caenorhabditis elegans, programmed death of the linker cell, which leads gonadal elongation, proceeds independently of caspases and apoptotic effectors. To identify genes promoting linker-cell death, we performed a genome-wide RNA interference screen. We show that linker-cell death requires the gene pqn-41, encoding an endogenous polyglutamine-repeat protein. pqn-41 functions cell-autonomously and is expressed at the onset of linker-cell death. pqn-41 expression is controlled by the mitogen-activated protein kinase kinase SEK-1, which functions in parallel to the zinc-finger protein LIN-29 to promote cellular demise. Linker-cell death is morphologically similar to cell death associated with normal vertebrate development and polyglutamine-induced neurodegeneration. Our results may therefore provide molecular inroads to understanding nonapoptotic cell death in metazoan development and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":8531111,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":17}}},"text":"The \"calcium antagonist\" TMB-8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester] is a potent, non-competitive, functional antagonist at diverse nicotinic acetylcholine receptor subtypes.\n[3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester] (TMB-8) has seen wide use as an \"intracellular Ca2+ antagonist.\" However, this study shows that TMB-8 acts as a noncompetitive, functional antagonist at diverse nicotinic acetylcholine receptor (nAChR) subtypes with potencies that exceed those for other reported effects of TMB-8, including inhibition of intracellular Ca2+ mobilization. TMB-8 is a potent inhibitor (IC50 approximately 400 nM) of agonist-stimulated ion flux mediated by functional human muscle nAChR or ganglionic alpha 3 beta 4-nAChR subtypes expressed by TE671\/RD or SH-SY5Y cells. TMB-8 is also a potent inhibitor (IC50 approximately 500 nM) of a functional, central nervous system nAChR subtype that mediates nicotinic agonist-stimulated [3H]dopamine release from rat brain synaptosomes. TMB-8 is much less potent (IC50 approximately 30-200 microM) as an inhibitor of high-affinity 3H-labeled acetylcholine or 125I-labeled alpha-bungarotoxin binding to human muscle nAChR, ganglionic alpha 3 beta 4-nAChR, or ganglionic alpha 7-nAChR subtypes. Moreover, functional inhibition by TMB-8 of muscle-type nAChR is due to a reduction in agonist efficacy, but not potency, and is proportionately stronger with increasing agonist concentration, thereby suggesting that TMB-8 acts as a noncompetitive inhibitor. Similar effects are observed for local anesthetics such as tetracaine and procaine (functional IC50 values of approximately 5 and approximately 50 microM, respectively), although TMB-8 is the most potent of these agents. Studies with TMB-8 or BAPTA [1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid] analogues indicate that the amino group of TMB-8 is essential and that Ca2+ chelation is not required for inhibition of nAChR function.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":10896919,"dup_signals":{"dup_doc_count":41,"dup_dump_count":22,"dup_details":{"curated_sources":3,"2023-50":7,"2023-40":3,"2023-23":1,"2023-14":1,"2023-06":2,"2022-49":2,"2022-40":1,"2022-27":4,"2022-21":1,"2022-05":1,"2021-43":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2024-22":1,"2024-18":2,"2024-30":1}}},"text":"The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea.\nGermline mutations in E-cadherin (CDH1) have been reported in families with early onset, diffuse gastric cancer. More recently, mutations in CDH1 have been described in colorectal cancer cell lines. We have investigated if germline mutations in CDH1 occur among different groups of Korean gastric and colorectal cancer patients, with and without a positive family history. We studied 131 patients and 168 normal controls (88 Korean and 80 non-Korean). Patients were divided into five groups: group I, 20 gastric cancer patients with a family history; group II, 26 colorectal cancer patients with a family history of gastric cancer (those from familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) kindred were excluded); group III, 16 HNPCC patients without identified germline mutations in hMLH1 and hMSH2; group IV, 35 gastric cancer patients without a family history; and group V, 34 colorectal cancer patients without a family history. Polymerase chain reaction, single strand conformational polymorphism analysis, direct sequencing, and genotyping for identified variants were performed. Several germline changes in CDH1 were found. In addition to previously described polymorphisms, we found three novel changes, two of which were missense changes (T340A and L599V). T340A was present in one patient in group III and one in group V. L599V was present in one patient in group II, in two in group III, and in one in group IV. T340A was not found in normal controls while L599V was present in two of 88 Korean controls. Patients with these variants may appear to have a tendency to early onset cancer with a positive family history, although differences in frequencies did not reach statistical significance. Genotyping results suggest that these variants might have a common origin, particularly T340A. We have described two new missense germline variants in CDH1 in various groups of Korean gastrointestinal cancer patients. Further work is required to assess if these variants increase the risk of gastrointestinal cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":24610668,"dup_signals":{"dup_doc_count":13}},"text":"Comparative Study of Teicoplanin vs Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteraemia.\nForty patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia were randomised to receive either teicoplanin or vancomycin therapy to compare the clinical efficacy and safety of these glycopeptides. Treatment was successful in 17 (85%) of 20 patients who were randomised to the teicoplanin group, with 6 cures and 11 improvements, and in 15 (75%) of 20 patients randomised to the vancomycin group, with 8 cures and 7 improvements (p = 0.69). Microbiologically, all MRSA pathogens isolated were susceptible to both glycopeptides by the disc diffusion test. The mean zone of inhibition for teicoplanin was 18 \u00b1 2mm (range 16 to 20mm) and 20 \u00b1 2mm (range 16 to 24mm) for vancomycin. The minimum inhibitory concentration required to inhibit the growth of 90% of organisms in culture (MIC90) for all MRSA isolates was 2.0 mg\/L (range 0.5 to 4 mg\/L) for teicoplanin and 2.0 mg\/L (range 0.5 to 2 mg\/L) for vancomycin. The microbiological eradication rate was 85% (17 of 20 isolates) for teicoplanin and 75% (15 of 20 isolates) for vancomycin. None of the failures were due to the emergence of resistant pathogens. Adverse reactions occurred in 19% of patients treated with teicoplanin and 60% of patients treated with vancomycin. There was no significant difference in the occurrence of skin rash (p = 0.60) or in elevation of aminotransferase (p = 0.18). However, nephrotoxicity was significantly greater in the vancomycin group than in the teicoplanin group (50 vs 9.5%, p < 0.05).In conclusion, the results of this study demonstrate that teicoplanin appears to be a valuable alternative to vancomycin because it is as efficacious as vancomycin, has fewer adverse reactions, and is conveniently administered.","subset":"pubmed_abstract"} +{"meta":{"pmid":27527887,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"[Mania induced by antibiotic therapy].\nWe report two cases of adults who developed mania after taking the antibiotic clarithromycin. Clarithromycin is a frequently used antibiotic, but it can lead to a rare but significant psychiatric complication in the form of a manic episode. Mania is commonly associated with bipolar disorder, but the causes can be pharmacological, metabolic or neurologic, particularly when it occurs in patients who themselves or whose families have no past history of psychiatric illness. New-onset mania calls for detailed clinical and laboratory testing and neuro-imaging so that somatic causes can be ruled out. It is important that the currently used medication is included in the differential diagnosis of mania. The first step in treatment is to discontinue the antibiotic therapy. The pharmacological treatment for mania caused by antibiotic therapy is largely the same as for mania in bipolar disorder; this means starting with anti-manic and anti-psychotic medication and providing a structured and calming environment. Most cases of pharmacologically induced mania are resolved if the aetiology is determined and treated. Mania that has pharmacological causes generally does not require prophylactic mood-stabilising treatment. Nevertheless, a psychiatric follow-up is advisable. If these steps are taken, the prognosis is favourable.","subset":"pubmed_abstract"} +{"meta":{"pmid":35253911,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Physical environmental designs in residential care to improve quality of life of older people.\nThe demand for residential aged care is increasing due to the ageing population. Optimising the design or adapting the physical environment of residential aged care facilities has the potential to influence quality of life, mood and function. To assess the effects of changes to the physical environment, which include alternative models of residential aged care such as a 'home-like' model of care (where residents live in small living units) on quality of life, behaviour, mood and depression and function in older people living in residential aged care. CENTRAL, MEDLINE, Embase, six other databases and two trial registries were searched on 11 February 2021. Reference lists and grey literature sources were also searched. Non-randomised trials, repeated measures or interrupted time series studies and controlled before-after studies with a comparison group were included. Interventions which had modified the physical design of a care home or built a care home with an alternative model of residential aged care (including design alterations) in order to enhance the environment to promote independence and well-being were included. Studies which examined quality of life or outcomes related to quality of life were included. Two reviewers independently assessed the abstracts identified in the search and the full texts of all retrieved studies. Two reviewers independently extracted data, assessed the risk of bias in each included study and evaluated the certainty of evidence according to GRADE criteria. Where possible, data were represented in forest plots and pooled. Twenty studies were included with 77,265 participants, although one large study included the majority of participants (n = 74,449). The main comparison was home-like models of care incorporating changes to the scale of the building which limit the capacity of the living units to smaller numbers of residents and encourage the participation of residents with domestic activities and a person-centred care approach, compared to traditional designs which may include larger-scale buildings with a larger number of residents, hospital-like features such as nurses' stations, traditional hierarchical organisational structures and design which prioritises safety. Six controlled before-after studies compared the home-like model and the traditional environment (75,074 participants), but one controlled before-after study included 74,449 of the participants (estimated on weighting). It is uncertain whether home-like models improve health-related quality of life, behaviour, mood and depression, function or serious adverse effects compared to traditional designs because the certainty of the evidence is very low. The certainty of the evidence was downgraded from low-certainty to very low-certainty for all outcomes due to very serious concerns due to risk of bias, and also serious concerns due to imprecision for outcomes with more than 400 participants. One controlled before-after study examined the effect of home-like models on quality of life. The author stated \"No statistically significant differences were observed between the intervention and control groups.\" Three studies reported on global behaviour (N = 257). One study found little or no difference in global behaviour change at six months using the Neuropsychiatric Inventory where lower scores indicate fewer behavioural symptoms (mean difference (MD) -0.04 (95% confidence interval (CI) -0.13 to 0.04, n = 164)), and two additional studies (N = 93) examined global behaviour, but these were unsuitable for determining a summary effect estimate. Two controlled before-after studies examined the effect of home-like models of care compared to traditional design on depression. After 18 months, one study (n = 242) reported an increase in the rate of depressive symptoms (rate ratio 1.15 (95% CI 1.02 to 1.29)), but the effect of home-like models of care on the probability of no depressive symptoms was uncertain (odds ratio 0.36 (95% CI 0.12 to 1.07)). One study (n = 164) reported little or no difference in depressive symptoms at six months using the Revised Memory and Behaviour Problems Checklist where lower scores indicate fewer depressive symptoms (MD 0.01 (95% CI -0.12 to 0.14)). Four controlled before-after studies examined function. One study (n = 242) reported little or no difference in function over 18 months using the Activities of Daily Living long-form scale where lower scores indicate better function (MD -0.09 (95% CI -0.46 to 0.28)), and one study (n = 164) reported better function scores at six months using the Interview for the Deterioration of Daily Living activities in Dementia where lower scores indicate better function (MD -4.37 (95% CI -7.06 to -1.69)). Two additional studies measured function but could not be included in the quantitative analysis. One study examined serious adverse effects (physical restraints), and reported a slight reduction in the important outcome of physical restraint use in a home-like model of care compared to a traditional design (MD between the home-like model of care and traditional design -0.3% (95% CI -0.5% to -0.1%), estimate weighted n = 74,449 participants at enrolment). The remaining studies examined smaller design interventions including refurbishment without changes to the scale of the building, special care units for people with dementia, group living corridors compared to a non-corridor design, lighting interventions, dining area redesign and a garden vignette. There is currently insufficient evidence on which to draw conclusions about the impact of physical environment design changes for older people living in residential aged care. Outcomes directly associated with the design of the built environment in a supported setting are difficult to isolate from other influences such as health changes of the residents, changes to care practices over time or different staff providing care across shifts. Cluster-randomised trials may be feasible for studies of refurbishment or specific design components within residential aged care. Studies which use a non-randomised design or cluster-randomised trials should consider approaches to reduce risk of bias to improve the certainty of evidence.","subset":"pubmed_abstract"} +{"meta":{"pmid":9474828,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Thunderstorm-associated asthma: the effect on GP consultations.\nEvidence shows that asthma attacks can be brought on by adverse weather conditions such as those experienced during a thunderstorm; a prime example of such an occasion being a thunderstorm episode on 24 June 1994, which resulted in a well-documented increase in medical attendances made by those suffering with asthma and respiratory disorders. However, most of these studies have concerned admissions to accident and emergency departments. The aim of this paper was to ascertain whether a similar increase in consultations was observed in the primary care setting.","subset":"pubmed_abstract"} +{"meta":{"pmid":11368974,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"Involvement of enhanced sensitivity of N-methyl-D-aspartate receptors in vulnerability of developing cortical neurons to methylmercury neurotoxicity.\nThe developing cortical neurons have been well documented to be extremely vulnerable to the toxic effect of methylmercury (MeHg). In the present study, a possible involvement of N-methyl-D-aspartate (NMDA) receptors in MeHg neurotoxicity was examined because the sensitivity of cortical neurons to NMDA neurotoxicity has a similar developmental profile. Rats on postnatal day 2 (P2), P16, and P60 were orally administered MeHg (10 mg\/kg) for 7 consecutive days. The most severe neuronal damage was observed in the occipital cortex of P16 rats. When MK-801 (0.1 mg\/kg), a non-competitive antagonist of NMDA, was administered intraperitoneally with MeHg, MeHg-induced neurodegeneration was markedly ameliorated. Furthermore, there was a marked accumulation of nitrotyrosine, a reaction product of peroxynitrite and L-tyrosine, after chronic treatment of MeHg in the occipital cortex of P16 rats. The accumulation of nitrotyrosine was also significantly suppressed by MK-801. In the present electrophysiological study, the amplitude of synaptic responses mediated by NMDA receptors recorded in cortical neurons of P16 rats was significantly larger than those from P2 and P60 rats. These observations strongly suggest that a generation of peroxynitrite through activation of NMDA receptors is a major causal factor for MeHg neurotoxicity in the developing cortical neurons. Furthermore, enhanced sensitivity of NMDA receptors may make the cortical neurons of P16 rats most susceptible to MeHg neurotoxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":2499737,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Stability of multiple antigen receptor gene rearrangements and immunophenotype in Hodgkin's disease-derived cell line L428 and variant subline L428KSA.\nThe Hodgkin's disease (HD) derived cell line L428 and a phorbol ester-selected subline L428KSA, which have been independently passaged in tissue culture for several years, were studied for possible antigen receptor gene and immunophenotypic differences. Multiple but identical alterations of these genes were found, including: the deletion of one and rearrangement of the other immunoglobulin (Ig) heavy chain allele; the rearrangement of one kappa and one lambda light chain allele; and the rearrangement of one T cell receptor (TCR) beta allele. Restriction mapping of the Ig heavy chain locus indicated that rearrangement of the retained allele produced a JH-C gamma 4 fusion product by an isotype switch mechanism. The 14q+ chromosome [t(14q32;?)] present in both cell cultures derived either from translocation 5' (telomeric) to the rearranged JH allele or 3' (centromeric) to the deleted Ig heavy chain allele and did not involve detectable rearrangement of the c-myc, bcl 1, or bcl 2 oncogenes. No differences in the immunophenotype were found between the L428 and L428KSA cells: both expressed leukocyte activation antigens and some determinants associated with myelomonocytic cells but no lymphoid markers. It is postulated that these phenotypic characteristics derived from secondary genetic events\/differentiative reprogramming which produced extinction of primary lymphoid characters, including terminal deoxynucleotidyl transferase (TdT) essential to generation of the Ig and TCR gene rearrangements, and expression of an incomplete set of myelomonocytic markers.","subset":"pubmed_abstract"} +{"meta":{"pmid":17047686,"dup_signals":{"dup_doc_count":28,"dup_dump_count":23,"dup_details":{"curated_sources":1,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-50":2,"2020-29":2,"2020-16":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-39":1,"2019-35":1,"2018-39":1,"2018-34":1,"2018-13":1,"2018-05":1,"2017-30":1,"2017-17":1,"2023-40":1}}},"text":"Bridging the regeneration gap: genetic insights from diverse animal models.\nSignificant progress has recently been made in our understanding of animal regenerative biology, spurred on by the use of a wider range of model organisms and an increasing ability to use genetic tools in traditional models of regeneration. This progress has begun to delineate differences and similarities in the regenerative capabilities and mechanisms among diverse animal species, and to address some of the key questions about the molecular and cell biology of regeneration. Our expanding knowledge in these areas not only provides insights into animal biology in general, but also has important implications for regenerative medicine and stem-cell biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":23010075,"dup_signals":{"dup_doc_count":22,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":3,"2024-18":1,"unknown":14}}},"text":"Basal but not luminal mammary epithelial cells require PI3K\/mTOR signaling for Ras-driven overgrowth.\nThe mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V) together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor-initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia.","subset":"pubmed_abstract"} +{"meta":{"pmid":24765338,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"US and MDCT findings in a caudal blind ending bifid ureter with calculi.\nHerein we present a rare ureteric duplication anomaly; blind ending bifid ureter with calculi which is asymptomatic unless complicated by infection, reflux, calculi or malignancy. The diagnosis is often missed at intravenous urography (IVU) and US because the ipsilateral ureter and kidney are grossly normal. In this case the diagnosis was established with ultrasound (US) and mainly with multidetector computerized tomography (MDCT) imaging using multiplanar reformats and 3-D reconstructions which were unique to this case. MDCT scans not only revealed the exact diagnosis and anatomic relationships but also ruled out other pathologies included in the differential diagnosis as well, such as ureter and bladder diverticula.","subset":"pubmed_abstract"} +{"meta":{"pmid":19794357,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Psychotic disorders and comorbidity: somatic illness vs. side effect.\nSchizophrenia often co-occurs with chronic medical illnesses. Beside comorbid somatic illness, somatic symptoms appear as a result of side effects of antipsychotics during treatment of psychotic disorders, which may lead to certain diagnostic problems in deciding regarding the origin of such symptoms (somatic illness vs. side effects). The aim of this article is to review literature regarding comorbidity of psychotic disorders and somatic disorders and to point at possible diagnostic problems in differentiating comorbid somatic illness from side effects of antipsychotics. Literature research included structured searches of Medline and other publications on the subject of comorbidity of psychotic disorders and somatic disorders and possible diagnostic problems in differentiating comorbid somatic illnesses from side effects of antipsychotics. Co-occurrence of schizophrenia and somatic illnesses is frequent. Genetic factors, sedentary life style, poor diet, risk behaviors and smoking are some important factors that contribute to such comorbidity. Side effects of antipsychotics may cause diagnostic problems in deciding regarding the origin of such symptoms (somatic illness vs. side effects) during treatment of psychotic disorders. Bearing in mind frequent comorbidity between of psychotic and somatic disorders, early recognition of such comorbidity is important, as well as the selection of antipsychotics. It is important to recognize psychotic symptoms in patients with somatic illnesses, as well as somatic illness in patients primarily treated because of psychotic disorder.","subset":"pubmed_abstract"} +{"meta":{"pmid":28402800,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Assessment of dysglycemia risk in the Kitikmeot region of Nunavut: using the CANRISK tool.\nThe Public Health Agency of Canada adapted a Finnish diabetes screening tool (FINDRISC) to create a tool (CANRISK) tailored to Canada's multi-ethnic population. CANRISK was developed using data collected in seven Canadian provinces. In an effort to extend the applicability of CANRISK to northern territorial populations, we completed a study with the mainly Inuit population in the Kitikmeot region of Nunavut. We obtained CANRISK questionnaires, physical measures and blood samples from participants in five Nunavut communities in Kitikmeot. We used logistic regression to test model fit using the original CANRISK risk factors for dysglycemia (prediabetes and diabetes). Dysglycemia was assessed using fasting plasma glucose (FPG) alone and\/or oral glucose tolerance test. We generated participants' CANRISK scores to test the functioning of this tool in the Inuit population. A total of 303 individuals participated in the study. Half were aged less than 45 years, two-thirds were female and 84% were Inuit. A total of 18% had prediabetes, and an additional 4% had undiagnosed diabetes. The odds of having dysglycemia rose exponentially with age, while the relationship with BMI was U-shaped. Compared with lab test results, using a cut-off point of 32 the CANRISK tool achieved a sensitivity of 61%, a specificity of 66%, a positive predictive value of 34% and an accuracy rate of 65%. The CANRISK tool achieved a similar accuracy in detecting dysglycemia in this mainly Inuit population as it did in a multi-ethnic sample of Canadians. We found the CANRISK tool to be adaptable to the Kitikmeot region, and more generally to Nunavut.","subset":"pubmed_abstract"} +{"meta":{"pmid":29418076,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Viral-based nanomaterials for plasmonic and photonic materials and devices.\nOver the last decade, viruses have established themselves as a powerful tool in nanotechnology. Their proteinaceous capsids benefit from biocompatibility, chemical addressability, and a variety of sizes and geometries, while their ability to encapsulate, scaffold, and self-assemble enables their use for a wide array of purposes. Moreover, the scaling up of viral-based nanotechnologies is facilitated by high capsid production yield and speed, which is particularly advantageous when compared with slower and costlier lithographic techniques. These features enable the bottom-up fabrication of photonic and plasmonic materials, which relies on the precise arrangement of photoactive material at the nanoscale to control phenomena such as electromagnetic wave propagation and energy transfer. The interdisciplinary approach required for the fabrication of such materials combines techniques from the life sciences and device engineering, thus promoting innovative research. Materials with applications spanning the fields of sensing (biological, chemical, and physical sensors), nanomedicine (cellular imaging, drug delivery, phototherapy), energy transfer and conversion (solar cells, light harvesting, photocatalysis), metamaterials (negative refraction, artificial magnetism, near-field amplification), and nanoparticle synthesis are considered with exclusive emphasis on viral capsids and protein cages. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.","subset":"pubmed_abstract"} +{"meta":{"pmid":19965474,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":4,"2024-18":1,"unknown":6}}},"text":"Global signatures and dynamical origins of the Little Ice Age and Medieval Climate Anomaly.\nGlobal temperatures are known to have varied over the past 1500 years, but the spatial patterns have remained poorly defined. We used a global climate proxy network to reconstruct surface temperature patterns over this interval. The Medieval period is found to display warmth that matches or exceeds that of the past decade in some regions, but which falls well below recent levels globally. This period is marked by a tendency for La Ni\u00f1a-like conditions in the tropical Pacific. The coldest temperatures of the Little Ice Age are observed over the interval 1400 to 1700 C.E., with greatest cooling over the extratropical Northern Hemisphere continents. The patterns of temperature change imply dynamical responses of climate to natural radiative forcing changes involving El Ni\u00f1o and the North Atlantic Oscillation-Arctic Oscillation.","subset":"pubmed_abstract"} +{"meta":{"pmid":7909561,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Dynorphin A-induced rat spinal cord injury: evidence for excitatory amino acid involvement in a pharmacological model of ischemic spinal cord injury.\nDynorphin A reduced lumbosacral blood flow, elevated cerebrospinal fluid lactic acid concentrations and caused flaccid hindlimb paralysis and striking neuropathological changes after its injection into the spinal subarachnoid space in rats. Coadministration of the vasodilator hydralazine substantially eliminated the paralytic, anaerobic metabolic and neuropathological responses to dynorphin A. In contrast, in concentrations up to 1 mM, dynorphin A did not alter the viability of cultured rat spinal cord neurons. Thus, it appears that this peptide lacks direct neurotoxic effects and that neuronal injuries in vivo result primarily from ischemia associated with dynorphin A-induced blood flow reductions. NMDA receptor antagonists significantly improved recovery from dynorphin A-induced hindlimb paralysis, and substantially eliminated neuropathological changes without attenuating the acute blood flow reductions or lactic acid elevations. Additionally, glutamate and aspartate concentrations were increased significantly in spinal cord cerebrospinal fluid samples removed during the time that peptide-induced spinal cord blood flow reductions were observed. In contrast, neither amino acid concentration was elevated in media removed after 1-hr exposure of spinal cord neuronal cell cultures to 100 microM concentrations of dynorphin A. These results indicate that the paralysis and spinal cord injuries produced in rats after spinal subarachnoid injection of dynorphin A result predominantly from spinal cord ischemia, and further identify excitatory amino acids and N-methyl-D-aspartate receptor mechanisms as important mediators in this injury model.","subset":"pubmed_abstract"} +{"meta":{"pmid":31920634,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-23":1,"2022-40":1,"2022-33":2,"2021-43":2,"2021-21":2,"2021-10":1,"2020-50":1,"2020-45":1,"2020-34":1,"2020-24":1,"2023-40":1,"2024-30":1}}},"text":"Incidences of Hypothyroidism Associated With Surgical Procedures for Thyroid Disorders: A Nationwide Population-Based Study.\nBackground and Aim: Limited information available about different types of thyroid surgeries with risk for postoperative hypothyroidism. This study aimed to investigate the risk of developing early and late-onset postoperative hypothyroidism in patients with thyroid disorders. Methods: We used a large cohort data from the Taiwan National Health Insurance Research Data Base (NHIRDB) and identified 9,693 (9, 348) patients from January 1998 to December 2010, admitted for thyroid disorder surgeries. We used the surgical procedures time as the index date. Our observational retrospective cohort study excluded the subjects diagnosed with hypoparathyroidism and hypothyroidism before any surgeries. We analyzed the data using the Cox regression model to calculate the hazard ratio. Result: Postoperative hypothyroidism associated with bilateral-total (HR, 4.27; 95% CI, 3.32-5.50), one-side total and another subtotal (HR, 3.16; 95% CI, 2.59-3.86), bilateral-subtotal (HR, 1.65; 95% CI, 1.37-1.98), and unilateral-total (HR, 1.17; 95% CI, 0.95-1.44) surgical procedures. The time intervals for thyroid disorders were 320 cases developed postoperative hypoparathyroidism in eight weeks, 480 cases the second month, and 1000 cases in the first year after surgery. Conclusion: Findings suggest that thyroidectomy was associated with transient postoperative hypothyroidism in thyroid disorder patients. The bilateral-total surgical procedure was strongly associated with temporary postoperative hypothyroidism.","subset":"pubmed_abstract"} +{"meta":{"pmid":33188087,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"From particle attachment to space-filling coral skeletons.\nReef-building corals and their aragonite (CaCO3) skeletons support entire reef ecosystems, yet their formation mechanism is poorly understood. Here we used synchrotron spectromicroscopy to observe the nanoscale mineralogy of fresh, forming skeletons from six species spanning all reef-forming coral morphologies: Branching, encrusting, massive, and table. In all species, hydrated and anhydrous amorphous calcium carbonate nanoparticles were precursors for skeletal growth, as previously observed in a single species. The amorphous precursors here were observed in tissue, between tissue and skeleton, and at growth fronts of the skeleton, within a low-density nano- or microporous layer varying in thickness from 7 to 20 \u00b5m. Brunauer-Emmett-Teller measurements, however, indicated that the mature skeletons at the microscale were space-filling, comparable to single crystals of geologic aragonite. Nanoparticles alone can never fill space completely, thus ion-by-ion filling must be invoked to fill interstitial pores. Such ion-by-ion diffusion and attachment may occur from the supersaturated calcifying fluid known to exist in corals, or from a dense liquid precursor, observed in synthetic systems but never in biogenic ones. Concomitant particle attachment and ion-by-ion filling was previously observed in synthetic calcite rhombohedra, but never in aragonite pseudohexagonal prisms, synthetic or biogenic, as observed here. Models for biomineral growth, isotope incorporation, and coral skeletons' resilience to ocean warming and acidification must take into account the dual formation mechanism, including particle attachment and ion-by-ion space filling.","subset":"pubmed_abstract"} +{"meta":{"pmid":12372733,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum.\nLeukoencephalopathies of unknown origin constitute a considerable problem in child neurology. The purpose of our ongoing study of the subject was to define new disease entities among them by using primarily MR imaging pattern recognition. We identified seven unrelated patients with a distinct MR imaging pattern consisting of hypomyelination and atrophy of the basal ganglia (neostriatum) and cerebellum (H-ABC). We reviewed the clinical, MR imaging, MR spectroscopic, and laboratory data. Clinically, the patients' diseases were characterized by variably disturbed early development followed by increasing extrapyramidal movement abnormalities, ataxia, and spasticity. Mental capacity was variably affected, but it appeared to be relatively preserved. Parents were not related, and none of their siblings were affected. No metabolic defect was found. Follow-up MR imaging demonstrated atrophy of the cerebral white matter, neostriatum, and cerebellum, which was most pronounced in the most clinically severe cases. Single-voxel proton MR spectroscopic results were normal in the parietal cortex. In the cerebral white matter, myo-inositol and creatine levels were elevated; this finding was compatible with gliosis. N-acetylaspartate and choline levels were normal, suggesting that neither axonal loss nor active demyelination occurred. Proton MR spectroscopic imaging revealed relatively decreased N-acetylaspartate levels in the frontal region. The uniform and highly characteristic MR imaging findings, in combination with the similarities in the clinical findings, provide evidence of a distinct nosologic entity. The acronym H-ABC is offered to indicate patients sharing these clinical and MR imaging features.","subset":"pubmed_abstract"} +{"meta":{"pmid":33684068,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Open Waste Canals as Potential Sources of Antimicrobial Resistance Genes in Aerosols in Urban Kanpur, India.\nUnderstanding the movement of antimicrobial resistance genes (ARGs) in the environment is critical to managing their spread. To assess potential ARG transport through the air via urban bioaerosols in cities with poor sanitation, we quantified ARGs and a mobile integron (MI) in ambient air over periods spanning rainy and dry seasons in Kanpur, India (n = 53), where open wastewater canals (OWCs) are prevalent. Gene targets represented major antibiotic groups-tetracyclines (tetA), fluoroquinolines (qnrB), and beta-lactams (blaTEM)-and a class 1 mobile integron (intI1). Over half of air samples located near, and up to 1 km from OWCs with fecal contamination (n = 45) in Kanpur had detectable targets above the experimentally determined limits of detection (LOD): most commonly intI1 and tetA (56% and 51% of samples, respectively), followed by blaTEM (8.9%) and qnrB (0%). ARG and MI densities in these positive air samples ranged from 6.9 \u00d7 101 to 5.2 \u00d7 103 gene copies\/m3 air. Most (7\/8) control samples collected 1 km away from OWCs were negative for any targets. In comparing experimental samples with control samples, we found that intI1 and tetA densities in air are significantly higher (P = 0.04 and P = 0.01, respectively, alpha = 0.05) near laboratory-confirmed fecal contaminated waters than at the control site. These data suggest increased densities of ARGs and MIs in bioaerosols in urban environments with inadequate sanitation. In such settings, aerosols may play a role in the spread of AR.","subset":"pubmed_abstract"} +{"meta":{"pmid":17846166,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":10}}},"text":"Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling.\nCa(2+) release from intracellular stores is controlled by complex interactions between multiple proteins. Triadin is a transmembrane glycoprotein of the junctional sarcoplasmic reticulum of striated muscle that interacts with both calsequestrin and the type 1 ryanodine receptor (RyR1) to communicate changes in luminal Ca(2+) to the release machinery. However, the potential impact of the triadin association with RyR1 in skeletal muscle excitation-contraction coupling remains elusive. Here we show that triadin binding to RyR1 is critically important for rapid Ca(2+) release during excitation-contraction coupling. To assess the functional impact of the triadin-RyR1 interaction, we expressed RyR1 mutants in which one or more of three negatively charged residues (D4878, D4907, and E4908) in the terminal RyR1 intraluminal loop were mutated to alanines in RyR1-null (dyspedic) myotubes. Coimmunoprecipitation revealed that triadin, but not junctin, binding to RyR1 was abolished in the triple (D4878A\/D4907A\/E4908A) mutant and one of the double (D4907A\/E4908A) mutants, partially reduced in the D4878A\/D4907A double mutant, but not affected by either individual (D4878A, D4907A, E4908A) mutations or the D4878A\/E4908A double mutation. Functional studies revealed that the rate of voltage- and ligand-gated SR Ca(2+) release were reduced in proportion to the degree of interruption in triadin binding. Ryanodine binding, single channel recording, and calcium release experiments conducted on WT and triple mutant channels in the absence of triadin demonstrated that the luminal loop mutations do not directly alter RyR1 function. These findings demonstrate that junctin and triadin bind to different sites on RyR1 and that triadin plays an important role in ensuring rapid Ca(2+) release during excitation-contraction coupling in skeletal muscle.","subset":"pubmed_abstract"} +{"meta":{"pmid":23569502,"dup_signals":{"dup_doc_count":14}},"text":"The first case of Horn Kolb Syndrome in Turkey, diagnosed prenatally at the 23(rd) week of a pregnancy: A very rare and unusual case far from the original geography.\nThe aim of this report was to evaluate and announce the first documented appearance of Horn Kolb syndrome in Turkey. Acheiropodia (Horn Kolb Syndrome) is the bilateral congenital amputation of the distal parts of the 4 extremities. It is an autosomal recessive developmental disorder. The characteristic features are amputation of the upper and lower extremities with aplasia of the hands and feet. The disorder affects only the extremities without other systemic manifestations. In this report, we present the first known case of Horn Kolb syndrome in Turkey, along with the diagnostic features. Severe dysmorphic skeletal anomalies should be excluded as soon as the earlier gestational weeks in every pregnancy by visualizing all 4 limbs of the fetus in routine prenatal ultrasound screening.","subset":"pubmed_abstract"} +{"meta":{"pmid":9120291,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"IL-2 gene delivery within an established murine tumor causes its regression without proliferation of preexisting antitumor-specific CTL.\nRegression of P815 tumors established on naive syngeneic mice can be obtained by the intratumoral injection of a single dose of an adenoviral vector expressing the IL-2 gene (Ad.IL2). Injection triggers local IL-2 production for at least 10 days. We measured a number of immunologic parameters in situ following intratumoral Ad.IL2 treatment. We also analyzed the situation of regression obtained upon challenge with P815 cells of mice previously immunized against the tumor and compared both systems. While IFN-gamma messenger RNA expression was found to be elevated in both situations of tumor regression, the level of infiltration by tumor-specific CTL was different. A small amount of tumor-specific CD8+ T cells were present in growing, untreated tumors. Such cells are found in much larger numbers in tumors rejected upon challenge, consistent with a CTL-mediated rejection. In contrast, they were found not to proliferate following Ad.IL2 injection. The latter caused an increased infiltration of a polyclonal, presumably nonspecific, T cell population. These results suggest that the initial regression of established P815 tumors following Ad.IL2 treatment in vivo is mostly due to nonspecific effectors.","subset":"pubmed_abstract"} +{"meta":{"pmid":16780379,"dup_signals":{"dup_doc_count":13,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2019-13":2,"2018-51":1,"2018-47":1,"2018-39":2,"2018-17":2,"2017-47":2,"2017-39":2}}},"text":"Universal behaviour of gel formation from acrylamide-carrageenan mixture around the gel point: a fluorescence study.\nThe steady state fluorescence (SSF) technique was used to study the sol-gel transition, for the solution free radical crosslinking copolymerization of acrylamide (AAm) with various carrageenan content. N, N'- methylenebis (acrylamide) (BIS) and ammonium persulfate (APS) are used as crosslinker and an initiator, respectively. Pyranine (8-hydroxypyrene-1, 3,6-trisulfonic acid, trisodium salt, HPTS) was added as a floroprobe for monitoring the polymerization. Pyranine molecules start to bind to acrylamide polymer chains upon the initiation of the polymerization; thus, the spectra of the bonded pyranines shift to the shorter wavelengths. Fluorescence spectra from the bonded pyranines allows one to monitor the sol-gel transition, without disturbing the system mechanically, and to test the universality of the sol-gel transition as a function of some kinetic parameters like polymer concentration. Observations around the critical point show that the gel fraction exponent beta obeyed the percolation result for low carrageenan concentrations (< 2.0%) however classical results were produced at higher carrageenan concentration (> 2.0%).","subset":"pubmed_abstract"} +{"meta":{"pmid":30238923,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The Effect of Chemerin on Cardiac Parameters and Gene Expressions in Isolated Perfused Rat Heart\nChemerin is a novel chemoattractant adipokine expressed in cardiovascular system, and its receptor has been detected in the epicardial adipose tissue. To determine the effects of chemerin on the cardiac parameters and gene expressions in the isolated perfused rat heart. Animal experiment. The hearts were retrogradely perfused with Langendorff technique to measure the cardiac parameters. The experimental groups were acutely treated with 10, 100, and 1000 nM doses of chemerin. Another group was given 10 \u03bcM L-nitric oxide synthase inhibitor for 5 min before 1000 nM chemerin administration. The real-time polymerase chain reaction was performed for detecting the expression of target genes. All doses of chemerin significantly decreased the left ventricular developed pressure (max 35.33 \u0394%, p<0.001), and +dP\/dtmax (max 31.3 \u0394%, p<0.001), which are the indexes of cardiac contractile force. In addition, 1000 nM chemerin reduced the coronary flow (max 31 \u0394%, p<0.001). N(W)-nitro-L-arginine methyl ester antagonized the negative inotropic effect of chemerin on contractility. Chemerin induced a 2.16-fold increase in endothelial nitric oxide synthase mRNA and increased the cyclic guanosine monophosphate levels (p<0.001) but decreased the PI3K\u03b3 gene expression (1.8-fold, p<0.001). Furthermore, all doses of chemerin decreased the CaV1.2 gene expression (1.69-fold, p<0.001). Acute chemerin treatment induces a negative inotropic action with the involvement of nitric oxide pathway, CaV1.2, and PI3K\u03b3 on isolated rat heart.","subset":"pubmed_abstract"} +{"meta":{"pmid":26588361,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-05":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-10":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2022-33":1}}},"text":"FAST Conformational Searches by Balancing Exploration\/Exploitation Trade-Offs.\nMolecular dynamics simulations are a powerful means of understanding conformational changes. However, it is still difficult to simulate biologically relevant time scales without the use of specialized supercomputers. Here, we introduce a goal-oriented sampling method, called fluctuation amplification of specific traits (FAST), for extending the capabilities of commodity hardware. This algorithm rapidly searches conformational space for structures with desired properties by balancing trade-offs between focused searches around promising solutions (exploitation) and trying novel solutions (exploration). FAST was inspired by the hypothesis that many physical properties have an overall gradient in conformational space, akin to the energetic gradients that are known to guide proteins to their folded states. For example, we expect that transitioning from a conformation with a small solvent-accessible surface area to one with a large surface area will require passing through a series of conformations with steadily increasing surface areas. We demonstrate that such gradients are common through retrospective analysis of existing Markov state models (MSMs). Then we design the FAST algorithm to exploit these gradients to find structures with desired properties by (1) recognizing and amplifying structural fluctuations along gradients that optimize a selected physical property whenever possible, (2) overcoming barriers that interrupt these overall gradients, and (3) rerouting to discover alternative paths when faced with insurmountable barriers. To test FAST, we compare its performance to other methods for three common types of problems: (1) identifying unexpected binding pockets, (2) discovering the preferred paths between specific structures, and (3) folding proteins. Our conservative estimate is that FAST outperforms conventional simulations and an adaptive sampling algorithm by at least an order of magnitude. Furthermore, FAST yields both the proper thermodynamics and kinetics, allowing for a direct connection with kinetic experiments that is impossible with many other advanced sampling algorithms because they provide only thermodynamic information. Therefore, we expect FAST to be of great utility for a wide range of applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":33222161,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Chrono-nutrition: From molecular and neuronal mechanisms to human epidemiology and timed feeding patterns.\nThe circadian timing system governs daily biological rhythms, synchronising physiology and behaviour to the temporal world. External time cues, including the light-dark cycle and timing of food intake, provide daily signals for entrainment of the central, master circadian clock in the hypothalamic suprachiasmatic nuclei (SCN), and of metabolic rhythms in peripheral tissues, respectively. Chrono-nutrition is an emerging field building on the relationship between temporal eating patterns, circadian rhythms, and metabolic health. Evidence from both animal and human research demonstrates adverse metabolic consequences of circadian disruption. Conversely, a growing body of evidence indicates that aligning food intake to periods of the day when circadian rhythms in metabolic processes are optimised for nutrition may be effective for improving metabolic health. Circadian rhythms in glucose and lipid homeostasis, insulin responsiveness and sensitivity, energy expenditure, and postprandial metabolism, may favour eating patterns characterised by earlier temporal distribution of energy. This review details the molecular basis for metabolic clocks, the regulation of feeding behaviour, and the evidence for meal timing as an entraining signal for the circadian system in animal models. The epidemiology of temporal eating patterns in humans is examined, together with evidence from human intervention studies investigating the metabolic effects of morning compared to evening energy intake, and emerging chrono-nutrition interventions such as time-restricted feeding. Chrono-nutrition may have therapeutic application for individuals with and at-risk of metabolic disease and convey health benefits within the general population.","subset":"pubmed_abstract"} +{"meta":{"pmid":16707648,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-23":2,"2022-49":1,"2022-40":1,"2022-05":1,"2021-25":1,"2021-04":1,"2020-34":1,"2020-24":2,"2020-10":1,"2018-51":1,"2024-18":1,"2024-30":1}}},"text":"Distribution of influenza vaccine to high-risk groups.\nVaccine distribution programs have historically targeted individuals at high risk of complications due to influenza. Despite recommendations from the Advisory Committee on Immunization Practices, vaccination coverage among high-risk populations has been generally low. This review systematically summarizes the recent literature evaluating programs in different settings, from within medical settings to venue-based and community-based approaches, in an effort to identify successful program components. The published literature was identified by using the MEDLINE database from 1990 to 2006 covering studies that reported on interventions or programs aimed at vaccinating high-risk populations. The authors reviewed 56 studies. In the United States, the Healthy People 2010 goals included 90% vaccination coverage for adults aged > or = 65 years and 60% for high-risk adults aged 18-64 years. Only a handful of the studies reviewed managed to meet those goals. Interventions that increased vaccination coverage to Healthy People 2010 goals included advertising, provider and patient mailings, registry-based telephone calls, patient and staff education, standing orders coupled with standardized forms, targeting of syringe exchange customers, and visiting nurses. Few studies evaluated the impact of vaccination programs by race\/ethnicity and socioeconomic status. Few studies targeted individuals outside of the health-care and social services sectors. Given the growing disparities in health and health-care access, understanding the way in which interventions can remedy disparities is crucial.","subset":"pubmed_abstract"} +{"meta":{"pmid":21531818,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Dopamine blocks stress-mediated ovarian carcinoma growth.\nIncreased adrenergic activity in response to chronic stress is known to promote tumor growth by stimulating the tumor microenvironment. The focus of the current study was to determine whether dopamine, an inhibitory catecholamine, could block the effects of chronic stress on tumor growth. Expression of dopamine receptors (DR1-DR5) was analyzed by reverse transcriptase-PCR and by Western blotting. In vitro effects of dopamine on cell viability, apoptosis, and migration were examined. For in vivo therapy, murine and human DR2-siRNAs were incorporated into chitosan nanoparticles (CH-NP). In this model of chronic stress, tumoral norepinephrine levels remained elevated whereas dopamine levels were significantly decreased compared with nonstressed animals. Daily restraint stress resulted in significantly increased tumor growth in both immunodeficient (SKOV3ip1 and HeyA8) and immunocompetent (ID8) ovarian cancer models. This increase was completely blocked with daily dopamine treatment. Dopamine treatment also blocked the stress-induced increase in angiogenesis. Endothelial and ovarian cancer cells expressed all dopamine receptors except for the lack of DR3 expression in ovarian cancer cells. DR2 was responsible for the inhibitory effects of dopamine on tumor growth and microvessel density as well as the stimulatory effect on apoptosis, as the DR2 antagonist eticlopride reversed these effects. Dopamine significantly inhibited cell viability and stimulated apoptosis in vitro. Moreover, dopamine reduced cyclic AMP levels and inhibited norepinephrine and vascular permeability factor\/VEGF-induced Src kinase activation. Dopamine depletion under chronic stress conditions creates a permissive microenvironment for tumor growth that can be reversed by dopamine replacement.","subset":"pubmed_abstract"} +{"meta":{"pmid":22244654,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":5,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":2}}},"text":"Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review.\nNeonatal interventions are largely focused on reduction of mortality and progression towards Millennium Development Goal 4 (child survival). However, little is known about the global burden of long-term consequences of intrauterine and neonatal insults. We did a systematic review to estimate risks of long-term neurocognitive and other sequelae after intrauterine and neonatal insults, especially in low-income and middle-income countries. We searched Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase for studies published between Jan 1, 1966, and June 30, 2011, that reported neurodevelopmental sequelae after preterm or neonatal insult. For unpublished studies and grey literature, we searched Dissertation Abstracts International and the WHO library. We reviewed publications that had data for long-term outcome after defined neonatal insults. We summarised the results with medians and IQRs, and calculated the risk of at least one sequela after insult. Of 28,212 studies identified by our search, 153 studies were suitable for inclusion, documenting 22,161 survivors of intrauterine or neonatal insults. The overall median risk of at least one sequela in any domain was 39\u00b74% (IQR 20\u00b70-54\u00b78), with a risk of at least one severe impairment in any insult domain of 18\u00b75% (7\u00b77-33\u00b73), of at least one moderate impairment of 5\u00b70% (0\u00b70-13\u00b73%), and of at least one mild impairment of 10\u00b70% (1\u00b74-17\u00b79%). The pooled risk estimate of at least one sequela (weighted mean) associated with one or more of the insults studied (excluding HIV) was 37\u00b70% (95% CI 27\u00b70-48\u00b70%) and this risk was not significantly affected by region, duration of the follow-up, study design, or period of data collection. The most common sequelae were learning difficulties, cognition, or developmental delay (n=4032; 59%); cerebral palsy (n=1472; 21%); hearing impairment (n=1340; 20%); and visual impairment (n=1228; 18%). Only 40 (26%) studies included data for multidomain impairments. These studies included 2815 individuals, of whom 1048 (37%) had impairments, with 334 (32%) having multiple impairments. Intrauterine and neonatal insults have a high risk of causing substantial long-term neurological morbidity. Comparable cohort studies in resource-poor regions should be done to properly assess the burden of these conditions, and long-term outcomes, such as chronic disease, and to inform policy and programme investments. The Bill & Melinda Gates Foundation, Saving Newborn Lives, and the Wellcome Trust.","subset":"pubmed_abstract"} +{"meta":{"pmid":36201130,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":2,"2024-18":4,"2024-10":1,"unknown":4}}},"text":"Conceptual Framework for Optimised Proxy Value Set Selection Through Supra-National Value Set Development for the EQ-5D Instruments.\nPreference differences between countries and populations justify the use of country-specific value sets for the EQ-5D instruments. There are no clear criteria based on which the selection of value sets for countries without a national value set should be made. As part of the European PECUNIA project, this study aimed to identify factors contributing to differences in preference-based valuations and develop supra-national value sets for homogenous country clusters in Europe. A literature review was conducted to identify factors relevant to variations in the EQ-5D-3L\/5L health state valuations across countries. Factors fulfilling the pre-specified criteria of validity, reliability, international feasibility and comparability were used to group 27 European Union member states, the European Free Trade Association countries and the UK. Clusters of countries were developed based on the frequency of their appearance in the same grouping. The supra-national value sets were estimated for these clusters from the coefficients of existing published valuation studies using the ordinary least-squares model. Ten factors were identified from 69 studies. From these, five grouping variables: (1) culture and religion; (2) linguistics; (3) healthcare system typology; (4) healthcare system financing; and (5) sociodemographic aspects were derived to define the groups of homogenous countries. Frequency-based grouping revealed five cohesive clusters: English-speaking, Nordic, Central-Western, Southern and Eastern European. European countries were clustered considering variables that may relate to differences in health state valuations. Supra-national value sets provide optimised proxy value set selection in the lack of a national value set and\/or for regional decision making.","subset":"pubmed_abstract"} +{"meta":{"pmid":12434052,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Cavity quantum electrodynamics: coherence in context.\nModern cavity quantum electrodynamics (cavity QED) illuminates the most fundamental aspects of coherence and decoherence in quantum mechanics. Experiments on atoms in cavities can be described by elementary models but reveal intriguing subtleties of the interplay of coherent dynamics with external couplings. Recent activity in this area has pioneered powerful new approaches to the study of quantum coherence and has fueled the growth of quantum information science. In years to come, the purview of cavity QED will continue to grow as researchers build on a rich infrastructure to attack some of the most pressing open questions in micro- and mesoscopic physics.","subset":"pubmed_abstract"} +{"meta":{"pmid":19881718,"dup_signals":{"dup_doc_count":22,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2016-44":3,"2016-40":1,"2016-36":3,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-40":1,"2015-32":1,"2015-22":2,"2015-18":2}}},"text":"Modulation Z-scan technique for characterization of photorefractive crystals.\nWe propose a simple single-beam configuration for characterization of the amplitude, speed of growth, and polarization properties of the photoinduced refractive-index change that is due to a drift photorefractive mechanism of nonlinearity in crystals, namely, the modulation Z-scan technique, based on the modulation of an externally applied electric field. The results of a simple theoretical model developed for one-dimensional parabolic photorefractive lens formation in this configuration are illustrated by original experiments with a semi-insulating GaAs crystal at lambda -1.06 microm.","subset":"pubmed_abstract"} +{"meta":{"pmid":11897110,"dup_signals":{"dup_doc_count":16,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2017-13":1,"unknown":7}}},"text":"Studies on the subtype selectivity of CP-101,606: evidence for two classes of NR2B-selective NMDA receptor antagonists.\nThe subtype-selectivity of racemic [(3)H]CP-101,606, a novel high-affinity NMDA receptor radioligand was determined using defined recombinant NMDA receptor subunits expressed in HEK 293 cells. [(3)H]CP-101,606 binds to adult rodent forebrain and NR1\/NR2B receptors expressed in HEK 293 cells with K(D)=4.2 nM and 6.0 nM, respectively. In contrast, no high affinity specific binding was detected to NR1, NR2A, NR2B subunits expressed alone or NR1\/NR2A receptors. HEK 293 cells were transfected with NR1, NR2A and NR2B receptor subunits and complexes comprising all three subunits were isolated by anti-NR2A immunoaffinity chromatography. Based on immunoblotting with subunit-selective antibodies, the immunopurified material contained all three NMDA receptor subunit polypeptides. However, in contrast to parallel studies in which high affinity [(3)H]Ro-25,6981 binding activity was observed, no high affinity [(3)H]CP-101,606 binding sites were detected to the immunopurified material. This study provides further evidence for two distinct classes of NR2B-directed NMDA receptor antagonists, one which binds with high affinity irrespective whether another NR2 subunit type is present (Ro-25,6981) and a second class which is affected significantly by the presence of another NR2 subunit type within the receptor complex, exemplified by CP-101,606.","subset":"pubmed_abstract"} +{"meta":{"pmid":19830349,"dup_signals":{"dup_doc_count":25,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2015-40":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":2,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2023-06":1,"2015-18":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1}}},"text":"Quality of life in pediatric patients with atopic dermatitis.\nTo measure the impact of atopic dermatitis (AD) on the quality of life of pediatric patients and their families, establishing correlations with scores of disease severity. This was an observational study of the correlations between clinical indicators of severity and two questionnaires on quality of life: IDQOL and DFI. The study also included scoring of eczema severity EASI. Forty-two children with AD, fulfilling established diagnostic criteria, and 44 children with other dermatologic diseases were investigated for the effect of eczema on quality of life. Pearson's correlation was used for the correlation analysis and the comparison between the groups was carried out using the Mann-Whitney test. Data analysis demonstrated significant differences between the scores for the two groups. The mean score in the eczema group was 9.2 (range 1-19) for IDQOL and 8.5 (range 0-17) for DFI. The highest scoring questions for IDQOL referred to itching and scratching, mood changes and problems caused by treatment. For the FDI, the highest impact domains were treatment-related expenditure and sleep disturbance affecting family members. AD has a negative impact on the quality of life of pediatric patients and their families. Data obtained in studies of quality of life in AD should be used to guide clinical practice in order to identify individual treatment strategies and should lead to the adoption of measures to reduce the impact of the disease on patients and their families.","subset":"pubmed_abstract"} +{"meta":{"pmid":21984546,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Wall structures of myocardial precapillary arterioles and postcapillary venules reexamined and reconstructed in vitro for studies on barrier functions.\nThe barrier functions of myocardial precapillary arteriolar and postcapillary venular walls (PCA or PCV, respectively) are of considerable scientific and clinical interest (regulation of blood flow and recruitment of immune defense). Using enzyme histochemistry combined with confocal microscopy, we reexamined the cell architecture of human PCA and PVC and reconstructed appropriate in vitro models for studies of their barrier functions. Contrary to current opinion, the PCA endothelial tube is encompassed not by smooth muscle cells but rather by a concentric layer of pericytes cocooned in a thick, microparticle-containing extracellular matrix (ECM) that contributes substantially to the tightness of the arteriolar wall. This core tube extends upstream into the larger arterioles, there additionally enwrapped by smooth muscle. PCV consist of an inner layer of large, contractile endothelial cells encompassed by a fragile, wide-meshed pericyte network with a weakly developed ECM. Pure pericyte and endothelial cell preparations were isolated from PCA and PCV and grown in sandwich cultures. These in vitro models of the PCA and PCV walls exhibited typical histological and functional features. In both plasma-like (PLM) and serum-containing (SCM) media, the PCA model (including ECM) maintained its low hydraulic conductivity (L(P) = 3.24 \u00b1 0.52\u00b710(-8)cm\u00b7s(-1)\u00b7cmH(2)O(-1)) and a high selectivity index for transmural passage of albumin (SI(Alb) = 0.95 \u00b1 0.02). In contrast, L(P) and SI(Alb) in the PCV model (almost no ECM) were 2.55 \u00b1 0.32\u00b710(-7)cm\u00b7s(-1)\u00b7cmH(2)O(-1) and 0.88 \u00b1 0.03, respectively, in PLM, and 1.39 \u00b1 0.10\u00b710(-6)cm\u00b7s(-1)\u00b7cmH(2)O(-1) and 0.49 \u00b1 0.04 in SCM. With the use of these models, systematic, detailed studies on the regulation of microvascular barrier properties now appear to be feasible.","subset":"pubmed_abstract"} +{"meta":{"pmid":22011065,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":1,"unknown":8}}},"text":"Skin care practices for newborns and infants: review of the clinical evidence for best practices.\nIn recent years, there have been continuing efforts to understand the effects of baby skin care routines and products on the healthy development of baby skin. Such efforts aim ultimately to determine the best infant skin care practices. The pediatric and dermatologic communities have not reached consensus on what constitutes an appropriate cleansing practice. In the United States, guidelines for neonatal skin care have been developed, propagated, and implemented. The accumulated knowledge has promoted evidence-based clinical practices and, therefore, may help to improve clinical outcomes, although these guidelines primarily cover the care of preterm newborns and the treatment of those with other health problems. High-level, long-term clinical evidence of the effective and safe cleansing of healthy, full-term newborns and infants is scarce. This review presents a comprehensive analysis of the scientific literature on baby skin development, cleansing practices, and related products (for healthy newborns and babies) since 1970. The evidence drawn from the reviewed literature can be summarized as follows: Bathing immersed in water seems generally superior to washing alone. Bathing or washing with synthetic detergents (syndets) or mild liquid baby cleansers seems comparable with or even superior to water alone. Nevertheless, larger randomized clinical trials with age-defined cohorts of babies as well as more-defined parameters are required to identify optimal practices and products for skin cleansing of healthy infants. These parameters may include standardized skin function parameters such as transepidermal water loss, stratum corneum hydration, skin surface pH, and sebum production. Clinical skin scores such as the Neonatal Skin Condition Score may be employed as outcome measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":29523571,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":14}}},"text":"Cognitive-behavioural therapy (CBT) for renal fatigue (BReF): a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients.\nFatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients. We aim to recruit 40 adult patients undergoing in-centre haemodialysis at secondary care outpatient dialysis units, who meet clinical levels of fatigue. Patients will be randomised individually (using a 1:1 ratio) to either a 4-6 weeks' CBT-based intervention (intervention arm) or to a waiting-list control (control arm). The primary feasibility outcomes include descriptive data on numbers within each recruiting centre meeting eligibility criteria, rates of recruitment, numbers retained postrandomisation and treatment adherence. To assess the potential benefits of the cognitive-behavioural therapy for renal fatigue intervention, secondary self-report outcomes include measures of fatigue severity (Chalder Fatigue Questionnaire), fatigue-related functional impairment (Work and Social Adjustment Scale), sleep quality (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Changes in fatigue perceptions (Brief Illness Perception Questionnaire), cognitive and behavioural responses to fatigue (Cognitive and Behavioural Responses to Symptoms Questionnaire), sleep hygiene behaviours (Sleep Hygiene Index) and physical activity (International Physical Activity Questionnaire-short form) will also be explored. These self-report measures will be collected at baseline and 3 months postrandomisation. Nested qualitative interviews will be conducted postintervention to explore the acceptability of the intervention and identify any areas in need of improvement. The statistician and assessor will be blinded to treatment allocation. A National Health Service (NHS) Research Ethics Committee approved the study. Any amendments to the protocol will be submitted to the NHS Committee and study sponsor. ISRCTN91238019;Pre-results.","subset":"pubmed_abstract"} +{"meta":{"pmid":7965831,"dup_signals":{"dup_doc_count":54,"dup_dump_count":40,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":1,"2023-06":2,"2022-40":2,"2022-21":2,"2021-49":1,"2021-39":1,"2021-25":1,"2021-21":1,"2021-10":3,"2021-04":1,"2020-50":3,"2020-45":1,"2020-40":1,"2020-29":2,"2020-24":1,"2019-47":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2024-30":3,"2024-26":1,"2024-10":1,"2017-13":1}}},"text":"Effects of hypercapnia on membrane potential and intracellular calcium in rat carotid body type I cells.\n1. An acid-induced rise in the intracellular calcium concentration ([Ca2+]i) of type I cells is thought to play a vital role in pH\/PCO2 chemoreception by the carotid body. In this present study we have investigated the cause of this rise in [Ca2+]i in enzymatically isolated, neonatal rat type I cells. 2. The rise in [Ca2+]i induced by a hypercapnic acidosis was inhibited in Ca(2+)-free media, and by 2 mM Ni2+. Acidosis also increased Mn2+ permeability. The rise in [Ca2+]i is dependent, therefore, upon a Ca2+ influx from the external medium. 3. The acid-induced rise in [Ca2+]i was attenuated by both nicardipine and methoxyverapamil (D600), suggesting a role for L-type Ca2+ channels. 4. Acidosis depolarized type I cells and often (approximately 50% of cells) induced action potentials. These effects coincided with a rise in [Ca2+]i. When membrane depolarization was prevented by a voltage clamp, acidosis failed to evoke a rise in [Ca2+]i. The acid-induced rise in [Ca2+]i is a consequence, therefore, of membrane depolarization. 5. Acidosis decreased the resting membrane conductance of type I cells. The reversal potential of the acid-sensitive current was about -75 mV. 6. A depolarization (30 mM [K+]o)-induced rise in [Ca2+]i was blocked by either the removal of extracellular Ca2+ or the presence of 2 mM Ni2+, and was also substantially inhibited by nicardipine. Under voltage-clamp conditions, [Ca2+]i displayed a bell-shaped dependence on membrane potential. Depolarization raises [Ca2+]i, therefore, through voltage-operated Ca2+ channels. 7. Caffeine (10 mM) induced only a small rise in [Ca2+]i (< 10% of that induced by 30 mM extracellular K+). Ca(2+)-induced Ca2+ release is unlikely, therefore, to contribute greatly to the rise in [Ca2+]i induced by depolarization. 8. Although the replacement of extracellular Na+ with N-methyl-D-glucamine (NMG), but not Li+, inhibited the acid-induced rise in [Ca2+]i, this was due to membrane hyperpolarization and not to the inhibition of Na(+)-Ca2+ exchange or Na(+)-dependent action potentials. 9. The removal of extracellular Na+ (NMG substituted) did not have a significant effect upon the resting [Ca2+]i, and only slowed [Ca2+]i recovery slightly following repolarization from 0 to -60 mV. Therefore, if present, Na(+)-Ca2+ exchange plays only a minor role in [Ca2+]i homeostasis. 10. In summary, in the neonatal rat type I cell, hypercapnic acidosis raises [Ca2+]i through membrane depolarization and voltage-gated Ca2+ entry.","subset":"pubmed_abstract"} +{"meta":{"pmid":27525254,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Patterns and trajectories of gestational weight gain: a prospective cohort study.\nGestational weight gain in excess of or below Health Canada's guidelines is known to increase the risk of adverse outcomes for both the woman and her baby. This study describes patterns and trajectories of total and rate of gestational weight gain in a large prospective cohort of pregnant women and adolescents in the Alberta Pregnancy Outcomes and Nutrition study. We collected weight and height data for 1541 pregnant adolescents and women (mean age 31 years, < 27 weeks' gestation) recruited through advertisements and physicians' offices in Calgary and Edmonton between May 2009 and November 2012. Data were collected once during each trimester following enrolment and once at about 3 months post partum. The participants were categorized according to their prepregnancy body mass index (BMI) as underweight, of normal weight, overweight or obese. We calculated distributions of total and weekly rates of weight gain and determined trajectories of weight gain for each prepregnancy BMI category. Of the 1541 participants, 761 (49.4%) exceeded Health Canada's guidelines for total gestational weight gain, and 272 (17.6%) gained less weight than recommended. A total of 63 (19.2%) and 38 (23.6%) participants categorized as overweight or obese, respectively, exceeded the recommended upper limit by 5 to less than 10 kg, and 53 (16.2%) and 27 (16.8%), respectively, exceeded the upper limit by at least 10 kg. Ninety-five participants (30.3%) in the overweight group and 59 (39.6%) of those in the obese group gained weight at more than double the recommended rate between the second and third trimesters. The median weight gain for participants in the normal, overweight and obese categories had exceeded recommended upper limits by about 30, 20 and 18 weeks' gestation, respectively. Adherence to Health Canada's guidelines for gestational weight gain was low. Excess gestational weight gain was most marked among those with a prepregnancy BMI in the overweight or obese category. The findings suggest that weight management in pregnancy is challenging and complex. Messages and supports that are tailored for women in different prepregnancy BMI categories may help to improve guideline-concordant gestational weight gain.","subset":"pubmed_abstract"} +{"meta":{"pmid":12908981,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Low propensity for aerial dispersal in specialist spiders from fragmented landscapes.\nAerial dispersal by ballooning is a passive flight, by which wind drag generates an upward lift on a silk thread. It is likely to reflect an aerial lottery, in which the absence of flight direction control is a serious cost for long-distance dispersal in a fragmented landscape. For species occurring in one patchily distributed habitat type, dispersal should evolve in a different way from morphological traits, directly linked to active dispersal. Therefore, we expect that if the risk of landing in an unsuitable habitat is lower than the probability of reaching a suitable habitat, selection should benefit a well-developed ballooning behaviour. We investigated interspecific variation in the ballooning-initiating tiptoe behaviour as it is linked to spider dispersal performance. Our results indeed indicate that ballooning performance is negatively related to habitat specialization in spiders from patchy grey dunes, so habitat specialists are characterized by poorly developed dispersal behaviour. These findings are concordant with recent insights that dispersal is selected as risk spreading in generalists, while it is selected against in specialist species.","subset":"pubmed_abstract"} +{"meta":{"pmid":28165541,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Obstructive sleep-disordered breathing, enuresis and combined disorders in children: chance or related association?\nNocturnal enuresis is usually diagnosed and treated by a primary paediatrician or family practitioner; if there is any doubt, the children may be referred to a paediatric urologist. Obstructive sleep-disordered breathing is a complex, multifactorial disorder. Adenotonsillar hypertrophy is considered an important factor associated with obstructive sleep apnoea syndrome. Enuresis and obstructive sleep-disordered breathing are both frequent problems of sleep in childhood. We conducted an electronic search in Medline, Scopus and the ISI Web of Science to look for published material and identify a putative link between nocturnal enuresis and obstructive sleep-disordered breathing. A total number of 98 documents were found, but 24 of these had to be excluded after an attentive reading of the title, abstract or full text because the information therein was not suitable for the aims of our search. Studies have found that children with obstructive sleep apnoea syndrome frequently also have nocturnal enuresis. Both disorders have an underlying sleep disturbance characterised by an altered arousal response and sleep fragmentation. The pathophysiology of enuretic events is seemingly linked to nocturnal obstructive events, causing increased intra-abdominal pressure and altered systemic blood pressure that induces natriuresis and polyuria by altering levels of antidiuretic hormone, and atrial and brain natriuretic peptides. We found 17 studies regarding the urological outcome of treatment for obstructive sleep-disordered breathing in children with enuresis. Although a vast amount of information is now available regarding the relationship between nocturnal enuresis and obstructive sleep-disordered breathing, many of the published studies were uncontrolled, retrospective or prospective cohort studies (grade C recommendation). Resolution of enuresis after medical or surgical treatment for obstructive sleep-disordered breathing has been emphasised. Consequently, symptoms such as snoring, sleep apnoeas and restless sleep should be sought for all children with enuresis. Confirmed obstructive sleep-disordered breathing should be treated promptly; subsequently, the persistence of enuresis requires treatment following the standard protocol.","subset":"pubmed_abstract"} +{"meta":{"pmid":10401553,"dup_signals":{"dup_doc_count":55,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-50":2,"2023-14":2,"2022-49":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":2,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":2,"2020-50":3,"2020-40":2,"2020-16":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-39":1,"2018-30":2,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":3,"2017-43":2,"2017-34":2,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-22":1,"2017-13":1,"2024-30":1}}},"text":"Comparative effects of cyclo-oxygenase and nitric oxide synthase inhibition on the development and reversal of spinal opioid tolerance.\n1. This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L-NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. 2. Repeated administration of intrathecal morphine (15 micrograms), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co-administration of ketorolac (30 and 45 micrograms) or S(+) ibuprofen (10 micrograms) with morphine (15 micrograms) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L-NAME (100 micrograms) exerted weaker effects. Administration of S(+) but not R(-) ibuprofen (10 mg kg-1) had similar effects on systemic administration of morphine (15 mg kg-1). 3. Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not potentiate the acute actions of spinal or systemic morphine, but chronic intrathecal administration of these agents increased the potency of acute morphine. 4. In animals already tolerant to intrathecal morphine, subsequent administration of ketorolac (30 micrograms) with morphine (15 micrograms) partially restored the antinociceptive effect and ED50 value of acute morphine, reflecting the reversal of tolerance. Intrathecal L-NAME (100 micrograms) exerted a weaker effect. 5. These data suggest that spinal COX activity, and to a lesser extent NOS activity, contributes to the development and expression of opioid tolerance. Inhibition of COX may represent a useful approach for the prevention as well as reversal of opioid tolerance.","subset":"pubmed_abstract"} +{"meta":{"pmid":18284365,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination among civilians in the United States, January-October 2003.\nMyocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and\/or pericarditis (myo\/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo\/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo\/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo\/pericarditis among civilians.","subset":"pubmed_abstract"} +{"meta":{"pmid":11823226,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2018-51":1,"2018-39":1,"2018-26":1,"2018-09":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2021-17":1,"2017-13":1}}},"text":"Molecular relationship between two groups of the genus Leptospirillum and the finding that Leptospirillum ferriphilum sp. nov. dominates South African commercial biooxidation tanks that operate at 40 degrees C.\nIron-oxidizing bacteria belonging to the genus Leptospirillum are of great importance in continuous-flow commercial biooxidation reactors, used for extracting metals from minerals, that operate at 40 degrees C or less. They also form part of the microbial community responsible for the generation of acid mine drainage. More than 16 isolates of leptospirilla were included in this study, and they were clearly divisible into two major groups. Group I leptospirilla had G+C moles percent ratios within the range 49 to 52% and had three copies of rrn genes, and based on 16S rRNA sequence data, these isolates clustered together with the Leptospirillum ferrooxidans type strain (DSM2705 or L15). Group II leptospirilla had G+C moles percent ratios of 55 to 58% and had two copies of rrn genes, and based on 16S rRNA sequence data, they form a separate cluster. Genome DNA-DNA hybridization experiments indicated that three similarity subgroups were present among the leptospirilla tested, with two DNA-DNA hybridization similarity subgroups found within group I. The two groups could also be distinguished based on the sizes of their 16S-23S rRNA gene spacer regions. We propose that the group II leptospirilla should be recognized as a separate species with the name Leptospirillum ferriphilum sp. nov. Members of the two species can be rapidly distinguished from each other by amplification of their 16S rRNA genes and by carrying out restriction enzyme digests of the products. Several, but not all, isolates of the group II leptospirilla, but none from group I (L. ferrooxidans), were capable of growth at 45 degrees C. All the leptospirilla isolated from commercial biooxidation tanks in South Africa were from group II.","subset":"pubmed_abstract"} +{"meta":{"pmid":33147833,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Fouling of Polymeric Hollow Fiber Heat Exchangers by Air Dust.\nCurrently, liquid-to-gas heat exchangers in buildings, domestic appliances and the automotive industry are mainly made of copper and aluminum. Using plastic instead of metal can be very beneficial from an economic and environmental point of view. However, it is required that a successful plastic design meets all the requirements of metal heat exchangers. The polymeric hollow fiber heat exchanger studied in this work is completive to common metal finned heat exchangers. Due to its unique design (the use of thousands of thin-walled microtubes connected in parallel), it achieves a high level of compactness and thermal performance, low pressure drops and high operation pressure. This paper focuses on an important aspect of heat exchanger operation-its fouling in conditions relevant to building and domestic application. In heating, ventilation and air conditioning (HVAC) and automotive and domestic appliances, outdoor and domestic dust are the main source of fouling. In this study, a heat exchanger made of polymeric hollow fibers was tested in conditions typical for indoor HVAC equipment, namely with the 20 \u00b0C room air flowing through the hot water coil (water inlet 50 \u00b0C) with air velocity of 1.5 m\/s. ASHRAE test dust was used as a foulant to model domestic dust. A polymeric heat exchanger with fibers with an outer diameter of 0.6 mm (1960 fibers arranged into 14 layers in total) and a heat transfer area of 0.89 m2 was tested. It was proven that the smooth polypropylene surface of hollow fibers has a favorable antifouling characteristic. Fouling evolution on the metallic heat transfer surfaces of a similar surface density was about twice as quick as on the plastic one. The experimental results on the plastic heat exchanger showed a 38% decrease in the heat transfer rate and a 91% increase in pressure drops after eighteen days of the experiment when a total of 4000 g\/m2 of the test dust had been injected into the air duct. The decrease in the heat transfer rate of the heat exchanger was influenced mainly by clogging in the frontal area because the first layers were fouled significantly more than the deeper layers.","subset":"pubmed_abstract"} +{"meta":{"pmid":11806903,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":12}}},"text":"A mathematical model predicts that calreticulin interacts with the endoplasmic reticulum Ca(2+)-ATPase.\nA robust mathematical model developed from single cell calcium (Ca(2+)) dynamics has enabled us to predict the consequences of over-expression of endoplasmic reticulum-located chaperones. Model predictions concluded that calreticulin interacts with the lumenal domain of the sarcoplasmic and endoplasmic reticulum Ca(2+)-activated ATPase (SERCA) pump, altering pump affinity for Ca(2+) (K(1\/2) switches from 247 to 431 nM) and hence generating Ca(2+) oscillations. Expression of calreticulin in the ER generated an average of six transient-decline oscillations during the Ca(2+) recovery phase, upon exposure to maximal levels of the agonist ATP. In contrast, normal cells produced a single Ca(2+) transient with few or no oscillations. By conditioning the model to experimental data, parameters for generation and decay of IP(3) and SERCA pump kinetics were determined. To elucidate the possible source of the oscillatory behavior three possible oscillators, 1) IP(3), 2) IP(3)R, and 3) SERCA pump, were investigated and parameters constrained by experimental data to produce the best candidate. Each of the three oscillators generated very good fits with experimental data. However, converting a normal exponential recovery to a transient-decline oscillator predicted that the SERCA pump is the most likely candidate for calreticulin-mediated Ca(2+) release, highlighting the role of this chaperone as a signal protein within the endoplasmic reticulum.","subset":"pubmed_abstract"} +{"meta":{"pmid":31362493,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2021-10":1,"2020-34":1,"2020-29":2,"2020-16":1,"2020-05":2,"2019-51":1,"2019-43":1,"2019-35":1,"2021-21":1,"2024-22":1}}},"text":"Nanoscale Mapping of Nonuniform Heterogeneous Nucleation Kinetics Mediated by Surface Chemistry.\nNucleation underlies the formation of many liquid-phase synthetic and natural materials with applications in materials chemistry, geochemistry, biophysics, and structural biology. Most liquid-phase nucleation processes are heterogeneous, occurring at specific nucleation sites at a solid-liquid interface; however, the chemical and topographical identity of these nucleation sites and how nucleation kinetics vary from site-to-site remain mysterious. Here we utilize in situ liquid cell electron microscopy to unveil counterintuitive nanoscale nonuniformities in heterogeneous nucleation kinetics on a macroscopically uniform solid-liquid interface. Time-resolved in situ electron microscopy imaging of silver nanoparticle nucleation at a water-silicon nitride interface showed apparently randomly located nucleation events at the interface. However, nanometric maps of local nucleation kinetics uncovered nanoscale interfacial domains with either slow or rapid nucleation. Interestingly, the interfacial domains vanished at high supersaturation ratio, giving way to rapid spatially uniform nucleation kinetics. Atomic force microscopy and nanoparticle labeling experiments revealed a topographically flat, chemically heterogeneous interface with nanoscale interfacial domains of functional groups similar in size to those observed in the nanometric nucleation maps. These results, along with a semiquantitative nucleation model, indicate that a chemically nonuniform interface presenting different free energy barriers to heterogeneous nucleation underlies our observations of nonuniform nucleation kinetics. Overall, our results introduce a new imaging modality, nanometric nucleation mapping, and provide important new insights into the impact of surface chemistry on microscopic spatial variations in heterogeneous nucleation kinetics that have not been previously observed.","subset":"pubmed_abstract"} +{"meta":{"pmid":19399172,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.\nThe human IgM B7-DC XAb protects mice from tumors in both therapeutic and prophylactic settings. Its mechanism of action is mediated by its binding to B7-DC\/PD-L2 molecules on the surface of dendritic cells (DCs) to induce a multimolecular cap and subsequent activation of signaling cascades that determine a unique combination of DC phenotypes. One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear. Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb. Signals emanating from CD40 are important, as CD40(-\/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3). CD40(-\/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro. Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo. These results indicate that B7-DC XAb modulation of DC phenotypes is through its ability to indirectly recruit common signaling molecules and elements of their endogenous signaling pathways through targeted binding to a cell-specific surface determinant.","subset":"pubmed_abstract"} +{"meta":{"pmid":12450647,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Repetition of suicidal behaviour in elderly Europeans: a prospective longitudinal study.\nThe aim of this study was to assess any predictive factors for repeated attempted suicide and completed suicide in a 1-year follow-up on a sample of elderly European suicide attempters (60 years and over). From 1990 to 1993, 63 subjects completed the first interview and were recontacted after 1 year. At follow-up, eight subjects (12.7%) had taken their lives and seven (11.1%) had repeated at least one suicide attempt. On comparison of repeaters and non-repeaters, differences emerged in terms of death of the father in childhood and for mean Suicidal Intent Score. At the end of follow-up period, repeaters reported a more frequent desire to repeat suicidal behaviour and judged their mental health and social assistance received to be worse. Suicides and non-repeaters differed especially in relation to death of father during childhood and number of contacts with General Practitioner. Interpretation of the results must take into account the smallness of the test sample, the difficulties in obtaining complete data for the follow-up interview, the lack of a control group and a diagnosis formulated in a hospital consultation setting. The study confirms, however, the high risk of repetition of suicidal behaviour in the elderly. In old age suicidal ideation is often sustained over long periods of time and requests for help are addressed to relatives and GPs. An interesting finding is the more frequent death of the father during childhood among repeaters.","subset":"pubmed_abstract"} +{"meta":{"pmid":32559611,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Increased dehydroepiandrosterone (DHEA) is associated with anxiety in adolescent girls.\nThe pubertal period is a time of rapid increase in the incidence of anxiety disorders, and thus, pubertal hormones may play a role in the precipitation of anxious psychopathology. DHEA, a steroid hormone that surges in adolescence, has been previously linked to anxiety, although the direction of this effect has been mixed. Using a cross-sectional design in a sample of 286 adolescent girls, the present study examined associations between salivary DHEA concentrations and self-report and interview-based measures of anxiety while controlling for pubertal status, menarche status, assessment time of day, and other hormones including testosterone, estradiol, and progesterone. Increased salivary DHEA concentrations were associated with more self-reported anxiety symptoms, increased anxiety symptom counts based on clinical interview, and increased probability of an anxiety disorder. Out of all anxiety symptom domains examined, generalized anxiety disorder symptoms were the best predictor of salivary DHEA concentrations after controlling for pubertal development. Collectively, our findings suggest relevance for DHEA in the development of anxiety in the pubertal period, as well as a robust relationship between DHEA and emerging symptoms of pathological worry during adolescence. The present study underscores the importance of examining associations between DHEA concentrations and anxiety in longitudinal designs.","subset":"pubmed_abstract"} +{"meta":{"pmid":29670584,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Comparative Microbiome Analysis of a Fusarium Wilt Suppressive Soil and a Fusarium Wilt Conducive Soil From the Ch\u00e2teaurenard Region.\nDisease-suppressive soils are soils in which specific soil-borne plant pathogens cause only limited disease although the pathogen and susceptible host plants are both present. Suppressiveness is in most cases of microbial origin. We conducted a comparative metabarcoding analysis of the taxonomic diversity of fungal and bacterial communities from suppressive and non-suppressive (conducive) soils as regards Fusarium wilts sampled from the Ch\u00e2teaurenard region (France). Bioassays based on Fusarium wilt of flax confirmed that disease incidence was significantly lower in the suppressive soil than in the conducive soil. Furthermore, we succeeded in partly transferring Fusarium wilt-suppressiveness to the conducive soil by mixing 10% (w\/w) of the suppressive soil into the conducive soil. Fungal diversity differed significantly between the suppressive and conducive soils. Among dominant fungal operational taxonomic units (OTUs) affiliated to known genera, 17 OTUs were detected exclusively in the suppressive soil. These OTUs were assigned to the Acremonium, Chaetomium, Cladosporium, Clonostachys, Fusarium, Ceratobasidium, Mortierella, Penicillium, Scytalidium, and Verticillium genera. Additionally, the relative abundance of specific members of the bacterial community was significantly higher in the suppressive and mixed soils than in the conducive soil. OTUs found more abundant in Fusarium wilt-suppressive soils were affiliated to the bacterial genera Adhaeribacter, Massilia, Microvirga, Rhizobium, Rhizobacter, Arthrobacter, Amycolatopsis, Rubrobacter, Paenibacillus, Stenotrophomonas, and Geobacter. Several of the fungal and bacterial genera detected exclusively or more abundantly in the Fusarium wilt-suppressive soil included genera known for their activity against F. oxysporum. Overall, this study supports the potential role of known fungal and bacterial genera in Fusarium wilt suppressive soils from Ch\u00e2teaurenard and pinpoints new bacterial and fungal genera for their putative role in Fusarium wilt suppressiveness.","subset":"pubmed_abstract"} +{"meta":{"pmid":24950819,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2018-34":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-14":1}}},"text":"Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: accumbens more promising than caudate.\nHigh-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.","subset":"pubmed_abstract"} +{"meta":{"pmid":22552579,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-14":1,"2019-26":1,"2019-18":1,"2019-13":1,"2018-51":1,"2018-34":1,"2018-30":1,"2018-09":1,"2018-05":1,"2017-47":2,"2017-39":4,"2023-40":1,"2024-18":1}}},"text":"Unmet refractive need and its determinants in Shahroud, Iran.\nUncorrected refractive error plays a significant role in poor vision and blindness, and its correction is the most cost-effective intervention in eye care. In this study, we report the status of the unmet refractive need and the role of economic inequality in determining the level of this need in Shahroud, Iran. This cross-sectional nested case-control study was performed on 5,190 individuals aged 40-64 years. Cases and controls were individuals with uncorrected visual acuity worse than 0.3 LogMAR in the better eye who showed at least 0.2 LogMAR improvement after correction. Cases were individuals whose presenting vision was worse than 0.3 in the better eye but improved by at least 0.2 LogMAR after correction. Controls were individuals in whom the difference between the presenting and corrected vision was less than 0.2 LogMAR. The prevalence of the unmet need was 5.7 % and it was more prevalent in women (6.5 %) than in men (4.6 %) (p = 0.003). There was a gap of 19.6 % between the two groups of high and low economic status. The Oaxaca-Blinder decomposition method revealed that differences in the education level of the two groups accounted for half of this gap. Spectacle usage is better in Iran than in some other developing countries; however, in this study, about 40 % of those who required spectacles did not have them.","subset":"pubmed_abstract"} +{"meta":{"pmid":32961555,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"An Osteopathic Modular Approach to Asthma: A Narrative Review.\nAsthma is among of the first ailments documented in the existing academic literature as being successfully managed with osteopathic manipulative treatment (OMT) techniques. Time-efficient and well-tolerated OMT techniques have been gradually added to the literature to manage this increasingly prevalent disease. In this narrative review, the authors discuss previously-published literature describing the history, diagnosis, and management of asthma related to osteopathic principles and practices and OMT application. They also present current and newly-approved medical managements, including biologics and inhaled corticosteroids. This article also includes supplemental videos showcasing OMT techniques for asthma management, which were developed by the authors based on recommendations indicated in the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":7974544,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Transcranial Doppler detection of vertebrobasilar vasospasm following subarachnoid hemorrhage.\nTranscranial Doppler sonography is of established value in the detection and monitoring of middle cerebral artery vasospasm. Little information exists on the utility of transcranial Doppler for detection of posterior circulation vasospasm. Cerebral angiography and conventional hand-held transcranial Doppler sonography were compared to determine sensitivity and specificity of transcranial Doppler for detection of vertebral and basilar artery vasospasm. Of 59 consecutive subarachnoid hemorrhage patients with transcranial Doppler angiogram correlations, 42 underwent posterior circulation angiography to evaluate 64 vertebral arteries and 42 basilar arteries during the period of risk for vasospasm and had technically adequate transcranial Doppler examinations within 24 hours of the angiogram. A mean flow velocity of 60 cm\/s and above was indicative of both vertebral and basilar artery vasospasm. For the vertebral artery, there were 7 true-positive test results, 42 true-negatives, 6 false-positives (unknown cause in 3, increased collateral flow in 1, adjacent vessel vasospasm in 1, hyperperfusion in 1), and 9 false-negatives (anatomic in 7, operator error in 2). Sensitivity was 44% and specificity was 87.5%. For the basilar artery, there were 10 true-positives, 23 true-negatives, 6 false-positives (unknown cause in 4, hyperemia\/hyperperfusion in 1, increased collateral flow in 1), and 3 false-negatives (operator error in 2, tortuous vessel course in 1). Sensitivity was 76.9% and specificity was 79.3%. When the diagnostic criterion was changed to > or = 80 cm\/s (vertebral artery) and > or = 95 cm\/s (basilar artery), all false-positive results were eliminated (specificity and positive predictive value, 100%). Our data suggest that transcranial Doppler has good specificity for the detection of vertebral artery vasospasm and good sensitivity and specificity for the detection of basilar artery vasospasm. Transcranial Doppler is highly specific (100%) for vertebral and basilar artery vasospasm when flow velocities are > or = 80 and > or = 95 cm\/s, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":1767584,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"Structure and morphogenesis of Dugbe virus (Bunyaviridae, Nairovirus) studied by immunogold electron microscopy of ultrathin cryosections.\nWe have studied the structure and morphogenesis of Dugbe (DUG) virus (Bunyaviridae, Nairovirus) in cultured porcine kidney (PS) cells and a tick cell line (Ra 243) using immunogold electron microscopy. DUG virus is a tickborne arbovirus, considered to be a low health hazard, that is antigenically and genetically related to Crimean Congo haemorrhagic fever (CCHF) virus (Marriott et al., 1990). We have investigated the maturation and intracellular transport of DUG virus particles as a model for other more pathogenic nairoviruses using monoclonal antibodies for immunogold labelling of ultrathin cryosections and immunofluorescence techniques. The spherical DUG virus particle measures about 90 nm in diameter, with a 5 nm thick membrane covered by 5-7 nm long projections or \"spikes\". These projections form hollow cylindrical morphological units, about 5 nm in diameter. DUG virus infection caused only a slight cytopathogenic effect in mammalian cells and none in tick cells. DUG virus particles assembled by budding from the Golgi complex, where the DUG virus glycoprotein G1 accumulated in vesicles originating from Golgi cisternae. The nucleocapsid protein N accumulated in scattered foci throughout the cytoplasm, and this appears to be related to the limited maturation of DUG virus particles that occurred. The reduced number of budding virus particles observed in tick cells was correlated with the reduced cytopathology observed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23299471,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Finite-element modeling of intrastromal ring segment implantation into a hyperelastic cornea.\nIntrastromal corneal-ring segments (ICRSs) are applied to improve highly distorted vision in keratoconic, myopic, and astigmatic patients. Selections of ICRS geometry and position are primarily based on empirical nomograms. We developed a finite-element model (FEM) predicting the corneal response to different ICRS geometries in normal and keratoconic corneas. A two-dimensional FEM was built in proprietary software (ANSYS-APDL), consisting of hyperelastic ocular tissues (cornea, limbus, sclera) and a triangular\/hexagonal ICRS of poly(methyl methacrylate). An incrustation model was developed considering the local material addition and rigidity increase at the ICRS position and also for the triangular ICRS the geometric difference between its base (plane) and corneal tunnel (parallel to corneal surface). Different ICRS heights (150-350 \u03bcm) and optical zones (4.4-6.6 mm) were simulated. An axis-symmetric model of keratoconus was studied, where corneal elasticity was decreased locally. ICRS GEOMETRY (HEIGHT AND OPTICAL ZONE) HAD A SIGNIFICANT INFLUENCE ON CORNEAL POWER: changes from 4.08 to -17.7 diopters (D) (healthy)\/3.31 to -20.5 D (keratoconic) were observed. Central corneal thickness was predicted to increase by up to 38.5 \u03bcm (healthy)\/97.9 \u03bcm (keratoconic). Spherical aberration also changed upon ICRS implantation. The protrusion of the posterior cornea behind the rings was well predicted. The model confirmed the clinically reported trends on the effect of ring geometry. FEM is a powerful tool to study the corneal response to ICRS implantation. The combination of FEM with individual biomechanical properties and geometry of patients holds promise to increase the predictability of ICRS surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":10586895,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mycobacterium ulcerans infection (Buruli ulcer): first reported case in a traveler.\nA chronic, painless sore developed over a 2-month period on the left calf of a Canadian man traveling for 8 months in Africa. A presumptive diagnosis of a Mycobacterium spp. infection was made despite initially negative biopsy and culture results, after failure of several courses of anti-bacterial antibiotics. Mycobacterium ulcerans was eventually isolated and the lesion progressed despite treatment with multiple anti-mycobacterial agents. The lesion finally responded to wide and repeated excision, aggressive treatment with anti-mycobacterial antibiotics, and split-thickness skin grafting. The isolation and treatment of this unusual organism are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":7657800,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2015-18":1,"unknown":7}}},"text":"Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.\nIt was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat\/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat\/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat\/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat\/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and\/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.","subset":"pubmed_abstract"} +{"meta":{"pmid":27609457,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Honokiol suppresses pancreatic tumor growth, metastasis and desmoplasia by interfering with tumor-stromal cross-talk.\nThe poor clinical outcome of pancreatic cancer (PC) is largely attributed to its aggressive nature and refractoriness to currently available therapeutic modalities. We previously reported antitumor efficacy of honokiol (HNK), a phytochemical isolated from various parts of Magnolia plant, against PC cells in short-term in vitro growth assays. Here, we report that HNK reduces plating efficiency and anchorage-independent growth of PC cells and suppresses their migration and invasiveness. Furthermore, significant inhibition of pancreatic tumor growth by HNK is observed in orthotopic mouse model along with complete-blockage of distant metastases. Histological examination suggests reduced desmoplasia in tumors from HNK-treated mice, later confirmed by immunohistochemical analyses of myofibroblast and extracellular matrix marker proteins (\u03b1-SMA and collagen I, respectively). At the molecular level, HNK treatment leads to decreased expression of sonic hedgehog (SHH) and CXCR4, two established mediators of bidirectional tumor-stromal cross-talk, both in vitro and in vivo . We also show that the conditioned media (CM) from HNK-treated PC cells have little growth-inducing effect on pancreatic stellate cells (PSCs) that could be regained by the addition of exogenous recombinant SHH. Moreover, pretreatment of CM of vehicle-treated PC cells with SHH-neutralizing antibody abolishes their growth-inducing potential on PSCs. Likewise, HNK-treated PC cells respond poorly to CM from PSCs due to decreased CXCR4 expression. Lastly, we show that the transfection of PC cells with constitutively active IKK\u03b2 mutant reverses the suppressive effect of HNK on nuclear factor-kappaB activation and partially restores CXCR4 and SHH expression. Taken together, these findings suggest that HNK interferes with tumor-stromal cross-talk via downregulation of CXCR4 and SHH and decreases pancreatic tumor growth and metastasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":17296473,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2017-13":1,"2024-22":1,"unknown":11}}},"text":"Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis.\nPrevious studies, such as the Women's Health Initiative, have shown that a low dose of vitamin D did not protect against colorectal cancer, yet a meta-analysis indicates that a higher dose may reduce its incidence. Five studies of serum 25(OH)D in association with colorectal cancer risk were identified using PubMed. The results of all five serum studies were combined using standard methods for pooled analysis. The pooled results were divided into quintiles with median 25(OH)D values of 6, 16, 22, 27, and 37 ng\/mL. Odds ratios were calculated by quintile of the pooled data using Peto's Assumption-Free Method, with the lowest quintile of 25(OH)D as the reference group. A dose-response curve was plotted based on the odds for each quintile of the pooled data. Data were abstracted and analyzed in 2006. Odds ratios for the combined serum 25(OH)D studies, from lowest to highest quintile, were 1.00, 0.82, 0.66, 0.59, and 0.46 (p(trend)<0.0001) for colorectal cancer. According to the DerSimonian-Laird test for homogeneity of pooled data, the studies were homogeneous (chi(2)=1.09, df=4, p=0.90. The pooled odds ratio for the highest quintile versus the lowest was 0.49 (p<0.0001, 95% confidence interval, 0.35-0.68). A 50% lower risk of colorectal cancer was associated with a serum 25(OH)D level > or =33 ng\/mL, compared to < or =12 ng\/mL. The evidence to date suggests that daily intake of 1000-2000 IU\/day of vitamin D(3) could reduce the incidence of colorectal with minimal risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":32286134,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":14}}},"text":"White Matter Microstructure Predicts Focal and Broad Functional Brain Dedifferentiation in Normal Aging.\nVentral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed \"dedifferentiation.\" The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20-89 years, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as fMRI to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure-function relationship became weaker with age and was no longer significant after the age of 70 years. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":18000629,"dup_signals":{"dup_doc_count":24,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":12}}},"text":"Hypothyroidism in children: diagnosis and treatment.\nTo present relevant and updated information on the status of hypothyroidism in the pediatric population (newborn infants to adolescents). Original and review articles and books containing relevant updated data. This review addressed data on the etiopathogeny of hypothyroidism and on the importance of screening for congenital hypothyroidism to assure early diagnosis and treatment of the newborn. We point out the difficulties experienced in the handling of subclinical hypothyroidism; we also address the importance of diagnosing autoimmune Hashimoto's thyroiditis, the high incidence of the disease among adolescents, mainly females, and the occurrence of a severe neurological condition, Hashimoto's encephalopathy. We indicate situations in which severe hypothyroidism may lead to puberty disorders (precocious or delayed puberty) and describe the importance of transcription factors in thyroid embryogenesis. Diagnostic and therapeutic criteria are also addressed. Thyroid hormones are necessary for normal growth and development since fetal life. Insufficient production or inadequate activity on the cellular or molecular level lead to hypothyroidism. These hormones are necessary for the development of the brain in the fetus and in the newborn infant. Neonatologists and pediatricians deal with child development issues in their practice, and many of these issues start during intrauterine life. Currently, with neonatal screening, neonatologists and pediatricians can prevent irreversible damage through early treatment. They should also be alert for dysfunctions such as subclinical hypothyroidism and Hashimoto's thyroiditis, which may provoke damage not only to growth, but also to the neurological and psychological development of these children and adolescents.","subset":"pubmed_abstract"} +{"meta":{"pmid":8424500,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Myocardial perfusion following acute subarachnoid hemorrhage in patients with an abnormal electrocardiogram.\nTo test the hypothesis that acute subarachnoid hemorrhage is associated with abnormal myocardial perfusion, we assessed myocardial blood flow with thallium scintigraphy in 19 patients with a confirmed subarachnoid hemorrhage and an abnormal electrocardiogram. A thallium scan was performed at the bedside of each patient 3 +\/- 2 days (mean +\/- SD) after subarachnoid hemorrhage and subsequently was analyzed both qualitatively and quantitatively. Patients averaged 58 +\/- 13 yr of age and 68% had one or more cardiac risk factors. The neurologic condition of patients on the day of the scan was II (median; range I-V) on the standard 5-point scale of Botterell. Abnormalities on a standard 12-lead electrocardiogram obtained on the same day as the scan consisted of repolarization changes in most patients; 10 had T wave inversions and 8 had nonspecific ST segment changes. Thirty-two percent (n = 6) of patients had an abnormal thallium scan. There were, however, no features of the clinical history, electrocardiogram pattern, or neurologic condition that were associated with a positive scan. For instance, 2 of 4 patients with diffuse deeply inverted T waves had a normal thallium scan, whereas the scan was abnormal in 2 of 8 patients with minor nonspecific electrocardiographic abnormalities. The thallium scan was also positive in neurologically intact (grade I) as well as severely injured (grade V) patients. Thus, abnormal myocardial perfusion and possibly myocardial ischemia occur frequently following subarachnoid hemorrhage, but no specific electrocardiographic characteristic identifies patients with a perfusion abnormality.","subset":"pubmed_abstract"} +{"meta":{"pmid":12562498,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Melatonin effects on bone: experimental facts and clinical perspectives.\nBone formation proceeds through a remodeling process that runs continuously, involving the resorption of old bone by osteoclasts, and the subsequent formation of new bone by osteoblasts. This is controlled by growth factors and cytokines produced in bone marrow microenvironment and by the action of systemic hormones, like parathyroid hormone, estradiol or growth hormone (GH). One candidate for hormonal modulation of osteoblast and osteoclast formation is melatonin. Because circulating melatonin declines with age, its possible involvement in post-menopausal and senescence osteoporosis is considered. This review article discusses early studies on melatonin-bone relationships and recent data that suggest a direct effect of melatonin on bone. Melatonin could act as an autacoid in bone cells as it is present in high quantities in bone marrow, where precursors of bone cells are located. Melatonin dose-dependently augmented proteins that are incorporated into the bone matrix, like procollagen type I c-peptide. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also augmented by melatonin in vitro. Another possible target cell for melatonin is the osteoclast, which degrades bone partly by generating free radicals. Melatonin through its free radical scavenger and antioxidant properties may impair osteoclast activity and bone resorption. At least in one study melatonin was both inhibitory to osteoclastic and osteoblastic cells. Therefore, the documented bone-protecting effect of melatonin in ovariectomized rats can depend in part on the free radical scavenging properties of melatonin. Additionally, melatonin may impair development of osteopenia associated with senescence by improving non-rapid eye movement sleep and restoring GH secretion. Whether melatonin can be used as a novel mode of therapy for augmenting bone mass in diseases deserves to be studied.","subset":"pubmed_abstract"} +{"meta":{"pmid":8557411,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Syringe exchange: HIV prevention, key findings, and future directions.\nHIV among injecting drug users (IDUs) has now been documented in over 60 countries in the world, and there are an additional 40 countries where injecting drug use has been reported including widespread epidemics in Southeast and southern Asia and in Latin America. At present HIV infection is almost always fatal, and there is no promise that a preventive vaccine will become available soon. Given the enormity of the HIV epidemic among IDUs and the critical need to reduce the spread of HIV transmission to and from IDUs, prevention efforts are essential. Syringe-exchange programs have become a major component of HIV prevention strategies in most developed countries and work within the philosophy of harm reduction. Increasing access to sterile syringes has been met with considerable controversy. Opponents of syringe exchange have generally argued that increasing access to sterile syringes would simultaneously increase the number of injecting drug users, increase the frequency of injection for already active IDUs, and appear to \"condone\" an illegal behavior. To date many research studies and four major reviews of syringe exchange literature have been conducted. All studies thus far have shown no increase in illicit drug injection associated with syringe exchanges, and significant decrease in drug risk behaviors.","subset":"pubmed_abstract"} +{"meta":{"pmid":29669565,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":2,"2024-10":2,"unknown":10}}},"text":"Human alveolar macrophages predominately express combined classical M1 and M2 surface markers in steady state.\nAlveolar macrophages (AM) are critical to the homeostasis of the inflammatory environment in the lung. Differential expression of surface markers classifies macrophages to either classically (M1) or alternatively activated (M2). We investigated the phenotype of human alveolar macrophages (AM) in adults living in two different geographical locations: UK and Malawi. We show that the majority of AM express high levels of M1 and M2 markers simultaneously, with the M1\/M2 phenotype being stable in individuals from different geographical locations. The combined M1\/M2 features confer to AM a hybrid phenotype, which does not fit the classic macrophage classification. This hybrid phenotype may confer to alveolar macrophages an ability to quickly switch between M1 or M2 associated functions allowing for appropriate responses to stimuli and tissue environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":28274248,"dup_signals":{"dup_doc_count":27,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":2,"2022-33":1,"2022-27":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-17":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-47":1,"2023-40":1,"2024-26":1,"2024-10":1,"2024-30":1}}},"text":"A Bayesian spatio-temporal model for forecasting the prevalence of antibodies to Ehrlichia species in domestic dogs within the contiguous United States.\nDogs in the United States are hosts to a diverse range of vector-borne pathogens, several of which are important zoonoses. This paper describes factors deemed to be significantly related to the prevalence of antibodies to Ehrlichia spp. in domestic dogs, including climatic conditions, geographical factors, and societal factors. These factors are used in concert with a spatio-temporal model to construct an annual seroprevalence forecast. The proposed method of forecasting and an assessment of its fidelity are described. Approximately twelve million serological test results for canine exposure to Ehrlichia spp. were used in the development of a Bayesian approach to forecast canine infection. Data used were collected on the county level across the contiguous United States from routine veterinary diagnostic tests between 2011-2015. Maps depicting the spatial baseline Ehrlichia spp. prevalence were constructed using Kriging and head-banging smoothing methods. Data were statistically analyzed to identify factors related to antibody prevalence via a Bayesian spatio-temporal conditional autoregressive (CAR) model. Finally, a forecast of future Ehrlichia seroprevalence was constructed based on the proposed model using county-level data on five predictive factors identified at a workshop hosted by the Companion Animal Parasite Council and published in 2014: annual temperature, percentage forest coverage, percentage surface water coverage, population density and median household income. Data were statistically analyzed to identify factors related to disease prevalence via a Bayesian spatio-temporal model. The fitted model and factor extrapolations were then used to forecast the regional seroprevalence for 2016. The correlation between the observed and model-estimated county-by-county Ehrlichia seroprevalence for the five-year period 2011-2015 is 0.842, demonstrating reasonable model accuracy. The weighted correlation (acknowledging unequal sample sizes) between 2015 observed and forecasted county-by-county Ehrlichia seroprevalence is 0.970, demonstrating that Ehrlichia seroprevalence can be forecasted accurately. The forecast presented herein can be an a priori alert to veterinarians regarding areas expected to see expansion of Ehrlichia beyond the accepted endemic range, or in some regions a dynamic change from historical average prevalence. Moreover, this forecast could potentially serve as a surveillance tool for human health and prove useful for forecasting other vector-borne diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":24825393,"dup_signals":{"dup_doc_count":34,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2022-21":1,"2020-45":2,"2020-40":1,"2020-24":1,"2019-18":1,"2019-13":1,"2018-51":1,"2018-47":2,"2018-39":2,"2018-34":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-13":2,"2018-05":2,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2022-27":1,"2024-18":1}}},"text":"A label-free microfluidic assay to quantitatively study antibiotic diffusion through lipid membranes.\nWith the rise in antibiotic resistance amongst pathogenic bacteria, the study of antibiotic activity and transport across cell membranes is gaining widespread importance. We present a novel, label-free microfluidic assay that quantifies the permeability coefficient of a broad spectrum fluoroquinolone antibiotic, norfloxacin, across lipid membranes using the UV autofluorescence of the drug. We use giant lipid vesicles as highly controlled model systems to study the diffusion through lipid membranes. Our technique directly determines the permeability coefficient without requiring the measurement of the partition coefficient of the antibiotic.","subset":"pubmed_abstract"} +{"meta":{"pmid":29425913,"dup_signals":{"dup_doc_count":13}},"text":"Retraction of publications in nursing and midwifery research: A systematic review.\nRates of manuscript retraction in academic journals are increasing. Papers are retracted because of scientific misconduct or serious error. To date there have been no studies that have examined rates of retraction in nursing and midwifery journals. A systematic review of Journal Citation Report listed nursing science journals. The Medline database was searched systematically from January 1980 through July 2017, and www.retractionwatch.com was manually searched for relevant studies that met the inclusion criteria. Two researchers undertook title and abstract and full text screening. Data were extracted on the country of the corresponding author, journal title, impact factor, study design, year of retraction, number of citations after retraction, and reason for retraction. Journals retraction index was also calculated. Twenty-nine retracted papers published in nursing science journals were identified, the first in 2007. This represents 0.029% of all papers published in these journals since 2007. We observed a significant increase in the retraction rate of 0.44 per 10,000 publications per year (95% CI; 0.03-0.84, p = .037). There was a negative association between a journal's retraction index and impact factor with a significant reduction in retraction index of -0.57 for a one-point increase in impact factor (95% CI; -1.05 to -0.09, p = .022). Duplicate publication was the most common reason for retraction (n = 18, 58%). The mean number of citations manuscripts received after retraction was seven, the highest was 52. Most (n = 27, 93.1%) of the retracted papers are still available online (with a watermark indicating they are retracted). Compared to more established academic disciplines, rates of retraction in nursing and midwifery are low. Findings suggest that unsound research is not being identified and that the checks and balances incumbent in the scientific method are not working. In a clinical discipline, this is concerning and may indicate that research that should have been removed from the evidence base continues to influence nursing and midwifery care.","subset":"pubmed_abstract"} +{"meta":{"pmid":26334050,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Identifying Shared Brain Networks in Individuals by Decoupling Functional and Anatomical Variability.\nThe connectivity architecture of the human brain varies across individuals. Mapping functional anatomy at the individual level is challenging, but critical for basic neuroscience research and clinical intervention. Using resting-state functional connectivity, we parcellated functional systems in an \"embedding space\" based on functional characteristics common across the population, while simultaneously accounting for individual variability in the cortical distribution of functional units. The functional connectivity patterns observed in resting-state data were mapped in the embedding space and the maps were aligned across individuals. A clustering algorithm was performed on the aligned embedding maps and the resulting clusters were transformed back to the unique anatomical space of each individual. This novel approach identified functional systems that were reproducible within subjects, but were distributed across different anatomical locations in different subjects. Using this approach for intersubject alignment improved the predictability of individual differences in language laterality when compared with anatomical alignment alone. Our results further revealed that the strength of association between function and macroanatomy varied across the cortex, which was strong in unimodal sensorimotor networks, but weak in association networks.","subset":"pubmed_abstract"} +{"meta":{"pmid":22470238,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":13}}},"text":"Biofilm: A dental microbial infection.\nRecent advances in research technology have allowed researchers to study bacteria in their natural environment. Dental biofilm forms via an ordered sequence of events, resulting in structured and functionally organized species rich microbial community and modern molecular biological techniques have identified about 1000 different bacterial species in the dental biofilm, twice as many as can be cultured. Sites for biofilm formation include all kinds of surfaces: natural materials above and below ground, metals, plastics, medical implant materials-even plant and body tissue. Wherever you find a combination of moisture, nutrients and a surface, you are likely to find biofilm. The biofilm is used to describe the communities of micro-organisms attached to a surface; such microbes are usually spatially organized into three-dimension structure and are enclosed in matrix of extracellular material derived both from the cells themselves and from the environment. Dental biofilm pathogenicity in the oral cavity is magnified by specific biofilm characteristics and modern molecular biological techniques have identified about 1000 different bacterial species in the dental biofilm, twice as many as can be cultured. Adaptation to a biofilm lifestyle involves regulation of a vast set of genes, and the micro-organisms are thus able to optimize phenotypic properties for the particular environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":1429272,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Performance and health of weanling bulls after butorphanol and xylazine administration at castration.\nA total of 268 crossbred, 6- to 9-mo-old, bull calves (214 +\/- 19 kg) were used in two separate 27-d experiments to assess the effects of butorphanol and xylazine administration (BXA) on the subsequent performance and health of beef calves. In each experiment, calves were randomly allotted to four treatment groups: 1) castration with BXA, 2) castration without BXA, 3) no castration with BXA, and 4) no castration without BXA. There were two replicates within each experiment. The intravenous administration of .07 mg\/kg of butorphanol and .02 mg\/kg of xylazine occurred 90 s before tail hold and castration procedures. Calves were placed in a squeeze chute and manually restrained by tail elevation. In Exp. 2, the cattle also were scored for chute activity (on a 1 to 5 scale with 5 being the most active). Cattle were weighed at the beginning and end of the experiment, feed intake was recorded daily, and cattle were monitored daily for respiratory disease. There were no castration x BXA interactions (P greater than .51). Castration reduced (P less than .01) daily gain and gain\/feed and tended (P = .13) to reduce feed intake. The administration of BXA had no effect (P greater than .05) on gain or gain\/feed but did tend (P = .13) to reduce feed intake. No differences (P greater than .45) were observed in morbidity or mortality due to either BXA or castration. Castration and BXA increased (P less than .01) blood cortisol levels on d 3, whereas control animals had reduced cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":30482818,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":17}}},"text":"Reflections on a field across time and space: the emergent medical and health humanities in South Africa.\nIn this paper, we draw on our own cross-cultural experience of engaging with different incarnations of the medical and health humanities (MHH) in the UK and South Africa to reflect on what is distinct and the same about MHH in these locations. MHH spaces, whether departments, programmes or networks, have espoused a common critique of biomedical dualism and reductionism, a celebration of qualitative evidence and the value of visual and performative arts for their research, therapeutic and transformative social potential. However, there have also been differences, and importantly a different 'identity' among some leading South African scholars and practitioners, who have felt that if MHH were to speak from the South as opposed to the North, they would say something quite different. We seek to contextualise our personal reflections on the development of the field in South Africa over recent years within wider debates about MHH in the context of South African academia and practice, drawing in part on interviews conducted by one of the authors with South African researchers and practitioners and our own reflections as 'Northerners' in the 'South'.","subset":"pubmed_abstract"} +{"meta":{"pmid":32273003,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":14}}},"text":"The effect of different antimicrobial treatment regimens on the faecal shedding of ESBL-producing Escherichia coli in horses.\nFourth-generation cephalosporins can select for extended-spectrum \u03b2-lactamase (ESBL)-producing Enterobacteriaceae in horses, but it is unknown to what extent this occurs compared to penicillin\/gentamicin combination treatment. The objective was to evaluate the effect of different antimicrobial treatments on faecal shedding and diversity of ESBL-producing Escherichia coli (ESBL-EC) in horses. Upon hospital admission, 86 horses in need of antimicrobial treatment or prophylaxis were randomly allocated to receive penicillin and gentamicin (PG) or cefquinome (CEF). Untreated horses were included as controls (NOAMD, n = 33). Faecal samples from admission (T1), 3 days after admission (T2), and faecal swabs 28 days after discharge (T3) were cultured selectively. Differences in prevalence (T1, T2, T3) and counts (T1, T2) of ESBL-EC between groups and over time were analysed. On a subset of ESBL-EC isolates, antimicrobial susceptibility testing (n = 45) and whole-genome sequencing followed by SNP-analysis (n = 46) were performed. The prevalence of ESBL-EC at T1 was 12 % with no significant difference between groups. In all groups, significantly higher carriage rates were observed at T2 and T3 compared to T1. Carriage and counts of ESBL-EC at T2 were significantly higher in treated compared to untreated horses. There was no significant difference between PG and CEF at any time points. Despite a large genetic diversity, indistinguishable ESBL clones were observed in different horses over time. In conclusion, antimicrobial treatment and hospitalization increased prevalence and counts of ESBL-EC, and transmission of ESBL-EC in the hospital was suspected. These findings highlight the importance of antimicrobial stewardship and infection control practices in equine medicine.","subset":"pubmed_abstract"} +{"meta":{"pmid":17655355,"dup_signals":{"dup_doc_count":21,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":11}}},"text":"A new class of bioactive and biodegradable soybean-based bone fillers.\nThe reconstruction of large bone defects in periodontal, maxillofacial, and orthopedic surgery relies on the implantation of biomaterials able to support the growth of new tissue. None of the materials currently available is able to combine all the properties required, which are (i) easy handling, (ii) biodegradation, (iii) low immunogenicity, and more importantly, (iv) induction of tissue regeneration. A new class of biodegradable biomaterials has been obtained by simple thermosetting of defatted soybean curd. The final material can be processed into films, porous scaffolds, and granules for different surgical needs. When incubated in physiological solutions the material shows water uptake of 80%, elongation at break of 0.9 mm\/mm, and 25% (w\/w) degradation in 7 days. Soybean-based biomaterial granules are shown to reduce the activity of the monocytes\/macrophages and of the osteoclasts and to induce osteoblast differentiation in vitro, thus demonstrating a bone regeneration potential suitable for many clinical applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":24727244,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"HDAC signaling in neuronal development and axon regeneration.\nThe development and repair of the nervous system requires the coordinated expression of a large number of specific genes. Epigenetic modifications of histones represent an essential principle by which neurons regulate transcriptional responses and adapt to environmental cues. The post-translational modification of histones by chromatin-modifying enzymes histone acetyltransferases (HATs) and histone deacetylases (HDACs) shapes chromatin to adjust transcriptional profiles during neuronal development. Recent observations also point to a critical role for histone acetylation and deacetylation in the response of neurons to injury. While HDACs are mostly known to attenuate transcription through their deacetylase activity and their interaction with co-repressors, these enzymes are also found in the cytoplasm where they display transcription-independent activities by regulating the function of diverse proteins. Here we discuss recent studies that go beyond the traditional use of HDAC inhibitors and have begun to dissect the roles of individual HDAC isoforms in neuronal development and repair after injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":23688472,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"A thermosensitive carrageenan-based polymer: synthesis, characterization and interactions with a cationic surfactant.\nNovel polyelectrolytes were obtained by grafting N-isopropylacrylamide (NIPAM) on the \u03b9-carrageenan (CAR) chain. Two polymers with different grafting degrees were synthesized. The polymers were found to show the lower critical solution temperature (LCST) close to that of PNIPAM. The LCST values were dependent on the concentration of salt and cationic surfactant. The interactions of CAR-graft-PNIPAM with a model cationic surfactant-dodecyltrimethyl ammonium chloride (DTAC) in water and 0.15M NaCl were studied. It was found that both \u03b9-carrageenan and CAR-graft-PNIPAM polymers interact with DTAC. The presence of CAR-graft-PNIPAM in the solution of DTAC induces formation of surfactant aggregates at the critical aggregation concentration much lower than the cmc of the surfactant. Cac increased with ionic strength. The values of cac for CAR-graft-PNIPAM - DTAC system and standard free enthalpy changes attributed to the complexation process were determined. The results obtained for CAR-graft-PNIPAM were compared with these for the non-modified \u03b9-carrageenan. The surfactant interactions with non-modified and grafted polymers were found to be different in nature.","subset":"pubmed_abstract"} +{"meta":{"pmid":1472459,"dup_signals":{"dup_doc_count":78,"dup_dump_count":43,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":3,"2023-23":1,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":3,"2022-21":2,"2022-05":1,"2021-43":2,"2021-39":1,"2021-31":2,"2021-21":2,"2021-17":2,"2021-04":3,"2020-45":1,"2020-40":2,"2020-24":1,"2019-47":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-34":1,"2018-30":2,"2018-22":2,"2018-17":2,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":2,"2017-43":3,"2017-34":3,"2017-26":2,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":2,"2024-22":4,"2024-18":2,"2017-13":2,"2024-30":1}}},"text":"Homologies between enzymes involved in steroid and xenobiotic carbonyl reduction in vertebrates, invertebrates and procaryonts.\nEvidence is reported for the existence of a structurally and functionally related and probably evolutionarily conserved class of membrane-bound liver carbonyl reductases\/hydroxysteroid dehydrogenases involved in steroid and xenobiotic carbonyl metabolism. Carbonyl reduction was investigated in liver microsomes of 8 vertebrate species, as well as in insect larvae total homogenate and in purified 3 alpha-hydroxysteroid dehydrogenase preparations of the procaryont Pseudomonas testosteroni, using the ketone compound 2-methyl-1,2 di-(3-pyridyl)-1-propanone (metyrapone) as substrate. The enzyme activities involved in the metyrapone metabolism were screened for their sensitivity to several steroids as inhibitors. In all fractions tested, steroids of the adrostane or pregnane class strongly inhibited xenobiotic carbonyl reduction, whereas only in the insect and procaryotic species could ecdysteroids inhibit this reaction. Immunoblot analysis with antibodies against the respective microsomal mouse liver metyrapone reductase revealed strong crossrections in all fractions tested, even in those of the insect and the procaryont. A similar crossreaction pattern was achieved when the same fractions were incubated with antibodies against 3 alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni. The mutual immunoreactivity of the antibody species against proteins from vertebrate liver microsomes, insects and procaryonts suggests the existence of structural homologies within these carbonyl reducing enzymes. This is further confirmed by limited proteolysis of purified microsomal mouse liver carbonyl reductase and subsequent analysis of the peptide fragments with antibodies specifically purified by immunoreactivity against this respective crossreactive antigen. These immunoblot experiments revealed a 22 kDa peptide fragment which was commonly recognized by all antibodies and which might represent a conserved domain of the enzyme.","subset":"pubmed_abstract"} +{"meta":{"pmid":29077226,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Species composition of the international shark fin trade assessed through a retail-market survey in Hong Kong.\nThe shark fin trade is a major driver of shark exploitation in fisheries all over the world, most of which are not managed on a species-specific basis. Species-specific trade information highlights taxa of particular concern and can be used to assess the efficacy of management measures and anticipate emerging threats. The species composition of the Hong Kong Special Administrative Region of China, one of the world's largest fin trading hubs, was partially assessed in 1999-2001. We randomly selected and genetically identified fin trimmings (n = 4800), produced during fin processing, from the retail market of Hong Kong in 2014-2015 to assess contemporary species composition of the fin trade. We used nonparametric species estimators to determine that at least 76 species of sharks, batoids, and chimaeras supplied the fin trade and a Bayesian model to determine their relative proportion in the market. The diversity of traded species suggests species substitution could mask depletion of vulnerable species; one-third of identified species are threatened with extinction. The Bayesian model suggested that 8 species each comprised >1% of the fin trimmings (34.1-64.2% for blue [Prionace glauca], 0.2-1.2% for bull [Carcharhinus leucas] and shortfin mako [Isurus oxyrinchus]); thus, trade was skewed to a few globally distributed species. Several other coastal sharks, batoids, and chimaeras are in the trade but poorly managed. Fewer than 10 of the species we modeled have sustainably managed fisheries anywhere in their range, and the most common species in trade, the blue shark, was not among them. Our study and approach serve as a baseline to track changes in composition of species in the fin trade over time to better understand patterns of exploitation and assess the effects of emerging management actions for these animals.","subset":"pubmed_abstract"} +{"meta":{"pmid":2611816,"dup_signals":{"dup_doc_count":18,"dup_dump_count":9,"dup_details":{"curated_sources":6,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2014-52":1,"2014-49":2,"2014-42":3,"2016-44":1}}},"text":"Relative importance of intracellular glutathione peroxidase and catalase in vivo for prevention of peroxidation to the heart.\nThe relative importance in vivo of catalase and the selenoenzyme glutathione peroxidase for protection against peroxidation was assessed in the rat heart. Each of these enzymes was modulated by feeding animals a low selenium diet either unsupplemented or supplemented with 0.5 parts per million of selenium, with or without the catalase inhibitor, 3-amino-1,2,4-triazole, in their drinking water. After 8 weeks, selenium deficient rats had 88% reductions in cytosolic and mitochondrial glutathione peroxidase activities. These reductions were accompanied by increased peroxidation in heart homogenates and mitochondrial suspensions. Since increased mitochondrial peroxidation only occurred when both the cytosolic and mitochondrial glutathione peroxidase activities were compromised, these selenoenzymes appear to work in tandem and reductions in both are a prerequisite for increased peroxidation in this organ. Peroxidation did not occur in aminotriazole treated animals even though cytosolic catalase activity was inhibited by 65-80%. Moreover, inhibition of catalase activity did not exacerbate the level of peroxidation in selenium deficient animals depleted of glutathione peroxidase activity. Because increased peroxidation was only associated with reductions in glutathione peroxidase activity irrespective of catalase activity, the selenoenzyme appears to be more important for detoxification of hydrogen peroxide in the heart.","subset":"pubmed_abstract"} +{"meta":{"pmid":23440447,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Pollution pathways of pharmaceutical residues in the aquatic environment on the island of Mallorca, Spain.\nThis work determines the principal environmental pollution pathways of pharmaceuticals on the island of Mallorca (Spain). The evaluation was made on the basis of the quantification of pharmaceutical residues by liquid chromatography-tandem mass spectrometry in several environmental water samples, including wastewater-treatment plant effluents, municipal solid waste landfill leachates, groundwater (GW), and marine water. An overall set of 19 pharmaceuticals has been identified in the environment of the 27 human pharmaceuticals investigated in this study. WWTP effluents are the main source of discharge of the pharmaceuticals into the aquatic environment. The data indicate that reuse of treated domestic wastewater for irrigation (which supplies some 30 % of the total water demand in Mallorca) contributes to the contamination of GW. In addition, leaching from landfills is identified as another, but minor, possible source of introduction of pharmaceuticals to GW aquifers. Finally, WWTP effluents ending in the Mediterranean Sea, primarily highly urbanized coastal areas, cause pharmaceutical residues to occur in marine water bodies.","subset":"pubmed_abstract"} +{"meta":{"pmid":28132415,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Older people receiving family-based support in the community: a survey of quality of life among users of 'Shared Lives' in England.\nShared Lives (adult placement) is a model of community-based support where an adult who needs support and\/or accommodation moves into or regularly visits the home of an approved Shared Lives carer, after they have been matched for compatibility. It is an established but small service which has been used mainly by people with learning disabilities but which has the potential to offer an alternative to traditional services for some older people. However, there is little research on the outcomes for older users of Shared Lives. This paper presents findings from a survey of 150 older people using Shared Lives support across 10 Shared Lives schemes in England, which took place between June 2013 and January 2014. The aim was to identify outcomes for older users of Shared Lives and compare these to outcomes for older users of other social care services. In the absence of an ideal study design involving randomised allocation, statistical matching was used to generate a comparison group from the Adult Social Care Survey from 2011\/12, with 121 cases matched to 121 Shared Lives cases. The main outcome measures were Social Care-Related Quality of Life (measured by the ASCOT) and overall quality of life. Findings indicated that Shared Lives can deliver good outcomes for older people, particularly for overall quality of life. In comparison to the matched group of older people using other forms of support, there was some evidence that Shared Lives may deliver better outcomes in some aspects of quality of life. Limitations to the research mean, however, that more work is needed to fully understand the role Shared Lives could play in supporting older people.","subset":"pubmed_abstract"} +{"meta":{"pmid":24879635,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Targeting the Warburg effect with a novel glucose transporter inhibitor to overcome gemcitabine resistance in pancreatic cancer cells.\nGemcitabine resistance remains a significant clinical challenge. Here, we used a novel glucose transporter (Glut) inhibitor, CG-5, as a proof-of-concept compound to investigate the therapeutic utility of targeting the Warburg effect to overcome gemcitabine resistance in pancreatic cancer. The effects of gemcitabine and\/or CG-5 on viability, survival, glucose uptake and DNA damage were evaluated in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cell lines. Mechanistic studies were conducted to determine the molecular basis of gemcitabine resistance and the mechanism of CG-5-induced sensitization to gemcitabine. The effects of CG-5 on gemcitabine sensitivity were investigated in a xenograft tumor model of gemcitabine-resistant pancreatic cancer. In contrast to gemcitabine-sensitive pancreatic cancer cells, the resistant Panc-1 and Panc-1(GemR) cells responded to gemcitabine by increasing the expression of ribonucleotide reductase M2 catalytic subunit (RRM2) through E2F1-mediated transcriptional activation. Acting as a pan-Glut inhibitor, CG-5 abrogated this gemcitabine-induced upregulation of RRM2 through decreased E2F1 expression, thereby enhancing gemcitabine-induced DNA damage and inhibition of cell survival. This CG-5-induced inhibition of E2F1 expression was mediated by the induction of a previously unreported E2F1-targeted microRNA, miR-520f. The addition of oral CG-5 to gemcitabine therapy caused greater suppression of Panc-1(GemR) xenograft tumor growth in vivo than either drug alone. Glut inhibition may be an effective strategy to enhance gemcitabine activity for the treatment of pancreatic cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":26491540,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"Poly (3, 4-ethylenedioxythiophene)-ionic liquid coating improves neural recording and stimulation functionality of MEAs.\nIn vivo multi-electrode arrays (MEAs) can sense electrical signals from a small set of neurons or modulate neural activity through micro-stimulation. Electrode's geometric surface area (GSA) and impedance are important for both unit recording and neural stimulation. Smaller GSA is preferred due to enhanced selectivity of neural signal, but it tends to increase electrode impedance. Higher impedance leads to increased electrical noise and signal loss in single unit neural recording. It also yields a smaller charge injection window for safe neural stimulation. To address these issues, poly (3, 4-ethylenedioxythiophene) - ionic liquid (PEDOT-IL) conducting polymers were electrochemically polymerized on the surface of the microelectrodes. The PEDOT-IL coating reduced the electrode impedance modulus by over 35 times at 1 kHz. It also exhibited compelling nanostructure in surface morphology and significant impedance reduction in other physiologically relevant range (100Hz-1000Hz). PEDOT-IL coated electrodes exhibited a Charge Storage Capacity (CSC) that was about 20 times larger than that of bare electrodes. The neural recording performance of PEDOT-IL coated electrodes was also compared with uncoated electrodes and PEDOT-poly (styrenesulfonate) (PSS) coated electrodes in rat barrel cortex (SI). Spontaneous neural activity and sensory evoked neural response were utilized for characterizing the electrode performance. The PEDOT-IL electrodes exhibited a higher unit yield and signal-to-noise ratio (SNR) in vivo. The local field potential recording was benefited from the low impedance PEDOT-IL coating in noise and artifact reduction as well. Moreover, cell culture on PEDOT-IL coating demonstrated that the material is safe for neural tissue and reduces astrocyte fouling. Taken together, PEDOT-IL coating has the potential to benefit neural recording and stimulation electrodes, especially when integrated with novel small GSA electrode arrays designed for high recording density, minimal insertion damage and alleviated tissue reaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":30094168,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":19}}},"text":"Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI.\nClassification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification. Anatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC). The bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.570, p = 0.11). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.646 (p = 0.021). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.680, p = 0.005). FTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.","subset":"pubmed_abstract"} +{"meta":{"pmid":24184713,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Cadence, peak vertical acceleration, and peak loading rate during ambulatory activities: implications for activity prescription for bone health.\nPrevious research has reported peak vertical acceleration and peak loading rate thresholds beneficial to bone mineral density (BMD). Such thresholds are difficult to translate into meaningful recommendations for physical activity. Cadence (steps\/min) is a more readily interpretable measure of ambulatory activity. To examine relationships between cadence, peak vertical acceleration and peak loading rate during ambulation and identify the cadence associated with previously reported bone-beneficial thresholds for peak vertical acceleration (4.9 g) and peak loading rate (43 BW\/s). Ten participants completed 8 trials each of: slow walking, brisk walking, slow running, and fast running. Acceleration data were captured using a GT3\u00d7+ accelerometer worn at the hip. Peak loading rate was collected via a force plate. Strong relationships were identified between cadence and peak vertical acceleration (r = .96, P < .05) and peak loading rate (r = .98, P < .05). Regression analyses indicated cadences of 157 \u00b1 12 steps\/min (2.6 \u00b1 0.2 steps\/s) and 122 \u00b1 10 steps\/min (2.0 \u00b1 0.2 steps\/s) corresponded with the 4.9 g peak vertical acceleration and 43 BW\/s peak loading rate thresholds, respectively. Cadences \u2265 2.0 to 2.6 steps\/s equate to acceleration and loading rate thresholds related to bone health. Further research is needed to investigate whether the frequency of daily occurrences of this cadence is associated with BMD.","subset":"pubmed_abstract"} +{"meta":{"pmid":8329312,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Health, employment, and financial outcomes in workers with occupational asthma.\nTo study the health, employment, and financial outcome of occupational asthma. A follow study of workers with confirmed occupational asthma. A specialist occupational lung disease clinic. All workers had a diagnosis of occupational asthma made at least one year earlier. Diagnosis was confirmed by serial peak expiratory flow measurement, specific bronchial provocation testing, or specific immunology. Respiratory symptoms, medication, pulmonary function, employment state, and financial position. 112 of a total of 140 eligible workers were followed up. 32% of patients remained exposed to the causative agent. These workers had more symptoms at follow up than those removed and a greater number were taking inhaled steroids. Continued exposure was also associated with a fall in % predicted forced expiratory volume in one second (FEV1) of 3% compared with that at presentation. Their median loss of annual income due to occupational asthma was 35%. Those removed from exposure were worse off financially (median loss 54% of annual income), had fewer respiratory symptoms than the group who remained exposed, and their % predicted FEV1 had improved by 4.6%. Statutory compensation and that obtained by common law suits did not match the loss of earnings due to the development of occupational asthma. Of the workers removed from exposure, those who no longer complained of breathlessness had been diagnosed significantly earlier after the onset of their first symptom (48 v 66 months, p = 0.001) and had a significantly higher FEV1 at presentation (90% v 73% predicted, p = 0.008) compared with those who were still breathless. They had developed symptoms earlier after first exposure (48 v 66 months, p > 0.05) and had been removed from exposure sooner (eight v 12 months, p > 0.05). Removal from exposure after diagnosis of occupational asthma is beneficial in terms of symptoms and lung function, but is associated with a loss of income. Early diagnosis is important for symptomatic improvement after removal from exposure. Inadequate compensation may contribute to the workers' decision to remain exposed after diagnosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29228016,"dup_signals":{"dup_doc_count":28,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2021-04":2,"2020-45":2,"2020-29":1,"2020-16":2,"2020-05":4,"2019-51":3,"2019-47":1,"2019-43":1,"2019-39":1,"2019-30":1,"2019-09":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2021-49":1}}},"text":"Prevalence and molecular profiling of Epstein Barr virus (EBV) among healthy blood donors from different nationalities in Qatar.\nThe Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis. EBV is highly prevalent lymphotropic herpesvirus and has been linked to several malignancies. Transmission is generally by oral secretions, but can be through blood transfusions and organ transplantations. This study aimed to determine the seroprevalence, viremia rates, and circulating genotypes of EBV in healthy blood donors in Qatar. Blood samples from 673 blood donors of different nationalities residing in Qatar (mainly Qatar, Egypt, Syria, Jordan, Pakistan, and India) were collected and tested for anti-EBV capsid (VCA; IgG & IgM), nuclear (EBNA; IgG), and early (EA-D; IgG) antigens. Avidity testing was determined when active infection was suspected. DNA was extracted from the buffy coat and subjected to EBV-DNA quantification using qRT-PCR. Genotyping was performed using nested-PCR targeting EBV-EBNA2 gene, and phylogeny by sequence analysis of the LMP-1 gene. 97.9% (673\/659) of the samples were seropositive as indicated by the presence VCA-IgG, while 52.6% (354\/673) had detectible EBV-DNA. EBV seroprevalence and viremia rates increased significantly with age. Genotyping of 51 randomly selected samples showed predominance of Genotype 1 (72.5%, 37\/51) as compared to genotype 2 (3.5%), and mixed infections were detected in 4% of the samples. Sub-genotyping for these samples revealed that the Mediterranean strain was predominant (65.3%), followed by B95.8 prototype and North Carolina strains (12.2% each), and China1 strain (6%). As a first study to evaluate EBV infection in highly diverse population in Qatar, where expatriates represent more than 85% of the population, our results indicated high seroprevalence and viremia rate of EBV in different nationalities, with genotype 1 and Mediterranean strain being predominant. Clinical significance of these finding have not been investigated and shall be evaluated in future studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":30295070,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Artificial Intelligence-Based Breast Cancer Nodal Metastasis Detection: Insights Into the Black Box for Pathologists.\nNodal metastasis of a primary tumor influences therapy decisions for a variety of cancers. Histologic identification of tumor cells in lymph nodes can be laborious and error-prone, especially for small tumor foci. To evaluate the application and clinical implementation of a state-of-the-art deep learning-based artificial intelligence algorithm (LYmph Node Assistant or LYNA) for detection of metastatic breast cancer in sentinel lymph node biopsies. Whole slide images were obtained from hematoxylin-eosin-stained lymph nodes from 399 patients (publicly available Camelyon16 challenge dataset). LYNA was developed by using 270 slides and evaluated on the remaining 129 slides. We compared the findings to those obtained from an independent laboratory (108 slides from 20 patients\/86 blocks) using a different scanner to measure reproducibility. LYNA achieved a slide-level area under the receiver operating characteristic (AUC) of 99% and a tumor-level sensitivity of 91% at 1 false positive per patient on the Camelyon16 evaluation dataset. We also identified 2 \"normal\" slides that contained micrometastases. When applied to our second dataset, LYNA achieved an AUC of 99.6%. LYNA was not affected by common histology artifacts such as overfixation, poor staining, and air bubbles. Artificial intelligence algorithms can exhaustively evaluate every tissue patch on a slide, achieving higher tumor-level sensitivity than, and comparable slide-level performance to, pathologists. These techniques may improve the pathologist's productivity and reduce the number of false negatives associated with morphologic detection of tumor cells. We provide a framework to aid practicing pathologists in assessing such algorithms for adoption into their workflow (akin to how a pathologist assesses immunohistochemistry results).","subset":"pubmed_abstract"} +{"meta":{"pmid":17948793,"dup_signals":{"dup_doc_count":20,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2015-18":3,"2015-11":3,"2015-06":3,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":4}}},"text":"Identification of volatile\/semivolatile products derived from chemical remediation of cis-1,3-dichloropropene by thiosulfate.\nThe prevalent use of soil fumigants has resulted in air pollution in some agricultural regions. Our previous research showed that application of thiosulfate fertilizers at the soil surface may offer an effective and economical approach to reduce the emission of halogenated fumigants via a chemical remediation process. In this fumigant emission-reduction strategy, volatile 1,3-dichloropropene (1,3-D) reacts with thiosulfate to generate a nonvolatile Bunte salt (thiosulfate derivative of 1,3-D). However, the decomposition of the Bunte salt may be associated with the production of perceptible odors. This study investigated the stability of this reaction product in different environmental media. Hydrolysis experiments demonstrated that the thiosulfate derivative was relatively stable in neutral and moderately acidic aqueous solutions. In contrast, the thiosulfate derivative was readily converted to a dialkyl disulfide via a base hydrolysis process in pH 10 buffer solution. In a strongly acidic solution, a mercaptan and a dialkyl disulfide compound were detected as two primary hydrolysis products. In soil, this initial reaction product underwent a series of biotic conversions to generate several volatile or semivolatile organic sulfur compounds. The formation and distribution of four volatile\/semivolatile products in the air and soil were detected in different soils treated with the thiosulfate derivative of 1,3-D. This study indicated that odors occurring in soil treated with halogenated fumigants and thiosulfate fertilizers might arise from the generation and release of these and other volatile\/semivolatile organic sulfur products. The environmental fate and effects of such volatile\/semivolatile sulfur compounds should be considered in the application of sulfur-containing fertilizers in fumigated fields.","subset":"pubmed_abstract"} +{"meta":{"pmid":17236500,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A microsurgical study of the anatomy and course of the ophthalmic artery and its possibly dangerous anastomoses.\nThe authors studied the microsurgical anatomy of the ophthalmic artery (OphA), paying particular attention to its possibly dangerous anastomoses with the middle meningeal artery (MMA). The microsurgical anatomy of the OphA and its anastomoses with the MMA were studied in 14 vessels from seven adult cadaveric heads. The origination order of the OphA branches varies in relation to whether the artery, along its intraorbital course, crosses above or below the optic nerve (ON). The central retinal artery is the first branch to course from the OphA when it crosses over the ON, and it is the second branch to course from the OphA when the artery crosses under the ON. Anastomoses between branches of the MMA and the OphA were present in the majority of the specimens examined. Detailed knowledge of the microanatomy of the OphA and recognition of anastomoses between the external carotid artery and the OphA are critically important in avoiding disastrous complications during endovascular procedures.","subset":"pubmed_abstract"} +{"meta":{"pmid":3319478,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"[Liver apudoma simulating cystic liver].\nA 36-year-old man in otherwise good general condition and with completely normal laboratory results suffered from right upper abdominal pain. Hepatomegaly was diagnosed as due to cystic liver disease after ultrasound, computed tomography and magnetic resonance imaging. Recurrent abdominal pain continued over several months. Open liver biopsy eventually revealed trabecular-tubular carcinoma (APUDoma). Silver reaction was positive in many tumour cells. Electronmicroscopy demonstrated membrane-bound granules typical for endocrine cells. Immunohistological examinations of various hormones and of neurone-specific enolase were negative, but repeatedly measured high serum levels of pancreatic polypeptide and of beta-HCG nonetheless suggested an endocrine tumour. This case demonstrates that nonparasitic cystic changes in the liver, especially multiple ones, should have a firm diagnosis established by invasive means. Endocrine tumours can be mistaken for polycystic liver disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":15760288,"dup_signals":{"dup_doc_count":28,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2017-13":1,"2015-06":3,"2014-10":1,"2013-48":3,"2013-20":3,"2024-18":1,"unknown":14}}},"text":"Economic causes and consequences of obesity.\nObesity is not only a health but also an economic phenomenon. This chapter (a) examines underlying economic causes, such as technological advancements, behind the obesity epidemic; (b) describes economic consequences of obesity, including increasing obesity-related medical expenditures; and (c) discusses the role of government in combating the obesity epidemic. Because of the high costs of obesity, and the fact that the majority of these costs are financed by taxpayers, there is a clear motivation for government to try to reduce these costs. However, because obesity may result from poor information and addictive behavior and\/or as a result of living in an increasingly obesogenic environment, interventions will need to be multifaceted to ensure the best chance of success.","subset":"pubmed_abstract"} +{"meta":{"pmid":32352147,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Deep brain stimulation modulates directional limbic connectivity in obsessive-compulsive disorder.\nDeep brain stimulation is effective for patients with treatment-refractory obsessive-compulsive disorder. Deep brain stimulation of the ventral anterior limb of the internal capsule rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects, we studied functional interactions within the affective amygdala circuit. We compared resting state functional MRI data during chronic stimulation versus 1 week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test-retest effects. Imaging data were analysed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following deep brain stimulation was associated with reduced amygdala-insula functional connectivity. Directional connectivity analysis revealed that deep brain stimulation increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of obsessive-compulsive disorder, and suggest a neural systems model through which negative mood and anxiety are modulated by stimulation of the ventral anterior limb of the internal capsule for obsessive-compulsive disorder and possibly other psychiatric disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":9950239,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":14}}},"text":"Independent and joint effects of family history and lifestyle on colorectal cancer risk: implications for prevention.\nIt has been suggested that, for a substantial proportion of \"sporadic\" colorectal cancers (CRCs), inheritance determines individual susceptibility and that lifestyle determines which susceptible individuals express cancer. Because the genetic basis of this inherited susceptibility remains undefined, we used family history of the disease as a proxy for a genetic predisposition to examine its interactions with a variety of lifestyle factors in a large population-based case-control study of CRC. The subjects were 698 male and 494 female Japanese, Caucasian, Filipino, Hawaiian, and Chinese patients diagnosed with CRC in Hawaii during 1987-1991 and 1192 population controls matched to cases on age, sex, and ethnicity. Fourteen percent of the cases and 6% of the controls reported a family history of CRC among parents or siblings. After adjusting for other covariates, significant interactions with family history were found for beef and ethanol intakes in males (P = 0.03). Relative to men without a family history and whose intake fell in the lower third, odds ratios (ORs) for CRC for men with a family history and in the upper tertile of intake were 10.8 [95% confidence interval (CI), 4.2-27.6] and 7.5 (CI, 3.1-18.2) for beef and ethanol, respectively. The corresponding ORs for men without a family history and in the upper tertile were 1.5 (CI, 1.0-2.3) and 1.4 (CI, 1.0-1.9), respectively. No interactions were detected in women. Using a summary measure of lifestyle, we found that family history was not associated with CRC among men who were at the lower-risk tertile for all of the lifestyle risk factors. In contrast, the OR for men with a family history and at the higher-risk tertile for all of the lifestyle variables was 11.7 (CI, 5.8-23.9). In the absence of a family history, this OR was 4.8 (CI, 3.2-7.2). These data suggest that family history increases the risk of sporadic CRC in men mainly through its interaction with lifestyle exposures, primarily a high beef and ethanol intake, and are consistent with recent reports of effect modifications of dietary associations by metabolic genes. Computation of population attributable risks also suggested that a comprehensive reduction in exposure to lifestyle risk factors--and more specifically to ethanol and beef for individuals with a familial predisposition for the disease--may have a large beneficial effect on CRC incidence.","subset":"pubmed_abstract"} +{"meta":{"pmid":23005087,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":2,"unknown":11}}},"text":"Nonequilibrium thermodynamics in sheared hard-sphere materials.\nWe combine the shear-transformation-zone (STZ) theory of amorphous plasticity with Edwards' statistical theory of granular materials to describe shear flow in a disordered system of thermalized hard spheres. The equations of motion for this system are developed within a statistical thermodynamic framework analogous to that which has been used in the analysis of molecular glasses. For hard spheres, the system volume V replaces the internal energy U as a function of entropy S in conventional statistical mechanics. In place of the effective temperature, the compactivity X=\u2202V\/\u2202S characterizes the internal state of disorder. We derive the STZ equations of motion for a granular material accordingly, and predict the strain rate as a function of the ratio of the shear stress to the pressure for different values of a dimensionless, temperature-like variable near a jamming transition. We use a simplified version of our theory to interpret numerical simulations by Haxton, Schmiedeberg, and Liu, and in this way are able to obtain useful insights about internal rate factors and relations between jamming and glass transitions.","subset":"pubmed_abstract"} +{"meta":{"pmid":35610270,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":3,"unknown":11}}},"text":"Competent immune responses to SARS-CoV-2 variants in older adults following two doses of mRNA vaccination.\nAging is associated with a reduced magnitude of primary immune responses to vaccination. mRNA-based SARS-CoV-2 vaccines have shown efficacy in older adults but virus variant escape is still unclear. Here we analyze humoral and cellular immunity against an early-pandemic viral isolate and compare that to the P.1 (Gamma) and B.1.617.2 (Delta) variants in two cohorts (<50 and >55 age) of mRNA vaccine recipients. We further measure neutralizing antibody titers for B.1.617.1 (Kappa) and B.1.595, with the latter SARS-CoV-2 isolate bearing the spike mutation E484Q. Robust humoral immunity is measured following second vaccination, and older vaccinees manifest cellular immunity comparable to the adult group against early-pandemic SARS-CoV-2 and more recent variants. More specifically, the older cohort has lower neutralizing capacity at 7-14 days following the second dose but equilibrates with the younger cohort after 2-3 months. While long-term vaccination responses remain to be determined, our results implicate vaccine-induced protection in older adults against SARS-CoV-2 variants and inform thinking about boost vaccination.","subset":"pubmed_abstract"} +{"meta":{"pmid":12435556,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"Gender inequalities, intimate partner violence and HIV preventive practices: findings of a South African cross-sectional study.\nThe aim of the paper is to investigate associations between a range of markers of gender inequity, including financial, psychological and physical violence, and two proximal practices in HIV prevention, namely discussion of HIV between partners and the woman suggesting condom use. The paper presents an analysis of data from a cross-sectional study of a representative sample of women from three South African Provinces which was primarily undertaken as an epidemiological study of gender-based violence. A multi-stage sampling design was used with clusters sampled with probability proportional to number of households. Households were randomly selected from within clusters. One randomly selected woman aged 18-49 years was interviewed in each selected home. One thousand three hundred and six women were interviewed (90.3% of eligible women). One thousand one hundred sixty four women had a partner in the previous year and were asked questions related to HIV prevention and gender inequalities in the relationship. The results indicate that discussion of HIV was significantly positively associated with education, living in Mpumalanga Province, the man being a migrant, the woman having multiple partners in the past year and having no confidante. It was significantly negatively associated with living in the Northern Province, the relationship being poor and there being a substantial age difference between partners. The woman suggesting condom use was significantly positively associated with her education, her having multiple partners, domestic violence prior to the past year and financial abuse. It was negatively associated with the relationship being poor. We conclude that this suggests that some indicators of gender inequalities are significantly associated with discussion of HIV and condom use but the direction of association found was both positive and negative. This highlights the need for a more nuanced understanding of gender inequalities and their relationship to HIV risk. Suggestions for key research questions are made.","subset":"pubmed_abstract"} +{"meta":{"pmid":28280833,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Improving the capacity of lithium-sulfur batteries by tailoring the polysulfide adsorption efficiency of hierarchical oxygen\/nitrogen-functionalized carbon host materials.\nThe use of monolithic carbons with structural hierarchy and varying amounts of nitrogen and oxygen functionalities as sulfur host materials in high-loading lithium-sulfur cells is reported. The primary focus is on the strength of the polysulfide\/carbon interaction with the goal of assessing the effect of (surface) dopant concentration on cathode performance. The adsorption capacity - which is a measure of the interaction strength between the intermediate lithium polysulfide species and the carbon - was found to scale almost linearly with the nitrogen level. Likewise, the discharge capacity of lithium-sulfur cells increased linearly. This positive correlation can be explained by the favorable effect of nitrogen on both the chemical and electronic properties of the carbon host. The incorporation of additional oxygen-containing surface groups into highly nitrogen-functionalized carbon helped to further enhance the polysulfide adsorption efficiency, and therefore the reversible cell capacity. Overall, the areal capacity could be increased by almost 70% to around 3 mA h cm-2. We believe that the design parameters described here provide a blueprint for future carbon-based nanocomposites for high-performance lithium-sulfur cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":22227987,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"High proportion of false-positive Clostridium difficile enzyme immunoassays for toxin A and B in pediatric patients.\nTo determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity. Nested case-control. Two tertiary care pediatric hospitals. As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive\/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays. Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%-7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii. Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.","subset":"pubmed_abstract"} +{"meta":{"pmid":17685827,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Primary care provider turnover and quality in managed care organizations.\nTo examine the association between primary care provider turnover in managed care organizations and measures of member satisfaction and preventive care. Retrospective cohort study of a national sample of 615 managed care organizations that reported HEDIS data to the National Committee for Quality Assurance from 1999 through 2001. Multivariable hierarchical regression modeling was used to evaluate the association between health plan primary care provider turnover rate and member satisfaction and preventive care measures, including childhood immunization, well-child visits, cholesterol, diabetes management, and breast and cervical cancer screening, adjusting for patient and organizational characteristics, time, and repeated measures. The median primary care provider turnover rate was 7.1% (range, 0%-53.3%). After adjustment for plan characteristics, health plans with higher primary care provider turnover rates had significantly lower measures of member satisfaction, including overall rating of healthcare (P < .01). A 10% higher primary care provider turnover rate was associated with 0.9% fewer members rating high overall satisfaction with healthcare. Health plans with higher provider turnover rates also had lower rates of preventive care, including childhood immunization (P = .045), well-child visits (P = .002), cholesterol screening after cardiac event (P = .042), and cervical cancer screening (P = .024). For example, a 10% higher primary care provider turnover was associated with a 2.7% lower rate of child-members receiving well-child visits in the first 15 months of life. Primary care provider turnover is associated with several measures of care quality, including aspects of member satisfaction and preventive care. Future studies should evaluate whether interventions to reduce primary care provider turnover can improve quality of care and patient outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19476971,"dup_signals":{"dup_doc_count":44,"dup_dump_count":24,"dup_details":{"curated_sources":1,"2022-49":1,"2022-21":1,"2021-49":1,"2021-31":2,"2020-24":1,"2020-10":1,"2019-22":1,"2018-51":1,"2018-47":4,"2018-43":1,"2018-34":2,"2018-30":2,"2018-26":7,"2018-22":2,"2018-17":2,"2018-13":2,"2018-09":3,"2018-05":3,"2017-51":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-26":1,"2023-50":1}}},"text":"Who made the Aurignacian and other early Upper Paleolithic industries?\nThe Aurignacian is typically taken as a marker of the spread of anatomically modern humans into Europe. However, human remains associated with this industry are frustratingly sparse and often limited to teeth. Some have suggested that Neandertals may, in fact, be responsible for the Aurignacian and the earliest Upper Paleolithic industries. Although dental remains are frequently considered to be taxonomically undiagnostic in this context, recent research shows that Neandertals possess a distinct dental pattern relative to anatomically modern humans. Even so, it is rare to find mandibles or maxillae that preserve all or most of their teeth; and, the probability of correctly identifying individuals represented by only a few teeth or a single tooth is unknown. We present a Bayesian statistical approach to classifying individuals represented exclusively by teeth into two possible groups. The classification is based on dental trait frequencies and sample sizes for 'known' samples of 95 Neandertals and 63 Upper Paleolithic modern humans. In a cross validation test of the known samples, 89% of the Neandertals and 89% of the Upper Paleolithic modern humans were classified correctly. We then classified an 'unknown' sample of 52 individuals: 34 associated with Aurignacian or other (non-Ch\u00e2telperronian) early Upper Paleolithic industries, 15 associated with the Ch\u00e2telperronian, and three unassociated. Of the 34 early Upper Paleolithic-associated individuals, 29 were assigned to modern humans, which is well within the range expected (95% of the time 26-33) with an 11% misclassification rate for an entirely modern human sample. These results provide some of the strongest evidence that anatomically modern humans made the Aurignacian and other (non-Ch\u00e2telperronian) early Upper Paleolithic industries.","subset":"pubmed_abstract"} +{"meta":{"pmid":18063684,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells.\nProgesterone induces decidual transformation of estrogen-primed human endometrial stromal cells (hESCs), critical for implantation and maintenance of pregnancy, through activation of many signaling pathways involving protein kinase A and signal transducer and activator of transcription (STAT)-5. We have previously shown that kinase activation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase is closely associated with decidualization and that SRC is indispensable for maximal decidualization in mice. To address whether SRC kinase activity is essential for decidualization in humans, hESCs were infected with adenoviruses carrying enhanced green fluorescent protein alone (Ad-EGFP), a kinase-inactive dominant-negative mutant (Ad-SRC\/K295R), or an inactive autophosphorylation site mutant (Ad-SRC\/Y416F). The cells were cultured in the presence of estradiol and progesterone (EP) to induce decidualization and subjected to RT-PCR, immunoblot, and ELISA analyses. Ad-EGFP-infected hESCs exhibited decidual transformation and up-regulation of decidualization markers including IGF binding protein 1 and prolactin in response to 12-d treatment with EP. In contrast, hESCs infected with Ad-SRC\/K295R remained morphologically fibroblastoid without production of IGF binding protein 1 and prolactin even after EP treatment. Ad-SRC\/Y416F displayed similar but less inhibitory effects on decidualization, compared with Ad-SRC\/K295R. During decidualization, STAT5 was phosphorylated on tyrosine 694, a well-known SRC phosphorylation site. Phosphorylation was markedly attenuated by Ad-SRC\/K295R but not Ad-EGFP. These results indicate that the SRC-STAT5 pathway is essential for decidualization of hESCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":8211164,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Altered fluid transport across airway epithelium in cystic fibrosis.\nIn cystic fibrosis (CF), absence or dysfunction of a phosphorylation-regulated chloride channel [CF transmembrane conductance regulator (CFTR)] leads to the loss or reduction of chloride secretion into the airways. Active sodium absorption is also increased in CF, and both of these ion transport changes could alter fluid transport across the airways. Under baseline conditions, cultured human airway epithelia from normal individuals absorbed fluid, and this absorption was increased in epithelia from patients with CF. In normal and CF epithelial cultures fluid absorption was inhibited by amiloride. Adenosine 3',5'-monophosphate stimulated fluid secretion in normal epithelial cultures but not in cultures from individuals with CF. In contrast, fluid secretion induced by nucleotide triphosphates (uridine triphosphate or adenosine triphosphate) was unaltered in cultures of epithelia from patients with CF, suggesting an approach to the treatment of CF.","subset":"pubmed_abstract"} +{"meta":{"pmid":28782064,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The extraordinary impact of Michael Faraday on chemistry and related subjects.\nBiographers of Michael Faraday, as well as many dictionaries of science, often describe him as a physicist, which he certainly was. But he was also an astonishingly effective chemist: in fact, he was the Fullerian Professor of Chemistry (at the Royal Institution, RI) from 1834 until the time of his death in August, 1867. To mark the sesquicentenary of his passing, this editorial, by one of his distant successors as Director and Fullerian Professor at the RI, focuses on Faraday's output and influence as a scientist.","subset":"pubmed_abstract"} +{"meta":{"pmid":12845627,"dup_signals":{"dup_doc_count":11}},"text":"The development of optimal pathological assessment of sentinel lymph nodes for melanoma.\n1158 sentinel lymph nodes (SLNs), excised from patients with primary cutaneous melanoma, were assessed pathologically using histology with immunohistochemistry (IHC) on all nodes, and RT-PCR for Mart-1 and tyrosinase on 55 nodes. RT-PCR was compared with the histology and IHC assessed on the same nodes. The evaluation of progressively more detailed protocols for histology and IHC modulated by the RT-PCR results led to a procedure that consistently detects metastases in 34% of patients submitted to SLN biopsy for cutaneous melanomas with a vertical growth phase and a mean thickness of 2.02 mm (range 0.25, with regression, to 19 mm). As this technique is virtually free of false positives and produces only a marginally lower detection rate than RT-PCR, which was subject to false positives of 7% in our study, it is suggested that this extended protocol should be the basis on which further evaluation of the place of RT-PCR in SLN assessment takes place. The evolved protocol described here has been adopted by the EORTC as the standard procedure for pathological handling of sentinel lymph nodes for melanoma when SLN status is a criterion in their clinical trials or studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":18057375,"dup_signals":{"dup_doc_count":34,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2022-49":1,"2022-27":1,"2021-39":1,"2020-50":1,"2020-40":1,"2020-16":1,"2019-30":1,"2018-47":1,"2018-39":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2023-23":1}}},"text":"Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.\nThe GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28005604,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-14":3,"2023-06":1,"2022-21":1,"2021-43":1,"2021-25":1,"2020-50":1,"2020-40":1,"2020-16":1,"2024-22":2,"2024-10":1,"2024-26":1}}},"text":"Trends in net survival from colon cancer in six European Latin countries: results from the SUDCAN population-based study.\nColon cancer represents a major public health issue. The aim of the SUDCAN collaborative study was to compare the net survival from colon cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and provide trends in net survival and dynamics of the excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. Results were reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modeling strategy. There were few differences between countries in age-standardized net survivals (2000-2004). During the 2000-2004 period, the 5-year net survival ranged between 57 (Spain and Portugal) and 61% (Belgium and Switzerland). The age-standardized survival at 1 and 5 years after diagnosis increased between 1992 and 2004. This increase was observed at ages 60 and 70, but was less marked at 80. This increase was linked to a marked decrease in the excess mortality rate between 1992 and 2004 until 18 months after diagnosis. Beyond this period, the decrease in the excess mortality rates among countries was modest and nearly the same whatever the year of diagnosis. There were minor differences in survival after colon cancer between European Latin countries. A considerable improvement in the 5-year net survival was observed in all countries, but the gain was mainly limited to the first 18 months after diagnosis. Further improvements are expected through the implementation of mass screening programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":10986060,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Late effects of treatment in survivors of childhood acute myeloid leukemia.\nTo investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). Of 77 survivors (median follow-up duration, 16. 7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z: score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z: score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":19716177,"dup_signals":{"dup_doc_count":25,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2019-43":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2020-24":1,"2024-26":4,"2024-22":4,"2024-18":2,"2017-13":1,"2024-30":1}}},"text":"Drosophila lamin mutations cause melanotic mass formation and lamellocyte differentiation.\nThe fruit fly immune system is a valuable model for invertebrate and innate immunity. Cellular immune reactions in Drosophila are of great interest, especially the molecular genetic mechanisms of hemocyte differentiation and the encapsulation of foreign bodies. Here we report that changes in the lamin gene cause melanotic masses. These darkened clusters of cells result from autoimmune-like encapsulation of self-tissue, as shown by the presence in lam larvae of lamellocytes, effector hemocytes that appear in larvae following wounding or parasitization. Lamins thus affect immunity in Drosophila, and lam mutations can serve as genetic tools to dissect cellular immune signaling and effector pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":27136617,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":1,"2021-39":1,"2020-40":1,"2020-34":1,"2020-29":1,"2019-51":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2023-40":1,"2024-22":1}}},"text":"Is economic valuation of ecosystem services useful to decision-makers? Lessons learned from Australian coastal and marine management.\nEconomic valuation of ecosystem services is widely advocated as being useful to support ecosystem management decision-making. However, the extent to which it is actually used or considered useful in decision-making is poorly documented. This literature blindspot is explored with an application to coastal and marine ecosystems management in Australia. Based on a nation-wide survey of eighty-eight decision-makers representing a diversity of management organizations, the perceived usefulness and level of use of economic valuation of ecosystem services, in support of coastal and marine management, are examined. A large majority of decision-makers are found to be familiar with economic valuation and consider it useful - even necessary - in decision-making, although this varies across groups of decision-makers. However, most decision-makers never or rarely use economic valuation. The perceived level of importance and trust in estimated dollar values differ across ecosystem services, and are especially high for values that relate to commercial activities. A number of factors are also found to influence respondent's use of economic valuation. Such findings concur with conclusions from other studies on the usefulness and use of ESV in environmental management decision-making. They also demonstrate the strength of the survey-based approach developed in this application to examine this issue in a variety of contexts.","subset":"pubmed_abstract"} +{"meta":{"pmid":23744480,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Challenges and advances in the field of self-assembled membranes.\nSelf-assembled membranes are of vital importance in biological systems e.g. cellular and organelle membranes, however, more focus is being put on synthetic self-assembled membranes not only as an alternative for lipid membranes but also as an alternative for lithographic methods. More investigations move towards self-assembly processes because of the low-cost preparations, structural self-regulation and the ease of creating composite materials and tunable properties. The fabrication of new smart membrane materials via self-assembly is of interest for delivery vessels, size selective separation and purification, controlled-release materials, sensors and catalysts, scaffolds for tissue engineering, low dielectric constant materials for microelectronic devices, antireflective coatings and proton exchange membranes for polymer electrolyte membrane fuel cells. Polymers and nanoparticles offer the most straightforward approaches to create membrane structures. However, alternative approaches using small molecules or composite materials offer novel ultra-thin membranes or multi-functional membranes, respectively. Especially, the composite material membranes are regarded as highly promising since they offer the possibility to combine properties of different systems. The advantages of polymers which provide elastic and flexible yet stable matrices can be combined with nanoparticles being either inorganic, organic or even protein-based which offers pore-size control, catalytic activity or permeation regulation. It is therefore believed that at the interface of different disciplines with each offering different materials or approaches, the most novel and interesting membrane structures are going to be produced. The combinations and approaches presented in this review offer non-conventional self-assembled membrane materials which exhibit a high potential to advance membrane science and find more practical applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":23434780,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Selective mobilization of saturated fatty acids in isolated adipocytes of hibernating 13-lined ground squirrels Ictidomys tridecemlineatus.\nFatty acids are not mobilized from adipocyte triacylglycerols uniformly but rather some are preferentially mobilized while others are preferentially retained. In many vertebrate species, the pattern of differential mobilization is determined by the physical and chemical properties of each fatty acid. Fatty acids with shorter chains and more double bonds tend to be more readily mobilized than others, a pattern observed both in whole-animal studies and in isolated adipocytes. Several hibernating species seem to break this pattern, however, and retain 18:2\u03c96 (linoleic acid) while mobilizing saturated fatty acids such as 18:0. We sought to confirm this pattern in adipocytes of a hibernator, the 13-lined ground squirrel Ictidomys tridecemlineatus, and to investigate mobilization patterns for the first time at hibernation temperature. We isolated adipocytes from summer active and winter torpid squirrels and incubated them with 1 \u03bcM norepinephrine at 4\u00b0C (7 h) and 37\u00b0C (90 min). We measured the proportion of each fatty acid in the adipose tissue and in the buffer at the end of incubation. Patterns of mobilization were similar in both seasons and incubation temperatures. Saturated fatty acids (18:0 and 16:0) were highly mobilized relative to the average, while some unsaturated fatty acids (notably, 18:1\u03c99 and 18:2\u03c96) were retained. We conclude that hibernators have unique mechanisms at the level of adipose tissue that preferentially mobilize saturated fatty acids. Additionally, we found that adipocytes from hibernating squirrels produced more glycerol than those from summer squirrels (regardless of temperature), indicating a higher lipolytic capacity in hibernating squirrels.","subset":"pubmed_abstract"} +{"meta":{"pmid":24847198,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Encoding of forelimb forces by corticospinal tract activity in the rat.\nIn search of a solution to the long standing problems encountered in traditional brain computer interfaces (BCI), the lateral descending tracts of the spinal cord present an alternative site for taping into the volitional motor signals. Due to the convergence of the cortical outputs into a final common pathway in the descending tracts of the spinal cord, neural interfaces with the spinal cord can potentially acquire signals richer with volitional information in a smaller anatomical region. The main objective of this study was to evaluate the feasibility of extracting motor control signals from the corticospinal tract (CST) of the rat spinal cord. Flexible substrate, multi-electrode arrays (MEA) were implanted in the CST of rats trained for a lever pressing task. This novel use of flexible substrate MEAs allowed recording of CST activity in behaving animals for up to three weeks with the current implantation technique. Time-frequency and principal component analyses (PCA) were applied to the neural signals to reconstruct isometric forelimb forces. Computed regression coefficients were then used to predict isometric forces in additional trials. The correlation between measured and predicted forces in the vertical direction averaged across six animals was 0.67 and R (2) value was 0.44. Force regression in the horizontal directions was less successful, possibly due to the small amplitude of forces. Neural signals above and near the high gamma band made the largest contributions to prediction of forces. The results of this study support the feasibility of a spinal cord computer interface (SCCI) for generation of command signals in paralyzed individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":19588342,"dup_signals":{"dup_doc_count":44,"dup_dump_count":4,"dup_details":{"curated_sources":6,"2024-26":1,"2024-22":1,"2017-13":1,"2024-30":1,"unknown":34}}},"text":"WITHDRAWN: Ergonomic and physiotherapeutic interventions for treating work-related complaints of the arm, neck or shoulder in adults.\nConservative interventions such as physiotherapy and ergonomic adjustments (such as keyboard adjustments or ergonomic advice) play a major role in the treatment of most work-related complaints of the arm, neck or shoulder (CANS). This systematic review aims to determine whether conservative interventions have a significant impact on outcomes for work-related CANS in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2005) and Cochrane Rehabilitation and Related Therapies Field Specialised Register (March 2005), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2005), PubMed, EMBASE, CINAHL, AMED and reference lists of articles. The date of the last search was March 2005. No language restrictions were applied. We included randomised controlled trials studying conservative interventions (e.g. exercises, relaxation, physical applications, biofeedback, myofeedback and work-place adjustments) for adults suffering CANS. Two authors independently selected trials from the search yield, assessed the methodological quality using the Delphi list, and extracted relevant data. We pooled data or, in the event of clinical heterogeneity or lack of data, we used a rating system to assess levels of evidence. For this update we included six additional studies; 21 trials in total. Seventeen trials included people with chronic non-specific neck or shoulder complaints, or non-specific upper extremity disorders. Over 25 interventions were evaluated; five main subgroups of interventions could be determined: exercises, manual therapy, massage, ergonomics, and energised splint. Overall, the quality of the studies was poor.In 14 studies a form of exercise was evaluated, and contrary to the previous review we now found limited evidence about the effectiveness of exercises when compared to massage and conflicting evidence when exercises are compared to no treatment. In this update there is limited evidence for adding breaks during computer work; massage as add-on treatment on manual therapy, manual therapy as add-on treatment on exercises; and some keyboard designs when compared to other keyboards or placebo in participants with carpal tunnel syndrome. There is limited evidence for the effectiveness of keyboards with an alternative force-displacement of the keys or an alternative geometry, and limited evidence for the effectiveness of exercises compared to massage; breaks during computer work compared to no breaks; massage as an add-on treatment to manual therapy; and manual therapy as an add-on treatment to exercises.","subset":"pubmed_abstract"} +{"meta":{"pmid":4049442,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Racial differences in the distribution of posterior circulation occlusive disease.\nWe compared clinical and arteriographic features in 27 white and 24 black patients with symptomatic posterior circulation occlusive disease. The degree of arterial stenosis was measured independently by two examiners at 12 sites within the vertebrobasilar territory. Racial comparisons were made based upon the distribution of extra- and intracranial occlusive lesions and symptomatic sites of the lesions. White patients had significantly more angina pectoris, more lesions of the origin of the left vertebral artery and more high grade lesions of the extracranial vertebral arteries. Black patients had significantly higher mean diastolic blood pressure, more diabetes mellitus, more lesions of the distal basilar artery, more high grade lesions of intracranial branch vessels and more symptomatic intracranial branch disease. Race was found to be the only factor increasing the risk of intracranial posterior circulation occlusive disease. Knowledge of the contribution of race to the distribution of posterior circulation lesions will help guide evaluation and treatment strategies for patients with vertebrobasilar occlusive disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":22722679,"dup_signals":{"dup_doc_count":22,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-49":2,"2022-40":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-24":1,"2019-22":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":2,"2018-09":1,"2017-47":1,"2017-39":1}}},"text":"Newborn lamb as a new model for studying gastroesophageal reflux.\nWe aimed to determine whether the newborn lamb at term is a valid model for studying gastroesophageal reflux. Seven bottle-fed lambs, ages 2 to 3 days, underwent esophageal multichannel intraluminal impedance-pH monitoring (MII-pH). A total of 196 reflux episodes were recorded, including 73% alkaline and 27% weakly acidic. No acid refluxes were observed. Median bolus clearance time was 4 seconds (3; 5.5), and proximal reflux extent was 35% (26). This first report of MII-pH in the newborn mammal sets the foundations for future studies with physiological and clinical relevance to human neonates.","subset":"pubmed_abstract"} +{"meta":{"pmid":19734220,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Induction of alloantigen-specific human T regulatory cells by vasoactive intestinal peptide.\nT regulatory cells (Tregs) are instrumental in the maintenance of immunological tolerance. Although Treg-based immunotherapy proved successful in preclinical autoimmunity and transplantation, factors involved in the generation of human Ag-specific Tregs are poorly known. In this study, we show that treatment of human CD4+CD25- T cells with the cytokine-like vasoactive intestinal peptide (VIP) during in vitro stimulation induces an anergic FoxP3+CD4+CD25(high) T cell subset displaying potent regulatory activities against allospecific effector T cells, irrespective of the presence of naturally occurring Tregs. VIP-tolerant T cells are characterized by incapability to progress to S phase of cell cycle during stimulation with HLA-disparate APCs by negatively affecting the synthesis of cyclins D3 and E, the activation of cyclin-dependent kinases (cdk)2 and cdk4, and the down-regulation of the cdk inhibitor p27(kip1). VIP interaction with the type 1 VIP receptor and subsequent activation of cAMP\/protein kinase A pathway play a major role in all these effects. Moreover, VIP-tolerant T cells protect against acute graft-vs-host disease in a mouse model of allogeneic bone marrow transplantation. The infusion of VIP-tolerant T cells together with the graft significantly reduces the clinical signs and mortality rate typical of the graft-vs-host disease. These effects are mediated by impairing allogeneic haplotype-specific responses of donor CD4+ cells in the transplanted animals. Our results suggest that including alloantigen-specific VIP-generated Tregs may be a valuable tool in therapeutic interventions to promote immunotolerance toward allogeneic grafts and to reduce the need of general immunosuppressive drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":22189194,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Ergogenic dietary aids for the elderly.\nErgogenic dietary aids might be useful adjunctive therapy to enhance the effects of exercise in the elderly, who lose physical function with age. Many such aids have been tested in athletes and untrained younger persons in laboratory and athletic performance settings, with positive results, although not all studies have demonstrated benefit. Some substances have been tested in the elderly, including creatine, caffeine, \u03b2-hydroxy-\u03b2-methylbutyrate, ubiquinone, and carnitine. The published medical evidence for the use of these substances is considered in this review article. All studies have involved a few subjects for a short period. Studies of creatine alone or together with exercise in old persons have yielded mixed results. These studies have confirmed that creatine in older individuals, as in younger individuals, can increase the short-term capacity to perform quick, repeated episodes of intense activity. An investigation of caffeine has suggested that in older as in younger individuals, caffeine increases endurance but may not improve other parameters of exercise capacity. Evidence has implied \u03b2-hydroxy-\u03b2-methylbutyrate can increase the ability to perform certain short-term activities requiring strength, but not others. Carnitine has been reported to decrease fatigue and increase endurance in older persons. An investigation of ubiquinone has shown no benefit. Further testing has involved the combinations of agents, such as creatine and caffeine, and combinations of \u03b2-hydroxy-\u03b2-methylbutyrate, showing some small improvements in physical function. Future research with these and potentially other combinations over a longer duration will be needed to establish the safety and efficacy of ergogenic dietary aids.","subset":"pubmed_abstract"} +{"meta":{"pmid":31512599,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Expression of mycolic acid in response to stress and association with differential clinical manifestations of tuberculosis.\nExtrapulmonary tuberculosis (EPTB), accounting for 10%-20% of all cases of tuberculosis (TB), is known to be determined by host immunity. However, the contribution of bacterial factors to the development of EPTB has not been studied extensively. Mycolic acids are predominant lipids constituting the cell wall of Mycobacterium tuberculosis, and keto-mycolic acid is involved in the synthesis of foamy macrophages that facilitate persistence of mycobacteria. Hence, the present study was performed to gain an insight into variable expression of mycolic acids in clinical isolates of M. tuberculosis under stress. Pansusceptible clinical isolates of M. tuberculosis from patients with lymph node TB (LNTB) (n = 10) and pulmonary TB (PTB) (n = 10) were subjected to sodium dodecyl sulfate (SDS) stress, and the expression of mycolic acid and its biosynthetic genes was compared. Any bias arising due to the genotype of the clinical isolates was ruled out by performing single-nucleotide polymorphism cluster grouping (SCG), wherein no significant difference was observed between the SCG of LNTB or PTB isolates. The expression of \u03b1-mycolic acid during the exposure to SDS was high in 7\/10 (70%) LNTB and 6\/10 (60%) PTB isolates. Methoxy mycolic acid showed an increased expression in 7\/10 (70%) LNTB isolates and 4\/10 (40%) PTB isolates. Increased expression of keto-mycolic acid on exposure with SDS was observed in 8\/10 (80%) M. tuberculosis LNTB and 3\/10 (30%) PTB isolates. Similarly, the mycolic acid synthesis gene, fas, was upregulated more in LNTB isolates than PTB isolates in vitro and ex vivo. SCG 3a was the most common SCG observed in 40% (8\/20) of the isolates, followed by SCG 3b in 30% (6\/20) of the isolates. There was no significant difference between the SCG of LNTB or PTB isolates. The higher expression of keto-mycolic acid in LNTB as against PTB isolates may indicate better survival in LNTB isolates in the presence of stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":18252861,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":2,"unknown":13}}},"text":"High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia.\nTo determine whether aberrantly activated tyrosine kinases other than FLT3 and c-KIT contribute to acute myeloid leukemia (AML) pathogenesis, we used high-throughput (HT) DNA sequence ana-lysis to screen exons encoding the activation loop and juxtamembrane domains of 85 tyrosine kinase genes in 188 AML patients without FLT3 or c-KIT mutations. The screen identified 30 nonsynonymous sequence variations in 22 different kinases not previously reported in single-nucleotide polymorphism (SNP) databases. These included a novel FLT3 activating allele and a previously described activating mutation in MET (METT1010I). The majority of novel sequence variants were stably expressed in factor-dependent Ba\/F3 cells. Apart from one FLT3 allele, none of the novel variants showed constitutive phosphorylation by immunoblot analysis and none transformed Ba\/F3 cells to factor-independent growth. These findings indicate the majority of these alleles are not potent tyrosine kinase activators in this cellular context and that a significant proportion of nonsynonymous sequence variants identified in HT DNA sequencing screens may not have functional significance. Although some sequence variants may represent SNPs, these data are consistent with recent reports that a significant fraction of such sequence variants are \"passenger\" rather than \"driver\" alleles and underscore the importance of functional assessment of candidate disease alleles.","subset":"pubmed_abstract"} +{"meta":{"pmid":19684272,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Drinking behavior in nursery pigs: determining the accuracy between an automatic water meter versus human observers.\nAssimilating accurate behavioral events over a long period can be labor-intensive and relatively expensive. If an automatic device could accurately record the duration and frequency for a given behavioral event, it would be a valuable alternative to the traditional use of human observers for behavioral studies. Therefore, the objective of this study was to determine the accuracy in the time spent at the waterer and the number of visits to the waterer by individually housed nursery pigs between human observers scoring video files using Observer software (OBS) and an automatic water meter Hobo (WM, control) affixed onto the waterline. Eleven PIC USA genotype gilts (22 +\/- 2 d of age; 6.5 +\/- 1.4 kg of BW) were housed individually in pens with ad libitum access to a corn-based starter ration and one nipple waterer. Behavior was collected on d 0 (day of weaning), 7, and 14 of the trial using 1 color camera positioned over 4 attached pens and a RECO-204 DVR at 1 frame per second. For the OBS method, 2 experienced observers recorded drinking behavior from the video files, which was defined as when the gilt placed her mouth over the nipple waterer. Data were analyzed using nonparametric methods and the general linear model and regression procedures in SAS. The experimental unit was the individual pen housing 1 gilt. The GLM model included the method of observation (WM vs. OBS) and time (24 h) as variables, and the gilt nested within method was used as the error term. Gilts consumed more water (P = 0.04) on d 14 than on d 0. The time of day affected (P < 0.001) the number of visits and the time spent at the waterer regardless of the method. However, the OBS method underestimated (P < 0.001) the number of visits to the waterer (3.48 +\/- 0.33 visits\/h for OBS vs. 4.94 +\/- 0.33 for WM) and overestimated (P < 0.001) the time spent at the waterer (22.6 +\/- 1.46 s\/h for OBS vs. 13.9 +\/- 1.43 for WM) compared with WM. The relationship between the 2 methods for prediction of time spent at the waterer and number of visits made by the gilts was weak (R(2) = 0.56 and 0.69, respectively). Collectively, these data indicate that the use of the traditional OBS method for quantifying drinking behavior in pigs can be misleading. Quantifying drinking behavior and perhaps other behavioral events via the OBS method must be more accurately validated.","subset":"pubmed_abstract"} +{"meta":{"pmid":29665863,"dup_signals":{"dup_doc_count":11}},"text":"Effect of combined treatment with bisphosphonate and vitamin D on atherosclerosis in patients with systemic lupus erythematosus: a propensity score-based analysis.\nPremature atherosclerosis is one of the major complications of systemic lupus erythematosus (SLE). Recently, the biological linkage between atherosclerosis and osteoporosis has garnered much attention. The aim of this study is to explore correlation between the development of atherosclerosis and anti-osteoporotic treatment. Consecutive patients with SLE (n = 117) who underwent carotid ultrasonography were retrospectively analyzed using propensity scoring. Of the 117 patients, 42 (36%), 27 (23%), and 30 (26%) were receiving bisphosphonates and vitamin D (BP + VD), bisphosphonates alone, or vitamin D alone, respectively. Low bone mineral density was more frequent, and carotid plaque was less prevalent in the BP + VD group compared with other treatment groups. Age (OR = 1.57) and BP + VD treatment (OR = 0.24) were shown by multivariate analysis to be associated with the presence of carotid plaque. In all strata divided using the propensity score, carotid plaque was statistically significantly less prevalent (p = 0.015, Mantel-Haenszel test) in the BP + VD group relative to the other treatment groups. Combined treatment with bisphosphonate and vitamin D may have a role in preventing atherosclerosis in patients with SLE.","subset":"pubmed_abstract"} +{"meta":{"pmid":7014108,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"The role of vitamin D metabolites in the osteomalacia of renal disease.\nOsteomalacia is commonly found in patients with severe renal impairment. Its aetiology is multifactional and not simply due to deficient production of active metabolites of vitamin D. Decreased availability of calcium and phosphate and the accumulation of aluminium is some dialysis-treated patients are also important aetiological factors. The treatment of osteomalacia depends, in part, upon its accurate diagnosis, and identifying and reversing the underlying cause.","subset":"pubmed_abstract"} +{"meta":{"pmid":31540988,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Using the Endogenous CRISPR-Cas System of Heliobacterium modesticaldum To Delete the Photochemical Reaction Center Core Subunit Gene.\nIn Heliobacterium modesticaldum, as in many Firmicutes, deleting genes by homologous recombination using standard techniques has been extremely difficult. The cells tend to integrate the introduced plasmid into the chromosome by a single recombination event rather than perform the double recombination required to replace the targeted locus. Transformation with a vector containing only a homologous recombination template for replacement of the photochemical reaction center gene pshA produced colonies with multiple genotypes, rather than a clean gene replacement. To address this issue, we required an additional means of selection to force a clean gene replacement. In this study, we report the genetic structure of the type I-A and I-E CRISPR-Cas systems from H. modesticaldum, as well as methods to leverage the type I-A system for genome editing. In silico analysis of the CRISPR spacers revealed a potential consensus protospacer adjacent motif (PAM) required for Cas3 recognition, which was then tested using an in vivo interference assay. Introduction of a homologous recombination plasmid that carried a miniature CRISPR array targeting sequences in pshA (downstream of a naturally occurring PAM sequence) produced nonphototrophic transformants with clean replacements of the pshA gene with \u223c80% efficiency. Mutants were confirmed by PCR, sequencing, optical spectroscopy, and growth characteristics. This methodology should be applicable to any genetic locus in the H. modesticaldum genome.IMPORTANCE The heliobacteria are the only phototrophic members of the largely Gram-positive phylum Firmicutes, which contains medically and industrially important members, such as Clostridium difficile and Clostridium acetobutylicum Heliobacteria are of interest in the study of photosynthesis because their photosynthetic system is unique and the simplest known. Since their discovery in the early 1980s, work on the heliobacteria has been hindered by the lack of a genetic transformation system. The problem of introducing foreign DNA into these bacteria has been recently rectified by our group; however, issues still remained for efficient genome editing. The significance of this work is that we have characterized the endogenous type I CRISPR-Cas system in the heliobacteria and leveraged it to assist in genome editing. Using the CRISPR-Cas system allowed us to isolate transformants with precise replacement of the pshA gene encoding the main subunit of the photochemical reaction center.","subset":"pubmed_abstract"} +{"meta":{"pmid":22459122,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Interactions between genome-wide significant genetic variants and circulating concentrations of insulin-like growth factor 1, sex hormones, and binding proteins in relation to prostate cancer risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.\nGenome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":23988999,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Resident participation in cadaveric temporal bone dissection correlates with improved performance on a standardized skill assessment instrument.\nIncreasing numbers of cadaveric temporal bone (CTB) dissection translates to improved scores on a timed microdissection of a CTB. Recent literature regarding resident education has focused on virtual learning. However, advocates for virtual temporal bone drilling admit that there is not yet a substitute for drilling a CTB. Retrospective review of resident performance on a standardized instrument during a timed microdissection of CTBs. Resident performance on the graded dissection was compared with the number of CTBs drilled during the year. Graded performance was also compared with the total number of CTBs dissected over 4 years of residency. Faculty assessed intraoperative skill of the senior residents. These rankings were compared with the number of CTBs drilled. Comparisons were made using Pearson's and Spearman's correlations. Comparison of test scores from the most recent resident year to the number of CTBs drilled during the corresponding year correlated well (r = 0.41, p = 0.002). The correlation between the score during the highest year of training and the cumulative number of CTB drilled during residency was even stronger (r = 0.604, p = 0.005). Faculty rankings correlated well comparing general surgical skills with TB surgical skills (r = 0.655, p = 0.008). Comparing faculty rankings of TB surgical skill with the number of CTB drilled during the final year of residency yielded a negative correlation (r = -0.8) but was not significant (p = 0.1). Greater exposure to CTB dissection correlates with improved scoring on a standardized instrument. Residents who struggle with temporal bone surgery tend to use CTB dissection more than those who are more facile.","subset":"pubmed_abstract"} +{"meta":{"pmid":22251819,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-06":1,"2014-10":1,"2013-48":3,"2013-20":2,"2015-11":1,"unknown":3}}},"text":"A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients.\nThe newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF\/MET pathway. Deregulation of HGF\/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients. The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays. Over a mean follow up period of 5.3 (\u00b1 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05). For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.","subset":"pubmed_abstract"} +{"meta":{"pmid":28270721,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2018-17":2,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-30":2,"2017-22":1,"2017-17":1,"2017-13":2}}},"text":"The Hospital at Home program: no place like home.\nThe treatment of children with cancer is associated with significant burden for the entire family. Frequent clinic visits and extended hospital stays can negatively affect quality of life for children and their families. Here, we describe the development of a Hospital at Home program (H@H) that delivers therapy to pediatric hematology, oncology, and blood and marrow transplant (bmt) patients in their homes. The services provided include short infusions of chemotherapy, supportive-care interventions, antibiotics, post-chemotherapy hydration, and teaching. From 2013 to 2015, the H@H program served 136 patients, making 1701 home visits, for patients mainly between the ages of 1 and 4 years. Referrals came from oncology in 82% of cases, from hematology in 11%, and from bmt in 7%. Since inception of the program, no adverse events have been reported. Family surveys suggested less disruption in daily routines and appreciation of specialized care by hematology and oncology nurses. Staff surveys highlighted a perceived benefit of H@H in contributing to early discharge of patients by supporting out-of-hospital monitoring and teaching. The development of a H@H program dedicated to the pediatric hematology, oncology, or bmt patient appears feasible. Our pilot program offers a potential contribution to improvement in patient quality of life and in cost-benefit for parents and the health care system.","subset":"pubmed_abstract"} +{"meta":{"pmid":26325472,"dup_signals":{"dup_doc_count":11}},"text":"Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle.\nThe sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P < 0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin\/MHC, nebulin\/actin, and nebulin\/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres.","subset":"pubmed_abstract"} +{"meta":{"pmid":26016518,"dup_signals":{"dup_doc_count":17,"dup_dump_count":10,"dup_details":{"curated_sources":6,"2023-40":1,"2023-14":2,"2022-33":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2023-50":1,"2024-18":1,"2024-22":1}}},"text":"Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.\nIron-sulfur (Fe-S) clusters function as protein cofactors for a wide variety of critical cellular reactions. In human mitochondria, a core Fe-S assembly complex [called SDUF and composed of NFS1, ISD11, ISCU2, and frataxin (FXN) proteins] synthesizes Fe-S clusters from iron, cysteine sulfur, and reducing equivalents and then transfers these intact clusters to target proteins. In vitro assays have relied on reducing the complexity of this complicated Fe-S assembly process by using surrogate electron donor molecules and monitoring simplified reactions. Recent studies have concluded that FXN promotes the synthesis of [4Fe-4S] clusters on the mammalian Fe-S assembly complex. Here the kinetics of Fe-S synthesis reactions were determined using different electron donation systems and by monitoring the products with circular dichroism and absorbance spectroscopies. We discovered that common surrogate electron donor molecules intercepted Fe-S cluster intermediates and formed high-molecular weight species (HMWS). The HMWS are associated with iron, sulfide, and thiol-containing proteins and have properties of a heterogeneous solubilized mineral with spectroscopic properties remarkably reminiscent of those of [4Fe-4S] clusters. In contrast, reactions using physiological reagents revealed that FXN accelerates the formation of [2Fe-2S] clusters rather than [4Fe-4S] clusters as previously reported. In the preceding paper [Fox, N. G., et al. (2015) Biochemistry 54, DOI: 10.1021\/bi5014485], [2Fe-2S] intermediates on the SDUF complex were shown to readily transfer to uncomplexed ISCU2 or apo acceptor proteins, depending on the reaction conditions. Our results indicate that FXN accelerates a rate-limiting sulfur transfer step in the synthesis of [2Fe-2S] clusters on the human Fe-S assembly complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":29079505,"dup_signals":{"dup_doc_count":13}},"text":"A constitutively-active IKK-complex at the axon initial segment.\nPrevious studies provided evidence for an accumulation of I\u03baB-kinase (IKK) \u03b1\/\u03b2 at the axon initial segment (AIS), a neuronal compartment defined by ankyrin-G expression. Here we explored whether the presence of the IKK-complex at the AIS was associated with the activation of IKK signaling at this site. Proximity-ligation assays (PLAs) using pan-IKK\u03b1\/\u03b2, phospho-IKK\u03b1\/\u03b2-specific as well as ankyrin-G specific antibodies validated their binding to proximal epitopes in the AIS, while antibodies to other phosphorylated signaling proteins showed no preference for the AIS. Small-hairpin mediated silencing of IKK\u03b2 significantly reduced anti-phospho-IKK\u03b1\/\u03b2-immunoreactivities in the AIS. ank3 gene-deficient cerebellar Purkinje cells also exhibited no phosphorylated IKK\u03b1\/\u03b2 at the proximal region of their axons. Transient ankyrin-G overexpression in PC12 cells augmented NF-\u03baB transactivation in an ankyrin-G death-domain dependent manner. Finally, small molecule inhibitors of IKK-activity, including Aspirin, inhibited the accumulation of activated IKK proteins in the AIS. Our data suggest the existence of a constitutively-active IKK signaling complex in the AIS.","subset":"pubmed_abstract"} +{"meta":{"pmid":20964537,"dup_signals":{"dup_doc_count":34,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":1,"2022-49":1,"2022-40":2,"2022-33":4,"2022-27":2,"2022-05":1,"2021-49":1,"2021-43":4,"2021-10":1,"2020-50":2,"2020-40":1,"2020-34":1,"2020-24":1,"2020-10":1,"2019-47":2,"2024-26":1,"2024-18":1,"2024-30":1}}},"text":"Picbreeder: a case study in collaborative evolutionary exploration of design space.\nFor domains in which fitness is subjective or difficult to express formally, interactive evolutionary computation (IEC) is a natural choice. It is possible that a collaborative process combining feedback from multiple users can improve the quality and quantity of generated artifacts. Picbreeder, a large-scale online experiment in collaborative interactive evolution (CIE), explores this potential. Picbreeder is an online community in which users can evolve and share images, and most importantly, continue evolving others' images. Through this process of branching from other images, and through continually increasing image complexity made possible by the underlying neuroevolution of augmenting topologies (NEAT) algorithm, evolved images proliferate unlike in any other current IEC system. This paper discusses not only the strengths of the Picbreeder approach, but its challenges and shortcomings as well, in the hope that lessons learned will inform the design of future CIE systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":30584681,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-40":3,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2024-10":1,"2024-26":1}}},"text":"Perinatal mortality and morbidity in triplet pregnancy according to chorionicity: systematic review and meta-analysis.\nThe incidence of perinatal mortality and morbidity in triplet pregnancies according to chorionicity is yet to be established. The aim of this systematic review was to quantify perinatal mortality and morbidity in trichorionic triamniotic (TCTA), dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplets. MEDLINE, EMBASE and CINAHL databases were searched in December 2017 for literature published in English describing outcomes of DCTA, TCTA and\/or MCTA triplet pregnancies. Primary outcomes were intrauterine death (IUD), neonatal death, perinatal death (PND) and gestational age at birth. Secondary outcomes comprised respiratory, neurological and infectious morbidity, as well as a composite score of neonatal morbidity. Data regarding outcomes were extracted from the included studies. Random-effects meta-analysis was used to estimate the risk of mortality and morbidity and to compute the difference in gestational age at birth between TCTA and DCTA triplet pregnancies. Nine studies (1373 triplet pregnancies, of which 1062 were TCTA, 261 DCTA and 50 MCTA) were included in the analysis. The risk of PND was higher in DCTA than in TCTA triplet pregnancies (odds ratio (OR), 3.3 (95% CI, 1.3-8.0)), mainly owing to the higher risk of IUD in DCTA triplet pregnancies (OR, 4.6 (95% CI, 1.8-11.7)). There was no difference in gestational age at birth between TCTA and DCTA triplets (mean difference, 1.1 weeks (95% CI, -0.3 to 2.5 weeks); I2 = 85%; P = 0.12). Neurological morbidity occurred in 2.0% (95% CI, 1.1-3.3%) of TCTA and in 11.6% (95% CI, 1.1-40.0%) of DCTA triplets. Respiratory and infectious morbidity affected 28.3% (95% CI, 20.7-36.8%) and 4.2% (95% CI, 2.8-5.9%) of TCTA and 34.0% (95% CI, 21.5-47.7%) and 7.1% (95% CI, 2.7-13.3%) of DCTA triplets, respectively. The incidence of composite morbidity in TCTA and DCTA triplets was 29.6% (95% CI, 21.1-38.9%) and 34.0% (95% CI, 21.5-47.7%), respectively. When translating these figures into a risk analysis, the risk of neurological morbidity (OR, 5.4 (95% CI, 1.6-18.3)) was significantly higher in DCTA than in TCTA triplets, while there was no significant difference in the other morbidities explored. Only one study reported on outcomes of MCTA pregnancies, hence, no formal comparison with the other groups was performed. DCTA triplets are at higher risk of perinatal mortality and morbidity than are TCTA triplets. Copyright \u00a9 2018 ISUOG. Published by John Wiley & Sons Ltd.","subset":"pubmed_abstract"} +{"meta":{"pmid":28950880,"dup_signals":{"dup_doc_count":11}},"text":"Abundant expression of somatic transposon-derived piRNAs throughout Tribolium castaneum embryogenesis.\nPiwi-interacting RNAs (piRNAs) are a class of short (~26-31-nucleotide) non-protein-coding RNAs expressed in the metazoan germline. The piRNA pathway in arthropods is best understood in the ovary of Drosophila melanogaster, where it acts to silence active transposable elements (TEs). Maternal loading of piRNAs in oocytes is further required for the inheritance of piRNA-mediated transposon defence. However, our understanding of the diversity, evolution and function of the piRNA complement beyond drosophilids is limited. The red flour beetle, Tribolium castaneum, is an emerging model organism separated from Drosophila by ~ 350 million years of evolution that displays a number of features ancestral to arthropods, including short germ embryogenesis. Here, we characterize the maternally deposited and zygotically expressed small RNA and mRNA complements throughout T. castaneum embryogenesis. We find that beetle oocytes and embryos of all stages are abundant in heterogeneous ~ 28-nucleotide RNAs. These small RNAs originate from discrete genomic loci enriched in TE sequences and display the molecular signatures of transposon-derived piRNAs. In addition to the maternally loaded primary piRNAs, Tribolium embryos produce secondary piRNAs by the cleavage of zygotically activated TE transcripts via the ping-pong mechanism. The two Tribolium piRNA pathway effector proteins, Tc-Piwi\/Aub and Tc-Ago3, are also expressed throughout the soma of early embryos. Our results show that the piRNA pathway in Tribolium is not restricted to the germline, but also operates in the embryo and may act to antagonize zygotically activated transposons. Taken together, these data highlight a functional divergence of the piRNA pathway between insects.","subset":"pubmed_abstract"} +{"meta":{"pmid":22932701,"dup_signals":{"dup_doc_count":62,"dup_dump_count":38,"dup_details":{"curated_sources":2,"2021-21":1,"2021-10":1,"2021-04":2,"2020-40":1,"2020-16":1,"2019-47":1,"2019-39":2,"2019-30":1,"2019-22":1,"2018-51":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":2,"2017-43":3,"2017-39":2,"2017-34":1,"2017-30":1,"2017-26":2,"2017-22":4,"2017-09":4,"2017-04":2,"2016-50":3,"2016-44":1,"2016-40":4,"2016-36":3,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-40":1,"2021-31":1,"2017-13":2}}},"text":"A VASP-Rac-soluble guanylyl cyclase pathway controls cGMP production in adipocytes.\nThe ubiquitous second messenger cyclic guanosine monophosphate (cGMP) plays an important role in metabolism and promotes brown adipocyte differentiation. We showed that ablation of the gene encoding vasodilator-stimulated phosphoprotein (VASP), a major downstream component of the cGMP signaling cascade, increased cellular cGMP content in brown and white adipocytes and mouse embryonic fibroblasts. VASP-deficient cells showed increased activation of Rac1, which in turn increased the abundance of the cGMP-producing enzyme soluble guanylyl cyclase (sGC), the main receptor for nitric oxide. Consequently, loss of VASP caused increased cGMP concentrations and enhanced brown adipocyte differentiation. Consistent with the in vitro data, we found increased energy expenditure in VASP-deficient mice and exposure to cold triggered enhanced lipolysis and cellular respiration in VASP-deficient brown fat cells. In addition, VASP-deficient mice exhibited increased development of brown-like adipocytes in white fat. Our data revealed that a VASP to Rac to sGC negative feedback loop limited cGMP production, thereby regulating adipogenesis and energy homeostasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":22624215,"dup_signals":{"dup_doc_count":19,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":2,"2017-13":1,"unknown":8}}},"text":"Changes in diatom patch-size distribution and degradation in a spatially self-organized intertidal mudflat ecosystem.\nSelf-organized spatial patterns have been proposed as possible indicators for regime shifts in ecosystems. Until now, this hypothesis has only been tested in drylands. Here, we focus on intertidal mudflats where regular spatial patterns develop in early spring from the interaction between diatom growth and sedimentation but disappear when benthic herbivore abundance increases in early summer, accompanied by a dramatic shift to a bare mudflat. We followed the patch-size distributions of diatom biofilms during this degradation process. As time progressed, we found a temporal change in the spatial configuration occurring simultaneously with the loss of the diatom-sediment feedback. This indicates a gradual failure in time of the self-organization process that underlies regular patterning in this ecosystem. The path to degradation co-occurred with the loss of the larger patches in the ecosystem, which resulted in a decrease of the truncation in the patch-size distribution. Hence, our study in mudflat ecosystems confirms the general hypothesis that spatial patterns can provide important clues about the level of degradation. Nevertheless, our study highlights the need for thorough study about the type of spatial patterns and the nature of the underlying feedbacks before a reliable assessment of ecosystem status can be made, as changes in patch-size distribution differed markedly with those observed in other ecosystems.","subset":"pubmed_abstract"} +{"meta":{"pmid":22533449,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":16}}},"text":"Betaproteobacterial symbionts of the ciliate Euplotes: origin and tangled evolutionary path of an obligate microbial association.\nThe Polynucleobacter-Euplotes association is an obligatory symbiotic system between a monophyletic group of ciliate species belonging to the genus Euplotes and bacteria of the species Polynucleobacter necessarius (Betaproteobacteria). Both organisms are unable to survive independently. Several studies revealed the existence of free-living populations of Polynucleobacter bacteria which are phylogenetically closely related to the endosymbiotic ones, but never share associations with Euplotes in the natural environment. Hence, following the most parsimonious explanation on the origin of the association, this symbiosis should represent a synapomorphic character for the hosts' clade. Nevertheless, phylogenetic analyses performed on an increased number of strains here presented suggest that Euplotes species, during their evolution, recruited Polynucleobacter bacteria as symbionts more than once. Moreover, in three cases, we observed different bacteria as obligate symbionts. These symbionts are the first characterized representatives of a phylogenetic lineage branching in a basal position with respect to the genus Polynucleobacter. The hypothesis that the original obligate symbionts belonged to this newly discovered clade and that, only subsequently, in most cases they have been replaced by Polynucleobacter bacteria recruited from the environment is proposed and discussed. The evolutionary path of this association seems anyway to have been more complex than so far supposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":19394257,"dup_signals":{"dup_doc_count":25,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":16}}},"text":"Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency.\nSpecific mutations in the gene encoding phenylalanine hydroxylase (PAH), located on chromosome 12q22-24.1, are linked to tetrahydrobiopterin (BH4; sapropterin)-responsive phenylketonuria (PKU). Diagnosis is usually done through the newborn screening for PKU, followed by a BH4 loading test. So far, more than 60 mutant alleles, presenting with a substantial residual PAH activity (average approximately 47%), were identified in more than 500 patients worldwide. We investigated the predictive value of BH4-responsive PAH mutations in Croatian population. From a group of 127 PKU patients, 62 were selected (based on the genotype) as potentially BH4-responsive and 39 loaded with BH4 (20 mg\/kg). The overall frequency of BH4-responsiveness (>30% blood phenylalanine reduction within 24 h) was 36% (14 out of 39 patients with 23 different genotypes), significantly less than expected. The best responders were patients with mild hyperphenylalaninemia (4\/4; 100%), followed by mild PKU (8\/9; 89%), and classical PKU (2\/26; 8%). The most common BH(4)-responsive genotypes were p.E390G\/p.R408W and p.P281L\/p.E390G. These genotypes correspond for approximately >30% residual PAH activity. The p.E390G mutation was 100% associated with BH4-responsiveness, regardless of the second allele (p.R408W, p.P281L, p.F55Lfs, p.L249P). With regard to the predicted relative PAH activity of recombinantly expressed mutant alleles, there was a significant (p<0.002) difference between BH4-responders and non-responders. In a general Croatian PKU population, disease-causing mutations were identified on 226 alleles (99%). There were 35 different mutations: 21 missense, 8 splice site, 3 nonsense, 2 single nucleotide deletions, and 1 in-frame deletion. Four mutations are reported for the first time: p.E76D, p.L333P, p.G346E, and IVS8-2A>G. Five mutations accounted for over two-thirds of investigated alleles: p.L48S, p.R261Q, p.P281L, p.E390G, and p.R408W. Thus, the Croatian PKU population seems to be more homogenous than some other Mediterranean or Central European populations. This study reveals the importance of a full genotype for the prediction of BH4-responsiveness. In contrast to previous assumption and with exception of the p.E390G mutation, single allele mutations are not reliable for the selection of potential PKU candidates for pharmacological therapy with BH4.","subset":"pubmed_abstract"} +{"meta":{"pmid":23913003,"dup_signals":{"dup_doc_count":21,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2021-43":1,"2020-29":1,"2019-43":1,"2019-18":1,"2018-47":1,"2018-26":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-49":1,"2024-10":1,"2017-13":1,"2024-22":1}}},"text":"Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice.\nCalcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor \u03b2 (PDGF-R\u03b2) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-R\u03b2. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":23527195,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"2024-18":1,"unknown":6}}},"text":"LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.\nDespite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD) remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6) that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His). LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.","subset":"pubmed_abstract"} +{"meta":{"pmid":32375678,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":15}}},"text":"Ancestry and frequency of genetic variants in the general population are confounders in the characterization of germline variants linked to cancer.\nPediatric high-grade gliomas (pHGGs) are incurable malignant brain cancers. Clear somatic genetic drivers are difficult to identify in the majority of cases. We hypothesized that this may be due to the existence of germline variants that influence tumor etiology and\/or progression and are filtered out using traditional pipelines for somatic mutation calling. In this study, we analyzed whole-genome sequencing (WGS) datasets of matched germlines and tumor tissues to identify recurrent germline variants in pHGG patients. We identified two structural variants that were highly recurrent in a discovery cohort of 8 pHGG patients. One was a ~ 40 kb deletion immediately upstream of the NEGR1 locus and predicted to remove the promoter region of this gene. This copy number variant (CNV) was present in all patients in our discovery cohort (n = 8) and in 86.3% of patients in our validation cohort (n = 73 cases). We also identified a second recurrent deletion 55.7 kb in size affecting the BTNL3 and BTNL8 loci. This BTNL3-8 deletion was observed in 62.5% patients in our discovery cohort, and in 17.8% of the patients in the validation cohort. Our single-cell RNA sequencing (scRNA-seq) data showed that both deletions result in disruption of transcription of the affected genes. However, analysis of genomic information from multiple non-cancer cohorts showed that both the NEGR1 promoter deletion and the BTNL3-8 deletion were CNVs occurring at high frequencies in the general population. Intriguingly, the upstream NEGR1 CNV deletion was homozygous in ~ 40% of individuals in the non-cancer population. This finding was immediately relevant because the affected genes have important physiological functions, and our analyses showed that NEGR1 expression levels have prognostic value for pHGG patient survival. We also found that these deletions occurred at different frequencies among different ethnic groups. Our study highlights the need to integrate cancer genomic analyses and genomic data from large control populations. Failure to do so may lead to spurious association of genes with cancer etiology. Importantly, our results showcase the need for careful evaluation of differences in the frequency of genetic variants among different ethnic groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":6363167,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Anti-beta-cell immunity in insulinopenic diabetic dogs.\nAnti-islet immunity was studied in six spontaneously insulin-dependent diabetic (IDD) dogs, using mouse islets of Langerhans cells as targets, in vitro. Insulinopenia was demonstrated in all dogs by an i.v. glucose tolerance test. A significant lymphocytopenia was detected in the peripheral blood of this diabetic group. Pancreatic tissue from one of these animals was obtained shortly after death and the islets displayed a marked loss in beta cells without significant changes in the other types of islet cells. No insulitis was observed. Circulating mononuclear cells from the diabetic dogs induced an increased basal insulin (IRI) release from islet cells and a suppressed stimulated IRI release. Damage to or depth of beta cells may account for these findings. The stimulated IRI release was also suppressed when islets were incubated with the diabetic sera + complement, while the D-cell response to arginine was not altered, and the A-cell response was reduced but not abolished. A lysis of islet cells in the presence of IDD sera + complement was demonstrated by an increased release of 51Cr from labeled cells. These anomalies were observed neither when complement was heat-inactivated nor in the presence of control sera + complement. Canine IDD may be a new animal model for the study of anti-islet cellular and humoral immunities.","subset":"pubmed_abstract"} +{"meta":{"pmid":8972214,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain.\nPhosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule that is recruited to activated growth factor receptors after growth factor stimulation of cells. Activation of PI 3-kinase results in increased intracellular levels of 3' phosphorylated inositol phospholipids and the induction of signaling responses, including the activation of the protein kinase Akt, which is also known as RAC-PK or PKB. We tested the possibility that the phospholipid products of PI 3-kinase directly mediate the activation of Akt. We have previously described a constitutively active PI 3-kinase, p110, which can stimulate Akt activity. We used purified p110 protein to generate a series of 3' phosphorylated inositol phospholipids and tested whether any of these lipids could activate Akt in vitro. Phospholipid vesicles containing PI3,4 bisphosphate (P2) specifically activated Akt in vitro. By contrast, the presence of phospholipid vesicles containing PI3P or PI3,4,5P3 failed to increase the kinase activity of Akt. Akt could also be activated by synthetic dipalmitoylated PI3,4P2 or after enzymatic conversion of PI3,4,5P3 into PI3,4P2 with the signaling inositol polyphosphate 5' phosphatase SIP. We show that PI3,4P2-mediated activation is dependent on a functional pleckstrin homology domain in Akt, since a point mutation in the pleckstrin homology domain abrogated the response to PI3,4P2. Our findings show that a phospholipid product of PI 3-kinase can directly stimulate an enzyme known to be an important mediator of PI 3-kinase signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":33105650,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":8}}},"text":"Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions.\nContinuous-flow production of liposomes using microfluidic reactors has demonstrated advantages compared to batch methods, including greater control over liposome size and size distribution and reduced reliance on post-production processing steps. However, the use of microfluidic technology for the production of nanoscale vesicular systems (such as liposomes) has not been fully translated to industrial scale yet. This may be due to limitations of microfluidic-based reactors, such as low production rates, limited lifetimes, and high manufacturing costs. In this study, we investigated the potential of millimeter-scale flow reactors (or millireactors) with a serpentine-like architecture, as a scalable and cost-effective route to the production of nanoscale liposomes. The effects on liposome size of varying inlet flow rates, lipid type and concentration, storage conditions, and temperature were investigated. Liposome size (i.e., mean diameter) and size dispersity were characterised by dynamic light scattering (DLS); z-potential measurements and TEM imaging were also carried out on selected liposome batches. It was found that the lipid type and concentration, together with the inlet flow settings, had significant effects on the properties of the resultant liposome dispersion. Notably, the millifluidic reactor was able to generate liposomes with size and dispersity ranging from 54 to 272 nm, and from 0.04 to 0.52 respectively, at operating flow rates between 1 and 10 mL\/min. Moreover, when compared to a batch ethanol-injection method, the millireactor generated liposomes with a more therapeutically relevant size and size dispersity.","subset":"pubmed_abstract"} +{"meta":{"pmid":18301734,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-27":1,"2021-43":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-24":1,"2020-10":1,"2019-47":1,"2014-23":1,"2023-23":1}}},"text":"Baselines and degradation of coral reefs in the Northern Line Islands.\nEffective conservation requires rigorous baselines of pristine conditions to assess the impacts of human activities and to evaluate the efficacy of management. Most coral reefs are moderately to severely degraded by local human activities such as fishing and pollution as well as global change, hence it is difficult to separate local from global effects. To this end, we surveyed coral reefs on uninhabited atolls in the northern Line Islands to provide a baseline of reef community structure, and on increasingly populated atolls to document changes associated with human activities. We found that top predators and reef-building organisms dominated unpopulated Kingman and Palmyra, while small planktivorous fishes and fleshy algae dominated the populated atolls of Tabuaeran and Kiritimati. Sharks and other top predators overwhelmed the fish assemblages on Kingman and Palmyra so that the biomass pyramid was inverted (top-heavy). In contrast, the biomass pyramid at Tabuaeran and Kiritimati exhibited the typical bottom-heavy pattern. Reefs without people exhibited less coral disease and greater coral recruitment relative to more inhabited reefs. Thus, protection from overfishing and pollution appears to increase the resilience of reef ecosystems to the effects of global warming.","subset":"pubmed_abstract"} +{"meta":{"pmid":22936774,"dup_signals":{"dup_doc_count":13}},"text":"Radiative absorption enhancements due to the mixing state of atmospheric black carbon.\nAtmospheric black carbon (BC) warms Earth's climate, and its reduction has been targeted for near-term climate change mitigation. Models that include forcing by BC assume internal mixing with non-BC aerosol components that enhance BC absorption, often by a factor of ~2; such model estimates have yet to be clearly validated through atmospheric observations. Here, direct in situ measurements of BC absorption enhancements (E(abs)) and mixing state are reported for two California regions. The observed E(abs) is small-6% on average at 532 nm-and increases weakly with photochemical aging. The E(abs) is less than predicted from observationally constrained theoretical calculations, suggesting that many climate models may overestimate warming by BC. These ambient observations stand in contrast to laboratory measurements that show substantial E(abs) for BC are possible.","subset":"pubmed_abstract"} +{"meta":{"pmid":18218832,"dup_signals":{"dup_doc_count":40,"dup_dump_count":32,"dup_details":{"curated_sources":3,"2018-13":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2018-22":1,"2015-11":1,"2015-06":1,"2015-18":1}}},"text":"Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease.\nAmiloride improves mucociliary clearance (MC) by blocking airway epithelial sodium channels (ENaC) and expanding airway surface liquid (ASL). However, the low potency and rapid absorption of amiloride by airway epithelia translated into a short duration of efficacy as an aerosolized therapy for cystic fibrosis (CF) patients. To improve ENaC blocker CF pharmacotherapy, a more potent and durable ENaC blocker tailored for aerosol delivery was synthesized. Parion compound N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02) was tested for potency and reversibility of ENaC block, epithelial absorption and biotransformation, selectivity, durability of ASL expansion under isotonic and hypertonic conditions in canine and human CF bronchial epithelial cells, and drug dissociation on ENaC in Xenopus oocytes. Short-circuit current assessed compound potency and reversibility, patch-clamp recordings of ENaC current assessed drug off-rate (k(off)), a gravimetric method and confocal microscopy measured mucosal water retention and ASL height, and drug absorption and biotransformation were assessed using liquid chromatography-mass spectrometry. Amiloride and 552-02 were tested in vivo for MC activity in sheep immediately and 4 to 6 h after aerosol dosing. Compared with amiloride, compound 552-02 was 60 to 100-fold more potent, it was 2 to 5-fold less reversible, it was slower at crossing the epithelium, and it exhibited a 170-fold slower k(off) value. 552-02 exhibited greater ASL expansion over 8 h in vitro, and it was more effective than amiloride at increasing MC immediately and 4 to 6 h after dosing. When combining hypertonic saline and 552-02, a synergistic effect on ASL expansion was measured in canine or CF bronchial epithelia. In summary, the preclinical data support the clinical use of 552-02 +\/- hypertonic saline for CF lung disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":9370507,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"The risks of risk adjustment.\nRisk adjustment is essential before comparing patient outcomes across hospitals. Hospital report cards around the country use different risk adjustment methods. To examine the history and current practices of risk adjusting hospital death rates and consider the implications for using risk-adjusted mortality comparisons to assess quality. This article examines severity measures used in states and regions to produce comparisons of risk-adjusted hospital death rates. Detailed results are presented from a study comparing current commercial severity measures using a single database. It included adults admitted for acute myocardial infarction (n=11880), coronary artery bypass graft surgery (n=7765), pneumonia (n=18016), and stroke (n=9407). Logistic regressions within each condition predicted in-hospital death using severity scores. Odds ratios for in-hospital death were compared across pairs of severity measures. For each hospital, z scores compared actual and expected death rates. The severity measure called Disease Staging had the highest c statistic (which measures how well a severity measure discriminates between patients who lived and those who died) for acute myocardial infarction, 0.86; the measure called All Patient Refined Diagnosis Related Groups had the highest for coronary artery bypass graft surgery, 0.83; and the measure, MedisGroups, had the highest for pneumonia, 0.85 and stroke, 0.87. Different severity measures predicted different probabilities of death for many patients. Severity measures frequently disagreed about which hospitals had particularly low or high z scores. Agreement in identifying low- and high-mortality hospitals between severity-adjusted and unadjusted death rates was often better than agreement between severity measures. Severity does not explain differences in death rates across hospitals. Different severity measures frequently produce different impressions about relative hospital performance. Severity-adjusted mortality rates alone are unlikely to isolate quality differences across hospitals.","subset":"pubmed_abstract"} +{"meta":{"pmid":27561726,"dup_signals":{"dup_doc_count":34,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":3,"2024-22":2,"2024-18":1,"2024-10":1,"2017-13":1,"unknown":21}}},"text":"Assessment of Metformin-Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized[1-13C]Pyruvate.\nMetformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment on heart and liver pyruvate metabolism in rats in vivo. Both oral treatment for 4 weeks and a single intravenous metformin infusion significantly increased the cardiac [1-13C]lactate:[1-13C]pyruvate ratio but had no effect on the [1-13C]bicarbonate + 13CO2:[1-13C]pyruvate ratio, an index of pyruvate dehydrogenase flux. These changes were paralleled by a significant increase in the heart and liver cytosolic redox state, estimated from the [lactate]:[pyruvate] ratio but not the whole-cell [NAD+]\/[NADH] ratio. Hyperpolarized MRI localized the increase in cardiac lactate to the left ventricular myocardium, implying a direct myocardial effect, though metformin had no effect on systolic or diastolic cardiac function. These findings demonstrate the ability of hyperpolarized pyruvate magnetic resonance spectroscopy to detect metformin-induced changes in cytosolic redox biology, suggest that metformin has a previously unrecognized effect on cardiac redox state, and help to refine the design of impending hyperpolarized magnetic resonance studies in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":10367027,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2022-21":1,"2021-25":1,"2020-45":1,"2020-16":1,"2019-26":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2023-14":1,"2017-13":1}}},"text":"Fracture incidence in Olmsted County, Minnesota: comparison of urban with rural rates and changes in urban rates over time.\nUsing the data resources of the Rochester Epidemiology Project, we carried out a descriptive study of fracture incidence among the residents of Olmsted County, Minnesota. During the 3-year period 1989-91, 2901 County residents > or = 35 years of age experienced 3665 separate fractures. The age- and sex-adjusted (to 1990 United States whites) incidence of any fracture was 2205 per 100,000 person-years (95% CI, 2123 to 2286) and that of all fractures was 2797 per 100,000 (95% CI, 2705 to 2889). Age-adjusted fracture rates were 40% greater among women. Incidence rates increased with age in both sexes. One-third of the fractures involved the hip, spine or distal forearm - the skeletal sites traditionally associated with osteoporosis. The age- and sex-adjusted incidence of fractures due to moderate trauma (2205 per 100,000 person-years; 95% CI, 2106 to 2303) was twice that of fractures due to more severe trauma (1164 per 100,000; 95% CI, 1106 to 1223) and 12 times that of pathological fractures (178 per 100,000; 95% CI, 133 to 222). Overall fracture rates were 15% greater among residents of the central city of Rochester compared with the rural portion of Olmsted County. The incidence of limb fractures among Rochester residents was 14% higher than comparable rates documented for this community 20 years earlier in 1969-71, due mainly to a substantial increase in the incidence of leg fractures.","subset":"pubmed_abstract"} +{"meta":{"pmid":38096464,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Evaluating the Quality of Pain Management Satisfaction Among Oncology Patients in a Hospital Setting: Psychometric Properties of the Arabic Version of Pain Care Quality Survey.\nThe purpose of this mixed-methods psychometric study was to translate and adapt the Arabic Pain Care Quality (APainCQ) Survey to Arabic and to measure the quality of pain care provided to Arab patients. This study used an iterative, mixed-methods approach that employed cognitive interviews, expert content analysis, and factor analysis to develop the APainCQ Survey. The study was conducted at Dubai Hospital, Dubai Health Authority, United Arab Emirates. Arabic-speaking patients admitted to the oncology\/hematology inpatient units with a minimum 24-hour stay were eligible for the study. The sample consisted of 155 patients. The iterative exploratory factor analysis process resulted in the sequential removal of three items. The results of the significant Bartlett test (P < .001) of sphericity and Kaiser-Meyer-Olkin test of 0.93 for both the health care team scale and the nurse scale. The total variance explained was 76.17% for the health care team scale and 60.91% for the nurse scale, which explained 56.51% for factor 1 with 14 items and 4.40% for factor 2. Regarding internal consistency reliability, Cronbach's alpha and McDonald's omega for the health care team scale and nurse scale were high; both values were .95. Internal consistency reliability of pain assessment and pain management subscales of nurse scales were also high, with values of 0.96 and 0.79, respectively. Moreover, there was a moderate correlation (r = 0.66; P < .001) between the two subscales in the nurse scale. This study provides evidence that the APainCQ is a reliable and valid measure of pain dimensions, including pain management and monitoring. This APainCQ scale can potentially expand research and clinical assessment in the Arab world.","subset":"pubmed_abstract"} +{"meta":{"pmid":25861916,"dup_signals":{"dup_doc_count":11}},"text":"Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine.\nOpioid treatment for chronic pain is a known risk factor for falls and\/or fractures in elderly patients. The latter cause a significant cost to the National Health Service and the Personal Social Services in the UK. Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population. A model was developed to assess the cost effectiveness of tramadol compared with transdermal buprenorphine over a 1-year time horizon and a patient population of high-risk patients (female patients age 75 or older). To estimate the total cost and quality-adjusted life years (QALYs) of treatment, published odds ratios are used in combination with the published incidence rates of four types of fracture: hip, wrist, humerus and other. The model shows tramadol to be associated with 1,058 more fractures per 100,000 patients per year compared with transdermal buprenorphine, resulting in transdermal buprenorphine being cost-effective with an incremental cost-effectiveness ratio of less than \u00a37,000 compared with tramadol. Sensitivity analysis found this result to be robust. In the UK data, there is uncertainty regarding the transdermal buprenorphine odds ratios for fractures. Odds ratios published in Danish and Swedish studies show similar point estimates but are associated with less uncertainty. Transdermal buprenorphine is cost-effective compared to tramadol at a willingness-to-pay threshold of \u00a320,000 per QALY.","subset":"pubmed_abstract"} +{"meta":{"pmid":15758723,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Anastomotic contracture and incontinence after radical prostatectomy: a graded approach to management.\nWe present a heterogeneous group of men presenting with varying degrees of anastomotic contracture (AC) and associated stress urinary incontinence (SUI) following radical prostatectomy. It is particularly important that AC should be resolved before artificial urinary sphincter (AUS) implantation, because instrumentation through the AUS can risk erosion. The records of 54 consecutive men who were referred for the management of AC and associated SUI were reviewed. Patient treatment and outcomes were stratified according to their unique characteristics. A total of 54 patients underwent radical prostatectomy alone (48), or in combination with radiation therapy (7) or cryotherapy (1). In group 1, 35 patients had previously undiscovered AC, or 1 or more prior contracture incisions (CIs) with SUI. CI and AUS were performed simultaneously in 33 patients and sequentially in 2. In group 2, 7 patients with intractable AC following multiple CIs\/dilations and self-calibration, or an indwelling urethral or suprapubic catheter underwent simultaneous (3) or sequential (2) CI\/AUS or CI only (2). Five patients required temporary self-calibration. In group 3, in 12 patients with total outlet obliteration recanalization was accomplished with combined antegrade\/retrograde endoscopy and CI. Ten patients had re-obliteration, of whom 1 underwent suprapubic diversion and 9 underwent repeat recanalization with placement of a UroLume stent (American Medical Systems, Minnetonka, Minnesota) across the anastomosis. Eight patients underwent artificial urinary sphincter (AUS) placement 4 to 6 weeks later and 1 awaits an AUS. Of those implanted with an AUS 2 required repeat endoscopic procedures because of recurrent but manageable stent ingrowth. Most ACs are treated successfully with simultaneous, aggressive CI\/AUS. A history of many CIs or long, dense contractures suggest the need for staged management. In those with obliterated outlets we prefer to reestablish patency and if rapid recurrence develops, we place a UroLume stent. Regardless of a history of radiation therapy, continence is restored with an AUS.","subset":"pubmed_abstract"} +{"meta":{"pmid":22264221,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":2,"2014-10":1,"unknown":8}}},"text":"Epidemiology of Shiga toxin producing Escherichia coli in Australia, 2000-2010.\nShiga toxin-producing Escherichia coli (STEC) are an important cause of gastroenteritis in Australia and worldwide and can also result in serious sequelae such as haemolytic uraemic syndrome (HUS). In this paper we describe the epidemiology of STEC in Australia using the latest available data. National and state notifications data, as well as data on serotypes, hospitalizations, mortality and outbreaks were examined. For the 11 year period 2000 to 2010, the overall annual Australian rate of all notified STEC illness was 0.4 cases per 100,000 per year. In total, there were 822 STEC infections notified in Australia over this period, with a low of 1 notification in the Australian Capital Territory (corresponding to a rate of 0.03 cases per 100,000\/year) and a high of 413 notifications in South Australia (corresponding to a rate of 2.4 cases per 100,000\/year), the state with the most comprehensive surveillance for STEC infection in the country. Nationally, 71.2% (504\/708) of STEC infections underwent serotype testing between 2001 and 2009, and of these, 58.0% (225\/388) were found to be O157 strains, with O111 (13.7%) and O26 (11.1%) strains also commonly associated with STEC infections. The notification rate for STEC O157 infections Australia wide between 2001-2009 was 0.12 cases per 100,000 per year. Over the same 9 year period there were 11 outbreaks caused by STEC, with these outbreaks generally being small in size and caused by a variety of serogroups. The overall annual rate of notified HUS in Australia between 2000 and 2010 was 0.07 cases per 100,000 per year. Both STEC infections and HUS cases showed a similar seasonal distribution, with a larger proportion of reported cases occurring in the summer months of December to February. STEC infections in Australia have remained fairly steady over the past 11 years. Overall, the incidence and burden of disease due to STEC and HUS in Australia appears comparable or lower than similar developed countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":25271353,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mechanisms of Resistance to an Azole Fungicide in the Grapevine Powdery Mildew Fungus, Erysiphe necator.\nWe studied the mechanisms of azole resistance in Erysiphe necator by quantifying the sensitivity to myclobutanil (EC50) in 65 isolates from the eastern United States and 12 from Chile. From each isolate, we sequenced the gene for sterol 14\u03b1-demethylase (CYP51), and measured the expression of CYP51 and homologs of four putative efflux transporter genes, which we identified in the E. necator transcriptome. Sequence variation in CYP51 was relatively low, with sequences of 40 U.S. isolates identical to the reference sequence. Nine U.S. isolates and five from Chile carried a previously identified A to T nucleotide substitution in position 495 (A495T), which results in an amino acid substitution in codon 136 (Y136F) and correlates with high levels of azole resistance. We also found a nucleotide substitution in position 1119 (A1119C) in 15 U.S. isolates, whose mean EC50 value was equivalent to that for the Y136F isolates. Isolates carrying mutation A1119C had significantly greater CYP51 expression, even though A1119C does not affect the CYP51 amino acid sequence. Regression analysis showed no significant effects of the expression of efflux transporter genes on EC50. Both the Y136F mutation in CYP51 and increased CYP51 expression appear responsible for azole resistance in eastern U.S. populations of E. necator.","subset":"pubmed_abstract"} +{"meta":{"pmid":11006150,"dup_signals":{"dup_doc_count":28,"dup_dump_count":13,"dup_details":{"curated_sources":6,"2023-14":4,"2023-06":1,"2022-49":1,"2022-40":5,"2022-33":3,"2022-27":1,"2021-21":1,"2020-45":1,"2020-40":1,"2019-30":1,"2019-09":1,"2018-47":1,"2023-50":1}}},"text":"Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour.\nOxytocin is used widely for the induction and augmentation of labour, but there is little information about the dynamics of oxytocin receptors in human myometrium during parturition, and the possible effect of oxytocin infusion. This information is important because G protein-coupled receptors, such as the oxytocin receptor, undergo desensitization after prolonged or repeated stimulation. The concentration of myometrial oxytocin receptors and the steady state of its mRNA were measured in patients undergoing Caesarean sections before or during spontaneous or induced labour. The concentration of receptors before labour was 477 (175-641) fmol mg(-1) protein (median, quartile range), and decreased to 140 (72-206; P < 0.05) and 118 (69-75; P < 0.01) fmol mg(-1) protein during prolonged oxytocin-augmented and oxytocin-induced labour, respectively. The corresponding oxytocin receptor mRNA concentrations decreased by 60- and 300-fold, respectively. The decrease in receptor binding and mRNA in women receiving oxytocin infusion indicates that homologous receptor desensitization occurs in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":1730883,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Structural diversity of the classical H-2 genes: K, D, and L.\nTwenty-three class I DNA sequences, representing alleles of the H-2K, D, and L loci, were analyzed to assess patterns of nucleotide and amino acid diversity. Comparisons of the allelic and nonallelic sequences revealed locus specificity in regions encoding the leader peptides and the carboxyl-terminal segments of the Ag presenting molecules. Analyses focusing on the sequences that determine the Ag binding domains revealed weak or insignificant allelic associations, a finding that is in sharp contrast to previously observed relationships among the homologous human sequences. The amino acid positions exhibiting high diversity in the encoded glycoproteins in both mice and humans are localized primarily to the Ag binding site. In the mouse, diverse amino acids were positioned similarly in the K and D\/L glycoproteins, although in humans, the A and B glycoproteins exhibit distinctive differences in their locations within the Ag binding site. The absence of locus specificity among the sequences that determine the Ag binding domains of the mouse is consistent with the hypothesis that ectopic gene conversion leads to interlocus exchange of class I sequences. Comparable interlocus exchanges among human class I genes have not played a similar role in shaping human A and B sequences. The basis of this difference between mice and humans is not clear. The nature of amino acid substitutions distinguishing class I loci in mice and humans are comparable, and the role of natural selection in determining diversity appears to be similar in the two species.","subset":"pubmed_abstract"} +{"meta":{"pmid":28268189,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":11}}},"text":"Validation of an International Statistical Classification of Diseases and Related Health Problems 10th Revision Coding Algorithm for Hospital Encounters with Hypoglycemia.\nTo determine the positive predictive value and sensitivity of an International Statistical Classification of Diseases and Related Health Problems, 10th Revision, coding algorithm for hospital encounters concerning hypoglycemia. We carried out 2 retrospective studies in Ontario, Canada. We examined medical records from 2002 through 2014, in which older adults (mean age, 76) were assigned at least 1 code for hypoglycemia (E15, E160, E161, E162, E1063, E1163, E1363, E1463). The positive predictive value of the algorithm was calculated using a gold-standard definition (blood glucose value <4 mmol\/L or physician diagnosis of hypoglycemia). To determine the algorithm's sensitivity, we used linked healthcare databases to identify older adults (mean age, 77) with laboratory plasma glucose values <4 mmol\/L during a hospital encounter that took place between 2003 and 2011. We assessed how frequently a code for hypoglycemia was present. We also examined the algorithm's performance in differing clinical settings (e.g. inpatient vs. emergency department, by hypoglycemia severity). The positive predictive value of the algorithm was 94.0% (95% confidence interval 89.3% to 97.0%), and its sensitivity was 12.7% (95% confidence interval 11.9% to 13.5%). It performed better in the emergency department and in cases of more severe hypoglycemia (plasma glucose values <3.5 mmol\/L compared with \u22653.5 mmol\/L). Our hypoglycemia algorithm has a high positive predictive value but is limited in sensitivity. Although we can be confident that older adults who are assigned 1 of these codes truly had a hypoglycemia event, many episodes will not be captured by studies using administrative databases.","subset":"pubmed_abstract"} +{"meta":{"pmid":26321019,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-10":1,"2017-13":1,"2024-26":1,"unknown":8}}},"text":"The Social Salience Hypothesis of Oxytocin.\nOxytocin is a nonapeptide that also serves as a neuromodulator in the human central nervous system. Over the last decade, a sizeable body of literature has examined its effects on social behavior in humans. These studies show that oxytocin modulates various aspects of social behaviors such as empathy, trust, in-group preference, and memory of socially relevant cues. Several theoretical formulations have attempted to explain the effects of oxytocin. The prosocial account argues that oxytocin mainly enhances affiliative prosocial behaviors; the fear\/stress theory suggests that oxytocin affects social performance by attenuating stress; and the in-\/out-group approach proposes that oxytocin regulates cooperation and conflict among humans in the context of intergroup relations. Nonetheless, accumulating evidence reveals that the effects of oxytocin are dependent on a variety of contextual aspects and the individual's characteristics and can induce antisocial effects including aggression and envy. In an attempt to reconcile these accounts, we suggest a theoretical framework that focuses on the overarching role of oxytocin in regulating the salience of social cues through its interaction with the dopaminergic system. Crucially, the salience effect modulates attention orienting responses to external contextual social cues (e.g., competitive vs. cooperative environment) but is dependent on baseline individual differences such as gender, personality traits, and degree of psychopathology. This view could have important implications for the therapeutic applications of oxytocin in conditions characterized with aberrant social behavior.","subset":"pubmed_abstract"} +{"meta":{"pmid":28251498,"dup_signals":{"dup_doc_count":19,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-30":1,"2022-49":1}}},"text":"Radiological anatomy of spontaneous splenorenal shunts in patients with chronic liver disease.\nWe evaluated anatomical variations of spontaneous splenorenal shunt (SSRS) and the prevalence of portosystemic shunts in patients with chronic liver disease by CT. A total of 451 patients with chronic liver disease underwent contrast-enhanced computed tomography between October 2010 and April 2011. The prevalence of portosystemic shunts including SSRS and gastrorenal shunt, and the frequency of hepatic encephalopathy were examined. The course of the shunt and the point of confluence with the renal vein of the SSRS were analyzed. SSRSs or gastrorenal shunts were found in 11.1 and 5.0% of the patients, respectively. Anatomical variations were classified into three types according to the point of confluence as follows: type 1 = the SSRS joined the inferior phrenic vein (n = 33), type 2 = the SSRS joined the gonadal vein (n = 7), and type 3 = the SSRS joined the left renal vein (n = 14). The course of the SSRS from the splenic hilum was classified as medial (n = 46), posterior (n = 2), or anterolateral (n = 2). SSRSs were classified into three types depending on the confluence point with the renal vein, and into three types of course. These findings are useful for preoperative information.","subset":"pubmed_abstract"} +{"meta":{"pmid":18311106,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"unknown":8}}},"text":"Randomized controlled trial of yogic meditation techniques for patients with obsessive-compulsive disorder.\nThe objective of this study was to compare efficacy of two meditation protocols for treating patients with obsessive-compulsive disorder (OCD). Patients were randomized to two groups-matched for sex, age, and medication status-and blinded to the comparison protocol. They were told the trial would last for 12 months, unless one protocol proved to be more efficacious. If so, groups would merge, and the group that received the less efficacious treatment would also be afforded 12 months of the more effective one. The study was conducted at Children's Hospital, San Diego, Calif. Patients were selected according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) criteria and recruited by advertisements and referral. At baseline, Group 1 included 11 adults and 1 adolescent, and Group 2 included 10 adults. Group 1 employed a kundalini yoga meditation protocol and Group 2 employed the Relaxation Response plus Mindfulness Meditation technique. Baseline and 3-month interval testing was conducted using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Symptoms Checklist-90-Revised Obsessive Compulsive (SCL-90-R OC) and Global Severity Index (SCL-90-R GSI) scales, Profile of Moods scale (POMS), Perceived Stress Scale (PSS), and Purpose in Life (PIL) test. Seven adults in each group completed 3 months of therapy. At 3 months, Group 1 demonstrated greater improvements (Student's independent groups t-test) on the Y-BOCS, SCL-90-R OC and GSI scales, and POMS, and greater but nonsignificant improvements on the PSS and PIL test. An intent-to-treat analysis (Y-BOCS) for the baseline and 3-month tests showed that only Group 1 improved. Within-group statistics (Student's paired t-tests) showed that Group 1 significantly improved on all six scales, but Group 2 had no improvements. Groups were merged for an additional year using Group 1 techniques. At 15 months, the final group (N=11) improved 71%, 62%, 66%, 74%, 39%, and 23%, respectively, on the Y-BOCS, SCL-90-R OC, SCL-90-R GSI, POMS, PSS, and PIL; P<0.003 (analysis of variance). This study demonstrates that kundalini yoga techniques are effective in the treatment of OCD.","subset":"pubmed_abstract"} +{"meta":{"pmid":24822196,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":1,"2024-10":1,"unknown":5}}},"text":"Laparoscopic resection for rectal cancer: what is the evidence?\nLaparoscopic colectomy for colon cancer is a well-established procedure supported by several well-conducted large-scale randomised controlled trials. Patients could now be conferred the benefits of the minimally invasive approach while retaining comparable oncologic outcomes to the open approach. However, the benefits of laparoscopic proctectomy for rectal cancer remained controversial. While the laparoscopic approach is more technically demanding, results from randomised controlled trials regarding long term oncologic outcomes are only beginning to be reported. The impacts of bladder and sexual functions following proctectomy are considerable and are important contributing factors to the patients' quality of life in the long-term. These issues present a delicate dilemma to the surgeon in his choice of operative approach in tackling rectal cancer. This is compounded further by the rapid proliferation of various laparoscopic techniques including the hand assisted, robotic assisted, and single port laparoscopy. This review article aims to draw on the significant studies which have been conducted to highlight the short- and long-term outcomes and evidence for laparoscopic resection for rectal cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":30859890,"dup_signals":{"dup_doc_count":26,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2020-34":2,"2020-29":1,"2020-24":1,"2019-47":11,"2019-43":5,"2019-39":1,"2020-40":1}}},"text":"Clustering of Physical Activity and Sedentary Behavior Associated to Risk for Metabolic Syndrome in Older Adults.\nThis study aimed to investigate the clustering patterns of physical activity, sedentary time (ST), and breaks in ST, and the association between the identified clusters at risk for metabolic syndrome associated with obesity in older adults. Participants included 212 users of community health centers in Brazil. A questionnaire about sociodemographic characteristics was used to describe the sample, and physical activity, ST, and breaks in ST were evaluated using accelerometers. Waist circumference was measured as an indicator of the risk for metabolic syndrome. A two-step cluster analysis and logistic regression analysis were conducted. The following four clusters were identified: sitters (37.7%), inactive (28.3%), active (25.5%), and all-day sitters\/lightly active (8.5%). Participants in the active cluster were 60% less likely to be at risk for metabolic syndrome. This study may contribute to a comprehensive understanding of which older adult groups need more attention in the context of community health centers.","subset":"pubmed_abstract"} +{"meta":{"pmid":33188134,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":16}}},"text":"Fluid biomarkers in frontotemporal dementia: past, present and future.\nThe frontotemporal dementia (FTD) spectrum of neurodegenerative disorders includes a heterogeneous group of conditions. However, following on from a series of important molecular studies in the early 2000s, major advances have now been made in the understanding of the pathological and genetic underpinnings of the disease. In turn, alongside the development of novel methodologies for measuring proteins and other molecules in biological fluids, the last 10 years have seen a huge increase in biomarker studies within FTD. This recent past has focused on attempting to develop markers that will help differentiate FTD from other dementias (particularly Alzheimer's disease (AD)), as well as from non-neurodegenerative conditions such as primary psychiatric disorders. While cerebrospinal fluid, and more recently blood, markers of AD have been successfully developed, specific markers identifying primary tauopathies or TDP-43 proteinopathies are still lacking. More focus at the moment has been on non-specific markers of neurodegeneration, and in particular, multiple studies of neurofilament light chain have highlighted its importance as a diagnostic, prognostic and staging marker of FTD. As clinical trials get under way in specific genetic forms of FTD, measures of progranulin and dipeptide repeat proteins in biofluids have become important potential measures of therapeutic response. However, understanding of whether drugs restore cellular function will also be important, and studies of key pathophysiological processes, including neuroinflammation, lysosomal function and synaptic health, are also now becoming more common. There is much still to learn in the fluid biomarker field in FTD, but the creation of large multinational cohorts is facilitating better powered studies and will pave the way for larger omics studies, including proteomics, metabolomics and lipidomics, as well as investigations of multimodal biomarker combinations across fluids, brain imaging and other domains. Here we provide an overview of the past, present and future of fluid biomarkers within the FTD field.","subset":"pubmed_abstract"} +{"meta":{"pmid":29741531,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":1,"2022-05":1,"2021-25":1,"2021-21":2,"2021-17":2,"2020-50":1,"2020-45":1,"2020-40":1,"2020-16":1,"2020-10":2,"2019-47":1,"2019-39":1,"2023-50":1,"2024-10":1}}},"text":"Cost-effectiveness of physical fitness training for stroke survivors.\nBackground Physical fitness is impaired after stroke, yet fitness training after stroke reduces disability. Several international guidelines recommend that fitness training be incorporated as part of stroke rehabilitation. However, information about cost-effectiveness is limited. Methods A decision tree model was used to estimate the cost-effectiveness of a fitness programme for stroke survivors vs. relaxation (control group). This was based on a published randomised controlled trial, from which evidence about quality of life was used to estimate Quality Adjusted Life Years. Costs were based on the cost of the provision of group fitness classes within local community centres and a cost per Quality Adjusted Life Year was calculated. Results The results of the base case analysis found an incremental cost per Quality Adjusted Life Year of \u00a32,343. Conclusions Physical fitness sessions after stroke are a cost-effective intervention for stroke survivors. This information will help make the case for the development of new services.","subset":"pubmed_abstract"} +{"meta":{"pmid":7806687,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Long-term safety and clinical acceptability of venlafaxine and imipramine in outpatients with major depression.\nThe antidepressant efficacy and safety of venlafaxine was shown previously in 6-week, placebo-controlled trials. We evaluated the long-term safety and clinical acceptability of venlafaxine and imipramine in a double-blind, parallel-group, comparative study. Two hundred ninety depressed outpatients were treated with venlafaxine, and an additional 91 received imipramine for as long as clinically necessary, up to 1 year. The total daily dose of each drug could vary from 75 to 225 mg. The Clinical Global Impressions Scale and a therapeutic response rate that was based on Clinical Global Impressions Scale-Improvement and incorporated discontinuation information were used to evaluate efficacy. Safety determinations and patient subjective ratings were used to evaluate safety and clinical acceptability. During the study, the adverse events were generally mild to moderate and most subsided with continued treatment; the most frequent were nausea for venlafaxine and dry mouth for imipramine. The anticholinergic side effect burden was significantly higher in the imipramine group than in the venlafaxine group. Venlafaxine was judged significantly more acceptable than imipramine, on the basis of the subjective ratings by patients. Fewer venlafaxine-treated patients than imipramine-treated patients withdrew because of adverse events and unsatisfactory response. There was a consistent trend in the therapeutic response rates in favor of venlafaxine that reached statistical significance at months 2, 6, and 12. In this long-term study, patient acceptability was greater for venlafaxine than for imipramine, suggesting therapeutic advantages for venlafaxine in the long-term treatment of depression. Additional studies with other active comparators are underway to confirm and extend these encouraging results.","subset":"pubmed_abstract"} +{"meta":{"pmid":29202952,"dup_signals":{"dup_doc_count":17}},"text":"Factors Influencing Pediatric Outpatient Transthoracic Echocardiography Utilization Before Appropriate Use Criteria Release: A Multicenter Study.\nAlthough pediatric appropriate use criteria (AUC) for outpatient transthoracic echocardiography (TTE) are available, little is known about TTE utilization patterns before their release. The aims of this study were to determine the relation between AUC and TTE utilization and to identify patient and physician factors associated with discordance between the AUC and clinical practice. A retrospective review of 3,000 initial outpatient pediatric cardiology encounters at six centers was performed. Investigator-determined indications were classified using AUC definitions. Concordance between AUC and TTE utilization was determined. Multivariate analysis was performed to identify patient and physician factors associated with TTE's being performed for rarely appropriate and TTE's not being performed for appropriate indications. Concordance between AUC and TTE utilization was 88%. TTE was performed for rarely appropriate indications in 9% and was associated with patient age < 3 months, indications of murmur, noninvasive imaging physician subspecialty, and physician volume. No TTE was ordered for appropriate indications in 3% and was associated with indications including prior test result (primarily abnormal electrocardiographic findings), older patients, and physician subspecialty other than generalist or imaging. There was high variability in TTE utilization among centers. There was a reasonable degree of concordance between AUC and clinical practice before AUC publication. Several patient and physician factors were associated with discordance with the AUC. These findings should be considered in efforts to disseminate the AUC and in the development of future iterations. The causes for variation among centers deserve further exploration.","subset":"pubmed_abstract"} +{"meta":{"pmid":6209285,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Monoclonal antibody characterization of the C proteins of heterogeneous nuclear ribonucleoprotein complexes in vertebrate cells.\nThe C proteins (C1 and C2) are major constituents of the 40S subparticle of heterogeneous nuclear ribonucleoprotein complexes (hnRNPs) (Beyer, A.L., M.E. Christensen, B.W. Walker, and W.M. LeStourgeon, 1977, Cell, 11:127-138) and are two of the most prominent proteins that become cross-linked by ultraviolet light to heterogeneous nuclear RNA (hnRNA) in vivo. Studies are described here on the characterization of the C proteins in vertebrate cells using monoclonal and polyclonal antibodies. Monoclonal antibodies to genuine RNP proteins, including the C proteins, were obtained by immunizing mice with purified complexes of poly(A)+ hnRNA and poly(A)+ mRNA with their contacting proteins in vivo obtained by ultraviolet cross-linking the complexes in intact cells (Dreyfuss, G., Y.D. Choi, and S.A. Adam, 1984, Mol. Cell. Biol., 4:1104-1114). One of the monoclonal antibodies identified the C proteins in widely divergent species ranging from human to lizard. In all species examined, there were two C proteins in the molecular weight range of from 39,000 to 42,000 for C1, and from 40,000 to 45,000 for C2. The two C proteins were found to be highly related to each other; they were recognized by the same monoclonal antibodies and antibodies raised against purified C1 reacted also with C2. In avian, rodent, and human cells the C proteins were phosphorylated and were in contact with hnRNA in vivo. Immunofluorescence microscopy demonstrated that the C proteins are segregated to the nucleus. Within the nucleus the C proteins were not found in nucleoli and were not associated with chromatin as seen in cells in prophase. These findings demonstrate that C proteins with similar characteristics to those in humans are ubiquitous components of hnRNPs in vertebrates.","subset":"pubmed_abstract"} +{"meta":{"pmid":24188643,"dup_signals":{"dup_doc_count":77,"dup_dump_count":37,"dup_details":{"curated_sources":4,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2018-30":1,"2018-05":1,"2017-30":2,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":2,"2016-26":1,"2016-22":2,"2016-18":1,"2016-07":2,"2015-48":2,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":2,"2014-42":7,"2014-41":3,"2014-35":2,"2014-23":5,"2014-15":4,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2}}},"text":"Migration and persistence of human influenza A viruses, Vietnam, 2001-2008.\nUnderstanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001-2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year.","subset":"pubmed_abstract"} +{"meta":{"pmid":27621612,"dup_signals":{"dup_doc_count":21,"dup_dump_count":3,"dup_details":{"curated_sources":4,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":14}}},"text":"Do self-management interventions in COPD patients work and which patients benefit most? An individual patient data meta-analysis.\nSelf-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most. This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most. Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search. Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models. Fourteen trials representing 3,282 patients were included. Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality. Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026). In none of these subgroups, a consistent effect was shown on all relevant outcomes. Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice. Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended.","subset":"pubmed_abstract"} +{"meta":{"pmid":27527083,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Antistaphylococcal \u03b2-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.\nThe phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal \u03b2-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.","subset":"pubmed_abstract"} +{"meta":{"pmid":29774897,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Development of highly sensitive fluorescent probes for the detection of \u03b2-galactosidase activity - application to the real-time monitoring of senescence in live cells.\nWe report the development of four novel fluorescent probes to monitor the activity of the \u03b2-galactosidase enzyme (\u03b2-gal), in vitro and in living cells. The fluorophores are based on a 6-amino-styryl-benzothiazole push-pull core and display a strong ICT emission. The probes encompass the fluorescent motif that is connected to a \u03b2-d-galactopyranoside moiety through a self-immolative benzyl carbamate linker (\u03b2Gal-1-4). The screening of four different fluorophores enabled us to access new light-up and two-band ratiometric reporters. The four probes, \u03b2Gal-1-4, exhibited an extremely fast response and over 200-fold fluorescence enhancement (\u03b2Gal-1) following the enzymatic cleavage of the \u03b2-d-galactopyranoside unit. This rapid and extremely sensitive response allowed the detection of senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) activity; a widely used biomarker of senescence. More importantly, \u03b2Gal-1 also enabled us to monitor, in real-time, the emergence of senescence in live cells, i.e. the phenotypic transformation from normal to senescent cell. These findings underpin the fact that \u03b2Gal-1 may find useful applications in biomedical research. Importantly, \u03b2Gal-1 is suitable for epifluorescence and confocal microscopies, and flow cytometry techniques, which are among the most common analytical tools in biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":32683443,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Enlighten2: molecular dynamics simulations of protein-ligand systems made accessible.\nExperimental structural data can allow detailed insight into protein structure and protein-ligand interactions, which is crucial for many areas of bioscience, including drug design and enzyme engineering. Typically, however, little more than a static picture of protein-ligand interactions is obtained, whereas dynamical information is often required for deeper understanding and to assess the effect of mutations. Molecular dynamics (MD) simulations can provide such information, but setting up and running these simulations is not straightforward and requires expert knowledge. There is thus a need for a tool that makes protein-ligand simulation easily accessible to non-expert users. We present Enlighten2: efficient simulation protocols for protein-ligand systems alongside a user-friendly plugin to the popular visualization program PyMOL. With Enlighten2, non-expert users can straightforwardly run and visualize MD simulations on protein-ligand models of interest. There is no need to learn new programs and all underlying tools are free and open source. The Enlighten2 Python package and PyMOL plugin are free to use under the GPL3.0 licence and can be found at https:\/\/enlighten2.github.io. We also provide a lightweight Docker image via DockerHub that includes Enlighten2 with all the required utilities.","subset":"pubmed_abstract"} +{"meta":{"pmid":32124007,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2022-49":1,"2022-33":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2023-40":1,"2024-22":1,"2024-26":1}}},"text":"Physiological mechanisms determining eccrine sweat composition.\nThe purpose of this paper is to review the physiological mechanisms determining eccrine sweat composition to assess the utility of sweat as a proxy for blood or as a potential biomarker of human health or nutritional\/physiological status. This narrative review includes the major sweat electrolytes (sodium, chloride, and potassium), other micronutrients (e.g., calcium, magnesium, iron, copper, zinc, vitamins), metabolites (e.g., glucose, lactate, ammonia, urea, bicarbonate, amino acids, ethanol), and other compounds (e.g., cytokines and cortisol). Ion membrane transport mechanisms for sodium and chloride are well established, but the mechanisms of secretion and\/or reabsorption for most other sweat solutes are still equivocal. Correlations between sweat and blood have not been established for most constituents, with perhaps the exception of ethanol. With respect to sweat diagnostics, it is well accepted that elevated sweat sodium and chloride is a useful screening tool for cystic fibrosis. However, sweat electrolyte concentrations are not predictive of hydration status or sweating rate. Sweat metabolite concentrations are not a reliable biomarker for exercise intensity or other physiological stressors. To date, glucose, cytokine, and cortisol research is too limited to suggest that sweat is a useful surrogate for blood. Final sweat composition is not only influenced by extracellular solute concentrations, but also mechanisms of secretion and\/or reabsorption, sweat flow rate, byproducts of sweat gland metabolism, skin surface contamination, and sebum secretions, among other factors related to methodology. Future research that accounts for these confounding factors is needed to address the existing gaps in the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":28288414,"dup_signals":{"dup_doc_count":33,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2022-33":1,"2022-05":2,"2021-49":1,"2021-39":2,"2021-31":1,"2021-21":2,"2020-50":2,"2020-05":1,"2019-26":2,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":2,"2017-22":1,"2017-17":2,"2022-40":1,"2017-13":2}}},"text":"Butyrate induces ROS-mediated apoptosis by modulating miR-22\/SIRT-1 pathway in hepatic cancer cells.\nButyrate is one of the short chain fatty acids, produced by the gut microbiota during anaerobic fermentation of dietary fibres. It has been shown that it can inhibit tumor progression via suppressing histone deacetylase and can induce apoptosis in cancer cells. However, the comprehensive pathway by which butyrate mediates apoptosis and growth arrest in cancer cells still remains unclear. In this study, the role of miR-22 in butyrate-mediated ROS release and induction of apoptosis was determined in hepatic cells. Intracellular expression of miR-22 was increased when the Huh 7 cells were incubated with sodium butyrate. Over-expression of miR-22 or addition of sodium butyrate inhibited SIRT-1 expression and enhanced the ROS production. Incubation of cells with anti-miR-22 reversed the effects of butyrate. Butyrate induced apoptosis via ROS production, cytochrome c release and activation of caspase-3, whereas addition of N-acetyl cysteine or anti-miR-22 reversed these butyrate-induced effects. Furthermore, sodium butyrate inhibited cell growth and proliferation, whereas anti-miR-22 inhibited these butyrate-mediated changes. The expression of PTEN and gsk-3 was found to be increased while p-akt and \u03b2-catenin expression was decreased significantly by butyrate. These data showed that butyrate modulated both apoptosis and proliferation via miR-22 expression in hepatic cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23512326,"dup_signals":{"dup_doc_count":12,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":5}}},"text":"Determinants of adjuvant oxaliplatin receipt among older stage II and III colorectal cancer patients.\nControversy exists regarding adjuvant oxaliplatin treatment among older patients with stage II and III colorectal cancer (CRC). This study sought to identify patient\/tumor, physician, hospital, and geographic factors associated with oxaliplatin use among older patients. Individuals diagnosed at age > 65 with stage II or III CRC from 2004 through 2007 undergoing surgical resection and receiving adjuvant chemotherapy were identified using the Surveillance, Epidemiology and End Results program (SEER)-Medicare database, which includes patient\/tumor and hospital characteristics. Physician information was obtained from the American Medical Association. Poisson regression was used to identify independent predictors of oxaliplatin receipt. The discriminatory ability of each category of characteristics to predict oxaliplatin receipt was assessed by comparing the area under the receiver operating curve from logistic regression models. We identified 4388 individuals who underwent surgical resection at 773 hospitals and received chemotherapy from 1517 physicians. Adjuvant oxaliplatin use was higher among stage III (colon = 56%, rectum = 51%) compared to stage II patients (colon = 37%, rectum = 35%). Overall, patients who were older; diagnosed before 2006; separated, divorced, or widowed; living in a higher poverty census tract or in the East or Midwest; or with higher levels of comorbidity were less likely to receive oxaliplatin. Patient factors and calendar year accounted for most of the variation in oxaliplatin receipt (area under the curve = 75.8%). Adjuvant oxaliplatin use increased rapidly from 2004 through 2007 despite uncertainties regarding its effectiveness in older patients. Physician and hospital characteristics had little influence on adjuvant oxaliplatin receipt among older patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":7962683,"dup_signals":{"dup_doc_count":45,"dup_dump_count":30,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":2,"2021-21":1,"2021-17":3,"2021-10":1,"2021-04":1,"2020-45":2,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-13":2,"2017-51":2,"2017-43":2,"2017-34":2,"2023-50":1,"2024-30":3,"2024-26":4,"2024-22":1}}},"text":"Attenuation of the prolactin-stimulating and hyperthermic effects of nefazodone after subacute treatment.\nThe acute administration of the antidepressant drug nefazodone (100 mg orally) to healthy male volunteers increased prolactin concentrations in plasma and elevated oral temperature. After repeated treatment with 100 mg of nefazodone twice daily for 7 days, these effects were attenuated. We propose that the ability of nefazodone given acutely to increase prolactin concentrations and oral temperature is mediated via metabolism to the 5-hydroxytryptamine1C (5-HT1C) receptor agonist meta-chlorophenylpiperazine. The attenuation of these effects after subacute treatment could be due to an adaptive down-regulation of 5-HT1C receptors or to direct blockade of 5-HT1C receptors by nefazodone and its metabolite hydroxynefazodone (OH-nefazodone), the concentrations in plasma of which increase substantially during the 7-day treatment period.","subset":"pubmed_abstract"} +{"meta":{"pmid":27777755,"dup_signals":{"dup_doc_count":19}},"text":"Serious electronic games as behavioural change interventions in healthcare-associated infections and infection prevention and control: a scoping review of the literature and future directions.\nThe uptake of improvement initiatives in infection prevention and control (IPC) has often proven challenging. Innovative interventions such as 'serious games' have been proposed in other areas to educate and help clinicians adopt optimal behaviours. There is limited evidence about the application and evaluation of serious games in IPC. The purposes of the study were: a) to synthesise research evidence on the use of serious games in IPC to support healthcare workers' behaviour change and best practice learning; and b) to identify gaps across the formulation and evaluation of serious games in IPC. A scoping study was conducted using the methodological framework developed by Arksey and O'Malley. We interrogated electronic databases (Ovid MEDLINE, Embase Classic + Embase, PsycINFO, Scopus, Cochrane, Google Scholar) in December 2015. Evidence from these studies was assessed against an analytic framework of intervention formulation and evaluation. Nine hundred sixty five unique papers were initially identified, 23 included for full-text review, and four finally selected. Studies focused on intervention inception and development rather than implementation. Expert involvement in game design was reported in 2\/4 studies. Potential game users were not included in needs assessment and game development. Outcome variables such as fidelity or sustainability were scarcely reported. The growing interest in serious games for health has not been coupled with adequate evaluation of processes, outcomes and contexts involved. Explanations about the mechanisms by which game components may facilitate behaviour change are lacking, further hindering adoption.","subset":"pubmed_abstract"} +{"meta":{"pmid":11442067,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-14":1,"2023-06":1,"2022-05":1,"2021-21":1,"2021-17":1,"2019-13":1,"2018-43":2,"2018-22":1,"2018-09":1,"2023-40":1}}},"text":"Empowering radiologic education on the Internet: a new virtual website technology for hosting interactive educational content on the World Wide Web.\nWe describe a virtual web site hosting technology that enables educators in radiology to emblazon and make available for delivery on the world wide web their own interactive educational content, free from dependencies on in-house resources and policies. This suite of technologies includes a graphically oriented software application, designed for the computer novice, to facilitate the input, storage, and management of domain expertise within a database system. The database stores this expertise as choreographed and interlinked multimedia entities including text, imagery, interactive questions, and audio. Case-based presentations or thematic lectures can be authored locally, previewed locally within a web browser, then uploaded at will as packaged knowledge objects to an educator's (or department's) personal web site housed within a virtual server architecture. This architecture can host an unlimited number of unique educational web sites for individuals or departments in need of such service. Each virtual site's content is stored within that site's protected back-end database connected to Internet Information Server (Microsoft Corp, Redmond WA) using a suite of Active Server Page (ASP) modules that incorporate Microsoft's Active Data Objects (ADO) technology. Each person's or department's electronic teaching material appears as an independent web site with different levels of access--controlled by a username-password strategy--for teachers and students. There is essentially no static hypertext markup language (HTML). Rather, all pages displayed for a given site are rendered dynamically from case-based or thematic content that is fetched from that virtual site's database. The dynamically rendered HTML is displayed within a web browser in a Socratic fashion that can assess the recipient's current fund of knowledge while providing instantaneous user-specific feedback. Each site is emblazoned with the logo and identification of the participating institution. Individuals with teacher-level access can use a web browser to upload new content as well as manage content already stored on their virtual site. Each virtual site stores, collates, and scores participants' responses to the interactive questions posed on line. This virtual web site strategy empowers the educator with an end-to-end solution for creating interactive educational content and hosting that content within the educator's personalized and protected educational site on the world wide web, thus providing a valuable outlet that can magnify the impact of his or her talents and contributions.","subset":"pubmed_abstract"} +{"meta":{"pmid":26596250,"dup_signals":{"dup_doc_count":20,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2020-05":1,"2019-47":1,"2019-35":1,"2019-09":1,"2018-51":1,"2018-47":2,"2018-39":1,"2018-34":2,"2018-26":2,"2018-22":1,"2018-13":1,"2018-09":2,"2018-05":1,"2017-34":1,"2023-50":1}}},"text":"Children's thoughts and feelings related to visiting critically ill relatives in an adult ICU: A qualitative study.\nTo describe and understand children's thoughts and feelings related to visiting critically ill relatives or family members in an adult intensive care unit. A qualitative descriptive study. Twenty-eight children (14 girls; 14 boys) that had visited a critically ill relative or family member in an adult intensive care unit were invited to participate in an interview. The material was analysed inspired by Gadamer's hermeneutic philosophy and Doverborg and Pramling Samuelsson's method about interviews and dialogues with children. Children with a seriously ill\/injured relative suffer. However, visiting seems to alleviate suffering. Visiting and being present as a part of the situation brought positive feelings of involvement and made it possible to show that they wanted to care for the relative. The sick relative was always on the child's mind and seeing and being with them in the intensive care unit resulted in relief and calmness, even if the relative's situation sometimes evoked feelings of despair and fear. Knowledge and awareness of the fact that children are affected by the relative's condition and for their wellbeing needs to visit, caring actions must focus on helping the child become involved in the relative's situation in order to alleviate suffering.","subset":"pubmed_abstract"} +{"meta":{"pmid":29052865,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":3,"2024-26":1,"unknown":8}}},"text":"Research Review: Is anxiety associated with negative interpretations of ambiguity in children and adolescents? A systematic review and meta-analysis.\nThe tendency to interpret ambiguity as threat (negative interpretation) has been implicated in cognitive models of anxiety. A significant body of research has examined the association between anxiety and negative interpretation, and reviews suggest there is a robust positive association in adults. However, evidence with children and adolescents has been inconsistent. This study aimed to provide a systematic quantitative assessment of the association between anxiety and negative interpretation in children and adolescents. Following systematic searches and screening for eligibility, 345 effects sizes from 77 studies were meta-analysed. Overall a medium positive association was found between anxiety and negative interpretation in children and adolescents ( d^ = .62). Two variables significantly moderated this effect. Specifically, the association increased in strength with increasing age and when the content of ambiguous scenarios matched the anxiety subtype under investigation. Results extend findings from adult literature by demonstrating an association in children and adolescents with evidence for content specificity in the association. Age effects imply a role for development. Results raise considerations for when and for whom clinical treatments for anxiety focusing on interpretation bias are appropriate. The vast majority of studies included in the review have used correlational designs and there are a limited number of studies with young children. The results should be considered with these limitations in mind.","subset":"pubmed_abstract"} +{"meta":{"pmid":23519026,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":8}}},"text":"From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome.\nApert syndrome is a congenital disorder characterized by severe skull malformations and caused by one of two missense mutations, S252W and P253R, on fibroblast growth factor receptor 2 (FGFR2). The molecular bases underlying differential Apert syndrome phenotypes are still poorly understood and it is unclear why cleft palate is more frequent in patients carrying the S252W mutation. Taking advantage of Apert syndrome mouse models, we performed a novel combination of morphometric, histological and immunohistochemical analyses to precisely quantify distinct palatal phenotypes in Fgfr2(+\/S252W) and Fgfr2(+\/P253R) mice. We localized regions of differentially altered FGF signaling and assessed local cell patterns to establish a baseline for understanding the differential effects of these two Fgfr2 mutations. Palatal suture scoring and comparative 3D shape analysis from high resolution \u03bcCT images of 120 newborn mouse skulls showed that Fgfr2(+\/S252W) mice display relatively more severe palate dysmorphologies, with contracted and more separated palatal shelves, a greater tendency to fuse the maxillary-palatine sutures and aberrant development of the inter-premaxillary suture. These palatal defects are associated with suture-specific patterns of abnormal cellular proliferation, differentiation and apoptosis. The posterior region of the developing palate emerges as a potential target for therapeutic strategies in clinical management of cleft palate in Apert syndrome patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":25262928,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-10":1,"2019-47":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-06":1,"2017-13":1}}},"text":"Alteration in Pimephales promelas mucus production after exposure to nanosilver or silver nitrate.\nThe fish gill's ability to produce mucus effectively is a critical part of the stress response and protection against xenobiotic toxicity. Adult fathead minnows were exposed to silver nitrate (0.82 \u00b5g\/L or 13.2 \u00b5g\/L), polyvinylpyrrolidone-coated silver nanoparticles (11.1 \u00b5g\/L or 208 \u00b5g\/L), and citrate-coated silver nanoparticles (10.1 \u00b5g\/L or 175 \u00b5g\/L) for 96 h. Mucus concentrations based on glucose as a surrogate were determined at 0 h, 1 h, 2 h, 3 h, 4 h and 24 h after re-dosing each day. Higher mucus production rates following silver treatment were observed at the beginning as compared to controls and compared to after 3 d of exposure. Control fish produced consistent mucus concentrations throughout the exposure (0.62 mg\/L and 0.40 mg\/L at 24 h and 96 h, respectively). Following 24 h of exposure, all silver treatment groups produced significantly more mucus than controls. Following 96 h of exposure, mucus concentrations in treatment groups were significantly reduced compared with each respective treatment at 24 h. Reduced mucus production following long-term silver exposure could prevent the gills from removing silver, and thus increase toxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":31389520,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Fibrosis: a distinguishing feature in the pathology of neural leprosy.\nFibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":28170258,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-26":1,"unknown":12}}},"text":"Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification.\nThe current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis. The library was designed to yield derivatives with ranging polarities and the ability to engage in both covalent and noncovalent interactions, while still remaining within the drimane sesquiterpene scaffold. The prepared compounds were screened against 14 relevant marine micro- and macrofouling species. Several of the polygodial analogues displayed inhibitory activities at sub-microgram\/mL concentrations. These antifouling effects were most pronounced against the macrofouling ascidian Ciona savignyi and the barnacle Balanus improvisus, with inhibitory activities observed for selected compounds comparable or superior to several commercial antifouling products. The inhibitory activity against the microfouling bacteria and microalgae was reversible and significantly less pronounced than for the macrofoulers. This study illustrates that the macro- and microfoulers are targeted by the compounds via different mechanisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":22958795,"dup_signals":{"dup_doc_count":41,"dup_dump_count":26,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":2,"2023-14":3,"2022-49":1,"2022-33":1,"2022-27":1,"2022-21":1,"2021-49":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":2,"2021-04":3,"2020-40":2,"2020-29":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-26":1,"2019-18":1,"2024-30":2,"2024-22":1,"2024-18":2,"2024-10":1}}},"text":"Feline acromegaly.\nAcromegaly, or hypersomatotropism, results from chronic, excessive secretion of growth hormone in the adult animal. The anabolic effects of growth hormone are exerted through the intermediary hormone, insulin-like growth factor 1, which is produced in the liver under the influence of growth hormone. Feline acromegaly is caused by a pituitary adenoma that secretes excessive amounts of growth hormone. Characteristic effects of excessive growth hormone secretion include the development of diabetes mellitus and growth of the acral segments of the body (jaw, extremities, skull, etc.). Acromegaly occurs in older, predominately male cats and is often associated with diabetes mellitus. Other clinical signs include stridor, enlargement of the jaw and extremities, lean weight gain, and organomegaly (heart, liver, kidney, etc.). Diagnosis is made by documentation of increased levels of growth hormone or insulin-like growth factor (or both) and demonstration of a pituitary mass via magnetic resonance imaging or computed tomography. The most effective treatment to date has been radiation therapy. Prognosis is fair to good with proper treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":28551541,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-16":1,"2023-23":1}}},"text":"Variation partitioning of benthic diatom community matrices: Effects of multiple variables on benthic diatom communities in an Austral temperate river system.\nThis study explores diatom community dynamics in a highly modified semi-arid temperate region river system characterised by inconsistent river flow. Various water and sediment environmental variables were assessed using a multi-faceted analysis approach to determine the spatio-temporal drivers of benthic diatom communities in the river system. Overall, the diatom community was generally dominated by pollution tolerant species, reflecting the anthropogenic intensity and activities on the river system. Diatom community composition was found to be largely determined by water column chemistry variables particularly nutrient concentrations in comparison to sediment chemistry and physical variables. Strong seasonal diatom species composition was also observed and this was driven by strong seasonal variations in nutrient loads and metal concentrations, a result of the variable water flow across the two seasons. However, the greater temporal variation in communities was observed in the smaller systems with the mainstream river system being more homogenous over time. In addition, diatom community composition and environmental variables were found to be different and more pronounced between streams and mainstream sites, than between canals and streams. The study highlights the complex interaction between water column, sediment and physical variables in determining the diatom species composition in small river systems. It also highlights the importance of river flow inconsistency as an indirect variable that alters primary drivers such as nutrient concentrations in the water column and heavy metal levels in the sediment.","subset":"pubmed_abstract"} +{"meta":{"pmid":21337412,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":13}}},"text":"Estimation of tensors and tensor-derived measures in diffusional kurtosis imaging.\nThis article presents two related advancements to the diffusional kurtosis imaging estimation framework to increase its robustness to noise, motion, and imaging artifacts. The first advancement substantially improves the estimation of diffusion and kurtosis tensors parameterizing the diffusional kurtosis imaging model. Rather than utilizing conventional unconstrained least squares methods, the tensor estimation problem is formulated as linearly constrained linear least squares, where the constraints ensure physically and\/or biologically plausible tensor estimates. The exact solution to the constrained problem is found via convex quadratic programming methods or, alternatively, an approximate solution is determined through a fast heuristic algorithm. The computationally more demanding quadratic programming-based method is more flexible, allowing for an arbitrary number of diffusion weightings and different gradient sets for each diffusion weighting. The heuristic algorithm is suitable for real-time settings such as on clinical scanners, where run time is crucial. The advantage offered by the proposed constrained algorithms is demonstrated using in vivo human brain images. The proposed constrained methods allow for shorter scan times and\/or higher spatial resolution for a given fidelity of the diffusional kurtosis imaging parametric maps. The second advancement increases the efficiency and accuracy of the estimation of mean and radial kurtoses by applying exact closed-form formulae.","subset":"pubmed_abstract"} +{"meta":{"pmid":2040705,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Minimally modified low density lipoprotein is biologically active in vivo in mice.\nMinimally modified low density lipoprotein (MM-LDL), derived by mild iron oxidation or prolonged storage at 4 degrees C, has been shown to induce certain inflammatory responses in vascular cells in tissue culture. These include induction of monocyte (but not neutrophil) adherence to endothelial cells (EC), induction of EC production of colony stimulating factors (CSF), and induction of EC and smooth muscle cell production of monocyte chemotactic protein (MCP-1). To test for biologic activity in vivo, microgram quantities of MM-LDL were injected into mice, sera were assayed for CSF activity, and tissues were subjected to Northern analysis. After injection of MM-LDL, CSF activity increased approximately 7-26-fold but remained near control levels after injection of native LDL. Essentially all of the induced CSF activity was due to macrophage CSF as judged by antibody inhibition. Injection of MM-LDL into a mouse strain (C3H\/HeJ) that is resistant to bacterial LPS gave similar results, indicating that the induction of CSF was not due to contaminating LPS and suggesting that there are differences in the pathways by which LPS and MM-LDL trigger cytokine production. In addition, after injection of MM-LDL, mRNA for JE, the mouse homologue of MCP-1, was markedly induced in various tissues, but was not induced after injection of native LDL. We conclude, therefore, that MM-LDL is biologically active in vivo and may contribute to the early stages of atherosclerosis by acting as an inflammatory agent.","subset":"pubmed_abstract"} +{"meta":{"pmid":32620835,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":12}}},"text":"Anatomically and functionally distinct thalamocortical inputs to primary and secondary mouse whisker somatosensory cortices.\nSubdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices.","subset":"pubmed_abstract"} +{"meta":{"pmid":35116732,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2024-26":1,"unknown":12}}},"text":"Nav1.5-E3 antibody inhibits cancer progression.\nNav1.5, an isoform of voltage-gated sodium channel alpha subunits, has been found to be over-expressed in cancer cells and linked to disease progression. Nav1.5-third extracellular region antibody (E3Ab) specifically targets the E3 of Nav1.5 and can lead to a subtype-specific inhibition of Nav1.5. We were interested in the therapeutic potential of E3Ab in cancer. The Nav1.5 expression in Caov-3 cells was assessed by immunocytochemistry. The effect of E3Ab on tumor growth in vivo was evaluated by using a nude mouse xenograft model derived from Caov-3 cells. In vitro, SiHa, MDA-MB-231, and Caov-3 cells were treated with E3Ab and cell migration, invasion, and proliferation were evaluated by transwell assays and EdU. Metal matrix protease-9 (MMP-9) expression was analyzed by Western blot. We found that Caov-3 cells highly expressed Nav1.5 and its binding with E3Ab was confirmed. In vivo, the growth of Caov-3 xenografts was significantly inhibited by E3Ab or lidocaine compared to control. The treatment with E3Ab and lidocaine significantly reduced the mitotic activity in tumor. E3Ab, as well as lidocaine, could inhibit the migration and invasion ability of cancer cells in vitro. These findings suggest that E3Ab is a potential new therapeutic antibody for treatment of cancers expressing Nav1.5.","subset":"pubmed_abstract"} +{"meta":{"pmid":23729908,"dup_signals":{"dup_doc_count":16}},"text":"Modeling temperature entrainment of circadian clocks using the Arrhenius equation and a reconstructed model from Chlamydomonas reinhardtii.\nEndogenous circadian rhythms allow living organisms to anticipate daily variations in their natural environment. Temperature regulation and entrainment mechanisms of circadian clocks are still poorly understood. To better understand the molecular basis of these processes, we built a mathematical model based on experimental data examining temperature regulation of the circadian RNA-binding protein CHLAMY1 from the unicellular green alga Chlamydomonas reinhardtii, simulating the effect of temperature on the rates by applying the Arrhenius equation. Using numerical simulations, we demonstrate that our model is temperature-compensated and can be entrained to temperature cycles of various length and amplitude. The range of periods that allow entrainment of the model depends on the shape of the temperature cycles and is larger for sinusoidal compared to rectangular temperature curves. We show that the response to temperature of protein (de)phosphorylation rates play a key role in facilitating temperature entrainment of the oscillator in Chlamydomonas reinhardtii. We systematically investigated the response of our model to single temperature pulses to explain experimentally observed phase response curves.","subset":"pubmed_abstract"} +{"meta":{"pmid":25996290,"dup_signals":{"dup_doc_count":16}},"text":"Systems-based approach to investigate unsafe pedestrian behaviour at level crossings.\nCrashes at level crossings are a major issue worldwide. In Australia, as well as in other countries, the number of crashes with vehicles has declined in the past years, while the number of crashes involving pedestrians seems to have remained unchanged. A systematic review of research related to pedestrian behaviour highlighted a number of important scientific gaps in current knowledge. The complexity of such intersections imposes particular constraints to the understanding of pedestrians' crossing behaviour. A new systems-based framework, called Pedestrian Unsafe Level Crossing framework (PULC) was developed. The PULC organises contributing factors to crossing behaviour on different system levels as per the hierarchical classification of Jens Rasmussen's Framework for Risk Management. In addition, the framework adapts James Reason's classification to distinguish between different types of unsafe behaviour. The framework was developed as a tool for collection of generalizable data that could be used to predict current or future system failures or to identify aspects of the system that require further safety improvement. To give it an initial support, the PULC was applied to the analysis of qualitative data from focus groups discussions. A total number of 12 pedestrians who regularly crossed the same level crossing were asked about their daily experience and their observations of others' behaviour which allowed the extraction and classification of factors associated with errors and violations. Two case studies using Rasmussen's AcciMap technique are presented as an example of potential application of the framework. A discussion on the identified multiple risk contributing factors and their interactions is provided, in light of the benefits of applying a systems approach to the understanding of the origins of individual's behaviour. Potential actions towards safety improvement are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":9129538,"dup_signals":{"dup_doc_count":32,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2021-21":1,"2021-04":1,"2020-50":1,"2020-34":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-47":1,"2019-43":2,"2019-39":1,"2019-30":1,"2019-26":1,"2019-22":3,"2019-18":2,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2021-25":1}}},"text":"Release of reactive oxygen species by phagocytic cells in response to live parasites in mice infected with Trypanosoma cruzi.\nThe release of reactive oxygen intermediates (ROI), mediators of inflammatory reactions, was evaluated in murine Trypanosoma cruzi infection. In acutely infected BALB\/c mice, spleen cells were stimulated, either with epimastigote or trypomastigote forms of the parasite, and the effect was enhanced by serum from infected mice. Only opsonized parasites triggered the release of ROI by normal mouse cells and this response was several times lower than in infected mice. This seems to indicate that cells from acutely infected mice reacted to T. cruzi and that neither parasites nor serum factors blocked the release of ROI. During the acute stage of the infection, both the parasitemia and the release of ROI by spleen cells were higher in BALB\/c than in C3H mice (ROI generated in response to a phagocytic stimulation was 12 and 3 times the normal levels, respectively). In addition, in BALB\/c mice infected with different numbers of parasites, the production of ROI was related to parasitemia. On the other hand, during the chronic stage of the infection, the inflammatory reaction in myocardium was greater in C3H than in BALB\/c mice, and the increase in ROI production was 30% and 100% above the normal levels in BALB\/c and C3H mice, respectively. This suggests that the increased ROI production paralleled the parasite burden in the acute phase, and could be related to inflammatory processes after the control of the parasitemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":30460896,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":17}}},"text":"Adverse factors responsible for below-normal platelet count after laparoscopic splenectomy and azygoportal disconnection.\nSplenectomy is regarded as an effective curative treatment for thrombocytopenia caused by hypersplenism in patients with cirrhosis. However, in clinical practice, thrombocytopenia is not resolved by splenectomy in all patients. This study aimed to evaluate the adverse factors responsible for platelet (PLT) counts below the normal lower limit following laparoscopic splenectomy and azygoportal disconnection (LSD). We retrospectively evaluated the outcomes of 123 cirrhotic patients with portal hypertensive bleeding and secondary hypersplenism, who underwent LSD and who had PLT counts <125\u00d7109\/L (non-normal group) or >125\u00d7109\/L (normal group) at the postoperative month (POM) 3, between April 2014 and March 2017. Sixteen patients (13.01%) had PLT counts <125\u00d7109\/L at POM 3 after LSD, while the remaining 107 patients had normal counts. We analyzed 25 perioperative variables in both groups. A logistic multivariate regression identified age (relative risk [RR] 1.082, 95% confidence interval [CI] 1.018-1.150) and longitudinal spleen diameter (RR 0.977, 95% CI 0.955-1.000) as significant independent factors for the PLT count <125\u00d7109\/L at POM 3. Bivariate correlation analysis showed that age >50 years and longitudinal spleen diameter <160 mm were threshold values for an increased risk of the PLT count <125\u00d7109\/L at POM 3 after LSD. Age was an independent positive predictor and longitudinal spleen diameter an independent negative predictor of PLT count <125\u00d7109\/L at POM 3 after LSD.","subset":"pubmed_abstract"} +{"meta":{"pmid":24135583,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":18}}},"text":"Potential risk factors associated with contact dermatitis, lameness, negative emotional state, and fear of humans in broiler chicken flocks.\nThe objectives of this study were to 1) identify determinants of poor welfare in commercial broiler chicken flocks by studying the associations between selected resource-based measures (RBM, potential risk factors), such as litter quality and dark period, and animal-based welfare indicators (ABM), such as foot pad dermatitis and lameness, and 2) establish the breadth of effect of a risk factor by determining the range of animal welfare indicators associated with each of the risk factors (i.e., the number of ABM related to a specific RBM). Eighty-nine broiler flocks were inspected in 4 European countries (France, Italy, the United Kingdom, and the Netherlands) in a cross-sectional study. The ABM were contact dermatitis (measured using scores of foot-pad dermatitis and hock burn, respectively), lameness (measured as gait score), fear of humans (measured by the avoidance distance test and the touch test), and negative emotional state (measured using qualitative behavior assessment, QBA). In a first step, risk factors were identified by building a multiple linear regression model for each ABM. Litter quality was identified as a risk factor for contact dermatitis. Length of dark period at 3 wk old (DARK3) was a risk factor for the touch test result. DARK3 and flock age were risk factors for lameness, and the number of different stockmen and DARK3 were risk factors for QBA results. Next, the ABM were grouped according to risk factor and counted. Then, in a second step, associations between the ABM were investigated using common factor analysis. The breadth of a risk factor's effect was judged by combining the number (count) of ABM related to this factor and the strength of association between these ABM. Flock age and DARK3 appeared to affect several weakly correlated ABM, thus indicating a broad range of effects. Our findings suggest that manipulation of the predominant risk factors identified in this study (DARK3, litter quality, and slaughter age) could generate improvements in the related ABM and thereby enhance the birds' overall welfare status.","subset":"pubmed_abstract"} +{"meta":{"pmid":15818419,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":3}}},"text":"[Overwhelming course of HCV disease in patients with hypogammaglobulinemia associated with cellular immunity deficiency].\nKnowledge of the physiopathological basis of the fibrogenesis in the hepatopathy by hepatitis C virus (HCV) is critical. We describe the evolution of the infection by HCV after a ten-year follow-up in patients with antibody immunodeficiency (common variable immunodeficiency (n=3) (IDVC), IgG subclasses deficiency (n=2), specific deficiency of antibodies formation (n=1). The patients were treated with a prepared intravenous immunoglobulin that was associated later with an HCV hepatitis outbreak. Five of the six patients had a positive overwhelming course (CRP) for HCV and all have changes in their hepatic biochemistry during the exposure period [ Analine Aminotransferase (ALT) (from 280 to 2720 U\/L) and Aspartate Aminotransferase (AST) (from 400 to 2600) U\/L)]. In less than one year, two patients with IDVC developed cirrhosis and the other patient with IDVC, an active chronic hepatitis while the other patients cured the infection without the treatment. The patients with IDVC presented lower IgG levels than the patients with antibodies deficiency before the exposure (average: seric IgG = 697 mg\/dl and 1480 mg\/dl respectively) and had, in addition, lower T CD4+ lymphocytes [average: T CD4+ lymphocytes = 22% (413 x 106 cells\/l) and 33% (869 x 106 cells\/l) respectively)]. One combination of components of humoral and cellular immunodeficiency could play a role in the accelerated evolutive course of the hepatopathy by HCV in patients with IDVC.","subset":"pubmed_abstract"} +{"meta":{"pmid":24731094,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Treatment approach, surveillance, and outcome of well-differentiated thyroid cancer in childhood and adolescence.\nWell-differentiated thyroid carcinoma in children and adolescents is a rare disease with favorable prognosis despite regional and distant metastasis at presentation in many patients. Treatment recommendations are varied and there is little consensus on follow-up guidelines for these patients. Medical records of patients less than 22 years of age treated at our institution were reviewed. One hundred twelve patients treated between 1969 and 2009 were selected for further analysis. Effects of patient and tumor characteristics on progression-free survival (PFS) were evaluated along with the predictive value of whole-body (131)I scintigraphy in the follow-up setting. Overall survival at 20 years and 30 years was 100% and 94.4%, respectively. PFS at 10, 20, and 30 years was 71%, 62%, and 55%, respectively. Although male patients and younger patients presented with more advanced disease, sex, and age at diagnosis had no effect on risk of PFS. Additionally, neither the presence of vascular invasion, capsular extension, positive margins, nor soft tissue invasion had an effect on PFS. Mean time to recurrence in patients who underwent immediate postoperative (131)I therapy was 3.8 years compared to 14.1 years in patients who either never received (131)I therapy or were treated in the salvage setting (p<0.0001). Negative posttreatment whole-body (131)I scintigraphy was strongly predictive for decreased risk of recurrence, especially in patients with three consecutive negative scans. Pediatric patients are more likely to present with advanced disease and for this reason, the majority of patients treated at our institution receive postoperative (131)I. Long-term surveillance is required in this population because of the risk of late recurrences. Whole-body (131)I scintigraphy is useful for risk stratification; after three consecutive negative scans, the risk of recurrence is low.","subset":"pubmed_abstract"} +{"meta":{"pmid":28735818,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2021-21":1,"2020-50":2,"2020-34":1,"2020-24":1,"2019-35":1,"2019-26":1,"2018-39":1,"2018-26":1,"2018-09":1,"2017-51":1,"2017-43":1,"2021-49":1}}},"text":"Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial.\nType 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg\/day plus piperine 10mg\/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86\u00b125.78 versus -17.06\u00b141.51, respectively; p=0.023), non-HDL-C (-23.42\u00b125.13 versus -16.84\u00b141.42, respectively; p=0.014) and Lp(a) (-1.50\u00b11.61 versus -0.34\u00b11.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56\u00b14.25 versus -0.22\u00b14.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.","subset":"pubmed_abstract"} +{"meta":{"pmid":9950730,"dup_signals":{"dup_doc_count":21,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-21":1,"2022-05":4,"2021-49":4,"2021-43":1,"2020-50":1,"2020-29":1,"2019-51":1,"2019-35":1,"2019-18":1,"2019-09":1,"2022-33":1}}},"text":"Propagating distributions up directed acyclic graphs.\nIn a previous article, we considered game trees as graphical models. Adopting an evaluation function that returned a probability distribution over values likely to be taken at a given position, we described how to build a model of uncertainty and use it for utility-directed growth of the search tree and for deciding on a move after search was completed. In some games, such as chess and Othello, the same position can occur more than once, collapsing the game tree to a directed acyclic graph (DAG). This induces correlations among the distributions at sibling nodes. This article discusses some issues that arise in extending our algorithms to a DAG. We give a simply described algorithm for correctly propagating distributions up a game DAG, taking account of dependencies induced by the DAG structure. This algorithm is exponential time in the worst case. We prove that it is #P complete to propagate distributions up a game DAG correctly. We suggest how our exact propagation algorithm can yield a fast but inexact heuristic.","subset":"pubmed_abstract"} +{"meta":{"pmid":32116930,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":2,"unknown":16}}},"text":"A Theory of Challenge and Threat States in Athletes: A Revised Conceptualization.\nThe Theory of Challenge and Threat States in Athletes (TCTSA) provides a psychophysiological framework for how athletes anticipate motivated performance situations. The purpose of this review is to discuss how research has addressed the 15 predictions made by the TCTSA, to evaluate the mechanisms underpinning the TCTSA in light of the research that has emerged in the last 10 years, and to inform a revised TCTSA (TCTSA-R). There was support for many of the 15 predictions in the TCTSA, with two main areas for reflection identified: to understand the physiology of challenge and to re-evaluate the concept of resource appraisals. This re-evaluation informs the TCTSA-R, which elucidates the physiological changes, predispositions, and cognitive appraisals that mark challenge and threat states. First, the relative strength of the sympathetic nervous system response is outlined as a determinant of challenge and threat patterns of reactivity and we suggest that oxytocin and neuropeptide Y are also key indicators of an adaptive approach to motivated performance situations and can facilitate a challenge state. Second, although predispositions were acknowledged within the TCTSA, how these may influence challenge and threat states was not specified. In the TCTSA-R, it is proposed that one's propensity to appraise stressors is a challenge that most strongly dictates acute cognitive appraisals. Third, in the TCTSA-R, a more parsimonious integration of Lazarusian ideas of cognitive appraisal and challenge and threat is proposed. Given that an athlete can make both challenge and threat primary appraisals and can have both high or low resources compared to perceived demands, a 2 \u00d7 2 bifurcation theory of challenge and threat is proposed. This reflects polychotomy of four states: high challenge, low challenge, low threat, and high threat. For example, in low threat, an athlete can evince a threat state but still perform well so long as they perceive high resources. Consequently, we propose suggestions for research concerning measurement tools and a reconsideration of resources to include social support. Finally, applied recommendations are made based on adjusting demands and enhancing resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":19953239,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Contrasting species-environment relationships in communities of testate amoebae, bryophytes and vascular plants along the fen-bog gradient.\nWe studied the vegetation, testate amoebae and abiotic variables (depth of the water table, pH, electrical conductivity, Ca and Mg concentrations of water extracted from mosses) along the bog to extremely rich fen gradient in sub-alpine peatlands of the Upper Engadine (Swiss Alps). Testate amoeba diversity was correlated to that of mosses but not of vascular plants. Diversity peaked in rich fen for testate amoebae and in extremely rich fen for mosses, while for testate amoebae and mosses it was lowest in bog but for vascular plants in extremely rich fen. Multiple factor and redundancy analyses (RDA) revealed a stronger correlation of testate amoebae than of vegetation to water table and hydrochemical variables and relatively strong correlation between testate amoeba and moss community data. In RDA, hydrochemical variables explained a higher proportion of the testate amoeba and moss data than water table depth. Abiotic variables explained a higher percentage of the species data for testate amoebae (30.3% or 19.5% for binary data) than for mosses (13.4%) and vascular plants (10%). These results show that (1) vascular plant, moss and testate amoeba communities respond differently to ecological gradients in peatlands and (2) testate amoebae are more strongly related than vascular plants to the abiotic factors at the mire surface. These differences are related to vertical trophic gradients and associated niche differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":11872855,"dup_signals":{"dup_doc_count":11}},"text":"The accuracy of reported sensitive sexual behaviour in Britain: exploring the extent of change 1990-2000.\nThe 1990-1 British national probability sample survey of sexual attitudes and lifestyles (Natsal 1990) was repeated in 1999-2001 (Natsal 2000) to update population estimates of risk behaviours, and assess change over time. We examine whether changes in prevalence estimates may partly result from changes in measurement accuracy. Taking Natsal 2000 (11 161 respondents) and Natsal 1990 (13 765 respondents aged 16-44) we compared the response rate, sample representativeness, reporting of abortion last year (relative to official statistics), and selected attitudes. Among the common birth cohort eligible for both surveys (aged 16-34 Natsal 1990, 26-44 Natsal 2000), we compared reporting of experiences before 1990. The response rate (66.8% Natsal 1990, 65.4% Natsal 2000) and completeness of reporting abortion were unchanged (84% Natsal 1990, 86% Natsal 2000). Attitudes were significantly changed in Natsal 2000 relative to Natsal 1990--for example, increased tolerance of male homosexual sex, OR (95% CI) 2.10 (1.93-2.29) men and 2.95 (2.74 to 3.18) women. In the common birth cohort reporting of heterosexual intercourse before 16 (OR 1.15 (1.02 to 1.29) men, 1.49 (1.31 to 1.69) women), and homosexual experience (OR 1.80 (1.46 to 2.21) men, 2.00 (1.61 to 2.48) women) were significantly increased. The results are consistent with improved reporting accuracy for some sensitive behaviours in Natsal 2000, in line with greater social tolerance and improved survey methodology. However, the evidence is not conclusive, and may not be generalisable to all such behaviours. The increase found in the reported prevalence of STI risk behaviours between Natsal 1990 and Natsal 2000 is likely to be somewhat overstated.","subset":"pubmed_abstract"} +{"meta":{"pmid":32788283,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":18}}},"text":"Metabolomic Signatures of Long-term Coffee Consumption and Risk of Type 2 Diabetes in Women.\nCoffee may protect against multiple chronic diseases, particularly type 2 diabetes, but the mechanisms remain unclear. Leveraging dietary and metabolomic data in two large cohorts of women (the Nurses' Health Study [NHS] and NHSII), we identified and validated plasma metabolites associated with coffee intake in 1,595 women. We then evaluated the prospective association of coffee-related metabolites with diabetes risk and the added predictivity of these metabolites for diabetes in two nested case-control studies (n = 457 case and 1,371 control subjects). Of 461 metabolites, 34 were identified and validated to be associated with total coffee intake, including 13 positive associations (primarily trigonelline, polyphenol metabolites, and caffeine metabolites) and 21 inverse associations (primarily triacylglycerols [TAGs] and diacylglycerols [DAGs]). These associations were generally consistent for caffeinated and decaffeinated coffee, except for caffeine and its metabolites that were only associated with caffeinated coffee intake. The three cholesteryl esters positively associated with coffee intake showed inverse associations with diabetes risk, whereas the 12 metabolites negatively associated with coffee (5 DAGs and 7 TAGs) showed positive associations with diabetes. Adding the 15 diabetes-associated metabolites to a classical risk factor-based prediction model increased the C-statistic from 0.79 (95% CI 0.76, 0.83) to 0.83 (95% CI 0.80, 0.86) (P < 0.001). Similar improvement was observed in the validation set. Coffee consumption is associated with widespread metabolic changes, among which lipid metabolites may be critical for the antidiabetes benefit of coffee. Coffee-related metabolites might help improve prediction of diabetes, but further validation studies are needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":17623736,"dup_signals":{"dup_doc_count":27,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2024-18":1,"2017-13":1,"2015-18":3,"2015-11":3,"2015-06":3,"2014-10":3,"2013-48":2,"2024-30":1,"unknown":9}}},"text":"Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.\nIn patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g\/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.","subset":"pubmed_abstract"} +{"meta":{"pmid":24205357,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Scleral micro-RNA signatures in adult and fetal eyes.\nIn human eyes, ocular enlargement\/growth reflects active extracellular matrix remodeling of the outer scleral shell. Micro-RNAs are small non-coding RNAs that regulate gene expression by base pairing with target sequences. They serve as nodes of signaling networks. We hypothesized that the sclera, like most tissues, expresses micro-RNAs, some of which modulate genes regulating ocular growth. In this study, the scleral micro-RNA expression profile of rapidly growing human fetal eyes was compared with that of stable adult donor eyes using high-throughput microarray and quantitative PCR analyses. Scleral samples from normal human fetal (24 wk) and normal adult donor eyes were obtained (n=4 to 6, each group), and RNA extracted. Genome-wide micro-RNA profiling was performed using the Agilent micro-RNA microarray platform. Micro-RNA target predictions were obtained using Microcosm, TargetScan and PicTar algorithms. TaqMan\u00ae micro-RNA assays targeting micro-RNAs showing either highest significance, detection, or fold differences, and collagen specificity, were applied to scleral samples from posterior and peripheral ocular regions (n=7, each group). Microarray data were analyzed using R, and quantitative PCR data with 2^-deltaCt methods. Human sclera was found to express micro-RNAs, and comparison of microarray results for adult and fetal samples revealed many to be differentially expressed (p<0.01, min p= 6.5x10(11)). Specifically, fetal sclera showed increased expression of mir-214, let-7c, let-7e, mir-103, mir-107, and mir-98 (1.5 to 4 fold changes, p<0.01). However, no significant regionally specific differences .i.e., posterior vs. peripheral sclera, were observed for either adult or fetal samples. For the first time, micro-RNA expression has been catalogued in human sclera. Some micro-RNAs show age-related differential regulation, higher in the sclera of rapidly growing fetal eyes, consistent with a role in ocular growth regulation. Thus micro-RNAs represent potential targets for ocular growth manipulation, related to myopia and\/or other disorders such as scleral ectasia.","subset":"pubmed_abstract"} +{"meta":{"pmid":31475104,"dup_signals":{"dup_doc_count":20,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2023-40":2,"2022-49":1,"2022-40":7,"2022-21":1,"2022-05":2,"2021-49":1,"2021-43":2}}},"text":"Association of Polo-Like Kinase 3 and PhosphoT273 Caspase 8 Levels With Disease-Related Outcomes Among Cervical Squamous Cell Carcinoma Patients Treated With Chemoradiation and Brachytherapy.\nIntroduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT. Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset. Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses. Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.","subset":"pubmed_abstract"} +{"meta":{"pmid":27239319,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Association of diabetes with tooth loss in Hispanic\/Latino adults: findings from the Hispanic Community Health Study\/Study of Latinos.\nTo investigate the association between diabetes mellitus and missing teeth in Hispanic\/Latino adults from diverse heritage groups who reside in the USA. The Hispanic Community Health Study\/Study of Latinos (HCHS\/SOL) is a multicenter, population-based study of 18-74 years old who underwent a physical and oral examination (n=15 945). Glycemic status was categorized as diabetes, impaired, or normal, based on medication use, and American Diabetes Association criteria for fasting glucose and glycosylated hemoglobin (HbA1c). HbA1c<7% indicated good glycemic control, and HbA1c>7% indicated uncontrolled diabetes. We estimated ORs and 95% CIs for missing >9 teeth and being edentulous (missing all natural teeth), after adjustment for age, income, education, Hispanic background, study site\/center, nativity, last dental visit, health insurance, diet quality, cigarette smoking, obesity, periodontitis, and C reactive protein. Persons with uncontrolled diabetes had a significant increased likelihood of missing >9 teeth and being edentulous as compared with persons with normal glycemic status (adjusted OR=1.92, 95% CI 1.44 to 2.55 and adjusted OR=1.73, 95% CI 1.22 to 2.46, respectively). The association appeared to be stronger at younger ages (18-44 years old; p for interaction <0.0001). However, we found no associations of either impaired glycemia or controlled diabetes with tooth loss in adjusted models. Dentists should be aware of their Hispanic patients' diabetes status and whether or not they are well controlled, because these may affect tooth loss and impair oral function, which can lead to poor nutrition and complications of diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29781528,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":9}}},"text":"Assessing the Competency and Acceptability of Community Health Worker Provision of Standard Days Method\u00ae in Family Planning Services in Gisagara District, Rwanda.\nThis study assesses the competency and acceptability of community-based provision of Standard Days Method\u00ae (SDM) to first-time users in Rwanda. The national strategy equips community health workers (CHWs) to resupply pills, injectables and condoms to existing clients. With the aim of expanding access, SDM provision to first-time users was added to the method mix in Gisagara district and assessed with a 12 month prospective, mixed methods study. Thirty percent of SDM clients had never used a method of family planning and 58 percent had not been using a method for at least three months. Eighty-seven percent of CHWs correctly screened clients to use SDM and 92 percent accurately explained how to use CycleBeads to prevent pregnancy. After being counseled by the CHWs, 89 percent of clients reported knowledge of all key steps required in using SDM to prevent pregnancy. Nearly all SDM clients (99 percent) believed that CHWs were able to counsel them adequately. These results suggest that CHWs were able to offer SDM as part of their family planning responsibilities, and the study adds to the evidence on the role of CHWs in expanding contraceptive access and choice.","subset":"pubmed_abstract"} +{"meta":{"pmid":18949379,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Gene expression profile of the intima and media of experimentally induced cerebral aneurysms in rats by laser-microdissection and microarray techniques.\nCerebral aneurysm is a common disease with a high prevalence and can cause a catastrophic subarachnoid hemorrhage. To elucidate the molecular mechanism of the formation and progression of cerebral aneurysms, gene expression profiling was performed in experimentally induced rat cerebral aneurysms. The intima and media of cerebral arterial walls in rats with or without aneurysm induction were dissected respectively by a laser-microdissection technique. Changes in gene expression in the intima and media of aneurysmal walls were analyzed using Agilent Rat Oligo Microarrays, followed by a specific pathway analysis using GeneSpring software. Of the 41,012 genes examined, 633 were differentially expressed between a normal cerebral artery and a cerebral aneurysm in the intima, with 395 showing increased expression and 238 showing decreased expression. In the media, 1344 were differentially expressed, with 928 showing increased expression and 416 showing decreased expression. Specific pathway analysis revealed that increased gene expression was associated with proteinase, reactive oxygen species, growth factor, chemokine, complement, adhesion molecule and apoptosis in both the intima and the media of aneurysmal walls. Some genes showed an opposite expression pattern between the intima and the media indicating a different role between endothelial cells and vascular smooth muscle cells in cerebral aneurysm formation and progression. These data suggest that cerebral aneurysmal formation and progression are closely related to vascular inflammation, degeneration of extracellular matrix and apoptosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":22673858,"dup_signals":{"dup_doc_count":14}},"text":"Age of first words predicts cognitive ability and adaptive skills in children with ASD.\nAcquiring useful language by age 5 has been identified as a strong predictor of positive outcomes in individuals with Autism Spectrum Disorders (ASD). This study examined the relationship between age of language acquisition and later functioning in children with ASD (n = 119). First word acquisition at a range of ages was probed for its relationship to cognitive ability and adaptive behaviors at 52 months. Results indicated that although producing first words predicted better outcome at every age examined, producing first words by 24 months was a particularly strong predictor of better outcomes. This finding suggests that the historic criterion for positive prognosis (i.e., \"useful language by age 5\") can be updated to a more specific criterion with an earlier developmental time point.","subset":"pubmed_abstract"} +{"meta":{"pmid":29387575,"dup_signals":{"dup_doc_count":14,"dup_dump_count":11,"dup_details":{"curated_sources":3,"2021-49":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-05":1,"2019-22":1,"2019-13":1,"2019-09":1,"2022-33":1}}},"text":"Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats.\nLiterature has confirmed the pathogenic role of cadmium (Cd) and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO) prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Rats were pretreated with VCO polyphenols (10, 20 and 50 mg\/kg body weight; orally) 2 weeks prior to concurrent Cd administration (5 mg\/kg) for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as reduced glutathione (GSH) and malondialdehyde (MDA) contents were analyzed. Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":29045551,"dup_signals":{"dup_doc_count":31,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-21":1,"2021-10":2,"2021-04":1,"2020-40":1,"2020-24":1,"2020-05":2,"2019-51":1,"2019-43":1,"2019-35":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2023-40":1,"2024-18":2,"2024-10":1}}},"text":"Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy.\nRadiotherapy is an effective treatment of intermediate\/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS). Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.","subset":"pubmed_abstract"} +{"meta":{"pmid":22964113,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":2,"2013-20":2,"2014-10":1,"unknown":4}}},"text":"Impact of a reduced red and processed meat dietary pattern on disease risks and greenhouse gas emissions in the UK: a modelling study.\nConsumption of red and processed meat (RPM) is a leading contributor to greenhouse gas (GHG) emissions, and high intakes of these foods increase the risks of several leading chronic diseases. The aim of this study was to use newly derived estimates of habitual meat intakes in UK adults to assess potential co-benefits to health and the environment from reduced RPM consumption. Modelling study using dietary intake data from the National Diet and Nutrition Survey of British Adults. British general population. Respondents were divided into fifths by energy-adjusted RPM intakes, with vegetarians constituting a sixth stratum. GHG emitted in supplying the diets of each stratum was estimated using data from life-cycle analyses. A feasible counterfactual UK population was specified, in which the proportion of vegetarians measured in the survey population doubled, and the remainder adopted the dietary pattern of the lowest fifth of RPM consumers. Reductions in risks of coronary heart disease, diabetes and colorectal cancer, and GHG emissions, under the counterfactual. Habitual RPM intakes were 2.5 times higher in the top compared with the bottom fifth of consumers. Under the counterfactual, statistically significant reductions in population aggregate risks ranged from 3.2% (95% CI 1.9 to 4.7) for diabetes in women to 12.2% (6.4 to 18.0) for colorectal cancer in men, with those moving from the highest to lowest consumption levels gaining about twice these averages. The expected reduction in GHG emissions was 0.45 tonnes CO(2) equivalent\/person\/year, about 3% of the current total, giving a reduction across the UK population of 27.8 million tonnes\/year. Reduced consumption of RPM would bring multiple benefits to health and environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":21799770,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Proteomic biomarkers for acute interstitial lung disease in gefitinib-treated Japanese lung cancer patients.\nInterstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated \u223c7 million tandem mass spectrometry (MS\/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0\u00d710(-25)), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS\/MS platform implementing strict quality control.","subset":"pubmed_abstract"} +{"meta":{"pmid":20826793,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":9}}},"text":"Intermolecular autophosphorylation regulates myosin IIIa activity and localization in parallel actin bundles.\nMyosin IIIa (Myo3A) transports cargo to the distal end of actin protrusions and contains a kinase domain that is thought to autoregulate its activity. Because Myo3A tends to cluster at the tips of actin protrusions, we investigated whether intermolecular phosphorylation could regulate Myo3A biochemical activity, cellular localization, and cellular function. Inactivation of Myo3A 2IQ kinase domain with the point mutation K50R did not alter maximal ATPase activity, whereas phosphorylation of Myo3A 2IQ resulted in reduced maximal ATPase activity and actin affinity. The rate and degree of Myo3A 2IQ autophosphorylation was unchanged by the presence of actin but was found to be dependent upon Myo3A 2IQ concentration within the range of 0.1 to 1.2 \u03bcm, indicating intermolecular autophosphorylation. In cultured cells, we observed that the filopodial tip localization of Myo3A lacking the kinase domain decreased when co-expressed with kinase-active, full-length Myo3A. The cellular consequence of reduced Myo3A tip localization was decreased filopodial density along the cell periphery, identifying a novel cellular function for Myo3A in mediating the formation and stability of actin-based protrusions. Our results suggest that Myo3A motor activity is regulated through a mechanism involving concentration-dependent autophosphorylation. We suggest that this regulatory mechanism plays an essential role in mediating the transport and actin bundle formation\/stability functions of Myo3A.","subset":"pubmed_abstract"} +{"meta":{"pmid":29311170,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Integrating Community Health Workers Into Medical Homes.\nThough evidence supports the value of community health workers (CHWs) in chronic disease self-management support, and authorities have called for expanding their roles within patient-centered medical homes (PCMHs), few PCMHs in Minnesota have incorporated these health workers into their care teams. We undertook a qualitative study to (1) identify facilitators and barriers to utilizing a CHW model among PCMHs in Minnesota, and (2) define roles played by this workforce within the PCMH team. We conducted 51 semistructured, key-informant interviews of clinic leaders, clinicians, care coordinators, CHWs, and staff from 9 clinics (5 with community health workers, 4 without). Qualitative analysis consisted of thematic coding aligned with interview topics. Four key conceptual themes emerged as facilitators and barriers to utilizing a CHW model: the presence of leaders with knowledge of CHWs who championed the model, a clinic culture that favored piloting innovation vs maintaining established care models, clinic prioritization of patients' nonmedical needs, and leadership perceptions of sustainability. These health care workers performed common and clinic-specific roles that included outreach, health education and coaching, community resource linkage, system navigation, and facilitating communication between clinician and patient. We identified facilitators and barriers to adopting CHW roles as part of PCMH care teams in Minnesota and documented their roles being played in these settings. Our findings can be used when considering strategies to enhance utilization and integration of this emerging workforce.","subset":"pubmed_abstract"} +{"meta":{"pmid":21205147,"dup_signals":{"dup_doc_count":17,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":8}}},"text":"Hepatitis B virus resistance to antiviral drugs: where are we going?\nChronic hepatitis B virus (HBV) infections remain a major public health problem worldwide. According to World Health Organization estimates, more than 300 million people are chronically infected and exposed to the risk of developing severe complications including cirrhosis and hepatocellular carcinoma (HCC). Major progress in the treatment of chronic hepatitis B (CHB) has been made during the last decade with the development of antivirals that inhibit viral polymerase activity. Antiviral drug resistance is an important factor in determining the success of long-term therapy for CHB. The development of resistance to nucleoside analogues (NUCs) has been associated with exacerbations of liver disease. Sequential therapy increases the risk of the emergence of multidrug resistance. The selection of a potent antiviral with a high barrier to resistance as a first-line therapy provides the best chance of achieving long-term treatment goals and should be used whenever possible. This has led to a significant decrease in drug resistance in countries where this strategy is affordable. However, the barrier to resistance of a given antiviral agent is influenced by the genetic barrier, drug potency, patient adherence, pharmacological barrier, viral fitness, the drug mechanisms of action and cross resistance. Furthermore, because of specific viral kinetics, prolonged treatment with NUCs does not result in the clearance of the viral genome from the infected liver. It is therefore important to continue research to identify new viral and immune targets and develop novel antiviral strategies for controlling viral replication as well as preventing drug resistance and its complications in the long term.","subset":"pubmed_abstract"} +{"meta":{"pmid":23754147,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Determination of fossil carbon content in Swedish waste fuel by four different methods.\nThis study aimed to determine the content of fossil carbon in waste combusted in Sweden by using four different methods at seven geographically spread combustion plants. In total, the measurement campaign included 42 solid samples, 21 flue gas samples, 3 sorting analyses and 2 investigations using the balance method. The fossil carbon content in the solid samples and in the flue gas samples was determined using (14)C-analysis. From the analyses it was concluded that about a third of the carbon in mixed Swedish waste (municipal solid waste and industrial waste collected at Swedish industry sites) is fossil. The two other methods (the balance method and calculations from sorting analyses), based on assumptions and calculations, gave similar results in the plants in which they were used. Furthermore, the results indicate that the difference between samples containing as much as 80% industrial waste and samples consisting of solely municipal solid waste was not as large as expected. Besides investigating the fossil content of the waste, the project was also established to investigate the usability of various methods. However, it is difficult to directly compare the different methods used in this project because besides the estimation of emitted fossil carbon the methods provide other information, which is valuable to the plant owner. Therefore, the choice of method can also be controlled by factors other than direct determination of the fossil fuel emissions when considering implementation in the combustion plants.","subset":"pubmed_abstract"} +{"meta":{"pmid":17990319,"dup_signals":{"dup_doc_count":22,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2016-18":1,"2015-48":1,"2015-40":1,"2015-32":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":3,"2014-23":1,"2014-15":1,"2016-22":1,"2017-13":1}}},"text":"Protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenstr\u00f6m macroglobulinemia.\nProtein electrophoresis is used for the detection, evaluation and follow-up of monoclonal gammopathy (MG) conditions such as Waldenstr\u00f6m macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal gammopathy, were then followed for a median of 17 years (range, 13-25). The monoclonal gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations.","subset":"pubmed_abstract"} +{"meta":{"pmid":35870597,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-10":2,"2024-30":1,"unknown":6}}},"text":"Methane and carbon dioxide cycles in lakes of the King George Island, maritime Antarctica.\nFreshwater ecosystems are important contributors to the global greenhouse gas budget and a comprehensive assessment of their role in the context of global warming is essential. Despite many reports on freshwater ecosystems, relatively little attention has been given so far to those located in the southern hemisphere and our current knowledge is particularly poor regarding the methane cycle in non-perennially glaciated lakes of the maritime Antarctica. We conducted a high-resolution study of the methane and carbon dioxide cycle in a lake of the Fildes Peninsula, King George Island (Lat. 62\u00b0S), and a succinct characterization of 10 additional lakes and ponds of the region. The study, done during the ice-free and the ice-seasons, included methane and carbon dioxide exchanges with the atmosphere (both from water and surrounding soils) and the dissolved concentration of these two gases throughout the water column. This characterization was complemented with an ex-situ analysis of the microbial activities involved in the methane cycle, including methanotrophic and methanogenic activities as well as the methane-related marker gene abundance, in water, sediments and surrounding soils. The results showed that, over an annual cycle, the freshwater ecosystems of the region are dominantly autotrophic and that, despite low but omnipresent atmospheric methane emissions, they act as greenhouse gas sinks.","subset":"pubmed_abstract"} +{"meta":{"pmid":30856943,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Virulence Characterization of Single-Zoospore Isolates of Sclerospora graminicola from Pearl Millet.\nSclerospora graminicola, the causal agent of downy mildew in pearl millet, is well-known for variation in its virulence pattern. Nine single-zoospore isolates (Sg 026-Z-1 to Sg 026-Z-9) derived from an oosporic isolate Sg 026 from a pearl millet F1 hybrid cultivar Nath 4209 grown in a farmer's field in a village, Veelad, in Maharashtra state, India, and three controls (Sg 026, Field-1, and Field-2) were evaluated for their virulence in two experimental runs in a greenhouse. The isolates were maintained on pot-grown seedlings of a highly susceptible pearl millet line, 7042S, in a greenhouse through asexual (sporangial) generations. Pot-grown seedlings of six pearl millet potential differential lines\/cultivars (7042S, NHB 3, MBH 110, ICMH 451, 843B, and 852B) were spray-inoculated with a sporangial suspension (5 \u00d7 105 sporangia ml-1) and maintained in a greenhouse at 25 \u00b1 2\u00b0C. Data were recorded for latent period (days) and disease incidence (%), from which a virulence index (incidence \u00d7 latent period-1) was calculated to quantify disease-causing potential of isolates. Results indicated significant variation in latent period, incidence, and virulence index among isolates. The isolates were classified into four distinct pathotype groups based on their virulence indices on six pearl millet lines. Because of the significant variation for virulence in the S. graminicola population infecting Nath 4209, it is recommended that the hybrid be regularly monitored for downy mildew infection in farmers' fields, and be replaced by a resistant cultivar that is genetically unrelated to the parental lines of Nath 4209. This will help delay or avoid development of downy mildew epidemics and the resulting heavy loss to pearl millet farmers in the region.","subset":"pubmed_abstract"} +{"meta":{"pmid":30465202,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":2,"unknown":9}}},"text":"Conditional Genetic Ablation Mouse Models as a Tool to Study Cancer Immunosurveillance In Vivo.\nOver the last decades, it has been established that the immune system is crucial for the impediment of cancer development by recognizing and destroying transformed cells. This process has been termed cancer immunosurveillance. Small animal models have significantly facilitated our understanding of it. Dissecting the contribution of any specific immune cell type participating in this process requires the ability to specifically target it while leaving the other immune components as well as the cancer model system unperturbed in vivo. Here, we provide a simple and rapid protocol for the generation of transgenic mice expressing Cre recombinase in a cell type-specific manner-in our example we chose cells expressing Ncr1, which encodes for the surface protein NKp46-and the use of those mice to ablate NKp46+ cells in order to study their role in a model of cancer immunosurveillance against experimental pulmonary metastases. This protocol can easily be adapted to target other cell types and other cancer models.","subset":"pubmed_abstract"} +{"meta":{"pmid":1951614,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"How high do we jump? The effect of reimbursement on occupational therapy.\nThis paper explores the extent to which third-party reimbursement dictates occupational therapy practice. A literature review was used to examine the history and meaning of reimbursement in regard to occupational therapy. It was found that the profession has altered its definition, practice, management, ethics, and professional response as a result of changes in reimbursement. Reimbursement policies reflect societal influences and are shaping occupational therapy in several ways. Control has shifted to third-party payers, allowing them to define occupational therapy; use of the medical model is being rewarded by reimbursement; the language used to discuss the profession has changed to accommodate the insurance and other industries; and values that dominate society are being reinforced. Conflict between the values of society and the values of the occupational therapy profession is a source of struggle for many clinicians. If the causes of the reimbursement-imposed constraints on practice are understood, occupational therapists will be free to be proactive in issues of health care policy.","subset":"pubmed_abstract"} +{"meta":{"pmid":15851561,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Human corneal endothelial cell precursors isolated by sphere-forming assay.\nTo isolate precursors of human corneal endothelial cells (HCECs) in vitro. HCECs were subjected to a sphere-forming assay in which spheres floated in serum-free medium containing growth factors. To promote differentiation, the isolated sphere colonies were plated in dishes coated with poly-L-lysine (PLL)\/laminin or fetal bovine endothelium extracellular matrix. Marker expression of neural and mesenchymal cells was examined in the sphere colonies and their progenies by immunocytochemistry and\/or reverse transcription-polymerase chain reaction (RT-PCR). Adherent differentiated cells from the sphere colonies were evaluated morphologically and functionally. HCECs formed primary and secondary spherical colonies, as shown by sphere-forming assay in vitro. The colonies expressed nestin, beta3-tublin, glial fibrillary acidic protein, and alpha-smooth muscle actin on immunocytochemistry. The progeny, proliferating on extracellular matrix derived from bovine corneal endothelium, but not on PLL\/laminin-coated and noncoated dishes, expressed nestin and beta3-tublin. These markers were confirmed by RT-PCR. Adherent differentiated cells from the sphere colonies had an HCEC-like hexagonal shape and satisfactory transport activity that is essential in HCECs. These findings indicate that the HCEC contains precursor cells with a propensity to differentiate into HCECs and that these cells can also produce neuronal and mesenchymal cell proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":9521984,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.\nChronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of patients without an HLA-identical sibling, but the morbidity and mortality associated with such transplants have been cause for concern. We analyzed the safety and efficacy of transplants from unrelated donors for the treatment of chronic myeloid leukemia and identified variables that predict a favorable outcome. Between May 1985 and December 1994, 196 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase received marrow transplants from unrelated donors. The median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5 percent of patients who could be evaluated. Acute graft-versus-host disease of grade III or IV severity was observed in 35 percent of patients who received HLA-matched transplants, and the estimated cumulative incidence of relapse at five years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57 percent. Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years. Survival was improved by the prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of survival at five years was 74 percent (95 percent confidence interval, 62 to 86 percent) for patients who were 50 years of age or younger who received a transplant from an HLA-matched donor within one year after diagnosis. Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with chronic myeloid leukemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":33407003,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":7}}},"text":"First-language influence on second language speech perception depends on task demands.\nWhile listening to non-native speech, second language users filter the auditory input through their native language. We examined how bilinguals perceived second language (L2 English) sound sequences that conflicted with native-language (L1 Spanish) constraints across three experiments with different task demands. We used the L1 Spanish phonotactic constraint (i.e., rule for combining speech sounds) that vowels must precede s+consonant clusters (e.g., Spanish: estricto, \"strict\"). This L1 Spanish constraint may influence Spanish-English bilinguals' processing of L2 English words such as strict because of a missing initial vowel, as in estrict. We found that the extent to which bilinguals were influenced by the L1 during L2 processing depended on task demands. When metalinguistic awareness demands were low, as in the AX word discrimination task (Experiment 1), cross-linguistic effects were not observed. When metalinguistic awareness demands were high, as in the vowel detection (Experiment 2) and lexical decision (Experiment 3) tasks, response times demonstrated that bilinguals were influenced by the L1 constraint when processing L2 words beginning with an s+consonant. We conclude that bilinguals are cross-linguistically influenced by L1 phonotactic constraints during L2 processing when metalinguistic demands are higher, suggesting that L2 input may be mapped onto L1 sub-lexical representations during perception. These results extend previous research on language co-activation and speech perception by providing a more fine-grained understanding of task demands and elucidating when and where cross-linguistic phonotactic access is present during bilingual comprehension.","subset":"pubmed_abstract"} +{"meta":{"pmid":37691474,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":4,"2024-10":1,"2024-26":1,"unknown":5}}},"text":"Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.\nFluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.","subset":"pubmed_abstract"} +{"meta":{"pmid":24750783,"dup_signals":{"dup_doc_count":11}},"text":"von Willebrand disease and aging: an evolving phenotype.\nBecause the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related differences in bleeding phenotype between elderly VWD patients and those < 65 years. We also studied co-morbidity in elderly patients. We included VWD patients with VWF levels \u2264 30 U dL(-1) in the nationwide cross-sectional 'Willebrand in the Netherlands' (WiN-) study. Patients reported bleeding episodes and treatment of VWD in the year preceding inclusion and during life. This was compared between VWD patients older (n = 71) and younger (16-64 years, n = 593) than 65 years. In elderly patients, age-related changes in VWF and FVIII levels were studied longitudinally by including all historically measured levels. All medical records were examined for co-morbidity. In elderly type 1 patients, a decade age increase was associated with a 3.5 U dL(-1) (95% CI, -0.6 to 7.6) VWF:Ag increase and 7.1 U dL(-1) (95% CI, 0.7 to 13.4) FVIII:C increase. This increase was not observed in elderly type 2 patients. Elderly type 2 patients reported significantly more bleeding symptoms in the year preceding inclusion than younger patients (16\/27, 59% vs. 87\/221, 39%; P = 0.048), which was not observed in type 1 VWD. von Willebrand factor parameters and bleeding phenotype evolve with increasing age in VWD. VWF and FVIII levels increase with age in type 1 patients with no mitigation in bleeding phenotype. In type 2 patients VWF parameters do not increase with age and in these patients aging is accompanied by increased bleeding.","subset":"pubmed_abstract"} +{"meta":{"pmid":8989692,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Screw epiphysiodesis for ankle valgus.\nProgressive ankle valgus is an insidious deformity that may develop during childhood due to a variety of etiologies including neuromuscular disease, skeletal dysplasia, chromosomal anomalies, and clubfoot. This may be concomitant with, or mistaken for, hindfoot valgus. The surgical options for treatment include supramalleolar osteotomy or hemiepiphysiodesis of the medial distal tibial physis. We report the rationale and technique of retarding medial malleolar growth by means of inserting a single 4.5-mm vertical screw. In a population of 31 children (50 feet), we have observed satisfactory improvement of ankle valgus with low morbidity and without permanent physeal closure. This represents a safe, predictable, and effective solution for children who present with progressive and symptomatic ankle valgus.","subset":"pubmed_abstract"} +{"meta":{"pmid":21795004,"dup_signals":{"dup_doc_count":26,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-48":1,"unknown":24}}},"text":"Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome.\nA recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum\/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.","subset":"pubmed_abstract"} +{"meta":{"pmid":29755812,"dup_signals":{"dup_doc_count":19,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-43":1,"2019-22":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-39":1,"2018-34":1,"2018-26":4,"2018-17":1,"2018-13":1,"2020-24":1}}},"text":"Is Bilateral Staged Muscle-Sparing Thoracotomy Performed within 1 Week for Lung Hydatid Cysts Safe for Pediatric Patients?\nMedian sternotomy or staged thoracotomies are generally the preferred surgical treatment options for bilateral lung hydatid cysts. According to literature, it is usually recommended to wait from 3 weeks to 3 months between bilateral staged thoracotomies. The aim of this study is to compare postoperative complications, hospitalization days and morbidity and mortality ratios between unilateral thoracotomy and bilateral staged thoracotomy groups and to evaluate the safety of performing bilateral staged thoracotomy within 1 week for lung hydatid cysts in pediatric patients. In total, 112 patients under the age of 16 years who underwent surgery between 2000 and 2016 because of pulmonary hydatid cysts were included in this study. The patients were classified into two groups as Group 1 (unilateral muscle-sparing thoracotomy) and Group 2 (bilateral staged muscle-sparing thoracotomy applied within 1 week). There were 91 patients in Group 1 and 21 patients in Group 2. No statistically significant differences were detected when both groups were compared by age, gender, perforation rates, follow-up period and postoperative complications. To prevent hydatid cysts complications, the elapsed time between two thoracotomies should be not only long enough to evaluate the postoperative complications but also relatively short to prevent possible complications that may develop in the other lung. In our opinion, a patient follow-up of 3-7 days between thoracotomies is sufficient for the assessment of patients' clinical status and possible complications.","subset":"pubmed_abstract"} +{"meta":{"pmid":16769388,"dup_signals":{"dup_doc_count":37,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2014-10":2,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":29}}},"text":"Definition of metabolic syndrome in preadolescent girls.\nTo compare and contrast proposed definitions of metabolic syndrome in pediatrics, and to determine prevalence of metabolic syndrome in preadolescent females when applying different criteria. A literature review on definitions of metabolic syndrome and cardiovascular \"risk factor clustering\" in children and adolescents published in the past decade. Pediatric definitions of metabolic syndrome were then applied to a community-based study of 261 black preadolescent females (Girls Health Enrichment MultiSite studies [GEMS]) and a school-based, cross-sectional study of 240 ethnically-diverse preadolescent females (Girls Activity, Movement and Environmental Strategy [GAMES]) who had a baseline physical examination and fasting morning blood sample. Agreement among pediatric definitions of metabolic syndrome was poor. The prevalence of MS and cardiovascular risk factor clustering ranged from 0.4% to 23.0% for GEMS and 2.0% to 24.6% for GAMES with definitions adapted from the National Cholesterol Education Program Adult Treatment Panel III, and 0% to 15.3% for GEMS and 0.4% to 15.8% for GAMES using modified criteria from the World Health Organization. The prevalence of metabolic syndrome in preadolescent girls varies widely because of disagreement among proposed definitions of metabolic syndrome in pediatrics. Further investigation is needed to determine which metabolic factors and their respective cut points should be used to identify children at risk for development of clinical disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":23016940,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":1,"2022-27":2,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-26":1}}},"text":"HomeoDB2: functional expansion of a comparative homeobox gene database for evolutionary developmental biology.\nHomeobox gene database (HomeoDB), a manually curated database of homeobox genes and their classification, has been well received since its release in 2008. Here, we report HomeoDB2, an expansion and improvement of the original database that provides greater functionality for the user. HomeoDB2 includes all homeobox loci from 10 animal genomes (human, mouse, chicken, frog, zebrafish, amphioxus, nematode, fruitfly, beetle, honeybee) plus tools for downloading sequences, comparing between species and BLAST searching. HomeoDB2 provides a resource for studying the dynamics of homeobox gene evolution, and is freely accessible at http:\/\/homeodb.zoo.ox.ac.uk.","subset":"pubmed_abstract"} +{"meta":{"pmid":32032220,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Long-term Outcomes Following Vickers Ligament Release and Growth Modulation for the Treatment of Madelung Deformity.\nMadelung deformity arises from a partial distal radial growth disturbance in combination with an abnormal hypertrophic ligament spanning the volar radius and carpus, termed, the Vickers ligament. The purpose of this study is to report long-term clinical and radiographic outcomes following Vickers ligament release and distal radial physiolysis in a population of skeletally immature patients with symptomatic Madelung deformity. Medical records were retrospectively reviewed of patients with Madelung deformity surgically treated between 1994 and 2005. All eligible patients who underwent a Vickers ligament release and distal radial physiolysis were contacted and invited to return to the clinic for follow-up. Six patients (8 wrists) with Madelung deformity underwent Vickers ligament release and distal radial physiolysis. All were white females with a mean age at initial presentation of 11.4 years (10 to 12.8 y). Mean age at the time of initial surgery was 12.0 years (10.0 to 14.5 y). The median follow-up time was 10.6 years (5.8 to 21.9 y) and the average age at last follow-up was 23.1 years (17.5 to 32.2 y). Pain alone or in combination with concerns for deformity was the chief complaint in 6 of 8 of the wrists. At 1 year of clinical follow-up, 7 of 8 wrists were reported to be pain-free, and 6 of the 8 were noted to be completely pain-free at last follow-up. Motion in flexion, extension, pronation, supination, radial, or ulnar deviation was similar between the preoperative status and long-term follow-up. The average preoperative ulnar tilt was 35.1 degrees (SD: 8.5 degrees), average preoperative lunate subsidence was 1.9 degrees (SD: 1.8 degrees), and average preoperative palmar carpal displacement was 21.9 degrees (SD: 2.9 degrees). At the final follow-up, there was a large progression in lunate subsidence, but minimal change in ulnar tilt and palmar carpal displacement. At last clinical follow-up, 2 of the 6 patients had undergone a subsequent procedure including 1 radial dome osteotomy and 1 ulnar shortening osteotomy. In the skeletally immature patient population with Madelung deformity with growth potential remaining, distal radial physiolysis and Vickers ligament release is associated with relief of pain, preservation of motion, and, a reasonable rate of reoperation. This was a therapeutic study. Level II.","subset":"pubmed_abstract"} +{"meta":{"pmid":23568328,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"Deconstructing the default: cortical subdivision of the default mode\/intrinsic system during self-related processing.\nRecent brain imaging research has highlighted a new global system of areas termed the Default Mode network (DM), which appears to specialize in intrinsically oriented functions. However, it is still unresolved to what extent this system contains functional subsystems as in the better known sensory and motor cortices. Here, we report that functional subdivisions can be revealed within individual nodes of the DM, such as the Inferior Parietal Lobule (IPL), through the use of different categories of self-oriented tasks. Subjects underwent BOLD fMRI scans during which they were asked to recall self-related positive and negative information in the categories of people and food. These tasks elicited distinct regions of activation within the DM. Importantly, the observed activations were above the activity level in the baseline, no-task condition for these regions. The main subdivision within the DM was observed in the inferior and posterior parietal cortex. Analysis of coherent resting state fluctuations (functional connectivity analysis) revealed that these regions of activation were part of a distinct network of regions within the DM. These results argue against viewing the DM as a unitary system, and are compatible with the notion that, similar to the rest of the cerebral cortex, the DM consists of distinct, functionally specialized subregions.","subset":"pubmed_abstract"} +{"meta":{"pmid":19703908,"dup_signals":{"dup_doc_count":27,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-24":1,"2019-39":1,"2019-30":2,"2019-18":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-10":1,"2024-30":1}}},"text":"Leukaemia survival trends in children with Down's syndrome in Great Britain, 1971-2000: a population-based study.\nChildren with Down's syndrome (DS) who developed leukaemia have had a worse prognosis than other children with leukaemia in the past. In the 1970s and early 1980s, some children with DS who developed leukaemia received fewer cycles of chemotherapy or were advised not to have treatment. In this population-based study, trends in 5-year survival from leukaemia were evaluated for children with and without DS who were diagnosed in Great Britain during 1971-2000 and followed to the end of 2004. For all children, with and without DS, survival has increased dramatically over the 30 year study period. For lymphoid leukaemia, survival in children with DS increased, but remains lower than for other children (5-year survival 59% vs 83% during 1996-2000). For acute non-lymphoblastic leukaemia (ANLL), however, 5-year survival improved substantially for children with DS, from less than 1% in the early 1970s to over 80% in the 1990s. For other children, survival increased from 6% to 64% during the same period. Survival for all children diagnosed with leukaemia has improved during the last three decades. For lymphoid leukaemia, the inferior outcome observed on more recent treatment protocols in children with DS remains an area for concern. For ANLL, the improvement in survival for children with DS is due to a number of factors, namely increased recruitment of these children to clinical trials, changes in clinical practice and important differences in the biology of myeloid leukaemia in young children with DS, resulting in a better response to some chemotherapeutic agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":19116438,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"High-intensity kayak performance after adaptation to intermittent hypoxia.\nLive-high train-low altitude training produces worthwhile gains in performance for endurance athletes, but the benefits of adaptation to various forms of artificial altitude are less clear. To quantify the effects of intermittent hypoxic exposure on kayak performance. In a crossover design with a 6-week washout, we randomized 10 subelite male sprint kayak paddlers to hypoxia or control groups for 3 weeks (5 days\/week) of intermittent hypoxic exposure using a nitrogen-filtration device. Each day's exposure consisted of alternately breathing hypoxic and ambient air for 5 minutes each over 1 hour. Performance tests were an incremental step test to estimate peak power, maximal oxygen uptake, exercise economy, and lactate threshold; a 500-m time trial; and 5 x 100-m sprints. All tests were performed on a wind-braked kayak ergometer 7 and 3 days pretreatment and 3 and 10 days posttreatment. Hemoglobin concentration was measured at 1 day pretreatment, 5 and 10 days during treatment, and 3 days after treatment. Relative to control, at 3 days posttreatment the hypoxia group showed the following increases: peak power 6.8% (90% confidence limits, + or - 5.2%), mean repeat sprint power 8.3% (+ or - 6.7%), and hemoglobin concentration 3.6% (+ or - 3.2%). Changes in lactate threshold, mean 500-m power, maximal oxygen uptake, and exercise economy were unclear. Large effects for peak power and mean sprint speed were still present 10 days posthypoxia. These effects of intermittent hypoxic exposure should enhance performance in kayak racing. The effects might be mediated via changes in oxygen transport.","subset":"pubmed_abstract"} +{"meta":{"pmid":30489607,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.\nWhole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. To assess whether xerostomia is a toxic effect of WBRT. This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use. Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":30863200,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Study of the underlying event in top quark pair production in p p collisions at 13 Te .\nMeasurements of normalized differential cross sections as functions of the multiplicity and kinematic variables of charged-particle tracks from the underlying event in top quark and antiquark pair production are presented. The measurements are performed in proton-proton collisions at a center-of-mass energy of 13 Te , and are based on data collected by the CMS experiment at the LHC in 2016 corresponding to an integrated luminosity of 35.9 fb - 1 . Events containing one electron, one muon, and two jets from the hadronization and fragmentation of b quarks are used. These measurements characterize, for the first time, properties of the underlying event in top quark pair production and show no deviation from the universality hypothesis at energy scales typically above twice the top quark mass.","subset":"pubmed_abstract"} +{"meta":{"pmid":16737550,"dup_signals":{"dup_doc_count":30,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2018-09":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-44":1,"2016-36":1,"2016-26":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":2,"2014-41":1,"2014-35":1,"2014-23":2,"2018-17":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1}}},"text":"Pathogenesis and vertical transmission of a transplacental rat cytomegalovirus.\nCytomegalovirus (CMV) congenital infection is the major viral cause of well-documented birth defects in human. Because CMV is species-specific, the main obstacle to developing animal models for congenital infection is the difference in placental architecture, which preludes virus transmission across the placenta. The rat placenta, resembling histologically to that of human, could therefore facilitate the study of CMV congenital infection in human. In this report, we present clear evidences of the transplacental property of a new rat CMV (RCMV), namely ALL-03, which had been isolated from placenta and uterus of the house rat. Our study signifies the detection of infectious virus, virus particles, viral protein and DNA as well as immune response to demonstrate a natural model of acute CMV infection including the immunocompetent and immunocompromised host associated with or without pregnancy. It is characterized by a full range of CMV related clinical signs; lesions and anatomical virus distribution to uterus, placenta, embryo, fetus, neonate, lung, kidney, spleen, liver and salivary gland of the infected rats in addition to the virus-specific seroconversion. The preference of the virus for different organs mimics the situation in immunocompromised man. Most interestingly, the placenta was observed to be involved in the maternofetal infection and hence confirmed the hypothesis that the RCMV strain ALL-03 is capable to cross the placenta and infect the offsprings congenitally. The maternal viremia leading to uterine infection which subsequently infecting to the fetus through the placenta is the most likely phenomenon of CMV vertical transmission in our study.","subset":"pubmed_abstract"} +{"meta":{"pmid":8385978,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2021-43":2,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-17":2,"2018-09":1,"2018-05":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1}}},"text":"Tumour markers for prediction of survival and monitoring of remission in small cell lung cancer.\nLevels of the tumour markers neurone specific enolase (NSE), lactate dehydrogenase (LDH), chromogranin A (ChrA) and carcinoembryonic antigen (CEA) were measured in serum taken at presentation and during treatment, remission and relapse from 154 patients who received chemotherapy for small cell lung cancer at a single centre over a 6 year period. At presentation NSE was the most frequently elevated marker, being raised in 81% of patients and significantly higher in extensive as opposed to limited disease, as were LDH and ChrA. The response rate to therapy was best correlated with presentation level of ChrA, being 79% for those whose levels were within twice the upper limit of normal and 51% above (P < 0.01). Multivariate regression analysis showed NSE, performance status and albumin at presentation to be the best independent predictors of survival. Patients with NSE below twice the upper limit of normal, Karnofsky performance status of 80 or above and albumin 35 g l-1 or above had a median survival of 15 months with 25% alive at 2 years, whilst those with NSE above twice normal, Karnofsky below 80 and albumin less that 35 g l-1 had all died by 8 months. Changes in marker levels during therapy were of low predictive value for outcome although the finding of rising NSE during chemotherapy after an initial fall correlated with significantly reduced duration of remission. There was a strong inverse correlation between the NSE level at the time of response and duration of remission (P < 0.0001). Prediction of relapse was most reliable with ChrA, 52% of patients having rising levels before clinical evidence of disease recurrence.","subset":"pubmed_abstract"} +{"meta":{"pmid":23815527,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Mechanosignaling in bone health, trauma and inflammation.\nMechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-\u03baB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and\/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-\u03baB signaling cascade. Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health.","subset":"pubmed_abstract"} +{"meta":{"pmid":18281334,"dup_signals":{"dup_doc_count":30,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2018-05":1,"2017-30":1,"2015-35":1,"2015-32":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":4,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-23":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1}}},"text":"Vortex wake and flight kinematics of a swift in cruising flight in a wind tunnel.\nIn this paper we describe the flight characteristics of a swift (Apus apus) in cruising flight at three different flight speeds (8.0, 8.4 and 9.2 m s(-1)) in a low turbulence wind tunnel. The wingbeat kinematics were recorded by high-speed filming and the wake of the bird was visualized by digital particle image velocimetry (DPIV). Certain flight characteristics of the swift differ from those of previously studied species. As the flight speed increases, the angular velocity of the wingbeat remains constant, and so as the wingbeat amplitude increases, the frequency decreases accordingly, as though the flight muscles were contracting at a fixed rate. The wings are also comparatively inflexible and are flexed or retracted rather little during the upstroke. The upstroke is always aerodynamically active and this is reflected in the wake, where shedding of spanwise vorticity occurs throughout the wingbeat. Although the wake superficially resembles those of other birds in cruising flight, with a pair of trailing wingtip vortices connected by spanwise vortices, the continuous shedding of first positive vorticity during the downstroke and then negative vorticity during the upstroke suggests a wing whose circulation is gradually increasing and then decreasing during the wingbeat cycle. The wake (and implied wing aerodynamics) are not well described by discrete vortex loop models, but a new wake-based model, where incremental spanwise and streamwise variations of the wake impulse are integrated over the wingbeat, shows good agreement of the vertical momentum flux with the required weight support. The total drag was also estimated from the wake alone, and the calculated lift:drag ratio of approximately 13 for flapping flight is the highest measured yet for birds.","subset":"pubmed_abstract"} +{"meta":{"pmid":23970173,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":4,"unknown":8}}},"text":"[Adolphe Quetelet and biopolitics as secularized theology].\nThe article recaptures the work of an author who has been forgotten by the contemporary social sciences, that is, the Belgium polymath Adolphe Quetelet. Focusing on his main work, Sur l'homme et le d\u00e9veloppement de ses facult\u00e9s, ou Essai de physique sociale, the study underscores how the secularization of theological principles within the realm of science was important to the construction of Quetelet's work. His dual engagement in science and politics is pertinent here, as he was the main nineteenth-century force behind the incorporation of statistics as a science essential to the State's ability to govern its people. He also played a relevant role in the realization of the hegemonic political project of modernity, biopolitics, and its influence in the field of biomedicine in the nineteenth and twentieth centuries.","subset":"pubmed_abstract"} +{"meta":{"pmid":30972253,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Spatial variation in allometric growth of invasive lionfish has management implications.\nLionfish (Pterois volitans\/miles) are an invasive species in the Western Atlantic and the Caribbean. Improving management of invasive lionfish populations requires accurate total biomass estimates, which depend on accurate estimates of allometric growth; sedentary species like lionfish often exhibit high levels of spatial variation in life history characteristics. We reviewed 17 published length-weight relationships for lionfish taken throughout their invasive range and found regional differences that led to significant misestimates when calculating weight from length observations. The spatial pattern we observed is consistent with findings from other studies focused on genetics or length-at-age. Here, the use of ex situ parameter values resulted in total biomass estimates between 76.2% and 140% of true observed biomass, and up to a threefold under- or overestimation of total weight for an individual organism. These findings can have implications for management in terms of predicting effects on local ecosystems, evaluating the effectiveness of removal programs, or estimating biomass available for harvest.","subset":"pubmed_abstract"} +{"meta":{"pmid":12297674,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Id: a target of BMP signaling.\nCytokines of the transforming growth factor-beta (TGF-beta) superfamily transduce their signals by activating receptor-regulated Smads (R-Smads). Distinct R-Smads or combinations of R-Smads are activated by TGF-beta, activin, or bone morphogenetic proteins (BMPs). R-Smads activated by BMPs induce expression of Id proteins, which act as inhibitors of differentiation and stimulators of cell growth by inhibiting the function of basic helix-loop-helix transcription factors. In endothelial cells, TGF-beta binds to two distinct type I receptor serine-threonine kinases, ALK-5 and ALK-1; the latter activates the same R-Smads that are activated by BMP and induces synthesis of Id (inhibitor of differentiation or inhibitor of DNA binding) proteins. Growing evidence suggests that Id proteins may play crucial roles in angiogenesis, neurogenesis, and osteogenesis and act as key molecules in regulating biological responses induced by BMPs and TGF-beta.","subset":"pubmed_abstract"} +{"meta":{"pmid":35148172,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"Convolutional neural network-based reconstruction for acceleration of prostate T2 weighted MR imaging: a retro- and prospective study.\nThe aim of this study was to develop a deep neural network (DNN)-based parallel imaging reconstruction for highly accelerated 2D turbo spin echo (TSE) data in prostate MRI without quality degradation compared to conventional scans. 155 participant data were acquired for training and testing. Two DNN models were generated according to the number of acquisitions (NAQ) of input images: DNN-N1 for NAQ = 1 and DNN-N2 for NAQ = 2. In the test data, DNN and TSE images were compared by quantitative error metrics. The visual appropriateness of DNN reconstructions on accelerated scans (DNN-N1 and DNN-N2) and conventional scans (TSE-Conv) was assessed for nine parameters by two radiologists. The lesion detection was evaluated at DNNs and TES-Conv by prostate imaging-reporting and data system. The scan time was reduced by 71% at NAQ = 1, and 42% at NAQ = 2. Quantitative evaluation demonstrated the better error metrics of DNN images (29-43% lower NRMSE, 4-13% higher structure similarity index, and 2.8-4.8 dB higher peak signal-to-noise ratio; p < 0.001) than TSE images. In the assessment of the visual appropriateness, both radiologists evaluated that DNN-N2 showed better or comparable performance in all parameters compared to TSE-Conv. In the lesion detection, DNN images showed almost perfect agreement (\u03ba > 0.9) scores with TSE-Conv. DNN-based reconstruction in highly accelerated prostate TSE imaging showed comparable quality to conventional TSE. Our framework reduces the scan time by 42% of conventional prostate TSE imaging without sequence modification, revealing great potential for clinical application.","subset":"pubmed_abstract"} +{"meta":{"pmid":24876027,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2016-44":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-32":1,"2015-27":1,"2015-22":2,"2021-43":1,"2015-18":1}}},"text":"Diversity-multiplexing tradeoff in mode-division multiplexing.\nThe capacity of mode-division multiplexing (MDM) systems is limited, for a given outage probability, by mode-dependent loss (MDL) and gain. Modal degrees of freedom may be exploited to increase transmission rate (multiplexing gain) or lower outage probability (diversity gain), but there is a fundamental tradeoff between the achievable multiplexing and diversity gains. In this Letter, we present the diversity-multiplexing tradeoff in MDM systems for the first time, studying the impact of signal-to-noise ratio, MDL, and frequency diversity order on the tradeoff in the strong-mode-coupling regime.","subset":"pubmed_abstract"} +{"meta":{"pmid":31065232,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Standardised inventories of spiders (Arachnida, Araneae) of Macaronesia I: The native forests of the Azores (Pico and Terceira islands).\nThe data presented here come from samples collected as part of two recent research projects (NETBIOME - ISLANDBIODIV and FCT - MACDIV) which aimed at understanding the drivers of community assembly in Macaronesian islands. We applied the sampling protocol COBRA (Conservation Oriented Biodiversity Rapid Assessment, Cardoso 2009) in sixteen 50 m x 50 m native forest plots in the Azorean Islands of Pico (6 plots) and Terceira (10 plots) to assess spider diversity. Through this publication, we contribute to the knowledge of the arachnofauna of the Azores and, more specifically, to that of the islands of Pico and Terceira. The collected samples yielded 8,789 specimens, of which 45% were adults (3,970) belonging to 13 families, 36 species and three morphospecies that have yet to be described. Species of the family Linyphiidae dominated the samples, with 17 species and two morphospecies that have yet to be described (48% of the taxa). Out of the identified (morpho)species, 16 were introduced, 13 Azorean endemic (three of which were undescribed) and seven native (five of them Macaronesian endemics). We report the first record of the introduced species Haplodrassus signifer and Agyneta decora in Pico Island.","subset":"pubmed_abstract"} +{"meta":{"pmid":32733221,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Cortical Activation During Shoulder and Finger Movements in Healthy Adults: A Functional Near-Infrared Spectroscopy (fNIRS) Study.\nCharacterization of cortical activation patterns during movement of the upper extremity in healthy adults is helpful in understanding recovery mechanisms following neurological disorders. This study explores cortical activation patterns associated with movements of the shoulder and fingers in healthy adults using functional near-infrared spectroscopy (fNIRS). Twelve healthy right-handed participants were recruited. Two motor tasks (shoulder abduction and finger extension) with two different trial lengths (10 s and 20 s) were performed in a sitting position at a rate of 0.5 Hz. The hemodynamic response, as indicated by oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR), over both hemispheres was acquired using a 54-channel fNIRS system. We found a generalized bilateral cortical activation during both motor tasks with greater activation in the contralateral compared to the ipsilateral primary motor cortex. Particularly in the more medial part of the contralateral hemisphere, significant higher activation was found during the shoulder compared to finger movements. Furthermore, cortical activation patterns are affected not only by motor tasks but also by trial lengths. HbO is more sensitive to detect cortical activation during finger movements in longer trials, while HbR is a better surrogate to capture active areas during shoulder movement in shorter trials. Based on these findings, reporting both HbO and HbR is strongly recommended for future fNIRS studies, and trial lengths should be taken into account when designing experiments and explaining results. Our findings demonstrating distinct cortical activation patterns associated with shoulder and finger movements in healthy adults provide a foundation for future research to study recovery mechanisms following neurological disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":21436451,"dup_signals":{"dup_doc_count":34,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2017-26":2,"2017-22":1,"2017-09":4,"2016-50":2,"2016-44":1,"2016-40":4,"2016-36":4,"2016-30":3,"2016-22":1,"2016-18":2,"2016-07":4,"2017-13":2}}},"text":"The Buttermilk Creek complex and the origins of Clovis at the Debra L. Friedkin site, Texas.\nCompelling archaeological evidence of an occupation older than Clovis (~12.8 to 13.1 thousand years ago) in North America is present at only a few sites, and the stone tool assemblages from these sites are small and varied. The Debra L. Friedkin site, Texas, contains an assemblage of 15,528 artifacts that define the Buttermilk Creek Complex, which stratigraphically underlies a Clovis assemblage and dates between ~13.2 and 15.5 thousand years ago. The Buttermilk Creek Complex confirms the emerging view that people occupied the Americas before Clovis and provides a large artifact assemblage to explore Clovis origins.","subset":"pubmed_abstract"} +{"meta":{"pmid":26817582,"dup_signals":{"dup_doc_count":31,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-10":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-34":2,"2017-26":2,"2017-22":2,"2017-17":1,"2023-50":1,"2017-13":2}}},"text":"Factors associated with return to work in men and women with work-related traumatic brain injury.\nSymptoms that persist subsequent to a work-related traumatic brain injury (wrTBI) influence the ability to return to work (RTW) and indicate areas of functional disability, as classified in the International Classification of Functioning, Disability and Health (ICF) framework. The purpose of this study was to describe the relationship between RTW status and ICF framework domains in men and women with a wrTBI. A retrospective chart review of 209 consecutive workers with TBI (mild TBI: 71.8%; mean age: 40.2 \u00b1 11.1, men: 71.3%) was conducted. Workers were assessed during the chronic post-injury phase, at the neurology service of a large rehabilitation hospital in Ontario, Canada in 2003. Frequency distributions were calculated and chi-square tests performed. At the point of assessment, 78.0% of workers were in receipt of disability benefits, while the remainder had returned to work on a full- or part-time basis. Significant differences were observed in the Body Functions and Structures domain of the ICF model, specifically clinical diagnoses of depression, anxiety, pain disorders; self-perceived cognitive disturbance, and certain psychosocial factors (p < 0.05), between workers who had returned to work and those who had not. When stratified according to sex, these associations remained significant only in men. The factors outlined above should be subject to further TBI research, as indicators for RTW. The lack of significant findings in women warrants further exploration of variables within the physical and social environmental domains of the ICF.","subset":"pubmed_abstract"} +{"meta":{"pmid":11953628,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Patellar component resection arthroplasty for the severely compromised patella.\nWhen severe bone loss precludes reimplantation of a new patellar component during revision knee arthroplasty, the treatment options include patellar bone grafting, patellar component resection arthroplasty, and patellectomy. The purpose of this study was to evaluate the clinical and functional results of patellar component resection arthroplasty for the severely compromised patella for which insertion of another patellar component was not possible. Thirty-five knees (31 patients) were treated with patellar component resection arthroplasty for aseptic patellar component failure associated with severely compromised patellar bone stock. Followup averaged 7.9 years (range, 2-18 years). There was a significant improvement in Knee Society pain and function scores. Pain relief was more dramatic than functional improvement. The range of motion also improved significantly and in particular preoperative extensor lag was resolved in the majority of patients. Patients treated with isolated patellar resection arthroplasty were more likely to have continuing pain and require reoperation compared with patients who had concomitant revision of the tibial and femoral components. Correct positioning and the stability of tibial and femoral components should be tested carefully at the time of patellar resection arthroplasty and considered for revision if malpositioned either axially or rotationally.","subset":"pubmed_abstract"} +{"meta":{"pmid":22044660,"dup_signals":{"dup_doc_count":27,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2022-49":1,"2022-40":1,"2022-33":1,"2022-21":1,"2022-05":1,"2021-43":2,"2021-31":2,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":3,"2020-24":1,"2020-16":1,"2020-10":1,"2020-05":1,"2023-50":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in a prospective study.\nOxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up. We included 260 cases with lung cancer and a subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collected at entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association between lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03-1.31)], never-smokers [IRR: 9.94 (1.04-94.7)], and former smokers [IRR: 1.19 (1.07-1.33)]. There was no significant interaction with the OGG1 genotype, although the IRR was 1.14 (0.98-1.34) among subjects homozygous for Cys326. The association between urinary 8-oxoGua excretion and lung cancer risk among former and never-smokers suggests that oxidative stress with damage to DNA is important in this group.","subset":"pubmed_abstract"} +{"meta":{"pmid":7486938,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Pharmacokinetics of azithromycin in pediatric patients with acute otitis media.\nThe objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg\/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +\/- 120 ng\/ml, 1.8 +\/- 0.4 h, 1,841 +\/- 651 ng.h\/ml, and 31.6 +\/- 6.6 h, respectively. Concentrations in serum (means +\/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +\/- 26, 47 +\/- 21, 27 +\/- 17, and 17 +\/- 13 ng\/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.","subset":"pubmed_abstract"} +{"meta":{"pmid":21224365,"dup_signals":{"dup_doc_count":40,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":2,"2022-40":2,"2022-21":2,"2021-49":1,"2021-43":2,"2021-31":2,"2021-17":2,"2021-04":2,"2020-45":4,"2020-40":2,"2020-24":1,"2019-47":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2024-30":2,"2024-18":1}}},"text":"Impact of exploratory biomarkers on the treatment effect of bevacizumab in metastatic breast cancer.\nThe addition of bevacizumab to cytotoxic chemotherapy has demonstrated a progression-free survival (PFS) benefit in the first-line and second-line treatment of advanced or metastatic breast cancer (MBC). However, the addition of bevacizumab to capecitabine in heavily pretreated MBC patients did not show a PFS benefit (AVF2119g phase III trial). The aim of this study was to evaluate the expression of novel putative biomarkers as predictors of benefit from bevacizumab in retrospective subset analyses of the AVF2119g trial. In the AVF2119g trial, 462 patients with MBC were randomly assigned to receive capecitabine or capecitabine plus bevacizumab. Primary tumor tissue and outcome data were available for 223 patients. Biomarker expression was assessed by in situ hybridization (VEGF-A, VEGF-B, thrombospondin-2 and Flt4) or immunohistochemistry (VEGF-C, PDGF-C, neuropilin-1, delta-like ligand (Dll) 4, Bv8, p53 and thymidine phosphorylase) on formalin-fixed, paraffin-embedded tissue. PFS was associated with these variables in retrospective subset analyses. Patients with low scores for Dll4, VEGF-C, and neuropilin-1 showed trends toward improvement in PFS associated with the addition of bevacizumab to capecitabine (P values = 0.01, 0.05, and 0.07, respectively). These observations were not statistically significant following correction for multiple hypothesis testing. These retrospective subset analyses suggest that expression of Dll4, VEGF-C, and neuropilin-1 may predict benefit from bevacizumab. Such observations are not conclusive but warrant additional testing.","subset":"pubmed_abstract"} +{"meta":{"pmid":29781395,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":1,"2024-10":1,"unknown":5}}},"text":"Judicialization 2.0: Understanding right-to-health litigation in real time.\nOver the past two decades, debate over the whys, the hows, and the effects of the ever-expanding phenomenon of right-to-health litigation ('judicialization') throughout Latin America have been marked by polarised arguments and limited information. In contrast to claims of judicialization as a positive or negative trend, less attention has been paid to ways to better understand the phenomenon in real time. In this article, we propose a new approach-Judicialization 2.0-that recognises judicialization as an integral part of democratic life. This approach seeks to expand access to information about litigation on access to medicines (and health care generally) in order to better characterise the complexity of the phenomenon and thus inform new research and more robust public discussions. Drawing from our multi-disciplinary perspectives and field experiences in highly judicialized contexts, we thus describe a new multi-source, multi-stakeholder mixed-method approach designed to capture the patterns and heterogeneity of judicialization and understand its medical and socio-political impact in real time, along with its counterfactuals. By facilitating greater data availability and open access, we can drive advancements towards transparent and participatory priority setting, as well as accountability mechanisms that promote quality universal health coverage.","subset":"pubmed_abstract"} +{"meta":{"pmid":15550214,"dup_signals":{"dup_doc_count":14}},"text":"Sexual power and HIV risk, South Africa.\nGender power inequities are believed to play a key role in the HIV epidemic through their effects on women's power in sexual relationships. We hypothesized that lack of sexual power, measured with a four-point relationship control scale and by a woman's experience of forced sex with her most recent partner, would decrease the likelihood of consistent condom use and increase the risk for HIV infection among sexually experienced, 15- to 24-year-old women in South Africa. While limited sexual power was not directly associated with HIV, it was associated with inconsistent condom use: women with low relationship control were 2.10 times more likely to use condoms inconsistently (95% confidence interval [CI] 1.17-3.78), and women experiencing forced sex were 5.77 times more likely to use condoms inconsistently (95% CI 1.86-17.91). Inconsistent condom use was, in turn, significantly associated with HIV infection (adjusted odds ratio 1.58, 95% CI 1.10-2.27).","subset":"pubmed_abstract"} +{"meta":{"pmid":24187119,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"Breastfeeding and complementary food: randomized trial of community doula home visiting.\nDespite recent efforts to increase breastfeeding, young African American mothers continue to breastfeed at low rates, and commonly introduce complementary foods earlier than recommended. This study examines the effects of a community doula home visiting intervention on infant feeding practices among young mothers. Low-income, African American mothers (n = 248) under age 22 years participated in a randomized trial of a community doula intervention. Intervention-group mothers received services from paraprofessional doulas: specialized home visitors trained as childbirth educators and lactation counselors. Doulas provided home visits from pregnancy through 3 months postpartum, and support during childbirth. Control-group mothers received usual prenatal care. Data were obtained from medical records and maternal interviews at birth and 4 months postpartum. Intent-to-treat analyses showed that doula-group mothers attempted breastfeeding at a higher rate than control-group mothers (64% vs 50%; P = .02) and were more likely to breastfeed longer than 6 weeks (29% vs 17%; P = .04), although few mothers still breastfed at 4 months. The intervention also impacted mothers' cereal\/solid food introduction (P = .008): fewer doula-group mothers introduced complementary foods before 6 weeks of age (6% vs 18%), while more waited until at least 4 months (21% vs 13%) compared with control-group mothers. Community doulas may be effective in helping young mothers meet breastfeeding and healthy feeding guidelines. The intervention's success may lie in the relationship that develops between doula and mother based on shared cultural background and months of prenatal home visiting, and the doula's presence at the birth, where she supports early breastfeeding experiences.","subset":"pubmed_abstract"} +{"meta":{"pmid":21878437,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":8}}},"text":"Genome-wide association study of circulating retinol levels.\nRetinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30\u00d7 10(-17)) and rs10882272 (P =6.04\u00d7 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49\u00d7 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31\u00d7 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":23011592,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Neuropeptide Y1 receptor in immune cells regulates inflammation and insulin resistance associated with diet-induced obesity.\nRecruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat-fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity.","subset":"pubmed_abstract"} +{"meta":{"pmid":21523800,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":6,"2013-20":1,"2024-22":1,"unknown":3}}},"text":"Waldenstr\u00f6m macroglobulinemia: 2011 update on diagnosis, risk stratification, and management.\nWaldenstr\u00f6m macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Presence of IgM monoclonal protein associated with 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Age, hemoglobin level, platelet count, b2-microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analogue, or both. The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Bortezomib, thalidomide, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":8576675,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Treatment of herpes zoster with Clinacanthus nutans (bi phaya yaw) extract.\nA randomized, placebo-controlled trial of the efficacy of topical formulation of Clinacanthus nutans (Bi Phaya Yaw) extract was carried out in 51 patients with varicella-zoster virus infection. The study medication was applied five times daily for 7-14 days until the lesions were healed. The number of patients with lesion crusting within 3 days and with lesion healing within 7 days and 10 days were significantly greater in the C. nutans extract-treated group than the placebo group (p < 0.01). Pain scores were reduced more rapidly in the C. nutans extract-treated group than in the placebo group. There were no side effects of the study medication.","subset":"pubmed_abstract"} +{"meta":{"pmid":519947,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Effect of isoprenaline on the plasma concentrations of angiotensin III in rats.\n1. A new column-chromatographic method is described for the simple and reproducible determination of the concentration of [des-Asp1]angiotensin II (angiotensin III) in rat plasma. 2. The method uses the different abilities of the ion-exchange resins Dowex 1 (X8) and Bio Rex 70 to bind angiotensin II and angiotensin III. Under the conditions used, Bio Rex 70 binds only angiotensin III. Angiotensin II and its hexapeptide metabolite [des-Asp1,des-Arg2]angiotensin II pass the resin with the effluent. Dowex 1 (X8) binds angiotensin II and the hexapeptide metabolite, whereas it does not extract angiotensin III. It does not separate angiotensin II from the hexapeptide. Therefore the sum of both peptides is expressed as angiotensin II-like activity. The ratio of the concentrations, angiotensin II\/hexapeptide, was 5:1. 3. In normal rats the plasma concentration of angiotensin III was 20 fmol\/ml (SD 15; n = 8), and angiotensin II-like activity was 60 fmol\/ml (SD 35; n = 8). 4. The beta-sympathomimetic amine isoprenaline caused a time- and dose-dependent increase in plasma angiotensin III and angiotensin II-like activities. 5. Under the conditions studied angiotensin III contributed approximately 25% to the total amount of angiotensins in plasma.","subset":"pubmed_abstract"} +{"meta":{"pmid":14971773,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Design of adaptive treatment margins for non-negligible measurement uncertainty: application to ultrasound-guided prostate radiation therapy.\nDaily imaging during the course of a fractionated radiotherapy treatment has the potential for frequent intervention and therefore effective adaptation of the treatment to the individual patient. The treatment information gained from such images can be analysed and updated daily to obtain a set of patient individualized parameters. However, in many situations, the uncertainty with which these parameters are estimated cannot be neglected. In this work this methodology is applied to the adaptive estimation of setup errors, the derivation of a daily optimal pre-treatment correction strategy, and the daily update of the treatment margins after application of these corrections. For this purpose a dataset of 19 prostate cancer patients was analysed retrospectively. The position of the prostate was measured daily with an optically guided 3D ultrasound localization system. The measurement uncertainty of this system is approximately 2 mm. The algorithm finds the most likely position of the target maximizing an a posteriori probability given the set of measurements. These estimates are used for the optimal corrections applied to the target volume. The results show that the application of the optimal correction strategy allows a reduction in the treatment margins in a systematic way with increasing progression of the treatment. This is not the case using corrections based only on the measured values that do not take the measurement uncertainty into account.","subset":"pubmed_abstract"} +{"meta":{"pmid":30851587,"dup_signals":{"dup_doc_count":13,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2022-40":2,"2022-05":2,"2021-25":1,"2021-17":1,"2021-04":1,"2020-50":2,"2020-05":1,"2019-47":1,"2019-13":1}}},"text":"The effects of bisphenol A, benzyl butyl phthalate, and di(2-ethylhexyl) phthalate on estrogen receptor alpha in estrogen receptor-positive cells under hypoxia.\nEndocrine-disrupting chemicals (EDCs) are widely used in various consumer goods. Consequently, humans are constantly exposed to EDCs, which is associated with a variety of endocrine-related diseases. In this study, we demonstrated the effects of bisphenol A (BPA), benzyl butyl phthalate (BBP), and di(2-ethylhexyl) phthalate (DEHP) on estrogen receptor alpha (ER\u03b1) expression under normoxia and hypoxia. First, we confirmed the effects of EDCs on ER activity using OECD Test Guideline 455. Compared to the 100% activity induced by 1 nM 17-\u03b2-estradiol (positive control), BPA and BBP exhibited 50% ER\u03b1 activation at concentrations of 1.31 \u03bcM and 4.8 \u03bcM, respectively. In contrast, and consistent with previous reports, DEHP did not activate ER\u03b1. ER\u03b1 is activated and degraded by hypoxia in breast cancer cells. BPA, BBP, and DEHP enhanced ER\u03b1-mediated transcriptional activity under hypoxia. All three EDCs decreased ER\u03b1 protein levels under hypoxia in MCF-7 cells. The transcriptional activity of hypoxia-inducible factor-1 was decreased and secretion of vascular endothelial growth factor (VEGF) was increased by BPA and BBP under hypoxia in MCF-7 cells, but not by DEHP. All three EDCs decreased the ER\u03b1 protein expression level in Ishikawa human endometrial adenocarcinoma cells, and DEHP caused a weak decrease in VEGF secretion under hypoxia. These results demonstrate down-regulation of ER\u03b1 by EDCs may influence the pathological state associated with hypoxia.","subset":"pubmed_abstract"} +{"meta":{"pmid":30024207,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Social Participation and Navigation (SPAN) program for adolescents with acquired brain injury: Pilot findings.\nOur goal was to examine the feasibility and preliminary efficacy of an app-based coaching intervention (Social Participation and Navigation; SPAN) to help survivors of acquired brain injury attain social participation goals. Research Method\/Design: This is a nonrandomized pilot trial of SPAN, including 15 adolescents (9 with traumatic brain injury, 6 with brain tumor) between the ages of 14-22. The SPAN intervention consisted of a mobile app to support the development and implementation of social participation goals, weekly video-conference coaching sessions to identify goals and step-by-step action plans, and online didactic materials. Assessments were completed pre- and postintervention. Satisfaction with the intervention, confidence in the adolescents' ability to participate in and plan social activities and manage their emotions and behaviors, and frequency and satisfaction with social participation were assessed via self- and parent-report questionnaires developed for this project. Behavior problems, social competence, and social problems were measured by using the Child Behavior Checklist and the Youth Self-Report. High levels of participant and parent satisfaction were reported. Increases in parent-reported frequency of social participation and teen-reported confidence in their ability to participate and develop social participation goals and plans were observed. A decline in parent-reported total problems, internalizing problems, externalizing problems, and social problems was noted. Results support the feasibility of the program, because participants were able to successfully meet with their coaches and use the app to develop and accomplish social participation goals. Further research will be needed to refine the app and program, particularly when reaching out to populations beyond traumatic brain injury. (PsycINFO Database Record","subset":"pubmed_abstract"} +{"meta":{"pmid":22567089,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Estimating grizzly and black bear population abundance and trend in Banff National Park using noninvasive genetic sampling.\nWe evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears (N= 73.5, 95% CI = 64-94 in 2006; N= 50.4, 95% CI = 49-59 in 2008) and black bears (N= 62.6, 95% CI = 51-89 in 2006; N= 81.8, 95% CI = 72-102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males (\u03bb= 0.93, 95% CI = 0.74-1.17) and females (\u03bb= 0.90, 95% CI = 0.67-1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap\/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains.","subset":"pubmed_abstract"} +{"meta":{"pmid":33242050,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":8}}},"text":"The state of the field: from inception to commercialization of metal-organic frameworks.\nAs chemists and materials scientists, it is our duty to synthesize and utilize materials for a multitude of applications that promote the development of society and the well-being of its citizens. Since the inception of metal-organic frameworks (MOFs), researchers have proposed a variety of design strategies to rationally synthesize new MOF materials, studied their porosity and gas sorption performances, and integrated MOFs onto supports and into devices. Efforts have explored the relevance of MOFs for applications including, but not limited to, heterogeneous catalysis, guest delivery, water capture, destruction of nerve agents, gas storage, and separation. Recently, several start-up companies have undertaken MOF commercialization within industrial sectors. Herein, we provide a brief overview of the state of the MOF field from their design and synthesis to their potential applications, and finally, to their commercialization.","subset":"pubmed_abstract"} +{"meta":{"pmid":17546496,"dup_signals":{"dup_doc_count":27,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-16":1,"2019-47":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-43":1,"2018-05":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":2,"2016-44":1,"2016-40":1,"2016-36":1,"2023-40":1,"2017-13":1}}},"text":"Access to housing as a structural intervention for homeless and unstably housed people living with HIV: rationale, methods, and implementation of the housing and health study.\nHomelessness and unstable housing have been associated with HIV risk behavior and poorer health among persons living with HIV\/AIDS (PLWHA), yet prior research has not tested causal associations. This paper describes the challenges, methods, and baseline sample of the Housing and Health Study, a longitudinal, multi-site, randomized controlled trial investigating the effects of providing immediate rental housing assistance to PLWHA who were homeless or at severe risk of homelessness. Primary outcomes included HIV disease progression, medical care access and utilization, treatment adherence, mental and physical health, and risks of transmitting HIV. Across three study sites, 630 participants completed baseline sessions and were randomized to receive either immediate rental housing assistance (treatment group) or assistance finding housing according to local standard practice (comparison group). Baseline sessions included a questionnaire, a two-session HIV risk-reduction counseling intervention, and blood sample collection to measure CD4 counts and viral load levels. Three follow-up visits occurred at 6, 12, and 18 months after baseline. Participants were mostly male, Black, unmarried, low-income, and nearly half were between 40 and 49 years old. At 18 months, 84% of the baseline sample was retained. The retention rates demonstrate the feasibility of conducting scientifically rigorous housing research, and the baseline results provide important information regarding characteristics of this understudied population that can inform future HIV prevention and treatment efforts.","subset":"pubmed_abstract"} +{"meta":{"pmid":11295583,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"Cardiac transplant outcome of patients supported on left ventricular assist device vs. intravenous inotropic therapy.\nAlthough the left ventricular assist device (LVAD) has been increasingly used as a bridge to transplant, its effect on post-transplant outcome is uncertain. We, therefore, designed this study using the Cardiac Transplant Research Database to compare patients supported on an LVAD before transplant with those treated with intravenous inotropic medical therapy. Of the 5,880 patients transplanted between 1990 and 1997, a total of 502 received support from LVADs and 2,514 received intravenous inotropic medical therapy at the time of transplant. Kaplan-Meier analysis showed no significant difference in post-transplant survival between the LVAD and medical-therapy groups (p = 0.09). Results of a multivariate Cox regression analysis were consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a significant risk factor for mortality. The percentage of patients who received LVADs as a function of total transplants increased from 2% in 1990 to 16% in 1997. Furthermore, although the number of extracorporeal LVADs remained relatively constant, the number of intracorporeal LVADs increased over time. Multivariate parametric analysis found that the risk factors for post-transplant death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time (p < 0.0001), and earlier year of transplant (p = 0.03). Given a limited donor supply, the intracorporeal LVAD helps the sickest patients survive to transplant and provides post-transplant outcome similar to that of patients supported on inotropic medical therapy. Therefore, patients supported on LVADs before transplant may receive the greatest marginal benefit when compared with other transplant candidates.","subset":"pubmed_abstract"} +{"meta":{"pmid":23280626,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Protein kinase C\u03b2 is required for lupus development in Sle mice.\nTo evaluate the requirement for protein kinase C\u03b2 (PKC\u03b2) in the development of lupus in mice, and to explore the potential of targeting PKC\u03b2 as a therapeutic strategy in lupus. Congenic mice bearing the disease loci Sle1 or Sle1 and Sle3, which represent different stages of severity in the development of lupus, were crossed with PKC\u03b2-deficient mice. The effect of PKC\u03b2 deficiency in lupus development was analyzed. In addition, the effects of the PKC\u03b2-specific inhibitor enzastaurin on the survival of B cells from mice with lupus and human 9G4-positive B cells as well as the in vivo effect of enzastaurin treatment on the development of lupus in Sle mice were investigated. In Sle mice, PKC\u03b2 deficiency abrogated lupus-associated phenotypes, including high autoantibody levels, proteinuria, and histologic features of lupus nephritis. Significant decreases in spleen size and in the peritoneal B-1 cell population, reduced numbers of activated CD4 T cells, and normalized CD4:CD8 ratios were observed. PKC\u03b2 deficiency induced an anergic B cell phenotype and preferentially inhibited autoreactive plasma cells and autoantibodies in mice with lupus. Inhibition of PKC\u03b2 enhanced apoptosis of both B cells from Sle mice and human autoreactive B cells (9G4 positive). Treatment of Sle mice with the PKC\u03b2-specific inhibitor enzastaurin prevented the development of lupus. This study identifies PKC\u03b2 as a central mediator of lupus pathogenesis, suggesting that PKC\u03b2 represents a promising therapeutic target for the treatment of systemic lupus erythematosus. Moreover, the results indicate the feasibility of using a PKC\u03b2 inhibitor for the treatment of lupus.","subset":"pubmed_abstract"} +{"meta":{"pmid":28553408,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Identification of Cysteine Ubiquitylation Sites on the Sec23A Protein of the COPII Complex Required for Vesicle Formation from the ER.\nCOPII is a multiprotein complex that surrounds carrier vesicles budding from the Endoplasmic Reticulum and allows the recruitment of secretory proteins. The Sec23a protein plays a crucial role in the regulation of the dynamics of COPII formation ensuring the proper function of the secretory pathway. Since few evidences suggest that ubiquitylation could have a role in the COPII regulation, the present study was aimed to establish whether the Sec23a component of the vesicular envelope COPII could be ubiquitylated. Sec23a ubiquitylation was revealed by co-immunoprecipitation experiments. Recombinant Sec23a was gel-purified and analyzed by mass spectrometry subjected to trypsin proteolysis. Signature peptides were identified by the presence of Gly-Gly remnants from the C-terminus of the ubiquitin attached to the amino acid residues of the substrate. Recombinant Sec23a proteins bearing mutations in the ubiquitylation sites were used to evaluate the effect of ubiquitylation in the formation of COPII. We identified two cysteine ubiquitylation sites showed at position 432 and 449 of the Sec23a protein sequence. Interestingly, we revealed that the amino acid residues of Sec23a joined to ubiquitin were cysteine instead of the conventional lysine residues. This unconventional ubiquitylation consists of the addition of one single ubiquitin moiety that is not required for Sec23a degradation. Immunofluorescence results showed that Sec23a ubiquitylation might influence COPII formation by modulating Sec23a interaction with the ER membrane. Presumably, this regulation could occur throughout continual ubiquitylation\/de-ubiquityliation cycles. Our results suggest a novel regulatory mechanism for the Sec23a function that could be crucial in several pathophysiological events known to alter COPII recycling.","subset":"pubmed_abstract"} +{"meta":{"pmid":19484917,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Safety and tolerability of the rivastigmine patch: results of a 28-week open-label extension.\nThe primary objective of the open-label extension was to evaluate the long-term safety and tolerability of a transdermal rivastigmine patch up to 1 year, as a novel approach to treatment in Alzheimer disease. This was a 28-week extension to a 24-week, double-blind, double-dummy, placebo-controlled, and active-controlled study evaluating rivastigmine patches [9.5 mg\/24 h (10 cm2) and 17.4 mg\/24 h (20 cm2)] and oral capsules (3 to 6 mg twice-daily). Patients entering the extension were switched directly to 9.5 mg\/ 24 h rivastigmine patch and increased to 17.4 mg\/24 h patch, irrespective of their double-blind study treatment. Primary measures included safety and tolerability assessments, including adverse events and serious adverse events. Of 1195 patients randomized to treatment, 870 (72.8%) completed the double-blind study and entered the open-label extension. During weeks 1 to 4 of the extension, 9.5 mg\/24 h rivastigmine patch was well tolerated overall by patients formerly randomized to rivastigmine capsule or patch groups: < or =2.5% reported nausea and < or =1.9% reported vomiting. No unexpected safety issues arose, and skin tolerability was good; similar to the double-blind study. During the 28-week, open-label extension phase, the patch seemed to be well tolerated with a favorable safety profile.","subset":"pubmed_abstract"} +{"meta":{"pmid":10523634,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Point mutations in yeast CBF5 can abolish in vivo pseudouridylation of rRNA.\nIn budding yeast (Saccharomyces cerevisiae), the majority of box H\/ACA small nucleolar RNPs (snoRNPs) have been shown to direct site-specific pseudouridylation of rRNA. Among the known protein components of H\/ACA snoRNPs, the essential nucleolar protein Cbf5p is the most likely pseudouridine (Psi) synthase. Cbf5p has considerable sequence similarity to Escherichia coli TruBp, a known Psi synthase, and shares the \"KP\" and \"XLD\" conserved sequence motifs found in the catalytic domains of three distinct families of known and putative Psi synthases. To gain additional evidence on the role of Cbf5p in rRNA biosynthesis, we have used in vitro mutagenesis techniques to introduce various alanine substitutions into the putative Psi synthase domain of Cbf5p. Yeast strains expressing these mutated cbf5 genes in a cbf5Delta null background are viable at 25 degrees C but display pronounced cold- and heat-sensitive growth phenotypes. Most of the mutants contain reduced levels of Psi in rRNA at extreme temperatures. Substitution of alanine for an aspartic acid residue in the conserved XLD motif of Cbf5p (mutant cbf5D95A) abolishes in vivo pseudouridylation of rRNA. Some of the mutants are temperature sensitive both for growth and for formation of Psi in the rRNA. In most cases, the impaired growth phenotypes are not relieved by transcription of the rRNA from a polymerase II-driven promoter, indicating the absence of polymerase I-related transcriptional defects. There is little or no abnormal accumulation of pre-rRNAs in these mutants, although preferential inhibition of 18S rRNA synthesis is seen in mutant cbf5D95A, which lacks Psi in rRNA. A subset of mutations in the Psi synthase domain impairs association of the altered Cbf5p proteins with selected box H\/ACA snoRNAs, suggesting that the functional catalytic domain is essential for that interaction. Our results provide additional evidence that Cbf5p is the Psi synthase component of box H\/ACA snoRNPs and suggest that the pseudouridylation of rRNA, although not absolutely required for cell survival, is essential for the formation of fully functional ribosomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":2327956,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Testosterone-mediated regulation of mouse renal cytochrome P-450 isoenzymes.\nWe have studied the extent to which mouse renal cytochrome P-450 isoenzymes are sexually differentiated, and the factor(s) regulating this dimorphism. Intriguingly, sex differences were not seen in the expression of a single cytochrome P-450 enzyme, but were observed in the expression of all P-450 isoenzymes detectable, encoded by six gene families or sub-families. This effect was mediated by testosterone, which had the capacity to both induce and repress P-450 gene expression, and which was independent of growth hormone. The changes in protein content were mirrored in all but one case by changes in the levels of mRNA, indicating that these genes contain hormone-responsive elements. These findings are consistent with numerous reports of sex differences in the susceptibility of the mouse kidney to the toxic and carcinogenic effects of drugs and environmental chemicals, many of which are metabolized to cytotoxic products by the cytochrome P-450-dependent mono-oxygenases. These data imply that circulating androgen levels will be an important factor in susceptibility of the kidney to toxic or carcinogenic compounds which require metabolic activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":19306932,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Bayesian model selection for group studies.\nBayesian model selection (BMS) is a powerful method for determining the most likely among a set of competing hypotheses about the mechanisms that generated observed data. BMS has recently found widespread application in neuroimaging, particularly in the context of dynamic causal modelling (DCM). However, so far, combining BMS results from several subjects has relied on simple (fixed effects) metrics, e.g. the group Bayes factor (GBF), that do not account for group heterogeneity or outliers. In this paper, we compare the GBF with two random effects methods for BMS at the between-subject or group level. These methods provide inference on model-space using a classical and Bayesian perspective respectively. First, a classical (frequentist) approach uses the log model evidence as a subject-specific summary statistic. This enables one to use analysis of variance to test for differences in log-evidences over models, relative to inter-subject differences. We then consider the same problem in Bayesian terms and describe a novel hierarchical model, which is optimised to furnish a probability density on the models themselves. This new variational Bayes method rests on treating the model as a random variable and estimating the parameters of a Dirichlet distribution which describes the probabilities for all models considered. These probabilities then define a multinomial distribution over model space, allowing one to compute how likely it is that a specific model generated the data of a randomly chosen subject as well as the exceedance probability of one model being more likely than any other model. Using empirical and synthetic data, we show that optimising a conditional density of the model probabilities, given the log-evidences for each model over subjects, is more informative and appropriate than both the GBF and frequentist tests of the log-evidences. In particular, we found that the hierarchical Bayesian approach is considerably more robust than either of the other approaches in the presence of outliers. We expect that this new random effects method will prove useful for a wide range of group studies, not only in the context of DCM, but also for other modelling endeavours, e.g. comparing different source reconstruction methods for EEG\/MEG or selecting among competing computational models of learning and decision-making.","subset":"pubmed_abstract"} +{"meta":{"pmid":15374846,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Loss of bone density with inhaled triamcinolone in Lung Health Study II.\nInhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":17080358,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Evolutionary and ecological causes of the latitudinal diversity gradient in hylid frogs: treefrog trees unearth the roots of high tropical diversity.\nWhy are there more species in the tropics than in temperate regions? In recent years, this long-standing question has been addressed primarily by seeking environmental correlates of diversity. But to understand the ultimate causes of diversity patterns, we must also examine the evolutionary and biogeographic processes that directly change species numbers (i.e., speciation, extinction, and dispersal). With this perspective, we dissect the latitudinal diversity gradient in hylid frogs. We reconstruct a phylogeny for 124 hylid species, estimate divergence times and diversification rates for major clades, reconstruct biogeographic changes, and use ecological niche modeling to identify climatic variables that potentially limit dispersal. We find that hylids originated in tropical South America and spread to temperate regions only recently (leaving limited time for speciation). There is a strong relationship between the species richness of each region and when that region was colonized but not between the latitudinal positions of clades and their rates of diversification. Temperature seasonality seemingly limits dispersal of many tropical clades into temperate regions and shows significant phylogenetic conservatism. Overall, our study illustrates how two general principles (niche conservatism and the time-for-speciation effect) may help explain the latitudinal diversity gradient as well as many other diversity patterns across taxa and regions.","subset":"pubmed_abstract"} +{"meta":{"pmid":31465817,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":19}}},"text":"Ethnoveterinary knowledge of farmers in bilingual regions of Switzerland - is there potential to extend veterinary options to reduce antimicrobial use?\nIn the pre-antibiotic era, a broad spectrum of medicinal plants was used to treat livestock. This knowledge was neglected in European veterinary medicine for decades but kept alive by farmers. Emergence of multidrug resistant bacterial strains requires a severely restricted use of antibiotics in veterinary medicine. We conducted a survey on the ethnoveterinary knowledge of farmers in the bilingual (French and German speaking) Western region of Switzerland, namely the cantons of Fribourg, Neuch\u00e2tel and Jura, and in the French speaking part of the canton of Bern. To find out whether differences exist in plants used by farmers in French speaking and bilingual regions of Switzerland as compared to our earlier studies conducted in Switzerland. Additional focus was on plants that are used in diseases which commonly are treated with antimicrobials, on plants used in skin afflictions, and on plants used in animal species such as horses, for which the range of veterinary medicinal products is limited. We conducted in 2015 semistructured interviews with 62 dialog partners, mainly cattle keeping farmers but also 18 horse keeping farmers. Of these, 41 were native French (FNS) and 21 native German speakers (GNS). Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. A total of 345 homemade remedies were reported, of which 240 contained only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). A total of 289 use reports (UR) were mentioned for the 240 HSHR, and they comprised 77 plant species belonging to 41 botanical families. Of these, 35 plant species were solely reported from FNS, 20 from GNS, and 22 from both. Taking into account earlier ethnoveterinary studies conducted in Switzerland only 10 (FNS) and 6 (GNS) plant species connected with 7% of FNS and GNS UR respectively were \"unique\" to the respective language group. The majority of the UR (219) was for treatment of cattle, while 38 UR were intended to treat horses. The most UR were for treatment of gastrointestinal and skin diseases. The most frequently mentioned plants were Linum usitatissimum L., Coffea L., Matricaria chamomilla L., Camellia sinensis (L.) Kuntze, and Quercus robur L. for gastrointestinal diseases, and Calendula officinalis L., Hypericum perforatum L. and Sanicula europaea L. for skin afflictions. No clear differences were found between the medicinal plants used by French native speakers and German native speakers. Several of the reported plants seem to be justified to widen the spectrum of veterinary therapeutic options in gastrointestinal and dermatological disorders in cattle and horses, and to reduce, at least to a certain degree, the need for antibiotic treatments. Our findings may help to strengthen the role of medicinal plants in veterinary research and practice, and to consider them as a further measure in official strategies for lowering the use of antibiotics.","subset":"pubmed_abstract"} +{"meta":{"pmid":37366593,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":6,"unknown":7}}},"text":"Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A.\nThe persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. Here, we investigate the ability of MTM to reverse in vivo models of inflammatory and chemotherapy-induced peripheral neuropathy (CIPN) pain and explore MTM's underlying mechanisms. Mithramycin reversed inflammatory heat hyperalgesia induced by complete Freund adjuvant and cisplatin-induced heat and mechanical hypersensitivity. In addition, MTM reversed both short-term and long-term (1 month) oxaliplatin-induced mechanical and cold hypersensitivity, without the rescue of intraepidermal nerve fiber loss. Mithramycin reversed oxaliplatin-induced cold hypersensitivity and oxaliplatin-induced TRPM8 overexpression in dorsal root ganglion (DRG). Evidence across multiple transcriptomic profiling approaches suggest that MTM reverses inflammatory and neuropathic pain through broad transcriptional and alternative splicing regulatory actions. Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":9062362,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Absence of P-selectin delays fatty streak formation in mice.\nP-selectin is expressed on activated endothelium and platelets where it can bind monocytes, neutrophils, stimulated T cells, and platelets. Because recruitment of these cells is critical for atherosclerotic lesion development, we examined whether P-selectin might play a role in atherosclerosis. We intercrossed P-selectin-deficient mice with mice lacking the low density lipoprotein receptor (LDLR) because these mice readily develop atherosclerotic lesions on diets rich in saturated fat and cholesterol. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules of LDLR-deficient mice, and the increase in adhesiveness of the vessels was P-selectin-dependent. Most likely due to the reduced leukocyte interaction with the vessel wall, P-selectin-deficient mice on diet for 8-20 wk formed significantly smaller fatty streaks in the cusp region of the aortae than did P-selectin-positive mice. This difference was more prominent in males. At 37 wk on diet, the lesions in the LDLR-deficient animals progressed to the fibrous plaque stage and were distributed throughout the entire aorta; their size or distribution was no longer dependent on P-selectin. Our results show that P-selectin-mediated adhesion is an important factor in the development of early atherosclerotic lesions, and that adhesion molecules such as P-selectin are involved in the complex process of atherosclerosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":16344403,"dup_signals":{"dup_doc_count":44,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":2,"2023-23":1,"2023-14":3,"2023-06":4,"2022-49":1,"2022-27":2,"2022-05":2,"2021-39":4,"2021-31":2,"2021-17":2,"2021-04":2,"2020-45":1,"2020-40":1,"2019-22":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2024-22":3,"2024-18":1,"2024-10":1}}},"text":"nNOS gene deletion exacerbates pathological left ventricular remodeling and functional deterioration after myocardial infarction.\nThe neuronal isoform of nitric oxide synthase (nNOS) has been implicated in the regulation of basal and beta-adrenergic inotropy in normal and chronically infarcted hearts. Furthermore, myocardial nNOS expression and activity increase in failing hearts, raising the possibility that nNOS may influence left ventricular (LV) remodeling progression and functional deterioration after myocardial infarction (MI). We compared LV remodeling at 1, 4, and 8 weeks after MI in nNOS-knockout mice (nNOS(-\/-)) and their wild-type (WT) littermates matched for infarct size by using a highly accurate 3-dimensional echocardiographic technique. Basal LV hemodynamics and the inotropic response to dobutamine infusion (4 and 16 ng.g(-1).min(-1)) were also evaluated 8 weeks after MI. Sham-operated nNOS(-\/-) mice showed enhanced basal LV contractility (P<0.03 versus WT, as evaluated by preload-recruitable stroke work) but an attenuated inotropic response to dobutamine infusion (P<0.01 versus WT). Both basal and beta-adrenergic LV relaxations were significantly impaired in nNOS(-\/-) mice. Survival after MI did not differ between groups. However, nNOS(-\/-) mice developed a faster and more severe LV dilation compared with WT mice (P<0.05 for both end-systolic and end-diastolic volume indices). WT mice maintained a positive inotropic response to dobutamine 8 weeks after MI. In contrast, infarcted nNOS(-\/-) mice responded to dobutamine with a dramatic fall in LV contractility (P<0.01 for preload-recruitable stroke work). nNOS plays a crucial role in preventing adverse LV remodeling and maintaining myocardial beta-adrenergic reserve after MI. Taken together, our findings suggest that upregulation of myocardial nNOS in infarcted hearts may be an important adaptive mechanism.","subset":"pubmed_abstract"} +{"meta":{"pmid":24140695,"dup_signals":{"dup_doc_count":23,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2021-31":1,"2021-21":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":2,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2021-49":1,"2024-18":2,"2024-10":1,"2024-26":1}}},"text":"Integument colouration in relation to persistent organic pollutants and body condition in arctic breeding black-legged kittiwakes (Rissa tridactyla).\nVertebrates cannot synthetize carotenoids de novo but have to acquire them through their diet. In birds, carotenoids are responsible for the yellow to red colouration of many secondary sexual traits. They are also involved in physiological functions such as immunostimulation and immunoregulation. Consequently, carotenoid-based colouration is very often considered as a reliable signal for health and foraging abilities. Although a few studies have suggested that carotenoid-based coloured traits could be sensitive to environmental pollution such as persistent organic pollutants (POPs) contamination, the relationships between pollutants and colouration remain unclear. Here, we examined the relationships between the colouration of carotenoid-based integuments and individual POP levels in pre-laying female black-legged kittiwakes from very high latitudes. In this area, these arctic seabirds are exposed to high POPs contamination. Additionally, we investigated the relationships between colouration and body condition, a frequently used index of individual quality. We found a negative relationship between POP levels and several components of integument colouration: saturation of eye-ring, gapes and tongue, suggesting that POPs could disrupt colouration of labile integuments in female kittiwakes. In addition, we found that females in better body condition displayed more orange and brighter gapes and tongue than females in poor body condition. These results demonstrate that hue and brightness are sensitive to the current health and nutritional status of female kittiwakes. Overall, our study shows that carotenoid-based colour integuments can be affected by several environmental-driven variables.","subset":"pubmed_abstract"} +{"meta":{"pmid":21536589,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2015-18":1,"unknown":13}}},"text":"FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.\nAtaxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3), binds to target gene promoters and modulates transcription by interaction with transcriptional regulators. Here, we show that ATXN3 interacts with the forkhead box O (FOXO) transcription factor FOXO4 and activates the FOXO4-dependent transcription of the manganese superoxide dismutase (SOD2) gene. Upon oxidative stress, ATXN3 and FOXO4 translocate to the nucleus, concomitantly bind to the SOD2 gene promoter and increase the expression of the antioxidant enzyme SOD2. Compared with normal ATXN3, mutant ATXN3 has a reduced capability to activate the FOXO4-mediated SOD2 expression and interferes with binding of FOXO4 to the SOD2 gene promoter. These findings are consistent with a downregulation of SOD2 in pontine brain tissue and lymphoblastoid cell (LC) lines of SCA3 patients. In response to oxidative stress, LCs from SCA3 patients show a specific impairment to upregulate SOD2 expression in correlation with a significantly increased formation of reactive oxygen species and cytotoxicity. The impairment to increase the expression of SOD2 under oxidative stress conditions is associated with a significantly reduced binding of FOXO4 to the SOD2 gene promoter in SCA3-LCs. Finally and consistent with a regulatory role of ATXN3 in SOD2 expression, knockdown of endogenous ATXN3 by RNA interference represses the expression of SOD2. These findings support that ATXN3 plays an important role in regulating the FOXO4-dependent antioxidant stress response via SOD2 and suggest that a decreased antioxidative capacity and increased susceptibility towards oxidative stress contributes to neuronal cell death in SCA3.","subset":"pubmed_abstract"} +{"meta":{"pmid":30573967,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Physician Parents Attending Work Despite Own Sick Children: A Qualitative Study on Caregiver Presenteeism Among Norwegian Hospital Physicians.\nStudies have shown that physicians manifest a clear duty to work, even in the face of personal risk, and despite their own symptoms of ill health; this is termed presenteeism. We lack knowledge on their willingness to attend work when their children are sick or in times of concern for their unborn; this is termed caregiver presenteeism. To gain a comprehensive knowledge on the occurrence of presenteeism among physicians, it is important to include caregiver presenteeism. The aim of this study is to explore the perception and experience with caregiver presenteeism among hospital physicians who are parents or pregnant and to explore its foundations and its consequences. Secondary thematic analysis of semi-structured interviews of hospital physicians (N = 18). Positive and negative dimensions associated with (1) situations with severe pregnancy symptoms or responsibility for sick children; (2) the perceived impact on their work commitments, personal health, and adequate care for own children; (3) accompanying moderators in the organisational structure and professional culture; and (4) proposed approaches to resolve caregiver and work responsibilities simultaneously contributing to caregiver presenteeism. The study underlines the impact of factors in organisational structure, professional culture, and the personal sphere affecting caregiver presenteeism. It appears that targeting factors contributing to attendance pressure in physicians, including those who are pregnant, is particularly important. This includes changing attitudes towards caregiver responsibilities among physician colleagues, department leaders, and physicians themselves, as well as simple cost-efficient organisational interventions in staffing, routines of absence, and work adjustment.","subset":"pubmed_abstract"} +{"meta":{"pmid":21621458,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2022-21":1,"2021-43":1,"2021-31":1,"2019-47":1,"2019-43":1,"2019-35":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2022-27":1,"2024-22":2,"2024-18":1}}},"text":"Exercise prescription for patients with type 2 diabetes and pre-diabetes: a position statement from Exercise and Sport Science Australia.\nType 2 diabetes mellitus (T2DM) and pre-diabetic conditions such as impaired fasting glucose (IFG) and\/or impaired glucose tolerance (IGT) are rapidly increasing in prevalence. There is compelling evidence that T2DM is more likely to develop in individuals who are insufficiently active. Exercise training, often in combination with other lifestyle strategies, has beneficial effects on preventing the onset of T2DM and improving glycaemic control in those with pre-diabetes. In addition, exercise training improves cardiovascular risk profile, body composition and cardiorespiratory fitness, all strongly related to better health outcomes. Based on the evidence, it is recommended that patients with T2DM or pre-diabetes accumulate a minimum of 210 min per week of moderate-intensity exercise or 125 min per week of vigorous intensity exercise with no more than two consecutive days without training. Vigorous intensity exercise is more time efficient and may also result in greater benefits in appropriate individuals with consideration of complications and contraindications. It is further recommended that two or more resistance training sessions per week (2-4 sets of 8-10 repetitions) should be included in the total 210 or 125 min of moderate or vigorous exercise, respectively. It is also recommended that, due to the high prevalence and incidence of comorbid conditions in patients with T2DM, exercise training programs should be written and delivered by individuals with appropriate qualifications and experience to recognise and accommodate comorbidities and complications.","subset":"pubmed_abstract"} +{"meta":{"pmid":29659166,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Strategies to improve tumor penetration of nanomedicines through nanoparticle design.\nNanoparticles (NPs) have emerged as an effective means to deliver therapeutic drugs for cancer treatment, as they can preferentially accumulate at tumor site through the enhanced permeability and retention effect. Various forms of NPs including liposomes, polymeric micelles, and inorganic particles have been used for therapeutic applications. However, the therapeutic benefits of nanomedicines are suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumor penetration can be a vital obstacle. Tumor develops characteristic pathological environment, such as abnormal vasculature, elevated interstitial fluid pressure, and dense extracellular matrix, which intrinsically hinder the transport of nanomedicines in the tumor parenchyma. The physicochemical properties of the NPs such as size, shape, and surface charge have profound effect on tumor penetration. In this review, we will highlight the factors that affect the transport of NPs in solid tumor, and then elaborate on designing strategies to improve NPs' penetration and uniform distribution inside the tumor interstitium. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":19660659,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2022-27":3,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":2,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-18":2,"2019-09":1,"2022-49":1}}},"text":"Progesterone as a neuroprotective factor in traumatic and ischemic brain injury.\nThe search for a \"magic bullet\" drug targeting a single receptor for the treatment of stroke or traumatic brain injury (TBI) has failed thus far for a variety of reasons. The pathophysiology of ischemic brain injury and TBI involves a number of mechanisms leading to neuronal injury, including excitotoxicity, free radical damage, inflammation, necrosis, and apoptosis. Brain injury also triggers auto-protective mechanisms, including the up-regulation of anti-inflammatory cytokines and endogenous antioxidants. In these conditions an agent with pleiotropic consequences is more likely to provide effective neuroprotection and repair than one operating primarily on a single, or a small number of, injury mechanisms. There is growing evidence, including recently published clinical trials, that progesterone and perhaps its metabolite allopregnanolone exert neuroprotective effects on the injured central nervous system (CNS). Laboratories around the world have shown that progesterone and allopregnanolone act through numerous metabolic and physiological pathways that can affect the injury response in many different tissues and organ systems. Furthermore, progesterone is a natural hormone, synthesized in both males and females, that can act as a pro-drug for other metabolites with their own distinct mode of action in CNS repair. These properties make progesterone a unique and compelling natural agent to consider for testing in clinical trial for CNS injuries including TBI and stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":15939015,"dup_signals":{"dup_doc_count":13,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":3}}},"text":"The bacterial helicase-primase interaction: a common structural\/functional module.\nThe lack of a high-resolution structure for the bacterial helicase-primase complex and the fragmented structural information for the individual proteins have been hindering our detailed understanding of this crucial binary protein interaction. Two new structures for the helicase-interacting domain of the bacterial primases from Escherichia coli and Bacillus stearothermophilus have recently been solved and both revealed a unique and surprising structural similarity to the amino-terminal domain of the helicase itself. In this minireview, the current data are discussed and important new structural and functional aspects of the helicase-primase interaction are highlighted. An attractive structural model with direct biological significance for the function of this complex and also for the development of new antibacterial compounds is examined.","subset":"pubmed_abstract"} +{"meta":{"pmid":11713826,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Induction of immunity using oral DNA vaccines expressing the measles virus nucleocapsid protein.\nIn this study, we have examined the feasibility of immunisation against measles with plasmid DNA administered by the oral route. After the oral administration, in two 50 microg doses, of poly(DL-lactide-co-glycolide) (PLGA)-encapsulated DNA expressing measles virus nucleoprotein, increasing titres of N-specific serum IgG antibodies were observed in three of ten C3H\/He mice over a period of three months. In comparison, oral vaccination of mice with a replication-defective recombinant adenovirus expressing the same transgene induced serum IgG in all animals tested. We also obtained preliminary indication of adjuvant-like activity of PLGA particles when coadministered intraperitoneally (i.p.) with naked plasmid DNA. These experiments demonstrate that oral delivery of either PLGA-encapsulated plasmid DNA or viral vectored DNA is capable of eliciting strong immune responses in mice. We propose that oral administration of biodegradable microparticles offers a novel strategy for future vaccine design for the safe delivery of DNA to mucosal surfaces.","subset":"pubmed_abstract"} +{"meta":{"pmid":2580000,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"Immunoregulation in the rat: ontogeny of B cell responses to types 1, 2, and T-dependent antigens.\nThe development of rat B cells has been examined in neonatal and adult Fischer rats through the use of type 1 (TNP-Brucella abortus), type 2 (TNP-LPS(Ph), TNP-Ficoll) and T cell-dependent (TD) (SRBC) antigens. In vivo splenic PFC responses to TNP-Brucella abortus could be induced in newborn rats and by 12 days of age had reached adult levels. In contrast, the responses to the type 2 and TD antigens were 30% and 70%, respectively, of the adult levels at 30 days of age. Adoptive transfer of the B cells from neonatal and young rats into irradiated adult hosts demonstrated that the kinetics in the development of responses to these antigens (early for type 1, intermediate for TD, and late for type 2) were not due to limiting accessory cell or T cell help in immature rats. In vitro cultures of purified B cells from neonatal and adult rats were responsive to TNP-BA and TNP-LPS(Ph) but not to TNP-Ficoll and SRBC. However, the addition of spleen cell-derived Con A supernatant to the B cell cultures resulted in responses to all four antigens, which arose as a function of B cell age, with kinetics that were identical to those observed in vivo. Fluorescent staining of B cells from rats of various ages for cell surface IgM and analysis on the fluorescence-activated cell sorter (FACS) revealed that all splenic B cells from rats 4 days of age expressed a relatively high level of sIgM, and that a subpopulation that expressed a relatively low level of sIgM increased with age until it represented approximately 50% of the adult splenic B cells. Challenging Con A supernatant-supplemented cultures of FACS-prepared low sIgM+ and high sIgM+ cells revealed that B cells responsive to TNP-Ficoll were confined to the ontogenically late-arising low sIgM+ subpopulation but that B cells responsive to TNP-BA, TNP-LPS(Ph), and SRBC were present in both subpopulations.","subset":"pubmed_abstract"} +{"meta":{"pmid":21785567,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Dampening Host Sensing and Avoiding Recognition in Pseudomonas aeruginosa Pneumonia.\nPseudomonas aeruginosa is an opportunistic pathogen and causes a wide range of acute and chronic infections. P. aeruginosa infections are kept in check by an effective immune surveillance in the healthy host, while any imbalance or defect in the normal immune response can manifest in disease. Invasive acute infection in the immunocompromised patients is mediated by potent extracellular and cell bound bacterial virulence factors. Life-threatening chronic infection in cystic fibrosis patients is maintained by pathogenic variants that contribute to evade detection and clearance by the immune system. Here, we reviewed the molecular basis of receptor-mediated recognition of P. aeruginosa and their role in initiating inflammation and the colonization. In addition, the consequence of the P. aeruginosa genetic adaptation for the antibacterial defence and the maintaining of chronic infection are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26928975,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The effects of framework dynamics on the behavior of water adsorbed in the [Zn(l-L)(Cl)] and Co-MOF-74 metal-organic frameworks.\nThe effects of framework flexibility on the structural and dynamical properties of water adsorbed in two prototypical metal-organic frameworks are investigated through molecular dynamics simulations. It is found that water molecules in the pores of a flexible model of [Zn(l-L)(Cl)] exhibit slower dynamics than when the framework is artificially held rigid in the simulations. In contrast, the water dynamics in Co-MOF-74 is predicted to be accelerated by the framework vibrations. The origin of this different behavior directly relates to how water interacts with the two frameworks, which, in turn, determines different hydrogen-bond patterns in the pores. While the first water molecules adsorbed in [Zn(l-L)(Cl)] donate a single hydrogen bond to the Zn-Cl groups and point the other hydrogen atom towards the center of the pore, water molecules adsorbed in Co-MOF-74 initially bind to the cobalt atoms of the framework via their oxygen atoms, thus leaving each molecule free to form two hydrogen bonds with additional molecules adsorbed at higher loading. The simulation results indicate that taking into account the framework flexibility in computer simulations is necessary for a quantitative modeling of adsorption and transport processes in metal-organic frameworks.","subset":"pubmed_abstract"} +{"meta":{"pmid":24035728,"dup_signals":{"dup_doc_count":22,"dup_dump_count":21,"dup_details":{"curated_sources":1,"2021-31":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2019-51":1,"2019-39":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2021-49":1}}},"text":"Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?\nTo evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles.","subset":"pubmed_abstract"} +{"meta":{"pmid":28790014,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-40":1,"2022-33":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-25":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-40":1,"2020-29":1,"2023-14":1,"2024-26":1,"2024-18":1,"2024-30":1}}},"text":"BMP2 expression in the endocardial lineage is required for AV endocardial cushion maturation and remodeling.\nDistal outgrowth, maturation and remodeling of the endocardial cushion mesenchyme in the atrioventricular (AV) canal are the essential morphogenetic events during four-chambered heart formation. Mesenchymalized AV endocardial cushions give rise to the AV valves and the membranous ventricular septum (VS). Failure of these processes results in several human congenital heart defects. Despite this clinical relevance, the mechanisms governing how mesenchymalized AV endocardial cushions mature and remodel into the membranous VS and AV valves have only begun to be elucidated. The role of BMP signaling in the myocardial and secondary heart forming lineage has been well studied; however, little is known about the role of BMP2 expression in the endocardial lineage. To fill this knowledge gap, we generated Bmp2 endocardial lineage-specific conditional knockouts (referred to as Bmp2 cKOEndo) by crossing conditionally-targeted Bmp2flox\/flox mice with a Cre-driver line, Nfatc1Cre, wherein Cre-mediated recombination was restricted to the endocardial cells and their mesenchymal progeny. Bmp2 cKOEndo mouse embryos did not exhibit failure or delay in the initial AV endocardial cushion formation at embryonic day (ED) 9.5-11.5; however, significant reductions in AV cushion size were detected in Bmp2 cKOEndo mouse embryos when compared to control embryos at ED13.5 and ED16.5. Moreover, deletion of Bmp2 from the endocardial lineage consistently resulted in membranous ventricular septal defects (VSDs), and mitral valve deficiencies, as evidenced by the absence of stratification of mitral valves at birth. Muscular VSDs were not found in Bmp2 cKOEndo mouse hearts. To understand the underlying morphogenetic mechanisms leading to a decrease in cushion size, cell proliferation and cell death were examined for AV endocardial cushions. Phospho-histone H3 analyses for cell proliferation and TUNEL assays for apoptotic cell death did not reveal significant differences between control and Bmp2 cKOEndo in AV endocardial cushions. However, mRNA expression of the extracellular matrix components, versican, Has2, collagen 9a1, and periostin was significantly reduced in Bmp2 cKOEndo AV cushions. Expression of transcription factors implicated in the cardiac valvulogenesis, Snail2, Twist1 and Sox9, was also significantly reduced in Bmp2 cKOEndo AV cushions. These data provide evidence that BMP2 expression in the endocardial lineage is essential for the distal outgrowth, maturation and remodeling of AV endocardial cushions into the normal membranous VS and the stratified AV valves.","subset":"pubmed_abstract"} +{"meta":{"pmid":11348945,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Expiratory flow limitation and orthopnea in massively obese subjects.\nMorbidly obese subjects, who often complain about breathlessness when lying down, breathe at low lung volume with a reduced expiratory reserve volume (ERV). Therefore, during tidal breathing the expiratory flow reserve is decreased, promoting expiratory flow limitation (EFL), which is more likely to occur in the supine position, when the relaxation volume of the respiratory system, and hence the functional residual capacity (FRC), decrease because of the gravitational effect of the abdominal contents. The aim of the study was to assess EFL and orthopnea in massively obese subjects and to evaluate whether orthopnea was associated with the development of supine EFL. In 46 healthy obese subjects (18 men) with a mean (+\/- SD) age of 44 +\/- 11 years and a mean body mass index (BMI) of 51 +\/- 9 kg\/m(2), we assessed EFL in both the seated and the supine positions by the negative expiratory pressure method and assessed postural changes in FRC by measuring the variations in the inspiratory capacity (IC) with recumbency. Simultaneously, dyspnea was evaluated in either position using the Borg scale dyspnea index (BSDI) to determine the presence of orthopnea, which was defined as any increase of the BSDI in the supine position. Partial EFL was detected in 22% and 59%, respectively, of the overall population in seated and supine position. The mean increase in the supine IC amounted to 120 +\/- 200 mL (4.1 +\/- 6.4%), indicating a limited decrease in FRC with recumbency in these subjects. Orthopnea, although mild (mean BSDI, 1.7 +\/- 1.3), was claimed by 20 subjects, and in 15 of them EFL occurred or worsened in the supine position. Orthopnea was associated with lower values of seated ERV (p < 0.05) and was marginally related to supine EFL values (p = 0.07). No significant effect of age, BMI, obstructive sleep apnea-hypopnea syndrome, FEV(1), and forced expiratory flow at 75% of vital capacity was found on either orthopnea or EFL. In morbidly obese subjects, EFL and dyspnea frequently occur with the subject in the supine position, and both supine EFL and low-seated ERV values are related to orthopnea, suggesting that dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure may be partly responsible for orthopnea in massively obese subjects.","subset":"pubmed_abstract"} +{"meta":{"pmid":19908143,"dup_signals":{"dup_doc_count":21,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2015-18":1,"unknown":14}}},"text":"Women's decisions regarding tamoxifen for breast cancer prevention: responses to a tailored decision aid.\nTamoxifen reduces primary breast cancer incidence, yet causes serious side effects. To date, few women with increased breast cancer risk have elected to use tamoxifen for chemoprevention. The objective of the study was to determine women's knowledge of and attitudes toward tamoxifen following exposure to a tailored decision aid (DA). A total of 632 women with a 5-year risk of breast cancer > or = 1.66% (Mean = 2.56, range = 1.7-17.3) were recruited from two healthcare organizations. Participants viewed an online DA that informed them about their 5-year risk of breast cancer and presented individually tailored content depicting the risks\/benefits of tamoxifen prophylaxis. Outcome measures included behavioral intentions (to seek additional information about tamoxifen, to talk to a physician about tamoxifen, and to take tamoxifen); knowledge; and perceived risks and benefits of tamoxifen. After viewing the DA, 29% of participants said they intended to seek more information or talk to their doctor about tamoxifen, and only 6% believed they would take tamoxifen. Knowledge was considerable, with 63% of women answering at least 5 of 6 knowledge questions correctly. Participants were concerned about the risks of tamoxifen, and many believed that the benefits of tamoxifen did not outweigh the risks. This study is the largest to date to test women's preferences for taking tamoxifen and one of the largest to have tested the impact of a tailored DA. After viewing the DA, women demonstrated good understanding of tamoxifen's risks and benefits, but most were not interested in taking tamoxifen for breast cancer chemoprevention.","subset":"pubmed_abstract"} +{"meta":{"pmid":21998713,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":12}}},"text":"Proline and COMT status affect visual connectivity in children with 22q11.2 deletion syndrome.\nIndividuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis. We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals. Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback\/feedforward ratios, which was moderated by the COMT(158) genotype. These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":27490469,"dup_signals":{"dup_doc_count":24,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-26":1,"unknown":19}}},"text":"Disability Divides in India: Evidence from the 2011 Census.\nUnderstanding the socioeconomic and regional divides in disability prevalence in India has considerable relevance for designing public health policies and programs. The aim of the present study is to quantify the prevalence of disability by gender, region (rural and urban; states and districts), and caste. We also examine the association between disability prevalence and the major socio-demographic and socioeconomic characteristics of the districts in India. Age-standardized disability prevalence (ASDP) was calculated using 2011 census data and applying the WHO World Standard Population. A regression analysis was carried out to examine the association between disability prevalence and demographic and socioeconomic characteristics across districts of India. The study found that ASDP varies substantially across districts and is higher among women, rural dwellers, and members of scheduled tribes (STs) and scheduled castes (SCs). The regression model showed that the disability rate in districts rises with increasing proportions of the population who are urban dwellers, aged 65 or older, members of STs, and living in dilapidated housing; and that the disability prevalence decreases with increasing proportions of the female population who are literate, and of the general population who are working and have access to safe drinking water. As the burden of disability falls disproportionately across geographic regions and socioeconomic groups, public health policies in India should take this variation into account. The definition of disability used in the census should be modified to generate internationally comparable estimates of disability prevalence.","subset":"pubmed_abstract"} +{"meta":{"pmid":34839166,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":2,"2024-10":1,"unknown":13}}},"text":"What do biomarkers add: Mapping quantitative imaging biomarkers research.\nTo understand the contribution of the concept of \"biomarker\" to quantitative imaging research. The study consists of a bibliometric and a network analysis of quantitative imaging biomarkers research based on publication data retrieved from the Web of Science (WoS) for the period 1976-2017. Co-authorship is used as a proxy for scientific collaboration among research groups. Research groups are disambiguated and assigned to an institutional sector and to a medical specialty or academic discipline. Co-occurrence maps of specialties are built to delineate the collaborative network structure of this emerging field. Two very distinct growth patterns emerged from the 5432 publications retrieved from WoS. Scientific production on \u00abquantitative imaging biomarkers\u00bb (QIB) began 20 years after the first publications on \u00abquantitative imaging\u00bb (QI). The field of QIB has exhibited rapid growth becoming the most used term since 2011. Among the 12,882 institutions identified, 56% include the term QIB and 44% include the term QI; among the 14,734 different research groups identified, 60% include the term QIB and 40% the term QI. QIB is characterized by a well-established community of researchers whose largest contributors are in medical specialties (radiology 17%, neurology 16%, mental 10%, oncology 10%), while QI shows a more fragmented and diverse community (radiology 13%, engineering 13%, physics 10%, oncology 9%, neurology 6%, biology 4%, nuclear 3%, computing 3%). This suggests a qualitative difference between QIB and QI networks. Adding biomarkers to quantitative imaging suggests that medical imaging is rapidly evolving, driven by the efforts to translate quantitative imaging research into clinical practice.","subset":"pubmed_abstract"} +{"meta":{"pmid":14666229,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":2}}},"text":"[Evaluative research on occupational rehabilitation: the effectiveness of a health care service subject to dismantlement].\nThis article deals with the results obtained from 1995 to 1997 by an innovative occupational rehabilitation model for individuals with repetitive strain injury\/work related musculoskeletal disorder (RSI\/WRMD), developed by the Campinas Occupational Rehabilitation Center under the Brazilian National Institute for Social Security. The study had two objectives: 1) to reconstruct the program as a precondition for evaluation and 2) to evaluate the model's effectiveness in reestablishing the autonomy of individuals with RSI\/WRMD. The methodology involved document analysis in order to reconstruct the program's background in terms of problem identification, organizational participation, awareness-raising, staff characteristics and responsibilities, and profile of the clientele. An analysis of 221 patient files provided the basis for constructing an evaluative instrument consisting of different dimensions, variables, and indicators, which was applied to a sample of 47 patient histories prior and subsequent to rehabilitative intervention. High effectiveness was observed in the model, with variations in the different target dimensions.","subset":"pubmed_abstract"} +{"meta":{"pmid":22201683,"dup_signals":{"dup_doc_count":40,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2017-13":3,"2015-18":3,"2015-11":3,"2015-06":3,"2013-48":2,"2013-20":1,"2024-26":1,"unknown":20}}},"text":"Obesity is associated with hypothalamic injury in rodents and humans.\nRodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.","subset":"pubmed_abstract"} +{"meta":{"pmid":30563451,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-24":1,"2019-30":1,"2019-22":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"iMGEins: detecting novel mobile genetic elements inserted in individual genomes.\nRecent advances in sequencing technology have allowed us to investigate personal genomes to find structural variations, which have been studied extensively to identify their association with the physiology of diseases such as cancer. In particular, mobile genetic elements (MGEs) are one of the major constituents of the human genomes, and cause genome instability by insertion, mutation, and rearrangement. We have developed a new program, iMGEins, to identify such novel MGEs by using sequencing reads of individual genomes, and to explore the breakpoints with the supporting reads and MGEs detected. iMGEins is the first MGE detection program that integrates three algorithmic components: discordant read-pair mapping, split-read mapping, and insertion sequence assembly. Our evaluation results showed its outstanding performance in detecting novel MGEs from simulated genomes, as well as real personal genomes. In detail, the average recall and precision rates of iMGEins are 96.67 and 100%, respectively, which are the highest among the programs compared. In the testing with real human genomes of the NA12878 sample, iMGEins shows the highest accuracy in detecting MGEs within 20 bp proximity of the breakpoints annotated. In order to study the dynamics of MGEs in individual genomes, iMGEins was developed to accurately detect breakpoints and report inserted MGEs. Compared with other programs, iMGEins has valuable features of identifying novel MGEs and assembling the MGEs inserted.","subset":"pubmed_abstract"} +{"meta":{"pmid":17620483,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":11}}},"text":"The new neurobiology of autism: cortex, connectivity, and neuronal organization.\nThis review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism.","subset":"pubmed_abstract"} +{"meta":{"pmid":30092782,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Sodium and potassium excretion in an adult Caribbean population of African descent with a high burden of cardiovascular disease.\nHigh sodium diets with inadequate potassium and high sodium-to-potassium ratios are a known determinant of hypertension and cardiovascular disease (CVD). The Caribbean island of Barbados has a high prevalence of hypertension and mortality from CVD. Our objectives were to estimate sodium and potassium excretion, to compare estimated levels with recommended intakes and to identify the main food sources of sodium in Barbadian adults. A sub-sample (n = 364; 25-64 years) was randomly selected from the representative population-based Health of the Nation cross-sectional study (n = 1234), in 2012-13. A single 24-h urine sample was collected from each participant, following a strictly applied protocol designed to reject incomplete samples, for the measurement of sodium and potassium excretion (in mg), which were used as proxy estimates of dietary intake. In addition, sensitivity analyses based on estimated completeness of urine collection from urine creatinine values were undertaken. Multiple linear regression was used to examine differences in sodium and potassium excretion, and the sodium-to-potassium ratio, by age, sex and educational level. Two 24-h recalls were used to identify the main dietary sources of sodium. All analyses were weighted for the survey design. Mean sodium excretion was 2656 (2488-2824) mg\/day, with 67% (62-73%) exceeding the World Health Organization (WHO) recommended limit of 2000 mg\/d. Mean potassium excretion was 1469 (1395-1542) mg\/d; < 0.5% met recommended minimum intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9-2.1); not one participant had a ratio that met WHO recommendations. Higher potassium intake and lower sodium-to-potassium ratio were independently associated with age and tertiary education. Sensitivity analyses based on urine creatinine values did not notably alter these findings. In this first nationally representative study with objective assessment of sodium and potassium excretion in a Caribbean population in over 20 years, levels of sodium intake were high, and potassium intake was low. Younger age and lower educational level were associated with the highest sodium-to-potassium ratios. These findings provide baseline values for planning future policy interventions for non-communicable disease prevention.","subset":"pubmed_abstract"} +{"meta":{"pmid":28941595,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":13}}},"text":"Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men.\nThere is a need for early markers to track and predict the development of type 2 diabetes mellitus (T2DM) from the state of normal glucose tolerance through prediabetes. In this study we tested whether the plasma molecular lipidome has biomarker potential to predicting the onset of T2DM. We applied global lipidomic profiling on plasma samples from well-phenotyped men (107 cases, 216 controls) participating in the longitudinal METSIM study at baseline and at five-year follow-up. To validate the lipid markers, an additional study with a representative sample of adult male population (n=631) was also conducted. A total of 277 plasma lipids were analyzed using the lipidomics platform based on ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Lipids with the highest predictive power for the development of T2DM were computationally selected, validated and compared to standard risk models without lipids. A persistent lipid signature with higher levels of triacylglycerols and diacyl-phospholipids as well as lower levels of alkylacyl phosphatidylcholines was observed in progressors to T2DM. Lysophosphatidylcholine acyl C18:2 (LysoPC(18:2)), phosphatidylcholines PC(32:1), PC(34:2e) and PC(36:1), and triacylglycerol TG(17:1\/18:1\/18:2) were selected to the full model that included metabolic risk factors and FINDRISC variables. When further adjusting for BMI and age, these lipids had respective odds ratios of 0.32, 2.4, 0.50, 2.2 and 0.31 (all p<0.05) for progression to T2DM. The independently-validated predictive power improved in all pairwise comparisons between the lipid model and the respective standard risk model without the lipids (integrated discrimination improvement IDI>0; p<0.05). Notably, the lipid models remained predictive of the development of T2DM in the fasting plasma glucose-matched subset of the validation study. This study indicates that a lipid signature characteristic of T2DM is present years before the diagnosis and improves prediction of progression to T2DM. Molecular lipid biomarkers were shown to have predictive power also in a high-risk group, where standard risk factors are not helpful at distinguishing progressors from non-progressors.","subset":"pubmed_abstract"} +{"meta":{"pmid":30854632,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2020-24":1,"2020-16":2,"2019-51":4,"2019-39":1,"2019-35":9,"2020-50":1}}},"text":"Parallel pattern of differentiation at a genomic island shared between clinal and mosaic hybrid zones in a complex of cryptic seahorse lineages.\nDiverging semi-isolated lineages either meet in narrow clinal hybrid zones, or have a mosaic distribution associated with environmental variation. Intrinsic reproductive isolation is often emphasized in the former and local adaptation in the latter, although both reduce gene flow between groups. Rarely are these two patterns of spatial distribution reported in the same study system. Here, we report that the long-snouted seahorse Hippocampus guttulatus is subdivided into discrete panmictic entities by both types of hybrid zones. Along the European Atlantic coasts, a northern and a southern lineage meet in the southwest of France where they coexist in sympatry-i.e., in the same geographical zone-with little hybridization. In the Mediterranean Sea, two lineages have a mosaic distribution, associated with lagoon-like and marine habitats. A fifth lineage was identified in the Black Sea. Genetic homogeneity over large spatial scales contrasts with isolation maintained in sympatry or close parapatry at a fine scale. A high variation in locus-specific introgression rates provides additional evidence that partial reproductive isolation must be maintaining the divergence. We find that fixed differences between lagoon and marine populations in the Mediterranean Sea belong to the most differentiated SNPs between the two Atlantic lineages, against the genome-wide pattern of structure that mostly follow geography. These parallel outlier SNPs cluster on a single chromosome-wide island of differentiation. Since Atlantic lineages do not map to lagoon-sea habitat variation, genetic parallelism at the genomic island suggests a shared genetic barrier contributes to reproductive isolation in contrasting contexts-i.e., spatial versus ecological. We discuss how a genomic hotspot of parallel differentiation could have evolved and become associated both with space and with a patchy environment in a single study system.","subset":"pubmed_abstract"} +{"meta":{"pmid":18534266,"dup_signals":{"dup_doc_count":45,"dup_dump_count":37,"dup_details":{"curated_sources":2,"2022-33":1,"2021-25":1,"2020-40":1,"2020-29":1,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":1,"2014-23":2,"2014-15":3,"2022-40":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry.\nThe purpose of this study was to investigate the long-term safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. Long-term clinical outcomes after DES implantation for ULMCA disease have not yet been ascertained. From April 2002 to April 2004, 358 consecutive patients who underwent PCI with DES implantation for de novo lesions on ULMCA were retrospectively selected and analyzed in 7 European and U.S. tertiary care centers. No patients were excluded from the analysis, and all patients had a minimum follow-up of 3 years. Technical success rate was 100%. Procedural success rate was 89.6%. After 3 years, major adverse cardiovascular events (MACE)-free survival in the whole population was 73.5%. According to the Academic Research Consortium definitions, cardiac death occurred in 9.2% of patients, and reinfarction, target lesion revascularization (TLR), and target vessel revascularization (TVR) occurred in 8.6%, 5.8%, and 14.2% of patients, respectively. Definite stent thrombosis occurred in 2 patients (specifically at 0 and 439 days). In elective patients, the 3-year MACE-free survival was 74.2%, with mortality, reinfarction, TLR, and TVR rates of 6.2%, 8.3%, 6.6%, and 16%, respectively. In the emergent group the 3-year MACE-free survival was 68.2%, with mortality, reinfarction, TLR, and TVR rates of 21.4%, 10%, 2.8%, and 7.1%, respectively. Routine DES implantation in ULMCA disease seems encouraging, with favorable long-term clinical results.","subset":"pubmed_abstract"} +{"meta":{"pmid":6360598,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Problems of mothers in management of children with diabetes.\nThis study was designed to determine which aspects of diabetic management were perceived by mothers of children with diabetes to be the most problematic. A secondary purpose was to explore how age and sex of the child, age at diagnosis, illness duration, marital status, and socioeconomic status of the mother were related to the mother's perception of problematic aspects of care. The 84 subjects in this study were asked to complete the Diabetic Management Concern Questionnaire, which measures concern about 11 dimensions of diabetes management, along with a personal-situational information sheet. Results indicated that the three dimensions classified by mothers as most problematic were future concerns, hypoglycemia, and diabetic control. The younger the child, the greater the maternal concern about hypoglycemic reactions and availability of help\/support. The younger the child was at diagnosis, the more the mother was concerned with hypoglycemic reactions. A shorter duration of illness was related to concern about insulin injections. Subjects with lower socioeconomic status were concerned about finances, the availability of help\/support, and the psychological stigma of diabetes. Single mothers were also concerned about financial aspects of management. There were no differences in concerns between mothers of boys and girls. Implications of the findings for clinical practice are presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":24135989,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":10}}},"text":"Real-time label-free surface plasmon resonance biosensing with gold nanohole arrays fabricated by nanoimprint lithography.\nIn this work we present a surface plasmon resonance sensor based on enhanced optical transmission through sub-wavelength nanohole arrays. This technique is extremely sensitive to changes in the refractive index of the surrounding medium which result in a modulation of the transmitted light. The periodic gold nanohole array sensors were fabricated by high-throughput thermal nanoimprint lithography. Square periodic arrays with sub-wavelength hole diameters were obtained and characterized. Using solutions with known refractive index, the array sensitivities were obtained. Finally, protein absorption was monitored in real-time demonstrating the label-free biosensing capabilities of the fabricated devices.","subset":"pubmed_abstract"} +{"meta":{"pmid":29786547,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Protective effect of breastfeeding on recurrent cough in adulthood.\nBreastfeeding protects from respiratory infections in early life but its relationship to recurrent cough and other respiratory outcomes in adult life is not well established. Infant feeding practices were assessed prospectively in the Tucson Children's Respiratory Study, a non-selected birth cohort and categorised into formula from birth or introduced <1 month, formula introduced \u22651 to <4 months and exclusive breastfeeding for \u22654 months. Infant feeding was assessed as an ordinal variable representing an increasing dose of breastmilk across the three categories. Recurrent cough was defined at 22, 26 and 32 years as \u22652 episodes of cough without a cold lasting 1 week during the past year. Covariates included participant sex, race\/ethnicity and smoking as well as parental smoking, education, age and asthma. Covariates were evaluated as potential confounders for the relation between infant feeding and adult outcomes. Of the 786 participants, 19% breastfed <1 month, 50% breastfed \u22651 to <4 months and 31% breastfed \u22654 months. The prevalence of recurrent cough at 22, 26 and 32 years was 17%, 15% and 16%, respectively. Each ordinal increase in breastfeeding duration was associated with a decreased risk of recurrent cough in adult life: adjusted OR=0.71, (95% CI: 0.56 to 0.89), p=0.004. Additional adjustment for concurrent adult asthma, wheeze, smoking and lung volume did not change these results. Longer duration of breastfeeding reduces the risk of recurrent cough in adult life, regardless of smoking and other respiratory symptoms, suggesting long-term protective effects on respiratory health.","subset":"pubmed_abstract"} +{"meta":{"pmid":2992285,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Role of serotonin type 2 receptors in regulation of aldosterone production.\nIt is well recognized that serotonin stimulates aldosterone production by the adrenal glands. To investigate the possible roles of serotonin type 1 and 2 receptors in the regulation of aldosterone production, we examined the effects of cyproheptadine (a serotonin antagonist that inhibits both type 1 and 2 receptors) and ketanserin (a serotonin type 2 selective antagonist) on aldosterone and cAMP production in collagenase dispersed rat adrenal capsular cells. Serotonin, ranging in concentration from 10(-9) to 10(-3) M, significantly increased aldosterone production in a dose-dependent fashion after 2 h of incubation at 37 degrees C. Cyproheptadine and ketanserin showed comparable inhibitory effects on basal aldosterone production. These serotonin antagonists preferentially inhibited serotonin-induced aldosterone production. Serotonin significantly increased cAMP production at a dose of 10(-6) M. Both cyproheptadine and ketanserin significantly decreased basal cAMP production at doses of 10(-5) M. These serotonin antagonists preferentially inhibited serotonin-stimulated cAMP production. These results suggest that adrenal serotonin type 2 receptors may be coupled with adenylate cyclase activity and that these receptors are involved in the regulation of aldosterone production. Whether serotonin plays an important role in the regulation of aldosterone secretion in vivo remains to be elucidated.","subset":"pubmed_abstract"} +{"meta":{"pmid":20452957,"dup_signals":{"dup_doc_count":54,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2023-40":3,"2023-14":4,"2022-49":2,"2022-33":4,"2022-27":5,"2022-21":1,"2022-05":2,"2021-43":3,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":2,"2021-10":3,"2020-50":3,"2020-40":4,"2023-50":1,"2024-26":5,"2024-22":1,"2024-10":3}}},"text":"Tied up in loops: positive and negative autoregulation of p53.\nThe tumor suppressor p53 is a master sensor of stress that controls many biological functions, including implantation, cell-fate decisions, metabolism, and aging. In response to a defined stress signal such as gamma radiation, the response of p53 is heterogeneous in vivo. Like a complex barcode, the ability of p53 to function as a central hub that integrates defined stress signals into decisive cellular responses, in a time- and cell-type dependent manner, is facilitated by the extraordinary complexity of its regulation. Key components of this barcode are the autoregulation loops, which positively or negatively regulate p53's activities. Thus, this article focuses on reviewing our current understanding of how autoregulation loops formed between p53 and how its transcriptional targets regulate the activities of p53 at a variety of levels, through mdm2-dependent and -independent pathways. Knowing that a large number of autoregulation loops exist that influence p53's activity, our future challenge is to elucidate which of these play a central role in regulating p53, under which conditions, in response to what stress, and at which particular stage of our lives. Such knowledge may ultimately lead to the development of more effective anticancer therapeutics.","subset":"pubmed_abstract"} +{"meta":{"pmid":8596930,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2019-26":2,"2019-09":1,"2017-51":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2016-50":1,"2016-44":1,"2020-29":1}}},"text":"Requirement of U12 snRNA for in vivo splicing of a minor class of eukaryotic nuclear pre-mRNA introns.\nA conserved sequence element in a minor class of eukaryotic pre-messenger RNA (pre-mRNA) introns was previously proposed to base pair with a complementary sequence in the U12 small nuclear RNA (snRNA) in a manner analogous to the pairing of US snRNA with the branch site sequence of the major class of introns. Here, mutations generated in this conserved sequence element block the splicing of a member of this minor intron class in vivo. The block was relieved by coexpression of a U12 snRNA containing compensatory mutations that restore the proposed base pairing interaction. These results show that this minor class of pre-mRNA introns is a distinct class existing alongside the major class of introns in animal genomes, and these results also establish an in vivo function for U12 snRNA.","subset":"pubmed_abstract"} +{"meta":{"pmid":22366736,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":13}}},"text":"Advanced imaging of skeletal manifestations of systemic mastocytosis.\nSystemic mastocytosis comprises a group of clonal disorders of the mast cell that most commonly involves the skeletal system. Imaging can be helpful in the detection and characterization of the osseous manifestations of this disease. While radiography and bone scans are frequently used for this assessment, low-dose multidetector computed tomography and magnetic resonance imaging can be more sensitive for the detection of marrow involvement and for the demonstration of the various disease patterns. In this article, we review the pathophysiological and clinical features of systemic mastocytosis, discuss the role of imaging for staging and management, and illustrate the various cross-sectional imaging appearances. Awareness and knowledge of the imaging features of this disorder will increase the accuracy of image interpretation and can contribute important information for management decisions.","subset":"pubmed_abstract"} +{"meta":{"pmid":3381628,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Prevalence of thyroid dysfunction in elderly subjects. A randomized study in a Norwegian rural community (Naer\u00f8y).\nThe prevalence of thyroid dysfunction was investigated in a small, rural community located at the coast in Middle Norway. Two hundred persons (114 women and 86 men) of the total 802 persons over 70 years of age in the community were examined regarding thyroid dysfunction. Blood samples were drawn from 197 (113 women and 84 men). In women previously diagnosed hypothyroidism was found in 3.5% and previously diagnosed hyperthyroidism in 0.9%. In men no previously diagnosed thyroid disease was found. Undiagnosed primary hypothyroidism (TT4 less than 70 nmol\/l and TSH greater than 6 mU\/l) was found in 1.8% and 1.2% of women and men, respectively. Latent hypothyroidism (TT4 70-150 nmol\/l and TSH greater than 6 mU\/l) was found in 3.5% and 2.4%, and borderline hypothyroidism (TSH 4.5-6.0 mU\/l) in 3.5% and 2.4%, respectively. Undiagnosed hyperthyroidism was not found in women but in 1.2% of men. Antibody to the thyroid microsomal antigen (TMA) greater than or equal to 400 was detected in 17.5% of women and 9.6% of men. Clearly elevated serum thyrotropin (TSH) concentrations or previously diagnosed thyroid disease were found in 21.7% and 37.5% of the TMA positive women and men, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":8612715,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Differential expression of PTP1D, a protein tyrosine phosphatase with two SH2 domains, in a slow and fast skeletal muscle fibers.\nWe show that PTP1D, a protein tyrosine phosphatase that contains two SH2 domains, is preferentially expressed in slow skeletal muscle fibers. Immunohistochemical staining using polyclonal antibodies against PTP1D demonstrated that PTP1D was expressed in a subpopulation of rodent muscle fibers. These fibers were identified as slow Type I fibers based on histochemical ATPase assays and slow myosin heavy chain expression. Northern and Western analyses showed that PTP1D levels were higher in predominantly slow muscles than in predominantly fast muscles. This differential expression of PTP1D in slow muscle fibers appeared by birth. In cultures of mouse myogenic cells, PTP1D was expressed after MyoD and myogenin and appeared in myotubes derived from embryonic, fetal, and postnatal myoblasts. Remarkably, PTP1D was organized into sarcomeres in a pattern coincident with myosin heavy chain, suggesting that PTP1D associates with a component of the thick filament. These results show that PTP1D is preferentially expressed in slow muscle fibers. We speculate that PTP1D may play a role in slow muscle fiber function and differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29516222,"dup_signals":{"dup_doc_count":11}},"text":"Burden and trend of diet-related non-communicable diseases in Australia and comparison with 34 OECD countries, 1990-2015: findings from the Global Burden of Disease Study 2015.\nDiet is a major determining factor for many non-communicable chronic diseases (NCDs). However, evidence on diet-related NCD burden remains limited. We assessed the trends in diet-related NCDs in Australia from 1990 to 2015 and compared the results with other countries of the Organization for Economic Co-operation and Development (OECD). We used data and methods from the Global Burden of Disease (GBD) 2015 study to estimate the NCD mortality and disability-adjusted life years (DALYs) attributable to 14 dietary risk factors in Australia and 34 OECD nations. Countries were further ranked from the lowest (first) to highest (35th) burden using an age-standardized population attributable fraction (PAF). In 2015, the estimated number of deaths attributable to dietary risks was 29,414 deaths [95% uncertainty interval (UI) 24,697 - 34,058 or 19.7% of NCD deaths] and 443,385 DALYs (95% UI 377,680-511,388 or 9.5% of NCD DALYs) in Australia. Young (25-49 years) and middle-age (50-69 years) male adults had a higher PAF of diet-related NCD deaths and DALYs than their female counterparts. Diets low in fruits, vegetables, nuts and seeds and whole grains, but high in sodium, were the major contributors to both NCD deaths and DALYs. Overall, 42.3% of cardiovascular deaths were attributable to dietary risk factors. The age-standardized PAF of diet-related NCD mortality and DALYs decreased over the study period by 28.2% (from 27.0% in 1990 to 19.4% in 2015) and 41.0% (from 14.3% in 1990 to 8.4% in 2015), respectively. In 2015, Australia ranked 12th of 35 examined countries in diet-related mortality. A small improvement of rank was recorded compared to the previous 25 years. Despite a reduction in diet-related NCD burden over 25 years, dietary risks are still the major contributors to a high burden of NCDs in Australia. Interventions targeting NCDs should focus on dietary behaviours of individuals and population groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":24365835,"dup_signals":{"dup_doc_count":23,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2016-44":1,"2016-40":1,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":3,"2015-27":2,"2015-22":2,"2019-47":1}}},"text":"Compressive single-pixel snapshot x-ray diffraction imaging.\nWe present a method for realizing snapshot, depth-resolved material identification using only a single, energy-sensitive pixel. To achieve this result, we employ a coded aperture with subpixel features to modulate the energy spectrum of coherently scattered photons and recover the object properties using an iterative inversion algorithm based on compressed sensing theory. We demonstrate high-fidelity object estimation at x-ray wavelengths for a variety of compression ratios exceeding unity.","subset":"pubmed_abstract"} +{"meta":{"pmid":8581887,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Circular nodes in neural networks.\nIn the usual construction of a neural network, the individual nodes store and transmit real numbers that lie in an interval on the real line; the values are often envisioned as amplitudes. In this article we present a design for a circular node, which is capable of storing and transmitting angular information. We develop the forward and backward propagation formulas for a network containing circular nodes. We show how the use of circular nodes may facilitate the characterization and parameterization of periodic phenomena in general. We describe applications to constructing circular self-maps, periodic compression, and one-dimensional manifold decomposition. We show that a circular node may be used to construct a homeomorphism between a trefoil knot in R3 and a unit circle. We give an application with a network that encodes the dynamic system on the limit cycle of the Kuramoto-Sivashinsky equation. This is achieved by incorporating a circular node in the bottleneck layer of a three-hidden-layer bottleneck network architecture. Exploiting circular nodes systematically offers a neural network alternative to Fourier series decomposition in approximating periodic or almost periodic functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":24470935,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":3,"2013-48":2,"2013-20":2,"unknown":8}}},"text":"No clinical or biological difference between Chikungunya and Dengue Fever during the 2010 Gabonese outbreak.\nChikungunya (CHIKV) and Dengue (DENV) viruses, both arboviruses, have caused multiple outbreaks worldwide. Their clinical features are poorly described in Africa and there is no comparative study, although Chikungunya is considered as a dengue-like disease. We conducted a comparative study of clinical and biological data from CHIKV and DENV positive patients during the 2010 Gabonese outbreak. Patients consulting with general symptoms and having laboratory confirmation for CHIKV or DENV were included. Clinical and biological data were recorded. Statistical analyses were performed using Epi Info. A P value < 0.05 was considered significant. In all, 270 CHIKV+, 53 DENV+ and 20 co-infected patients were included in the study. Headaches, hemorrhage, leukopenia and lymphopenia were significantly (P respectively 0.01, 0.001, 0.02 and 0.001) more frequent in DENV+ patients than in CHIKV+. There was no additive effect of the two viruses.These clinical and hematological disorders are non specific and cannot assist for the differential diagnosis. These diseases are clinically indistinguishable, and need for laboratory confirmation.","subset":"pubmed_abstract"} +{"meta":{"pmid":31066658,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Proposal for changes in the International Code of Nomenclature of Prokaryotes: granting priority to Candidatus names.\nCurrently, the description of taxa designated Candidatus requires gene sequences and other taxonomically relevant available information in the absence of an isolated pure culture, and Candidatus names are provisional, i.e. without formal standing in nomenclature. If gene sequences are accepted as suitable type material for the description of prokaryotic species, many taxa designated Candidatus would fulfil all the requirements in the International Code of Nomenclature of Prokaryotes for priority. Here we propose that upon acceptance of sequence data as type material, all Candidatus names published before 1 January 2020 which are otherwise in accordance with the rules of the Code will have their priority based upon their date of publication in the International Journal of Systematic and Evolutionary Microbiology, either within a paper, a list of names of Candidatus taxa, or a Validation List, unless a synonymous name already exists based upon deposition of type cultures. We further propose that modifications of the superscript 'T' be used to identify the nomenclatural types. If the type material is a culture, the superscript 'T' will continue to be used. If the type material is a sequence, the superscript 'Ts' will be used. If the type material is some other form of description, the superscript 'Td' will be used.","subset":"pubmed_abstract"} +{"meta":{"pmid":17243233,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Integrated biological treatment and biogas production in a small-scale slaughterhouse in rural Ghana.\nA small-scale anaerobic slaughter waste treatment plant in rural Ghana was tested for the production of energy and a microbiologically clean effluent suitable for use in irrigation. A typical day's slaughter, comprising 4 cattle, 12 sheep, and 12 goats, produced 8.5 m3 of biogas. Annually, this is equivalent to the energy from 17 metric tons of fuel wood, which is the annual productivity of 2 ha of savanna vegetation. Fecal indicator bacteria were reduced by 2 to 3 logs, nitrates by 86 to 90%, phosphates by 23%, biochemical oxygen demand by 42 to 92%, and suspended solids and dissolved solids by 73 to 86% and 19 to 37%, respectively. The effluent is used for irrigation, and the organic biomass from the digester is used as a biofertilizer. Besides energy and a cleaner effluent, the community benefited from a lessening dependency on fuel wood and reductions in unpleasant smells and nuisance animals, such as flies, dogs, and vultures.","subset":"pubmed_abstract"} +{"meta":{"pmid":15937548,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes.\nThe progression of immune responses is generally associated with an increase in the overall avidity of antigen-specific T cell populations for peptide-MHC. This is thought to result from preferential expansion of high-avidity clonotypes at the expense of their low-avidity counterparts. Since T cell antigen-receptor genes do not mutate, it is puzzling that high-avidity clonotypes do not predominate from the outset. Here we provide a developmental basis for this phenomenon in the context of autoimmunity. We have carried out comprehensive studies of the diabetogenic CD8 T cell population that targets residues 206-214 of the beta cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)) and undergoes avidity maturation as disease progresses. We find that the succession of IGRP(206-214)-specific clonotypes with increasing avidities during the progression of islet inflammation to overt diabetes in nonobese diabetic mice is fueled by autoimmune inflammation but opposed by systemic tolerance. As expected, naive high-avidity IGRP(206-214)-specific T cells respond more efficiently to antigen and are significantly more diabetogenic than their intermediate- or low-avidity counterparts. However, central and peripheral tolerance selectively limit the contribution of these high-avidity T cells to the earliest stages of disease without abrogating their ability to progressively accumulate in inflamed islets and kill beta cells. These results illustrate the way in which incomplete deletion of autoreactive T cell populations of relatively high avidity can contribute to the development of pathogenic autoimmunity in the periphery.","subset":"pubmed_abstract"} +{"meta":{"pmid":19806655,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-18":2,"2013-48":1,"2013-20":1,"unknown":5}}},"text":"Morphology of the quadrate in the Eocene anseriform Presbyornis and extant galloanserine birds.\nDespite the notoriety, phylogenetic significance, and large number of available specimens of Presbyornis, its cranial anatomy has never been studied in detail, and its quadrate has been partly misinterpreted. We studied five quadrates of Presbyornis that reveal features hitherto unknown in the anseriforms but otherwise present in galliforms. As a result, we analyzed the variable quadrate characters among all extant galloanserine families and identified synapomorphies and other morphological variation among the major galloanserine clades. In terms of quadrate morphology, Presbyornis is more plesiomorphic than any extant anseriform (including the Anhimidae) and shares ancestral galloanserine characters with the Megapodiidae, the earliest branch of extant galliforms. The quadrate's morphology is inconsistent with the currently accepted anseriform phylogeny that nests Presbyornis within the crown-group as a close relative of the Anatidae. The presbyornithid quadrates exhibit an unusual variation in the presence of a caudomedial pneumatic foramen, which we interpret as a result of a discontinuous change in the growth path of the pneumatic diverticulum. Another episode of morphogenetic imbalance in the growth path of the pneumatic diverticulum may have accompanied the disappearance of the basiorbital pneumatic foramen (along with the pneumatization of the pterygoid) at the origin of the crown-group anseriforms. This episode is marked by the striking individual variation in the presence and location of pneumatic foramina in the mandibular part of the quadrate in the Anhimidae.","subset":"pubmed_abstract"} +{"meta":{"pmid":18369246,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Individual differences in incompetence avoidance.\nThis study compared the fear of failure and perfectionism constructs by analyzing their latent structure as well as their motivational antecedents and consequences. College students (N = 372) enrolled in physical activity classes completed a battery of questionnaires assessing fear of failure, perfectionism, approach and avoidance motivational temperaments, and 2 x 2 achievement goals. Structural equation modeling revealed that responses were best summarized by two correlated factors representing perfectionistic strivings and concerns. Avoidance temperament was positively associated with both forms of incompetence avoidance; however, approach temperament was positively related only to perfectionist strivings. Perfectionistic concerns were positively related to the adoption of mastery-avoidance and performance-avoidance goals and negatively related to the adoption of mastery-approach goals. Perfectionistic strivings were positively associated with both approach goals. These results indicate that strivings to avoid incompetence can be distinguished with respect to their latent structure, temperamental antecedents, and motivational consequences.","subset":"pubmed_abstract"} +{"meta":{"pmid":32113941,"dup_signals":{"dup_doc_count":34,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":2,"2023-14":3,"2023-06":2,"2022-49":2,"2022-27":3,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":2,"2020-40":2,"2023-50":1,"2024-30":2,"2024-22":1,"2024-18":2}}},"text":"European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention.\nInvasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women's Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography-computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.","subset":"pubmed_abstract"} +{"meta":{"pmid":23511225,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":12}}},"text":"N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR).\nWe measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels \u2265 100 pg\/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (\u2265 100 pg\/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD.","subset":"pubmed_abstract"} +{"meta":{"pmid":29135770,"dup_signals":{"dup_doc_count":13}},"text":"An Electronic Health Record-based Algorithm to Ascertain the Date of Second Breast Cancer Events.\nStudies of cancer recurrences and second primary tumors require information on outcome dates. Little is known about how well electronic health record-based algorithms can identify dates or how errors in dates can bias analyses. We assessed rule-based and model-fitting approaches to assign event dates using a previously published electronic health record-based algorithm for second breast cancer events (SBCE). We conducted a simulation study to assess bias due to date assignment errors in time-to-event analyses. From a cohort of 3152 early-stage breast cancer patients, 358 women accurately identified as having had an SBCE served as the basis for this analysis. Percent of predicted SBCE dates identified within \u00b160 days of the true date was the primary measure of accuracy. In the simulation study, bias in hazard ratios (HRs) was estimated by averaging the difference between HRs based on algorithm-assigned dates and the true HR across 1000 simulations each with simulated N=4000. The most accurate date algorithm had a median difference between the true and predicted dates of 0 days with 82% of predicted dates falling within 60 days of the true date. Bias resulted when algorithm sensitivity and specificity varied by exposure status, but was minimal when date assignment errors were of the magnitude observed for our date assignment method. SBCE date can be relatively accurately assigned based on a previous algorithm. While acceptable in many scenarios, algorithm-assigned dates are not appropriate to use when operating characteristics are likely to vary by the study exposure.","subset":"pubmed_abstract"} +{"meta":{"pmid":38095060,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"The PDLIM family of actin-associated proteins and their emerging role in membrane trafficking.\nThe PDZ and LIM domain (PDLIM) proteins are associated with the actin cytoskeleton and have conserved in roles in metazoan actin organisation and function. They primarily function as scaffolds linking various proteins to actin and its binding partner \u03b1-actinin via two conserved domains; an N-terminal postsynaptic density 95, discs large and zonula occludens-1 (PDZ) domain, and either single or multiple C-terminal LIN-11, Isl-1 and MEC-3 (LIM) domains in the actinin-associated LIM protein (ALP)- and Enigma-related proteins, respectively. While their role in actin organisation, such as in stress fibres or in the Z-disc of muscle fibres is well known, emerging evidence also suggests a role in actin-dependent membrane trafficking in the endosomal system. This is mediated by a recently identified interaction with the sorting nexin 17 (SNX17) protein, an adaptor for the trafficking complex Commander which is itself intimately linked to actin-directed formation of endosomal recycling domains. In this review we focus on the currently understood structural basis for PDLIM function. The PDZ domains mediate direct binding to distinct classes of PDZ-binding motifs (PDZbms), including \u03b1-actinin and other actin-associated proteins, and a highly specific interaction with the type III PDZbm such as the one found in the C-terminus of SNX17. The structures of the LIM domains are less well characterised and how they engage with their ligands is completely unknown. Despite the lack of experimental structural data, we find that recently developed machine learning-based structure prediction methods provide insights into their potential interactions and provide a template for further studies of their molecular functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":33177817,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Chronic Obstructive Pulmonary Disease and Incidence of Hip Fracture: A Nested Case-Control Study in the EpiChron Cohort.\nTo determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for hip fracture and identify other factors associated with hip fracture. Observational nested case-control study was conducted in Aragon, Spain in 2010. We included COPD patients aged >40 years, in the EpiChron cohort. Each COPD patient was matched for age, sex, and number of comorbidities with a control subject without COPD. Patients with an existing diagnosis of osteoporosis and those with hip fracture before 2011 were excluded. We collected baseline demographic, comorbidity, and pharmacological treatment data. During a 5-year follow-up period, we recorded the incidence of hip fracture. A logistic regression model was constructed to identify factors associated with hip fracture. The study population consisted of 26,517 COPD patients and the same number of controls (median [interquartile range] age, 74 [17] years; women, 24.7%). Smoking and heart failure were more frequent in COPD patients, and obesity, hypertension, diabetes, dyslipidemia, stroke, arthritis, and visual or hearing impairment were less frequent (all p<0.001). Consumption of benzodiazepines (p=0.037), bronchodilators (p<0.001), and corticosteroids (p<0.001) was higher in the COPD group, while that of beta-blockers and thiazides was lower (both p<0.001). During follow-up, 898 (1.7%) patients experienced hip fracture, with no differences observed between COPD and control patients. Multivariate analysis revealed that independent of COPD status, age, female sex, chronic liver disease, heart failure, and benzodiazepine use were independently associated with a higher risk of hip fracture, and obesity with a lower risk. In COPD patients, use of inhaled anticholinergics was independently associated with hip fracture (OR, 1.390; 95% CI 1.134-1.702; p=0.001). COPD is not a risk factor for a hip fracture within 5 years. The association between the use of inhaled anticholinergics and risk of hip fracture warrants further study.","subset":"pubmed_abstract"} +{"meta":{"pmid":29774926,"dup_signals":{"dup_doc_count":17,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2021-10":2,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-43":2,"2018-34":2,"2018-22":3}}},"text":"An anionic shell shields a cationic core allowing for uptake and release of polyelectrolytes within core-shell responsive microgels.\nTo realize carriers for drug delivery, cationic containers are required for anionic guests. Nevertheless, the toxicity of cationic carriers limits their practical use. In this study, we investigate a model system of polyampholyte N-isopropylacrylamide (NIPAM)-based microgels with a cationic core and an anionic shell to study whether the presence of a negative shell allows the cationic core to be shielded while still enabling the uptake and release of the anionic guest polyelectrolytes. These microgels are loaded with polystyrene sulfonate of different molecular weights to investigate the influence of their chain length on the uptake and release process. By means of small-angle neutron scattering, we evaluate the spatial distribution of polystyrene sulfonate within the microgels. The guest molecules are located in different parts of the core-shell microgels depending on their size. By combining these scattering results with UV-vis spectroscopy, electrophoretic mobility and potentiometric titrations we gain complementary results to investigate the uptake and release process of polyelectrolytes in polyampholyte core-shell microgels. Moreover, Brownian molecular dynamic simulations are performed to compare the experimental and theoretical results of this model. Our findings demonstrate that the presence of a shell still enables efficient uptake of guest molecules into the cationic core. These anionic guest molecules can be released through an anionic shell. Furthermore, the presence of a shell enhances the stability of the microgel-polyelectrolyte complexes with respect to the cationic precursor microgel alone.","subset":"pubmed_abstract"} +{"meta":{"pmid":26449781,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-30":1,"unknown":11}}},"text":"To What Extent do Sleep Quality and Duration Mediate the Effect of Perceived Discrimination on Health? Evidence from Philadelphia.\nLittle research investigates whether sleep mediates the adverse effect of perceived discrimination on health and even less is known about whether sleep quality and sleep duration mediate the relationships in the same fashion. We applied a recently developed mediation analysis approach to a survey administered in 2008 in Philadelphia, PA, that includes 9042 adults. Health was measured with self-rated health, stress, and mental illness. Perceived discrimination was operationalized with self-reported discriminatory experience in two social contexts, namely health care system and housing market. Sleep quality and duration were measured with a five-point Likert scale and the self-reported sleep time at night, respectively. After controlling for one's demographic, socioeconomic, and health-related characteristics, the mediation analysis quantified how much sleep quality and duration can account for the effect of perceived discrimination on these health outcomes. The key findings are: (a) sleep quality and duration accounted for approximately 15 to 25% of the adverse effect of perceived discrimination. (b) Sleep quality is more important than sleep duration in mediating the relationship between perceived discrimination and health. (c) The proportion of the effect mediated by sleep differs by the social context where perceived discrimination occurred. It was confirmed that sleep mediates the relationship between perceived discrimination and health and the interventions to improve sleep, particularly sleep quality, should help to attenuate the effect of perceived discrimination on health.","subset":"pubmed_abstract"} +{"meta":{"pmid":30287021,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2023-14":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-40":1}}},"text":"Fabrication and characterization of Gum arabic-cl-poly(acrylamide) nanohydrogel for effective adsorption of crystal violet dye.\nNatural biopolymers are better adsorbents due to better functionality, surface area, bio-compatibility and ease of procurement. The gum arabic in natural biopolymer derived from Acacia Arabic species. In the present work a novel nanohydrogel of gum arabic with acrylamide has been fabricated using microwave synthesis for adsorption of noxious crystal violet dye from aqueous medium. The prepared gum arabic-cl-poly(acrylamide) nanohydrogel (GA-cl-poly(AAm)) NHG was characterized by numerous techniques including SEM, XRD, TEM and FTIR. The GA-cl-poly(AAm) NHG showed promising adsorption ability for crystal violet dye. The effect of various adsorption factors such as concentration of GA-cl-poly(AAm) NHG and crystal violet, pH, temperature and time has been studied and reported. For understanding the adsorption mechanism three models Langmuir, Freundlich and Temkin were applied to adsorption data The kinetics and thermodynamics of adsorption were also investigated The adsorption capacity of crystal violet onto GA-cl-poly(AAm) NHG according to Langmuir model is found to be 90.90 mg\/g.","subset":"pubmed_abstract"} +{"meta":{"pmid":26991360,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2017-13":1,"2024-30":1,"unknown":7}}},"text":"High-Throughput Screening of Na(V)1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument.\nVoltage-gated sodium (Na(V)) channels have an essential role in the initiation and propagation of action potentials in excitable cells, such as neurons. Of these channels, Na(V)1.7 has been indicated as a key channel for pain sensation. While extensive efforts have gone into discovering novel Na(V)1.7 modulating compounds for the treatment of pain, none has reached the market yet. In the last two years, new compound screening technologies have been introduced, which may speed up the discovery of such compounds. The Sophion Qube(\u00ae) is a next-generation 384-well giga-seal automated patch clamp (APC) screening instrument, capable of testing thousands of compounds per day. By combining high-throughput screening and follow-up compound testing on the same APC platform, it should be possible to accelerate the hit-to-lead stage of ion channel drug discovery and help identify the most interesting compounds faster. Following a period of instrument beta-testing, a Na(V)1.7 high-throughput screen was run with two Pfizer plate-based compound subsets. In total, data were generated for 158,000 compounds at a median success rate of 83%, which can be considered high in APC screening. In parallel, IC50 assay validation and protocol optimization was completed with a set of reference compounds to understand how the IC50 potencies generated on the Qube correlate with data generated on the more established Sophion QPatch(\u00ae) APC platform. In summary, the results presented here demonstrate that the Qube provides a comparable but much faster approach to study Na(V)1.7 in a robust and reliable APC assay for compound screening.","subset":"pubmed_abstract"} +{"meta":{"pmid":19584318,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Vascular extracellular matrix and arterial mechanics.\nAn important factor in the transition from an open to a closed circulatory system was a change in vessel wall structure and composition that enabled the large arteries to store and release energy during the cardiac cycle. The component of the arterial wall in vertebrates that accounts for these properties is the elastic fiber network organized by medial smooth muscle. Beginning with the onset of pulsatile blood flow in the developing aorta, smooth muscle cells in the vessel wall produce a complex extracellular matrix (ECM) that will ultimately define the mechanical properties that are critical for proper function of the adult vascular system. This review discusses the structural ECM proteins in the vertebrate aortic wall and will explore how the choice of ECM components has changed through evolution as the cardiovascular system became more advanced and pulse pressure increased. By correlating vessel mechanics with physiological blood pressure across animal species and in mice with altered vessel compliance, we show that cardiac and vascular development are physiologically coupled, and we provide evidence for a universal elastic modulus that controls the parameters of ECM deposition in vessel wall development. We also discuss mechanical models that can be used to design better tissue-engineered vessels and to test the efficacy of clinical treatments.","subset":"pubmed_abstract"} +{"meta":{"pmid":16834455,"dup_signals":{"dup_doc_count":22,"dup_details":{"curated_sources":2,"unknown":20}}},"text":"\"Key to the future\": British American tobacco and cigarette smuggling in China.\nCigarette smuggling is a major public health issue, stimulating increased tobacco consumption and undermining tobacco control measures. China is the ultimate prize among tobacco's emerging markets, and is also believed to have the world's largest cigarette smuggling problem. Previous work has demonstrated the complicity of British American Tobacco (BAT) in this illicit trade within Asia and the former Soviet Union. This paper analyses internal documents of BAT available on site from the Guildford Depository and online from the BAT Document Archive. Documents dating from the early 1900s to 2003 were searched and indexed on a specially designed project database to enable the construction of an historical narrative. Document analysis incorporated several validation techniques within a hermeneutic process. This paper describes the huge scale of this illicit trade in China, amounting to billions of (United States) dollars in sales, and the key supply routes by which it has been conducted. It examines BAT's efforts to optimise earnings by restructuring operations, and controlling the supply chain and pricing of smuggled cigarettes. Our research shows that smuggling has been strategically critical to BAT's ongoing efforts to penetrate the Chinese market, and to its overall goal to become the leading company within an increasingly global industry. These findings support the need for concerted efforts to strengthen global collaboration to combat cigarette smuggling.","subset":"pubmed_abstract"} +{"meta":{"pmid":31249273,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":17}}},"text":"Portuguese recommendations for the use of ultrasound in rheumatology.\nUltrasound (US) is a relatively cheap, easily available and reliable method to improve the care of rheumatic patients. However, its use in rheumatology practice is very heterogeneous and needs to be standardized. To develop recommendations for the use of US in rheumatic diseases endorsed by the Portuguese Society of Rheumatology. A systematic literature review of the available recommendations on the use of ultrasound in rheumatic diseases was performed and presented in a Portuguese Society of Rheumatology meeting to a subgroup of rheumatologists and rheumatology trainees with special interest in the subject. The most important topics to be addressed were selected and assigned to subgroups for literature review and draft recommendations. Following an iterative process of consensus, the final recommendations were developed, and their level of agreement voted anonymously online. A recommendation was approved when the average level of agreement was \u2265 7.5 in a 10-point Likert scale. Fourteen recommendations were produced regarding nine rheumatology topics: rheumatoid arthritis, spondyloarthritis, connective tissue diseases, polymyalgia rheumatica, vasculitis, crystal-deposition diseases, soft tissue rheumatism, osteoarthritis and ultrasound-guided procedures. We developed an up-to-date guidance in the form of recommendations for the use of US in nine different areas of rheumatology. As ultrasound is an important imaging modality with increasing use in the rheumatology setting, and there are frequent technological advances in the ultrasound machines and probes, in parallel with continuous associated research, these recommendations should be regularly updated.","subset":"pubmed_abstract"} +{"meta":{"pmid":29389217,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Foot Kinetic and Kinematic Profile in Type 2 Diabetes Mellitus with Peripheral Neuropathy A Hospital-Based Study from South India.\nA kinetic change in the foot such as altered plantar pressure is the most common etiological risk factor for foot ulcers in people with diabetes mellitus. Kinematic alterations in joint angle and spatiotemporal parameters of gait have also been frequently observed in participants with diabetic peripheral neuropathy (DPN). Diabetic peripheral neuropathy leads to various microvascular and macrovascular complications of the foot in type 2 diabetes mellitus. There is a gap in the literature for biomechanical evaluation and assessment of type 2 diabetes mellitus with DPN in the Indian population. We sought to assess and determine the biomechanical changes, including kinetics and kinematics, of the foot in DPN. This cross-sectional study was conducted at a diabetic foot clinic in India. Using the purposive sampling method, 120 participants with type 2 diabetes mellitus and DPN were recruited. Participants with active ulceration or amputation were excluded. The mean \u00b1 SD age, height, weight, body mass index, and diabetes duration were 57 \u00b1 14 years, 164 \u00b1 11 cm, 61 \u00b1 18 kg, 24 \u00b1 3 kg\/m2, and 12 \u00b1 7 years, respectively. There were significant changes in the overall biomechanical profile and clinical manifestations of DPN. The regression analysis showed statistical significance for dynamic maximum plantar pressure at the forefoot with age, weight, height, diabetes duration, body mass index, knee and ankle joint angle at toe-off, pinprick sensation, and ankle reflex ( R = 0.71, R2 = 0.55, F12,108 = 521.9 kPa; P = .002). People with type 2 diabetes mellitus and DPN have significant changes in their foot kinetic and kinematic parameters. Therefore, they could be at higher risk for foot ulceration, with underlying neuropathy and biomechanically associated problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":23303523,"dup_signals":{"dup_doc_count":32,"dup_dump_count":27,"dup_details":{"curated_sources":3,"2022-49":2,"2022-40":1,"2022-05":1,"2021-43":1,"2020-45":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-34":1,"2017-26":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Loci influencing blood pressure identified using a cardiovascular gene-centric array.\nBlood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped \u223c50 000 single-nucleotide polymorphisms (SNPs) that capture variation in \u223c2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3\/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 \u00d7 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.","subset":"pubmed_abstract"} +{"meta":{"pmid":35146382,"dup_signals":{"dup_doc_count":12}},"text":"Large balancing areas and dispersed renewable investment enhance grid flexibility in a renewable-dominant power system in China.\nRenewable energy is poised to play a major role in achieving China's carbon neutrality goal by 2060; however, reliability and flexibility is a big concern of a renewable-dominant power system. Various strategies of enhancing flexibility are under discussion to ensure the reliability of such a system, but no detailed quantitative analysis has been reported yet in China. We combine the advantages of a capacity expansion model, SWITCH-China, with a production simulation model, PLEXOS, and analyze flexibility options under different scenarios of a renewable-dominant power system in China. We find that a larger balancing area offers direct flexibility benefits. Regional balancing could reduce the renewable curtailment rate by 5-7%, compared with a provincial balancing strategy. National balancing could further reduce the power cost by about 16%. However, retrofitting coal power plants for flexible operation would only improve the system flexibility marginally.","subset":"pubmed_abstract"} +{"meta":{"pmid":38088316,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Enlarged Vestibular Aqueduct and Associated Inner Ear Malformations: Hearing Loss Prognostic Factors and Data Modeling from an International Cohort.\nThere is a need to operationalize existing clinical data to support precision medicine in progressive hearing loss (HL). By utilizing enlarged vestibular aqueduct (EVA) and its associated inner ear abnormalities as an exemplar, we model data from a large international cohort, confirm prognostic factors for HL, and explore the potential to generate a prediction model to optimize current management paradigms. An international retrospective cohort study. Regression analyses were utilized to model frequency-specific HL and identify prognostic factors for baseline average HL severity and progression. Elastic-net regression and machine learning (ML) techniques were utilized to predict future average HL progression based upon routinely measurable clinical, genetic, and radiological data. Higher frequencies of hearing were lost more severely. Prognostic factors for HL were the presence of incomplete partition type 2 (coefficient 12.95 dB, P=.011, 95% CI 3.0-22 dB) and presence of sac signal heterogeneity (P=.009, 95% CI 0.062-0.429) on magnetic resonance imaging. Elastic-net regression outperformed the ML algorithms (R2 0.32, mean absolute error 11.05 dB) with coefficients for baseline average hearing level and the presence of sac heterogeneity contributing the most to prediction outcomes. Incomplete partition type 2 and endolymphatic sac signal heterogeneity phenotypes should be monitored closely for hearing deterioration and need for early audiological rehabilitation\/cochlear implant. Preliminary prediction models have been generated using routinely collected health data in EVA. This study showcases how international collaborative research can use exemplar techniques to improve precision medicine in relatively rare disease entities.","subset":"pubmed_abstract"} +{"meta":{"pmid":24876930,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1}}},"text":"Bisphosphonates and bone quality.\nBisphosphonates (BPs) are bone-avid compounds used as first-line medications for the prevention and treatment of osteoporosis. They are also used in other skeletal pathologies such as Paget's and metastatic bone disease. They effectively reduce osteoclast viability and also activity in the resorptive phase of bone remodelling and help preserve bone micro-architecture, both major determinants of bone strength and ultimately of the susceptibility to fractures. The chemically distinctive structure of each BP used in the clinic determines their unique affinity, distribution\/penetration throughout the bone and their individual effects on bone geometry, micro-architecture and composition or what we call 'bone quality'. BPs have no clinically significant anabolic effects. This review will touch upon some of the components of bone quality that could be affected by the administration of BPs.","subset":"pubmed_abstract"} +{"meta":{"pmid":21504022,"dup_signals":{"dup_doc_count":11}},"text":"Parallel AFM imaging and force spectroscopy using two-dimensional probe arrays for applications in cell biology.\nAtomic force microscopy (AFM) investigations of living cells provide new information in both biology and medicine. However, slow cell dynamics and the need for statistically significant sample sizes mean that data collection can be an extremely lengthy process. We address this problem by parallelizing AFM experiments using a two-dimensional cantilever array, instead of a single cantilever. We have developed an instrument able to operate a two-dimensional cantilever array, to perform topographical and mechanical investigations in both air and liquid. Deflection readout for all cantilevers of the probe array is performed in parallel and online by interferometry. Probe arrays were microfabricated in silicon nitride. Proof-of-concept has been demonstrated by analyzing the topography of hard surfaces and fixed cells in parallel, and by performing parallel force spectroscopy on living cells. These results open new research opportunities in cell biology by measuring the adhesion and elastic properties of a large number of cells. Both properties are essential parameters for research in metastatic cancer development.","subset":"pubmed_abstract"} +{"meta":{"pmid":10742315,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Symptoms associated with infant teething: a prospective study.\nStudies of infant teething have been retrospective, small, or conducted on institutionalized infants. To conduct a large, prospective study of healthy infants to determine which symptoms may be attributed to teething and to attempt to predict tooth emergence from an infant's symptoms. Prospective cohort. Setting. Clinic-based pediatric group practice. One hundred twenty-five consecutive well children of consenting Cleveland Clinic employees. Parents daily recorded 2 tympanic temperatures, presence or absence of 18 symptoms, and all tooth eruptions in their infants, from the 4-month well-child visit until the child turned 1 year old. Daily symptom data were available for 19 422 child-days and 475 tooth eruptions. Symptoms were only significantly more frequent in the 4 days before a tooth emergence, the day of the emergence, and 3 days after it, so this 8-day window was defined as the teething period. Increased biting, drooling, gum-rubbing, sucking, irritability, wakefulness, ear-rubbing, facial rash, decreased appetite for solid foods, and mild temperature elevation were all statistically associated with teething. Congestion, sleep disturbance, stool looseness, increased stool number, decreased appetite for liquids, cough, rashes other than facial rashes, fever over 102 degrees F, and vomiting were not significantly associated with tooth emergence. Although many symptoms were associated with teething, no symptom occurred in >35% of teething infants, and no symptom occurred >20% more often in teething than in nonteething infants. No teething child had a fever of 104 degrees F and none had a life-threatening illness. Many mild symptoms previously thought to be associated with teething were found in this study to be temporally associated with teething. However, no symptom cluster could reliably predict the imminent emergence of a tooth. Before caregivers attribute any infants' signs or symptoms of a potentially serious illness to teething, other possible causes must be ruled out.teething, tooth eruption, teeth, deciduous dentition.","subset":"pubmed_abstract"} +{"meta":{"pmid":25871206,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2021-39":1,"2021-25":1,"2021-10":1,"2020-40":1,"2020-34":1,"2020-10":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2021-43":1,"2024-18":1}}},"text":"Near-field acoustic streaming jet.\nA numerical and experimental investigation of the acoustic streaming flow in the near field of a circular plane ultrasonic transducer in water is performed. The experimental domain is a parallelepipedic cavity delimited by absorbing walls to avoid acoustic reflection, with a top free surface. The flow velocities are measured by particle image velocimetry, leading to well-resolved velocity profiles. The theoretical model is based on a linear acoustic propagation model, which correctly reproduces the acoustic field mapped experimentally using a hydrophone, and an acoustic force term introduced in the Navier-Stokes equations under the plane-wave assumption. Despite the complexity of the acoustic field in the near field, in particular in the vicinity of the acoustic source, a good agreement between the experimental measurements and the numerical results for the velocity field is obtained, validating our numerical approach and justifying the planar wave assumption in conditions where it is a priori far from obvious. The flow structure is found to be correlated with the acoustic field shape. Indeed, the longitudinal profiles of the velocity present a wavering linked to the variations in acoustic intensity along the beam axis and transverse profiles exhibit a complex shape strongly influenced by the transverse variations of the acoustic intensity in the beam. Finally, the velocity in the jet is found to increase as the square root of the acoustic force times the distance from the origin of the jet over a major part of the cavity, after a strong short initial increase, where the velocity scales with the square of the distance from the upstream wall.","subset":"pubmed_abstract"} +{"meta":{"pmid":27455072,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model.\nLow molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits.","subset":"pubmed_abstract"} +{"meta":{"pmid":26967991,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Congenital scoliosis treated with posterior vertebral column resection in patients younger than 18 years: longer than 10-year follow-up.\nOBJECTIVE There have been no reports on the long-term radiographic outcomes of posterior vertebral column resection (PVCR) in patients with congenital scoliosis. The purpose of this study was to evaluate the surgical outcomes and complications after PVCR and its long-term effects on correcting this deformity in children with congenital scoliosis. METHODS The authors retrospectively analyzed the medical records of 45 patients with congenital scoliosis who were younger than 18 years at the time of surgery and who underwent PVCR and fusion with pedicle screw fixation (PSF). The mean age of the patients at the time of surgery was 11.3 years (range 2.4-18.0 years), and the mean length of follow-up was 12.8 years (range 10.1-18.2 years). RESULTS The mean Cobb angle of the main curve was 46.5\u00b0 before PVCR, 13.7\u00b0 immediately after PVCR, and 17.6\u00b0 at the last follow-up. For the compensatory cranial curve, PVCR corrected the preoperative Cobb angle of 21.2\u00b0 to 9.1\u00b0 postoperatively and maintained it at 10.9\u00b0 at the last follow-up. For the compensatory caudal curve, the preoperative Cobb angle of 23.8\u00b0 improved to 7.7\u00b0 postoperatively and was 9.8\u00b0 at the last follow-up. The authors noted 22 complications, and the overall incidence of complications was 48.9%. CONCLUSIONS Posterior vertebral column resection is an effective procedure for managing congenital scoliosis in patients younger than 18 years. Use of PVCR and fusion with PSF for congenital scoliosis achieved rigid fixation and satisfactory deformity correction that was maintained over the long term. However, the authors note that PVCR is a technically demanding procedure and entails risks for major complications and excessive blood loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":16051710,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Effect of intermittent fasting and refeeding on insulin action in healthy men.\nInsulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function. We mimicked the fluctuations in eight healthy young men [25.0 +\/- 0.1 yr (mean +\/- SE); body mass index: 25.7 +\/- 0.4 kg\/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +\/- 2.3 kg; coefficient of variation: 0.8 +\/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +\/- 18 and 0.06 +\/- 0.02 mM, respectively, after overnight fast but increased (P < 0.05) to 423 +\/- 86 and 0.10 +\/- 0.04 mM after 20-h fasting, confirming that the subjects were fasting. Insulin-mediated whole body glucose uptake rates increased from 6.3 +\/- 0.6 to 7.3 +\/- 0.3 mg.kg(-1).min(-1) (P = 0.03), and insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (P = 0.05). After the 20-h fasting periods, plasma adiponectin was increased compared with the basal levels before and after the intervention (5,922 +\/- 991 vs. 3,860 +\/- 784 ng\/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.","subset":"pubmed_abstract"} +{"meta":{"pmid":19476357,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Direct measurement of photoinduced charge separation distances in donor-acceptor systems for artificial photosynthesis using OOP-ESEEM.\nThe distance over which two photogenerated charges are separated in electron donor-acceptor systems for artificial photosynthesis depends on the structure of the system, while the lifetime of the charge separation and, ultimately, its ability to carry out useful redox chemistry depend on the electronic coupling between the oxidized donor and reduced acceptor. The radical ions produced by charge separation are frequently delocalized over the pi systems of the final oxidized donor and reduced acceptor, so that there is often significant uncertainty as to the average distance between the separated charges, especially in low dielectric constant media, where the Coulomb attraction of the ions may be significant and the charge distribution of the ions may be distorted, so that the average distance between them may be shorter than that implied by their chemical structures. The charge separation distances between photogenerated radical ions in three donor-acceptor molecules having different donor-acceptor distances were measured directly from their dipolar spin-spin interactions using out-of-phase electron spin echo envelope modulation (OOP-ESEEM). The measured distances in toluene at 85 K compare favorably to the calculated distances between the centroids of the spin distributions of the radical ions within the radical ion pairs. These results show that despite the intrinsically nonpolar nature of medium, the spin (and charge) distributions of the RPs are not significantly distorted by Coulomb attraction over these long distances. This study shows that OOP-ESEEM is well-suited for probing the detailed structural features of charge-separated intermediates that are essential to understanding how to design molecular structures that prolong and control charge separation for artificial photosynthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":18542418,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":11}}},"text":"Bloch oscillations in chirped layered structures with metamaterials.\nWe analyze the Bloch oscillations of electromagnetic waves in chirped layered structures with alternating layers of negative-index metamaterial and conventional dielectric under the condition of the zero average refractive index. We consider the case when the chirp is introduced by varying the thickness of the layers linearly across the structure. We demonstrate that such structures can support three different types of the Bloch oscillations for electromagnetic waves associated with either propagating or evanescent guided modes. In particular, we predict a novel type of the Bloch oscillations associated with coupling between surface waves excited at the interfaces separating the layers of negative-index metamaterial and the layers of the conventional dielectric.","subset":"pubmed_abstract"} +{"meta":{"pmid":21627811,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":3,"2015-11":3,"2015-06":2,"2014-10":3,"2013-48":2,"2013-20":2,"unknown":2}}},"text":"Diagnostic dilemmas of squamous differentiation in prostate carcinoma case report and review of the literature.\nWe report a case of pure squamous cell carcinoma involving the prostate and urinary bladder and describe the diagnostic dilemmas that we faced in trying to determine its origin. The patient was diagnosed ten years ago with prostatic adenocarcinoma treated with radioactive seed implantation. During the last year he also underwent a TURP procedure for urinary obstruction complicated by multiple infections. Postsurgery, the patient developed colo-urethral fistula and decision to perform cystoprostatectomy was taken. Excision illustrated a tumor mass replacing the entire prostate that microscopically proved to be squamous cell carcinoma. The challenge that we encountered was to determine its origin, the possibilities being divergent differentiation from adenocarcinoma post radiation therapy, de novo neoplasm or urothelial carcinoma with extensive squamous differentiation. Our literature review showed also that the etiology of prostatic squamous carcinoma is still unclear. We present our approach in an attempt to solve this dilemma.","subset":"pubmed_abstract"} +{"meta":{"pmid":28625833,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":1,"unknown":15}}},"text":"Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity.\nProteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data. Cell lines mirrored the proteomic aberrations of primary tumors, in particular for intrinsic programs. Tumor relationships of protein expression with DNA copy number aberrations and signatures of post-transcriptional regulation were recapitulated in cell lines. The 5 proteomic subtypes previously identified in tumors were represented among cell lines. Nonetheless, systematic differences between cell line and tumor proteomes were apparent, attributable to stroma, extrinsic signaling, and growth conditions. Contribution of tumor stroma obscured signatures of DNA mismatch repair identified in cell lines with a hypermutation phenotype. Global proteomic data showed improved utility for predicting both known drug-target relationships and overall drug sensitivity as compared with genomic or transcriptomic measurements. Inhibition of targetable proteins associated with drug responses further identified corresponding synergistic or antagonistic drug combinations. Our data provide evidence for CRC proteomic subtype-specific drug responses. Proteomes of established CRC cell line are representative of primary tumors. Proteomic data tend to exhibit improved prediction of drug sensitivity as compared with genomic and transcriptomic profiles. Our integrative proteogenomic analysis highlights the potential of proteome profiling to inform personalized cancer medicine.","subset":"pubmed_abstract"} +{"meta":{"pmid":19877025,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"De novo malignancies following liver transplantation: impact and recommendations.\n1. De novo malignancy is one of the leading causes of late mortality after liver transplantation. 2. The risks of skin cancers and lymphoma are more than 10-fold greater than the risks in an age-matched and sex-matched general population. 3. Some types of neoplasia, such as lung, head and neck, and colorectal cancer, are more frequent in liver transplant recipients than in an age-matched and sex-matched population. The risks of other frequent malignancies, such as prostate and breast cancer, do not seem to be increased. 4. The most important risks for posttransplant malignancy are Epstein-Barr virus seronegativity (for lymphoma), sun exposure (for skin cancer), smoking, and increasing age. 5. Despite the absence of evidence, general recommendations (such as avoidance of overimmunosuppression, sunlight protection, and cessation of smoking) should be given. Screening protocols may help to detect neoplasia at an early stage of disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":26492636,"dup_signals":{"dup_doc_count":14,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2021-25":1,"2021-21":1,"2020-10":1,"2020-05":1,"2019-51":3,"2019-47":1,"2019-43":1,"2022-21":1}}},"text":"Effect of Performance Level on the Prediction of Middle-Distance-Running Performances Using a Nomogram.\nThis study examined the effect of performance level on the validity and accuracy of middle-distance running-performance predictions obtained from the nomogram of Mercier et al in male runners. Official French track-running rankings for the 3000-, 5000-, and 10,000-m events from 2006 to 2014 were examined. The performance level was determined from the official reference table of the F\u00e9d\u00e9ration Fran\u00e7aise d'Athl\u00e9tisme, and the runners were divided in 3 groups (ie, low, moderate, and high levels). Only male runners who performed in the 3 distance events within the same year were included (N = 443). Each performance over any distance was predicted using the nomogram from the 2 other performances. No difference was found in low- and moderate-performance-level athletes (0.02 \u2264 effect size [ES] \u2264 0.06, 95% limits of agreement [LoA] \u2264 6%). By contrast, a small difference in high-performance-level athletes (P < .01, 0.23 \u2264 ES \u2264 0.45, 95% LoA \u2264 11.6%) was found. The study confirms the validity of the nomogram to predict track-running performance with a high level of accuracy, except for male runners with high performance level (ie, national or international). Consequently, the predictions from the nomogram may be used in training programs (eg, to prescribe tempo runs with realistic training velocities) and competitions (eg, to plan realistic split times to reach the best performance).","subset":"pubmed_abstract"} +{"meta":{"pmid":17110569,"dup_signals":{"dup_doc_count":44,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2021-17":1,"2021-10":1,"2020-29":1,"2020-24":1,"2019-43":1,"2019-22":1,"2018-47":2,"2018-30":1,"2018-13":2,"2018-09":1,"2017-51":1,"2017-34":2,"2017-30":1,"2017-26":2,"2017-17":1,"2017-09":2,"2016-50":3,"2016-40":3,"2016-36":4,"2016-30":2,"2016-18":1,"2016-07":2,"2021-21":1,"2017-13":2,"2013-48":1}}},"text":"Sequencing and analysis of Neanderthal genomic DNA.\nOur knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor approximately 706,000 years ago, and that the human and Neanderthal ancestral populations split approximately 370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.","subset":"pubmed_abstract"} +{"meta":{"pmid":28150857,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Long-term mental fatigue after traumatic brain injury and impact on employment status.\nLong-term mental fatigue following traumatic brain injury is endorsed as one of the most distressing symptoms, interfering considerably with return to work and social life. The objective of this cross-sectional study was to estimate the prevalence of long-term mental fatigue after traumatic brain injury and to evaluate its association with employment status. All patients (age range 19-65 years) diagnosed with traumatic brain injury irrespective of severity at Kung\u00e4lv Hospital, Kung\u00e4lv, Sweden, over a period of 5 years (n = 613) were invited by post to respond to questions about their injury, employment status and complete a questionnaire about mental fatigue, the Mental Fatigue Scale (MFS). A response rate of 38% was achieved. Among respondents, 39% scored above the MFS cut-off of 10.5. Higher MFS scores were associated with decreased employment status (p < 0.001). Rating on the MFS was higher for women, for those with a longer initial duration of acute post-traumatic brain injury symptoms, and for those who had previously experienced a traumatic brain injury. No association was found between mental fatigue and age, severity of injury, or time since injury. Long-term mental fatigue was frequent among people who had experienced a traumatic brain injury, and a higher rating on the MFS was associated with decreased employment status.","subset":"pubmed_abstract"} +{"meta":{"pmid":12215839,"dup_signals":{"dup_doc_count":15}},"text":"A genome-wide screen reveals evidence for a locus on chromosome 11 influencing variation in LDL cholesterol in the NHLBI Family Heart Study.\nA genome scan was performed for low-density lipoprotein cholesterol concentration (LDL-C) in white subjects who were ascertained through the NHLBI Family Heart Study (FHS). The NIH Mammalian Genotyping Service (Marshfield, Wis.) genotyped 401 autosomal markers spaced at approximate 10-cM intervals. Additional FHS families were genotyped by the FHS Molecular Laboratory at the University of Utah for 243 markers; 645 subjects were typed in both laboratories so that a combined map of the 644 markers from the two screening sets (average distance of 5.46 cM) could be produced. Analyses were done on 2,799 genotyped subjects in 500 families where at least two genotyped persons in the family had measured LDL-C levels (average number of genotyped family members=5.95). The variance components method was used as implemented in GeneHunter (Kruglyak et al. 1996). Prior to analysis, each phenotype was adjusted, within sex, for age, age squared, body mass index, waist-hip ratio, alcohol, smoking, medication status for diabetes and hypertension, estrogen use, and field center location. Linkage analyses were performed, first excluding 305 subjects on lipid-lowering medications, then again including the data from these subjects. The highest peak was on chromosome 11 at 56.3-56.4 cM, with a maximum lod score of 3.72. Two genome scans of lipid traits in other populations have found peaks in this region. Other scores at or above 1.9 occurred on chromosomes 5 (lod=1.89 at 1.6 cM), 10 (lod=2.47 at 127.1 cM), 17 (lod=2.33 at 116.3 cM), and 21 (lod=2.74 at 45.2 cM).","subset":"pubmed_abstract"} +{"meta":{"pmid":3754874,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":9}}},"text":"A chick neural retina adhesion and survival molecule is a retinol-binding protein.\nA 20,000-D protein called purpurin has recently been isolated from the growth-conditioned medium of cultured embryonic chick neural retina cells (Schubert, D., and M. LaCorbiere, 1985, J. Cell Biol., 101:1071-1077). Purpurin is a constituent of adherons and promotes cell-adheron adhesion by interacting with a cell surface heparan sulfate proteoglycan. It also prolongs the survival of cultured neural retina cells. This paper shows that purpurin is a secretory protein that has sequence homology with a human protein synthesized in the liver that transports retinol in the blood, the serum retinol-binding protein (RBP). Purpurin binds [3H]retinol, and both purpurin and chick serum RBP stimulate the adhesion of neural retina cells, although the serum protein is less active than purpurin. Purpurin and the serum RBP are, however, different molecules, for the serum protein is approximately 3,000 D larger than purpurin and has different silver-staining characteristics. Finally, purpurin supports the survival of dissociated ciliary ganglion cells, indicating that RBPs can act as ciliary neurotrophic factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":22193309,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":10}}},"text":"Quality-of-life and disability in patients with stroke.\nThe aim of this study was to assess the impact of stroke on health-related quality-of-life (HRQoL) and disability, the relationships between the two constructs, and to what extent these two constructs are affected when perceived health state changes. The World Health Organization Disability Assessment Schedule (WHO-DAS II) and the 36-Item Short-Form Health Survey (SF-36) were administered via mail to a sample of adult stroke survivors. Comparison against normative Italian values was made using one-sample t test. SF-36 and WHO-DAS II scores were compared between employed and unemployed patients and between patients self-reporting improved, unchanged, and decreased health state using analysis of variance with least significant difference post hoc test. The relationships between SF-36 and WHO-DAS II were assessed using Pearson correlation. A total of 111 patients were enrolled. The SF-36 and WHO-DAS II scores of stroke patients were worse in comparison with Italian normative values. Moderate to strong correlations between all scales and the summary score of WHO-DAS II and SF-36 were found: The worse the disability is, the lower the HRQoL. Patients reporting worse health status in the previous year reported higher levels of disability and lower HRQoL. Employed persons had higher HRQoL and lower disability levels. The generic HRQoL instrument and disability schedule used in this study demonstrated strong relationship between these two dimensions. It also gave a more detailed picture of the aspects of disability and HRQoL that are most relevant for the persons after stroke and that should be studied further in the future research.","subset":"pubmed_abstract"} +{"meta":{"pmid":29662975,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":18}}},"text":"Gene assembly via one-pot chemical ligation of DNA promoted by DNA nanostructures.\nCurrent gene synthesis methods are driven by enzymatic reactions. Here we report the one-pot synthesis of a chemically-ligated gene from 14 oligonucleotides. The chemical ligation benefits from the highly efficient click chemistry approach templated by DNA nanostructures, and produces modified DNA that is compatible with polymerase enzymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":23437268,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":14}}},"text":"In vitro model of tumor cell extravasation.\nTumor cells that disseminate from the primary tumor and survive the vascular system can eventually extravasate across the endothelium to metastasize at a secondary site. In this study, we developed a microfluidic system to mimic tumor cell extravasation where cancer cells can transmigrate across an endothelial monolayer into a hydrogel that models the extracellular space. The experimental protocol is optimized to ensure the formation of an intact endothelium prior to the introduction of tumor cells and also to observe tumor cell extravasation by having a suitable tumor seeding density. Extravasation is observed for 38.8% of the tumor cells in contact with the endothelium within 1 day after their introduction. Permeability of the EC monolayer as measured by the diffusion of fluorescently-labeled dextran across the monolayer increased 3.8 fold 24 hours after introducing tumor cells, suggesting that the presence of tumor cells increases endothelial permeability. The percent of tumor cells extravasated remained nearly constant from1 to 3 days after tumor seeding, indicating extravasation in our system generally occurs within the first 24 hours of tumor cell contact with the endothelium.","subset":"pubmed_abstract"} +{"meta":{"pmid":10606765,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"The influence of inorganic phosphate on the activity of adenosine kinase.\nThe enzyme adenosine kinase (AK; EC 188.8.131.52) shows a dependence upon inorganic phosphate (Pi) for activity. The degree of dependence varies among enzyme sources and the pH at which the activity is measured. At physiological pH, recombinant AK from Chinese hamster ovary (CHO) cells and AK from beef liver (BL) show higher affinities for the substrate adenosine (Ado), larger maximum velocities and lower sensitivities to substrate inhibition in the presence of Pi. At pH 6.2, both BL and CHO AK exhibit almost complete dependence on the presence of Pi for activity. The data show that both enzymes exhibit increasing relief from substrate inhibition upon increasing Pi and the inhibition of BL AK is almost completely alleviated by the addition of 50 mM Pi. The affinity of CHO AK for Ado increases asymptotically from K(m) 6.4 microM to a limit of 0.7 microM upon the addition of increasing Pi from 1 to 50 mM. The concentration of Ado necessary to invoke substrate inhibition also increases asymptotically from K(i) 32 microM to a limit of 69 microM at saturating concentrations of phosphate. In the presence of increasing amounts of Pi, the maximal velocity of activity increases hyperbolically. The effect that phosphate exerts on AK may be either to protect the enzyme from inactivation at high adenosine and H(+) concentrations or to stabilize substrate binding at the active site.","subset":"pubmed_abstract"} +{"meta":{"pmid":18544174,"dup_signals":{"dup_doc_count":16}},"text":"Spatial and multidimensional visualization of Indonesia's village health statistics.\nA community health assessment (CHA) is used to identify and address health issues in a given population. Effective CHA requires timely and comprehensive information from a wide variety of sources, such as: socio-economic data, disease surveillance, healthcare utilization, environmental data, and health resource allocation. Indonesia is a developing country with 235 million inhabitants over 13,000 islands. There are significant barriers to conducting CHA in developing countries like Indonesia, such as the high cost of computing resources and the lack of computing skills necessary to support such an assessment. At the University of Pittsburgh, we have developed the Spatial OLAP (On-Line Analytical Processing) Visualization and Analysis Tool (SOVAT) for performing CHA. SOVAT combines Geographic Information System (GIS) technology along with an advanced multidimensional data warehouse structure to facilitate analysis of large, disparate health, environmental, population, and spatial data. The objective of this paper is to demonstrate the potential of SOVAT for facilitating CHA among developing countries by using health, population, healthcare resources, and spatial data from Indonesia for use in two CHA cases studies. Bureau of Statistics administered data sets from the Indonesian Census, and the Indonesian village statistics, were used in the case studies. The data consisted of: healthcare resources (number of healthcare professionals and facilities), population (census), morbidity and mortality, and spatial (GIS-formatted) information. The data was formatted, combined, and populated into SOVAT for CHA use. Case study 1 involves the distribution of healthcare professionals in Indonesia, while case study 2 involves malaria mortality. Screen shots are shown for both cases. The results for the CHA were retrieved in seconds and presented through the geospatial and numerical SOVAT interface. The case studies show the potential of spatial and multidimensional analysis using SOVAT for community health assessment in developing countries. Since SOVAT is based primarily on open-source components and can be deployed using small personal computers, it is cost-effective for developing countries. Also, combining the strength in analysis and the ease of use makes tools like SOVAT ideal for healthcare professionals without extensive computer skills.","subset":"pubmed_abstract"} +{"meta":{"pmid":9475898,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"unknown":2}}},"text":"Transcervical amnioinfusion.\nAmnioinfusion is being used to treat intrapartum problems known to be associated with fetal compromise, including prophylactic treatment of oligohydramnios during labor and after premature rupture of the membranes, treatment of severe variable decelerations during labor and reducing the risk of meconium aspiration during labor in patients with thick meconium fluid. The procedure is considered effective and easy to perform, with the benefits outweighing the risks.","subset":"pubmed_abstract"} +{"meta":{"pmid":23444219,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Clinical correlates of promoter hypermethylation of four target genes in head and neck cancer: a cooperative group correlative study.\nPromoter hypermethylation is a well-documented mechanism for tumor-specific alteration of suppressor gene activity in human malignancy including head and neck cancer (HNC). The abrogation of specific suppressor gene activity may influence tumor behavior and clinical outcome. In this study we examined methylation of DCC, KIF1A, EDNRB, and p16(INK4a) in a large cohort of HNC patients from Eastern Cooperative Group (ECOG) 4393\/Radiation Therapy Oncology Group (RTOG) 9614 to identify clinical correlates of methylation of these genes. Methylation was assessed by quantitative methylation-specific PCR in DNA from tumor specimens and was considered as a continuous and a binary variable. Clinical data including demographics, stage, risk factor exposure, treatment, and outcome were collected by ECOG and RTOG. Methylation status was also correlated with mutation of TP53 (previously reported) and human papilloma virus status. Methylation results were available for 368 cases, 353 of which also have p53 mutation status. At least one methylation event was present in all tumors. In multivariate analysis of the entire cohort, methylation of p16 was associated with decreased survival (HR = 1.008; P = 0.045). However, in tumors with disruptive TP53 mutation (poor prognostic group), the additional presence of methylation of p16 was protective (P = 0.019 considering p16 methylation as a continuous variable). Methylation of tumor-related genes contributes to the biological behavior of HNC and influences overall survival in conjunction with other known prognostic molecular events.","subset":"pubmed_abstract"} +{"meta":{"pmid":17290726,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention.\nTo compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention. Smokers were randomized to receive a nicotine inhaler, bupropion, or both for 3 months. At 3 months, smoking-abstinent study participants were randomized to their initial medications or placebo. Participants who were smoking at 3 months were randomized to an alternative treatment regimen or placebo. This study was conducted from July 2001 to January 2003. A total of 1700 smokers were randomized to treatment (phase 1) for 3 months. Among the 941 study participants eligible for randomization to the phase 2 trial, 837 continued in the study. For the phase 2 trial, 405 smoking-abstinent participants were randomized to relapse prevention for 9 additional months, and 432 smokers were randomized to re-treatment for an additional 3 months. At the end of the initial 3 months of treatment (phase 1), 82 (14%) of 566, 145 (26%) of 567, and 194 (34%) of 567 study participants receiving a nicotine inhaler, bupropion, or both, respectively, were abstinent from smoking. Of the 405 smoking-abstinent participants at the end of 3 months, the bupropion group had more smokers than the placebo group (mean No. of smokers, 1.5 vs 1.1; P < .001), and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group. Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention, but this difference disappeared after the initial 3 months. Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen, the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo (8 [7%] of 111 vs 0 [0%] of 112; P = .003), and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates (6 [6%] of 104 vs 3 [3%] of 105; P = -.50). Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates. Continuation of the initial combination therapy does not appear to prevent relapse to smoking. Timing of re-treatment and alternative approaches to relapse prevention should be further examined.","subset":"pubmed_abstract"} +{"meta":{"pmid":18364835,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2024-22":1,"unknown":10}}},"text":"Relationship of light scattering at an angle in the backward direction to the backscattering coefficient.\nWe revisit the problem of computing the backscattering coefficient based on the measurement of scattering at one angle in the back direction. Our approach uses theory and new observations of the volume scattering function (VSF) to evaluate the choice of angle used to estimate b(b). We add to previous studies by explicitly treating the molecular backscattering of water (b(bw)) and its contribution to the VSF shape and to b(b). We find that there are two reasons for the tight correlation between observed scattering near 120 degrees and the backscattering coefficient reported by Oishi [Appl. Opt. 29, 4658, (1990)], namely, that (1) the shape of the VSF of particles (normalized to the backscattering) does not vary much near that angle for particle assemblages of differing optical properties and size, and (2) the ratio of the VSF to the backscattering is not sensitive to the contribution by water near this angle. We provide a method to correct for the water contribution to backscattering when single-angle measurements are used in the back direction (for angles spanning from near 90 degrees to 160 degrees ) that should provide improved estimates of the backscattering coefficient.","subset":"pubmed_abstract"} +{"meta":{"pmid":22326378,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-09":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-51":2,"2017-43":1,"2017-34":1,"2019-51":1,"2013-20":1}}},"text":"Value chains of herbal medicines--research needs and key challenges in the context of ethnopharmacology.\nValue chain analyses are commonly used to understand socioeconomic and power relationships in the production chain from the initial starting material to a final (generally high value) product. These analyses help in terms of understanding economic processes but also have been used in the context of socioeconomic and socioecological research. However, there is a gap in the ethnopharmacological literature in terms of understanding what relevance a critical analysis of value chains of herbal medicines could have. Here we provide a research framework for achieving such an analysis. An extensive review of the literature available on value chains and their analysis was conducted, based both on a systematic online search of the relevant literature and a hand search of bibliographies and discussions with experts in value chain analysis While the concept of value chains is commonly used in the relevant industries, very few studies investigate the value chains of herbal medicines and products derived from them. The studies identified mostly look at socio-ecological aspects, especially in the context of sustainable resource use. We suggest an analytical framework which can help in understanding value chains in the context of ethnopharmacology and can serve as a basis for addressing questions related to value chains and their relevance in ethnopharmacology. We identified a crucial gap in current ethnopharmacological and medicinal plant research which impacts on a wide-range of factors relevant for a sustainable, socio-culturally equitable and safe supply of herbal medicines.","subset":"pubmed_abstract"} +{"meta":{"pmid":33389424,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-22":1,"unknown":15}}},"text":"Intraoperative efficacy and clinical outcomes of two commercial staining solutions used in idiopathic epiretinal membrane surgery.\nTo compare two commercially available staining solutions (MembraneBlue Dual\u00ae by D.O.R.C., Netherlands, and TWIN by AL.CHI.MI.A. S.R.L., Italy), in terms of intraoperative handling, staining efficacy and safety, in eyes undergoing surgery for idiopathic epiretinal membrane (ERM). In this observational cross-sectional study, the performance of the dyes used during the procedure (cohesion, ERM and internal limiting membrane [ILM] staining efficacy) was scored by the surgeon using a customized questionnaire after 10 procedures with each of the two dyes. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), blue-light fundus autofluorescence (BAF), and microperimetry-determined retinal sensitivity were reviewed preoperatively and then at 1 and 3 months after surgery. ILM staining efficacy with TWIN was scored 2.89 \u00b1 0.33 by the surgeons, which turned out to be higher than with MembraneBlue Dual\u00ae (1.90 \u00b1 0.31, P = 0.0002). The cohesion score was 2.70 \u00b1 0.48 for TWIN and resulted significantly higher than with MembraneBlue Dual\u00ae (1.60 \u00b1 0.51, P = 0.0010). BCVA, CFT and retinal sensitivity were similar in the two groups, 1 and 3 months postoperatively (P nonsignificant for all). Both TWIN and MembraneBlue Dual\u00ae dyes showed suitable staining properties and equivalent safety and efficacy profiles, both intra- and postoperatively. The TWIN dye might offer a solution for surgeons who prefer a more cohesive and stable dye.","subset":"pubmed_abstract"} +{"meta":{"pmid":20824046,"dup_signals":{"dup_doc_count":25,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-33":2,"2022-27":2,"2022-05":3,"2021-49":1,"2021-39":2,"2021-31":2,"2021-17":2,"2021-04":2,"2020-40":2,"2023-50":1,"2024-10":1}}},"text":"Assessment of acute antivascular effects of vandetanib with high-resolution dynamic contrast-enhanced computed tomographic imaging in a human colon tumor xenograft model in the nude rat.\nTumor size is not a reliable marker for the assessment of early antivascular effects of antiangiogenics. In the present study, we used 200-microm in-plane high-resolution dynamic contrast-enhanced computed tomography (DCE-CT) to noninvasively assess the immediate antivascular effects of vandetanib in a subcutaneous human colon cancer (LoVo) xenograft model in nude rats and to investigate correlation between changes in CT perfusion parameters and tumor volume or immunohistochemical end points. At 3 to 4 weeks after LoVo cell implantation, the animal was gavaged with either vandetanib (50 mg\/kg) or vehicle twice (22 hours apart) and scanned with a preclinical DCE-CT scanner before (0 hour) and after treatment (24 hours). Quantitative maps of blood flow (BF) and volume (BV) of the tumor were calculated from the acquired DCE-CT images. The rats were divided into nonhypovascular, hypovascular, and combined (regardless of vascularity) groups. In the nonhypovascular group, significant decreases in both tumor BF and BV were observed in the vandetanib-treated rats compared with increases in the vehicle-treated rats. A significant decrease in BV was detected in the vandetanib-treated rats in the combined group as well. No differences in tumor growth, vascular endothelial growth factor expression, microvessel density, or apoptosis were observed between vandetanib- and vehicle-treated rats in all three groups. These results demonstrate that BF and BV imaging biomarkers from DCE-CT imaging can be used for rapid monitoring of immediate (24 hours after) antimicrovascular effects of vandetanib on tumors, even in the absence of significant changes of tumor volume or clinically relevant immunohistochemical end points.","subset":"pubmed_abstract"} +{"meta":{"pmid":27277587,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2022-05":1}}},"text":"Acute intermittent porphyria leading to posterior reversible encephalopathy syndrome (PRES): a rare cause of abdominal pain and seizures.\nAcute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric symptoms. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). PRES is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral oedema, headaches, nausea and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This article describes a case of AIP and PRES in a young woman.","subset":"pubmed_abstract"} +{"meta":{"pmid":6482513,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-39":1,"2021-25":2,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-24":1,"2023-23":1,"2024-18":1}}},"text":"Surgical pathology of pure aortic stenosis: a study of 374 cases.\nThe gross surgical pathologic features of the aortic valve were reviewed in 374 patients who had had clinically pure aortic stenosis and aortic valve replacement at our institution during the years 1965, 1970, 1975, and 1980. The most common cause of aortic stenosis, accounting for 46% of our cases, was calcification of a congenitally bicuspid valve. In the remainder, stenosis was produced by postinflammatory fibrocalcific disease (including rheumatic disease) in 35%, by degenerative calcification of an aging valve in 10%, and by calcification of a congenitally unicommissural valve in 6%. The cause of aortic stenosis was indeterminate in 4%. Valvular lesions included various degrees of dystrophic calcification, commissural fusion, and cuspid fibrosis. Calcification tended to occur more extensively and at a younger age in men than in women. Furthermore, it tended to produce stenosis and to necessitate valve replacement earliest in patients with unicommissural valves (mean age, 48 years), later in those with bicuspid or postinflammatory valves (mean age, 59 and 60 years, respectively), and latest in those with degenerative stenosis (mean age, 72 years). In our study, the relative incidence of postinflammatory aortic stenosis remained unchanged from 1965 to 1980, despite the steadily decreasing incidence of acute rheumatic fever reported in western countries. Our data suggest that (1) the incidence of chronic rheumatic heart disease has not yet begun to decrease appreciably, (2) many episodes of acute rheumatic fever may be subclinical, or (3) some forms of nonrheumatic aortic valve disease may produce gross alterations indistinguishable from those of classic chronic rheumatic valvulitis.","subset":"pubmed_abstract"} +{"meta":{"pmid":28812033,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Epidemiology of Injuries Identified at the NFL Scouting Combine and Their Impact on Performance in the National Football League: Evaluation of 2203 Athletes From 2009 to 2015.\nAt the annual National Football League (NFL) Scouting Combine, the medical staff of each NFL franchise performs a comprehensive medical evaluation of all athletes potentially entering the NFL. Currently, little is known regarding the overall epidemiology of injuries identified at the combine and their impact on NFL performance. To determine the epidemiology of injuries identified at the combine and their impact on initial NFL performance. Cohort study; Level of evidence, 3. All previous musculoskeletal injuries identified at the NFL Combine from 2009 to 2015 were retrospectively reviewed. Medical records and imaging reports were examined. Game statistics for the first 2 seasons of NFL play were obtained for all players from 2009 to 2013. Analysis of injury prevalence and overall impact on the draft status and position-specific performance metrics of each injury was performed and compared with a position-matched control group with no history of injury or surgery. A total of 2203 athletes over 7 years were evaluated, including 1490 (67.6%) drafted athletes and 1040 (47.2%) who ultimately played at least 2 years in the NFL. The most common sites of injury were the ankle (1160, 52.7%), shoulder (1143, 51.9%), knee (1128, 51.2%), spine (785, 35.6%), and hand (739, 33.5%). Odds ratios (ORs) demonstrated that quarterbacks were most at risk of shoulder injury (OR, 2.78; P = .001), while running backs most commonly sustained ankle (OR, 1.39; P = .040) and shoulder injuries (OR, 1.55; P = .020) when compared with all other players. Ultimately, defensive players demonstrated a greater negative impact due to injury than offensive players, with multiple performance metrics significantly affected for each defensive position analyzed, whereas skilled offensive players (eg, quarterbacks, running backs) demonstrated only 1 metric significantly affected at each position. The most common sites of injury identified at the combine were (1) ankle, (2) shoulder, (3) knee, (4) spine, and (5) hand. Overall, performance in the NFL tended to worsen with injury history, with a direct correlation found between injury at a certain anatomic location and position of play. Defensive players tended to perform worse compared with offensive players if injury history was present.","subset":"pubmed_abstract"} +{"meta":{"pmid":27226795,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A Rare Case of Transfusion Transmission of Hepatitis A Virus to Two Patients with Haematological Disease.\nThis paper describes the transmission of hepatitis A virus (HAV) to two blood recipients from a healthy donor that later presented to the blood bank with jaundice. The RNA of HAV was detected by qualitative nested reverse transcription polymerase chain reaction (nested RT-PCR) and quantified by real-time RT-PCR. HAV RNA samples were genotyped by direct sequencing of PCR products. A sequence from a fragment of 168 bp from the VP1\/2A HAV region was used to construct a phylogenetic tree. A 31-year-old male donor accepted for donation of a whole blood unit returned to the blood bank with clinical jaundice 20 days after donation. His serological and NAT tests were negative for HBV and HCV. Serological tests for HAV IgM and IgG were negative on donation sample but positive on follow-up sample, confirming donor's HAV acute infection. Both recipients of red blood cells (R1) and platelet concentrate (R2) from the same implicated donation were HAV IgM-negative and IgG-positive. Qualitative PCR was positive on samples from all three individuals and phylogenetic analysis of viruses proved HAV transmission to the two recipients of blood products. HAV viral load on donor follow-up sample and the platelet recipient was 1.3 and 1.5 \u00d7 10(3) IU\/ml, respectively. The RBC recipient, also infected by HCV, was undergoing bone marrow transplantation and died from fulminant hepatitis, 26 days after the implicated HAV transfusion. The blood donor, a garbage collector, spontaneously returned to the blood bank when developing jaundice. This highlights the importance of donor education to immediately report to blood banks of any signs and symptoms related to infectious disease developed after blood donation. The fact that one immunocompromised patient with HCV infection died from fulminant hepatitis after receiving a HAV-contaminated platelet transfusion underpins the importance of a HAV vaccination program for these group of patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":27997473,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Impact of State Legislation on Hospital Breastfeeding Support in New York.\nThe purpose of this study was to evaluate whether 2 state mandates, both implemented in 2010, had an impact on NY hospitals providing maternity care. Specifically, we measured changes in hospital staff's awareness, attitudes, and promotion of breastfeeding (BF), maternity care practices, and hospital breastfeeding policies and tested whether they were related to implementation of the Breastfeeding Mothers' Bill of Rights or the mandate for public reporting of hospital-specific BF measures. In 2009 and 2011, written hospital BF policies were collected and evaluated using a 28-item review tool and hospital BF surveys were conducted. The surveys assessed hospital culture and staff attitudes associated with BF promotion and support and recommended maternity care practices. NY hospitals providing maternity care services and hospital staff. Changes over time in hospital BF policies (BF policy score) and implementation of recommended maternity care practices (9 of Ten Steps to Successful BF) were evaluated. The relationships and correlations between these changes in staff awareness, hospital culture, and BF promotion were determined. Between 2009 and 2011, there were increases in BF policy scores, maternity care practices implemented, and lactation staff (P < .001). Greater awareness by hospital administrators of BF measures was associated with more emphasis in promoting BF (P = .02). Hospitals reporting much more emphasis in promoting BF or reporting large changes in organizational culture had greater increases in BF policy scores and the recommended maternity care practices implemented (P < .05). These findings suggest that state mandates requiring key BF policies and support in hospitals and public reporting of BF rates may have led to increased emphasis and promotion of BF, improvement in hospital BF policies, and increased implementation of maternity care practices supporting BF. Implementation of similar policies by other states, combined with rigorous evaluation, is needed to replicate these findings and assess the long-term impact on maternal and infant health outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29259247,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia.\nJuvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.","subset":"pubmed_abstract"} +{"meta":{"pmid":23752981,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2017-13":2,"2015-18":2,"2015-11":2,"2015-06":2,"2013-20":1,"unknown":3}}},"text":"Rhazes in the renaissance of Andreas Vesalius.\nAndreas Vesalius' (1514-64) first publication was a Paraphrasis of the ninth book of the Liber ad Almansorem, written by the Arab-Persian physician and alchemist Rhazes (854-925). The role of Rhazes in Vesalius' oeuvre has thus far been much disregarded. The different ways Rhazes recurs reveal an intellectual evolution in Vesalius' work. In the Paraphrasis, Vesalius subjects Rhazes to the authority of Galen in the context of the early sixteenth-century humanist campaign for the substitution of Arab influences by Greek 'originals'. Over the years Vesalius continues his work on Rhazes, but his approach becomes more internationalistic. Ultimately, Vesalius criticises Galen while expressing sympathy for the Arab author. This may be the more significant as Rhazes could have influenced Vesalius in the act of criticising Galen - critical discussions of Galen were available to Vesalius in Latin translations of Rhazes's Liber Continens. Although Vesalius never refers to the work, it is hardly possible he was unaware of it: similarities in structure, rhetoric and form between the Continens and the De humani corporis fabrica could support this hypothesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":2162274,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Role of atrial natriuretic peptide in the increase in glomerular filtration rate induced by a protein meal.\n1. The increase in glomerular filtration rate after a protein meal is believed to be mediated by hormonal factors. Since natriuresis is often observed after a protein meal, it was postulated that the increase in glomerular filtration rate after a protein meal might be mediated by atrial natriuretic peptide. 2. Subjects were given a low, medium or high protein meal. Fluid intake was controlled so as to avoid significant extracellular fluid volume expansion. It was found that the creatinine clearance, the urea excretion, the fractional sodium excretion and the potassium excretion were elevated in all subjects after protein meals (P less than 0.05). These effects were not observed in subjects given a carbohydrate control meal. 3. The plasma atrial natriuretic peptide concentrations remained unchanged in all subjects except those given a high protein meal (P less than 0.05). There was no significant relationship between plasma atrial natriuretic peptide concentrations and creatinine clearance before or after a protein meal. 4. The data suggest that a high protein meal induces a minor increase in plasma atrial natriuretic peptide concentration, whereas a low or medium protein meal does not. It is unlikely that the change in creatinine clearance after a protein meal can be explained by a change in plasma atrial natriuretic peptide levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":17253554,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Treatment for IgG and IgA paraproteinaemic neuropathy.\nParaproteinaemic neuropathy refers to those neuropathies associated with a monoclonal gammopathy or paraprotein. Typically it presents with a chronic predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for IgG and IgA monoclonal gammopathy of uncertain significance neuropathies is not known. The objective of this review is to examine the efficacy of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We performed searches of the Cochrane Neuromuscular Disease Group Trials register (May 2005), MEDLINE (from January 1966 to May 2005), EMBASE (from January 1980 to May 2005). We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We included randomised and quasi-randomised controlled trials using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. People with IgM paraproteins were excluded. We excluded participants where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria. The full texts of potentially relevant studies were obtained and assessed and independent data extraction was performed by three authors. Additional data and clarification were received from one author. We identified only one randomised controlled trial with 18 participants which fulfilled the predetermined inclusion criteria. Four other trials were identified but these were not randomised controlled trials. The included trial revealed a modest short-term benefit of plasma exchange in IgG or IgA paraproteinaemic neuropathy, over a short follow-up period, when compared to sham plasma exchange. The evidence from randomised controlled trials for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More randomised controlled trials of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin and corticosteroids. These show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed randomised controlled trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":12590845,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Common and segregated neuronal networks for different languages revealed using functional magnetic resonance adaptation.\nThe effect of word repetition within and across languages was studied in English-Chinese bilinguals who read rapidly presented word pairs in a block design and an event-related fMRI study. Relatively less increase in MR signal was observed when the second word in a pair was identical in meaning to the first. This occurred in the English-only and mixed-languages conditions. Repetition-induced reductions in BOLD signal change were found in the left lateral prefrontal and lateral temporal regions in both types of conditions in the block experiment, suggesting that processing in these regions is sensitive to semantic features present in words and characters, and that part of the semantic neuronal networks serving English and Chinese is shared. In addition, these regions showed greater absolute signal change in the mixed-languages trials relative to the English-only trials. These findings were mostly replicated in an event-related experiment. Together, the experiments suggest that while the networks for Chinese and English word processing have shared components, there are also components that may be language specific.","subset":"pubmed_abstract"} +{"meta":{"pmid":26950163,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Controlled Release of Ciprofloxacin from Core-Shell Nanofibers with Monolithic or Blended Core.\nSustained controlled drug release is one of the prominent contributions for more successful treatment outcomes in the case of several diseases. However, the incorporation of hydrophilic drugs into nanofibers, a promising novel delivery system, and achieving a long-term sustained release still pose a challenging task. In this work we demonstrated a robust method of avoiding burst release of drugs and achieving a sustained drug release from 2 to 4 weeks using core-shell nanofibers with poly(methyl methacrylate) (PMMA) shell and monolithic poly(vinyl alcohol) (PVA) core or a novel type of core-shell nanofibers with blended (PVA and PMMA) core loaded with ciprofloxacin hydrochloride (CIP). It is also shown that, for core-shell nanofibers with monolithic core, drug release can be manipulated by varying flow rate of the core PVA solution, whereas for core-shell nanofibers with blended core, drug release can be manipulated by varying the ratios between PMMA and PVA in the core. During coaxial electrospinning, when the solvent from the core evaporates in concert with the solvent from the shell, the interconnected pores spanning the core and the shell are formed. The release process is found to be desorption-limited and agrees with the two-stage desorption model. Ciprofloxacin-loaded nanofiber mats developed in the present work could be potentially used as local drug delivery systems for treatment of several medical conditions, including periodontal disease and skin, bone, and joint infections.","subset":"pubmed_abstract"} +{"meta":{"pmid":27391688,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Pattern Completion in Symmetric Threshold-Linear Networks.\nThreshold-linear networks are a common class of firing rate models that describe recurrent interactions among neurons. Unlike their linear counterparts, these networks generically possess multiple stable fixed points (steady states), making them viable candidates for memory encoding and retrieval. In this work, we characterize stable fixed points of general threshold-linear networks with constant external drive and discover constraints on the coexistence of fixed points involving different subsets of active neurons. In the case of symmetric networks, we prove the following antichain property: if a set of neurons [Formula: see text] is the support of a stable fixed point, then no proper subset or superset of [Formula: see text] can support a stable fixed point. Symmetric threshold-linear networks thus appear to be well suited for pattern completion, since the dynamics are guaranteed not to get stuck in a subset or superset of a stored pattern. We also show that for any graph G, we can construct a network whose stable fixed points correspond precisely to the maximal cliques of G. As an application, we design network decoders for place field codes and demonstrate their efficacy for error correction and pattern completion. The proofs of our main results build on the theory of permitted sets in threshold-linear networks, including recently developed connections to classical distance geometry.","subset":"pubmed_abstract"} +{"meta":{"pmid":25886761,"dup_signals":{"dup_doc_count":11}},"text":"A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.\nPatient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (\u2265 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (\u2264 90 days old). The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (\u2265 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (\u2265 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.","subset":"pubmed_abstract"} +{"meta":{"pmid":22389502,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Hypertrophy in skeletal myotubes induced by junctophilin-2 mutant, Y141H, involves an increase in store-operated Ca2+ entry via Orai1.\nJunctophilins (JPs) play an important role in the formation of junctional membrane complexes (JMC) in striated muscle by physically linking the transverse-tubule and sarcoplasmic reticulum (SR) membranes. Researchers have found five JP2 mutants in humans with hypertrophic cardiomyopathy. Among these, Y141H and S165F are associated with severely altered Ca(2+) signaling in cardiomyocytes. We previously reported that S165F also induced both hypertrophy and altered intracellular Ca(2+) signaling in mouse skeletal myotubes. In the present study, we attempted to identify the dominant-negative role(s) of Y141H in primary mouse skeletal myotubes. Consistent with S165F, Y141H led to hypertrophy and altered Ca(2+) signaling (a decrease in the gain of excitation-contraction coupling and an increase in the resting level of myoplasmic Ca(2+)). However, unlike S165F, neither ryanodine receptor 1-mediated Ca(2+) release from the SR nor the phosphorylation of the mutated JP2 by protein kinase C was related to the altered Ca(2+) signaling by Y141H. Instead, abnormal JMC and increased SOCE via Orai1 were found, suggesting that the hypertrophy caused by Y141H progressed differently from S165F. Therefore JP2 can be linked to skeletal muscle hypertrophy via various Ca(2+) signaling pathways, and SOCE could be one of the causes of altered Ca(2+) signaling observed in muscle hypertrophy.","subset":"pubmed_abstract"} +{"meta":{"pmid":18301575,"dup_signals":{"dup_doc_count":43,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2016-44":3,"2016-40":2,"2016-36":5,"2016-30":3,"2016-22":2,"2016-18":2,"2016-07":3,"2015-48":2,"2015-40":1,"2015-35":3,"2015-32":3,"2015-27":2,"2015-22":5,"2017-39":1,"2015-18":2}}},"text":"Single scattering by red blood cells.\nA highly diluted suspension of red blood cells (hematocrit 0.01) was illuminated with an Ar or a dye laser in the wavelength range of 458-660 nm. The extinction and the angle-resolved intensity of scattered light were measured and compared with the predictions of Mie theory, the Rayleigh-Gans approximation, and the anomalous diffraction approximation. Furthermore, empirical phase functions were fitted to the measurements. The measurements were in satisfactory agreement with the predictions of Mie theory. However, better agreement was found with the anomalous diffraction model. In the Rayleigh-Gans approximation, only small-angle scattering is described appropriately. The scattering phase function of erythrocytes may be represented by the Gegenbauer kernel phase function.","subset":"pubmed_abstract"} +{"meta":{"pmid":29643119,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-40":1,"2020-34":1,"2019-51":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-43":1,"2018-34":1,"2020-45":1}}},"text":"Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control.\nAlmost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies, which are characterised by debilitating developmental defects that affect many tissues. Here, we report a new role for regulator of calcineurin 2 (RCAN2) in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing. In contrast to previous work where we showed that depletion of giantin by RNAi results in defects in ciliogenesis and in cilia length control, giantin knockout cells generate normal cilia after serum withdrawal. Furthermore, giantin knockout zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2 expression in giantin knockout cells results in the same defects in the control of cilia length that are seen upon RNAi of giantin itself. Together, these data define RCAN2 as a regulator of cilia function that can compensate for the loss of giantin function.","subset":"pubmed_abstract"} +{"meta":{"pmid":27798307,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":15}}},"text":"Mutation rate analysis via parent-progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation.\nMutation rates and recombination rates vary between species and between regions within a genome. What are the determinants of these forms of variation? Prior evidence has suggested that the recombination might be mutagenic with an excess of new mutations in the vicinity of recombination break points. As it is conjectured that domesticated taxa have higher recombination rates than wild ones, we expect domesticated taxa to have raised mutation rates. Here, we use parent-offspring sequencing in domesticated and wild peach to ask (i) whether recombination is mutagenic, and (ii) whether domesticated peach has a higher recombination rate than wild peach. We find no evidence that domesticated peach has an increased recombination rate, nor an increased mutation rate near recombination events. If recombination is mutagenic in this taxa, the effect is too weak to be detected by our analysis. While an absence of recombination-associated mutation might explain an absence of a recombination-heterozygozity correlation in peach, we caution against such an interpretation.","subset":"pubmed_abstract"} +{"meta":{"pmid":17330738,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2015-18":1,"2017-13":1,"unknown":14}}},"text":"Tolerance to white spot syndrome virus (WSSV) in the freshwater prawn Macrobrachium rosenbergii is associated with low VP28 envelope protein expression.\nThe freshwater prawn Macrobrachium rosenbergii was experimentally infected with white spot syndrome virus (WSSV) by intramuscular injection. Infection was confirmed by positive, single-step, WSSV polymerase chain reaction (PCR) assays targeting the VP28 gene from Day 2 up to Day 90 post injection (p.i.). Although no mortality of WSSV-infected prawns was observed, bioassays with the black tiger shrimp Penaeus monodon using hemolymph from Day 90 PCR-positive prawns resulted in white spot disease (WSD). Transcriptional analysis of the VP28 gene of WSSV by reverse transcriptase (RT)-PCR assays and Western blot assays revealed transient expression of the VP28-specific transcript in DNase-treated total RNA from hemolymph, gills, head soft tissue and eyestalks at 2 d p.i. By 3 d p.i., the VP28 transcript could no longer be detected in eyestalks and hemolymph but was still lightly detectable in head soft tissue and gills. It became undetectable there from 5 d p.i. onwards, despite the undiminished presence of the virus shown by single-step PCR targeting of the VP28 gene. VP28 was not detected by the less sensitive Western blot in hemolymph at any time during the study period, but it was detectable in all other tested tissues from Days 2 to 4 p.i. Our results demonstrated that M. rosenbergii is tolerant to a relatively constant level of persistent WSSV infection characterized by a low expression of VP28 and, possibly, other virion proteins. Despite this, M. rosenbergii can carry a level of infectious WSSV sufficient to represent a feasible threat to cultivated penaeid shrimp such as P. monodon. It remains to be seen whether a very low virion protein expression relative to the viral copy number may constitute a general decapod characteristic for persistent viral infections that produce no signs of disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":10477458,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"IgG reactivity to phospholipid-bound beta(2)-glycoprotein I is the main determinant of the fraction of lupus anticoagulant activity quenched by addition of hexagonal (II) phase phospholipid in patients with the clinical suspicion of antiphospholipid-antibody syndrome.\nAutoantibodies to beta(2)-glycoprotein I (beta(2)-GPI) and\/or prothrombin (FII) have been involved in the expression of lupus anticoagulant (LA) activity, an in vitro phenomenon associated with an increased risk of arterial and\/or venous thromboembolic events. However, LA activity sustained by anti-FII antibodies has a much weaker association with thrombosis than LA activity sustained by anti-beta(2)-GPI antibodies. Because assays aimed at detecting LA activity are now commercially available, we evaluated the relative sensitivity to anti-FII and anti-beta(2)-GPI antibodies of a commercial LA assay in a consecutive series of patients with the clinical suspicion of anti-phospholipid antibody (APA) syndrome. One hundred and ten consecutive patients with the clinical suspicion of APA syndrome (primary in 39) and 36 healthy controls were evaluated for the presence of LA activity (LA, Staclot, Stago), anticardiolipin antibodies (Quanta Lite aCL IgG, IgM, Inova Diagnostics), and IgG binding to solid-phase and\/or phospholipid (PL)-bound beta(2)-GPI and FII by ELISA assays developed an optimized in our laboratory. Odds ratios for the association of IgG binding activity with LA and the aCL IgG status were calculated. In LA patients, dependency of LA potency (as assessed by clotting time prolongation in absence or presence of hexagonal phospholipid) on autoantibody titers was analyzed by the generalized linear model. Total IgG fractions were purified from selected patients to evaluate their ability to inhibit prothrombin activation at low FII concentration. Anticardiolipin antibodies (aCL) of the IgG or IgM type were found in 64 and 23 patients and LA activity in 49 patients. Anti-beta(2)-GPI and anti-FII (solid-phase and PL-bound) IgG titers exceeding by more than 3 standard deviations the mean values observed in control subjects were found in 46 and 47 patients and in 56 and 30 patients respectively, with the highest titers detected in the subgroup of patients with both LA and aCL IgG. The relative risk of LA for patients free of anti-FII and\/or anti-beta(2)-GPI IgG was 0.03 after stratification for the aCL IgG status. Anti-beta(2)-GPI (solid-phase and PL-bound) IgG (RR 34.4 and 12.6) and anti-FII (solid-phase) IgG (RR 6.33) were all associated with LA activity. However, when taking into account co-existence of anti-FII and anti-beta(2)-GPI IgG in the same patients, the relative risk of LA for patients with isolated anti-FII IgG (solid-phase and\/or PL-bound) was 0.50, whereas it ranged from 4.24 to 8.70 for all the antibody combinations including anti-beta(2)-GPI IgG. Anti-beta(2)-GPI (PL-bound) and aCL IgG titers were the only significant predictors of LA potency determined in absence phospholipid (anti-beta(2)-GPI IgG) or in presence of hexagonal phospholipid (aCL IgG). Total IgG fractions purified from 12 patients (6 with anti-FII IgG) did not significantly inhibit factor II activity up to a 150-fold molar excess. These results highlight the high prevalence of anti-FII and anti-beta(2)-GPI IgG in patients with the clinical suspicion of APA syndrome and particularly in the subgroup of patients with LA activity. The fraction of LA activity which can be quenched by addition of hexagonal phospholipid is, however, only dependent on IgG directed to PL-bound beta(2)-GPI. Other antibodies associated with anticardiolipin IgG may explain residual clotting time prolongation observed in the presence of hexagonal phospholipid.","subset":"pubmed_abstract"} +{"meta":{"pmid":18942976,"dup_signals":{"dup_doc_count":21,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":11}}},"text":"Ontogenic resistance to powdery mildew in grape berries.\nABSTRACT Berries of Vitis vinifera are reported to be susceptible to infection by Uncinula necator until soluble solids levels (brix) reach 8%, and established colonies are reported to sporulate until brix reach 15%. However, our analysis of disease progress on fruit of selected V. vinifera cultivars indicated that severity became asymptotic several weeks earlier in fruit development. When mildew-free fruit clusters of V. vinifera 'Chardonnay', 'Riesling', 'Gew\u00fcrztraminer', and 'Pinot Noir' were inoculated at stages ranging from prebloom to 6 weeks postbloom, only fruit inoculated within 2 weeks of bloom developed severe powdery mildew. Substantial ontogenic resistance to infection was expressed in fruit nearly 6 weeks before fruit brix reached 8% and over 2 months before they reached 15%. Rachises of 'Chardonnay' and 'Riesling' fruit clusters developed severe powdery mildew when inoculated at bloom, and disease increased steadily over the next 60 days. The rachis of fruit clusters inoculated 31 days after bloom developed only trace levels of powdery mildew. Berry weight of all four cultivars at harvest was reduced when fruit clusters were inoculated at bloom or 16 days postbloom, primarily by splitting, rotting, and dehydration of mildewed berries, but the weight of later-inoculated berries was not reduced. Inoculation of berries just as ontogenic resistance increased markedly, approximately 3 to 4 weeks postbloom, resulted in the development of inconspicuous, diffuse, non-sporulating mildew colonies on berries, sometimes associated with a network of necrotic epidermal cells. Rather than a protracted and relatively static period of berry susceptibility lasting 3 months, fruit of V. vinifera appear to acquire ontogenic resistance rapidly after fruit set. A refocusing of disease management on this critical period of high fruit susceptibility should greatly improve the efficacy of fungicides directed against powdery mildew.","subset":"pubmed_abstract"} +{"meta":{"pmid":10896669,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Subunit composition determines Kv1 potassium channel surface expression.\nShaker-related or Kv1 voltage-gated K(+) channels play critical roles in regulating the excitability of mammalian neurons. Native Kv1 channel complexes are octamers of four integral membrane alpha subunits and four cytoplasmic beta subunits, such that a tremendous diversity of channel complexes can be assembled from the array of alpha and beta subunits expressed in the brain. However, biochemical and immunohistochemical studies have demonstrated that only certain complexes predominate in the mammalian brain, suggesting that regulatory mechanisms exist that ensure plasma membrane targeting of only physiologically appropriate channel complexes. Here we show that Kv1 channels assembled as homo- or heterotetrameric complexes had distinct surface expression characteristics in both transfected mammalian cells and hippocampal neurons. Homotetrameric Kv1.1 channels were localized to endoplasmic reticulum, Kv1.4 channels to the cell surface, and Kv1.2 channels to both endoplasmic reticulum and the cell surface. Heteromeric assembly with Kv1.4 resulted in dose-dependent increases in cell surface expression of coassembled Kv1.1 and Kv1.2, while coassembly with Kv1.1 had a dominant-negative effect on Kv1.2 and Kv1.4 surface expression. Coassembly with Kv beta subunits promoted cell surface expression of each Kv1 heteromeric complex. These data suggest that subunit composition and stoichiometry determine surface expression characteristics of Kv1 channels in excitable cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":24476899,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Optimising the selection of food items for FFQs using Mixed Integer Linear Programming.\nTo support the selection of food items for FFQs in such a way that the amount of information on all relevant nutrients is maximised while the food list is as short as possible. Selection of the most informative food items to be included in FFQs was modelled as a Mixed Integer Linear Programming (MILP) model. The methodology was demonstrated for an FFQ with interest in energy, total protein, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, total carbohydrates, mono- and disaccharides, dietary fibre and potassium. The food lists generated by the MILP model have good performance in terms of length, coverage and R 2 (explained variance) of all nutrients. MILP-generated food lists were 32-40 % shorter than a benchmark food list, whereas their quality in terms of R 2 was similar to that of the benchmark. The results suggest that the MILP model makes the selection process faster, more standardised and transparent, and is especially helpful in coping with multiple nutrients. The complexity of the method does not increase with increasing number of nutrients. The generated food lists appear either shorter or provide more information than a food list generated without the MILP model.","subset":"pubmed_abstract"} +{"meta":{"pmid":11021307,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Zinc fingers: DNA binding and protein-protein interactions.\nThe zinc finger domain is a very ubiquitous structural element whose hallmark is the coordination of a zinc atom by several amino acid residues (cysteines and histidines, and occasionally aspartate and glutamate). These structural elements are associated with protein-nucleic acid recognition as well as protein-protein interactions. The purpose of this review is to examine recent data on the DNA and protein binding properties of a few zinc fingers whose three dimensional structure is known.","subset":"pubmed_abstract"} +{"meta":{"pmid":27927009,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Efficacy and Safety of Guardcel Nasal Packing After Endoscopic Sinus Surgery: A Prospective, Single-Blind, Randomized Controlled Study.\nNasal packing after endoscopic sinus surgery is frequently used to control postoperative bleeding, enhance the wound healing process, and prevent lateralization of the middle turbinate, which causes insufficient ventilation. Many biodegradable materials have been developed to reduce pain and mucosal damage during packing removal. The purpose of this study was to compare the efficacy of Guardcel (Genewel Co.) middle meatal packing with a traditional nonabsorbable middle meatal packing, Merocel (Medtronic Xomed), on wound healing and patient satisfaction. In this prospective, single-blind, randomized controlled study, we enrolled 32 consecutive patients (64 nostrils) undergoing bilateral endoscopic sinus surgery at Korea University Guro Hospital from February 2015 to August 2015. Guardcel and Merocel were inserted postoperatively into a randomly assigned side. Objective findings about bleeding, hemostasis, adhesion, and infection were evaluated with nasal endoscopy. Patients' symptoms including pain and nasal obstruction were evaluated with a visual analog scale. Each evaluation was done at 2-3 days, 1 week, 2 weeks, and 4 weeks after surgery. At 2-3 days after endoscopic sinus surgery, the Guardcel side had a significantly less hemostasis time than the Merocel side (P=0.001). During this period, the pain during packing removal was significantly lower on the Guardcel-inserted side than the Merocel-inserted side (P=0.002). At two weeks after surgery, the adhesion score on the Guardcel side was significantly lower than that of the Merocel side (P=0.011). Other parameters during the study follow-up periods were not statistically significant. There were no severe adverse reactions. Guardcel, a newly developed packing material, appeared to shorten the hemostasis time and reduce pain sensation at 2-3 days after surgery; it also prevented adhesion formation 2 weeks after surgery when compared with the control. Guardcel can be an effective and safe candidate to replace conventional packing materials after endoscopic sinus surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":21518461,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2020-50":1,"2019-47":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-34":2,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-49":1,"2017-13":1}}},"text":"Iron overload in polytransfused patients without heart failure is associated with subclinical alterations of systolic left ventricular function using cardiovascular magnetic resonance tagging.\nIt remains incompletely understood whether patients with transfusion related cardiac iron overload without signs of heart failure exhibit already subclinical alterations of systolic left ventricular (LV) dysfunction. Therefore we performed a comprehensive evaluation of systolic and diastolic cardiac function in such patients using tagged and phase-contrast CMR. 19 patients requiring regular blood transfusions for chronic anemia and 8 healthy volunteers were investigated using cine, tagged, and phase-contrast and T2* CMR. LV ejection fraction, peak filling rate, end-systolic global midventricular systolic Eulerian radial thickening and shortening strains as well as left ventricular rotation and twist, mitral E and A wave velocity, and tissue e' wave and E\/e' wave velocity ratio, as well as isovolumic relaxation time and E wave deceleration time were computed and compared to cardiac T2*. Patients without significant iron overload (T2* > 20 ms, n = 9) had similar parameters of systolic and diastolic function as normal controls, whereas patients with severe iron overload (T2* < 10 ms, n = 5), had significant reduction of LV ejection fraction (54 \u00b1 2% vs. 62 \u00b1 6% and 65 \u00b1 6% respectively p < 0.05), of end-systolic radial thickening (+6 \u00b1 4% vs. +11 \u00b1 2 and +11 \u00b1 4% respectively p < 0.05) and of rotational twist (1.6 \u00b1 0.2 degrees vs. 3.0 \u00b1 1.2 and 3.5 \u00b1 0.7 degrees respectively, p < 0.05) than patients without iron overload (T2* > 20 ms) or normal controls. Patients with moderate iron overload (T2* 10-20 ms, n = 5), had preserved ejection fraction (59 \u00b1 6%, p = NS vs. pts. with T2* > 20 ms and controls), but showed reduced maximal LV rotational twist (1.8 \u00b1 0.4 degrees). The magnitude of reduction of LV twist (r = 0.64, p < 0.001), of LV ejection fraction (r = 0.44, p < 0.001), of peak radial thickening (r = 0.58, p < 0.001) and of systolic (r = 0.50, p < 0.05) and diastolic twist and untwist rate (r = -0.53, p < 0.001) in patients were directly correlated to the logarithm of cardiac T2*. Multiple transfused patients with normal ejection fraction and without heart failure have subclinical alterations of systolic and diastolic LV function in direct relation to the severity of cardiac iron overload. Among all parameters, left ventricular twist is affected earliest, and has the highest correlation to log (T2*), suggesting that this parameter might be used to follow systolic left ventricular function in patients with iron overload.","subset":"pubmed_abstract"} +{"meta":{"pmid":17596424,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Quantitative comparison between neural response in macaque inferotemporal cortex and behavioral discrimination of photographic images.\nInferotemporal (IT) cortex plays a critical role in the primate ability to perceive and discriminate between images, but the relationship between responses of single neurons and behavioral capacities is poorly understood. We studied this relationship by recording from IT neurons while monkeys performed a delayed-match-to-sample task with two images. On each day, two sample images were chosen to maximize the selectivity of the neuron and task difficulty was manipulated by varying sample duration and by masking the sample. On each trial, monkeys reported which of the two sample images was presented. Neural performance was described using an ideal-observer analysis. Across the population, neural and behavioral sensitivity to changes in sample duration were indistinguishable. Neural sensitivity was dependent on epoch used to analyze neural response; maximal neural sensitivity was achieved in the 128-ms epoch that began 85 ms after sample onset. At most sample durations, the epoch that yielded optimal neural performance was longer than the sample duration, suggesting that neural selectivity persisted after the presentation of the mask during performance of the task. A control experiment showed that neural and behavioral performance improved in the absence of the mask. These observations suggest that the responses of individual IT neurons contain sufficient information to allow behavioral discrimination of images in a demanding task.","subset":"pubmed_abstract"} +{"meta":{"pmid":3010074,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes.\n[3H]NECA (1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuronamide) is known to bind to both the A1 and A2 subtypes of adenosine receptor in rat striatal membranes. In order to study the putative A2 component of [3H]NECA binding, we examined several compounds for the ability to selectively eliminate the A1 component of binding; N6-cyclopentyladenosine was found to give the most satisfactory results. Binding of [3H]NECA in the presence of 50 nM N6-cyclopentyladenosine was characterized. The rank order of potency for inhibition of [3H]NECA binding was NECA much greater than 2-chloroadenosine greater than N6-[(R)-1-methyl-2-phenyl-ethyl]adenosine (R-PIA) greater than N6-cyclohexyladenosine greater than S-PIA, indicating that binding was to an A2 adenosine receptor. When affinities of compounds in [3H]NECA binding to A2 receptors were compared to their affinities in [3H]N6-cyclohexyladenosine binding to A1 receptors, N6-cyclopentyladenosine was the most A1-sensitive agonist (A1 Ki, 0.59 nM; A2 Ki, 460 nM; Ki ratio, 780), whereas the selective coronary vasodilator 2-(phenylamino)adenosine was the most A2-selective agonist (A1, 560 nM; A2, 120 nM; ratio, 0.21). The antagonist 8-cyclopentyltheophylline had considerable A1 selectivity (A1, 11 nM; A2, 1400 nM; ratio, 130), whereas alloxazine had slight A2 selectivity (A1, 5200 nM; A2, 2700; ratio, 0.52). [3H]NECA binding to A2 receptors was highest in striatum but was detectable at much lower levels in each of seven other brain areas. The regional distribution of [3H]NECA binding and the affinities of adenosine agonists and antagonists for inhibition of binding indicate that the site labeled by [3H]NECA belongs to the high affinity, or A2a, subclass of A2 receptor.","subset":"pubmed_abstract"} +{"meta":{"pmid":26453435,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Where frailty meets diabetes.\nDiabetes is a chronic illness that has an effect on multiple organ systems. Frailty is a state of increased vulnerability to stressors and a limited capacity to maintain homeostasis. It is a multidimensional concept and a dynamic condition that can improve or worsen over time. Frailty is either physical or psychological or a combination of these two components. Sarcopenia, which is the age-related loss of skeletal muscle mass and strength, is the main attributor to the physical form of frailty. Although the pathophysiology of diabetes is commonly focused on impaired insulin secretion, overload of gluconeogenesis and insulin resistance, newer insights broaden this etiologic horizon. Immunologic factors that create a chronic state of low-grade inflammation--'inflammaging'--have an influence on both the ageing process and diabetes. Persons with diabetes mellitus already tend to have an accelerated ageing process that places them at greater risk for developing frailty at an earlier age. The development of frailty--and sarcopenia--is multifactorial and includes nutritional, physical and hormonal elements; these elements are interlinked with those of diabetes. A lower muscle mass will lead to poorer glycaemic control through lower muscle glucose uptake. This leads to higher insulin secretion and insulin resistance, which is the stepping stone for diabetes itself.","subset":"pubmed_abstract"} +{"meta":{"pmid":9371617,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"E1A 12S and 13S of the transformation-defective adenovirus type 12 strain CS-1 inactivate proteins of the RB family, permitting transactivation of the E2F-dependent promoter.\nThe transformation-defective Vero cell host range mutant CS-1 of the highly oncogenic adenovirus type 12 (Ad12) (Ad12-CS-1) has a 69-bp deletion in the early region 1A (E1A) gene that removes the carboxy-terminal half of conserved region 2 and the amino-terminal half of the Ad12-specific so-called spacer that seems to play a pivotal role in the oncogenicity of the virus. Despite its deficiency in immortalizing and transforming primary rodent cells, we found that the E1A 13S protein of Ad12-CS-1 retains the ability to bind p105-RB, p107, and p130 in nuclear extract binding assays with glutathione S-transferase-E1A fusion proteins and Western blot analysis. Like wild-type E1A, the mutant protein was able to dissociate E2F from retinoblastoma-related protein-containing complexes, as judged from gel shift experiments with purified 12S and 13S proteins from transfection experiments with an E1A expression vector or from infection with the respective virus. Moreover, in transient expression assays, the 12S and 13S products of wild-type Ad12 and Ad12-CS-1 were shown to transactivate the Ad12 E1A promoter containing E2F-1 and E2F-5-motifs, respectively, in a comparable manner. The same results were obtained from transfection assays with the E2F motif-dependent E2 promoter of adenovirus type 5 or the human dihydrofolate reductase promoter. These data suggest that efficient infection by Ad12 and the correlated virus-induced reprogramming of the infected cells, including the induction of cell cycle-relevant mechanisms (e.g. E2F activation), can be uncoupled from the transformation properties of the virus.","subset":"pubmed_abstract"} +{"meta":{"pmid":31080379,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Association of Increased Risk of Pneumonia and Using Proton Pump Inhibitors in Patients With Type II Diabetes Mellitus.\nThis study explored the possible association between the use of proton pump inhibitors (PPIs) and the increased incidence of pneumonia in patients with type 2 diabetes mellitus (T2DM). We selected 4940 patients with T2DM of whom 988 and 3952 were enrolled in PPI and propensity score-matched control cohorts, respectively. All patients were followed from the index date until admission with pneumonia, withdrawal from the National Health Insurance program or the end of 2013. The PPIs associated with risk of incident pneumonia were examined. Furthermore, we assessed the risk of pneumonia according to annual defined daily doses in the PPI cohort. After a 14-year follow-up, the cumulative incidence of pneumonia in the PPI users was 11.4% higher than that in the controls (30.3% vs 18.9%). Compared to the controls, the PPI users had a 1.70-fold higher risk of pneumonia in the Cox proportional hazards model after adjustment for matched pairs. The risk of pneumonia increased with the annual PPI defined daily dose. The results of this population-based retrospective cohort study suggest that PPI use increased the risk of pneumonia in patients with T2DM. The effects were more prominent in patients administered higher doses of PPIs.","subset":"pubmed_abstract"} +{"meta":{"pmid":11001107,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Etiology of community-acquired pediatric viral diarrhea: a prospective longitudinal study in hospitals, emergency departments, pediatric practices and child care centers during the winter rotavirus outbreak, 1997 to 1998. The Pediatric Rotavirus Epidemiology Study for Immunization Study Group.\nTo determine the viral etiology of community-acquired diarrhea in children admitted to hospitals and presenting in emergency departments, pediatric practices and child care centers from November 1, 1997, to June 30, 1998. Children with diarrhea were identified in a prospective multisite cohort study and analyzed according to age, gender and duration of hospitalization. Stools were tested for rotavirus by enzyme immunoassay and for all other enteric viruses by electron microscopy. Of the 2524 children identified with diarrhea, stools of 1386 (55%) were tested by enzyme immunoassay for rotavirus, and of these 1365 (54%) were screened by electron microscopy for all identifiable enteric viruses. Rotavirus was found in 32% (n = 437), adenovirus in 4% (n = 55), torovirus in 3% (n = 44), Norwalk-like viruses in 2% (n = 25) and astrovirus (n = 14) and calicivirus (n = 7) in fewer than 1% of the specimens tested. The proportion of rotavirus was significantly higher in children 12 to 23 months of age (43% of tested stools, n = 159) and 24 to 35 months of age (38% of tested stools, n = 64) (P < 0.001) than in any other age group. Toroviruses were found to approximately the same extent in children > or =36 months of age (6% of tested stools, n = 19) as those <36 months of age. Rotavirus (36% of tested stools, n = 375, P < 0.0005) and torovirus (4% of tested stools, n = 43, P < 0.004) were most often found in hospitalized patients. In contrast Norwalk-like viruses (P < 0.001) and astroviruses (P < 0.01) were more commonly detected in specimens from patients who presented to physicians' offices and who were symptomatic for gastroenteritis in child care centers. This study demonstrates that although all known gastroenteritis viruses were diagnosed in symptomatic children, rotavirus was the etiologic agent in most cases of diarrhea managed in the community and in the hospital.","subset":"pubmed_abstract"} +{"meta":{"pmid":33675389,"dup_signals":{"dup_doc_count":12,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2022-49":1,"2022-27":1,"2022-05":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":2,"2023-14":1}}},"text":"A novel evolutionary-concordance lifestyle score is inversely associated with all-cause, all-cancer, and all-cardiovascular disease mortality risk.\nEvolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality. Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) study. The ECL score's components were: a previously reported evolutionary-concordance diet score, alcohol intake, physical activity, sedentary behavior, waist circumference, smoking history, and social network size. Diet was assessed using a Block 98 food frequency questionnaire and anthropometrics by trained personnel; other information was self-reported. Higher scores indicated higher evolutionary concordance. We used multivariable Cox proportional hazards regression models to estimate ECL score-mortality associations. Over a median follow-up of 10.3 years, 3771 deaths occurred (1177 from cardiovascular disease [CVD], 1002 from cancer). The multivariable-adjusted hazard ratios (HR) (95% confidence intervals [CI]) for those in the highest relative to the lowest ECL score quintiles for all-cause, all-CVD, and all-cancer mortality were, respectively, 0.45 (0.40, 0.50), 0.47 (0.39, 0.58), and 0.42 (0.34, 0.52) (all P trend < 0.01). Removing smoking and diet from the ECL score attenuated the estimated ECL score-all-cause mortality association the most, yielding fifth quintile HRs (95% CIs) of 0.56 (0.50, 0.62) and 0.50 (0.46, 0.55), respectively. Our findings suggest that a more evolutionary-concordant lifestyle may be inversely associated with all-cause, all-CVD, and all-cancer mortality. Smoking and diet appeared to have the greatest impact on the ECL-mortality associations.","subset":"pubmed_abstract"} +{"meta":{"pmid":17324744,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":11}}},"text":"Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat.\nTo investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH(4)) in any effect of folic acid by comparing the effect of BH(4) with that of folic acid in Dex hypertension. Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg\/kg\/d) or Dex (10 microg\/rat\/d). Folic acid (0.04 g\/L drinking) or BH(4) (10 mg\/kg\/d intraperitoneally) was started before (prevention) and during (reversal) glucocorticoid treatment. Saline, BH(4), vehicle for BH(4), or folic acid alone did not change systolic blood pressure (BP). Systolic BP was increased by ACTH and Dex. Folic acid, but not BH(4), prevented the development of hypertension caused by ACTH and Dex treatment. The ACTH and Dex hypertension were partially reversed by folic acid. The BH(4) increased plasma total biopterin concentrations. The Dex decreased plasma NOx concentrations but had no effect on plasma biopterin concentrations. The ACTH and Dex increased plasma F(2)-isoprostane concentrations and decreased serum homocysteine concentrations compared with control but had no effect on serum folate concentrations. Folic acid increased serum folate concentrations compared with control but had no effect on homocysteine concentrations. Folic acid prevented and partially reversed both ACTH and Dex hypertension in rats without modifying the increase in plasma F(2)-isoprostane concentrations. Given that BH(4) failed to prevent ACTH or Dex hypertension, folic acid is unlikely to be acting through increased BH(4) production. The precise mechanism for the BP-lowering effect of folic acid in this model of hypertension remains to be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":30382276,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-21":1,"2021-04":1,"2020-50":1,"2020-45":1,"2019-43":1,"2019-18":1,"2019-13":1,"2019-09":2,"2018-51":1,"2018-47":1,"2018-43":2,"2023-40":1,"2024-26":1}}},"text":"Using microgels to control the morphology and optoelectronic properties of hybrid organic-inorganic perovskite films.\nMicrogels (MGs) are crosslinked polymer colloid particles that swell in a good solvent. Although MGs have been studied for over 80 years their ability to control the morphology and optoelectronic properties of composite films containing photoactive materials is in its infancy. Solution processable hybrid organic-inorganic perovskites such as CH3NH3PbI3-zClz have attracted enormous fundamental and applied interest because of their outstanding optoelectronic properties. There is considerable interest in establishing methods to control perovskite film morphology, for example, using micropatterning. Here, hydrophilic poly(N-vinylformamide)-based MGs were dispersed in perovskite precursor solution which was then spin coated to deposit CH3NH3PbI3-zClz\/MG films for the first time. Remarkably, the CH3NH3PbI3-zClz\/MG composites formed disordered inverse opal (DIO) films. The CH3NH3PbI3-zClz\/MG composition ranges which gave DIO films are identified using a phase diagram. The pore wall thickness is shown to be controlled by the volume fraction of MGs used and a simple model is presented to explain this behaviour. The MGs not only caused CH3NH3PbI3-zClz to be more efficiently deposited but also increased light absorption and photoluminescence intensity. Demonstration solar cells constructed containing the DIO CH3NH3PbI3-zClz\/MG films had an average conversion efficiency of 6.58 \u00b1 0.81%. A mechanism for DIO film formation is discussed. The principles established in this study wherein MGs control the morphology and properties of CH3NH3PbI3-zClz\/MG films should also apply to other perovskite\/MG composites.","subset":"pubmed_abstract"} +{"meta":{"pmid":18987892,"dup_signals":{"dup_doc_count":30,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2022-40":1,"2022-33":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-10":1,"2020-45":2,"2014-42":4,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2024-26":1,"2024-22":1,"2014-10":1,"2013-48":1,"2024-30":1}}},"text":"Shifting trends: detecting environmentally mediated regulation in long-lived marine vertebrates using time-series data.\nAssessing the status and trends in animal populations is essential for effective species conservation and management practices. However, unless time-series abundance data demonstrate rapid and reliable fluctuations, objective appraisal of directionality of trends is problematic. We adopted a multiple-working hypotheses approach based on information-theoretic and Bayesian multi-model inference to examine the population trends and form of intrinsic regulation demonstrated by a long-lived species, the southern elephant seal. We also determined the evidence for density dependence in 11 other well-studied marine mammal species. (1) We tested the type of population regulation for elephant seals from Marion Island (1986-2004) and from 11 other marine mammal species, and (2) we described the trends and behavior of the 19-year population time series at Marion Island to identify changes in population trends. We contrasted five plausible trend models using information-theoretic and Bayesian-inference estimates of model parsimony. Our analyses identified two distinct phases of population growth for this population with the inflexion occurring in 1998. Thus, the population decreased between 1986 and 1997 (-3.7% per annum) and increased between 1997 and 2004 (1.9% per annum). An index of environmental stochasticity, the Southern Oscillation Index, explained some of the variance in r and N. We determined analytically that there was good evidence for density dependence in the Marion Island population and that density dependence was widespread among marine mammal species (67% of species showed evidence for population regulation). This approach demonstrates the potential functionality of a relatively simple technique that can be applied to short time series to identify the type of regulation, and the uncertainty associated with the phenomenon, operating in populations of large mammals.","subset":"pubmed_abstract"} +{"meta":{"pmid":29795460,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study.\nRecent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.","subset":"pubmed_abstract"} +{"meta":{"pmid":36147309,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":2,"unknown":9}}},"text":"INVESTIGATING THE EFFECT OF TAU DEPOSITION AND APOE ON HIPPOCAMPAL MORPHOMETRY IN ALZHEIMER'S DISEASE: A FEDERATED CHOW TEST MODEL.\nAlzheimer's disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. Tau tangle is the specific protein pathological hallmark of AD and plays a crucial role in leading to dementia-related structural deformations observed in magnetic resonance imaging (MRI) scans. The volume loss of hippocampus is mainly related to the development of AD. Besides, apolipoprotein E (APOE) also has significant effects on the risk of developing AD. However, few studies focus on integrating genotypes, MRI, and tau deposition to infer multimodal relationships. In this paper, we proposed a federated chow test model to study the synergistic effects of APOE and tau on hippocampal morphometry. Our experimental results demonstrate our model can detect the difference of tau deposition and hippocampal atrophy among the cohorts with different genotypes and subiculum and cornu ammonis 1 (CA1 subfield) were identified as hippocampal subregions where atrophy is strongly associated with abnormal tau in the homozygote cohort. Our model will provide novel insight into the neural mechanisms about the individual impact of APOE and tau deposition on brain imaging.","subset":"pubmed_abstract"} +{"meta":{"pmid":25556811,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":12}}},"text":"The impact of different aetiologies on the cognitive performance of frontal patients.\nNeuropsychological group study methodology is considered one of the primary methods to further understanding of the organisation of frontal 'executive' functions. Typically, patients with frontal lesions caused by stroke or tumours have been grouped together to obtain sufficient power. However, it has been debated whether it is methodologically appropriate to group together patients with neurological lesions of different aetiologies. Despite this debate, very few studies have directly compared the performance of patients with different neurological aetiologies on neuropsychological measures. The few that did included patients with both anterior and posterior lesions. We present the first comprehensive retrospective comparison of the impact of lesions of different aetiologies on neuropsychological performance in a large number of patients whose lesion solely affects the frontal cortex. We investigated patients who had a cerebrovascular accident (CVA), high (HGT) or low grade (LGT) tumour, or meningioma, all at the post-operative stage. The same frontal 'executive' (Raven's Advanced Progressive Matrices, Stroop Colour-Word Test, Letter Fluency-S; Trail Making Test Part B) and nominal (Graded Naming Test) tasks were compared. Patients' performance was compared across aetiologies controlling for age and NART IQ scores. Assessments of focal frontal lesion location, lesion volume, global brain atrophy and non-specific white matter (WM) changes were undertaken and compared across the four aetiology. We found no significant difference in performance between the four aetiology subgroups on the 'frontal' executive and nominal tasks. However, we found strong effects of premorbid IQ on all cognitive tasks and robust effects of age only on the frontal tasks. We also compared specific aetiology subgroups directly, as previously reported in the literature. Overall we found no significant differences in the performance of CVA and tumour patients, or LGT and HGT patients or LGT, HGT and meningioma's on our four frontal tests. No difference was found with respect to the location of frontal lesions, lesion volume, global brain atrophy and non-specific WM changes between the subgroups. Our results suggest that the grouping of frontal patients caused by different aetiologies is a pragmatic, justified methodological approach that can help to further understanding of the organisation of frontal executive functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":29466922,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.\nBone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% \u00b1 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":28039294,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":10}}},"text":"Process mapping evaluation of medication reconciliation in academic teaching hospitals: a critical step in quality improvement.\nMedication reconciliation (MedRec) has been a mandated or recommended activity in Canada, the USA and the UK for nearly 10 years. Accreditation bodies in North America will soon require MedRec for every admission, transfer and discharge of every patient. Studies of MedRec have revealed unintentional discrepancies in prescriptions but no clear evidence that clinically important outcomes are improved, leading to widely variable practices. Our objective was to apply process mapping methodology to MedRec to clarify current processes and resource usage, identify potential efficiencies and gaps in care, and make recommendations for improvement in the light of current literature evidence of effectiveness. Process engineers observed and recorded all MedRec activities at 3 academic teaching hospitals, from initial emergency department triage to patient discharge, for general internal medicine patients. Process maps were validated with frontline staff, then with the study team, managers and patient safety leads to summarise current problems and discuss solutions. Across all of the 3 hospitals, 5 general problem themes were identified: lack of use of all available medication sources, duplication of effort creating inefficiency, lack of timeliness of completion of the Best Possible Medication History, lack of standardisation of the MedRec process, and suboptimal communication of MedRec issues between physicians, pharmacists and nurses. MedRec as practised in this environment requires improvements in quality, timeliness, consistency and dissemination. Further research exploring efficient use of resources, in terms of personnel and costs, is required.","subset":"pubmed_abstract"} +{"meta":{"pmid":23614499,"dup_signals":{"dup_doc_count":63,"dup_dump_count":53,"dup_details":{"curated_sources":2,"2021-49":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":2,"2018-13":1,"2018-09":1,"2018-05":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":2,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":2,"2022-27":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2017-13":1}}},"text":"Epidemiology of human infections with avian influenza A(H7N9) virus in China.\nThe first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.","subset":"pubmed_abstract"} +{"meta":{"pmid":31525034,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"M\u00f6ssbauer Spectral Study of the Low-Temperature Electronic and Magnetic Properties of \u03b1-FePO4 and the Mixed Valence Iron(II\/III) Phosphate SrFe3(PO4)3.\nThe M\u00f6ssbauer spectra of trigonal \u03b1-FePO4, measured between 4.2 and 300 K, exhibit hyperfine parameters characteristic of high-spin iron(III) in a pseudotetrahedral oxygen environment. Between 24.5 and 300 K, the spectra show a paramagnetic quadrupole doublet and at 24.0 K the spectrum reveals the onset of antiferromagnetic exchange. At 4.2 and 16 K, a single magnetic sextet is observed with hyperfine fields of 51.36(1) and 42.74(1) T, respectively, with an angle, \u03b8, of 90\u00b0 between the principal axis of the electric field gradient tensor in the basal plane of the trigonal unit cell and the hyperfine field along the c axis. The spectra obtained between 21 and 18 K have been fitted with two equal-area magnetic sextets with \u03b8 angles of 25 and 85\u00b0, angles which indicate that the iron(III) magnetic moments are canted away from the c axis. The reduced hyperfine field versus reduced temperature plot indicates a departure from a Brillouin S = 5\/2 behavior, as a result of some magnetostriction at the N\u00e9el temperature. The M\u00f6ssbauer spectra of class 1 mixed-valence SrFe3(PO4)3, measured between 4.2 and 300 K, exhibit hyperfine parameters characteristic of two high-spin iron(II) ions and one high-spin iron(III) ion in a pseudooctahedral oxygen environment. At and above 40 K, the spectra show two paramagnetic quadrupole doublets, whereas at 39.0 K the spectrum reveals the onset of ferrimagnetic exchange. Between 4.2 and 30 K, the spectra have been fitted with two magnetic sextets with \u03b8 angles of 85 and 10\u00b0 for the iron(II) and iron(III) sites, respectively. The reduced hyperfine field versus reduced temperature plots for the iron(II) and iron(III) sites show a distinct departure from Brillouin S = 2 and S = 5\/2 behavior, respectively, a departure that suggests a first-order magnetic transition at 39.5(5) K with differing magnetostrictions at the iron(II) and iron(III) sites.","subset":"pubmed_abstract"} +{"meta":{"pmid":23976886,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Structure, Stiffness and Substates of the Dickerson-Drew Dodecamer.\nThe Dickerson-Drew dodecamer (DD) d-[CGCGAATTCGCG]2 is a prototypic B-DNA molecule whose sequence-specific structure and dynamics have been investigated by many experimental and computational studies. Here, we present an analysis of DD properties based on extensive atomistic molecular dynamics (MD) simulations using different ionic conditions and water models. The 0.6-2.4-\u00b5s-long MD trajectories are compared to modern crystallographic and NMR data. In the simulations, the duplex ends can adopt an alternative base-pairing, which influences the oligomer structure. A clear relationship between the BI\/BII backbone substates and the basepair step conformation has been identified, extending previous findings and exposing an interesting structural polymorphism in the helix. For a given end pairing, distributions of the basepair step coordinates can be decomposed into Gaussian-like components associated with the BI\/BII backbone states. The nonlocal stiffness matrices for a rigid-base mechanical model of DD are reported for the first time, suggesting salient stiffness features of the central A-tract. The Riemann distance and Kullback-Leibler divergence are used for stiffness matrix comparison. The basic structural parameters converge very well within 300 ns, convergence of the BI\/BII populations and stiffness matrices is less sharp. Our work presents new findings about the DD structural dynamics, mechanical properties, and the coupling between basepair and backbone configurations, including their statistical reliability. The results may also be useful for optimizing future force fields for DNA.","subset":"pubmed_abstract"} +{"meta":{"pmid":9056625,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Subdural hematoma and lupus anticoagulants.\nPatients with lupus anticoagulants do not typically have a bleeding tendency. However, a few reports of hemorrhage in patients with lupus anticoagulants in the absence of known risk factors for bleeding have been published, raising the question of an etiologic connection between lupus anticoagulants and certain types of hemorrhage. The presentation of three patients with subdural hematoma and lupus anticoagulants within only 1 year at our institutions and the report of two such patients in the literature led us to conduct a retrospective study to determine whether patients with lupus anticoagulants may have an increased risk for the development of subdural hematoma. All patients with a discharge diagnosis of nontraumatic subdural hematoma and lupus anticoagulant at three medical institutions between 1985 and 1996 were identified, and their medical histories and laboratory evaluations were reviewed. Of 733 patients with a discharge diagnosis of nontraumatic subdural hematoma, 5 were diagnosed as having a lupus anticoagulant (0.7%). All had known risk factors for the development of subdural hematoma: thrombocytopenia, hypoprothrombinemia, intracerebral venous hemorrhage, warfarin therapy, and advanced age with a history of a fall. This study suggests that presence of a lupus anticoagulant by itself is not associated with an increased incidence of nontraumatic subdural hematoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":30096203,"dup_signals":{"dup_doc_count":47,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":2,"2023-23":1,"2023-14":2,"2023-06":2,"2022-49":1,"2022-40":2,"2022-27":2,"2022-21":4,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":2,"2021-25":1,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":1,"2024-22":4,"2024-18":2}}},"text":"Cognitive and behavioural strategies for weight management in overweight adults: Results from the Oxford Food and Activity Behaviours (OxFAB) cohort study.\nThough many overweight and obese adults attempt to lose weight without formal support, little is known about the strategies used in self-directed weight loss attempts. We set out to assess cognitive and behavioural strategies for weight loss and their associations with weight change. Prospective, web-based cohort study of overweight UK adults (BMI\u226525kg\/m2) trying to lose weight through behaviour change. Strategy use was assessed using the OxFAB questionnaire and evaluated (1) at the domain level, (2) through exploratory factor analysis, and (3) in a model of strategies deemed a priori to be \"essential\" to weight management. Associations with weight change at 3 months were tested using linear regression. 486 participants answered all questions; 194 reported weight at baseline and at 3 months (mean weight change -3.3kg (SD 4.1)). Greater weight loss was significantly associated with the motivational support domain (-2.4kg, 95% CI -4.4 to -0.4), dietary impulse control (from factor analysis) (-0.6kg, 95% CI -1.1 to -0.03), and weight loss planning and monitoring (from factor analysis) (-1.3kg, 95% CI -2.0 to -0.5). Higher scores in the model of essential behavioural strategies were significantly associated with greater weight loss (compared to participants using 6 or fewer of the 9 strategies, using 7 or more of the 9 strategies was associated with a 2.13kg greater weight loss (SE 0.58, p<0.001)). Despite heterogeneity in the strategies employed for weight loss, coherent patterns of behaviours emerged for individual participants, some of which were associated with greater weight loss, including strategies relating to dietary impulse control, weight loss planning and monitoring, motivational support, information seeking and self-monitoring. Trials could test the effect of promoting use of these patterns on weight loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":34085928,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":7}}},"text":"Convalescent plasma use in the USA was inversely correlated with COVID-19 mortality.\nThe US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data. CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = -0.52, p=0.002) between CCP usage per hospital admission and deaths occurring 2 weeks after admission, and this finding was robust to examination of deaths taking place 1, 2, or 3 weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021. A strong inverse correlation between CCP use and mortality per admission in the USA provides population-level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths. There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.","subset":"pubmed_abstract"} +{"meta":{"pmid":32601688,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":7}}},"text":"The Effect of the Loading Rate on the Full-Field Strain Distribution on the Surface on the Intervertebral Discs.\nContrasting results are reported when the spine is tested at different strain rates. Tissue specimens from the ligaments or the intervertebral discs (IVD, including annulus fibrosus and nucleus pulposus) exhibit higher stiffness and lower dissipation at high strain rates. Counterintuitively, when spine segments are tested at high rates, the hysteresis area and loop width increase. It is unclear how the load is shared between the different structures at different loading rates. The hypotheses of this study were: (i) As the IVD stiffens at higher loading rates, the strain distribution around the disc would be different depending on the loading rate; (ii) Preconditioning attenuates the strain-rate dependency of the IVD, thus making differences in strain distribution smaller at the different rates. Six segments of three vertebrae (L4-L6) were extracted from porcine spines and tested in presso-flexion at different loading rates (reaching full load in 0.67, 6.7, and 67 s). The full-field strain maps were measured using digital image correlation on the surface of the IVDs from lateral. The posterior-to-anterior trends of the strain were computed in detail for each IVD, and compared between loading rates. The values and the direction of principal strain on the surface of the IVDs, vertebrae, and endplates remained unchanged at different rates. In the transition zone between IVD and vertebra, only slight differences due to the loading rate appeared but with no statistical significance. These findings will allow better understanding of the rate-dependent behavior and failure of the IVD.","subset":"pubmed_abstract"} +{"meta":{"pmid":23519305,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-06":1,"2014-10":1,"2013-20":1,"2015-18":1,"unknown":13}}},"text":"Five-year risks of CIN 3+ and cervical cancer among women with HPV-positive and HPV-negative high-grade Pap results.\nHigh-grade Pap results (e.g., atypical glandular cells [AGC], atypical squamous cells cannot rule out HSIL [ASC-H], and high-grade squamous intraepithelial lesion [HSIL]) predict high cancer risks, resulting in referral for colposcopy without HPV triage. However, new guidelines recommending cotesting for women 30 years and older imply that clinicians will often receive the HPV test result concurrently for high-grade Pap results. We examined whether HPV testing provides useful risk stratification in this context. From a cohort of 965,360 women aged 30 to 64 years undergoing cotesting at Kaiser Permanente Northern California, we estimated 5-year risks for cervical cancer and CIN 3+ after AGC (2,074 women), ASC-H (1,647 women), and HSIL (2,019 women) according to HPV test results. HPV positivity of AGC Pap results was 25% and decreased with age (30 to 34 vs 60 to 64 years, 44% vs 17%, p < .0001), whereas HPV positivity of ASC-H and HSIL was much higher (71% and 94%) and decreased less with age. Even for these high-grade Pap results, 5-year CIN 3+ risks differed substantially between HPV-positive and HPV-negative women (AGC, 33% vs 0.93%, p < .0001; ASC-H, 25% vs 3.5%, p < .0001; HSIL, 49% vs 30%, p = .006). However, except for AGC, cervical cancer risks differed less between HPV-positive and HPV-negative women (AGC, 9.0% vs 0.37%, p < .0001; ASC-H, 2.5% vs 2.1%, p = .8; HSIL, 6.6% vs 6.8%, p = .7). The risks of CIN 3+ among women with HPV-negative high-grade Pap results were lower than those among women with HPV-positive high-grade Pap results, especially after AGC. However, by the principle of \"equal management of equal risks,\" all HPV-negative high-grade Pap results had cancer risks high enough to warrant colposcopy, confirming that there is no current role for HPV triage of high-grade Pap results.","subset":"pubmed_abstract"} +{"meta":{"pmid":19492925,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2024-30":1,"unknown":12}}},"text":"Increased inositol phosphoglycan P-type in the second trimester in pregnant women with type 2 and gestational diabetes mellitus.\nA progressive insulin resistant state develops throughout human pregnancy. Inositol phosphoglycan P-type (P-IPG), a second messenger of insulin, was reported to negatively correlate with the degree of insulin resistance in non-pregnant diabetic subjects. Urinary levels of P-IPG were assessed in insulin resistant states during pregnancy such as gestational diabetes mellitus (GDM, n=44) and type 2 diabetes mellitus (type 2 DM, n=25) and in 69 normal pregnant women. Urinary levels of P-IPG were higher in GDM than controls with a positive trend of release throughout normal pregnancy (P<0.01). P-IPG excretion was higher in diabetic (GDM and type 2 DM) than in healthy women in the second trimester (P<0.05). A higher P-IPG urinary excretion occurs during the second trimester in pregnant women with clinically evident insulin resistance with a positive association with poor glycemic control.","subset":"pubmed_abstract"} +{"meta":{"pmid":23744257,"dup_signals":{"dup_doc_count":59,"dup_dump_count":30,"dup_details":{"curated_sources":3,"2018-09":1,"2017-47":1,"2017-39":2,"2017-30":1,"2017-22":2,"2017-09":2,"2017-04":1,"2016-44":2,"2016-40":2,"2016-36":1,"2016-30":1,"2016-07":2,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":1,"2014-42":6,"2014-41":4,"2014-15":1,"2018-17":1,"2015-18":3,"2015-11":2,"2015-06":2,"2014-10":1,"2017-13":1}}},"text":"Advanced interactive preintegrated volume rendering with a power series.\nPreintegrated volume rendering produces high-quality renderings without increased sampling rates. However, a look-up table of a conventional preintegrated volume rendering requires a dimensionality of two, which disturbs interactive renderings when the transfer function is changed. Furthermore, as the resolution of the volume data set increases, the memory space required is impractical or inefficient, especially on GPUs. In the past, several approximation methods have been proposed to reduce the complexity of both the time and memory requirement, but most of them do not correctly present thin opaque structures within slabs and ignore the self-attenuation. We propose an advanced interactive preintegrated volume rendering algorithm that achieves not only high-quality renderings comparable to the conventional ones, but also $(O(n))$ time and memory space requirements even with the self-attenuation within the slabs applied. The algorithm proposed in this paper decomposes the exponential term of the ray integration equation into a power series of a finite order in the form of a linear combination to build a one-dimensional look-up table. Moreover, the proposed algorithm effectively applies the self-attenuation that is caused by fully opaque isosurfaces, by introducing an opaque prediction table. Experimental results demonstrate that the proposed algorithm offers renderings visibly identical to existing preintegrated volume renderings without degrading rendering speed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26944837,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-06":1,"2022-49":1,"2022-33":1,"2022-05":2,"2021-39":1,"2021-25":2,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-50":1,"2024-18":1}}},"text":"Adherence to Asthma Guidelines in Children, Tweens, and Adults in Primary Care Settings: A Practice-Based Network Assessment.\nTo assess primary care adherence to 2007 US asthma guidelines. Patients with persistent asthma aged 5 to 65 years from 22 primary care participating practices provided the data for this analysis of baseline information from the pragmatic randomized clinical trial the Asthma Tools Study. Using a combination of abstracted medical record data and patient-reported demographic information, we assessed the medical record documentation for elements of the 2007 US asthma guidelines. Elements assessed included documentation of (1) assessment of control, (2) factors that affect control (medication adherence evaluation, inhaler technique education, and evaluation for triggers), (3) self-management support (action plan), and (4) asthma medications prescribed (short-acting \u03b2-agonists and daily maintenance therapy). The baseline data was collected from March 16, 2009, to May 1, 2014. In 1176 patients (285 children, 211 tweens, and 680 adults) from 16 family medicine and 6 pediatric practices across the United States, documented guideline adherence was highest for prescription of medications (88.0% for short-acting \u03b2-agonists and 70.4% for maintenance medications) and lowest for an asthma action plan (3.1%). Documentation of control (15.0%) and factors that affect control (inhaler technique education, 7.6%; medication adherence assessment, 32.5%; and allergy evaluation, 32.5%) was not common and even less common for adults compared with children. A total of 22.2% of the enrolled patients had no asthma-related visit in the year before enrollment. Adherence to the nonmedication elements were higher in practices located in cities of more than 250,000 people and cities that used electronic medical records. Older patient age was negatively associated with guideline adherence. Adherence to asthma guidelines is poor in primary care practices, leaving many opportunities for improvement.","subset":"pubmed_abstract"} +{"meta":{"pmid":19036889,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mice heterozygous for both A1 and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine.\nCaffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A(1)Rs and A(2A)Rs, achieved by deleting one of the two copies of the A(1)R and A(2A)R genes, would mimic some aspects of long-term caffeine ingestion. The A(1)R and A(2A)R double heterozygous (A(1)R-A(2A)R dHz) mice indeed had approximately one-half the number of A(1)R and A(2A)R, and there were little compensatory changes in A(2B) or A(3) adenosine receptor (A(2B)R or A(3)R) expression. The ability of a stable adenosine analog to activate receptors was shifted to the right by caffeine and in A(1)R-A(2A)R dHz tissue. Caffeine (0.3 g\/l in drinking water for 7-10 days) and A(1)R-A(2A)R dHz genotype increased locomotor activity (LA) and decreased heart rate without significantly influencing body temperature. The acute stimulatory effect of a single injection of caffeine was reduced in A(1)R-A(2A)R dHz mice and in mice treated long term with oral caffeine. Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R.","subset":"pubmed_abstract"} +{"meta":{"pmid":26043439,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-40":1,"2021-25":1,"2021-04":1,"2020-24":1,"2019-13":1,"2018-51":1,"2018-30":1,"2018-09":1,"2017-47":1,"2017-39":1,"2023-23":1}}},"text":"The balance of clinician and patient input into treatment decision-making in older women with operable breast cancer.\nPrimary endocrine therapy (PET) is an alternative to surgery for oestrogen receptor positive operable breast cancer in some older women. However the decision to offer PET involves complex trade-offs and is influenced by both patient choice and healthcare professional (HCP) preference. This study aimed to compare the views of patients and HCPs about this decision and explore decision-making (DM) preferences and whether these are taken into account during consultations. This multicentre, UK, mixed methods study had three components: (a) questionnaires to older women undergoing counseling about breast cancer treatment options which assessed their DM preferences and realities; (b) qualitative interviews with older women with operable breast cancer offered a choice of either surgery or PET and (c) qualitative interviews with HCPs (both of which focused on DM preferences in this setting). Thirty-three patients and 34 HCPs were interviewed. A range of opinions about patient involvement in DM were identified. Patients indicated varying preferences for DM involvement which were variably taken into account by HCPs. These qualitative findings were broadly supported by the questionnaire results. Most patients (536\/729; 73.5%) achieved their preferred DM style; however, the remainder felt that their DM preferences had not been taken into consideration. These results suggest that whilst many older women achieve their desired level of DM engagement, some do not, raising the possibility that they may be making choices which are not concordant with their treatment preferences.","subset":"pubmed_abstract"} +{"meta":{"pmid":32358562,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":1,"2020-34":1,"2020-24":1,"2023-50":1,"2024-18":1}}},"text":"Harnessing the potential of multimodal radiotherapy in prostate cancer.\nRadiotherapy in combination with androgen deprivation therapy (ADT) is a standard treatment option for men with localized and locally advanced prostate cancer. However, emerging clinical evidence suggests that radiotherapy can be incorporated into multimodality therapy regimens beyond ADT, in combinations that include chemotherapy, radiosensitizing agents, immunotherapy and surgery for the treatment of men with localized and locally advanced prostate cancer, and those with oligometastatic disease, in whom the low metastatic burden in particular might be treatable with these combinations. This multimodal approach is increasingly recognized as offering considerable clinical benefit, such as increased antitumour effects and improved survival. Thus, radiotherapy is becoming a key component of multimodal therapy for many stages of prostate cancer, particularly oligometastatic disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":37994554,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Point-by-Point Pulsed Field Ablation Using a Multimodality Generator and a Contact Force-Sensing Ablation Catheter: Comparison With Radiofrequency Ablation in a Remapped Chronic Swine Heart.\nPulsed field ablation (PFA) has emerged as an alternative to radiofrequency ablation. However, data on focal point-by-point PFA are scarce. The aim of this study was to compare lesion durability and collateral damage between focally delivered unipolar\/biphasic PFA versus radiofrequency in swine. Eighteen swine were randomized to low-dose PFA, high-dose PFA, and radiofrequency using a multimodality generator. Radiofrequency delivered by market-available generator served as control group. A contact force-sensing catheter was used to focally deliver PFA\/radiofrequency at the pulmonary veins and other predefined sites in the atria. Animals were remapped postprocedurally and 28 days postablation to test lesion durability followed by gross necroscopy and histology. All targeted sites were successfully ablated (contact force value, 13.9\u00b14.1 g). Follow-up remapping showed persistent pulmonary vein isolation in all animals (100%) with lesion durability at nonpulmonary vein sites proven in most (98%). Regardless of the energy source used, the lesion size was similar across the study groups. Transmurality was achieved in 95% of targeted sites and 100% at pulmonary veins. On histology, PFA animals showed more mature scar formation than their radiofrequency counterpart without myocardial necrosis or inflammation. Finally, no sign of collateral damage was observed in any of the groups. In a randomized preclinical study, focally delivered unipolar\/biphasic PFA guided by contact force values was associated with durable lesions on chronic remapping and with mature scar formation on histology without signs of collateral injury on necroscopy. Further studies are needed to investigate the long-term feasibility of this new approach to atrial fibrillation treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":22940634,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"A novel mutation in the interleukin-1 receptor antagonist associated with intrauterine disease onset.\nDeficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":29211039,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Association of Social Support and Medication Adherence in Chinese Patients with Type 2 Diabetes Mellitus.\nThe prevalence of diabetes is steadily increasing in China. When diabetes is uncontrolled, it generates dire consequences for health and well-being. Numerous studies have shown that health outcomes were associated with social support and medication adherence. Previous study confirmed that social support was associated with medication adherence in patients with heart failure, HIV diseases, and first-episode psychosis. However, the relationship between social support and medication adherence in patients with type 2 diabetes mellitus (T2DM) is remains unclear. This study aims to examine whether social support is associated with medication adherence in patients with T2DM. This study was conducted in the First Affiliated Hospital of the General Hospital of the People's Liberation Army (PLA). In Beijing, a systematic random sample of 412 patients with T2DM over 18 years was recruited at baseline, and demographic characteristics, clinical data and their assessment of social support were collected from medical records and self-reported questionnaires. 330 of these patients completed a self-report measure of medication adherence at the sixth month after baseline data collection. Regression analysis showed that social support presented a positive effect on medication adherence, additionally, support utilization and the subscale of social support exhibited a significantly strong influence on medication adherence in patients with T2DM. Although medication adherence was influenced by multiple factors, this finding confirmed that social support must be recognized as a core element in interventions aimed at improving in the management of patients with T2DM.","subset":"pubmed_abstract"} +{"meta":{"pmid":17087758,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":13}}},"text":"Reducing long-term remedial costs by transport modeling optimization.\nThe Department of Defense (DoD) Environmental Security Technology Certification Program and the Environmental Protection Agency sponsored a project to evaluate the benefits and utility of contaminant transport simulation-optimization algorithms against traditional (trial and error) modeling approaches. Three pump-and-treat facilities operated by the DoD were selected for inclusion in the project. Three optimization formulations were developed for each facility and solved independently by three modeling teams (two using simulation-optimization algorithms and one applying trial-and-error methods). The results clearly indicate that simulation-optimization methods are able to search a wider range of well locations and flow rates and identify better solutions than current trial-and-error approaches. The solutions found were 5% to 50% better than those obtained using trial-and-error (measured using optimal objective function values), with an average improvement of approximately 20%. This translated into potential savings ranging from 600,000 dollars to 10,000,000 dollars for the three sites. In nearly all cases, the cost savings easily outweighed the costs of the optimization. To reduce computational requirements, in some cases the simulation-optimization groups applied multiple mathematical algorithms, solved a series of modified subproblems, and\/or fit \"meta-models\" such as neural networks or regression models to replace time-consuming simulation models in the optimization algorithm. The optimal solutions did not account for the uncertainties inherent in the modeling process. This project illustrates that transport simulation-optimization techniques are practical for real problems. However, applying the techniques in an efficient manner requires expertise and should involve iterative modification to the formulations based on interim results.","subset":"pubmed_abstract"} +{"meta":{"pmid":16959197,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-31":1,"2021-17":1,"2021-04":1,"2019-43":1,"2019-18":1,"2018-47":1,"2018-05":1,"2017-30":1,"2017-17":1,"2023-50":1,"2024-22":1}}},"text":"The influence of perceptual speed regulation on speed perception, choice, and control: tunnel wall characteristics and influences.\nThe present work sought to determine if the type of visual pattern and presence of texture applied to transportation tunnel walls differentially affected driving performance. Choice of speed and speed control were measured with 32 participants who drove through a simulated transportation tunnel environment. Participants experienced three visual patterns consisting of vertical segments that decreased, increased, and remained a constant width throughout the length of the tunnel. Participants also drove a baseline control condition in which no visual pattern was present. Each of these conditions was presented either with or without a homogenous texture. When compared to the baseline condition, results indicated drivers gradually decreased speed when exposed to the decreasing width visual pattern and increased speed with the increasing width visual pattern. The presence of texture served to attenuate overall driving speed. Results suggest drivers' perception of speed and their subsequent response to such perceptions were modified by the visual pattern and texture expressed on the tunnel wall. The evident speed control opportunities afforded to the traffic engineer are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23453861,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2022-49":1,"2022-40":1,"2022-27":1,"2021-49":1,"2021-31":2,"2021-17":1,"2021-04":1,"2020-34":2,"2023-23":1,"2024-10":1}}},"text":"Systematic review of hypofractionated radiation therapy for prostate cancer.\nProstate cancer is the second most prevalent solid tumor diagnosed in men in the United States and Western Europe. Conventionally fractionated external beam radiation therapy (1.8-2.0 Gy\/fraction) is an established treatment modality for men in all disease risk groups. Emerging evidence from experimental and clinical studies suggests that the \u03b1\/\u03b2 ratio for prostate cancer may be as low as 1.5 Gy, which has prompted investigators around the world to explore moderately hypofractionated radiation therapy (2.1-3.5 Gy\/fraction). We review the impetus behind moderate hypofractionation and the current clinical evidence supporting moderate hypofractionated radiation therapy for prostate cancer. Although hypofractionated radiation therapy has many theoretical advantages, there is no clear evidence from prospective, randomized, controlled trials showing that hypofractionated schedules have improved outcomes or lower toxicity than conventionally fractionated regimens. Currently, hypofractionated schedules should only be used in the context of clinical trials. High dose rate brachytherapy and stereotactic body radiation therapy (fraction size 3.5 Gy and greater) are alternative approaches to hypofractionation, but are beyond the scope of this report.","subset":"pubmed_abstract"} +{"meta":{"pmid":22661222,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":15}}},"text":"P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells.\nThe P2X7 purinergic receptor is an ATP-gated cation channel with an emerging role in neoplasia. In this study we demonstrate that the human KG-1 cell line, a model of acute myelogenous leukaemia, expresses functional P2X7. RT-PCR and immunochemical techniques demonstrated the presence of P2X7 mRNA and protein respectively in KG-l cells, as well as in positive control multiple myeloma RPMI 8226 cells. Flow cytometric measurements demonstrated that ATP induced ethidium(+) uptake into KG-l cells suspended in sucrose medium (EC(50) of \u2248 3 \u03bcM), but not into cells in NaCl medium. In contrast, ATP induced ethidium(+) uptake into RPMI 8226 cells suspended in either sucrose or NaCl medium (EC(50) of \u2248 3 or \u2248 99 \u03bcM, respectively), as well as into RPMI 8226 cells in KCl medium (EC(50) of \u2248 18 \u03bcM). BzATP and to a lesser extent ATP\u03b3S and \u03b1\u03b2-methylene ATP, but not ADP or UTP, also induced ethidium(+) uptake into KG-1 cells. ATP-induced ethidium(+) uptake was completely impaired by the P2X7 antagonists, AZ10606120 and A-438079. ATP-induced ethidium(+) uptake was also impaired by probenecid but not by carbenoxolone, both pannexin-1 antagonists. ATP induced YO-PRO-1(2+) and propidium(2+) uptake into KG-1 cells. Finally, sequencing of full-length P2X7 cDNA identified several single nucleotide polymorphisms (SNPs) in KG-1 cells including H155Y, A348T, T357S and Q460R. RPMI 8226 cells contained A348T, A433V and H521Q SNPs. In conclusion, the KG-1 cell line expresses functional P2X7. This cell line may help elucidate the signalling pathways involved in P2X7-induced survival and invasiveness of myeloid leukaemic cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":22201680,"dup_signals":{"dup_doc_count":35,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":11,"2013-48":1,"unknown":21}}},"text":"Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice.\nIn the CNS, the hypothalamic arcuate nucleus (ARN) energy-balance circuit plays a key role in regulating body weight. Recent studies have shown that neurogenesis occurs in the adult hypothalamus, revealing that the ARN energy-balance circuit is more plastic than originally believed. Changes in diet result in altered gene expression and neuronal activity in the ARN, some of which may reflect hypothalamic plasticity. To explore this possibility, we examined the turnover of hypothalamic neurons in mice with obesity secondary to either high-fat diet (HFD) consumption or leptin deficiency. We found substantial turnover of neurons in the ARN that resulted in ongoing cellular remodeling. Feeding mice HFD suppressed neurogenesis, as demonstrated by the observation that these mice both generated fewer new neurons and retained more old neurons. This suppression of neuronal turnover was associated with increased apoptosis of newborn neurons. Leptin-deficient mice also generated fewer new neurons, an observation that was explained in part by a loss of hypothalamic neural stem cells. These data demonstrate that there is substantial postnatal turnover of the arcuate neuronal circuitry in the mouse and reveal the unexpected capacity of diet and leptin deficiency to inhibit this neuronal remodeling. This insight has important implications for our understanding of nutritional regulation of energy balance and brain function.","subset":"pubmed_abstract"} +{"meta":{"pmid":23403183,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Colorful brains: 14 years of display practice in functional neuroimaging.\nNeuroimaging results are typically graphically rendered and color-coded, which influences the process of knowledge generation within neuroscience as well as the public perception of brain research. Analyzing these issues requires empirical information on the display practice in neuroimaging. In our study we evaluated more than 9000 functional images (fMRI and PET) published between 1996 and 2009 with respect to the use of color, image structure, image production software and other factors that may determine the display practice. We demonstrate a variety of display styles despite a remarkable dominance of few image production sites and software systems, outline some tendencies of standardization, and identify shortcomings with respect to color scale explication in neuroimages. We discuss the importance of the finding for knowledge production in neuroimaging, and we make suggestions to improve the display practice in neuroimaging, especially on regimes of color coding.","subset":"pubmed_abstract"} +{"meta":{"pmid":27004726,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-30":1,"unknown":18}}},"text":"A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).\nThe standard 6-month four-drug regimen for the treatment of drug-sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II\/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development.","subset":"pubmed_abstract"} +{"meta":{"pmid":30093596,"dup_signals":{"dup_doc_count":11}},"text":"Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals.\nMammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species' blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors' lipid metabolism and\/or bloodstream oxidative environment affecting PON1's role in fatty acid oxidation. PON1 loss also eliminates marine mammals' main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.","subset":"pubmed_abstract"} +{"meta":{"pmid":25533678,"dup_signals":{"dup_doc_count":17,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2019-35":1,"2019-04":2,"2018-51":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-34":1,"2017-26":1,"2019-43":1}}},"text":"The use of skill tests to predict status in junior Australian football.\nThis study examined whether skill tests were predictive of status in junior Australian football. Players were recruited from the 2013 under 18 (U18) West Australian Football League competition and classified into two groups: elite (state U18 squad representative; n = 25; 17.9 \u00b1 0.5 years) and subelite (nonstate U18 squad representative; n = 25; 17.3 \u00b1 0.6 years). Both groups completed the Australian football kicking (AFK) and Australian football handballing (AFHB) tests, assessing kicking accuracy\/ball speed and handballing accuracy on dominant and nondominant sides. A multivariate analysis of variance (MANOVA) modelled the main effect of \"status\", whilst logistic regression models were built for the predictive analysis using the same test parameters. Between-group differences were noted across all parameters, with the combination of kicking accuracy and ball speed on the dominant and nondominant sides being the best predictor of status for the AFK test (wi = 0.25, AUC = 89.4%) and the combination of accuracy on the dominant and nondominant sides being the best predictor of status for the AFHB test (wi = 0.80, AUC = 88.4%). The AFK and AFHB tests are predictive of status, suggesting that their use is warranted as a means of talent identification in junior Australian football.","subset":"pubmed_abstract"} +{"meta":{"pmid":20577213,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-10":1,"2013-20":1,"2024-18":1,"unknown":10}}},"text":"Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus.\nLymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":24205592,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Fabrication of biomolecules self-assembled on Au nanodot array for bioelectronic device.\nIn the present study, an nano-platform composed of Au nanodot arrays on which biomolecules could be self-assembled was developed and investigated for a stable bioelectronic device platform. Au nanodot pattern was fabricated using a nanoporous alumina template. Two different biomolecules, a cytochrome c and a single strand DNA (ssDNA), were immobilized on the Au nanodot arrays. Cytochorme c and single stranded DNA could be immobilized on the Au nanodot using the chemical linker 11-MUA and thiol-modification by covalent bonding, respectively. The atomic structure of the fabricated nano-platform device was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The electrical conductivity of biomolecules immobilized on the Au nanodot arrays was confirmed by scanning tunneling spectroscopy (STS). To investigate the activity of biomolecule-immobilized Au-nano dot array, the cyclic voltammetry was carried out. This proposed nano-platform device, which is composed of biomolecules, can be used for the construction of a novel bioelectronic device.","subset":"pubmed_abstract"} +{"meta":{"pmid":22345652,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"Production of autoantibodies against citrullinated antigens\/peptides by human B cells.\nAutoantibodies against citrullinated protein Ags (ACPA) are associated with the development of rheumatoid arthritis (RA). This immune response against citrullinated protein Ags, which is thought to be facilitated by certain MHC HLA-DR alleles, is highly specific for this disease and has been speculated to be involved in the pathogenesis. We have previously studied cultures of B cells for the production of Abs against HLA Ags. The aim of the current study was to examine the role of B cells in the production of ACPA in patients with RA. Peripheral blood B cells from RA patients and healthy people were cultured with EL4-B5, a murine cell line expressing human CD40L, and with T cell factors to stimulate the in vitro production of Abs by B cells isolated from peripheral blood. ACPA were produced by cultured B cells from RA patients, as determined by reactivity to cyclic citrullinated peptide (CCP). The results showed that 22% of the healthy persons tested also had B cells that could produce ACPA. Patients with HLA-DR alleles carrying the RA-associated shared epitope appeared to have more B cells with autoimmune potential for CCP than those without such HLA alleles (odds ratio 8.1, p = 0.001). In healthy individuals, anti-CCP-producing B cells were also observed more frequently if the RA-associated MHC genes were present (odds ratio 8.0, p = 0.01). Analysis of B cells in cultures may shed light on the interaction of genetic and environmental factors in the development of RA.","subset":"pubmed_abstract"} +{"meta":{"pmid":28864475,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":18}}},"text":"Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse.\nThe biological significance of C5a receptor [(C5aR)2\/C5L2], a seven-transmembrane receptor binding C5a and C5adesArg, remains ill-defined. Specific ligation of C5aR2 inhibits C5a-induced ERK1\/2 activation, strengthening the view that C5aR2 regulates C5aR1-mediated effector functions. Although C5aR2 and C5aR1 are often coexpressed, a detailed picture of C5aR2 expression in murine cells and tissues is still lacking. To close this gap, we generated a floxed tandem dye (td)Tomato-C5aR2 knock-in mouse that we used to track C5aR2 expression in tissue-residing and circulating immune cells. We found the strongest C5aR2 expression in the brain, bone marrow, and airways. All myeloid-derived cells expressed C5aR2, although with different intensities. C5aR2 expression in blood and tissue neutrophils was strong and homogeneous. Specific ligation of C5aR2 in neutrophils from tdTomato-C5aR2 mice blocked C5a-driven ERK1\/2 phosphorylation, demonstrating functionality of C5aR2 in the reporter mice. In contrast to neutrophils, we found tissue-specific differences in C5aR2 expression in eosinophils, macrophages, and dendritic cell subsets. Naive and activated T cells stained negative for C5aR2, whereas B cells from different tissues homogeneously expressed C5aR2. Also, NK cell subsets in blood and spleen strongly expressed C5aR2. Activation of C5aR2 in NK cells suppressed IL-12\/IL-18-induced IFN-\u03b3 production. Intratracheal IL-33 challenge resulted in decreased C5aR2 expression in pulmonary eosinophils and monocyte-derived dendritic cells. In summary, we provide a detailed map of murine C5aR2 immune cell expression in different tissues under steady-state conditions and upon pulmonary inflammation. The C5aR2 knock-in mouse will help to reliably track and conditionally delete C5aR2 expression in experimental models of inflammation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28641299,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2021-25":1,"2021-10":1,"2020-05":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-05":1,"2017-51":1,"2017-47":1,"2021-39":1,"2024-10":1,"2024-26":1}}},"text":"Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia.\nThree human monocyte subsets are recognized with different functions in the immune system: CD14++\/CD16- classical monocytes (CM), CD14++\/CD16+ intermediate monocytes (IM) and CD14+\/CD16++ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng\/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers. After that, monocyte subset counts, activation\/differentiation status and chemokine levels were studied over 24 h. The numbers of all subsets were decreased by >95% after LPS injection. CM numbers recovered first (3- 6 h), followed by IM (6-8 h) and NCM numbers (8-24 h). Similarly, increased monocyte counts were observed first in CM (8 h), followed by IM and NCM (24 h). Monocytes did not display a clear activated phenotype (minor increase in CD11b and CD38 expression). Plasma levels of CCL2, CCL4 and CX3CL1 closely resembled the cell numbers of CM, IM and NCM, respectively. Our study provides critical insights into the earliest stages of acute inflammation and emphasizes the necessity to stain for different monocyte subsets when studying the role of monocytes in disease, as neither function nor kinetics of the subsets overlap.","subset":"pubmed_abstract"} +{"meta":{"pmid":9354805,"dup_signals":{"dup_doc_count":28,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":1,"2023-14":2,"2023-06":4,"2022-49":1,"2022-21":2,"2021-49":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":3,"2021-10":2,"2021-04":1,"2020-40":3,"2024-22":1}}},"text":"Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group.\nThe IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis. The mode of action of IDDM2 is complicated, however, by parent-of-origin effects and possible allelic heterogeneity within the two defined allele classes. We have now analysed transmission of specific VNTR alleles in 1,316 families and demonstrate that a particular class I allele does not predispose to disease when paternally inherited, suggestive of polymorphic imprinting. But this paternal effect is observed only when the father's untransmitted allele is a class III. This allelic interaction is reminiscent of epigenetic phenomena observed in plants (for example, paramutation; ref. 17) and in yeast (for example, trans-inactivation; ref. 18). If untransmitted chromosomes can have functional effects on the biological properties of transmitted chromosomes, the implications for human genetics and disease are potentially considerable.","subset":"pubmed_abstract"} +{"meta":{"pmid":15362375,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"An abnormal cervicovaginal cytology smear in uterine carcinosarcoma is an adverse prognostic sign: analysis of 25 cases.\nCarcinosarcoma of the uterus has been poorly characterized on cervicovaginal (Pap) smears, and we examine whether they effectively screen for carcinosarcoma and whether an abnormal Pap smear result has any clinical importance. Twenty-five patients with histologically confirmed carcinosarcoma had a conventional Pap smear shortly before diagnosis. Eleven smears (44%) originally were read as abnormal (malignant or atypical), and 4 additional cases were read as abnormal on retrospective review (15\/25 [60%]). All malignant elements were epithelial, and 2 cases (8%) had atypical spindle cells, but no diagnostic sarcoma. Cervical involvement was the only histologic parameter correlating with an abnormal Pap smear result (P = .04). Univariate analysis found stage III or IV disease was an adverse prognostic sign compared with stage I or II disease (mean survival, 8 vs 36 months, respectively; P = .001), and multivariate analysis indicated that an abnormal Pap smear result correlated with worse survival (P = .023). The conventional Pap smear is insensitive (60%) for detecting carcinosarcoma, but when the result is abnormal, the Pap is an important stage-independent adverse prognosticator.","subset":"pubmed_abstract"} +{"meta":{"pmid":27208304,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":2,"2019-47":1,"2018-26":1,"2018-09":1,"2017-43":1,"2016-40":1,"2020-34":1}}},"text":"Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases.\nPrevious studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control.","subset":"pubmed_abstract"} +{"meta":{"pmid":11230484,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Espa\u00f1ol de Linfomas\/Transplante Aut\u00f3logo de M\u00e9dula Osea Spanish Cooperative Group.\nTo analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). Detailed records from the Grupo Espa\u00f1ol de Linfomas\/Transplante Aut\u00f3logo de M\u00e9dula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.","subset":"pubmed_abstract"} +{"meta":{"pmid":30485316,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-27":2,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-05":1,"2019-30":1}}},"text":"Biomechanics of the peafowl's crest reveals frequencies tuned to social displays.\nFeathers act as vibrotactile sensors that can detect mechanical stimuli during avian flight and tactile navigation, suggesting that they may also detect stimuli during social displays. In this study, we present the first measurements of the biomechanical properties of the feather crests found on the heads of birds, with an emphasis on those from the Indian peafowl (Pavo cristatus). We show that in peafowl these crest feathers are coupled to filoplumes, small feathers known to function as mechanosensors. We also determined that airborne stimuli with the frequencies used during peafowl courtship and social displays couple efficiently via resonance to the vibrational response of their feather crests. Specifically, vibrational measurements showed that although different types of feathers have a wide range of fundamental resonant frequencies, peafowl crests are driven near-optimally by the shaking frequencies used by peacocks performing train-rattling displays. Peafowl crests were also driven to vibrate near resonance in a playback experiment that mimicked the effect of these mechanical sounds in the acoustic very near-field, reproducing the way peafowl displays are experienced at distances \u2264 1.5m in vivo. When peacock wing-shaking courtship behaviour was simulated in the laboratory, the resulting airflow excited measurable vibrations of crest feathers. These results demonstrate that peafowl crests have mechanical properties that allow them to respond to airborne stimuli at the frequencies typical of this species' social displays. This suggests a new hypothesis that mechanosensory stimuli could complement acoustic and visual perception and\/or proprioception of social displays in peafowl and other bird species. We suggest behavioral studies to explore these ideas and their functional implications.","subset":"pubmed_abstract"} +{"meta":{"pmid":29371905,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":13}}},"text":"Clinical Features and Treatment of Fibrous Histiocytomas of the Tongue: A Systematic Review.\nIntroduction Benign fibrous histiocytomas are common lesions of the skin that rarely affect the tongue. Such cases are available in the literature exclusively as case reports. Similarly, malignant fibrous histiocytoma, now classified as undifferentiated pleomorphic sarcoma, is exceedingly rare in the tongue and not fully understood. Objectives This study systematically reviews the available literature discussing the clinical and pathological features of malignant and benign fibrous histiocytomas. Data Synthesis A total of 20 cases were included in this review. Patient-level data were extracted from cases to include clinical presentation, workup, treatment, and outcome. Conclusion Benign fibrous histiocytomas are consistent in clinical and histopathologic presentation. Surgical treatment provides excellent outcome, with no recurrence in all excised cases. Malignant tumors have a more aggressive clinical and pathological presentation. Surgical treatment with possible adjuvant radiotherapy resulted in recurrence in 40% of cases (follow-up of 24 months), and death due to disease in 47% of patients (follow-up of 19 months).","subset":"pubmed_abstract"} +{"meta":{"pmid":11826999,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-14":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-21":2,"2021-10":1,"2021-04":1,"2020-50":1,"2020-24":1,"2023-50":1}}},"text":"Corneal shape change during accommodation.\nTo investigate whether accommodation induces any changes in central corneal curvature. Shape changes were measured on 14 subjects using a keratometer modified to enable a change in focus to occur without a change in vergence. All subjects were emmetropic and their ages ranged from approximately 20 to 28 years. In 11 of the 14 subjects a difference in central corneal curvature, of around 0.4 D in at least one principal meridian, was found when focus was changed between distant and near targets. In 9 subjects the curvature was greater for near focus in at least one meridian. In 5 subjects the change in one meridian was opposite in effect to what would be expected, i.e. the curvature was greater at distance than at near. The study suggests that accommodation may have some effect on corneal shape.","subset":"pubmed_abstract"} +{"meta":{"pmid":27427980,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Mapping Quantitative Trait Loci of Resistance to Tomato Spotted Wilt Virus and Leaf Spots in a Recombinant Inbred Line Population of Peanut (Arachis hypogaea L.) from SunOleic 97R and NC94022.\nPeanut is vulnerable to a range of diseases, such as Tomato spotted wilt virus (TSWV) and leaf spots which will cause significant yield loss. The most sustainable, economical and eco-friendly solution for managing peanut diseases is development of improved cultivars with high level of resistance. We developed a recombinant inbred line population from the cross between SunOleic 97R and NC94022, named as the S-population. An improved genetic linkage map was developed for the S-population with 248 marker loci and a marker density of 5.7 cM\/loci. This genetic map was also compared with the physical map of diploid progenitors of tetraploid peanut, resulting in an overall co-linearity of about 60% with the average co-linearity of 68% for the A sub-genome and 47% for the B sub-genome. The analysis using the improved genetic map and multi-season (2010-2013) phenotypic data resulted in the identification of 48 quantitative trait loci (QTLs) with phenotypic variance explained (PVE) from 3.88 to 29.14%. Of the 48 QTLs, six QTLs were identified for resistance to TSWV, 22 QTLs for early leaf spot (ELS) and 20 QTLs for late leaf spot (LLS), which included four, six, and six major QTLs (PVE larger than 10%) for each disease, respectively. A total of six major genomic regions (MGR) were found to have QTLs controlling more than one disease resistance. The identified QTLs and resistance gene-rich MGRs will facilitate further discovery of resistance genes and development of molecular markers for these important diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":16224524,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2015-18":1,"unknown":7}}},"text":"[Association between LMP2\/LMP7 gene polymorphism and the infection of hepatitis B virus].\nTo elucidate whether the antigen-processing gene (LMP2\/LMP7) polymorphisms could influence the infection of hepatitis B virus. Genomic DNA of 176 patients infected with HBV and 208 healthy volunteers were extracted from the peripheral blood leukocytes. Polymorphisms of LMP genes in HBV patients were determined by polymerase chain reaction-restriction fragment length polymorphism (RFLP), the controls by DNA sequencing. We used the software PHASE1.0 to construct the haplotypes of every individual. At last the unconditional Logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted by gender and age. The distributions of LMP2 genes between cases and controls did not differ. However, LMP7 gene frequency in patients was higher than that in controls [odds ratio 2.11(95% confidence interval 1.36-3.26); 2.66 (95% confidence interval 1.17-6.02), heterogenous or homologous respectively]. Similarly, we found the haplotype combinated by R-K had a significant difference in two groups [odds ratio 1.81 (95% confidence interval 1.19-2.76)]. These findings suggest that polymorphisms of LMP2\/LMP7 gene is one of the important host factors which independently affect on the infection of hepatitis B virus.","subset":"pubmed_abstract"} +{"meta":{"pmid":19152538,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Tonic activity level in the right prefrontal cortex predicts individuals' risk taking.\nHuman risk taking is characterized by a large amount of individual heterogeneity. In this study, we applied resting-state electroencephalography, which captures stable individual differences in neural activity, before subjects performed a risk-taking task. Using a source-localization technique, we found that the baseline cortical activity in the right prefrontal cortex predicts individual risk-taking behavior. Individuals with higher baseline cortical activity in this brain area display more risk aversion than do other individuals. This finding demonstrates that neural characteristics that are stable over time can predict a highly complex behavior such as risk-taking behavior and furthermore suggests that hypoactivity in the right prefrontal cortex might serve as a dispositional indicator of lower regulatory abilities, which is expressed in greater risk-taking behavior.","subset":"pubmed_abstract"} +{"meta":{"pmid":2515249,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"Isolation of plasmid DNA sequences that complement Rhodobacter sphaeroides mutants deficient in the capacity for CO2-dependent growth.\nMutants deficient in the proper regulation and derepression of ribulose-1.5-bisphosphate carboxylase oxygenase (RuBPC\/O) in Rhodobacter sphaeroides were isolated by ethyl methanesulphonate (EMS) and Tn5 mutagenesis of a recA parental strain. Mutants were identified by their ability to grow under conditions where the organism requires basal levels of RuBPC C\/O for growth yet fail to grow under conditions which require derepression of the enzyme (Aut-). The newly isolated Aut- mutants exhibited phenotypes distinguishable from the previously isolated Aut- mutant, strain KW25\/11. Rocket immunoelectrophoretic examination of RuBPC\/O levels revealed marked variance in the ability of mutants to derepress form I and form II RuBPC\/O in the absence of exogenous carbon. Evidence that some of the mutants possessed different mutations was substantiated by complementation of the EMS-generated mutants by entirely different genes isolated from a genomic library of R. sphaeroides constructed in the broad-host-range cosmid vector pVK102. Southern hybridization analysis of the complementing library isolates showed the complementing genes to be normally carried on the endogenous plasmids of R. sphaeroides. The gene complementing mutant strain KW25\/11 was mapped by Tn5 insertional inactivation and the complementing region found to reside on a 1.5 kb PstJ. BamHI fragment. Complemented strains were unable to match wild-type levels of RuBPC\/O under conditions requiring derepression of the enzyme, except for mutant strain EMS45. The Aut- phenotype, represented by the mutants isolated in this study, stems from a deficiency in some aspect of photoautotrophic growth.","subset":"pubmed_abstract"} +{"meta":{"pmid":38078329,"dup_signals":{"dup_doc_count":15,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":4,"2024-18":3,"2024-10":1,"2024-30":1,"unknown":2}}},"text":"Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.\nStatus epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1\u03b2 signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1\u03b2 converting enzyme (ICE)\/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.","subset":"pubmed_abstract"} +{"meta":{"pmid":17971849,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response.\nPoly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis.","subset":"pubmed_abstract"} +{"meta":{"pmid":11903920,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Altered periodic rectal motor activity: a mechanism for slow transit constipation.\nThe pathophysiology of slow transit constipation is poorly understood. Both decreased and increased distal colonic motility have been reported. In healthy humans, a 3 cycles per minute (cpm), periodic rectal motor activity (PRMA) has been described. Our aim was to investigate the characteristics of PRMA and to assess its role in the pathogenesis of constipation. A six-sensor solid-state probe was placed with the tip sensor in the mid-transverse colon, without sedation, and prolonged colonic motility was recorded in nine patients with slow transit constipation (1M, 8F) and in 11 healthy subjects (3M, 8F). Subjects were free to ambulate. We examined the frequency, nocturnal vs. diurnal variation, and characteristics of PRMA, and its relationship to proximal colonic motility. All subjects showed PRMA. The rhythm was similar (2.5-4 cpm) in both groups. However, constipated patients exhibited a greater (P < 0.001) number of PRMA cycles than controls. The duration of each cycle and amplitude of pressure waves during PRMA were also greater (P < 0.05) at night in patients compared with controls. In patients, 40% of PRMA cycles were associated with a proximal colonic motor event compared with 81% in controls (P < 0.02). The area under the curve of all colonic pressure waves and incidence of specialized propagating pressure waves was lower (P < 0.05) in patients during daytime. When compared with controls, constipated patients exhibited reduced daytime colonic pressure waves and a higher frequency of PRMA. Most of the PRMA was unrelated to proximal colonic activity in constipated patients in contrast with findings in control patients. In addition to decreased colonic motility, this excessive and unco-ordinated phasic rectal activity may further impede stool transport and contribute to the pathogenesis of slow transit constipation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21524567,"dup_signals":{"dup_doc_count":37,"dup_dump_count":31,"dup_details":{"curated_sources":1,"2022-49":1,"2022-27":1,"2021-49":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-40":1,"2020-34":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-23":1}}},"text":"Incomplete reporting of recruitment information in breast cancer trials published between 2003 and 2008.\nTo review the reporting of key items of recruitment information in trial reports and estimate the number needed to screen to recruit one additional participant. Review of breast cancer trials published in the years 2003-2005, 2007, and 2008. The search identified 1,570 potentially eligible studies. After a random selection of 20% from each year and checking against inclusion criteria, a total of 207 studies were included in the review. Some items of information were well reported, such as the number included in the analysis. Sample size calculations were often not presented, but reporting is slowly improving. Who recruits participants and how many individuals were screened are often not reported. The median number needed to screen to recruit one additional participant was two (range, 1-593). Without reporting the when, where, by whom, and how many of recruitment, trialists deny readers part of the contextual description they need to judge whether a trial's results are applicable to their own situation. Trialists and journal editors need to be more diligent in following the reporting recommendations of the Consolidated Standards of Reporting Trials statement.","subset":"pubmed_abstract"} +{"meta":{"pmid":24787207,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Magneto-optical Faraday rotation of semiconductor nanoparticles embedded in dielectric matrices.\nFaraday rotation has been studied for CdS, CdTe, and CdS:Mn semiconductor nanoparticles synthesized by colloidal chemistry methods. Additionally these materials were prepared in a form of semiconductor nanoparticles embedded in polyvinyl alcohol films. Transmission electron microscopy and atomic force microscopy analyses served as confirmation of nanocrystallinity and estimation of the average size of the nanoparticles. Spectral dependence of the Faraday rotation for the studied nanocrystals and nanocomposites is correlated with a blueshift of the absorption edge due to the confinement effect in zero-dimensional structures. Faraday rotation spectra and their temperature behavior in Mn-doped nanocrystals demonstrates peculiarities, which are associated with s, p-d exchange interaction between Mn\u00b2\u207a ions and band carriers in diluted magnetic semiconductor nanostructures.","subset":"pubmed_abstract"} +{"meta":{"pmid":27046166,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Stability and change in callous-unemotional traits: Longitudinal associations with potential individual and contextual risk and protective factors.\nThis longitudinal study examines developmental heterogeneity in callous-unemotional (CU) traits in a large sample of school-age children in Cyprus. Latent Class Growth Analysis revealed 4 trajectory groups of CU traits across 3 time points: stable high, increasing, decreasing, and low. Findings suggested that children in the stable high CU trajectory were more likely to (a) exhibit high and stable levels of conduct problems, attention-deficit\/hyperactivity disorder symptoms, impulsivity and narcissism, (b) experience low parental involvement and high parental distress, (c) report low peer support and school connectedness, and (d) score lower on academic performance, executive functioning, social competence, and self-regulation compared to children with low, decreasing, and increasing CU traits. These findings were verified by both parent and child reports. Repeated analysis of variance suggested that increases and decreases in CU traits were associated with similar changes in conduct problems, narcissism, impulsivity, and maternal involvement. Further, children in the decreasing trajectory group were not differentiated from children in the low risk group on measures of executive functioning, academic performance, school connectedness, and peer social support at the last wave of measurement. These findings provide evidence for the importance of taking longitudinal change into account for understanding developmental heterogeneity in CU traits and the association of these traits with possible protective (e.g., stable high maternal involvement) and risk (e.g., decreases in maternal involvement and increases in conduct problems, impulsivity and narcissism) variables. (PsycINFO Database Record","subset":"pubmed_abstract"} +{"meta":{"pmid":23993021,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"Challenges to the implementation of health sector decentralization in Tanzania: experiences from Kongwa district council.\nDuring the 1990s, the government of Tanzania introduced the decentralization by devolution (D by D) approach involving the transfer of functions, power and authority from the centre to the local government authorities (LGAs) to improve the delivery of public goods and services, including health services. This article examines and documents the experiences facing the implementation of decentralization of health services from the perspective of national and district officials. The study adopted a qualitative approach, and data were collected using semi-structured interviews and were analysed for themes and patterns. The results showed several benefits of decentralization, including increased autonomy in local resource mobilization and utilization, an enhanced bottom-up planning approach, increased health workers' accountability and reduction of bureaucratic procedures in decision making. The findings also revealed several challenges which hinder the effective functioning of decentralization. These include inadequate funding, untimely disbursement of funds from the central government, insufficient and unqualified personnel, lack of community participation in planning and political interference. The article concludes that the central government needs to adhere to the principles that established the local authorities and grant more autonomy to them, offer special incentives to staff working in the rural areas and create the capacity for local key actors to participate effectively in the planning process.","subset":"pubmed_abstract"} +{"meta":{"pmid":19404958,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study.\nTo determine the associations between serum levels of vitamin D, sunlight exposure, and knee cartilage loss cross-sectionally and longitudinally in older adults. A total of 880 randomly selected subjects (mean age 61 years [range 51-79 years], 50% women) were studied at baseline, and 353 of these subjects were studied 2.9 years later. Serum levels of 25-hydroxyvitamin D (25[OH]D) were assessed by radioimmunoassay, and sunlight exposure was assessed by questionnaire. T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine knee cartilage volume and defects. Knee radiographic osteoarthritis (OA) and knee pain were also assessed. The mean 25(OH)D serum level was 52.8 nmoles\/liter at baseline (range 13-119 nmoles\/liter). Winter sunlight exposure and serum 25(OH)D level were both positively associated with medial and lateral tibial cartilage volume, and a serum 25(OH)D level<50 nmoles\/liter was associated with increased medial tibiofemoral joint space narrowing (all P<0.05). Longitudinally, baseline serum 25(OH)D level predicted change in both medial and lateral tibial cartilage volume (beta=+0.04% per annum per nmole\/liter for both; P<0.05), and change in serum 25(OH)D level was positively associated with change in medial tibial cartilage volume. These associations were consistent in subjects with radiographic OA and knee pain and\/or in women, but not in men or in subjects without radiographic OA or knee pain. Sunlight exposure and serum 25(OH)D levels are both associated with decreased knee cartilage loss (assessed by radiograph or MRI). This is best observed using the whole range of 25(OH)D levels rather than predefined cut points and implies that achieving vitamin D sufficiency may prevent and\/or retard cartilage loss in knee OA.","subset":"pubmed_abstract"} +{"meta":{"pmid":10618103,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Prevalence of Campylobacter, Arcobacter, Helicobacter, and Sutterella spp. in human fecal samples as estimated by a reevaluation of isolation methods for Campylobacters.\nThe aims of this study were to investigate the prevalence of campylobacteria including Campylobacter jejuni subsp. jejuni (C. jejuni) and Campylobacter coli in human clinical samples and in samples from healthy individuals and to reevaluate the efficacies of conventional selective methods for isolation of Campylobacter spp. Two charcoal-based selective media, modified charcoal cefoperazone deoxycholate agar (mCCDA) and cefoperazone-amphotericin-teicoplanin (CAT) agar, were compared with Skirrow's blood-based medium and with a filter method (filter) applied to a yeast-enriched blood agar. A total of 1,376 specimens were tested on all four media, and the percentages of thermophilic Campylobacter-positive specimens isolated on Skirrow's medium, filters, CAT agar, and mCCDA were 82, 83, 85, and 95%, respectively. When additional samples were processed with the three selective media, mCCDA recovered significantly more thermophilic Campylobacter spp. than Skirrow's medium (P = 0.0034). No significant difference between Skirrow's medium and CAT agar was observed in this study. Another six taxa were identified, namely, Campylobacter concisus, Campylobacter curvus-like bacteria, Arcobacter butzleri, Arcobacter cryaerophilus, Helicobacter cinaedi, and Sutterella wadsworthensis. Most of these strains were isolated after 5 to 6 days of incubation by use of the filter technique. This paper provides evidence for the existence of S. wadsworthensis in human feces from clinical cases of gastrointestinal disorders and in feces from a healthy individual. Furthermore, C. concisus was isolated from a large number of diarrheal cases, particularly those at the extremes of age, but was additionally isolated from the feces of healthy people. Further investigations to establish the role of C. concisus and S. wadsworthensis in enteric disease is needed. We conclude that a range of campylobacteria may cause infections in Denmark.","subset":"pubmed_abstract"} +{"meta":{"pmid":11005744,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Rehabilitation of stroke patients with apraxia: the role of additional cognitive and motor impairments.\nThe present study investigated which additional cognitive and motor impairments were present in stroke patients with apraxia and which of these factors influenced the effects of treatment. A group of 33 patients with apraxia were treated according to the guidelines of a therapy programme based on teaching patients strategies to compensate for the presence of apraxia. Patients were treated at occupational therapy departments in general hospitals, rehabilitation centres and nursing homes. The outcome of the strategy training was studied in a pre-post test design; measurements were conducted at baseline and after 12 weeks of therapy. The pretreatment scores of the patients with apraxia were compared to normscores and scores of a control group of patients without apraxia (n = 36) to investigate which impairments are present. The following variables were analysed in order to determine which factors influence outcome: additional neuropsychological deficits (comprehension of language, cognitive impairments due to dementia, neglect and short term memory), level of motor functioning, severity of apraxia and performance on activities of daily living (ADL), and some relevant patient characteristics (gender, age, type of stroke, time since stroke, and location of treatment). The results showed that the presence of apraxia is associated with the presence of additional cognitive and motor impairments. The successful outcome of strategy training was not negatively influenced by cognitive comorbidity. The outcome seemed to be more prominent in patients who were more severely impaired at the start of rehabilitation in terms of the degree of motor impairments, the severity of apraxia and the initial ADL dependence. The ADL observations, however, displayed a ceiling effect, which was taken into account in discussing the results. Demographic variables, especially age, did not predict the outcome of treatment. We suggest that the effect of this training is stronger in more severely disabled patients. However, neither the presence of additional cognitive impairments nor the severity of motor problems nor old age should be an indication for refraining from treating apraxia.","subset":"pubmed_abstract"} +{"meta":{"pmid":25884299,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Amelotin: an enamel matrix protein that experienced distinct evolutionary histories in amphibians, sauropsids and mammals.\nAmelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein (SCPP) family, which originated in early vertebrates. In rodents, AMTN is expressed during the maturation stage of amelogenesis only. This expression pattern strongly differs from the spatiotemporal expression of other ameloblast-secreted SCPPs, such as the enamel matrix proteins (EMPs). Furthermore, AMTN was characterized in rodents only. In this study, we applied various approaches, including in silico screening of databases, PCRs and transcriptome sequencing to characterize AMTN sequences in sauropsids and amphibians, and compared them to available mammalian and coelacanth sequences. We showed that (i) AMTN is tooth (enamel) specific and underwent pseudogenization in toothless turtles and birds, and (ii) the AMTN structure changed during tetrapod evolution. To infer AMTN function, we studied spatiotemporal expression of AMTN during amelogenesis in a salamander and a lizard, and compared the results with available expression data from mouse. We found that AMTN is expressed throughout amelogenesis in non-mammalian tetrapods, in contrast to its expression limited to enamel maturation in rodents. Taken together our findings suggest that AMTN was primarily an EMP. Its functions were conserved in amphibians and sauropsids while a change occurred early in the mammalian lineage, modifying its expression pattern during amelogenesis and its gene structure. These changes likely led to a partial loss of AMTN function and could have a link with the emergence of prismatic enamel in mammals.","subset":"pubmed_abstract"} +{"meta":{"pmid":30096806,"dup_signals":{"dup_doc_count":21,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2023-50":4,"2023-40":1,"2023-23":4,"2023-14":1,"2022-49":2,"2024-22":3,"2024-18":1,"2024-26":1}}},"text":"Discovery of 4,5-Dihydro-1H-thieno[2',3':2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors.\nThe epidermal growth factor receptors (EGFRs), in which overexpression (known as upregulation) or overactivity have been associated with a number of cancers, has become an attractive molecular target for the treatment of selective cancers. We report here the design and synthesis of a novel series of 4,5-dihydro-1H-thieno [2',3':2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives and the screening for their inhibitory activity on the EGFR high-expressing human A549 cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). A Docking simulation was performed to fit compound 6g and gifitinib into the EGFR to determine the probable binding models, and the binding sites and modes conformation of 6g and gifitinib were exactly similar, the two compounds were stabilized by hydrogen bond interactions with MET769. Combining with the biological activity evaluation, compound 6g demonstrated the most potent inhibitory activity (IC50 = 9.68 \u00b1 1.95 \u03bcmol\u00b7L\u207b1 for A549). Conclusively, 4,5-dihydro-1H-thieno[2',3':2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives as the EGFR tyrosine kinase inhibitors were discovered, and could be used as potential lead compounds against cancer cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":24600020,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":11}}},"text":"Transpiration efficiency: new insights into an old story.\nProducing more food per unit of water has never been as important as it is at present, and the demand for water by economic sectors other than agriculture will necessarily put a great deal of pressure on a dwindling resource, leading to a call for increases in the productivity of water in agriculture. This topic has been given high priority in the research agenda for the last 30 years, but with the exception of a few specific cases, such as water-use-efficient wheat in Australia, breeding crops for water-use efficiency has yet to be accomplished. Here, we review the efforts to harness transpiration efficiency (TE); that is, the genetic component of water-use efficiency. As TE is difficult to measure, especially in the field, evaluations of TE have relied mostly on surrogate traits, although this has most likely resulted in over-dependence on the surrogates. A new lysimetric method for assessing TE gravimetrically throughout the entire cropping cycle has revealed high genetic variation in different cereals and legumes. Across species, water regimes, and a wide range of genotypes, this method has clearly established an absence of relationships between TE and total water use, which dismisses previous claims that high TE may lead to a lower production potential. More excitingly, a tight link has been found between these large differences in TE in several crops and attributes of plants that make them restrict water losses under high vapour-pressure deficits. This trait provides new insight into the genetics of TE, especially from the perspective of plant hydraulics, probably with close involvement of aquaporins, and opens new possibilities for achieving genetic gains via breeding focused on this trait. Last but not least, small amounts of water used in specific periods of the crop cycle, such as during grain filling, may be critical. We assessed the efficiency of water use at these critical stages.","subset":"pubmed_abstract"} +{"meta":{"pmid":24025704,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2016-22":1,"2016-18":1,"2016-07":1,"2015-32":1,"2015-14":1,"2014-52":1,"2014-42":3,"2016-26":1,"2013-48":1}}},"text":"Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD.\nAge-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay\u00ae Radiotherapy System, developed by Oraya\u00ae Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye-total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18\u00b0 to 34\u00b0 in 2\u00b0 increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26\u00b0 or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.","subset":"pubmed_abstract"} +{"meta":{"pmid":9336514,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Treatment of acute cholangitis due to choledocholithiasis in elderly and younger patients.\nTo evaluate management strategies for acute cholangitis in elderly patients (age, > or = 80 years). Nonrandomized control trial. A university hospital. Patients (n = 191) who underwent urgent biliary drainage for acute cholangitis due to choledocholithiasis. Thirty-seven patients were elderly, and 154 were younger (age, < 80 years). Surgical (8 elderly and 48 younger patients), percutaneous transhepatic (11 elderly and 47 younger patients), or endoscopic drainage (18 elderly and 59 younger patients). Clinical features of acute cholangitis and outcomes of biliary drainage. The elderly patients had higher incidences of septic shock or mental confusion (acute severe cholangitis)(43.2%) and concomitant diseases (81.1%) than the younger patients (25.3% and 42.9%, respectively). The elderly patients had significantly greater morbidity (37.8%) and mortality (10.8%), compared with the younger patients (16.9% and 3.2%, respectively). Mortality was 18.8% in elderly patients with severe cholangitis and 4.8% in those with nonsevere cholangitis. In the elderly patients, endoscopic drainage yielded lower morbidity (16.7%) and mortality (5.6%) than surgical (87.5% and 25.0%, respectively) and percutaneous drainage (36.4% and 9.1%, respectively). No complications occurred after endoscopic nasobiliary drainage without sphincterotomy. Elderly patients with acute cholangitis have high incidence of severe disease and concomitant medical problems. They should undergo endoscopic biliary drainage, especially nasobiliary drainage without sphincterotomy, because of its safety and effectiveness.","subset":"pubmed_abstract"} +{"meta":{"pmid":19590443,"dup_signals":{"dup_doc_count":16,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":5}}},"text":"Unilateral eosinophilic fasciitis: an under-recognized subtype?\nSymmetric skin thickening of the limbs with deep fascial inflammation is the hallmark of eosinophilic fasciitis. We describe a woman who presented with unilateral progressive skin thickening. Examination of a full thickness skin biopsy revealed an inflammatory process and fascial changes consistent with eosinophilic fasciitis. In contrast to other scleroderma mimics, eosinophilic fasciitis generally responds rapidly to glucocorticoid therapy. It is possible that unilateral eosinophilic fasciitis is under-recognized and can easily be misdiagnosed as another scleroderma variant if a full thickness biopsy is not reviewed by a dermatopathologist. Recognition of this subtype of eosinophilic fasciitis is important given the profound differences in prognosis of eosinophilic fasciitis and other scleroderma variants.","subset":"pubmed_abstract"} +{"meta":{"pmid":30845412,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effects of Oxygen Deprivation and Pythium Root Rot on Sugarcane Red Rot.\nThe effects of oxygen deprivation or poor drainage and Pythium root rot on development of red rot, caused by Colletotrichum falcatum, and spring shoot population of sugarcane were evaluated under controlled and field conditions. Detached stalks of five cultivars were exposed to low atmospheric oxygen (0.5 to 2.7%), created by enclosing stalks in sealed chambers through which humidified nitrogen gas was passed for 0, 1, or 2 weeks. Stalks were then inoculated with C. falcatum and maintained for 6 weeks with humidified air flow. Red rot severity, assessed as four disease traits, was not increased by previous oxygen deprivation. In field experiments, inoculation of stalks of three cultivars with C. falcatum before planting resulted in a reduction in shoot populations the following spring. Poor drainage resulted in an additional reduction in shoot populations developing from inoculated stalks. Soil atmospheric oxygen was reduced in the root zone below planted stalks under poor drainage conditions. However, only minor reductions in oxygen were detected in the zone of elevated rows in which planted stalks were located. The detrimental effect of poor drainage on shoot populations from inoculated stalks was alleviated by metalaxyl application. Pythium root rot, caused by Pythium arrhenomanes, reduced the initial root system and growth of shoots in greenhouse experiments. The combination of P. arrhenomanes and C. falcatum inoculation increased dead bud percentage in one of two cultivars and red rot severity for both. The results suggest that spring shoot populations developing from red rot-affected stalks exposed to poor drainage can be reduced by the combined effects of red rot and Pythium root rot.","subset":"pubmed_abstract"} +{"meta":{"pmid":16829952,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-23":1,"2019-39":1,"2019-30":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2018-05":1,"2017-51":1,"2023-50":1,"2024-26":1}}},"text":"SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production.\nHomologues of signal peptide peptidase (SPPLs) are putative aspartic proteases that may catalyse regulated intramembrane proteolysis of type II membrane-anchored signalling factors. Here, we show that four human SPPLs are each sorted to a different compartment of the secretory pathway. We demonstrate that SPPL2a and SPPL2b, which are sorted to endosomes and the plasma membrane, respectively, are functional proteases that catalyse intramembrane cleavage of tumour necrosis factor alpha (TNFalpha). The two proteases promoted the release of the TNFalpha intracellular domain, which in turn triggers expression of the pro-inflammatory cytokine interleukin-12 by activated human dendritic cells. Our study reveals a critical function for SPPL2a and SPPL2b in the regulation of innate and adaptive immunity.","subset":"pubmed_abstract"} +{"meta":{"pmid":26974430,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Effects of Group Drumming Interventions on Anxiety, Depression, Social Resilience and Inflammatory Immune Response among Mental Health Service Users.\nGrowing numbers of mental health organizations are developing community music-making interventions for service users; however, to date there has been little research into their efficacy or mechanisms of effect. This study was an exploratory examination of whether 10 weeks of group drumming could improve depression, anxiety and social resilience among service users compared with a non-music control group (with participants allocated to group by geographical location.) Significant improvements were found in the drumming group but not the control group: by week 6 there were decreases in depression (-2.14 SE 0.50 CI -3.16 to -1.11) and increases in social resilience (7.69 SE 2.00 CI 3.60 to 11.78), and by week 10 these had further improved (depression: -3.41 SE 0.62 CI -4.68 to -2.15; social resilience: 10.59 SE 1.78 CI 6.94 to 14.24) alongside significant improvements in anxiety (-2.21 SE 0.50 CI -3.24 to -1.19) and mental wellbeing (6.14 SE 0.92 CI 4.25 to 8.04). All significant changes were maintained at 3 months follow-up. Furthermore, it is now recognised that many mental health conditions are characterised by underlying inflammatory immune responses. Consequently, participants in the drumming group also provided saliva samples to test for cortisol and the cytokines interleukin (IL) 4, IL6, IL17, tumour necrosis factor alpha (TNF\u03b1), and monocyte chemoattractant protein (MCP) 1. Across the 10 weeks there was a shift away from a pro-inflammatory towards an anti-inflammatory immune profile. Consequently, this study demonstrates the psychological benefits of group drumming and also suggests underlying biological effects, supporting its therapeutic potential for mental health. ClinicalTrials.gov NCT01906892.","subset":"pubmed_abstract"} +{"meta":{"pmid":28009907,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Status and prospects in higher alcohols synthesis from syngas.\nHigher alcohols are important compounds with widespread applications in the chemical, pharmaceutical and energy sectors. Currently, they are mainly produced by sugar fermentation (ethanol and isobutanol) or hydration of petroleum-derived alkenes (heavier alcohols), but their direct synthesis from syngas (CO + H2) would comprise a more environmentally-friendly, versatile and economical alternative. Research efforts in this reaction, initiated in the 1930s, have fluctuated along with the oil price and have considerably increased in the last decade due to the interest to exploit shale gas and renewable resources to obtain the gaseous feedstock. Nevertheless, no catalytic system reported to date has performed sufficiently well to justify an industrial implementation. Since the design of an efficient catalyst would strongly benefit from the establishment of synthesis-structure-function relationships and a deeper understanding of the reaction mechanism, this review comprehensively overviews syngas-based higher alcohols synthesis in three main sections, highlighting the advances recently made and the challenges that remain open and stimulate upcoming research activities. The first part critically summarises the formulations and methods applied in the preparation of the four main classes of materials, i.e., Rh-based, Mo-based, modified Fischer-Tropsch and modified methanol synthesis catalysts. The second overviews the molecular-level insights derived from microkinetic and theoretical studies, drawing links to the mechanisms of Fischer-Tropsch and methanol syntheses. Finally, concepts proposed to improve the efficiency of reactors and separation units as well as to utilise CO2 and recycle side-products in the process are described in the third section.","subset":"pubmed_abstract"} +{"meta":{"pmid":23741346,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Ecological facilitation between two epiphytes through drought mitigation in a subtropical rainforest.\nPositive species interactions (facilitation) play an important role in shaping the structures and species diversity of ecological communities, particularly under stressful environmental conditions. Epiphytes in rainforests often grow in multiple-species clumps, suggesting interspecies facilitation. However, little is known about the patterns and mechanisms of epiphyte co-occurrence. We assessed the interactions of two widespread epiphyte species, Asplenium antiquum and Haplopteris zosterifolia, by examining their co-occurrence and size-class association in the field. To elucidate factors controlling their interactions, we conducted reciprocal-removal and greenhouse-drought experiments, and nutrient and isotope analyses. Forty-five percent of H. zosterifolia co-occurred with A. antiquum, whereas only 17% of A. antiquum co-occurred with H. zosterifolia. Removing the fronds plus substrate of A. antiquum reduced the relative frond length and specific leaf area of H. zosterifolia, but removing fronds only had little effect. Removing H. zosterifolia had no significant effects on the growth of A. antiquum. H. zosterifolia co-occurring and not co-occurring with A. antiquum had similar foliar nutrient concentrations and \u03b4(15)N values, suggesting that A. antiquum does not affect the nutrient status of H. zosterifolia. Reduced growth of H. zosterifolia with the removal of A. antiquum substrate, together with higher foliar \u03b4(13)C for H. zosterifolia growing alone than those co-occurring with A. antiquum, suggest that A. antiquum enhances water availability to H. zosterifolia. This enhancement probably resulted from water storage in the substrate of A. antiquum, which could hold water up to 6.2 times its dry weight, and from reduced evapotranspiration due to shading of A. antiquum fronds. Greater water loss occurred in the frond-clipped group than the unclipped group between days 3-13 of the drought treatment. Our results imply that drought mitigation by substrate-forming epiphytes is important for maintaining epiphyte diversity in tropic and subtropic regions with episodic water limitations, especially in the context of anthropogenic climate change.","subset":"pubmed_abstract"} +{"meta":{"pmid":10452303,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Feasibility of simultaneous stress 99mTc-sestamibi\/rest 201Tl dual-isotope myocardial perfusion SPECT in the detection of coronary artery disease.\nThis study assesses feasibility and diagnostic accuracy of simultaneous stress 99mTc-sestamibi\/rest 201 TI dual-isotope myocardial perfusion SPECT with Moore's correction method, in which contamination originating from lead x-rays produced in a collimator was subtracted in the 201TI windows. Eighty-one patients with suspected coronary artery disease received exercise 99mTc-sestamibi injection, followed by rest 201TI injection 50 min later, and dual-isotope SPECT was performed (group 1). These results were compared with coronary angiographic findings. Furthermore, to estimate the accuracy of Moore's correction method, 201TI crosstalk into the 99mTc acquisition window (group 2A, n = 20) and 99mTc crosstalk into the 201TI acquisition windows (group 2B, n = 20) were studied. For group 2A, stress 99mTc-sestamibi SPECT (single 99mTc-sestamibi SPECT) was performed, followed by 201TI injection at rest and dual-isotope SPECT acquisition 50 min later. For group 2B, rest 201TI SPECT (single 201TI SPECT) was performed, followed by 99mTc-sestamibi injection at rest and dual-isotope SPECT acquisition 30 min later. Sensitivity and specificity in group 1 were 83% and 99%, respectively, when > or =75% coronary artery narrowing was considered significant. In groups 2A and 2B, SPECT images were divided into 24 segments, and relative regional uptake in each segment was obtained. In group 2A, relative regional uptake of single 99mTc-sestamibi SPECT correlated well with that of dual-isotope SPECT (r = 0.942). In group 2B, relative regional uptake of single 201TI SPECT correlated well with that of dual-isotope SPECT (r = 0.935). Furthermore, in low 201TI uptake segments with relative regional uptake in both single- and dual-isotope SPECT of < or =70%, the degree of concordance between single- and dual-rest 201TI was considered to be high with Bland-Altman analysis and the kappa statistic. Comparison of perfusion defect type demonstrated that, of 22 stress defects within infarct zones, 95% were irreversible and 5% were reversible. In contrast, of 28 stress defects within stenosed vessel zones in noninfarct zones, 89% were reversible and 11% were irreversible (P < 0.0001 versus infarct zones). Simultaneous dual-isotope imaging with Moore's correction method is feasible, with acceptable accuracy for detection of coronary artery disease and a small amount of crosstalk into each window.","subset":"pubmed_abstract"} +{"meta":{"pmid":22244044,"dup_signals":{"dup_doc_count":12}},"text":"Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction.\nTo investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis. We enrolled 65 patients with acute myocardial infarction (AMI, n=22), unstable angina pectoris (UAP, n=16), and stable angina pectoris (SAP, n=27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) was measured by flow cytometry. In patients with AMI, TLR4 was more expressed on circulating CD14(+)CD16(+) monocytes than on CD14(+)CD16(-) monocytes (p<0.001). The expression levels of TLR4 on CD14(+)CD16(+) monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14(+)CD16(+) monocytes were significantly elevated at the culprit site compared with the systemic level (p=0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p<0.001). In addition, plasma levels of tumor necrosis factor-\u03b1 were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r=0.47, p=0.027). TLR overexpression on CD14(+)CD16(+) monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI.","subset":"pubmed_abstract"} +{"meta":{"pmid":11020452,"dup_signals":{"dup_doc_count":62,"dup_dump_count":44,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-21":2,"2021-49":1,"2021-43":1,"2021-31":2,"2021-21":2,"2021-10":2,"2020-50":2,"2020-45":1,"2020-40":1,"2020-05":1,"2019-35":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-34":1,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":2,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":2,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":2,"2017-04":2,"2023-50":1,"2024-18":1,"2017-13":2,"2024-30":1}}},"text":"Characterisation of the antitrypanosomal activity of peptidyl alpha-aminoalkyl phosphonate diphenyl esters.\nTwo groups of irreversible serine peptidase inhibitors, peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters, were examined for antitrypanosomal activity against the bloodstream form of Trypanosoma brucei brucei. Both peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters inhibited trypsin-like peptidases of the parasites and exhibited antitrypanosomal activity at micromolar concentrations. In live T. b. brucei, labelled analogues of both of these groups of inhibitors primarily targeted an 80-kDa peptidase, possibly a serine oligopeptidase known as oligopeptidase B. In an in vivo mouse model of infection, one of these inhibitors, carbobenzyloxyglycyl-4-amidinophenylglycine phosphonate diphenyl ester, was curative at 5 mg kg(-1) day(-1) but appeared toxic at higher doses. There was no significant correlation between the inhibitory potency (as evaluated against purified T. b. brucei oligopeptidase B) and the in vitro antitrypanosomal efficacy of either group of inhibitors, suggesting that these inhibitors were acting on multiple targets within the parasites, or had different cell permeability properties. These findings suggest that serine peptidases may represent novel chemotherapeutic targets in African trypanosomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":18984588,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":11}}},"text":"ATRMec1 phosphorylation-independent activation of Chk1 in vivo.\nThe conserved protein kinase Chk1 is a player in the defense against DNA damage and replication blocks. The current model is that after DNA damage or replication blocks, ATR(Mec1) phosphorylates Chk1 on the non-catalytic C-terminal domain. However, the mechanism of activation of Chk1 and the function of the Chk1 C terminus in vivo remains largely unknown. In this study we used an in vivo assay to examine the role of the C terminus of Chk1 in the response to DNA damage and replication blocks. The conserved ATR(Mec1) phosphorylation sites were essential for the checkpoint response to DNA damage and replication blocks in vivo; that is, that mutation of the sites caused lethality when DNA replication was stalled by hydroxyurea. Despite this, loss of the ATR(Mec1) phosphorylation sites did not change the kinase activity of Chk1 in vitro. Furthermore, a single amino acid substitution at an invariant leucine in a conserved domain of the non-catalytic C terminus restored viability to cells expressing the ATR(Mec1) phosphorylation site-mutated protein and relieved the requirement of an upstream mediator for Chk1 activation. Our findings show that a single amino acid substitution in the C terminus, which could lead to an allosteric change in Chk1, allows it to bypass the requirement of the conserved ATR(Mec1) phosphorylation sites for checkpoint function.","subset":"pubmed_abstract"} +{"meta":{"pmid":26829941,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":2,"2024-18":3,"2024-10":1,"unknown":9}}},"text":"Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells.\nIn previous studies human mesenchymal stromal cells (MSCs) maintained the \"stemness\" of human hematopoietic progenitor cells (HPCs) through direct cell-cell contact in two-dimensional co-culture systems. We establish a three-dimensional (3D) co-culture system based on a custom-made chip, the 3(D)-KITChip, as an in vitro model system of the human hematopoietic stem cell niche. This array of up to 625 microcavities, with 300 \u03bcm size in each orientation, was inserted into a microfluidic bioreactor. The microcavities of the 3(D)-KITChip were inoculated with human bone marrow MSCs together with umbilical cord blood HPCs. MSCs used the microcavities as a scaffold to build a complex 3D mesh. HPCs were distributed three-dimensionally inside this MSC network and formed \u00df-catenin- and N-cadherin-based intercellular junctions to the surrounding MSCs. Using RT(2)-PCR and western blots, we demonstrate that a proportion of HPCs maintained the expression of CD34 throughout a culture period of 14 days. In colony-forming unit assays, the hematopoietic stem cell plasticity remained similar after 14 days of bioreactor co-culture, whereas monolayer co-cultures showed increasing signs of HPC differentiation and loss of stemness. These data support the notion that the 3D microenvironment created within the microcavity array preserves vital stem cell functions of HPCs more efficiently than conventional co-culture systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":28769711,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2020-40":1,"2020-05":1,"2019-51":1,"2019-35":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2023-14":1}}},"text":"Description of the immature stages of Larinus vulpes and notes on its biology (Coleoptera, Curculionidae, Lixinae).\nMature larva and pupa of Larinus vulpes (Olivier, 1807) (Curculionidae: Lixinae: Lixini) are morphologically described for the first time and compared with known larvae and pupae of other Larinus species. Very high counts of larval body setae (pronotum with more than 25 setae and postdorsum on meso- and metathorax and also on abdominal segments I-VII with more than 12 setae) are characteristic features of the nominotypical subgenus Larinus. The biology of the species was studied in Ukraine. Echinops ruthenicus and E. sphaerocephalus were identified as host plants of both larvae and adults of this weevil based on the present research in Ukraine, which shows probably oligophagous. Overwintering beetles emerged at the end of May or earlier, then feeding and mating on the host plants. The highest level of adult activity was observed at the end of June. Larvae were endophagous within the flower heads. In July and August, the larvae pupated within inflorescences in a pupation cell. Adults exited the cells at the end of August and did not hibernate on the host plants. Sometimes, larvae and imagines of a new generation were found outside the flower heads in chambers constructed on the stems.","subset":"pubmed_abstract"} +{"meta":{"pmid":26120390,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Prevalence and patterns of physical activity among medical students in Bangalore, India.\nPhysical activity is one of the leading health indicators. The objective was to study the prevalence and patterns of physical activity among young adults. 259 Medical students (Men: Women = 116:143) in the age group of 18-22 yrs were interviewed using the official English long version of the International Physical Activity Questionnaire (IPAQ). The total level of physical activity and activity in each of the 4 life domains - work, transport, domestic and gardening and leisure-time were estimated and was expressed as metabolic equivalent-hours per week (MET-hour\/week). 41.3 % showed high levels of physical activity, 43.2% and 15.4 % of students showed moderate level and low level of physical activity respectively. 84.6 % (n=219) were engaged in work related activity and 80.7% (n= 209) showed transport related activity. Domestic and gardening physical activity represented 63.7 % (n=165) of individuals total activity and 67.2% of students showed leisure time activity. The average time spent in sitting was 7.06 hrs\/day. The median of the total physical activity for the whole sample was 39.13 MET\/hour\/week and 18.10 for work, 4.40 for transportation, 2.60 for domestic and gardening and 4 for leisure-time activity. There was significant gender difference observed with women having low physical activity. This study provides baseline information about the physical activity levels and patterns including sitting hours among Indian young adults using IPAQ that can used for comparison of data across different parts of world.","subset":"pubmed_abstract"} +{"meta":{"pmid":30571200,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Surgical Atrioventricular Valve Replacement With Melody Valve in Infants and Children.\nBackground Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes <15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P<0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https:\/\/www.clinicaltrials.gov. Unique identifier: NCT02505074.","subset":"pubmed_abstract"} +{"meta":{"pmid":11768520,"dup_signals":{"dup_doc_count":24,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2023-14":1,"2023-06":1,"2022-33":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":2,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-24":1,"2023-23":1,"2024-30":2,"2024-18":1,"2024-10":1,"2013-20":1}}},"text":"Magnetic resonance imaging of cerebral cortical necrosis (polioencephalomalacia) in a dog.\nA 3-year-old neutered female mixed breed dog was examined because of severe, generalized seizure activity, tetraparesis, and encephalopathic signs. Cerebrospinal fluid (CSF) evaluation was unremarkable except for a mild increase in protein. Serum and CSF titers for infectious diseases were negative. Magnetic resonance (MR) imaging examination of the brain was performed and lesions were found within the cerebral gray matter of the temporal and parietal lobes. The lesions had increased signal intensity on T1, T2, and proton density-weighted images. There was mild inhomogeneous enhancement following intravenous contrast medium administration. Neurologic status improved and the seizures were well controlled, but the dog never regained normal mentation and euthanasia was performed 10 weeks after initial evaluation. At necropsy, severe cerebral cortical necrosis was found in the regions corresponding to the lesions seen on MR imaging examination. Large numbers of fat-containing macrophages (gitter cells) were found within these areas, and are thought to be responsible for the characteristic hyperintensity seen on the MR images.","subset":"pubmed_abstract"} +{"meta":{"pmid":27919498,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2019-26":2,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2018-05":1,"2017-43":1,"2017-34":1}}},"text":"Association between exposure to farm animals and pets and risk of Multiple Sclerosis.\nThere exists inconsistent evidence regarding animals including pets as risk factors for the development of Multiple Sclerosis (MS). We investigated the association between farm animals and pets as possible environmental factors in MS development. Population based case-control study with 136 clinically definite MS cases and 272 controls randomly chosen from the community matched on sex and age. Data was collected from both questionnaire and a lifetime calendar detailing residence, occupation and pet\/animal exposure over the course of participant's lives. Exposure to farming, livestock, specific farm animals and remoteness of residence showed no significant association with MS risk. Exposure to cats prior to disease onset was associated with a greater risk of MS (Adjusted Odds Ratio 2.46 (1.17-5.18)) but without a clear dose-response (test for trend, p=0.76). In contrast to other literature, farming and exposure to farm animals were not associated with MS. While we identified an association between cat exposure and MS, there was no dose-response relationship, and previous studies showed inconsistent results, leaving us to conclude that there is no strong evidence that exposure to cats is associated with MS.","subset":"pubmed_abstract"} +{"meta":{"pmid":24797202,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":9}}},"text":"Using mirror therapy in the home environment: a case report.\nMirror therapy (MT) is a potential intervention to improve function after stroke. How to apply this intervention in practice is not clear. This case report illustrates the feasibility and effectiveness of a self-administered home-based MT program. A home-based MT program was practiced over 5 wk. The participant was encouraged to use MT for 30 min 5\u00d7\/wk. Therapist contact occurred 1\u00d7\/wk to monitor performance. An independent evaluator administered three outcome measures pre- and postintervention: Upper Extremity Sensory and Pain sections of the Fugl-Meyer Assessment; Jebsen-Taylor Test of Hand Function, and the Manual Ability Measure-20. The participant engaged in a mean of 39.23 (\u00b17.44) min of MT per day and used a variety of the recommended activities. Change scores indicated improvement on all of the included outcome measures. This case report suggests that a predominantly self-administered home-based MT program is feasible and effective at improving function after stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":23569557,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":2,"unknown":11}}},"text":"Bleichner's hernia - lumbar hernia.\nWe present a case of a lumbar hernia and a review of the literature of this rare hernia type. The case and the review will discuss the unusual presentations reported, common etiologies, the importance of early operative repair based on the high rate of incarceration and the recent recommendations regarding repair techniques. Lumbar hernias are rare cases, but should be pursued in diagnosis and treated aggressively because of the high rate of incarceration. Repair can be accomplished with a minimally invasive technique.","subset":"pubmed_abstract"} +{"meta":{"pmid":26820234,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Isotopic Ratio Outlier Analysis of the S. cerevisiae Metabolome Using Accurate Mass Gas Chromatography\/Time-of-Flight Mass Spectrometry: A New Method for Discovery.\nIsotopic ratio outlier analysis (IROA) is a (13)C metabolomics profiling method that eliminates sample to sample variance, discriminates against noise and artifacts, and improves identification of compounds, previously done with accurate mass liquid chromatography\/mass spectrometry (LC\/MS). This is the first report using IROA technology in combination with accurate mass gas chromatography\/time-of-flight mass spectrometry (GC\/TOF-MS), here used to examine the S. cerevisiae metabolome. S. cerevisiae was grown in YNB media, containing randomized 95% (13)C, or 5%(13)C glucose as the single carbon source, in order that the isotopomer pattern of all metabolites would mirror the labeled glucose. When these IROA experiments are combined, the abundance of the heavy isotopologues in the 5%(13)C extracts, or light isotopologues in the 95%(13)C extracts, follows the binomial distribution, showing mirrored peak pairs for the molecular ion. The mass difference between the (12)C monoisotopic and the (13)C monoisotopic equals the number of carbons in the molecules. The IROA-GC\/MS protocol developed, using both chemical and electron ionization, extends the information acquired from the isotopic peak patterns for formulas generation. The process that can be formulated as an algorithm, in which the number of carbons, as well as the number of methoximations and silylations are used as search constraints. In electron impact (EI\/IROA) spectra, the artifactual peaks are identified and easily removed, which has the potential to generate \"clean\" EI libraries. The combination of chemical ionization (CI) IROA and EI\/IROA affords a metabolite identification procedure that enables the identification of coeluting metabolites, and allowed us to characterize 126 metabolites in the current study.","subset":"pubmed_abstract"} +{"meta":{"pmid":26857427,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2017-13":1,"2024-30":1,"unknown":5}}},"text":"All-optical control of cardiac excitation: combined high-resolution optogenetic actuation and optical mapping.\nCardiac tissue is an excitable system that can support complex spatiotemporal dynamics, including instabilities (arrhythmias) with lethal consequences. While over the last two decades optical mapping of excitation (voltage and calcium dynamics) has facilitated the detailed characterization of such arrhythmia events, until recently, no precise tools existed to actively interrogate cardiac dynamics in space and time. In this work, we discuss the combined use of new methods for space- and time-resolved optogenetic actuation and simultaneous fast, high resolution optical imaging of cardiac excitation waves. First, the mechanisms, limitations and unique features of optically induced responses in cardiomyocytes are outlined. These include the ability to bidirectionally control the membrane potential using depolarizing and hyperpolarizing opsins; the ability to induce prolonged sustained voltage changes; and the ability to control refractoriness and the shape of the cardiac action potential. At the syncytial tissue level, we discuss optogenetically enabled experimentation on cell-cell coupling, alteration of conduction properties and termination of propagating waves by light. Specific attention is given to space- and time-resolved application of optical stimulation using dynamic light patterns to perturb ongoing activation and to probe electrophysiological properties at desired tissue locations. The combined use of optical methods to perturb and to observe the system can offer new tools for precise feedback control of cardiac electrical activity, not available previously with pharmacological and electrical stimulation. These new experimental tools for all-optical electrophysiology allow for a level of precise manipulation and quantification of cardiac dynamics comparable in robustness to the computational setting, and can provide new insights into pacemaking, arrhythmogenesis and suppression or cardioversion.","subset":"pubmed_abstract"} +{"meta":{"pmid":34001816,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":6}}},"text":"Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection.\nHigh-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown. This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay. A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P <0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P <0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P <0.001). Pain scores were comparable between groups. There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":8272581,"dup_signals":{"dup_doc_count":51,"dup_dump_count":33,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":1,"2023-23":2,"2023-14":2,"2022-49":2,"2022-27":2,"2022-05":2,"2021-39":2,"2021-25":2,"2021-21":1,"2021-10":2,"2020-50":1,"2020-45":1,"2020-40":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":2,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-22":2,"2024-18":1,"2017-13":1,"2024-30":1}}},"text":"Effects of midazolam and flumazenil on ventilation during sustained hypoxia in humans.\nThe purpose of this study was to investigate whether increases in gamma-aminobutyric acid (GABA) in the brain stem underlie the ventilatory decline observed during hypoxia in man. The ventilatory responses to sustained isocapnic hypoxia were studied in six adult male subjects on three separate days in three pharmacological conditions: (1) without any drug administration; (2) during infusion of midazolam (a drug which potentiates the effect of GABA); and (3) during infusion of flumazenil (a benzodiazepine antagonist). On each experimental day, the following protocol was repeated three times: end-tidal PO2 was held at 100 Torr for 10 min, then at 50 Torr for 20 min and finally at 100 Torr for 5 min. End-tidal PCO2 was held constant throughout. Responses in the three pharmacological conditions were similar. We conclude that neither potentiation of GABA transmission (midazolam) nor antagonism of this potentiation (flumazenil) greatly affect the decline in ventilation which occurs during extended exposure to hypoxia.","subset":"pubmed_abstract"} +{"meta":{"pmid":19096241,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Anterior chamber measurements by pentacam and AS-OCT in eyes with normal open angles.\nTo assess the reproducibility and agreement of anterior chamber measurements between the Pentacam (PTC) and the Anterior segment optical coherence tomography (AOCT) in normal healthy eyes with open angle. Prospective cross-sectional comparative case series. A total of 162 eyes of 81 healthy volunteers with normal open angle were included in this study. Anterior chamber angle (ACA) and anterior chamber depth (ACD) were measured with PTC and AOCT. Intra-observer variability and inter-methods agreement of both instruments for ACA and ACD were evaluated. Values of temporal and nasal ACA measured by two instruments were similar, and the results of ACD were also not significantly different between modalities (p > 0.01). ACA and ACD measurements by PTC and AOCT showed good intra-observer and inter-method agreements (all > 0.9). PTC and AOCT are presumed to be very useful for the anterior chamber angle examination. They may provide good images and quantitative data about the angle structures including ACA and ACD.","subset":"pubmed_abstract"} +{"meta":{"pmid":29786526,"dup_signals":{"dup_doc_count":38,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2022-40":1,"2022-33":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-31":2,"2021-21":3,"2021-17":1,"2021-04":1,"2020-40":3,"2020-34":2,"2019-13":2,"2019-04":2,"2018-51":2,"2018-43":3,"2018-39":1,"2018-34":1,"2018-30":3,"2018-22":1,"2023-06":1,"2024-22":1,"2024-30":1}}},"text":"Application of multiple behaviour change models to identify determinants of farmers' biosecurity attitudes and behaviours.\nIt has been recognised that few cattle farmers undertake biosecurity practices on their farms. Approaches that take into consideration individuals' preparedness for change, alongside beliefs thought to motivate the enactment of certain behaviours, may provide a framework for actuating tangible change. The aim of this study was to use a combination of behaviour change models to link beliefs with behaviour and identify possible key interventions to improve the uptake of biosecurity measures by dairy cattle farmers in Great Britain (GB). This is the first study to explore farmers' practices and attitudes in relation to the prevention of direct (animal to animal contact); indirect (via fomites); and other biosecurity measures using a multitheory approach. A cross-sectional study was carried out, with postal questionnaires sent to 2505 dairy cattle farmers. Questions were asked about the extent to which a host of biosecurity measures were used, the influence of various stakeholders (e.g. veterinarians, industry bodies) in informing biosecurity choices, and the perceived control farmers felt they had over biosecurity on their farms. Farmer attitudes towards biosecurity were also explored. Two behaviour change models, the Transtheoretical Model, and the Theory of Planned Behaviour, were utilised. A variety of analysis methods were used to interrogate the data, including multivariable logistic regression. A total of 908\/2505 (36.2%) farmers responded, with 757 responses (30.2%) deemed eligible for inclusion. Farmers generally fell into one of two categories: those that reported not applying biosecurity measures with no intention of doing so in the future, and those that reported undertaking biosecurity measures for some time. Farmers felt that biosecurity improved cattle health and welfare, but also felt that disease was inevitable. More farmers agreed with statements relating to their ability to control, rather than prevent disease. Analysis suggested a difference between influencing beliefs and whether specific types of measure were more likely to be undertaken. For example, farmers' beliefs about other stakeholders appeared to play a role in influencing the utilisation of measures preventing direct contact (e.g. nose to nose contact), rather than indirect contact (e.g. fomite transmission). The use of a combination of behaviour change models has identified key variables to use for interventional approaches targeted towards the different type of biosecurity measure (preventing direct or indirect transmission) to improve the uptake of biosecurity on dairy cattle farms in GB. Other industry stakeholders should be aware of these variables when working with farmers to achieve optimal cattle herd health.","subset":"pubmed_abstract"} +{"meta":{"pmid":11826079,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Podokinetic after-rotation following unilateral and bilateral podokinetic stimulation.\nPrevious studies demonstrated an aftereffect of walking on a rotating treadmill, involving inadvertent circular navigation with eyes closed [podokinetic after-rotation (PKAR)]. We compared PKAR following unilateral and bilateral podokinetic (PK) stimulation to determine whether the left and right legs could be independently adapted. Each subject performed two sessions of PK stimulation, stepping in place with one foot on either side of the axis of a rotating disk. Subjects experienced bilateral stimulation (i.e., both left and right feet stepped on the rotating disk) in one session and unilateral stimulation (i.e., the left foot stepped on the rotating disk and the right foot stepped on a stationary surface) in the other. Following stimulation, we recorded foot lift-off and touchdown times and pelvic angular velocity while subjects stepped in place on a stationary surface. PKAR velocity following unilateral stimulation was lower than that following bilateral stimulation. Following bilateral stimulation, pelvic rotation was in the counterclockwise (CCW) direction during single-limb support on both the left and right sides. Immediately following left unilateral stimulation, subjects demonstrated CCW pelvic rotation during left single-limb support but not during right single-limb support. Across the first 13 strides, the difference between left and right sides diminished; pelvic angular velocity was then CCW during single-limb support on both sides. This suggests that both the adapted left and the unadapted right limb influenced the final PKAR response with information from the two limbs being integrated over the first few strides.","subset":"pubmed_abstract"} +{"meta":{"pmid":21882907,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":3,"2020-05":1,"2019-51":1,"2019-43":1,"2019-39":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-39":1,"2017-26":1,"2017-17":1,"2017-09":1,"2016-50":1,"2020-40":1}}},"text":"Chiari malformation associated with craniosynostosis.\nChiari malformation (CM) Type I is frequently associated with craniosynostosis. Optimal management of CM in patients with craniosynostosis is not well-established. The goal of this study was to report on a series of pediatric patients with both craniosynostosis and CM and discuss their management. The authors searched the medical records of 383 consecutive patients treated for craniosynostosis at a single institution over a 15-year period to identify those with CM. They recorded demographic data as well as surgical treatment and outcomes for these patients. When MR imaging was performed, cerebellar tonsillar descent was recorded and any other associated findings, such as hydrocephalus or spinal syringes, were noted. A total of 29 patients with both CM and craniosynostosis were identified. Of these cases, 28% had associated occipital venous abnormalities, 45% were syndromic, and 52% also had hydrocephalus. Chiari malformation was more likely to be present in those patients with isolated lambdoid synostosis (55%), multisuture synostosis (35%), and pansynostosis (80%), compared with patients with coronal synostosis (6%) or sagittal synostosis (3%). All patients underwent surgical repair of craniosynostosis: 16 had craniosynostosis repair as well as CM decompression, and 13 patients did not undergo CM decompression. Of the 7 patients in whom craniosynostosis repair alone was performed, 5 had decreased tonsillar ectopia postoperatively and 5 had improved CSF flow studies postoperatively. Both patients with a spinal syrinx had imaging-documented syrinx regression after craniosynostosis repair. In 12 patients in whom CM was diagnosed after primary craniosynostosis repair, 5 had multiple cranial vault expansions and evidence of elevated intracranial pressure. In 5 cases, de novo CM development was documented following craniosynostosis repair at a mean of 3.5 years after surgery. Chiari malformation is frequently seen in patients with both multi- and single-suture lambdoid craniosynostosis. Chiari malformation, and even a spinal cord syrinx, will occasionally resolve following craniofacial repair. De novo development of CM after craniosynostosis repair is not unusual.","subset":"pubmed_abstract"} +{"meta":{"pmid":19388305,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":18}}},"text":"Pulse amplitude of intracranial pressure waveform in hydrocephalus.\nThere is increasing interest in evaluation of the pulse amplitude of intracranial pressure (AMP) in explaining dynamic aspects of hydrocephalus. We reviewed a large number of ICP recordings in a group of hydrocephalic patients to assess utility of AMP. From a database including approximately 2,100 cases of infusion studies (either lumbar or intraventricular) and overnight ICP monitoring in patients suffering from hydrocephalus of various types (both communicating and non-communicating), etiology and stage of management (non-shunted or shunted) pressure recordings were evaluated. For subgroup analysis we selected 60 patients with idiopathic NPH with full follow-up after shunting. In 29 patients we compared pulse amplitude during an infusion study performed before and after shunting with a properly functioning shunt. Amplitude was calculated from ICP waveforms using spectral analysis methodology. A large amplitude was associated with good outcome after shunting (positive predictive value of clinical improvement for AMP above 2.5 mmHg was 95%). However, low amplitude did not predict poor outcome (for AMP below 2.5 mmHg 52% of patients improved). Correlations of AMP with ICP and Rcsf were positive and statistically significant (N = 131 with idiopathic NPH; R = 0.21 for correlation with mean ICP and 0.22 with Rcsf; p< 0.01). Correlation with the brain elastance coefficient (or PVI) was not significant. There was also no significant correlation between pulse amplitude and width of the ventricles. The pulse amplitude decreased (p < 0.005) after shunting. Interpretation of the ICP pulse waveform may be clinically useful in patients suffering from hydrocephalus. Elevated amplitude seems to be a positive predictor for clinical improvement after shunting. A properly functioning shunt reduces the pulse amplitude.","subset":"pubmed_abstract"} +{"meta":{"pmid":23799943,"dup_signals":{"dup_doc_count":12}},"text":"Designing a valid randomized pragmatic primary care implementation trial: the my own health report (MOHR) project.\nThere is a pressing need for greater attention to patient-centered health behavior and psychosocial issues in primary care, and for practical tools, study designs and results of clinical and policy relevance. Our goal is to design a scientifically rigorous and valid pragmatic trial to test whether primary care practices can systematically implement the collection of patient-reported information and provide patients needed advice, goal setting, and counseling in response. This manuscript reports on the iterative design of the My Own Health Report (MOHR) study, a cluster randomized delayed intervention trial. Nine pairs of diverse primary care practices will be randomized to early or delayed intervention four months later. The intervention consists of fielding the MOHR assessment--addresses 10 domains of health behaviors and psychosocial issues--and subsequent provision of needed counseling and support for patients presenting for wellness or chronic care. As a pragmatic participatory trial, stakeholder groups including practice partners and patients have been engaged throughout the study design to account for local resources and characteristics. Participatory tasks include identifying MOHR assessment content, refining the study design, providing input on outcomes measures, and designing the implementation workflow. Study outcomes include the intervention reach (percent of patients offered and completing the MOHR assessment), effectiveness (patients reporting being asked about topics, setting change goals, and receiving assistance in early versus delayed intervention practices), contextual factors influencing outcomes, and intervention costs. The MOHR study shows how a participatory design can be used to promote the consistent collection and use of patient-reported health behavior and psychosocial assessments in a broad range of primary care settings. While pragmatic in nature, the study design will allow valid comparisons to answer the posed research question, and findings will be broadly generalizable to a range of primary care settings. Per the pragmatic explanatory continuum indicator summary (PRECIS) framework, the study design is substantially more pragmatic than other published trials. The methods and findings should be of interest to researchers, practitioners, and policy makers attempting to make healthcare more patient-centered and relevant. Clinicaltrials.gov: NCT01825746.","subset":"pubmed_abstract"} +{"meta":{"pmid":14599601,"dup_signals":{"dup_doc_count":13,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-10":1,"2020-05":1,"2019-51":2,"2019-43":1,"2019-39":2,"2019-30":1,"2021-21":1}}},"text":"Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is blocked by inhibiting MAP kinase.\nMutations in oncogenic Ras contribute to colorectal tumorigenesis. Loss of the cell adhesion protein E-cadherin is associated with tumor invasion and metastasis. Expression of oncogenic Ras was induced in intestinal epithelial cells. Changes in cell morphology, E-cadherin protein expression, and E-cadherin localization were examined by light microscopy, Western blot, and immunofluorescence respectively. Expression of E-cadherin in human colorectal tumors was examined by immunohistochemistry. Induction of oncogenic Ras results in an epithelial to mesenchymal transformation with loss of membranous E-cadherin expression and mis-localization to the cytoplasm. Removal of Ras stimulus or blockade of the MAP kinase pathway allowed reversion to a normal cellular phenotype and return of E-cadherin to the cell membrane. Loss of or decreased expression of E-cadherin was observed in seven of eight colorectal tumors. Oncogenic Ras contributes to malignant transformation and altered E-cadherin expression in intestinal epithelial cells. Similar dysregulation of E-cadherin is found in human colorectal tumors. Ras effects on E-cadherin are critical to malignant transformation in our in-vitro model and may be an important event in human colorectal tumors.","subset":"pubmed_abstract"} +{"meta":{"pmid":30738263,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2022-21":1,"2021-43":1,"2021-21":1,"2021-10":2,"2020-40":1,"2020-24":1,"2020-05":1,"2019-47":2,"2019-18":1,"2023-23":1,"2024-22":1}}},"text":"Combined effects of climate change and sea-level rise project dramatic habitat loss of the globally endangered Bengal tiger in the Bangladesh Sundarbans.\nThe Sundarbans, in southern coastal Bangladesh, is the world's largest surviving mangrove habitat and the last stronghold of tiger adapted to living in a mangrove ecosystem. Using MaxEnt (maximum entropy modeling), current distribution data, land-use\/land cover and bioclimatic variables, we modeled the likely future distribution of the globally endangered Bengal tiger (Panthera tigris tigris) in the Bangladesh Sundarbans. We used two climatic scenarios (i.e., RCP6.0 and RCP8.5) developed by the Intergovernmental Panel on Climate Change (IPCC) to provide projections of suitable habitats of Bengal tigers in 2050 and 2070. We also combined projected sea-level rise for the area in our models of future species distributions. Our results suggest that there will be a dramatic decline in suitable Bengal tiger habitats in the Bangladesh Sundarbans. Other than various aspects of local climate, sea-level rise is projected to have a substantial negative impact on Bengal tiger habitats in this low-lying area. Our model predicts that due to the combined effect of climate change and sea-level rise, there will be no suitable Bengal tiger habitat remaining in the Sundarbans by 2070. Enhancing terrestrial protected area coverage, regular monitoring, law enforcement, awareness-building among local residents among the key strategies needed to ensure long-term survival and conservation of the Bengal tiger in the Bangladesh Sundarbans.","subset":"pubmed_abstract"} +{"meta":{"pmid":22026324,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Effectiveness of a handwriting readiness program in head start: a two-group controlled trial.\nThis study measured skill improvement in prewriting skills, kindergarten readiness, first-name writing, and handwriting-nonspecific fine motor skills of students at Head Start who participated in Handwriting Without Tears-Get Set for School (HWT-GSS) programming. We conducted a two-group, nonrandomized controlled trial using a pretest-posttest design at a rural Head Start. The effectiveness of adding the HWT-GSS curriculum in one preschool classroom was compared with a control classroom. On posttesting, the experimental group made significant improvements compared with the control group in prewriting, kindergarten readiness, and fine motor skills. Both groups made significant improvements between pretesting and posttesting in prewriting, first name writing, and school readiness. Adding HWT-GSS to the Head Start program would be beneficial in improving handwriting readiness skills.","subset":"pubmed_abstract"} +{"meta":{"pmid":28420952,"dup_signals":{"dup_doc_count":24,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2022-27":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-39":1,"2019-30":2,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-39":2,"2018-30":1,"2018-26":1,"2018-22":1,"2018-13":1,"2022-49":1}}},"text":"Motion-Induced Position Shifts Activate Early Visual Cortex.\nThe ability to correctly determine the position of objects in space is a fundamental task of the visual system. The perceived position of briefly presented static objects can be influenced by nearby moving contours, as demonstrated by various illusions collectively known as motion-induced position shifts. Here we use a stimulus that produces a particularly strong effect of motion on perceived position. We test whether several regions-of-interest (ROIs), at different stages of visual processing, encode the perceived rather than retinotopically veridical position. Specifically, we collect functional MRI data while participants experience motion-induced position shifts and use a multivariate pattern analysis approach to compare the activation patterns evoked by illusory position shifts with those evoked by matched physical shifts. We find that the illusory perceived position is represented at the earliest stages of the visual processing stream, including primary visual cortex. Surprisingly, we found no evidence of percept-based encoding of position in visual areas beyond area V3. This result suggests that while it is likely that higher-level visual areas are involved in position encoding, early visual cortex also plays an important role.","subset":"pubmed_abstract"} +{"meta":{"pmid":12203015,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":2,"2021-49":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-40":1,"2020-29":1,"2023-50":1}}},"text":"Ultrastructural damage in chromium picolinate-treated cells: a TEM study. Transmission electron microscopy.\nChromium picolinate (CrPic) is a human dietary supplement that provides a bioavailable form of chromium(III). Its mechanism of action is unknown, and a number of toxic endpoints have been attributed to its use. Understanding the cellular effects of CrPic is important for confirmation or dismissal of these potential toxic effects. The purpose of this work was to characterize morphological damage caused by CrPic, picolinic acid, and chromic chloride in Chinese hamster ovary AA8 cells. A 48-h exposure to 80 micro g\/cm(2) CrPic (0.44 mg\/mL CrPic) produced 45% survival by colony formation. Transmission electron microscopy (TEM) showed 83% of analyzed cells having swollen mitochondria with degraded cristae. Apoptosis was identified by nuclear convolution and fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence microscopy with acridine orange\/ethidium bromide staining. At the 80 micro g\/cm(2) dose of CrPic, 37% of the cells were apoptotic cells at 48 h. An equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM induced 49% cell survival, and damaged 86% of the mitochondria, with 51% of the cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71% cell survival, and damaged 86% of the mitochondria, with 22% of the cells undergoing apoptosis. The amount of apoptosis correlated with overall cell survival by colony formation, but not with the amount of mitochondrial damage. The coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of Cr(III) to make chromium picolinate a toxic form of Cr(III).","subset":"pubmed_abstract"} +{"meta":{"pmid":16341266,"dup_signals":{"dup_doc_count":25,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":21}}},"text":"Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients.\nWe previously reported that human CD4+ Tregs secrete high levels of IL-10 when stimulated in the presence of dexamethasone and calcitriol (vitamin D3). We now show that following stimulation by allergen, IL-10-secreting Tregs inhibit cytokine secretion by allergen-specific Th2 cells in an IL-10-dependent manner. A proportion of patients with severe asthma fail to demonstrate clinical improvement upon glucocorticoid therapy, and their asthma is characterized as glucocorticoid resistant (SR, abbreviation derived from \"steroid resistant\"). Dexamethasone does not enhance secretion of IL-10 by their CD4+ T cells. Addition of vitamin D3 with dexamethasone to cultures of SR CD4+ T cells enhanced IL-10 synthesis to levels observed in cells from glucocorticoid-sensitive patients cultured with dexamethasone alone. Furthermore, pretreatment with IL-10 fully restored IL-10 synthesis in these cells in response to dexamethasone. Vitamin D3 significantly overcame the inhibition of glucocorticoid-receptor expression by dexamethasone while IL-10 upregulated glucocorticoid-receptor expression by CD4+ T cells, suggesting potential mechanisms whereby these treatments may overcome poor glucocorticoid responsiveness. We show here that administration of vitamin D3 to healthy individuals and SR asthmatic patients enhanced subsequent responsiveness to dexamethasone for induction of IL-10. This strongly suggests that vitamin D3 could potentially increase the therapeutic response to glucocorticoids in SR patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":24071876,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.\nThe management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical\/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and\/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.","subset":"pubmed_abstract"} +{"meta":{"pmid":23297923,"dup_signals":{"dup_doc_count":47,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":38}}},"text":"Syllable language models for Mandarin speech recognition: exploiting character language models.\nMandarin Chinese is based on characters which are syllabic in nature and morphological in meaning. All spoken languages have syllabiotactic rules which govern the construction of syllables and their allowed sequences. These constraints are not as restrictive as those learned from word sequences, but they can provide additional useful linguistic information. Hence, it is possible to improve speech recognition performance by appropriately combining these two types of constraints. For the Chinese language considered in this paper, character level language models (LMs) can be used as a first level approximation to allowed syllable sequences. To test this idea, word and character level n-gram LMs were trained on 2.8 billion words (equivalent to 4.3 billion characters) of texts from a wide collection of text sources. Both hypothesis and model based combination techniques were investigated to combine word and character level LMs. Significant character error rate reductions up to 7.3% relative were obtained on a state-of-the-art Mandarin Chinese broadcast audio recognition task using an adapted history dependent multi-level LM that performs a log-linearly combination of character and word level LMs. This supports the hypothesis that character or syllable sequence models are useful for improving Mandarin speech recognition performance.","subset":"pubmed_abstract"} +{"meta":{"pmid":22016799,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16\/FoxO exit dauer.\nParasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3) in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16\/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370);daf-16(mu86) mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.","subset":"pubmed_abstract"} +{"meta":{"pmid":22241748,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":2,"2014-10":1,"unknown":17}}},"text":"Radiotherapy and chemotherapy for elderly patients with stage I-II unresected lung cancer.\nRadiotherapy (RT) is the standard therapy for unresected stage I-II nonsmall cell lung cancer (NSCLC). Using population-based data, we compared survival and toxicity among unresected elderly patients treated with combined chemoradiotherapy (CRT) or RT alone. Using the Surveillance, Epidemiology and End Results (SEER) registry (National Cancer Institute, Bethesda, MD, USA) we identified 3,006 cases of unresected stage I-II NSCLC. We used propensity score methods to compare survival and rates of toxicity of patients treated with RT versus CRT. Overall, 844 (28%) patients received CRT. Adjusted analyses showed that CRT was associated with improved survival (hazard ratio 0.85, 95% CI 0.78-0.94). Combination therapy was also associated with better survival among stage I patients treated with intermediate complexity RT (HR 0.80, 95% CI 0.70-0.90); however, no difference in survival was observed among patients treated with complex RT. In stage II patients, CRT was associated with improved survival regardless of the RT technique (HR 0.61-0.72). CRT was associated with increased odds of toxicity. Despite increased toxicity, CRT may improve survival of elderly unresected patients with stage II disease as well as stage I NSCLC treated with intermediate RT complexity. Randomised trials are needed to clarify the balance of benefits and risk of CRT in unresected patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":19388489,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Self-measurement of blood pressure in arterial hypertension--preliminary results from the AMPA study.\nThe clinical usefulness of home blood pressure monitoring (HBPM) is still uncertain, and is currently a major topic of scientific debate. Some studies have stressed its potential role in the clinical decision-making process, but there have been few prospective studies addressing this subject. The AMPA study is intended to contribute to this debate, exploring the potential usefulness of this methodology in the clinical setting of arterial hypertension using a prospective, observational and multicenter design. The study included 685 hypertensive patients (346 female), with a mean age of 54.2 +\/- 11.1 years (range: 17-86 years). All patients were being followed in primary care centers by their family doctors, and were being treated for arterial hypertension and other comorbidities. Forty-seven patients were smokers (6%), 90 (13%) had a personal history of cardiovascular disease, 42 (6%) were diabetic, 255 (37%) had dyslipidemia, and 31 (5%) were both diabetic and dyslipidemic. Blood pressure (BP) was measured in the brachial artery with a validated automatic blood pressure measurement device (Colson MAM BP 3AA1-2; Colson, Paris). This device has solid state memory (sufficient for 60 measurements) and an adaptable printer. A cuff appropriate for the arm size of each patient was used. All patients were instructed on how to operate the device correctly and how to perform the measurements in compliance with the study protocol. BP was always measured after a 5-minute resting period in a seated position. The protocol consisted of an HBP program over a period of five working days. Each day the patient performed six BP measurements in two different periods: three in the morning (between 6 and 10 am) and three in the evening (between 6 and 10 pm). Other clinical and anthropometric data were also collected. The HBP reference values adopted were 135 mmHg for systolic and 85 mmHg for diastolic BP. Analysis of BP behavior over time demonstrated a significant white-coat effect, with regression to the mean of BP levels after the first day of the HBP program. As a consequence, the first day values were excluded in determining mean HBP. This behavior was independent of gender, and was more pronounced in diabetic patients. Analysis of diagnostic concordance between office BP and HBP showed discrepancies in 27.4% of the patients. This prompted a change in diagnosis based on HBP values, with 133 patients (19.4%) presenting uncontrolled office BP levels but normal HBP values, while 55 patients (8%) had elevated HBP in contrast to normal office BP. These first results of the AMPA study illustrate the superiority of HBP compared with office BP in the evaluation of hypertensive patients. HBP provides a better characterization of each patient's BP profile, and hence may help improve therapeutic and clinical decisions. Confirmation of the potential of HBP monitoring will be addressed in a prospective analysis (6-year follow-up) of the AMPA study in the near future.","subset":"pubmed_abstract"} +{"meta":{"pmid":19605550,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"RiceArrayNet: a database for correlating gene expression from transcriptome profiling, and its application to the analysis of coexpressed genes in rice.\nMicroarray data can be used to derive understanding of the relationships between the genes involved in various biological systems of an organism, given the availability of databases of gene expression measurements from the complete spectrum of experimental conditions and materials. However, there have been no reports, to date, of such a database being constructed for rice (Oryza sativa). Here, we describe the construction of such a database, called RiceArrayNet (RAN; http:\/\/www.ggbio.com\/arraynet\/), which provides information on coexpression between genes in terms of correlation coefficients (r values). The average number of coexpressed genes is 214, with sd of 440 at r >or= 0.5. Given the correlation between genes in a gene pair, the degrees of closeness between genes can be visualized in a relational tree and a relational network. The distribution of correlated genes according to degree of stringency shows how each gene is related to other genes. As an application of RAN, the 16-member L7Ae ribosomal protein family was explored for coexpressed genes and gene expression values within and between rice and Arabidopsis (Arabidopsis thaliana), and common and unique features in coexpression partners and expression patterns were observed for these family members. We observed a correlation pattern between Os01g0968800, a drought-responsive element-binding transcription factor, Os02g0790500, a trehalose-6-phosphate synthase, and Os06g0219500, a small heat shock factor, reflecting the fact that genes responding to the same biological stresses are regulated together. The RAN database can be used as a tool to gain insight into a particular gene by examining its coexpression partners.","subset":"pubmed_abstract"} +{"meta":{"pmid":15809578,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Treatment of chronic frontal sinus disease with the galeal-frontalis flap: a long-term follow-up.\nManagement of benign chronic frontal sinus disease is difficult. Patients are frequently seen by multiple specialties for medical treatment and endonasal procedures before they seek or require definitive treatment with frontal sinus obliteration. The progression of the disease may lead to serious or life-threatening conditions such as local bone destruction, periorbital abscess, osteomyelitis, meningitis, cranial epidural abscess, or septicemia. This study presents the use of the galeal-frontalis myofascial flap as part of the treatment of this disease. Thirty-one patients with chronic frontal sinus disease requiring obliteration were included in this study; all were approached through a coronal incision. The anterior wall of the frontal sinus was removed and the frontal sinus disease was evacuated. The sinus mucosa was completely removed, and the frontal sinus and nasofrontal duct were totally obliterated with either a unilateral flap or a bilateral galeal-frontalis flap. All patients had failed medical therapy and many had failed endonasal and endoscopic procedures. The mean follow-up was 43.6 months (range, 1 to 125 months). There were two early complications, a seroma and a hematoma. Sinus infection recurred in one patient 3 months postoperatively. The recurrent infection was treated in the same manner, using the available and viable galeal-frontalis flap to obliterate the frontal sinus, with no recurrence after 40 months. The galeal-frontalis flap has been investigated by angiography and is based on the supratrochlear and supraorbital vessels. Its location and vascularity make it reliable and effective for frontal sinus obliteration. In the head and neck area and elsewhere, filling defects with vascularized tissue prevents infection. A further advantage is that any residual defects are usually well tolerated by patients, and those requesting correction can be easily accommodated. The risks and complications from using exogenous materials and from performing secondary procedures for graft harvest are avoided. Considering that most patients presented with complications from advanced disease and that after one revision no patients have had recurrence of disease, obliterative treatment with the galeal-frontalis myofascial flap should be contemplated earlier in treating patients with chronic frontal sinus disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":6632937,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-10":1,"unknown":10}}},"text":"Preliminary pharmacological study of some Nigerian medicinal plants. 1.\nHerbalists in Nigeria use a variety of herbal remedies to treat various types of illness. Thirteen commonly used herbal plants in the Anambra State of Nigeria were identified and collected. Extracts were prepared and studied pharmacologically on various isolated and intact preparations. Toxicological and phytochemical studies were also conducted on most of these plants.","subset":"pubmed_abstract"} +{"meta":{"pmid":21991398,"dup_signals":{"dup_doc_count":31,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":28}}},"text":"Preexisting Japanese encephalitis virus neutralizing antibodies and increased symptomatic dengue illness in a school-based cohort in Thailand.\nDengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays; the clinical implications of this remain undefined. An improved understanding of whether and how JEV immunity modulates the clinical outcome of DENV infection is important as large-scale DENV vaccine trials will commence in areas where JEV is co-endemic and\/or JEV immunization is routine. The association between preexisting JEV neutralizing antibodies (NAbs) and the clinical severity of DENV infection was evaluated in a prospective school-based cohort in Thailand that captured asymptomatic, non-hospitalized, and hospitalized DENV infections. Covariates considered included age, baseline DENV antibody status, school of attendance, epidemic year, and infecting DENV serotype. 942 children experienced at least one DENV infection between 1998 and 2002, out of 3,687 children who were enrolled for at least one full year. In crude analysis, the presence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic infection (odds ratio [OR]= 1.55, 95% CI: 1.08-2.23) but not hospitalized illness or dengue hemorrhagic fever (DHF). The association was strongest in children with negative DENV serology (DENV-naive) (OR=2.75, 95% CI: 1.12-6.72), for whom the presence of JEV NAbs was also associated with a symptomatic illness of longer duration (5.4 days for JEV NAb+ versus 2.6 days for JEV NAb-, p=0.048). JEV NAbs were associated with increased DHF in younger children with multitypic DENV NAb profiles (OR=4.05, 95% CI: 1.18 to 13.87). Among those with JEV NAbs, the association with symptomatic illness did not vary by antibody titer. The prior existence of JEV NAbs was associated with an increased probability of symptomatic as compared to asymptomatic DENV illness. These findings are in contrast to previous studies suggesting an attenuating effect of heterologous flavivirus immunity on DENV disease severity.","subset":"pubmed_abstract"} +{"meta":{"pmid":19017578,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Medically intractable seizures originating from the primary somatosensory hand area.\nA 33-year-old woman had begun having intractable somatosensory seizures affecting the left hand since the age of 13 years. Occasionally, her seizures progressed to left arm posturing followed by secondary generalization. Scalp EEG revealed interictal epileptiform discharges in the right posterior quadrant, but with no ictal EEG correlates. Brain MRI showed a right temporal encephalomalacia, sparing mesial temporal structures, suggestive of a perinatal vascular insult. Ictal electrocorticogram, electrical stimulation mapping, and somatosensory evoked potentials localized the ictal onset to the hand area of the postcentral gyrus. Resection of that area resulted in total resolution of seizures with no significant lasting deficits. Potential complications of resecting the primary somatosensory hand area can be severe, as proprioceptive sensory loss may be permanent, resulting in significant disability. Such deficits may be temporary however, and the literature continues to report conflicting results regarding postsurgical outcome. Cortical plasticity may explain recovery of sensory deficits after partial resection of the primary somatosensory hand area. Multiple subpial transections of that area are sometimes performed to minimize functional deficits, but seizure control may be less optimal than with cortical resection.","subset":"pubmed_abstract"} +{"meta":{"pmid":20961469,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Chemotherapy against human African trypanosomiasis: is there a road to success?\nFor over fifty years, human African trypanosomiasis (HAT, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. Recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against T. brucei spp. and an acceptable toxicity index has remained astonishingly small. Clinical research continues to be difficult due to the economic constraints and the complexity of trials on a low prevalence disease in remote and impoverished African regions. Despite those limitations the situation for the patients is improving thanks to the combination of a number of critical factors. By the late 1990s the disease had reached epidemic levels that triggered political support. WHO would sign a donation agreement with the manufacturers for all drugs to treat HAT. A result of this agreement was that eflornithine which is much safer than melarsoprol became available and widely used by non-governmental organizations. The Impamel I and II programmes demonstrated that against all odds the conduct of clinical trials on HAT was feasible. This allowed the initiation of trials on combination therapies which eventually resulted in the nifurtimox-eflornithine combination treatment (NECT). This combination is currently being introduced as first line treatment, and there is even the prospect of having a new compound, fexinidazole, in the development pipeline. This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":29061844,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Alcohol control policies and alcohol consumption: an international comparison of 167 countries.\nAlcohol control policy has a fundamental role in limiting negative health, economic and social harm caused by alcohol consumption. However, there is substantial international heterogeneity in country-level policy adoption, implementation and monitoring. Comparative measures so far focused on Europe or the Organisation for Economic Co-operation and Development countries. We created an Alcohol Control Policy Index (ACPI) for 167 countries using five different methodological approaches. National policies were sourced from WHO's Global Information System on Alcohol and Health. We assessed ACPI's criterion-related validity by calculating the strength of the association among the different approaches. As for content validity, we tested whether the resulting scores explained variations in alcohol per capita consumption cross-nationally, controlling for gross domestic product, population age, urbanisation and world region using OLS and random coefficients models. Index scores and ranks from different methodological approaches are highly correlated (r=0.99). Higher scores were associated with lower consumption across the five methods. For each 1 score increase in the ACPI, the reduction in per capita alcohol consumption varies from -0.024 L (95% CI (-0.043 to -0.004) to -0.014 L (95% CI (-0.034 to 0.005). We obtain larger coefficients and p values <0.005 when estimating random coefficients. ACPI offers a measure of alcohol control policy across countries that makes use of a larger number of countries than its predecessors, as well as a wider range of methodologies for its calculation, both of which contribute to its validity. Furthermore, it shows that the statutory strictness of alcohol control policies is associated with lower levels of alcohol consumption.","subset":"pubmed_abstract"} +{"meta":{"pmid":32275148,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Comparison of the Performance of Machine Learning Models in Representing High-Dimensional Free Energy Surfaces and Generating Observables.\nFree energy surfaces of chemical and physical systems are often generated using a popular class of enhanced sampling methods that target a set of collective variables (CVs) chosen to distinguish the characteristic features of these surfaces. While some of these approaches are typically limited to low (\u223c1-3)-dimensional CV subspaces, methods such as driven adiabatic free-energy dynamics\/temperature-accelerated molecular dynamics have been shown to be capable of generating free energy surfaces of quite high dimension by sampling the associated marginal probability distribution via full sweeps over the CV landscape. These approaches repeatedly visit conformational basins, producing a scattering of points within the basins on each visit. Consequently, they are particularly amenable to synergistic combination with regression machine learning methods for filling in the surfaces between the sampled points and for providing a compact and continuous (or semicontinuous) representation of the surfaces that can be easily stored and used for further computation of observable properties. Given the central role of machine learning techniques in this combined approach, it is timely to provide a detailed comparison of the performance of different machine learning strategies and models, including neural networks, kernel ridge regression, support vector machines, and weighted neighbor schemes, for their ability to learn these high-dimensional surfaces as a function of the amount of sampled training data and, once trained, to subsequently generate accurate ensemble averages corresponding to observable properties of the systems. In this article, we perform such a comparison on a set of oligopeptides, in both gas and aqueous phases, corresponding to CV spaces of 2-10 dimensions and assess their ability to provide a global representation of the free energy surfaces and to generate accurate ensemble averages.","subset":"pubmed_abstract"} +{"meta":{"pmid":34036318,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"Increasing the availability and utilization of reliable data on population micronutrient (MN) status globally: the MN Data Generation Initiative.\nMicronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support.","subset":"pubmed_abstract"} +{"meta":{"pmid":21502632,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":14}}},"text":"Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans.\nPrevious in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 \u2192 3)-\u03b2-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg\/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 \u2192 3)-\u03b2-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg\/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg\/kg improved survival (85 to 95%) and reduced tissue burden and (1 \u2192 3)-\u03b2-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain.","subset":"pubmed_abstract"} +{"meta":{"pmid":22765382,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Using solid-state NMR to monitor the molecular consequences of Cryptococcus neoformans melanization with different catecholamine precursors.\nMelanins are a class of natural pigments associated with a wide range of biological functions, including microbial virulence, energy transduction, and protection against solar radiation. Because of their insolubility and structural heterogeneity, solid-state nuclear magnetic resonance (NMR) spectroscopy provides an unprecedented means to define the molecular architecture of these enigmatic pigments. The requirement of obligatory catecholamines for melanization of the pathogenic fungus Cryptococcus neoformans also offers unique opportunities for investigating melanin development. In the current study, pigments produced with L-dopa, methyl-L-dopa, epinephrine, and norepinephrine precursors are compared structurally using (13)C and (1)H magic-angle spinning (MAS) NMR. Striking structural differences were observed for both aromatic and aliphatic molecular constituents of the mature fungal pigment assemblies, thus making it possible to redefine the molecular prerequisites for formation of the aromatic domains of insoluble indole-based biopolymers, to rationalize their distinctive physical characteristics, and to delineate the role of cellular constituents in assembly of the melanized macromolecules with polysaccharides and fatty acyl chain-containing moieties. By achieving an augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly, such studies can guide future drug discovery efforts related to melanin-associated virulence, resistance to tumor therapy, and production of melanin mimetics under cell-free conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":19828470,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial.\nEosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitor-refractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated. Eleven adults with active EoO (>20 peak eosinophil number\/high power field (hpf) and dysphagia) were randomised to 750 mg of mepolizumab (n = 5) or placebo (n = 6) and received two intravenous infusions, 1 week apart. Those not in complete remission (<5 peak eosinophil number\/hpf) after 8 weeks received two further doses 4 weeks apart, 1500 mg of mepolizumab or placebo. The effect of mepolizumab was assessed clinically, endoscopically, histologically, and via blood and tissue biomarkers. As assessed by immunofluorescence, a marked reduction of mean oesophageal eosinophilia (p = 0.03) was seen in the mepolizumab group (-54%) compared with the placebo group (-5%) 4 weeks after initiation of treatment. No further reduction of eosinophil numbers was observed in response to the two additional infusions in either group. Mepolizumab reduced tenascin C (p = 0.033) and transforming growth factor beta1 (p = 0.05) expression in the oesophageal epithelial layer 13 weeks after initiation of treatment. Clinically, limited improvement of symptoms was seen, although a trend was seen between 4 and 13 weeks after initiation of mepolizumab treatment. Mepolizumab was well tolerated. Mepolizumab significantly reduced eosinophil numbers in oesophageal tissues in adult patients with active EoO, and changes in the expression of molecules associated with oesophageal remodelling were reversed. Minimal clinical improvement was achieved in a subgroup of patients with EoO. Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose level. NCT00274703.","subset":"pubmed_abstract"} +{"meta":{"pmid":23519441,"dup_signals":{"dup_doc_count":11}},"text":"Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory.\nTomosyn, a syntaxin-binding protein, is known to inhibit vesicle priming and synaptic transmission via interference with the formation of SNARE complexes. Using a lentiviral vector, we specifically overexpressed tomosyn1 in hippocampal dentate gyrus neurons in adult mice. Mice were then subjected to spatial learning and memory tasks and electrophysiological measurements from hippocampal slices. Tomosyn1-overexpression significantly impaired hippocampus-dependent spatial memory while tested in the Morris water maze. Further, tomosyn1-overexpressing mice utilize swimming strategies of lesser cognitive ability in the Morris water maze compared with control mice. Electrophysiological measurements at mossy fiber-CA3 synapses revealed impaired paired-pulse facilitation in the mossy fiber of tomosyn1-overexpressing mice. This study provides evidence for novel roles for tomosyn1 in hippocampus-dependent spatial learning and memory, potentially via decreased synaptic transmission in mossy fiber-CA3 synapses. Moreover, it provides new insight regarding the role of the hippocampal dentate gyrus and mossy fiber-CA3 synapses in swimming strategy preference, and in learning and memory.","subset":"pubmed_abstract"} +{"meta":{"pmid":26913836,"dup_signals":{"dup_doc_count":13}},"text":"Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.\nTo evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). Randomized, blinded study. Fifteen geriatric cats weighing 4.5 \u00b1 1.0 kg. Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. Mean \u00b1 standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 \u00b1 6.5% to 60.5 \u00b1 9.4% in group M, and from 51.8 \u00b1 5.0% to 64.1 \u00b1 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 \u00b1 12 to 56 \u00b1 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM. Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.","subset":"pubmed_abstract"} +{"meta":{"pmid":28719428,"dup_signals":{"dup_doc_count":20,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2021-49":1,"2021-43":1,"2021-21":1,"2021-17":1,"2021-04":2,"2020-24":1,"2019-47":1,"2019-13":1,"2018-51":1,"2018-47":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2022-49":1}}},"text":"Blood Product Utilization Among Trauma and Nontrauma Massive Transfusion Protocols at an Urban Academic Medical Center.\nHospital-wide massive transfusion protocols (MTPs) primarily designed for trauma patients may lead to excess blood products being prepared for nontrauma patients. This study characterized blood product utilization among distinct trauma and nontrauma MTPs at a large, urban academic medical center. A retrospective study of blood product utilization was conducted in patients who required an MTP activation between January 2011 and December 2015 at an urban academic medical center. Trauma MTP containers included 6 red blood cell (RBC) units, 5 plasma units, and 1 unit of apheresis platelets. Nontrauma MTP containers included 6 RBC and 3 plasma units. There were 334 trauma MTP activations, 233 nontrauma MTP activations, and 77 nontrauma MTP activations that subsequently switched to a trauma MTP (\"switched activations\"). All nontrauma MTP activations were among bleeding patients who did not have a traumatic injury (100% [233\/233]). Few patients with a nontrauma activation required ad hoc transfusion of RBC units (1.3% [95% confidence interval {CI}, 0.3%-3.7%]) or plasma (3.4% [95% CI, 1.5%-6.7%]), and only 45.5% (95% CI, 39.0%-52.1%) required ad hoc transfusion of apheresis platelets. Compared to trauma and switched activations, nontrauma activations transfused a lower median number of RBC, plasma, and apheresis platelet units (P < .001 for all comparisons). There was also a lower median number of prepared but unused plasma units for nontrauma activations (3; [interquartile range {IQR}, 3-5]) compared to trauma (7; [IQR, 5-10]; P < .001) and switched activations (8; [IQR, 5-11]; P < .001). The median number of unused apheresis platelet units was 1 (IQR, 1-2) for trauma activations and 0 (IQR, 0-1) for switched activations. There was a high proportion of trauma and switched activations in which all of the prepared apheresis platelet units were unused (28.1% [95% CI, 23.4%-33.3%] and 9.1% [95% CI, 3.7%-17.8%], respectively). The majority of initial nontrauma MTP activations did not require a switch to a trauma MTP. Patients remaining under a nontrauma MTP activation were associated with a lower number of transfused and unused plasma and apheresis platelet units. Future studies evaluating the use of hospital-wide nontrauma MTPs are warranted since an MTP designed for nontrauma patient populations may yield a key strategy to optimize blood product utilization in comparison to a universal MTP for both trauma and nontrauma patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":21329210,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-26":1,"unknown":12}}},"text":"Environmental proteomics: changes in the proteome of marine organisms in response to environmental stress, pollutants, infection, symbiosis, and development.\nEnvironmental proteomics, the study of changes in the abundance of proteins and their post-translational modifications, has become a powerful tool for generating hypotheses regarding how the environment affects the biology of marine organisms. Proteomics discovers hitherto unknown cellular effects of environmental stressors such as changes in thermal, osmotic, and anaerobic conditions. Proteomic analyses have advanced the characterization of the biological effects of pollutants and identified comprehensive and pollutant-specific sets of biomarkers, especially those highlighting post-translational modifications. Proteomic analyses of infected organisms have highlighted the broader changes occurring during immune responses and how the same pathways are attenuated during the maintenance of symbiotic relationships. Finally, proteomic changes occurring during the early life stages of marine organisms emphasize the importance of signaling events during development in a rapidly changing environment. Changes in proteins functioning in energy metabolism, cytoskeleton, protein stabilization and turnover, oxidative stress, and signaling are common responses to environmental change.","subset":"pubmed_abstract"} +{"meta":{"pmid":30929513,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2019-39":1,"2019-26":1,"2023-50":1,"2024-10":2,"2024-30":1}}},"text":"Placental Syncytiotrophoblast-Derived Extracellular Vesicles Carry Active NEP (Neprilysin) and Are Increased in Preeclampsia.\nNEP (neprilysin) is a widely expressed membrane-bound metalloprotease, which binds and cleaves a variety of peptides including vasodilators, natriuretics, and diuretics. Higher levels of NEP result in hypertension-a cardinal feature of the placental disease preeclampsia. Syncytiotrophoblast-derived extracellular vesicles (EVs), comprising microvesicles and exosomes, are released into the peripheral circulation in pregnancy and are postulated as a key mechanism coupling placental dysfunction and maternal phenotype in preeclampsia. We aimed to determine whether higher levels of active NEP are found in syncytiotrophoblast-derived EVs in preeclampsia compared with normal pregnancy. Using immunostaining and Western blotting, we first demonstrated that NEP levels are greater not only in preeclampsia placental tissue but also in syncytiotrophoblast-derived microvesicles and exosomes isolated from preeclampsia placentas ( P<0.05, n=5). We confirmed placental origin using antibody-coated magnetic beads to isolate NEP-bound vesicles, finding that they stain for placental alkaline phosphatase. NEP on syncytiotrophoblast-derived EVs is active and inhibited by thiorphan ( P<0.01, n=3; specific inhibitor). Syncytiotrophoblast-derived microvesicles, isolated from peripheral plasma, demonstrated higher NEP expression in preeclampsia using flow cytometry ( P<0.05, n=8). We isolated plasma exosomes using size-exclusion chromatography and showed greater NEP activity in preeclampsia ( P<0.05, n=8). These findings show that the placenta releases active NEP into the maternal circulation on syncytiotrophoblast-derived EVs, at significantly greater levels in preeclampsia. NEP has pathological roles in hypertension, heart failure, and amyloid deposition, all of which are features of preeclampsia. Circulating syncytiotrophoblast-derived EV-bound NEP thus may contribute to the pathogenesis of this disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":32673309,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Consistent sleep onset and maintenance of body weight after weight loss: An analysis of data from the NoHoW trial.\nSeveral studies have suggested that reduced sleep duration and quality are associated with an increased risk of obesity and related metabolic disorders, but the role of sleep in long-term weight loss maintenance (WLM) has not been thoroughly explored using prospective data. The present study is an ancillary study based on data collected on participants from the Navigating to a Healthy Weight (NoHoW) trial, for which the aim was to test the efficacy of an evidence-based digital toolkit, targeting self-regulation, motivation, and emotion regulation, on WLM among 1,627 British, Danish, and Portuguese adults. Before enrolment, participants had achieved a weight loss of \u22655% and had a BMI of \u226525 kg\/m2 prior to losing weight. Participants were enrolled between March 2017 and March 2018 and followed during the subsequent 12-month period for change in weight (primary trial outcome), body composition, metabolic markers, diet, physical activity, sleep, and psychological mediators\/moderators of WLM (secondary trial outcomes). For the present study, a total of 967 NoHoW participants were included, of which 69.6% were women, the mean age was 45.8 years (SD 11.5), the mean baseline BMI was 29.5 kg\/m2 (SD 5.1), and the mean weight loss prior to baseline assessments was 11.4 kg (SD 6.4). Objectively measured sleep was collected using the Fitbit Charge 2 (FC2), from which sleep duration, sleep duration variability, sleep onset, and sleep onset variability were assessed across 14 days close to baseline examinations. The primary outcomes were 12-month changes in body weight (BW) and body fat percentage (BF%). The secondary outcomes were 12-month changes in obesity-related metabolic markers (blood pressure, low- and high-density lipoproteins [LDL and HDL], triglycerides [TGs], and glycated haemoglobin [HbA1c]). Analysis of covariance and multivariate linear regressions were conducted with sleep-related variables as explanatory and subsequent changes in BW, BF%, and metabolic markers as response variables. We found no evidence that sleep duration, sleep duration variability, or sleep onset were associated with 12-month weight regain or change in BF%. A higher between-day variability in sleep onset, assessed using the standard deviation across all nights recorded, was associated with weight regain (0.55 kg per hour [95% CI 0.10 to 0.99]; P = 0.016) and an increase in BF% (0.41% per hour [95% CI 0.04 to 0.78]; P = 0.031). Analyses of the secondary outcomes showed that a higher between-day variability in sleep duration was associated with an increase in HbA1c (0.02% per hour [95% CI 0.00 to 0.05]; P = 0.045). Participants with a sleep onset between 19:00 and 22:00 had the greatest reduction in diastolic blood pressure (DBP) (P = 0.02) but also the most pronounced increase in TGs (P = 0.03). The main limitation of this study is the observational design. Hence, the observed associations do not necessarily reflect causal effects. Our results suggest that maintaining a consistent sleep onset is associated with improved WLM and body composition. Sleep onset and variability in sleep duration may be associated with subsequent change in different obesity-related metabolic markers, but due to multiple-testing, the secondary exploratory outcomes should be interpreted cautiously. The trial was registered with the ISRCTN registry (ISRCTN88405328).","subset":"pubmed_abstract"} +{"meta":{"pmid":28985104,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Sport Participation for Elite Athletes With Physical Disabilities: Motivations, Barriers, and Facilitators.\nThere are many reasons why individuals are motivated to participate in sports. Less attention, however, is given for studying motivation and athlete development in adapted sport. The purpose of this study was to identify the motivations, facilitators, and barriers to sports participation of elite athletes with a physical disability. Participants (N = 23, 17 males, six females, mean age: 24.3 years) were recruited through online listservs, e-mails, and snowball sampling. A semistructured interview guide was employed. Analysis was conducted and grounded in self-determination theory and literature surrounding barriers and facilitators of sports participation. Through coding by multiple researchers, six themes emerged. Themes indicated that athletes attributed participation to constructs of self-determination theory as well as overcoming specific barriers such as cost, time constraints, and lack of opportunity. Among facilitators to their athletic development, there were empowerment and advocacy, increased health, college scholarships, and achieving performance-related goals.","subset":"pubmed_abstract"} +{"meta":{"pmid":32470016,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Structure of cortical network activity across natural wake and sleep states in mice.\nCortical neurons fire intermittently and synchronously during non-rapid eye movement sleep (NREMS), in which active and silent periods are referred to as ON and OFF periods, respectively. Neuronal firing rates during ON periods (NREMS-ON-activity) are similar to those of wakefulness (W-activity), raising the possibility that NREMS-ON neuronal-activity is fragmented W-activity. To test this, we investigated the patterning and organization of cortical spike trains and of spike ensembles in neuronal networks using extracellular recordings in mice. Firing rates of neurons during NREMS-ON and W were similar, but showed enhanced bursting in NREMS with no apparent preference in occurrence, relative to the beginning or end of the on-state. Additionally, there was an overall increase in the randomness of occurrence of sequences comprised of multi-neuron ensembles in NREMS recorded from tetrodes. In association with increased burst firing, somatic calcium transients were increased in NREMS. The increased calcium transients associated with bursting during NREM may activate calcium-dependent, cell-signaling pathways for sleep related cellular processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":14659127,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"The best use of adjuvant endocrine treatments.\nEndocrine therapy remains important in the adjuvant treatment of pre- and postmenopausal women. Adjuvant ovarian ablation with or without tamoxifen produces effects which are equivalent to those of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in premenopausal women with oestrogen receptor (ER) and\/or progesterone receptor (PgR) positive breast cancer. Tamoxifen alone is also effective in these women. Concurrent use of tamoxifen and ovarian ablation may be even more effective, but more studies are needed. Tamoxifen remains a standard adjuvant therapy for postmenopausal women with ER and\/or PgR positive tumours. Current information supports the use of 5 years of tamoxifen but additional studies comparing 5 years to longer duration are ongoing. The aromatase inhibitor (AI) anastrozole has now been demonstrated to be better than tamoxifen in preventing recurrence in early reports from the Arimidex vs Tamoxifen And the Combination (ATAC) Trial. Ongoing trials of this and other AIs before, after, concurrent with, or substituted for tamoxifen in the adjuvant setting may soon revolutionize our approach for postmenopausal women. Adjuvant bisphosphonates have been shown to reduce the incidence of bone metastases and improve survival in two of three published adjuvant trials and are being further studied. Her-2 neu status is being explored as a predictive factor for selection of endocrine therapy, but is not yet considered standard for this purpose.","subset":"pubmed_abstract"} +{"meta":{"pmid":36265859,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"A second type of N7-guanine RNA cap methyltransferase in an unusual locus of a large RNA virus genome.\nThe order Nidovirales is a diverse group of (+)RNA viruses, with a common genome organization and conserved set of replicative and editing enzymes. In particular, RNA methyltransferases play a central role in mRNA stability and immune escape. However, their presence and distribution in different Nidovirales families is not homogeneous. In Coronaviridae, the best characterized family, two distinct methytransferases perform methylation of the N7-guanine and 2'-OH of the RNA-cap to generate a cap-1 structure (m7GpppNm). The genes of both of these enzymes are located in the ORF1b genomic region. While 2'-O-MTases can be identified for most other families based on conservation of both sequence motifs and genetic loci, identification of the N7-guanine methyltransferase has proved more challenging. Recently, we identified a putative N7-MTase domain in the ORF1a region (N7-MT-1a) of certain members of the large genome Tobaniviridae family. Here, we demonstrate that this domain indeed harbors N7-specific methyltransferase activity. We present its structure as the first N7-specific Rossmann-fold (RF) MTase identified for (+)RNA viruses, making it remarkably different from that of the known Coronaviridae ORF1b N7-MTase gene. We discuss the evolutionary implications of such an appearance in this unexpected location in the genome, which introduces a split-off in the classification of Tobaniviridae.","subset":"pubmed_abstract"} +{"meta":{"pmid":9705154,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-21":2,"2021-43":2,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-40":2,"2023-23":1,"2024-18":1,"2024-22":1}}},"text":"A monoclonal antibody directed against the non-toxic subunit of a dimeric phospholipase A2 neurotoxin, crotoxin, neutralizes its toxicity.\nCrotoxin is the main toxic component of the venom of the South-American rattlesnake Crotalus durissus terrificus. It is a phospholipase A2 neurotoxin constituted by the association of two subunits: an acidic, non-toxic and non-enzymatic subunit (CA) and a basic, weakly toxic phospholipase A2 (CB). A murine monoclonal antibody directed to the non-toxic subunit CA, A-56.36, was shown to fully neutralize the toxicity of crotoxin. When the in vitro pharmacological properties of crotoxin were further tested, A-56.36 was shown to enhance the enzymatic activity on negatively-charged phospholipids and to increase the acetylcholine release triggered by crotoxin on Torpedo synaptosomes. These effects were explained by the fast dissociation of the crotoxin complex in the presence of the monoclonal antibody A-56.36 and the immunocomplexation of CA, with CB being released in solution. CB is less toxic than crotoxin, has a higher enzymatic activity and triggers a higher acetylcholine release than crotoxin, due to its strong enzymatic activity. A single-chain variable fragment antibody was prepared from monoclonal antibody A-56.36. It binds to CA with a similar affinity than the parental immunoglobulin and exhibits similar effects on the in vitro pharmacological properties of crotoxin.","subset":"pubmed_abstract"} +{"meta":{"pmid":7513016,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2013-20":1,"2013-48":1,"unknown":6}}},"text":"Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells.\nTo understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.","subset":"pubmed_abstract"} +{"meta":{"pmid":29651456,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Systematic reconstruction of autism biology from massive genetic mutation profiles.\nAutism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module). These mutations do not recur or replicate at the variant level, but significantly and increasingly do so at gene and pathway levels. Genetic association reveals a novel gene + pathway dual-hit model, where the mutation burden becomes less relevant. In multiple independent analyses, hundreds of variants or genes repeatedly converge to several canonical pathways, either novel or literature-supported. These pathways define recurrent and systematic ASD biology, distinct from previously reported gene groups or networks. They also present a catalog of novel ASD risk factors including 118 variants and 72 genes. At a subpathway level, most variants disrupt the pathway-related gene functions, and in the same gene, they tend to hit residues extremely close to each other and in the same domain. Multiple interacting variants spotlight key modules, including the cAMP (adenosine 3',5'-monophosphate) second-messenger system and mGluR (metabotropic glutamate receptor) signaling regulation by GRKs (G protein-coupled receptor kinases). At a superpathway level, distinct pathways further interconnect and converge to three biology themes: synaptic function, morphology, and plasticity.","subset":"pubmed_abstract"} +{"meta":{"pmid":22520965,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":9}}},"text":"Characterization of a novel chaperone\/usher fimbrial operon present on KpGI-5, a methionine tRNA gene-associated genomic island in Klebsiella pneumoniae.\nSeveral strain-specific Klebsiella pneumoniae virulence determinants have been described, though these have almost exclusively been linked with hypervirulent liver abscess-associated strains. Through PCR interrogation of integration hotspots, chromosome walking, island-tagging and fosmid-based marker rescue we captured and sequenced KpGI-5, a novel genomic island integrated into the met56 tRNA gene of K. pneumoniae KR116, a bloodstream isolate from a patient with pneumonia and neutropenic sepsis. The 14.0 kb KpGI-5 island exhibited a genome-anomalous G + content, possessed near-perfect 46 bp direct repeats, encoded a \u03b31-chaperone\/usher fimbrial cluster (fim2) and harboured seven other predicted genes of unknown function. Transcriptional analysis demonstrated expression of three fim2 genes, and suggested that the fim2A-fim2K cluster comprised an operon. As fimbrial systems are frequently implicated in pathogenesis, we examined the role of fim2 by analysing KR2107, a streptomycin-resistant derivative of KR116, and three isogenic mutants (\u0394fim, \u0394fim2 and \u0394fim\u0394fim2) using biofilm assays, human cell adhesion assays and pair-wise competition-based murine models of intestinal colonization, lung infection and ascending urinary tract infection. Although no statistically significant role for fim2 was demonstrable, liver and kidney CFU counts for lung and urinary tract infection models, respectively, hinted at an ordered gradation of virulence: KR2107 (most virulent), KR2107\u2206fim2, KR2107\u2206fim and KR2107\u2206fim\u2206fim2 (least virulent). Thus, despite lack of statistical evidence there was a suggestion that fim and fim2 contribute additively to virulence in these murine infection models. However, further studies would be necessary to substantiate this hypothesis. Although fim2 was present in 13% of Klebsiella spp. strains investigated, no obvious in vitro or in vivo role for the locus was identified, although there were subtle hints of involvement in urovirulence and bacterial dissemination from the respiratory tract. Based on our findings and on parallels with other fimbrial systems, we propose that fim2 has the potential to contribute beneficially to pathogenesis and\/or environmental persistence of Klebsiella strains, at least under specific yet-to-be identified conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":27043092,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Rapid Development and Deployment of Ebola Readiness Training Across an Academic Health System: The Critical Role of Simulation Education, Consulting, and Systems Integration.\nIn this article, we describe an Ebola preparedness initiative with implementation across an academic health system. Key stakeholder centers of various disciplines and clinical experts collaborated in the development and design. Subject matter experts in the areas of Centers for Disease Control and Prevention and World Health Organization protocols for personal protective equipment donning and doffing conducted initial train-the-trainer sessions for program instructors. These trainers represented a cross-section of key clinical responders and environmental services. Through a parallel development process, a blended learning curriculum consisting of online modules followed by on-site training sessions was developed and implemented in both the simulation laboratory and the actual clinical care spaces in preparation for a Department of Health inspection. Lessons learned included identification of the need for iterative refinement based on instructor and trainee feedback, the lack of tolerance of practitioners in wearing full-body personal protective equipment for extended periods, and the ability of a large system to mount a rapid response to a potential public health threat through leveraging of expertise of its Simulation Program, Center for Quality, Safety and Innovation as well as a wide variety of clinical departments.","subset":"pubmed_abstract"} +{"meta":{"pmid":11297595,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial.\nWe hypothesized that the administration of troglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Four hundred and ten premenopausal women with PCOS in a multicenter, double blind trial were randomly assigned to 44 weeks of treatment with placebo (PBO) or troglitazone [150 mg\/day (TGZ-150), 300 mg\/day (TGZ-300), or 600 mg\/day (TGZ-600)]. We compared changes in ovulatory function (by monitoring the urinary level of pregnanediol-3-glucuronide daily), hirsutism (by a modified Ferriman-Gallwey scoring method), hormonal levels (total and free testosterone, androstenedione, sex hormone-binding globulin, LH, FSH, and the LH\/FSH ratio), and measures of glycemic parameters (fasting levels of glucose, insulin, hemoglobin A(1c), and the glucose and insulin areas under the curve during an oral glucose challenge) among study groups. Of the 410 patients recruited, 305 (74.4%) met evaluability criteria and were included in the analyses. The patients' baseline characteristics were similar across all treatment arms. Ovulatory rates were significantly greater for patients receiving TGZ-300 and TGZ-600 than for those receiving PBO (0.42 and 0.58 vs. 0.32; P < 0.05 and 0.0001, respectively). Of PCOS patients treated with TGZ-600, 57% ovulated over 50% of the time compared with 12% of placebo-treated patients. There was a significant decrease in the Ferriman-Gallwey score with TGZ-600 compared with PBO (0.22 +\/- 0.53 vs. -2.21 +\/- 0.49; P < 0.05, respectively). Free testosterone decreased and sex hormone-binding globulin increased in a dose-related fashion with troglitazone treatment, and all three troglitazone treatment groups were significantly different from placebo. Nearly all glycemic parameters showed dose-related decreases with troglitazone treatment. The total number and severity of adverse events (including elevations in liver enzymes) and the proportion of patients withdrawn from the study due to the development of adverse effects were similar between treatment groups. Troglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with a minimum of adverse effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":7472493,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Acetylcholine receptor aggregation at nerve-muscle contacts in mammalian cultures: induction by ventral spinal cord neurons is specific to axons.\nWe used a novel mammalian coculture system to study ACh receptor (AChR) redistribution and synaptic structure at nerve-muscle contacts. Ventral spinal cord (VSC) neurons were plated on cultures containing extensive myotubes but few fibroblasts. Neurite-induced redistribution of AChRs occurred within 6 hr after plating neurons and was maximal between 36-48 hr. This AChR redistribution appeared in two patterns: (1) AChR density at sites directly apposed to the neurite where neurites crossed preexisting AChR patches was sharply reduced, (2) Newly aggregated AChRs formed swaths lateral to the neurite path. VSC neurons induced more AChR aggregation than hippocampal, superior cervical ganglion and dorsal root ganglion neurons. The 43 and 58 kDa postsynaptic proteins were colocalized with AChR-enriched domains in all VSC neurite-induced aggregates whereas the colocalization of laminin was variable. Electron microscopy of regions with neurite-induced AChR aggregation showed postsynaptic membrane specializations characteristic of developing synapses and, in older cultures, features of more mature synaptic structure. Thus, the coculture system is useful for studying early stages of neuromuscular junction (NMJ) formation. Neurites in these cocultures were identified as axons or dendrites by morphological criteria and by their immunoreactivity for synaptophysin and phosphorylated heavy neurofilament subunits or for microtubule associated protein 2 (MAP2), respectively. Axons showed a 10-fold higher induction of AChR aggregation than did dendrites. Thus, at least one essential signaling molecule necessary for the induction of AChR aggregation at sites of interaction with muscle appears to be expressed in a polarized fashion in developing VSC neurons.","subset":"pubmed_abstract"} +{"meta":{"pmid":18826933,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":7}}},"text":"Inferring malaria parasite population structure from serological networks.\nThe malaria parasite Plasmodium falciparum is characterized by high levels of genetic diversity at antigenic loci involved in virulence and immune evasion. Knowledge of the population structure and dynamics of these genes is important for designing control programmes and understanding the acquisition of immunity to malaria; however, high rates of homologous and non-homologous recombination as well as complex patterns of expression within hosts have hindered attempts to elucidate these structures experimentally. Here, we analyse serological data from Kenya using a novel network technique to deconstruct the relationships between patients' immune responses to different parasite isolates. We show that particular population structures and expression patterns produce distinctive signatures within serological networks of parasite recognition, which can be used to discriminate between competing hypotheses regarding the organization of these genes. Our analysis suggests that different levels of immune selection occur within different groups of the same multigene family leading to mixed population structures.","subset":"pubmed_abstract"} +{"meta":{"pmid":22643050,"dup_signals":{"dup_doc_count":15,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":7}}},"text":"The impact of loneliness on self-rated health symptoms among victimized school children.\nLoneliness is associated with peer victimization, and the two adverse experiences are both related to ill health in childhood and adolescence. There is, however, a lack of knowledge on the importance of loneliness among victimized children. Therefore, possible modifying effects of loneliness on victimized school children's self-rated health were assessed. A population based cross-section study included 419 children in grades 1-10 from five schools. The prevalence of loneliness and victimization across grades was analyzed by linear test for trend, and associations of the adverse experiences with four health symptoms (sadness, anxiety, stomach ache, and headache) were estimated by logistic regression. In crude regression analysis, both victimization and loneliness showed positive associations with all the four health symptoms. However, in multivariable analysis, the associations of victimization with health symptoms were fully attenuated except for headache. In contrast, loneliness retained about the same strength of associations in the multivariable analysis as in the crude analysis. More detailed analyses demonstrated that children who reported both victimization and loneliness had three to seven times higher prevalence of health symptoms compared to children who reported neither victimization nor loneliness (the reference group). Rather surprisingly, victimized children who reported no loneliness did not have any higher prevalence of health symptoms than the reference group, whereas lonely children without experiences of victimization had almost the same prevalence of health symptoms (except for stomach ache) as children who were both victimized and lonely. Adverse effects of loneliness need to be highlighted, and for victimized children, experiences of loneliness may be an especially harsh risk factor related to ill health.","subset":"pubmed_abstract"} +{"meta":{"pmid":3370920,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Effect of hyperoxia and hypoxia on exercise-induced breathlessness in normal subjects.\n1. The subjective changes accompanying alterations in inspired oxygen concentration during heavy exercise have been investigated single blind, in normal subjects. 2. In particular, the intensity of the sensation of breathlessness was quantified using a visual analogue scale and changes were compared with those in objective ventilatory measures. 3. Eleven subjects performed three steady-state work-load exercise tests on different days and 100% O2, 15% O2 or air were randomly administered for a fixed interval during each test. 4. Compared with air breathing, all subjects felt less breathless during 100% O2 breathing, and ten of them felt more breathless when inspiring 15% O2; these changes were reversed on return to air breathing. 5. During and after 100% O2, the time course of changes in breathlessness was similar to those for ear arterial oxygen saturation and minute ventilation such that it could be a secondary response to either. However, during and after inspiration of 15% O2, changes in breathlessness occurred relatively more quickly than those in ventilation, more closely reflecting changes in oxygen saturation; this suggests that hypoxia, per se, could contribute to the genesis of this sensation. 6. Individual variability in breathlessness responses to exercise and changes in inspired oxygen concentration did not correlate with objective ventilatory changes; neither were changes in breathlessness in the group particularly associated with changes in respiratory frequency or tidal volume.","subset":"pubmed_abstract"} +{"meta":{"pmid":29645047,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Boolean-chemotaxis of logibots deciphering the motions of self-propelling microorganisms.\nWe demonstrate the feasibility of a self-propelling mushroom motor, namely a 'logibot', as a functional unit for the construction of a host of optimized binary logic gates. Emulating the chemokinesis of unicellular prokaryotes or eukaryotes, the logibots made stimuli responsive conditional movements at varied speeds towards a pair of acid-alkali triggers. A series of integrative logic operations and cascaded logic circuits, namely, AND, NAND, NOT, OR, NOR, and NIMPLY, have been constructed employing the decisive chemotactic migrations of the logibot in the presence of the pH gradient established by the sole or coupled effects of acid (HCl-catalase) and alkali (NaOH) drips inside a peroxide bath. The imposed acid and\/or alkali triggers across the logibots were realized as inputs while the logic gates were functionally reconfigured to several operational modes by varying the pH of the acid-alkali inputs. The self-propelling logibot could rapidly sense the external stimuli, decide, and act on the basis of intensities of the pH triggers. The impulsive responses of the logibots towards and away from the external acid-alkali stimuli were interpreted as the potential outputs of the logic gates. The external stimuli responsive self-propulsion of the logibots following different logic gates and circuits can not only be an eco-friendly alternative to the silicon-based computing operations but also be a promising strategy for the development of intelligent pH-responsive drug delivery devices.","subset":"pubmed_abstract"} +{"meta":{"pmid":24796357,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"How we developed Doctors Speak Up: an evidence-based language and communication skills open access resource for International Medical Graduates.\nSome International Medical Graduates (IMGs) need to develop language and communication skills for patient-centred care but have limited opportunities to do so. To develop an evidence-based, language and communication skills web resource for IMG doctors and supervisors, focussing on culturally challenging patient interviews. Forty-eight IMGs participated in four practice OSCEs. We video-recorded the interactions and applied discourse analytic methods to investigate salient language and communication features. The findings from the OSCE workshops showed that many participants demonstrated aspects of patient-centred interviewing but were hindered by limited interactional competence to elicit information and negotiate behaviours as well as a limited repertoire of English grammar, vocabulary, and phonological phrasing for effective interaction. These findings guided the choice of content and pedagogy for the development of the web-based resource Doctors Speak Up. Evaluation and uptake of the Doctors Speak Up website confirm the demand for a resource combining targeted communication skills and language instruction. Over 19 500 users visited the website between March 2012 and November 2013.","subset":"pubmed_abstract"} +{"meta":{"pmid":26043188,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"2017-13":1,"unknown":5}}},"text":"Can Impacts of Climate Change and Agricultural Adaptation Strategies Be Accurately Quantified if Crop Models Are Annually Re-Initialized?\nEstimates of climate change impacts on global food production are generally based on statistical or process-based models. Process-based models can provide robust predictions of agricultural yield responses to changing climate and management. However, applications of these models often suffer from bias due to the common practice of re-initializing soil conditions to the same state for each year of the forecast period. If simulations neglect to include year-to-year changes in initial soil conditions and water content related to agronomic management, adaptation and mitigation strategies designed to maintain stable yields under climate change cannot be properly evaluated. We apply a process-based crop system model that avoids re-initialization bias to demonstrate the importance of simulating both year-to-year and cumulative changes in pre-season soil carbon, nutrient, and water availability. Results are contrasted with simulations using annual re-initialization, and differences are striking. We then demonstrate the potential for the most likely adaptation strategy to offset climate change impacts on yields using continuous simulations through the end of the 21st century. Simulations that annually re-initialize pre-season soil carbon and water contents introduce an inappropriate yield bias that obscures the potential for agricultural management to ameliorate the deleterious effects of rising temperatures and greater rainfall variability.","subset":"pubmed_abstract"} +{"meta":{"pmid":11890826,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Theoretical determination of chromophores in the chromogenic effects of aromatic neurotoxicants.\nWe report the first computational study of the chromophores responsible for the chromogenic effects of aromatic neurotoxicants containing a 1,2-diacetyl moiety in their oxidation metabolites. A series of ab initio electronic structure calculations was performed on two representative aromatic compounds, 1,2-diacetylbenzene (1,2-DAB) and 1,2-diacetyl tetramethyl tetralin (1,2-DATT), the putative active metabolites of the neurotoxic aromatic hydrocarbon compounds 1,2-diethylbenzene (1,2-DEB) and acetyl ethyl tetramethyl tetralin (AETT), and on the products of their possible reactions with proteins that result in chromogenic effects. The electronic excitation energies determined by three different computational approaches were found to be consistent with each other. The calculated results are consistent with the conclusion\/prediction that the chromogenic effects of 1,2-DAB (or 1,2-DEB) and 1,2-DATT (or AETT) could result from ninhydrin-like reactions, rather than the formation of pyrrole-like compounds. Our pK(a) calculations further indicate that the chromophore, i.e., the product of the ninhydrin-like reaction showing the blue color, is deprotonated in neutral aqueous solution. The corresponding protonated structure has a different color as it absorbs in the blue region of the visible spectrum, and its chromogenic contribution would be significant in solution at low pH.","subset":"pubmed_abstract"} +{"meta":{"pmid":24604345,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Synthesis of a carborane-containing cholesterol derivative and evaluation as a potential dual agent for MRI\/BNCT applications.\nIn this study the synthesis and characterization of a new dual, imaging and therapeutic, agent is proposed with the aim of improving the efficacy of Boron Neutron Capture Therapy (BNCT) in cancer treatment. The agent (Gd-B-AC01) consists of a carborane unit (ten boron atoms) bearing a cholesterol unit on one side (to pursue the incorporation into the liposome bi-layer) and a Gd(iii)\/1,4,7,10-tetraazacyclododecane monoamide complex on the other side (as a MRI reporter to attain the quantification of the B\/Gd concentration). In order to endow the BNCT agent with specific delivery properties, the liposome embedded with the MRI\/BNCT dual probes has been functionalized with a pegylated phospholipid containing a folic acid residue at the end of the PEG chain. The vector allows the binding of the liposome to folate receptors that are overexpressed in many tumor types, and in particular, in human ovarian cancer cells (IGROV-1). An in vitro test on IGROV-1 cells demonstrated that Gd-B-AC01 loaded liposomes are efficient carriers for the delivery of the MRI\/BNCT probes to the tumor cells. Finally, the BNCT treatment of IGROV-1 cells showed that the number of surviving cells was markedly smaller when the cells were irradiated after internalization of the folate-targeted GdB10-AC01\/liposomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":7154893,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2020-45":1,"2020-40":2,"2020-16":1,"2020-10":1,"2020-05":1,"2019-22":1,"2018-47":3,"2018-39":1,"2018-34":1,"2023-23":1}}},"text":"Psychophysical bases of perceived exertion.\nThere is a great demand for perceptual effort ratings in order to better understand man at work. Such ratings are important complements to behavioral and physiological measurements of physical performance and work capacity. This is true for both theoretical analysis and application in medicine, human factors, and sports. Perceptual estimates, obtained by psychophysical ratio-scaling methods, are valid when describing general perceptual variation, but category methods are more useful in several applied situations when differences between individuals are described. A presentation is made of ratio-scaling methods, category methods, especially the Borg Scale for ratings of perceived exertion, and a new method that combines the category method with ratio properties. Some of the advantages and disadvantages of the different methods are discussed in both theoretical-psychophysical and psychophysiological frames of reference.","subset":"pubmed_abstract"} +{"meta":{"pmid":31484672,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":19}}},"text":"Excess Light Priming in Arabidopsis thaliana Genotypes with Altered DNA Methylomes.\nPlants must continuously react to the ever-fluctuating nature of their environment. Repeated exposure to stressful conditions can lead to priming, whereby prior encounters heighten a plant's ability to respond to future events. A clear example of priming is provided by the model plant Arabidopsis thaliana (Arabidopsis), in which photosynthetic and photoprotective responses are enhanced following recurring light stress. While there are various post-translational mechanisms underpinning photoprotection, an unresolved question is the relative importance of transcriptional changes toward stress priming and, consequently, the potential contribution from DNA methylation - a heritable chemical modification of DNA capable of influencing gene expression. Here, we systematically investigate the potential molecular underpinnings of physiological priming against recurring excess-light (EL), specifically DNA methylation and transcriptional regulation: the latter having not been examined with respect to EL priming. The capacity for physiological priming of photosynthetic and photoprotective parameters following a recurring EL treatment was not impaired in Arabidopsis mutants with perturbed establishment, maintenance, or removal of DNA methylation. Importantly, no differences in development or basal photoprotective capacity were identified in the mutants that may confound the above result. Little evidence for a causal transcriptional component of physiological priming was identified; in fact, most alterations in primed plants presented as a transcriptional 'dampening' in response to an additional EL exposure, likely a consequence of physiological priming. However, a set of transcripts uniquely regulated in primed plants provide preliminary evidence for a novel transcriptional component of recurring EL priming, independent of physiological changes. Thus, we propose that physiological priming of recurring EL in Arabidopsis occurs independently of DNA methylation; and that the majority of the associated transcriptional alterations are a consequence, not cause, of this physiological priming.","subset":"pubmed_abstract"} +{"meta":{"pmid":26993743,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm.\nMany conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate\/nitrite\/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.","subset":"pubmed_abstract"} +{"meta":{"pmid":28654597,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Involvement of the Interosseous and Lumbrical Muscle-Tendon Units in the Lateral and Spiral Cords in Dupuytren's Disease of the Middle Fingers.\nThe nature of intrinsic muscle involvement in Dupuytren's disease of the middle fingers (long and ring) remains poorly characterized. Over the years, the authors have observed that both the spiral and lateral digital cords in the middle fingers receive contribution from intrinsic muscle-tendon units. This report describes the anatomical characteristics and frequency of intrinsic muscle-tendon unit involvement in Dupuytren's disease of the middle fingers. Intrinsic muscle involvement in the middle digits was recorded in the operative reports of patients undergoing Dupuytren's surgery between October of 2013 and February of 2016. The anatomical variations of diseased fascia were delineated and classified. Of the 113 digits with Dupuytren's contracture operated on during this period, 52 involved the middle fingers (12 long and 40 ring fingers). Intrinsic muscles were found to be involved in the contracture of 14 of these digits. Two unique contracture patterns were identified: type I contracture, which involves a lateral digital cord originating from intrinsic muscle-tendon units and contracting only the proximal interphalangeal joint; and type II contracture, which involves a spiral cord receiving contribution from intrinsic muscle-tendon units and contracting both the metacarpophalangeal and proximal interphalangeal joints. The frequency of type I and type II contractures was 6 percent and 12 percent, respectively. Intrinsic hand muscles may contribute to Dupuytren's disease in the middle digits, and the authors suggest resecting cords as close as possible to their musculotendinous origin to improve postoperative outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":9343254,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Susceptibility of human immunodeficiency virus type 1 group O isolates to antiretroviral agents: in vitro phenotypic and genotypic analyses.\nWe investigated the phenotypic and genotypic susceptibility of 11 human immunodeficiency virus type 1 (HIV-1) group O strains to nucleoside and nonnucleoside reverse transcriptase (RT) inhibitors and protease inhibitors in vitro. Phenotypic susceptibility was determined by using a standardized in vitro assay of RT inhibition, taking into account the replication kinetics of each strain. HIV-1 group M and HIV-2 isolates were used as references. DNA from cocultured peripheral blood mononuclear cells was amplified by using pol-specific group O primers and cloned for sequencing. Group O isolates were highly sensitive to nucleoside inhibitors, but six isolates were naturally highly resistant to all of the nonnucleoside RT inhibitors tested. Phylogenetic analysis of the pol gene showed that these isolates formed a separate cluster within group O, and genotypic analysis revealed a tyrosine-to-cysteine substitution at residue 181. Differences in susceptibility to saquinavir and ritonavir (RTV) were not significant between group O and group M isolates, although the 50% inhibitory concentration of RTV for group O isolates was higher than that for the HIV-1 subtype B strains. The study of HIV-1 group O susceptibility to antiretroviral drugs revealed that the viruses tested had specific phenotypic characteristics contrasting with the group M phenotypic expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":7185852,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Auto-immune complications of D-penicillamine--a possible result of zinc and magnesium depletion and of pyridoxine inactivation.\nLong-term high-dosage penicillamine treatment of patients with advanced stages of diseases with autoimmune components has resulted in very few adverse reactions in a series of over 50 such patients also given selected nutrients: pyridoxine, zinc and magnesium (which penicillamine inactivates or chelates), and vitamins B1, B12, and E (which have sulfhydryl-protective activity). The patients on this regimen have been essentially free of the side effects that occur in about a third of patients treated with penicillamine without such supplements. Reports of myasthenia gravis--a disease with abnormalities of the thymus and of T-cells, as a side effect of penicillamine--suggest that zinc, magnesium, and pyridoxine might be the agents most likely to be protective. Pyridoxine is necessary for cellular accumulation of zinc and magnesium, deficiencies of which have caused thymic and other immunologic abnormalities. Whether the other vitamins administered contribute to the favorable results requires further study.","subset":"pubmed_abstract"} +{"meta":{"pmid":23515006,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial.\nDocosahexaenoic acid (DHA) is important for brain function, and its status is dependent on dietary intakes. Therefore, individuals who consume diets low in omega-3 (n-3) polyunsaturated fatty acids may cognitively benefit from DHA supplementation. Sex and apolipoprotein E genotype (APOE) affect cognition and may modulate the response to DHA supplementation. We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response. Healthy adults (n = 176; age range: 18-45 y; nonsmoking and with a low intake of DHA) completed a 6-mo randomized, placebo-controlled, double-blind intervention in which they consumed 1.16 g DHA\/d or a placebo. Cognitive performance was assessed by using a computerized cognitive test battery. For all tests, z scores were calculated and clustered into cognitive domains as follows: episodic and working memory, attention, reaction time (RT) of episodic and working memory, and attention and processing speed. ANCOVA was conducted with sex and APOE as independent variables. RTs of episodic and working memory improved with DHA compared with placebo [mean difference (95% CI): -0.18 SD (-0.33, -0.03 SD) (P = 0.02) and -0.36 SD (-0.58, -0.14 SD) (P = 0.002), respectively]. Sex \u00d7 treatment interactions occurred for episodic memory (P = 0.006) and the RT of working memory (P = 0.03). Compared with the placebo, DHA improved episodic memory in women [0.28 SD (0.08, 0.48 SD); P = 0.006] and RTs of working memory in men [-0.60 SD (-0.95, -0.25 SD); P = 0.001]. APOE did not affect cognitive function, but there were some indications of APOE \u00d7 sex \u00d7 treatment interactions. DHA supplementation improved memory and the RT of memory in healthy, young adults whose habitual diets were low in DHA. The response was modulated by sex. This trial was registered at the New Zealand Clinical Trials Registry (http:\/\/www.anzctr.org.au\/default.aspx) as ACTRN12610000212055.","subset":"pubmed_abstract"} +{"meta":{"pmid":26745853,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":2,"unknown":9}}},"text":"RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity.\nRUNX1\/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD\/MM). However, the molecular mechanism of FPD\/MM remains unknown. Here we show that murine Runx1(+\/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem\/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+\/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+\/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem\/progenitor cells and blocking myeloid differentiation in response to G-CSF.","subset":"pubmed_abstract"} +{"meta":{"pmid":26197759,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.\nAmidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 \u00b0C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 \u00b0C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different.","subset":"pubmed_abstract"} +{"meta":{"pmid":28717060,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Clinical data analysis of genotypes and phenotypes of deafness gene mutations in newborns: A retrospective study.\nWe retrospectively analyzed newborns with deafness gene mutations and summarized the relationship between genotype and phenotype to provide a basis for genetic counseling. We studied 582 subjects positive for deafness gene mutations that were treated in the otology outpatient department of Beijing Tongren Hospital, Capital Medical University, between April 2012 and April 2016. The subjects were divided into 3 categories: a diagnosed group (group A), which was further subdivided into subgroups A1 (homozygous and compound heterozygous GJB2 mutations) and A2 (homozygous and compound heterozygous SLC26A4 mutations); a drug-induced deafness group (group B, mitochondrial (Mt) gene mutations); and a mutation carrier group (group C), which was further subdivided into the subgroups C1 (GJB2 heterozygous mutations), C2 (SLC26A4 heterozygous mutations), C3 (GJB3 heterozygous mutations), and C4 (double gene mutations). Partial sequences positive for GJB2 or SLC26A4 were sequenced and analyzed for mutations. Subjects underwent otoscopic examination and comprehensive audiological evaluation, and temporal bone computerized tomography and\/or inner ear magnetic resonance imaging were performed. GJB2 235delC was the most common mutation locus. The highest proportion of deafness detected during universal newborn hearing screening was for drug-induced deafness, whereas the lowest was for the diagnosed group. GJB2 gene mutations mainly resulted in flat-type, profound-to-severe sensorineural hearing loss (SNHL). SLC26A4 gene mutation was mainly associated with high-frequency drop-type and profound-severe SNHL and was closely related to enlargement of the vestibular aqueduct.","subset":"pubmed_abstract"} +{"meta":{"pmid":3293891,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-40":1,"2022-33":1,"2022-05":2,"2021-49":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":2,"2020-16":2,"2022-49":1,"2024-10":1}}},"text":"A randomized controlled trial of the effect on blood pressure of dietary non-meat protein versus meat protein in normotensive omnivores.\n1. A randomized, controlled trial was carried out to examine whether changes in type and amount of dietary protein were responsible for earlier observations of blood-pressure-lowering effects of lacto-ovo-vegetarian diets. 2. Sixty-four subjects were pair-matched for sex, age, weight and sitting systolic blood pressure, and were randomly allocated to receive one of two types of protein supplement: one containing proteins from meat, the other proteins from non-meat sources. The supplements were balanced in terms of other nutrients. Consumption of other meat, poultry or fish was prohibited. 3. Sitting and standing blood pressures, weight, dietary intakes and plasma and urinary electrolytes were measured at regular intervals during the 12 weeks of trial. Urinary 3-methylhistidine was used as a measure of compliance. 4. Fifty subjects completed the trial. There were no statistically significant blood pressure differences between groups either at baseline or at end-of-trial, neither were there any substantive differences in mean blood pressure changes between baseline and end-of-trial. 3-Methyl-histidine excretion was significantly lower in subjects on the non-meat diet. 5. The results suggest that the protein components of the lacto-ovo-vegetarian diet are not responsible for the blood-pressure-lowering effects of that diet.","subset":"pubmed_abstract"} +{"meta":{"pmid":19702573,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-14":1,"2021-21":1,"2019-30":1,"2019-26":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-26":1,"2017-43":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-50":1,"2024-22":1,"2013-20":1,"2024-26":1}}},"text":"Cross currents in protein misfolding disorders: interactions and therapy.\nProtein Misfolding Disorders (PMDs) are a group of diseases characterized by the accumulation of abnormally folded proteins. Despite the wide range of proteins and tissues involved, PMDs share similar molecular and pathogenic mechanisms. Several epidemiological, clinical and experimental reports have described the co-existence of PMDs, suggesting a possible cross-talk between them. A better knowledge of the molecular basis of PMDs could have important implications for understanding the mechanism by which these diseases appear and progress and ultimately to develop novel strategies for treatment. Due to their similar molecular mechanisms, common therapeutic strategies could be applied for the diseases in this group.","subset":"pubmed_abstract"} +{"meta":{"pmid":28301572,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Far-infrared suppresses skin photoaging in ultraviolet B-exposed fibroblasts and hairless mice.\nUltraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Collagen, which is one of the main building blocks of human skin, is regulated by collagen synthesis and collagen breakdown. Autophagy was found to block the epidermal hyperproliferative response to UVB and may play a crucial role in preventing skin photoaging. In the present study, we investigated whether far-infrared (FIR) therapy can inhibit skin photoaging via UVB irradiation in NIH 3T3 mouse embryonic fibroblasts and SKH-1 hairless mice. We found that FIR treatment significantly increased procollagen type I through the induction of the TGF-\u03b2\/Smad axis. Furthermore, UVB significantly enhanced the expression of matrix metalloproteinase-1 (MMP-1) and MMP-9. FIR inhibited UVB-induced MMP-1 and MMP-9. Treatment with FIR reversed UVB-decreased type I collagen. In addition, FIR induced autophagy by inhibiting the Akt\/mTOR signaling pathway. In UVB-induced skin photoaging in a hairless mouse model, FIR treatment resulted in decreased skin thickness in UVB irradiated mice and inhibited the degradation of collagen fibers. Moreover, FIR can increase procollagen type I via the inhibition of MMP-9 and induction of TGF-\u03b2 in skin tissues. Therefore, our study provides evidence for the beneficial effects of FIR exposure in a model of skin photoaging.","subset":"pubmed_abstract"} +{"meta":{"pmid":17331214,"dup_signals":{"dup_doc_count":19,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2024-22":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2024-26":1,"unknown":10}}},"text":"Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats.\nIt is now well established that subthalamic nucleus high-frequency stimulation (STN HFS) alleviates motor problems in Parkinson's disease. However, its efficacy for cognitive function remains a matter of debate. The aim of this study was to assess the effects of STN HFS in rats performing a visual attentional task. Bilateral STN HFS was applied in intact and in bilaterally dopamine (DA)-depleted rats. In all animals, STN HFS had a transient debilitating effect on all the variables measured in the task. In DA-depleted rats, STN HFS did not alleviate the deficits induced by the DA lesion such as omissions and latency to make correct responses, but induced perseverative approaches to the food magazine, an indicator of enhanced motivation. In sham-operated controls, STN HFS significantly reduced accuracy and induced perseverative behaviour, mimicking partially the effects of bilateral STN lesions in the same task. These results are in line with the hypothesis that STN HFS only partially mimics inactivation of STN produced by lesioning and confirm the motivational exacerbation induced by STN inactivation.","subset":"pubmed_abstract"} +{"meta":{"pmid":16731015,"dup_signals":{"dup_doc_count":27,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":1,"2015-18":1,"unknown":24}}},"text":"Global gene expression during nitrogen starvation in the rice blast fungus, Magnaporthe grisea.\nEfficient regulation of nitrogen metabolism likely plays a role in the ability of fungi to exploit ecological niches. To learn about regulation of nitrogen metabolism in the rice blast pathogen Magnaporthe grisea, we undertook a genome-wide analysis of gene expression under nitrogen-limiting conditions. Five hundred and twenty genes showed increased transcript levels at 12 and 48 h after shifting the fungus to media lacking nitrate as a nitrogen source. Thirty-nine of these genes have putative functions in amino acid metabolism and uptake, and include the global nitrogen regulator in M. grisea, NUT1. Evaluation of seven nitrogen starvation-induced genes revealed that all were expressed during rice infection. Targeted gene replacement on one such gene, the vacuolar serine protease, SPM1, resulted in decreased sporulation and appressorial development as well as a greatly attenuated ability to cause disease. Data are discussed in the context of nitrogen metabolism under starvation conditions, as well as conditions potentially encountered during invasive growth in planta.","subset":"pubmed_abstract"} +{"meta":{"pmid":19691853,"dup_signals":{"dup_doc_count":27,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2013-48":2,"2024-18":1,"unknown":21}}},"text":"Excellent outcomes among HIV+ children on ART, but unacceptably high pre-ART mortality and losses to follow-up: a cohort study from Cambodia.\nAlthough HIV program evaluations focusing on mortality on ART provide important evidence on treatment effectiveness, they do not asses overall HIV program performance because they exclude patients who are eligible but not started on ART for whatever reason. The objective of this study was to measure mortality that occurs both pre-ART and during ART among HIV-positive children enrolled in two HIV-programs in Cambodia. Retrospective cohort study on 1168 HIV-positive children <15 years old registered in two HIV-programs over a four-year period. Mortality rates were calculated for both children on treatment and children not started on ART. Over half (53%) of children were 5 years or above and only 69(6%) were <18 months. Overall, 9% (105\/1168) of children died since the set-up of the programs. By the end of the observation period, 66(14.5%) patients not on ART had died compared to 39(5.5%) of those under treatment, and 100(22%) who did not start ART were lost-to-follow-up compared to 13(2%) on ART. 66\/105 (62.8%) of all in-program deaths occurred before starting ART, of which 56% (37\/66) and 79% (52\/66) occurred within 3 and 6 months of enrollment respectively. Mortality rate ratio between children not on ART and children on ART was 4.1 (95%CI: 2.7-6.2) (P < 0.001). The most common contributing cause of death in first 3 months of treatment and in first 3 months of program enrollment was tuberculosis. 41\/52 (79%) children who died within 6 months of enrollment had met the ART eligibility criteria before death. HIV-positive children experienced a high mortality and loss-to-follow-up rates before starting ART. These program outcomes may be improved by a more timely ART initiation. Measuring overall in-program mortality as opposed to only mortality on ART is recommended in order to more accurately evaluate pediatric HIV-programs performance.","subset":"pubmed_abstract"} +{"meta":{"pmid":27532626,"dup_signals":{"dup_doc_count":26,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":2,"2022-40":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-39":1,"2018-51":1,"2017-47":2,"2017-43":1,"2017-34":2,"2017-30":1,"2016-40":3,"2023-50":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"FRETBursts: An Open Source Toolkit for Analysis of Freely-Diffusing Single-Molecule FRET.\nSingle-molecule F\u00f6rster Resonance Energy Transfer (smFRET) allows probing intermolecular interactions and conformational changes in biomacromolecules, and represents an invaluable tool for studying cellular processes at the molecular scale. smFRET experiments can detect the distance between two fluorescent labels (donor and acceptor) in the 3-10 nm range. In the commonly employed confocal geometry, molecules are free to diffuse in solution. When a molecule traverses the excitation volume, it emits a burst of photons, which can be detected by single-photon avalanche diode (SPAD) detectors. The intensities of donor and acceptor fluorescence can then be related to the distance between the two fluorophores. While recent years have seen a growing number of contributions proposing improvements or new techniques in smFRET data analysis, rarely have those publications been accompanied by software implementation. In particular, despite the widespread application of smFRET, no complete software package for smFRET burst analysis is freely available to date. In this paper, we introduce FRETBursts, an open source software for analysis of freely-diffusing smFRET data. FRETBursts allows executing all the fundamental steps of smFRET bursts analysis using state-of-the-art as well as novel techniques, while providing an open, robust and well-documented implementation. Therefore, FRETBursts represents an ideal platform for comparison and development of new methods in burst analysis. We employ modern software engineering principles in order to minimize bugs and facilitate long-term maintainability. Furthermore, we place a strong focus on reproducibility by relying on Jupyter notebooks for FRETBursts execution. Notebooks are executable documents capturing all the steps of the analysis (including data files, input parameters, and results) and can be easily shared to replicate complete smFRET analyzes. Notebooks allow beginners to execute complex workflows and advanced users to customize the analysis for their own needs. By bundling analysis description, code and results in a single document, FRETBursts allows to seamless share analysis workflows and results, encourages reproducibility and facilitates collaboration among researchers in the single-molecule community.","subset":"pubmed_abstract"} +{"meta":{"pmid":24358312,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.\nGender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age \u00b1 SD: 40.9 \u00b1 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":27515700,"dup_signals":{"dup_doc_count":25,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2022-40":1,"2022-33":1,"2022-21":1,"2022-05":2,"2021-39":1,"2021-04":2,"2020-50":1,"2020-29":1,"2020-24":2,"2020-10":1,"2019-47":2,"2019-43":1,"2019-39":1,"2019-35":4,"2019-22":2,"2022-49":1}}},"text":"DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.\nThe Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes' promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology. We performed CpG methylation mapping focusing on the three genes' predicted CpG islands using the Sequenom EpiTYPER platform. DNA extracted from post-mortem brain tissue (BA10) from individuals who had lived with bipolar disorder (BD), major depressive disorder (MDD), as well as psychiatrically healthy individuals was used. Differences in methylation across all CpGs within a CpG island and between the three diagnostic groups were assessed by 2-way mixed model analyses of variance. We found no significant results for SYN1 or SYN3, but there was a significant group difference in SYN2 methylation, as well as an overall pattern of hypomethylation across the CpG island. Furthermore, we found a significant inverse correlation of DNA methylation with SYN2a mRNA expression. These findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":20858428,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2022-05":1,"2024-22":1}}},"text":"Kinesin recycling in stationary membrane tubes.\nCollections of motors dynamically organize to extract membrane tubes. These tubes grow but often pause or change direction as they traverse an underlying microtubule (MT) network. In vitro, membrane tubes also stall: they stop growing in length despite a large group of motors available at the tip to pull them forward. In these stationary membrane tubes in vitro, we find that clusters of processive kinesin motors form and reach the tip of the tube at regular time intervals. The average times between cluster arrivals depends on the time over which motors depart from the tip, suggesting that motors are recycled toward the tip. Numerical simulations of the motor dynamics in the membrane tube and on the MTs show that the presence of cooperative binding between motors quantitatively accounts for the clustering observed experimentally. Cooperative binding along the length of the MT and a nucleation point at a distance behind the tip define the recycling period. Based on comparison of the numerical results and experimental data, we estimate a cooperative binding probability and concentration regime where the recycling phenomenon occurs.","subset":"pubmed_abstract"} +{"meta":{"pmid":31308440,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"Establishing next-generation pest control services in rice fields: eco-agriculture.\nPesticides are commonly used in food crop production systems to control crop pests and diseases and ensure maximum yield with high market value. However, the accumulation of these chemical inputs in crop fields increases risks to biodiversity and human health. In addition, people are increasingly seeking foods in which pesticide residues are low or absent and that have been produced in a sustainable fashion. More than half of the world's human population is dependent on rice as a staple food and chemical pesticides to control pests is the dominant paradigm in rice production. In contrast, the use of natural enemies to suppress crop pests has the potential to reduce chemical pesticide inputs in rice production systems. Currently, predators and parasitoids often do not persist in rice production landscapes due to the absence of shelter or nutritional sources. In this study, we modified the existing rice landscape through an eco-engineering technique that aims to increase natural biocontrol agents for crop protection. In this system, planting nectar-rich flowering plants on rice bunds provides food and shelter to enhance biocontrol agent activity and reduce pest numbers, while maintaining grain yield. The abundance of predators and parasitoids and parasitism rates increased significantly in the eco-engineering plots compared to the insecticide-treated and control plots. Moreover, a significantly lower number of principal insect pests and damage symptoms were found in treatments where flowering plants were grown on bunds than in plots where such plants were not grown. This study indicates that manipulating habitat for natural enemies in rice landscapes enhances pest suppression and maintains equal yields while reducing the need for insecticide use in crop fields.","subset":"pubmed_abstract"} +{"meta":{"pmid":29045647,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation.\nTo support decision-making regarding prosthetic valve selection in non-elderly adults, we aim to provide a detailed overview of outcome after contemporary mechanical aortic valve replacement (AVR). A systematic review was conducted for papers reporting clinical outcome after AVR with bileaflet mechanical valves with a mean patient age \u226518 and \u226455 years, published between 1 January 1995 and 31 December 2015. Through meta-analysis outcomes were pooled and entered into a microsimulation model to calculate (event-free) life expectancy and lifetime event risk. Twenty-nine publications, encompassing a total of 5728 patients with 32 515 patient-years of follow-up (pooled mean follow-up: 5.7 years), were included. Pooled mean age at surgery was 48.0 years. Pooled early mortality risk was 3.15% (95% confidence interval (CI):2.37-4.23), late mortality rate was 1.55%\/year (95%CI:1.25-1.92); 38.7% of late deaths were valve-related. Pooled thromboembolism rate was 0.90%\/year (95%CI:0.68-1.21), major bleeding 0.85%\/year (95%CI:0.65-1.12), nonstructural valve dysfunction 0.39%\/year (95%CI:0.21-0.76), endocarditis 0.41%\/year (95%CI:0.29-0.57), valve thrombosis 0.14%\/year (95%CI:0.08-0.25), structural valve deterioration 0.00%\/year (zero events observed), and reintervention 0.51%\/year (95%CI:0.37-0.71), mostly due to nonstructural valve dysfunction and endocarditis. For a 45-year-old, for example, this translated to an estimated life expectancy of 19 years (general population: 34 years) and lifetime risks of thromboembolism, bleeding and reintervention of 18%, 15%, and 10%, respectively. This study demonstrates that outcome after mechanical AVR in non-elderly adults is characterized by suboptimal survival and considerable lifetime risk of anticoagulation-related complications, but also reoperation. Non-elderly adult patients who are facing prosthetic valve selection are entitled to conveyance of evidence-based estimates of the risks and benefits of both mechanical and biological valve options in a shared decision-making process.","subset":"pubmed_abstract"} +{"meta":{"pmid":2843494,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"A novel oncogene from a human hepatocellular carcinoma.\nPrimary human hepatocellular carcinomas (HCC) were surveyed for oncogenes by transformation assays using NIH 3T3 cells and calcium phosphate coprecipitation method. One new transforming DNA, called lca (for liver cancer) was obtained, and its properties were studied in detail. The lca DNA, localized in a 10.5 kb DNA fragment, was assigned to human chromosome 2. It showed identical restriction enzyme cleavage profiles as its counterpart DNA obtained from normal tissue, indicating that there is no extensive DNA rearrangement associated with activation process of the lca DNA. The normal counterpart DNA shows no transforming activity. Recombinant genes of the laca and its normal counterpart made in vitro have allowed localization of the site of \"activation\" to a limited region of the 10.5 kb fragment. An independently obtained transforming DNA from another HCC exhibited identical restriction enzyme cleavage profiles. Thus, lca DNA is likely to represent a commonly encountered transforming DNA in HCC.","subset":"pubmed_abstract"} +{"meta":{"pmid":28895227,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Comparing Generic Drug Markets in Europe and the United States: Prices, Volumes, and Spending.\nPolicy Points: Our study indicates that there are opportunities for cost savings in generic drug markets in Europe and the United States. Regulators should make it easier for generic drugs to reach the market. Regulators and payers should apply measures to stimulate price competition among generic drugmakers and to increase generic drug use. To meaningfully evaluate policy options, it is important to analyze historical context and understand why similar initiatives failed previously. Rising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs. We compared generic drug prices and market shares in 13 European countries, using data from 2013, to assess the amount of variation that exists between countries. To place these results in context, we reviewed evidence from recent studies on the prices and use of generics in Europe and the United States. We also surveyed peer-reviewed studies, gray literature, and books published since 2000 to (1) outline existing generic drug policies in European countries and the United States; (2) identify ways to increase generic drug use and to promote price competition among generic drug companies; and (3) explore barriers to implementing reform of generic drug policies, using a historical example from the United States as a case study. The prices and market shares of generics vary widely across Europe. For example, prices charged by manufacturers in Switzerland are, on average, more than 2.5 times those in Germany and more than 6 times those in the United Kingdom, based on the results of a commonly used price index. The proportion of prescriptions filled with generics ranges from 17% in Switzerland to 83% in the United Kingdom. By comparison, the United States has historically had low generic drug prices and high rates of generic drug use (84% in 2013), but has in recent years experienced sharp price increases for some off-patent products. There are policy solutions to address issues in Europe and the United States, such as streamlining the generic drug approval process and requiring generic prescribing and substitution where such policies are not yet in place. The history of substitution laws in the United States provides insights into the economic, political, and cultural issues influencing the adoption of generic drug policies. Governments should apply coherent supply- and demand-side policies in generic drug markets. An immediate priority is to convince more physicians, pharmacists, and patients that generic drugs are bioequivalent to branded products. Special-interest groups continue to obstruct reform in Europe and the United States.","subset":"pubmed_abstract"} +{"meta":{"pmid":32407533,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":17}}},"text":"MinReact: a systematic approach for identifying minimal metabolic networks.\nGenome-scale metabolic models are widely constructed and studied for understanding various design principles underlying metabolism, predominantly redundancy. Metabolic networks are highly redundant and it is possible to minimize the metabolic networks into smaller networks that retain the functionality of the original network. Here, we establish a new method, MinReact that systematically removes reactions from a given network to identify minimal reactome(s). We show that our method identifies smaller minimal reactomes than existing methods and also scales well to larger metabolic networks. Notably, our method exploits known aspects of network structure and redundancy to identify multiple minimal metabolic networks. We illustrate the utility of MinReact by identifying multiple minimal networks for 77 organisms from the BiGG database. We show that these multiple minimal reactomes arise due to the presence of compensatory reactions\/pathways. We further employed MinReact for a case study to identify the minimal reactomes of different organisms in both glucose and xylose minimal environments. Identification of minimal reactomes of these different organisms elucidate that they exhibit varying levels of redundancy. A comparison of the minimal reactomes on glucose and xylose illustrates that the differences in the reactions required to sustain growth on either medium. Overall, our algorithm provides a rapid and reliable way to identify minimal subsets of reactions that are essential for survival, in a systematic manner. Algorithm is available from https:\/\/github.com\/RamanLab\/MinReact. Supplementary data are available at Bioinformatics online.","subset":"pubmed_abstract"} +{"meta":{"pmid":22380508,"dup_signals":{"dup_doc_count":31,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":2,"2020-45":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-13":2,"2017-51":2,"2017-43":2,"2017-34":2,"2023-40":1,"2024-30":3,"2024-26":1,"2013-48":1}}},"text":"Cognitive reserve, cortical plasticity and resistance to Alzheimer's disease.\nThere are aspects of the ageing brain and cognition that remain poorly understood despite intensive efforts to understand how they are related. Cognitive reserve is the concept that has been developed to explain how it is that some elderly people with extensive neuropathology associated with dementia show little in the way of cognitive decline. Cognitive reserve is intimately related to cortical plasticity but this also, as it relates to ageing, remains poorly understood at the present time. Despite the shortcomings in understanding, we do have some knowledge on which to base efforts to minimise the likelihood of an elderly person developing dementia. For some risks the evidence is far from secure, but resistance to Alzheimer's disease (AD) appears from epidemiological studies to be contributed to by avoiding hypertension in middle life, obesity, depression, smoking and diabetes and head injury and by undertaking extended years of education, physical exercise, and social and intellectual pursuits in middle and late life. Nutritional factors may also promote healthy brain ageing. Resistance to AD is also contributed to by genetic factors, particularly apolipoprotein E2, but some combinations of other genetic polymorphisms as well. Although multiple factors and possible interventions may influence cognitive reserve and susceptibility to dementia, much more work is required on the mechanisms of action in order to determine which, if any, may improve the clinical and epidemiological picture. Understanding of how such factors operate may lead to new initiatives to keep the elderly population in the 21st century able to lead active and fulfilling lives.","subset":"pubmed_abstract"} +{"meta":{"pmid":30296293,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Immunomodulatory activity of a novel polysaccharide from Lonicera japonica in immunosuppressed mice induced by cyclophosphamide.\nLonicera japonica is a typical Chinese herbal medicine. We previously reported a method to isolate polysaccharides from Lonicera japonica (LJP). In this study, we first performed a qualitative analysis of LJP using the Fourier Transform Infrared Spectrometer (FT-IR) and explored the monosaccharide composition of LJP using the pre-column derivatization high performance liquid chromatography (HPLC) method. We then investigated the immunomodulatory function of LJP in cyclophosphamide (CTX)-induced immunosuppressed mouse models. The results showed that LJP had the characteristic absorption of typical polysaccharides consisting of 6 types of monosaccharides. In addition, LJP can increase significantly the organ index, splenic lymphocyte proliferation, macrophage phagocytosis, and natural killer (NK) cell activity in CTX-treated mice. LJP could also restore the levels of serum cytokines interleukin (IL-2), tumor necrosis factor (TNF-\u03b1) and Interferon-\u03b3 (IFN-\u03b3) in the CTX-treated mice. Finally, the results on measuring the T-lymphocytes subsets of spleen also confirmed LJP-induced immunomodulatory activity in immunosuppressed mice from another perspective. Therefore, LJP could be used as a potential immunomodulatory agent.","subset":"pubmed_abstract"} +{"meta":{"pmid":2506131,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Cloning, sequence determination, and expression of a 32-kilodalton-protein gene of Mycobacterium tuberculosis.\nWe describe the identification of the gene encoding an immunodominant 32-kilodalton (kDa) protein of Mycobacterium tuberculosis. The 32-kDa antigen is abundantly secreted into the culture supernatant of a variety of mycobacteria and appears to be a major stimulant of cellular and humoral immunity against mycobacteria. Recombinant clones expressing a 140- or 125-kDa beta-galactosidase fusion protein reactive with rabbit polyclonal anti-32 kDa protein serum were detected. The corresponding DNA sequence contains a 1,008-base-pair coding region. The deduced amino acid sequence corresponds to a 336-residue protein including the previously determined NH2-terminal sequence of the 32-kDa protein (J. De Bruyn, K. Huygen, R. Bosmans, M. Fauville, R. Lippens, J. P. Van Vooren, P. Falmagne, M. Weckx, H. G. Wiker, M. Harboe, and M. Turneer, Microb. Pathog. 2:351-366, 1987). Upstream of this NH2-terminal region, the gene codes for a signal peptide required for the secretion of a 294-amino-acid-long mature protein. A putative promoter sequence could be located upstream of the open reading frame. Comparison of the M. tuberculosis 32-kDa antigen with the Mycobacterium bovis BCG alpha-antigen (K. Matsuo, R. Yamaguchi, A. Yamazaki, H. Tasaka, and T. Yamada, J. Bacteriol. 170:3847-3854, 1988) revealed 73.8% homology between DNA sequences and 72.8% homology between amino acid sequences (signal and mature protein). Finally, the 140-kDa fusion protein could selectively be recognized by human tuberculous sera. This result confirms our previous finding that the 32-kDa antigen could be a valuable tool for the serological diagnosis of tuberculosis. Moreover, the availability of recombinant proteins opens perspectives for the localization of relevant B- and T-cell epitope regions on the 32-kDa antigen.","subset":"pubmed_abstract"} +{"meta":{"pmid":17249044,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Genetic basis of the major malate dehydrogenase isozymes in maize.\nThe mitochondrial MDH isozymes in the scutellum of the mature maize (Zea mays L.) kernel are encoded by three independently inherited nuclear genes. Mdh1 is located on chromosome 8, close to the breakpoint (8L.35) of a waxy-marked reciprocal translocation between chromosomes 8 and 9. Mdh2 is located in the distal region of the long arm of chromosome 6. Mdh3 is on the long arm of chromosome 3, approximately 2.6 map units from sh2. A modifier of the mitochondrial MDH isozymes (Mmm) maps approximately 27.5 units proximal to Adh1 in the central portion of the long arm of chromosome 1. Independently assorting duplicate genes code for the soluble MDH isozymes. Mdh4 is located in the same region of chromosome 1 as Mmm, approximately 29 map units proximal to Adh1. Mdh5 maps approximately 20 units distal to a2 in the short arm of chromosome 5.--Intergenic and interallelic heterodimer formation occurs among gene products that occupy the same subcellular compartment. MDH isozymes were purified and analyzed by native-SDS two-dimensional polyacrylamide gel electrophoresis. The proposed mitochondrial MDH intergenic heterodimer bands were found to be composed of two subunits, which differ in their migrations on SDS gels; whereas, genetically defined homodimers contained only one type of subunit.--This evidence is discussed in terms of two genetic models proposed for the maize mitochondrial MDH isozymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":21220074,"dup_signals":{"dup_doc_count":96,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-50":12,"2023-40":14,"2023-23":5,"2023-14":16,"2023-06":7,"2022-49":7,"2024-30":5,"2024-26":5,"2024-22":7,"2024-18":9,"2024-10":5,"2013-48":1,"2013-20":1}}},"text":"Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation.\nMany investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.","subset":"pubmed_abstract"} +{"meta":{"pmid":9639587,"dup_signals":{"dup_doc_count":24,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2021-10":1,"2020-10":1,"2019-39":1,"2019-13":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-34":1,"2017-26":2,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-50":1,"2024-10":2,"2017-13":1}}},"text":"A role of 5-HT2 receptors in the gill vasculature of the antarctic fish Pagothenia borchgrevinki.\nThis study was conducted to describe the cardiovascular responses to intra-arterial injections of serotonin in the Antarctic fish Pagothenia borchgrevinki and to elucidate the underlying mechanisms. Immunohistochemistry was used to localise serotonin-containing cells within the gills. Simultaneous and continuous recordings of ventral and dorsal aortic blood pressure, heart rate and ventral aortic blood flow (cardiac output) were made using standard cannulation procedures in combination with Doppler flow measurement. An extracorporeal loop with an in-line oxygen electrode allowed continuous measurements of arterial oxygen pressure PaO2. Pre-branchial injection of serotonin (5-hydroxytryptamine, 5-HT) or the 5-HT2 receptor agonist alpha-methylserotonin increased the branchial vascular resistance and ventral aortic pressure, while the 5-HT1 receptor agonist piperazine was without effect. The branchial vasoconstriction produced by serotonin injection was completely blocked by the 5-HT1\/5-HT2 receptor antagonist methysergide and the branchial vasoconstriction produced by WIDTH=\"9\" HEIGHT=\"12\" ALIGN=\"BOTTOM\" NATURALSIZEFLAG= alpha-methylserotonin injection was completely blocked by the specific 5-HT2 receptor antagonist LY53857. The results suggest that the 5-HT2 receptor alone mediates the branchial vasoconstriction. Serotonin also mediated a methysergide-sensitive reduction in PaO2, the reduction being greatest when the pre-injection PaO2 value was high. 5-HT-immunoreactive cells and nerve fibres were present within the gill tissues. All the 5-HT-immunoreactive cells were located on the efferent side of the filaments, but 5-HT-immunoreactive nerve fibres were found lining both of the branchial arteries. Our findings demonstrate a potential serotonergic control system for the gills in Pagothenia borchgrevinki. In contrast to its effects on the branchial vasculature, serotonin produced a methysergide-insensitive decrease in the systemic vascular resistance. However, neither the specific 5-HT1 nor 5-HT2 receptor agonists produced a decrease in the resistance of the systemic vasculature. The nature of the serotonergic receptor(s) inducing vasodilation in teleost fish is uncertain.","subset":"pubmed_abstract"} +{"meta":{"pmid":26034251,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A Comparison of the Request Process and Outcomes in Adult and Pediatric Organ Donation.\nAlthough existing studies suggest that factors affecting families' decisions regarding pediatric organ donation mirror those for adult patients, health professionals working in this area maintain that pediatric and adult decision-makers differ in significant ways. This study compared the request process, experiences, and authorization decisions between family decision-makers (FDMs) of adult and pediatric donors and nondonors. Perceptions of the donation request were collected via telephone interviews with 1601 FDMs approached by staff from 9 US organ procurement organizations (OPOs). Authorization regarding donation (ie, authorized\/refused) was obtained from FDM reports and verified by using OPO records. Tests of association were used to estimate differences between FDMs of adult and pediatric patients. A logistic regression analysis was conducted to identify variables predicting FDM authorization. FDMs of children were significantly more likely to authorize donation than were FDMs of adults (89.7% vs 83.2%; \u03c7(2) = 6.2, P = .01). Differences were found between pediatric and adult families' initial feelings toward donation, donation-related topics discussed, communication behaviors and techniques used, perceptions of the request, and receipt and preference of grief information. The likelihood of FDM authorization increased with the number of topics discussed and communication skills employed during requests. Authorization was not predicted by patient age (ie, adult versus pediatric). FDMs of children are willing to donate and experience no more psychological distress from the request for donation than do FDMs of adults. Communication emerged as a critical factor of family authorization, reinforcing its importance in requests for donation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22707367,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"An unusual cause for an optic disc haemorrhage.\nA 51-year-old male on chemotherapy for myeloma presented initially with a unilateral optic disc haemorrhage and signs of optic neuropathy. This rapidly progressed to affect both eyes and within a few days he developed retinal features suggestive of progressive outer retinal necrosis. He was treated with intravenous acyclovir that was subsequently changed to ganciclovir when serological tests for cytomegalovirus were found to be positive for immunoglobulin M antibodies. His visual loss continued to deteriorate despite treatment, and he subsequently developed a retinal detachment in one eye. The causes of optic neuropathy in immunocompromised patients and the importance of eliminating an infective cause are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":7942765,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Calendar effects in the analysis of seasonal data.\nA variety of statistical methods exist for analyzing seasonal patterns in epidemiologic data. As a simplification in the calculations, these methods often do not explicitly take into account certain calendar effects, such as the variation in month length, the irregular number of weekend days in each month, and the occurrence of holidays. This paper evaluates the bias caused by failing to recognize these effects. It is found that with the sample sizes commonly encountered in this type of analysis of epidemiologic data, calendar effects have a high probability of producing a spuriously significant seasonal effect, the amplitude of which may be of the same order of magnitude as the true underlying seasonal trend. Therefore, it is recommended that calendar effects be routinely taken into account, and some methods for doing so are proposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23082305,"dup_signals":{"dup_doc_count":65,"dup_dump_count":39,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-49":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-34":1,"2019-47":2,"2019-35":1,"2018-26":1,"2018-22":1,"2018-17":2,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":2,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":4,"2016-50":1,"2016-44":2,"2016-36":3,"2016-30":1,"2015-48":3,"2015-40":2,"2015-32":2,"2015-27":2,"2015-22":2,"2023-50":1,"2017-13":2,"2015-18":2}}},"text":"A comparison of Doppler optical coherence tomography methods.\nWe compare, in detail, the phase-resolved color Doppler (PRCD), phase-resolved Doppler variance (PRDV) and intensity-based Doppler variance (IBDV) methods. All the methods are able to quantify flow speed when the flow rate is within a certain range, which is dependent on the adjacent A-line time interval. While PRCD is most sensitive when the flow direction is along the probing beam, PRDV and IBDV can be used to measure the flow when the flow direction is near perpendicular to the probing beam. However, the values of PRDV and IBDV are Doppler angle-dependent when the Doppler angle is above a certain threshold. The sensitivity of all the methods can be improved by increasing the adjacent A-line time interval while still maintaining a high sampling density level. We also demonstrate for the first time, to the best of our knowledge, high resolution inter-frame PRDV method. In applications where mapping vascular network such as angiogram is more important than flow velocity quantification, IBDV and PRDV images show better contrast than PRCD images. The IBDV and PRDV show very similar characteristics and demonstrate comparable results for vasculature mapping. However, the IBDV is less sensitive to bulk motion and with less post-processing steps, which is preferred for fast data processing situations. In vivo imaging of mouse brain with intact skull and human skin with the three methods were demonstrated and the results were compared. The IBDV method was found to be able to obtain high resolution image with a relative simple processing procedure.","subset":"pubmed_abstract"} +{"meta":{"pmid":28261926,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.\nBile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. Ten morbidly obese women (BMI 42 \u00b1 2.6 kg m-2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day-1 ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin\/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m-2 ) served as controls. At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.","subset":"pubmed_abstract"} +{"meta":{"pmid":26585227,"dup_signals":{"dup_doc_count":31,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2020-45":1,"2020-40":1,"2020-34":5,"2019-47":2,"2019-43":4,"2019-39":2,"2019-35":4,"2019-30":5,"2019-26":5,"2021-17":1}}},"text":"Nax loci affect SOS1-like Na+\/H+ exchanger expression and activity in wheat.\nSalinity stress tolerance in durum wheat is strongly associated with a plant's ability to control Na(+) delivery to the shoot. Two loci, termed Nax1 and Nax2, were recently identified as being critical for this process and the sodium transporters HKT1;4 and HKT1;5 were identified as the respective candidate genes. These transporters retrieve Na(+) from the xylem, thus limiting the rates of Na(+) transport from the root to the shoot. In this work, we show that the Nax loci also affect activity and expression levels of the SOS1-like Na(+)\/H(+) exchanger in both root cortical and stelar tissues. Net Na(+) efflux measured in isolated steles from salt-treated plants, using the non-invasive ion flux measuring MIFE technique, decreased in the sequence: Tamaroi (parental line)>Nax1=Nax2>Nax1:Nax2 lines. This efflux was sensitive to amiloride (a known inhibitor of the Na(+)\/H(+) exchanger) and was mirrored by net H(+) flux changes. TdSOS1 relative transcript levels were 6-10-fold lower in Nax lines compared with Tamaroi. Thus, it appears that Nax loci confer two highly complementary mechanisms, both of which contribute towards reducing the xylem Na(+) content. One enhances the retrieval of Na(+) back into the root stele via HKT1;4 or HKT1;5, whilst the other reduces the rate of Na(+) loading into the xylem via SOS1. It is suggested that such duality plays an important adaptive role with greater versatility for responding to a changing environment and controlling Na(+) delivery to the shoot.","subset":"pubmed_abstract"} +{"meta":{"pmid":27465378,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":2,"2024-22":1,"unknown":10}}},"text":"Associations between nut consumption and inflammatory biomarkers.\nIncreased nut consumption has been associated with reduced risk of cardiovascular disease and type 2 diabetes, as well as a healthy lipid profile. However, the associations between nut consumption and inflammatory biomarkers are unclear. We investigated habitual nut consumption in relation to inflammatory biomarkers in 2 large cohorts of US men and women. We analyzed cross-sectional data from 5013 participants in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of diabetes. Nut intake, defined as intake of peanuts and other nuts, was estimated from food-frequency questionnaires, and cumulative averages from 1986 and 1990 in the NHS and from 1990 and 1994 in the HPFS were used. Plasma biomarkers were collected in 1989-1990 in the NHS and 1993-1995 in the HPFS. Multivariate linear regression was used to assess the associations of nut consumption with fasting plasma C-reactive protein (CRP, n = 4941), interleukin 6 (IL-6, n = 2859), and tumor necrosis factor receptor 2 (TNFR2, n = 2905). A greater intake of nuts was associated with lower amounts of a subset of inflammatory biomarkers, after adjusting for demographic, medical, dietary, and lifestyle variables. The relative concentrations (ratios) and 95% CIs comparing subjects with nut intake of \u22655 times\/wk and those in the categories of never or almost never were as follows: CRP: 0.80 (0.69, 0.90), P-trend = 0.0003; and IL-6: 0.86 (0.77, 0.97), P-trend = 0.006. These associations remained significant after further adjustment for body mass index. No significant association was observed with TNFR2. Substituting 3 servings of nuts\/wk for 3 servings of red meat, processed meat, eggs, or refined grains\/wk was associated with significantly lower CRP (all P < 0.0001) and IL-6 (P ranges from 0.001 to 0.017). Frequent nut consumption was associated with a healthy profile of inflammatory biomarkers.","subset":"pubmed_abstract"} +{"meta":{"pmid":7894321,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2023-06":2,"2022-49":1,"2022-21":1,"2021-43":2,"2020-40":1,"2019-13":1,"2018-30":1,"2017-51":1,"2016-44":1}}},"text":"Consumption of nitrate, nitrite, and nitrosodimethylamine and the risk of upper aerodigestive tract cancer.\nEvidence from animal studies indicates that various N-nitroso compounds are carcinogenic. We investigated whether consumption of foods and beverages containing nitrosodimethylamine, nitrites, and nitrates affected the risk of laryngeal, esophageal, and oral cancer. In a population-based case-control study in western Washington state, dietary consumption of these substances was measured in 645 cases (169 laryngeal, 125 esophageal, and 351 oral) and 458 controls. After adjustment for tobacco, alcohol, and other known risk factors, there was a 52% reduction in the risk of upper aerodigestive tract cancer for individuals who consumed higher amounts of nitrate (upper tertile) compared with the lowest tertile (P < 0.001 for trend). Nitrate intake was associated with a reduction in cancer risk at all three sites. The reduction in the risk of esophageal cancer with increasing nitrate consumption was more evident in frequent tea drinkers than in other subjects. There was no significant association between nitrite consumption and the risk of laryngeal or oral cancer. However, for individuals with a history of canker sores (an indicator of possible endogenous nitrosation), the risk of esophageal cancer was seven times greater in those with high versus low nitrite intake. Consumption of foods high in nitrosodimethylamine was associated with a 79% increased risk of upper aerodigestive tract cancer (P = 0.037 for trend). Cases consumed smoked fish more frequently than did controls [odds ratio (OR) = 3.03]. Daily intake of beer and of nitrite-containing meats were associated with an increased esophageal cancer risk (OR = 2.48 and 1.82, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":28332112,"dup_signals":{"dup_doc_count":12}},"text":"Perspectives on Exertional Rhabdomyolysis.\nExertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.","subset":"pubmed_abstract"} +{"meta":{"pmid":23600585,"dup_signals":{"dup_doc_count":21,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2021-04":2,"2020-24":1,"2020-16":7,"2020-10":1,"2019-18":3,"2019-13":3,"2019-04":1}}},"text":"Quantitative evaluation of the anatomical parameters for subaxial cervical spondylectomy: an anatomical study.\nThe object of this investigation was to conduct a morphometric study in cadavers to determine anatomical structures, their relationships, and their morphometry for subaxial cervical spondylectomy. Forty sides of 20 cadavers were used for this study. Dissections were performed in 2 stages (anteriorly and posteriorly). Twenty-one morphometric measurements were performed for both sides of the C3-6 vertebrae. Data were analyzed statistically. Morphometry of the laminas, tuberculum posterius, pedicle, corpus, foramen transversarium, and processus costalis were measured. Detailed quantitative anatomical knowledge for operations requiring wide dissection and resection, such as cervical spondylectomy, lowers the morbidity rate.","subset":"pubmed_abstract"} +{"meta":{"pmid":21451604,"dup_signals":{"dup_doc_count":30,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2018-09":1,"2017-39":1,"2016-44":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":2,"2015-40":3,"2015-35":1,"2015-32":2,"2015-27":3,"2015-22":2,"2018-34":1,"2015-18":2,"2017-13":1}}},"text":"Sculpturing of photonic crystals by ion beam lithography: towards complete photonic bandgap at visible wavelengths.\nThree dimensional (3D) ion beam lithography (IBL) is used to directly pattern 3D photonic crystal (PhC) structures in crystalline titania. The process is maskless and direct write. The slanted pore 3D structures with pore diameters of 100 nm having aspect ratio of 8 were formed. It is shown that chemical enhancement of titania removal up to 5.2 times is possible in XeF2 gas for the closest nozzle-to-sample distance; the enhancement was \u223c 1.5 times for the actual 3D patterning due to a sample tilt. Tolerances of structural parameters and optimization of IBL processing required for the fabrication of PhCs with full photonic bandgap in visible spectral range in rutile are outlined. Application potential of 3D-IBL is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":30487138,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":2,"unknown":12}}},"text":"Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.\nGenome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold\/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold\/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.","subset":"pubmed_abstract"} +{"meta":{"pmid":16396258,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":6}}},"text":"Brain magnetic resonance imaging characteristics in dogs and cats with congenital portosystemic shunts.\nAnimals with a portosystemic shunt (PSS) often have neurologic abnormalities. Diagnostic imaging, including brain magnetic resonance (MR) imaging, is not performed routinely in these animals. In this study, brain MR images were obtained in 13 dogs and three cats with a PSS, and in 15 dogs and five cats that were neurologically normal and used as controls. All animals with a PSS had widened sulci. In addition, 10 out of 13 dogs with a PSS and one out of three cats with a PSS had hyperintense focal areas in the lentiform nuclei on T1-weighted (T1W) images, which did not enhance after intravenous gadolinium. Following surgical correction of the PSS, MR imaging examinations were repeated in one dog and one cat. The hyperintensity of the lentiform nuclei had decreased. This study indicates that MR imaging findings of widened sulci and hyperintensity of the lentiform nuclei on T1W images may be found in dogs and cats with a PSS.","subset":"pubmed_abstract"} +{"meta":{"pmid":23799114,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evaluation of small intestine grafts decellularization methods for corneal tissue engineering.\nAdvances in the development of cornea substitutes by tissue engineering techniques have focused on the use of decellularized tissue scaffolds. In this work, we evaluated different chemical and physical decellularization methods on small intestine tissues to determine the most appropriate decellularization protocols for corneal applications. Our results revealed that the most efficient decellularization agents were the SDS and triton X-100 detergents, which were able to efficiently remove most cell nuclei and residual DNA. Histological and histochemical analyses revealed that collagen fibers were preserved upon decellularization with triton X-100, NaCl and sonication, whereas reticular fibers were properly preserved by decellularization with UV exposure. Extracellular matrix glycoproteins were preserved after decellularization with SDS, triton X-100 and sonication, whereas proteoglycans were not affected by any of the decellularization protocols. Tissue transparency was significantly higher than control non-decellularized tissues for all protocols, although the best light transmittance results were found in tissues decellularized with SDS and triton X-100. In conclusion, our results suggest that decellularized intestinal grafts could be used as biological scaffolds for cornea tissue engineering. Decellularization with triton X-100 was able to efficiently remove all cells from the tissues while preserving tissue structure and most fibrillar and non-fibrillar extracellular matrix components, suggesting that this specific decellularization agent could be safely used for efficient decellularization of SI tissues for cornea TE applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":17239241,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2024-22":1,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":6}}},"text":"Interleukin-10 inhibits osteoclastogenesis by reducing NFATc1 expression and preventing its translocation to the nucleus.\nIL-10 has a potent inhibitory effect on osteoclastogenesis. In vitro and in vivo studies confirm the importance of this cytokine in bone metabolism, for instance IL-10-deficient mice develop the hallmarks of osteoporosis. Although it is known that IL-10 directly inhibits osteoclastogenesis at an early stage, preventing differentiation of osteoclast progenitors to preosteoclasts, the precise mechanism of its action is not yet clear. Several major pathways regulate osteoclastogenesis, with key signalling genes such as p38, TRAF6, NF-kappaB and NFATc1 well established as playing vital roles. We have looked at gene expression in eleven of these genes using real-time quantitative PCR on RNA extracted from RANKL-treated RAW264.7 monocytes. There was no downregulation by IL-10 of DAP12, FcgammaRIIB, c-jun, RANK, TRAF6, p38, NF-kappaB, Gab2, Pim-1, or c-Fos at the mRNA level. However, we found that IL-10 significantly reduces RANKL-induced NFATc1 expression. NFATc1 is transcribed from two alternative promoters in Mus musculus and, interestingly, only the variant transcribed from promoter P1 and beginning with exon 1 was downregulated by IL-10 (isoform 1). In addition, immunofluorescence studies showed that IL-10 reduces NFATc1 levels in RANKL-treated precursors and suppresses nuclear translocation. The inhibitory effect of IL-10 on tartrate-resistant acid phosphatase-positive cell number and NFATc1 mRNA expression was reversed by the protein kinase C agonist phorbol myristate acetate, providing evidence that interleukin-10 disrupts NFATc1 activity through its effect on Ca2+ mobilisation. IL-10 acts directly on mononuclear precursors to inhibit NFATc1 expression and nuclear translocation, and we provide evidence that the mechanism may involve disruption of Ca2+ mobilisation. We detected downregulation only of the NFATc1 isoform 1 transcribed from promoter P1. This is the first report indicating that one of the ways in which IL-10 directly inhibits osteoclastogenesis is by suppressing NFATc1 activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":29669966,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"Effect of the National Stress Check Program on mental health among workers in Japan: A 1-year retrospective cohort study.\nThis retrospective cohort study evaluated the impact of the Stress Check Program, a recently introduced national policy and program aimed at reducing psychological distress among Japanese workers. A baseline survey was conducted from November 2015 to February 2016, the period when Japan began enforcing the Stress Check Program. A one-year follow-up survey was conducted in December 2016. In the follow-up survey, two exposure variables were collected: having taken the annual stress survey, and experiencing an improvement in the psychosocial work environment. Psychological distress was assessed using the Brief Job Stress Questionnaire (BJSQ) at baseline and 1-year follow-up. The two exposure variables were used to define four groups: \"Neither\", \"Stress survey (SS) only\", \"Psychosocial work environment improvement (WI) only\", and \"Both\". BJSQ results were analyzed using repeated measures general linear modeling (GLM). The study included 2,492 participants: 1,342 in the \"Neither\" group, 1,009 in the \"SS only\" group, 76 in the \"WI only\" group, and 65 in the \"Both\" group. Overall time-group interaction effects were not significant. The \"Both\" group showed significantly greater improvements in psychological distress than the \"Neither\" group (p = 0.02) at the 1-year follow-up, although the effect size was small (d = -0.14). Combination of the annual stress survey and improvement in psychosocial work environment may have been effective in reducing psychological distress in workers, although the effect size was small.","subset":"pubmed_abstract"} +{"meta":{"pmid":26130075,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-40":1,"2023-14":2,"2022-49":1,"2022-33":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-21":1,"2021-04":1,"2020-34":1,"2023-50":1,"2024-26":2,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"PRomotion Of Physical activity through structured Education with differing Levels of ongoing Support for people at high risk of type 2 diabetes (PROPELS): study protocol for a randomized controlled trial.\nThe prevention of type 2 diabetes is recognised as a health care priority. Lifestyle change has proven effective at reducing the risk of type 2 diabetes, but limitations in the current evidence have been identified in: the promotion of physical activity; availability of interventions that are suitable for commissioning and implementation; availability of evidence-based interventions using new technologies; and physical activity promotion among ethnic minorities. We aim to investigate whether a structured education programme with differing levels of ongoing support, including text-messaging, can increase physical activity over a 4 year period in a multi-ethnic population at high risk of diabetes. A multi-centre randomised controlled trial, with follow-up at 12 and 48 months. The primary outcome is change in ambulatory activity at 48 months. Secondary outcomes include changes to markers of metabolic, cardiovascular, anthropometric and psychological health along with cost-effectiveness. Participants aged 40-74 years for White European, or 25-74 years for South Asians, with an HbA1c value of between 6.0 and < 6.4% (42 and 47 mmol\/mol) or with a previously recorded plasma glucose level or HbA1c value within the high risk (prediabetes) range within the last five years, are invited to take part in the trial. Participants are identified through primary care, using an automated diabetes risk score within their practice database, or from a database of previous research participants. Participants are randomly assigned to either: 1) the control group who receive a detailed advice leaflet; 2) the Walking Away group, who receive the same leaflet and attend a 3 hour structured education programme with annual maintenance sessions delivered in groups; or 3) the Walking Away Plus group, who receive the leaflet, attend the structured education programme with annual maintenance sessions, plus receive follow-on support through highly-tailored text-messaging and telephone calls to help to aid pedometer use and behaviour change. This study will provide new evidence for the long-term effectiveness of a structured education programme focused on physical activity, conducted within routine care in a multi-ethnic population in the UK. It will also investigate the impact of different levels of ongoing support and the cost-effectiveness of each intervention. ISRCTN83465245 Trial registration date: 14\/06\/2012.","subset":"pubmed_abstract"} +{"meta":{"pmid":18474107,"dup_signals":{"dup_doc_count":18}},"text":"Traditional knowledge of wild edible plants used in Palestine (Northern West Bank): a comparative study.\nA comparative food ethnobotanical study was carried out in fifteen local communities distributed in five districts in the Palestinian Authority, PA (northern West Bank), six of which were located in Nablus, two in Jenin, two in Salfit, three in Qalqilia, and two in Tulkarm. These are among the areas in the PA whose rural inhabitants primarily subsisted on agriculture and therefore still preserve the traditional knowledge on wild edible plants. Data on the use of wild edible plants were collected for one-year period, through informed consent semi-structured interviews with 190 local informants. A semi-quantitative approach was used to document use diversity, and relative importance of each species. The study recorded 100 wild edible plant species, seventy six of which were mentioned by three informants and above and were distributed across 70 genera and 26 families. The most significant species include Majorana syriaca, Foeniculum vulgare, Malvasylvestris, Salvia fruticosa, Cyclamen persicum, Micromeria fruticosa, Arum palaestinum, Trigonella foenum-graecum, Gundelia tournefortii, and Matricaria aurea. All the ten species with the highest mean cultural importance values (mCI), were cited in all five areas. Moreover, most were important in every region. A common cultural background may explain these similarities. One taxon (Majoranasyriaca) in particular was found to be among the most quoted species in almost all areas surveyed. CI values, as a measure of traditional botanical knowledge, for edible species in relatively remote and isolated areas (Qalqilia, and Salfit) were generally higher than for the same species in other areas. This can be attributed to the fact that local knowledge of wild edible plants and plant gathering are more spread in remote or isolated areas. Gathering, processing and consuming wild edible plants are still practiced in all the studied Palestinian areas. About 26 % (26\/100) of the recorded wild botanicals including the most quoted and with highest mCI values, are currently gathered and utilized in all the areas, demonstrating that there are ethnobotanical contact points among the various Palestinian regions. The habit of using wild edible plants is still alive in the PA, but is disappearing. Therefore, the recording, preserving, and infusing of this knowledge to future generations is pressing and fundamental.","subset":"pubmed_abstract"} +{"meta":{"pmid":18375821,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-39":1,"2019-43":1,"2019-35":1,"2019-09":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2022-40":1,"2024-18":1}}},"text":"Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma.\nTumors are a mixture of neoplastic and host stromal cells, which establish a microenvironment that contributes to tumor progression. In this study, the contribution of tumor-associated macrophages (TAMs) to tumor growth and metastasis was examined using an orthotopic, immunocompetent murine model of diffuse malignant peritoneal mesothelioma. The expression profile of cytokines and chemokines in solid tumors was consistent with a M2-polarized, TAM-mediated immunosuppressive microenvironment. TAMs were targeted using liposome-encapsulated clodronate (CLIP). Exposure of tumor spheroids to CM-DiI-labeled CLIP in situ confirms targeting of macrophages and not mesothelioma cells. Intraperitoneal (i.p.) delivery of CLIP produced apoptosis in tumor spheroids and solid tumors in contrast to delivery of liposome-encapsulated PBS or PBS. Mice received an i.p. injection of mesothelioma cells with CLIP delivered i.p. every 5 days. This treatment protocol produces a 4-fold reduction in the number of tumors, a 17-fold reduction in the relative tumor burden, and a 5-fold reduction in invasion and metastasis when compared with mice exposed to liposome-encapsulated PBS or PBS. Following transplantation of tumor spheroids and treatment with CLIP, mice showed a 4-fold reduction in the number of tumors and a 15-fold reduction in relative tumor burden. Mice bearing established tumors showed a 2-fold reduction in the number of tumors and relative tumor burden when exposed to half the previous dose of CLIP delivered by repeated i.p. injection. These reductions in tumor burden are statistically significant and identify TAMs as an important host-derived cell that contributes to growth, invasion, and metastasis in diffuse malignant peritoneal mesothelioma.","subset":"pubmed_abstract"} +{"meta":{"pmid":9647315,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":9}}},"text":"Persistent loss of tyrosine hydroxylase immunoreactivity in the substantia nigra after neuroleptic withdrawal.\nA 37 year woman developed neuroleptic induced parkinsonism that persisted long after the drug had been discontinued. This prompted a study of the effect of an eight week course of haloperidol (HAL) followed by two week withdrawal, on dopaminergic neurons of the substantia nigra in rats. Animals treated with HAL showed a highly significant 32%-46% loss of tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra, and 20% contraction of the TH stained dendritic arbour. Neuroleptic drug induced downregulation of nigral dopaminergic neurons may help to explain the persistent parkinsonism found in many patients after withdrawal of medication.","subset":"pubmed_abstract"} +{"meta":{"pmid":29183406,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Coping Strategies in Mothers of Children with Intellectual Disabilities Showing Multiple Forms of Challenging Behaviour: Associations with Maternal Mental Health.\nIt is well documented that mothers of children with intellectual disabilities experience elevated mental health difficulties and that these are exacerbated by the presence of challenging behaviour. However, comparatively little is known about the effect of specific coping strategies for managing such behaviours. This paper aims to document coping strategies used by mothers of children showing multiple forms of challenging behaviour and to explore how these relate to positive and negative maternal mental health. Eighty-nine mothers of children with intellectual disabilities completed questionnaires assessing maternal mental health (Hospital Anxiety and Depression Scale, Positive and Negative Affect Scale) and maternal coping strategies (Brief COPE). Coping strategies were not associated with child age or ability, but were associated with maternal mental health. Higher levels of problem- and positive-coping strategies were associated with higher positive affect. Although active-avoidance coping was the least frequently reported, it was associated with higher levels of negative affect and increased anxiety and depression. Moderated mediation analyses identified that active-avoidance coping mediated the relationship between the number of forms of challenging behaviour and poor maternal mental health, but only in mothers with lower levels of problem-focused coping. Active-avoidance coping is associated with poorer negative mental health in mothers of children with intellectual disabilities who have average to low levels of problem-focused coping. This is reflective of that noted within a range of populations, highlighting it as a key area for intervention.","subset":"pubmed_abstract"} +{"meta":{"pmid":28808637,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Effects of air-abrasion pressure on the resin bond strength to zirconia: a combined cyclic loading and thermocycling aging study.\nTo determine the combined effect of fatigue cyclic loading and thermocycling (CLTC) on the shear bond strength (SBS) of a resin cement to zirconia surfaces that were previously air-abraded with aluminum oxide (Al2O3) particles at different pressures. Seventy-two cuboid zirconia specimens were prepared and randomly assigned to 3 groups according to the air-abrasion pressures (1, 2, and 2.8 bar), and each group was further divided into 2 groups depending on aging parameters (n = 12). Panavia F 2.0 was placed on pre-conditioned zirconia surfaces, and SBS testing was performed either after 24 hours or 10,000 fatigue cycles (cyclic loading) and 5,000 thermocycles. Non-contact profilometry was used to measure surface roughness. Failure modes were evaluated under optical and scanning electron microscopy. The data were analyzed using 2-way analysis of variance and \u03c72 tests (\u03b1 = 0.05). The 2.8 bar group showed significantly higher surface roughness compared to the 1 bar group (p < 0.05). The interaction between pressure and time\/cycling was not significant on SBS, and pressure did not have a significant effect either. SBS was significantly higher (p = 0.006) for 24 hours storage compared to CLTC. The 2 bar-CLTC group presented significantly higher percentage of pre-test failure during fatigue compared to the other groups. Mixed-failure mode was more frequent than adhesive failure. CLTC significantly decreased the SBS values regardless of the air-abrasion pressure used.","subset":"pubmed_abstract"} +{"meta":{"pmid":11083281,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints.\nTo examine the effect of insulin-like growth factor 1 (IGF-1) on the regulation of cartilage synthesis and other articular events in vivo. A first-generation adenoviral vector expressing human IGF-1 (AdIGF-1) from the cytomegalovirus promoter was constructed. Particles of AdIGF-1 (5 x 10(9)) were injected through the patellar tendon into normal rabbit knee joints and rabbit knee joints with antigen-induced arthritis (AIA), with the same dose of a control adenoviral vector injected into the contralateral knees. Lavage fluids were obtained from rabbit knee joints on days 3 and 7 postinjection and used for analysis of IGF-1 expression, white blood cell infiltration, and cartilage breakdown. Cartilage chips from rabbit joints were used for assay of new proteoglycan synthesis, and tissues also were harvested from the dissected knees for histologic study. Intraarticular injection of AdIGF-1 resulted in a mean of 180.6 ng\/ml of IGF-1 expression in the lavage fluid from rabbit joints. IGF-1 expression stimulated new proteoglycan synthesis in both naive and AIA rabbit knees, but had no significant chondroprotective or antiinflammatory effects. Histologic analysis showed that elevated levels of IGF-1 expression in both normal and arthritic knees had no adverse pathologic effects on synovium or adjacent muscles. Gene transfer of IGF-1 into rabbit knee joints promotes proteoglycan synthesis without significantly affecting inflammation or cartilage breakdown. In addition, no adverse effects following intraarticular IGF-1 gene delivery were observed. Thus, local gene transfer of IGF-1 to joints could serve as a therapeutic strategy to stimulate new matrix synthesis in both rheumatoid arthritis and osteoarthritis.","subset":"pubmed_abstract"} +{"meta":{"pmid":18977820,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Changes in psychomotor effects of L-dopa and methylphenidate after sustained dopaminergic therapy in Parkinson's disease.\nSustained drug therapy in Parkinson's disease may alter the psychomotor responses to acute challenges with dopaminergic drugs, L-dopa and methylphenidate, and cause cross sensitisation. The mood, psychomotor and reward potentiating effects of an acute challenge with L-dopa and methylphenidate on separate occasions were assessed under double blind (medication na\u00efve) conditions after a placebo and then the testing sessions were repeated in the same (medication experienced) patients following a median period of 16.7 months of continuous dopaminergic drug therapy. In the medication na\u00efve condition, affect was not changed by L-dopa or methylphenidate and only L-dopa improved motor function. In the medication experienced condition, active drugs improved positive affect compared with the medication na\u00efve condition and there was an enhanced effect of L-dopa on motor function. Reward responsivity was enhanced by both L-dopa and methylphenidate in medication na\u00efve and experienced conditions. Sustained dopaminergic drug therapy augments the motor effects of an acute challenge with L-dopa and induces euphoriant effects to L-dopa and methylphenidate challenges.","subset":"pubmed_abstract"} +{"meta":{"pmid":35682374,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Effort-Reward Imbalance among a Sample of Formal US Solid Waste Workers.\nBackground: Solid waste workers are exposed to a plethora of occupational hazards and may also experience work-related stress. Our study had three specific hypotheses: (1) waste workers experience effort\u2212reward imbalance (ERI) with high self-reported effort but low reward, (2) unionized workers experience greater ERI, and (3) workers with higher income have lower ERI. Methods: Waste workers from three solid waste sites in Michigan participated in this cross-sectional study. We characterized perceived work stress using the short-version ERI questionnaire. Descriptive statistics and linear tests for trend were assessed for each scale. Linear regression models were constructed to examine the relationship between structural factors of work stress and ERI. Gradient-boosted regression trees evaluated which factors of effort or reward best characterize workers' stress. Results: Among 68 participants, 37% of workers reported high effort and low reward from work (ERI > 1). Constant pressure due to heavy workload was most indicative of ERI among the solid waste workers. Union workers experienced 79% times higher ERI than non-unionized workers, while no significant differences were observed by income, after adjusting for confounders. Conclusions: Organizational-level interventions, such as changes related to workload, consideration of fair compensation, and increased support from supervisors, can decrease work stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":29381838,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Supporting Arthritis and Employment Across the Life Course: A Qualitative Study.\nTo examine the need for and availability and use of formal and informal workplace resources and to uncover differences across the life course in adults with arthritis. Focus groups and interviews were conducted with young (aged 18-34 years; n = 7), middle-aged (35-54 years; n = 13), and older adults (\u226555 years; n = 25) with a diagnosis of inflammatory arthritis, osteoarthritis, or other rheumatic disease. Participants were asked about their employment experiences, formal and informal workplace resource needs, and availability and use of workplace resources. Differences based on chronological, functional, psychosocial, organizational, and lifespan dimensions of age were examined. A modified grounded theory approach was used to inductively analyze the data. Young, middle-aged, and older adult participants required similar workplace resources. Across all participants, scheduling modifications tended to be the most needed workplace resource. In contrast, the perceived availability and use of formal workplace resources differed among participants. Young adult participants and those who were newer to their jobs reported that workplace resources were less available and utilized. Middle-aged and older adults reported greater availability of workplace resources. Scheduling accommodations and at-work modifications were the workplace resources that were used most by middle-aged and older adults, respectively. Similar workplace resources could meet the employment needs of individuals with arthritis across the life course. Attention should be paid to young adults and those who are new to their jobs, because they may perceive more barriers to accessing formal workplace resources and be susceptible to work disability.","subset":"pubmed_abstract"} +{"meta":{"pmid":25647735,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Ursolic acid and resveratrol synergize with chloroquine to reduce melanoma cell viability.\nMalignant melanoma is associated with a 5-year survival rate of less than 20% once metastasized. Malignant melanoma cells exhibit increased levels of autophagy, a process of intracellular digestion that allows cells to survive various stresses including chemotherapies, resulting in reduced patient survival. Autophagy can be inhibited by chemicals like chloroquine (CQ), which prevents fusion of autophagosomes to lysosomes, resulting in autophagosome accumulation in most systems. Here, we describe how tested CQ to see whether it could sensitize B16F10 metastatic mouse melanoma cells to the anticancer activities of the natural compounds ursolic acid (UA) and resveratrol (RES). CQ with UA or RES strongly and synergistically reduced the viability of B16F10 mouse melanoma and A375 human melanoma cells. Surprisingly, flow cytometry of acridine orange-stained cells showed that UA or RES in combination with CQ significantly reduced autophagosome levels. Western blotting analysis revealed that CQ plus UA or RES paradoxically increased LC3II, indicative of autophagosome accumulation. In addition, CQ plus RES synergistically decreased the levels of both autophagy initiator beclin-1 and autophagy supporter p62. These results indicate that CQ with UA or RES strongly and synergistically reduces the viability of B16F10 and A375 melanoma cells. However, studies on B16F10 cells have shown that the synergistic effect was not mediated by inhibition of autophagy induced by UA or RES. These compounds are well-tolerated in humans, and CQ has shown promise as an adjuvant therapy. These combinations may be valuable treatment strategies for melanoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":35491102,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-26":1,"2024-30":1,"unknown":6}}},"text":"A method for the generation of pseudovirus particles bearing SARS coronavirus spike protein in high yields.\nThe ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has threatened human health and the global economy. Development of additional vaccines and therapeutics is urgently required, but such development with live virus must be conducted with biosafety level 3 confinement. Pseudotyped viruses have been widely adopted for studies of virus entry and pharmaceutical development to overcome this restriction. Here we describe a modified protocol to generate vesicular stomatitis virus (VSV) pseudotyped with SARS-CoV or SARS-CoV-2 spike protein in high yield. We found that a large proportion of pseudovirions produced with the conventional transient expression system lacked coronavirus spike protein at their surface as a result of inhibition of parental VSV infection by overexpression of this protein. Establishment of stable cell lines with an optimal expression level of coronavirus spike protein allowed the efficient production of progeny pseudoviruses decorated with spike protein. This improved VSV pseudovirus production method should facilitate studies of coronavirus entry and development of antiviral agents.Key words: severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, pseudovirus, vesicular stomatitis virus (VSV), spike protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":19944347,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":1,"2013-20":2,"unknown":2}}},"text":"Anthropometric correlates of insulin-like growth factor 1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels by race\/ethnicity and gender.\nInsulin-like growth factor 1 (IGF-1) levels are positively related to some cancers and negatively related to cardiovascular disease. These conditions are also related to insulin resistance and high body weight, leading to the hypothesis that IGF-1 levels may, in part, mediate the association of high body weight with these health outcomes. Using the National Health and Nutrition Examination Survey (NHANES) III population, we examined the associations between IGF-1, IGF binding protein-3 (IGFBP-3), and the IGF-1\/IGFBP-3 molar ratio with anthropometric measures in a large, U.S. population-based study where these associations could also be stratified by race\/ethnicity and gender. The study population consisted of 3,168 women and 2,635 men (44% non-Hispanic white, 28.2% non-Hispanic black, and 27.7% Mexican-American). Anthropometric measures were obtained by trained personnel in the NHANES mobile examination centers. IGF-1 and IGFBP-3 were measured using immunoassays by staff at Diagnostic System Laboratories (DSL) Inc. (Webster, TX). Associations of IGF-1, IGFBP-3, and IGF-1\/IGFBP-3 molar ratio with anthropometric variables across race\/ethnicity and gender were evaluated by using linear regression modeling. Body mass index (BMI) was inversely associated with IGF-1 levels across all of the race\/ethnicity and gender subgroups. In contrast, BMI, waist to hip ratio (WHR), and waist circumference were positively associated with IGFBP-3 levels only in non-Hispanic black men and non-Hispanic white women. The IGF-1\/IGFBP-3 molar ratio was inversely associated with all anthropometric measures, except height, in all subgroups of the population. The significant inverse associations of BMI with IGF-1 levels and of all anthropometric variables, except height, with the IGF-1:IGFBP-3 molar ratio in all subgroups do not support existing hypotheses that associations of excess weight with negative health outcomes, such as specific cancer diagnoses, are mediated through high IGF-1 levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":16783368,"dup_signals":{"dup_doc_count":74,"dup_dump_count":44,"dup_details":{"curated_sources":2,"2023-50":5,"2023-40":1,"2023-23":2,"2023-14":1,"2022-49":2,"2022-27":2,"2022-21":1,"2022-05":2,"2021-49":1,"2021-39":3,"2021-31":2,"2021-25":1,"2021-21":1,"2021-10":3,"2020-50":3,"2020-45":2,"2020-40":1,"2020-16":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-39":1,"2018-34":1,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":2,"2018-09":1,"2017-51":4,"2017-43":3,"2017-34":3,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-22":2,"2024-18":2,"2017-13":1,"2024-30":1}}},"text":"Optimal decision making and the anterior cingulate cortex.\nLearning the value of options in an uncertain environment is central to optimal decision making. The anterior cingulate cortex (ACC) has been implicated in using reinforcement information to control behavior. Here we demonstrate that the ACC's critical role in reinforcement-guided behavior is neither in detecting nor in correcting errors, but in guiding voluntary choices based on the history of actions and outcomes. ACC lesions did not impair the performance of monkeys (Macaca mulatta) immediately after errors, but made them unable to sustain rewarded responses in a reinforcement-guided choice task and to integrate risk and payoff in a dynamic foraging task. These data suggest that the ACC is essential for learning the value of actions.","subset":"pubmed_abstract"} +{"meta":{"pmid":15146330,"dup_signals":{"dup_doc_count":29,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-22":1,"unknown":25}}},"text":"L -5-Hydroxytryptophan treatment of sleep terrors in children.\nTo test the hypothesis that the administration of L -5-hydroxytryptophan (L -5-HTP) might exert beneficial effects on sleep terrors, we carried out an open pharmacological trial in a group of children with sleep terrors compared to a group of children with the same disorder but without L -5-HTP treatment. Participants in the trial were 45 children (34 males and 11 females; age range 3.2-10.6 years), referred to the Sleep Centre of the Department of Developmental Neurology and Psychiatry of the University of Rome \"La Sapienza\", affected by sleep terrors. All subjects underwent: (1) complete medical and sleep history; (2) complete neurological examination and EEG recording whilst awake and sleeping, (3) a structured sleep diary for 2 months, (4) after 1 month, all subjects were examined again from the clinical and EEG points of view and (5) after 6 months, a structured interview in order to evaluate the clinical outcome. After the first visit, L -5-HTP was administered (2 mg\/kg per day) at bedtime to 31 randomly selected patients for a single period of 20 consecutive days. After 1 month of treatment, 29\/31 (93.5%) of patients showed a positive response. In the comparison group without drug therapy, after 1 month, the episodes disappeared only in four children (28.6%) while ten children (71.4%) showed the persistence of episodes with the same frequency as before. After 6 months, 26\/31 (83.9%) of children treated with L -5HTP were sleep terror-free, while in five children (16.1%) sleep terror episodes persisted. Of the children in the comparison group, ten (71.4%) continued to show sleep terrors at 6-month follow-up. to our knowledge, this is the first study demonstrating the efficacy of a new drug treatment for sleep terrors. These results confirm our initial hypothesis and represent evidence that treatment with L -5-hydroxytryptophan is able to modulate the arousal level in children and to induce a long-term improvement of sleep terrors.","subset":"pubmed_abstract"} +{"meta":{"pmid":33656141,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Systematic review on the biology, ecology, genetic diversity and parasite transmission potential of Panstrongylus geniculatus (Latreille 1811) in Latin America.\nPanstrongylus geniculatus (Latreille, 1811) is the triatomine with the largest geographic distribution in Latin America. It has been reported in 18 countries from southern Mexico to northern Argentina, including the Caribbean islands. Although most reports indicate that P. geniculatus has wild habitats, this species has intrusive habits regarding human dwellings mainly located in intermediate deforested areas. It is attracted by artificial light from urban and rural buildings, raising the risk of transmission of Trypanosoma cruzi. Despite the wide body of published information on P. geniculatus, many knowledge gaps exist about its biology and epidemiological potential. For this reason, we analysed the literature for P. geniculatus in Scopus, PubMed, Scielo, Google Scholar and the BibTriv3.0 databases to update existing knowledge and provide better information on its geographic distribution, life cycle, genetic diversity, evidence of intrusion and domiciliation, vector-related circulating discrete taxonomic units, possible role in oral T. cruzi transmission, and the effect of climate change on its biology and epidemiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":9122313,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample.\nData from a two-wave longitudinal study of an elderly community sample were used to assess whether cognitive complaints either predict subsequent cognitive decline or reflect past cognitive decline. Cognitive complaints and cognitive functioning were assessed on two occasions three and a half years apart. Cognitive complaints at Wave 1 were found not to predict future cognitive change on the Mini-Mental State Examination, an episodic memory test or a test of mental speed. Similarly, cognitive complaints at Wave 2 were unrelated to past cognitive changes on these tests after statistically controlling for the effects of anxiety and depression. Furthermore, cognitive complaints did not predict either mortality (after controlling for anxiety and depression) or future dementia. These results are evidence against the inclusion of cognitive complaints in diagnostic criteria for proposed disorders such as age-associated memory impairment, mild cognitive disorder and ageing-associated cognitive decline.","subset":"pubmed_abstract"} +{"meta":{"pmid":29314486,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-04":1,"2020-40":1,"2020-24":1,"2020-05":1,"2019-22":1,"2018-34":1,"2018-22":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Temperature sensitivity of soil organic carbon decomposition increased with mean carbon residence time: Field incubation and data assimilation.\nTemperature sensitivity of soil organic carbon (SOC) decomposition is one of the major uncertainties in predicting climate-carbon (C) cycle feedback. Results from previous studies are highly contradictory with old soil C decomposition being more, similarly, or less sensitive to temperature than decomposition of young fractions. The contradictory results are partly from difficulties in distinguishing old from young SOC and their changes over time in the experiments with or without isotopic techniques. In this study, we have conducted a long-term field incubation experiment with deep soil collars (0-70 cm in depth, 10 cm in diameter of PVC tubes) for excluding root C input to examine apparent temperature sensitivity of SOC decomposition under ambient and warming treatments from 2002 to 2008. The data from the experiment were infused into a multi-pool soil C model to estimate intrinsic temperature sensitivity of SOC decomposition and C residence times of three SOC fractions (i.e., active, slow, and passive) using a data assimilation (DA) technique. As active SOC with the short C residence time was progressively depleted in the deep soil collars under both ambient and warming treatments, the residences times of the whole SOC became longer over time. Concomitantly, the estimated apparent and intrinsic temperature sensitivity of SOC decomposition also became gradually higher over time as more than 50% of active SOC was depleted. Thus, the temperature sensitivity of soil C decomposition in deep soil collars was positively correlated with the mean C residence times. However, the regression slope of the temperature sensitivity against the residence time was lower under the warming treatment than under ambient temperature, indicating that other processes also regulated temperature sensitivity of SOC decomposition. These results indicate that old SOC decomposition is more sensitive to temperature than young components, making the old C more vulnerable to future warmer climate.","subset":"pubmed_abstract"} +{"meta":{"pmid":19049467,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Extensive backbone dynamics in the GCAA RNA tetraloop analyzed using 13C NMR spin relaxation and specific isotope labeling.\nConformational dynamics play a key role in the properties and functions of proteins and nucleic acids. Heteronuclear NMR spin relaxation is a uniquely powerful site-specific probe of dynamics in proteins and has found increasing applications to nucleotide base side chains and anomeric sites in RNA. Applications to the nucleic acid ribose backbone, however, have been hampered by strong magnetic coupling among ring carbons in uniformly 13C-labeled samples. In this work, we apply a recently developed, metabolically directed isotope labeling scheme that places 13C with high efficiency and specificity at the nucleotide ribose C2' and C4' sites. We take advantage of this scheme to explore backbone dynamics in the well-studied GCAA RNA tetraloop. Using a combination of CPMG (Carr-Purcell-Meiboom-Gill) and R(1rho) relaxation dispersion spectroscopy to explore exchange processes on the microsecond to millisecond time scale, we find an extensive pattern of dynamic transitions connecting a set of relatively well-defined conformations. In many cases, the observed transitions appear to be linked to C3'-endo\/C2'-endo sugar pucker transitions of the corresponding nucleotides, and may also be correlated across multiple nucleotides within the tetraloop. These results demonstrate the power of NMR spin relaxation based on alternate-site isotope labeling to open a new window into the dynamic properties of ribose backbone groups in RNA.","subset":"pubmed_abstract"} +{"meta":{"pmid":11869486,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Intra-uterine and genetic influences on the relationship between size at birth and height in later life: analysis in twins.\nEpidemiological studies have consistently shown a positive association between size at birth (i.e. birth weight or birth length) and height in children, adolescents and adults. To examine whether this association is explained by genetic or nongenetic (intra-uterine) factors, we investigated birth weight, birth length and height in 60 dizygotic and 68 monozygotic adolescent twin pairs still living with their parents. Birth weight of the twins was obtained from their mothers. Height was measured in a standardised way. The mean age was 17+\/-1.7 years for the dizygotic twins and 16+\/-1.8 years for the monozygotic twins. Both dizygotic and monozygotic twins with the lowest birth weight from each pair had a height that was lower compared to their co-twins with the highest birth weight (dizygotic twins: 172.2+\/-7.9 vs. 173.8+\/-9.4 cm [p = 0.05]; monozygotic twins: 171.1+\/-9.4 vs. 171.8+\/-9.5 cm [p = 0.01]). Similarly, both dizygotic and monozygotic twins with the shortest birth length from each pair had a height that was lower compared to their co-twins with the longest birth length (dizygotic twins: 172.3+\/-7.9 vs. 174.9plus minus9.7 cm [p < 0.05]; monozygotic twins: 168.9+\/-10.6 vs. 169.9+\/-10.2 cm [p < 0.01]). In addition, intra-pair differences in birth weight and birth length were significantly associated with differences in height in both dizygotic twins (regression coefficient: 4.3 cm\/kg [95% confidence interval: 1.0 to 7.5] and 0.96 cm\/cm [0.17 to 1.74], respectively) and monozygotic twins (2.8 cm\/kg [1.4 to 4.1] and 0.73 cm\/cm [0.40 to 1.06], respectively). These associations were stronger in dizygotic than in monozygotic twins, but this difference was not statistically significant (for birth weight p = 0.4; and for birth length p = 0.6). However, genetic model fitting indicated that models incorporating a genetic source of the covariance gave a better description of the observed association of birth weight and length with height in later life than models not incorporating this genetic source. The results were similar for data on adult height after 12 years of follow-up in a subgroup of these twin pairs. These data suggest that the association between size at birth and height in later life is influenced by non-genetic intra-uterine and by genetic factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":29198237,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Risk correlates for physical-mental multimorbidities in South Africa: a cross-sectional study.\nThe aim of this study was to identify the risk correlates for coexisting common mental disorders (CMDs) in the chronic care population in South Africa, with the view to identifying particularly vulnerable patient populations. The sample comprised 2549 chronic care patients enrolled in the baseline and endline rounds of a facility detection survey conducted by the Programme for Improving Mental Health Care in three large facilities in the Dr Kenneth Kaunda district in the North West province of South Africa. Participants were screened for depression using the Patient Health Questionnaire (PHQ9) and for alcohol misuse using the Alcohol Use Disorders Identification Test (AUDIT). Data were analysed according to the number of morbidities, disorder type (physical or mental) and demographic variables. Multimorbidity was defined as the presence of two or more disorders (physical and\/or mental). Just over one-third of the sample reported two or more physical conditions. Women were more at risk of being depressed than were men, with men more at risk of alcohol misuse. Those who were employed were at lower risk of having coexisting CMDs, while being younger, HIV positive, and food deprived were all found to be associated with higher risk for having coexisting CMDs. In the face of the large treatment gap for CMDs in South Africa, and the role that coexisting CMDs can play in exacerbating the burden of chronic physical diseases, mental health screening and treatment interventions should target HIV-positive, younger patients living in circumstances where there is household food insecurity.","subset":"pubmed_abstract"} +{"meta":{"pmid":18237326,"dup_signals":{"dup_doc_count":17,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":8}}},"text":"Meeting a binational research challenge: substance abuse among transnational Mexican farmworkers in the United States.\nTo help in understanding the manner in which community, individual, and other factors in the United States and Mexico contribute to drug use among transnational migrants, this paper introduces a binational social ecology model of substance abuse in this population. We draw on our 2 NIH-funded ethnographic studies-1 on problem drinking and the other on drug abuse-among transnational Mexican workers in the mushroom industry of southeastern Pennsylvania. Our model demonstrates that major reasons for substance abuse among transnational migrants include nontraditional living arrangements in labor camps and overcrowded apartments, the absence of kin and community deterrents to drug use, social isolation, the presence of drug use and binge drinking subcultures, the availability of drugs, family history of drugs, previous drug use or witnessing of drug use in Mexico, and drug use norms and drug availability in Mexico. It suggests the need for US and Mexican researchers to collaborate in binational teams and address factors on both sides of the border. Our binational social ecology model, together with our research recommendations, will assist alcohol and drug researchers to discover how community and individual factors in both the United States and abroad fit and interact beyond mere association and provide a more comprehensive research approach to substance abuse research among transnational migrants.","subset":"pubmed_abstract"} +{"meta":{"pmid":22234691,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2019-26":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-39":1,"2017-30":1,"2019-35":1}}},"text":"Macrophage LRP1 contributes to the clearance of von Willebrand factor.\nThe relationship between low-density lipoprotein receptor-related protein-1 (LRP1) and von Willebrand factor (VWF) has remained elusive for years. Indeed, despite a reported absence of interaction between both proteins, liver-specific deletion of LRP1 results in increased VWF levels. To investigate this discrepancy, we used mice with a macrophage-specific deficiency of LRP1 (macLRP1(-)) because we previously found that macrophages dominate VWF clearance. Basal VWF levels were increased in macLRP1(-) mice compared with control mice (1.6 \u00b1 0.4 vs 1.0 \u00b1 0.4 U\/mL). Clearance experiments revealed that half-life of human VWF was significantly increased in macLRP1(-) mice. Ubiquitous blocking of LRP1 or additional lipoprotein receptors by overexpressing receptor-associated protein in macLRP1(-) mice did not result in further rise of VWF levels (0.1 \u00b1 0.2 U\/mL), in contrast to macLRP1(+) mice (rise in VWF, 0.8 \u00b1 0.4 U\/mL). This points to macLRP1 being the only lipoprotein receptor regulating VWF levels. When testing the mechanism(s) involved, we observed that VWF-coated beads adhered efficiently to LRP1 but only when exposed to shear forces exceeding 2.5 dyne\/cm(2), implying the existence of shear stress-dependent interactions. Furthermore, a mechanism involving \u03b22-integrins that binds both VWF and LRP1 also is implicated because inhibition of \u03b22-integrins led to increased VWF levels in control (rise, 0.19 \u00b1 0.16 U\/mL) but not in macLRP1(-) mice (0.08 \u00b1 0.15 U\/mL).","subset":"pubmed_abstract"} +{"meta":{"pmid":29770240,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Diagnosis and prediction of periodontally compromised teeth using a deep learning-based convolutional neural network algorithm.\nThe aim of the current study was to develop a computer-assisted detection system based on a deep convolutional neural network (CNN) algorithm and to evaluate the potential usefulness and accuracy of this system for the diagnosis and prediction of periodontally compromised teeth (PCT). Combining pretrained deep CNN architecture and a self-trained network, periapical radiographic images were used to determine the optimal CNN algorithm and weights. The diagnostic and predictive accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve, area under the ROC curve, confusion matrix, and 95% confidence intervals (CIs) were calculated using our deep CNN algorithm, based on a Keras framework in Python. The periapical radiographic dataset was split into training (n=1,044), validation (n=348), and test (n=348) datasets. With the deep learning algorithm, the diagnostic accuracy for PCT was 81.0% for premolars and 76.7% for molars. Using 64 premolars and 64 molars that were clinically diagnosed as severe PCT, the accuracy of predicting extraction was 82.8% (95% CI, 70.1%-91.2%) for premolars and 73.4% (95% CI, 59.9%-84.0%) for molars. We demonstrated that the deep CNN algorithm was useful for assessing the diagnosis and predictability of PCT. Therefore, with further optimization of the PCT dataset and improvements in the algorithm, a computer-aided detection system can be expected to become an effective and efficient method of diagnosing and predicting PCT.","subset":"pubmed_abstract"} +{"meta":{"pmid":11800395,"dup_signals":{"dup_doc_count":12}},"text":"Cold acclimation of Arabidopsis thaliana results in incomplete recovery of photosynthetic capacity, associated with an increased reduction of the chloroplast stroma.\nThe effects of short-term cold stress and long-term cold acclimation on the light reactions of photosynthesis were examined in vivo to assess their contributions to photosynthetic acclimation to low temperature in Arabidopsis thaliana (L.) Heynh.. All photosynthetic measurements were made at the temperature of exposure: 23 degrees C for non-acclimated plants and 5 degrees C for cold-stressed and cold-acclimated plants. Three-day cold-stress treatments at 5 degrees C inhibited light-saturated rates of CO2 assimilation and O2 evolution by approximately 75%. The 3-day exposure to 5 degrees C also increased the proportion of reduced QA by 50%, decreased the yield of PSII electron transport by 65% and decreased PSI activity by 31%. In contrast, long-term cold acclimation resulted in a strong but incomplete recovery of light-saturated photosynthesis at 5 degrees C. The rates of light-saturated CO2 and O2 gas exchange and the in vivo yield of PSII activity under light-saturating conditions were only 35-40% lower, and the relative redox state of QA only 20% lower, at 5 degrees C after cold acclimation than in controls at 23 degrees C. PSI activity showed full recovery during long-term cold acclimation. Neither short-term cold stress nor long-term cold acclimation of Arabidopsis was associated with a limitation in ATP, and both treatments resulted in an increase in the ATP\/NADPH ratio. This increase in ATP\/NADPH was associated with an inhibition of PSI cyclic electron transport but there was no apparent change in the Mehler reaction activity in either cold-stressed or cold-acclimated leaves. Cold acclimation also resulted in an increase in the reduction state of the stroma, as indicated by an increased total activity and activation state of NADP-dependent malate dehydrogenase, and increased light-dependent activities of the major regulatory enzymes of the oxidative pentose-phosphate pathway. We suggest that the photosynthetic capacity during cold stress as well as cold acclimation is altered by limitations at the level of consumption of reducing power in carbon metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":21972234,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2023-23":1,"2021-21":1,"2021-10":1,"2019-26":1,"2019-18":2,"2018-51":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-40":1}}},"text":"Footwear characteristics and factors influencing footwear choice in patients with gout.\nGout is associated with foot pain, impairment, and disability. The aim of this study was to assess footwear characteristics and key factors influencing footwear choice in patients with gout. We also wanted to evaluate the relationship between footwear characteristics and foot disability. Fifty patients with a history of acute gout were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Footwear characteristics and the factors associated with choice of footwear were identified using validated assessment tools. Suitability of footwear was assessed using predetermined criteria for assessing adequacy of footwear, based on a previous study of foot pain. The patients had moderate to severe foot pain, impairment, and disability. Poor footwear characteristics included poor cushioning, lack of support, lack of stability, and motion control. More than 50% of shoes were \u226512 months old and demonstrated excessive wear patterns. Patients reported comfort (98%), fit (90%), support (90%), and cost (60%) as important factors in choosing their own footwear. No correlation was found between footwear characteristics (length and width) and foot characteristics (foot pain, impairment, and disability). Patients with poor footwear reported higher foot-related impairment and disability. Use of poor footwear is common in patients with chronic gout and is associated with foot disability and impairment.","subset":"pubmed_abstract"} +{"meta":{"pmid":24132007,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":18}}},"text":"Quantitative comparison of reconstruction methods for intra-voxel fiber recovery from diffusion MRI.\nValidation is arguably the bottleneck in the diffusion magnetic resonance imaging (MRI) community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the \"HARDI reconstruction challenge\" organized in the context of the \"ISBI 2012\" conference. Evaluated methods encompass a mixture of classical techniques well known in the literature such as diffusion tensor, Q-Ball and diffusion spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach. This information can be useful not only for enhancing current algorithms and develop the next generation of reconstruction methods, but also to assist physicians in the choice of the most adequate technique for their studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":22266732,"dup_signals":{"dup_doc_count":31,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2023-14":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2019-18":1,"2018-51":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-09":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2023-40":1,"2024-22":1}}},"text":"Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: similar improvements in saccadic and manual responses.\nThe purpose of this study was to determine whether the very large effects of saccadic latency distribution, generated by deep brain stimulation of the subthalamic nuclei are reflected in quantitatively corresponding changes for manual responses, rather than representing a reflection of the specific role of the subthalamus in controlling saccades. Saccadic and manual reaction times were measured under as nearly identical conditions as possible in six patients with implanted subthalamic electrodes and in six age-matched controls with the stimulation either on or off. Median latency was found to be reduced by stimulation in a similar way to saccadic latency; in neither case was there a significant change in the Linear Approach to Threshold with Ergotic Rate parameter \u03c3. For both types of response, the effect is to move the responses proportionately in the direction of average of responses in the control group. We therefore conclude that the previously described effects of stimulation on latency are not a phenomenon peculiar to saccades, increasing confidence in using saccadic latency measurements as a surrogate for more general responses when determining the efficacy of deep brain stimulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":23020625,"dup_signals":{"dup_doc_count":23,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-06":2,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":1,"2020-40":1,"2020-24":1,"2020-05":1,"2019-51":1,"2015-32":2,"2015-27":1,"2015-22":1,"2014-52":1,"2014-35":1,"2014-23":2,"2023-23":1,"2015-18":2}}},"text":"A duck RH panel and its potential for assisting NGS genome assembly.\nOwing to the low cost of the high throughput Next Generation Sequencing (NGS) technology, more and more species have been and will be sequenced. However, de novo assemblies of large eukaryotic genomes thus produced are composed of a large number of contigs and scaffolds of medium to small size, having no chromosomal assignment. Radiation hybrid (RH) mapping is a powerful tool for building whole genome maps and has been used for several animal species, to help assign sequence scaffolds to chromosomes and determining their order. We report here a duck whole genome RH panel obtained by fusing female duck embryonic fibroblasts irradiated at a dose of 6,000 rads, with HPRT-deficient Wg3hCl2 hamster cells. The ninety best hybrids, having an average retention of 23.6% of the duck genome, were selected for the final panel. To allow the genotyping of large numbers of markers, as required for whole genome mapping, without having to cultivate the hybrid clones on a large scale, three different methods involving Whole Genome Amplification (WGA) and\/or scaling down PCR volumes by using the Fluidigm BioMark(TM) Integrated Fluidic Circuits (IFC) Dynamic Array(TM) for genotyping were tested. RH maps of APL12 and APL22 were built, allowing the detection of intrachromosomal rearrangements when compared to chicken. Finally, the panel proved useful for checking the assembly of sequence scaffolds and for mapping EST located on one of the smallest microchromosomes. The Fluidigm BioMark(TM) Integrated Fluidic Circuits (IFC) Dynamic Array(TM) genotyping by quantitative PCR provides a rapid and cost-effective method for building RH linkage groups. Although the vast majority of genotyped markers exhibited a picture coherent with their associated scaffolds, a few of them were discordant, pinpointing potential assembly errors. Comparative mapping with chicken chromosomes GGA21 and GGA11 allowed the detection of the first chromosome rearrangements on microchromosomes between duck and chicken. As in chicken, the smallest duck microchromosomes appear missing in the assembly and more EST data will be needed for mapping them. Altogether, this underlines the added value of RH mapping to improve genome assemblies.","subset":"pubmed_abstract"} +{"meta":{"pmid":22761821,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":10}}},"text":"Molecular dynamics simulations suggest ligand's binding to nicotinamidase\/pyrazinamidase.\nThe research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding\/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding\/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":16987392,"dup_signals":{"dup_doc_count":13}},"text":"Physiological routes from intra-uterine seminal contents to advancement of ovulation.\nWhole boar semen or seminal plasma has been demonstrated to advance the time of ovulation in gilts. As a means of clarifying this influence, the contribution of uterine lymphatics and their white cell populations has been examined. After duct visualisation with Evan's blue, lymph was sampled from a mesometrial vessel in eight pre-ovulatory gilts whose uterine lumen was infused simultaneously with whole semen in one ligated horn and saline in the contralateral ligated horn. Lymph was collected from cannulated vessels for periods of up to four hours under general anaesthesia. Thereafter, mesometrial lymph nodes, utero-tubal junction and uterine wall tissues were sampled. The proportion of nucleated cells in the sampled lymph increased towards the end of the collection period, but erythrocytes were found in all instances preventing a meaningful differentiation and identification of leukocytes. Prominent uterine lymph nodes were present in the mesometrium on both sides of the reproductive tract in 7 of 10 gilts. Differences in cellular contents were demonstrated between the side of the tract infused with semen and that infused with saline control. Two of 4 gilts had lower values for CD4 (Cluster Differentiation) and 3 of 6 gilts higher values for MHC II (Major Histocompatibility Complex) markers on the side challenged with semen. In contrast, values remained constant for CD8 but ranged widely for CD18. Immunohistochemical analysis of uterine tissue samples for MHC II+ cells revealed significant differences (P < 0.05) between the control and semen-treated ligated portions of the horns, as well as between the tissue sample of uterine wall and that from the utero-tubal junction, but there were no significant differences for CD4+ cells. It therefore remains plausible that semen-induced cytokines in the uterine lymph undergo counter-current transfer to the ipsilateral ovary and accelerate the final maturation of pre-ovulatory Graafian follicles.","subset":"pubmed_abstract"} +{"meta":{"pmid":21341654,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The atomic structural dynamics of \u03b3-Al2O3 supported Ir-Pt nanocluster catalysts prepared from a bimetallic molecular precursor: a study using aberration-corrected electron microscopy and X-ray absorption spectroscopy.\nThis study describes a prototypical, bimetallic heterogeneous catalyst: compositionally well-defined Ir-Pt nanoclusters with sizes in the range of 1-2 nm supported on \u03b3-Al(2)O(3). Deposition of the molecular bimetallic cluster [Ir(3)Pt(3)(\u03bc-CO)(3)(CO)(3)(\u03b7-C(5)Me(5))(3)] on \u03b3-Al(2)O(3), and its subsequent reduction with hydrogen, provides highly dispersed supported bimetallic Ir-Pt nanoparticles. Using spherical aberration-corrected scanning transmission electron microscopy (C(s)-STEM) and theoretical modeling of synchrotron-based X-ray absorption spectroscopy (XAS) measurements, our studies provide unambiguous structural assignments for this model catalytic system. The atomic resolution C(s)-STEM images reveal strong and specific lattice-directed strains in the clusters that follow local bonding configurations of the \u03b3-Al(2)O(3) support. Combined nanobeam diffraction (NBD) and high-resolution transmission electron microscopy (HRTEM) data suggest the polycrystalline \u03b3-Al(2)O(3) support material predominantly exposes (001) and (011) surface planes (ones commensurate with the zone axis orientations frequently exhibited by the bimetallic clusters). The data reveal that the supported bimetallic clusters exhibit complex patterns of structural dynamics, ones evidencing perturbations of an underlying oblate\/hemispherical cuboctahedral cluster-core geometry with cores that are enriched in Ir (a result consistent with models based on surface energetics, which favor an ambient cluster termination by Pt) due to the dynamical responses of the M-M bonding to the specifics of the adsorbate and metal-support interactions. Taken together, the data demonstrate that strong temperature-dependent charge-transfer effects occur that are likely mediated variably by the cluster-support, cluster-adsorbate, and intermetallic bonding interactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":16507923,"dup_signals":{"dup_doc_count":11}},"text":"Neonatal nucleated red blood cells and the prediction of cerebral white matter injury in preterm infants.\nTo estimate whether neonates with cerebral white matter injury have significant elevations in nucleated red blood cell counts and to estimate their predictive ability in identifying injury. This case-control study identified 176 infants born at 23-34 weeks of gestation between November 1994 and October 2004 at a single university hospital and with cerebral white matter injury characterized by periventricular leukomalacia (PVL) or ventriculomegaly due to white matter atrophy. A control was matched to each case using the subsequent delivery within 7 days of that gestational age without brain injury. The gestational age at birth was 27 weeks for both groups, but the cases had a significantly lower birth weight (mean +\/- standard deviation: 958 +\/- 306 g compared with 1,038 +\/- 381 g, P = .001). There was no difference in cesarean delivery (48% cases compared with 44% controls, P = .59). The cases had a significant increase in nucleated red blood cells per 100 white blood cells (WBC) (median, 5th percentile and 95th percentile: 22, 3 and 374 cases compared with 14, 1 and 312 controls; P = .02). Markers of chronic hypoxia, such as intrauterine growth restriction and oligohydramnios, and markers of acute hypoxia, such as an umbilical arterial pH less than 7.0 or base excess less than -12 mM, were both associated with significantly elevated neonatal nucleated red blood cell counts. A neonatal nucleated red blood cell count of 18 per 100 WBCs had a sensitivity of 56.9%, specificity of 57.9%, positive predictive value of 57.9%, and negative predictive value of 56.9% in predicting the development of cerebral white matter injury in this matched case-control sample. Preterm neonates with cerebral white matter injury have significant increases in nucleated red blood cell counts. Both acute and chronic hypoxia-ischemia can increase these counts, which limits their usefulness in timing injury. The predictive value of nucleated red blood cell counts at birth in identifying injury is poor. II-2.","subset":"pubmed_abstract"} +{"meta":{"pmid":22384322,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":3,"2023-23":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2023-50":1,"2013-48":1,"2024-22":1}}},"text":"Translational Genomics in Legumes Allowed Placing In Silico 5460 Unigenes on the Pea Functional Map and Identified Candidate Genes in Pisum sativum L.\nTo identify genes involved in phenotypic traits, translational genomics from highly characterized model plants to poorly characterized crop plants provides a valuable source of markers to saturate a zone of interest as well as functionally characterized candidate genes. In this paper, an integrated view of the pea genetic map was developed. A series of gene markers were mapped and their best reciprocal homologs were identified on M. truncatula, L. japonicus, soybean, and poplar pseudomolecules. Based on the syntenic relationships uncovered between pea and M. truncatula, 5460 pea Unigenes were tentatively placed on the consensus map. A new bioinformatics tool, http:\/\/www.thelegumeportal.net\/pea_mtr_translational_toolkit, was developed that allows, for any gene sequence, to search its putative position on the pea consensus map and hence to search for candidate genes among neighboring Unigenes. As an example, a promising candidate gene for the hypernodulation mutation nod3 in pea was proposed based on the map position of the likely homolog of Pub1, a M. truncatula gene involved in nodulation regulation. A broader view of pea genome evolution was obtained by revealing syntenic relationships between pea and sequenced genomes. Blocks of synteny were identified which gave new insights into the evolution of chromosome structure in Papillionoids and Eudicots. The power of the translational genomics approach was underlined.","subset":"pubmed_abstract"} +{"meta":{"pmid":25270135,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Transnasal odontoid resection: is there an anatomic explanation for differing swallowing outcomes?\nSwallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":28737816,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Protein stability and dynamics influenced by ligands in extremophilic complexes - a molecular dynamics investigation.\nIn this study, we explore the structural and dynamic adaptations of the Tryptophan synthase \u03b1-subunit in a ligand bound state in psychrophilic, mesophilic and hyperthermophilic organisms at different temperatures by MD simulations. We quantify the global and local fluctuations in the 40 ns time scale by analyzing the root mean square deviation\/fluctuations. The distinct behavior of the active site and loop 6 is observed with the elevation of temperature. Protein stability relies more on electrostatic interactions, and these interactions might be responsible for the stability of varying temperature evolved proteins. The paper also focuses on the effect of temperature on protein dynamics and stability governed by the distinct behavior of the ligand associated with its retention, binding and dissociation over the course of time. The integration of principle component analysis and a free energy landscape was useful in identifying the conformational space accessible to ligand bound homologues and how the presence of the ligand alters the conformational and dynamic properties of the protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":35253835,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":8}}},"text":"BWA-MEME: BWA-MEM emulated with a machine learning approach.\nThe growing use of next-generation sequencing and enlarged sequencing throughput require efficient short-read alignment, where seeding is one of the major performance bottlenecks. The key challenge in the seeding phase is searching for exact matches of substrings of short reads in the reference DNA sequence. Existing algorithms, however, present limitations in performance due to their frequent memory accesses. This article presents BWA-MEME, the first full-fledged short read alignment software that leverages learned indices for solving the exact match search problem for efficient seeding. BWA-MEME is a practical and efficient seeding algorithm based on a suffix array search algorithm that solves the challenges in utilizing learned indices for SMEM search which is extensively used in the seeding phase. Our evaluation shows that BWA-MEME achieves up to 3.45\u00d7 speedup in seeding throughput over BWA-MEM2 by reducing the number of instructions by 4.60\u00d7, memory accesses by 8.77\u00d7 and LLC misses by 2.21\u00d7, while ensuring the identical SAM output to BWA-MEM2. The source code and test scripts are available for academic use at https:\/\/github.com\/kaist-ina\/BWA-MEME\/. Supplementary data are available at Bioinformatics online.","subset":"pubmed_abstract"} +{"meta":{"pmid":28027035,"dup_signals":{"dup_doc_count":25,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2021-04":2,"2020-40":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":2,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-34":1,"2018-13":1,"2017-39":1,"2017-30":1,"2017-22":1,"2021-17":1,"2017-13":1}}},"text":"Justice and U.S. Occupational Therapy Practice: A Relationship 100 Years in the Making.\nAt 99 years old, occupational therapy is a global health care profession with a growing orientation toward justice. Because much of the occupational justice discourse has developed outside the United States, parallels between the profession's ethos and its current focus on justice must be examined more closely in this country. Although occupational therapy practitioners in the United States are better equipped than their predecessors with language and theories that explicitly emphasize justice, the potential for bringing that focus to bear depends on practitioners' willingness to think differently about their practices. We argue that a focus on justice can be naturally integrated with curriculum standards by emphasizing the link between cultural humility, client-centeredness, and embodied habits of \"seeking out unknown others.\" Outside formal education, practitioners can be encouraged to think of justice as something that already intersects with practice, not something that practitioners must choose whether to take up.","subset":"pubmed_abstract"} +{"meta":{"pmid":906095,"dup_signals":{"dup_doc_count":15,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":3,"2013-48":2,"2013-20":3}}},"text":"Clinical, haematological and pathological studies in donkeys experimentally infected with Trypanosoma brucei.\nDonkeys experimentally infected with Trypanosoma brucei showed dullness, weakness, fever, inappetence, conjunctivitis, tachycardia and polydyspnoea soon after detectable parasitaemia. The parasitaemia was generally low with transient high peaks except in the terminal stage when there was sustained high parasitaemia. A moderate anaemia was present as from the second week of infection but it was not progressive. There was a marked leucopoenia within 24 h of patent parasitaemia. Death occurred 2 to 2 1\/2 months after infection and at necropsy there was severe emaciation as well as mild serous effusion. Histologically, there was a nonsuppurative encephalomyelitis, cranial neuritis, extensive haemosiderosis, hyperplasia of follicles in lymph nodes and spleen and giant cell reaction in lymph nodes. Trypanosomes were present in the cerebrospinal fluid, the eye and serous effusions. These observations are similar to those previously reported in other animals infected with T. brucei.","subset":"pubmed_abstract"} +{"meta":{"pmid":27577880,"dup_signals":{"dup_doc_count":14}},"text":"A prospective cohort study to assess the micro-epidemiology of Plasmodium falciparum clinical malaria in Ilha Josina Machel (Manhi\u00e7a, Mozambique).\nAfter the decrease in clinical malaria incidence observed in Mozambique until 2009, a steady resurgence of cases per year has been reported nationally, reaching alarming levels in 2014. However, little is known about the clinical profile of the cases presented, or the possible epidemiological factors contributing to the resurgence of cases. An analysis of surveillance data collected between July 2003 and June 2013 in the high malaria-transmission area of Ilha Josina Machel (Southern Mozambique) through a paediatric outpatient morbidity surveillance system was conducted to calculate hospital-based clinical malaria rates, slide-positivity rates, and minimum community-based incidence rates (MCBIRs) and incidence rate ratios per malaria season in children younger than 15 years of age. Clinical malaria was defined as a fever \u226537.5 \u00b0C or a reported fever in the previous 24 h with a positive blood smear. Yearly mean age, geometric mean parasitaemia (GMP) and mean packed cell volume (PCV) were also described for all clinical malaria cases and compared between seasons using DID analysis or ANOVA tests. During the study period, the percentage of outpatient visits presenting with confirmed clinical malaria decreased from 51 % in the 2003-2004 season to 23 % in 2008-2009, followed by an increase back to 51 % in 2012-2013. The yearly mean age of cases significantly increased from 2.9 (95 % CI 2.8-3.0) in 2003-2004 to 5.7 (95 % CI 5.6-5.7) in 2012-2013, compared to non-malaria cases. An increase in mean PCV levels was also observed (p < 0.001), as well as in GMPs: from 5778 parasites\/\u00b5L in 2002-2003 to 17,316 parasites\/\u00b5L in 2012-2013 (p < 0.001) mainly driven by an increase in GMP in children older than 1 year of age. MCBIRs in infants decreased by 70 % (RR = 0.3, p < 0.001) between 2003-2004 and 2012-2013. Incidence diminished by a third among children 1- to 4-years between 2003 and 2007, although such drop was unsustained as observed in 2012-2013 (RR = 1.0, 95 % CI 0.9-1.0). Finally, the incidence among children 5-14 years was 3.8 (95 % CI 3.4-4.3) times higher in 2012-2013 compared to 2003-2004. Since 2003, Ilha Josina Machel observed a significant reduction of clinical malaria cases which was followed by an upsurge, following the national trend. A shift in the age distribution towards older children was observed, indicating that the changes in the transmission intensity patterns resulted in a slower acquisition of the naturally acquired immunity to malaria in children.","subset":"pubmed_abstract"} +{"meta":{"pmid":7924989,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"The spatial and temporal dynamics of Sax1 (CHox3) homeobox gene expression in the chick's spinal cord.\nSax1 (previously CHox3) is a chicken homeobox gene belonging to the same homeobox gene family as the Drosophila NK1 and the honeybee HHO genes. Sax1 transcripts are present from stage 2 H&H until at least 5 days of embryonic development. However, specific localization of Sax1 transcripts could not be detected by in situ hybridization prior to stage 8-, when Sax1 transcripts are specifically localized in the neural plate, posterior to the hindbrain. From stages 8- to 15 H&H, Sax1 continues to be expressed only in the spinal part of the neural plate. The anterior border of Sax1 expression was found to be always in the transverse plane separating the youngest somite from the yet unsegmented mesodermal plate and to regress with similar dynamics to that of the segregation of the somites from the mesodermal plate. The posterior border of Sax1 expression coincides with the posterior end of the neural plate. In order to study a possible regulation of Sax1 expression by its neighboring tissues, several embryonic manipulation experiments were performed. These manipulations included: removal of somites, mesodermal plate or notochord and transplantation of a young ectopic notochord in the vicinity of the neural plate or transplantation of neural plate sections into the extraembryonic area. The results of these experiments revealed that the induction of the neural plate by the mesoderm has already occurred in full primitive streak embryos, after which Sax1 is autonomously regulated within the spinal part of the neural plate.","subset":"pubmed_abstract"} +{"meta":{"pmid":26200715,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":2,"2024-26":1,"unknown":14}}},"text":"Religious and spiritual interventions in mental health care: a systematic review and meta-analysis of randomized controlled clinical trials.\nDespite the extensive literature assessing associations between religiosity\/spirituality and health, few studies have investigated the clinical applicability of this evidence. The purpose of this paper was to assess the impact of religious\/spiritual interventions (RSI) through randomized clinical trials (RCTs). A systematic review was performed in the following databases: PubMed, Scopus, Web of Science, PsycINFO, Cochrane Collaboration, Embase and SciELO. Through the use of a Boolean expression, articles were included if they: (i) investigated mental health outcomes; (ii) had a design consistent with RCTs. We excluded protocols involving intercessory prayer or distance healing. The study was conducted in two phases by reading: (1) title and abstracts; (2) full papers and assessing their methodological quality. Then, a meta-analysis was carried out. Through this method, 4751 papers were obtained, of which 23 remained included. The meta-analysis showed significant effects of RSI on anxiety general symptoms (p < 0.001) and in subgroups: meditation (p < 0.001); psychotherapy (p = 0.02); 1 month of follow-up (p < 0.001); and comparison groups with interventions (p < 0.001). Two significant differences were found in depressive symptoms: between 1 and 6 months and comparison groups with interventions (p = 0.05). In general, studies have shown that RSI decreased stress, alcoholism and depression. RCTs on RSI showed additional benefits including reduction of clinical symptoms (mainly anxiety). The diversity of protocols and outcomes associated with a lack of standardization of interventions point to the need for further studies evaluating the use of religiosity\/spirituality as a complementary treatment in health care.","subset":"pubmed_abstract"} +{"meta":{"pmid":8081743,"dup_signals":{"dup_doc_count":55,"dup_dump_count":28,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-14":4,"2023-06":2,"2022-40":1,"2022-27":2,"2022-21":1,"2022-05":3,"2021-43":1,"2021-39":5,"2021-31":3,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":3,"2021-04":2,"2020-50":3,"2020-45":3,"2020-40":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-22":4,"2024-18":2,"2024-10":1,"2024-26":1}}},"text":"The structure and antigenicity of a type C foot-and-mouth disease virus.\nPicornaviruses are responsible for a wide range of mammalian diseases and, in common with other RNA viruses, show considerable antigenic variation. Foot-and-mouth disease viruses (FMDVs) constitute one genus of the picornavirus family and are classified into seven serotypes, each of which shows considerable intratypic variation. This antigenic variation leads to continuing difficulties in controlling the disease. To date the structure of only one serotype, O, has been reported. The three-dimensional structure of a serotype C (isolate C-S8c1) FMDV, has been determined crystallographically at 3.5 A resolution. The main chain conformation of the virion is very similar to that of type O1 virus. The immunodominant G-H loop of VP1, the presumed site of cell attachment, is disordered in both types of virus indicating a functional role for flexibility of this region. There are significant changes in the structure of other antigenic loops and in some internal regions involved in protomer-protomer contacts, including the entire amino-terminal portion of VP2, described here for the first time for a picornavirus. Antigenic sites have been identified by genetic and peptide mapping methods, and located on the capsid. The data reveal a major new discontinuous antigenic site (site D) which is located near to the three-fold axis and involves residues of VP1, VP2 and VP3 which lie adjacent to each other on the capsid. In FMDV type C, amino acid substitutions seen in mutants that are resistant to neutralization by monoclonal antibodies (MAbs) map to predominantly surface-oriented residues with solvent-accessible side-chains not involved in interactions with other amino acids, whereas residues which are accessible but not substituted are found to be more frequently involved in protein-protein interactions. This provides a molecular interpretation for the repeated isolation of the same amino acid substitutions in MAb-resistant variants, an observation frequently made with RNA viruses. This first comparison of two FMDV serotypes shows how subtle changes at antigenic sites are sufficient to cause large changes in antigenic specificity between serotypes.","subset":"pubmed_abstract"} +{"meta":{"pmid":5917768,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Time-dependent processes in memory storage.\nThese observations indicate that the long-lasting trace of an experience is not completely fixed, consolidated, or coded at the time of the experience. Consolidation requires time, and under at least some circumstances the processes of consolidation appear to be susceptible to a variety of influences- both facilitating and impairing- several hours after the experience. There must be, it seems, more than one kind of memory trace process (31). If permanent memory traces consolidate slowly over time, then other processes must provide a temporary basis for memory while consolidation is occurring. The evidence clearly indicates that trial-to-trial improvement, or learning, in animals cannot be based completely on permanent memory storage. Amnesia can be produced by electroshock and drugs even if the animals are given the treatment long after they have demonstrated \"learning\" of the task. Of particular interest is the finding that retention of the inhibitory avoidance response increases with time. In a sense this should be expected, for it has long been known (and ignored) that, within limits, learning is facilitated by increasing the interval between repeated trials (7, 30). Our result may be the simplest case of such an effect. Since the improvement in retention with time seemed not to be due solely to consolidation (as indicated by electroshock effects), it would seem that the \"distribution of practice\" effect, as it is typically designated, may be due in part to a time-dependent temporary memory storage process. In our work with animals we have found no analog of human immediate memory such as that required for repeating digits (or finishing sentences). Animals tested immediately on the task described above after a trial typically showed no evidence of memory. It could be that the poor performance is due to excessive fright, but the \"distribution of practice effect\" is also typically observed in learning experiments in which food reward is used rather than shock avoidance. Since the retention tasks require the animals to change their behavior in some way, it could well be that the growth of retention over the first few minutes after a trial is due to time dependent processes involved in the organization of processes necessary for changing behavior, in addition to those involved in temporary storage and retrieval. It is worth pointing out that there is evidence of an analogous process in human memory (32). A complex picture of memory storage is emerging. There may be three memory trace systems: one for immediate memory (and not studied in our laboratory); one for short-term memory which develops within a few seconds or minutes and lasts for several hours; and one which consolidates slowly and is relatively permanent. The nature of the durability of the longterm memory trace (that is, the nature and basis of forgetting) is a separate but important issue. There is increasing evidence and speculation (20, 21, 33) that memory storage requires a \"tritrace\" system, and our findings are at least consistent with such a view. If there are, as seems possible, at least three kinds of traces involved in memory storage, how are they related? Is permanent memory produced by activity of temporary traces (31), or are the trace systems relatively independent? Although available findings do not provide an answer to this question, there does seem to be increasing evidence that the systems are independent. Acquisition can occur, as we have seen, without permanent consolidation, and both short-term and long-term memory increase with time. All this evidence suggests (but obviously does not prove) that each experience triggers activity in each memory system. Each repeated training trial may, according to this view, potentiate short-term processes underlying acquisition while simultaneously enhancing independent underlying long-term consolidation. Obviously, acceptance of these conclusions will require additional research. If this view is substantially correct, it seems clear that any search for the engram or the basis of memory is not going to be successful. Recognition of the possibility that several independent processes may be involved at different stages of memory may help to organize the search. A careful examination of the time course of retention and memory trace consolidation, as well as examination of the bases of the effects of memory-impairing and memory-facilitating treatments, may help to guide the search. It is clear that a complete theory of memory storage must eventually provide an understanding of time-dependent processes in memory. In 1930 Lashley wrote (2), \"The facts of both psychology and neurology show a degree of plasticity, of organization, and of adaptation and behavior which is far beyond any present possibility of explanation.\" Although this conclusion is still valid, the current surge of interest in memory storage offers hope that this conclusion may soon need to be modified.","subset":"pubmed_abstract"} +{"meta":{"pmid":28740687,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":2,"2018-09":1,"2018-05":1,"2017-47":2,"2017-39":1,"2017-30":1,"2021-17":1}}},"text":"Infections causing central airway obstruction: role of bronchoscopy in diagnosis and management.\nCentral airway obstructive infections (CAOI) are challenging medical conditions that may represent an advanced and complicated process of ongoing infections. The epidemiology of CAOI is unknown as well as the pathophysiology and the mechanism of development. This is due to sparse data in the literature that consists mainly of case reports and retrospective case series. CAOI can be caused by fungal, bacterial, parasitic and viral infections. Most patients with CAOI can be diagnosed clinically and with chest imaging, which demonstrate obstruction of the central airways. However, bronchoscopy is commonly used to confirm and obtain a specific diagnosis to guide specific therapy. In recent years, interventional pulmonology (IP) is becoming widely available and offer a minimally invasive approach for the management of central airway diseases such as cancers, benign strictures, and other conditions. Various bronchoscopic modalities are used to treat central airway obstruction (CAO), such as mechanical debulking, endobronchial laser therapy, electrocautery, argon plasma coagulation, cryotherapy, and airway stenting. In patients with CAOI, the role of therapeutic bronchoscopy is not clearly defined, but many isolated reports in the literature described bronchoscopic intervention in combination with medical therapy as the initial management approach. In this paper, we present cases of CAOI that underwent bronchoscopic intervention as part of their management. We described the infectious etiology, locations, bronchoscopic findings and bronchoscopic modalities for airway management.","subset":"pubmed_abstract"} +{"meta":{"pmid":34677284,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":7}}},"text":"Semi-Supervised Domain Adaptation for Holistic Counting under Label Gap.\nThis paper proposes a novel approach for semi-supervised domain adaptation for holistic regression tasks, where a DNN predicts a continuous value y\u2208R given an input image x. The current literature generally lacks specific domain adaptation approaches for this task, as most of them mostly focus on classification. In the context of holistic regression, most of the real-world datasets not only exhibit a covariate (or domain) shift, but also a label gap-the target dataset may contain labels not included in the source dataset (and vice versa). We propose an approach tackling both covariate and label gap in a unified training framework. Specifically, a Generative Adversarial Network (GAN) is used to reduce covariate shift, and label gap is mitigated via label normalisation. To avoid overfitting, we propose a stopping criterion that simultaneously takes advantage of the Maximum Mean Discrepancy and the GAN Global Optimality condition. To restore the original label range-that was previously normalised-a handful of annotated images from the target domain are used. Our experimental results, run on 3 different datasets, demonstrate that our approach drastically outperforms the state-of-the-art across the board. Specifically, for the cell counting problem, the mean squared error (MSE) is reduced from 759 to 5.62; in the case of the pedestrian dataset, our approach lowered the MSE from 131 to 1.47. For the last experimental setup, we borrowed a task from plant biology, i.e., counting the number of leaves in a plant, and we ran two series of experiments, showing the MSE is reduced from 2.36 to 0.88 (intra-species), and from 1.48 to 0.6 (inter-species).","subset":"pubmed_abstract"} +{"meta":{"pmid":8619444,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Biological behavior of Leishmania amazonensis isolated from humans with cutaneous, mucosal, or visceral leishmaniasis in BALB\/C mice.\nLeishmania amazonensis causes a wide spectrum of disease in humans. In this study, we evaluated BALB\/c mice infected with five strains of L. amazonensis isolated from patients with either cutaneous, mucosal, or visceral leishmaniasis. Mice infected with cutaneous and mucosal isolates developed ulcerating footpad lesions with parasite-loaded macrophages and extensive tissue destruction. Skin metastases, early dissemination of parasites to the spleen, and high anti-Leishmania antibody levels were also noted. Mice infected with L. amazonensis strains isolated from patients with visceral disease had a controlled infection, with small footpad lesions with mononuclear cell infiltration, few infected macrophages, and granuloma formation. They had no skin metastases, delayed dissemination of the parasite to the spleen, lower levels of IgG and higher levels of IgG2a against L. amazonensis. These findings demonstrate an unexpected resistance of BALB\/c mice to the infection with L. amazonensis isolated from patients with visceral leishmaniasis. This resistance seems to be due to differences in these parasites that may be related to the altered course of the disease in humans and in isogenic BALB\/c mice.","subset":"pubmed_abstract"} +{"meta":{"pmid":32165585,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Structure of V-ATPase from the mammalian brain.\nIn neurons, the loading of neurotransmitters into synaptic vesicles uses energy from proton-pumping vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases). These membrane protein complexes possess numerous subunit isoforms, which complicates their analysis. We isolated homogeneous rat brain V-ATPase through its interaction with SidK, a Legionella pneumophila effector protein. Cryo-electron microscopy allowed the construction of an atomic model, defining the enzyme's ATP:proton ratio as 3:10 and revealing a homolog of yeast subunit f in the membrane region, which we tentatively identify as RNAseK. The c ring encloses the transmembrane anchors for cleaved ATP6AP1\/Ac45 and ATP6AP2\/PRR, the latter of which is the (pro)renin receptor that, in other contexts, is involved in both Wnt signaling and the renin-angiotensin system that regulates blood pressure. This structure shows how ATP6AP1\/Ac45 and ATP6AP2\/PRR enable assembly of the enzyme's catalytic and membrane regions.","subset":"pubmed_abstract"} +{"meta":{"pmid":15146415,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":2,"unknown":7}}},"text":"Expression of Toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis.\nCD16 (IgG Fcgamma receptor type IIIA [FcgammaRIIIA])-expressing CD14+ monocytes express high levels of Toll-like receptor 2 (TLR-2) and are able to efficiently produce proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). To understand the role of CD16 and TLR-2 in monocyte and macrophage activation in rheumatoid arthritis (RA), we investigated the expression of TLR-2 on CD16+ blood monocytes and synovial tissue macrophages and the effect of CD16 and TLR-2 activation on cytokine production. The expression of CD14, CD16, TLR-2, and TLR-4 on blood monocytes was measured by flow cytometric analysis. CD16 and TLR-2 expression in RA synovial tissue was detected by 2-color immunofluorescence labeling. CD16+ mature monocytes were prepared by incubating blood monocytes in plastic plates for 24 hours. These adhered monocytes were stimulated with lipoteichoic acid (LTA), anti-FcgammaRIII antibody, and Hsp60 for 5 hours, and culture supernatants were measured for various cytokines by immunoassay. The activation of NF-kappaB was detected by electrophoretic mobility shift assay. The frequency of CD16+ cells in all blood monocytes was significantly increased in patients with RA compared with healthy controls. TLR-2 was expressed at higher levels on CD16+ monocytes than on CD16- monocytes, while TLR-4 was expressed similarly on both monocytes. In RA synovial tissue, CD16+\/TLR-2+ cells were distributed mainly in the lining layer. TLR-2 expression on monocytes was enhanced by macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10), but was reduced by transforming growth factor beta1, while CD16 expression was inducible by these cytokines. Adhered monocytes ( approximately 50% CD16+) produced TNFalpha, IL-1beta, IL-6, IL-8, IL-12 p40, IL-1 receptor antagonist, and IL-10 after LTA stimulation. This cytokine response was inhibited significantly by anti-TLR-2 antibody and partly by anti-TLR-4 antibody. Anti-FcgammaRIII antibody stimulation markedly enhanced the LTA-induced TNFalpha response. Hsp60 could stimulate TNFalpha production by adhered monocytes, which was inhibited similarly by anti-TLR-2 antibody and anti-TLR-4 antibody. NF-kappaB activation in adhered monocytes was induced by LTA, but this NF-kappaB activity was not augmented by anti-FcgammaRIII antibody stimulation. These results suggest that CD16+ monocytes and synovial tissue macrophages with high TLR-2 expression may be induced by M-CSF and IL-10, and their production of TNFalpha could be simulated by endogenous TLR ligands such as Hsp60 and FcgammaRIIIA ligation by small immune complexes in RA joints.","subset":"pubmed_abstract"} +{"meta":{"pmid":18619722,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats.\nFor assessing carcinogenicity in animals, it is difficult and costly, an alternative strategy has been desired. We explored the possibility of applying a toxicogenomics approach by using comprehensive gene expression data in rat liver treated with various compounds. As prototypic non-genotoxic hepatocarcinogens, thioacetamide (TAA) and methapyrilene (MP) were selected and 349 commonly changed genes were extracted by statistical analysis. Taking both compounds as positive with six compounds, acetaminophen, aspirin, phenylbutazone, rifampicin, alpha-naphthylisothiocyanate, and amiodarone as negative, prediction analysis of microarray (PAM) was performed. By training and 10-fold cross validation, a classifier containing 112 probe sets that gave an overall success rate of 95% was obtained. The validity of the present discriminator was checked for 30 chemicals. The PAM score showed characteristic time-dependent increases by treatment with several non-genotoxic hepatocarcinogens, including TAA, MP, coumarin, ethionine and WY-14643, while almost all of the non-carcinogenic samples were correctly predicted. Measurement of hepatic glutathione content suggested that MP and TAA cause glutathione depletion followed by a protective increase, but the protective response is exhausted during repeated administration. Therefore, the presently obtained PAM classifier could predict potential non-genotoxic hepatocarcinogenesis within 24 h after single dose and the inevitable pseudo-positives could be eliminated by checking data of repeated administrations up to 28 days. Tests for carcinogenicity using rats takes at least 2 years, while the present work suggests the possibility of lowering the time to 28 days with high precision, at least for a category of non-genotoxic hepatocarcinogens causing oxidative stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":8014121,"dup_signals":{"dup_doc_count":33,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2024-22":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":23}}},"text":"Ontogeny and distribution of Fc gamma receptors in the human placenta. Transport or immune surveillance?\nThe human fetus acquires maternal IgG via the chorioallantoic placenta. Utilising antibodies against 3 characterised subtypes of IgG receptor (Fc gamma R) expressed by human leucocytes, we show by confocal immunofluorescence microscopy that these molecules are also expressed by cells of the placenta. Fc gamma RI (CD64) is expressed by undifferentiated mesenchymal or fibroblast cells of 1st trimester and term chorionic villi. Punctate immunoreactivity for Fc gamma RII (CDw32) is found on capillary endothelial cells of term and 1st trimester villi. Fc gamma RIII (CD16) expression is observed in the trophoblast surrounding chorionic villi that forms the functional 'barrier' between mother and fetus. In 1st trimester villi this receptor is associated with a population of marginated vesicular inclusions of the syncytiotrophoblast. In term villi the receptor is concentrated in the apex of the syncytiotrophoblast, suggesting a possible role in the maternofetal transmission of passive immunity. All 3 subtypes of receptor are expressed by Hofbauer cells. We have been unable to demonstrate these receptors in cytotrophoblast cells. Results obtained using immunofluorescence and immunoelectron microscopic detection of endogenous IgG are consistent with the hypothesis that IgG is internalised into clathrin-coated pits and vesicles. Endogenous IgG was not demonstrable in cytotrophoblast cells. The significance of our inability to demonstrate IgG or specific receptor molecules for IgG in cytotrophoblast cells, and possible roles of Fc gamma receptor-bearing cells of the placenta are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":9539254,"dup_signals":{"dup_doc_count":29,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2020-24":1,"2020-05":1,"2019-35":1,"2019-30":1,"2019-22":1,"2017-47":3,"2017-26":3,"2017-17":2,"2017-09":1,"2017-04":2,"2016-50":1,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":2,"2021-10":1,"2017-13":1}}},"text":"Vitamin D3 enhances mood in healthy subjects during winter.\nMood changes synchronised to the seasons exist on a continuum between individuals, with anxiety and depression increasing during the winter months. An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder (SAD) with carbohydrate craving, hypersomnia, lethargy, and changes in circadian rhythms also evident. It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3, the hormone of sunlight, leading to changes in brain serotonin. Forty-four healthy subjects were given 400 IU, 800 IU, or no vitamin D3 for 5 days during late winter in a random double-blind study. Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect. Results are discussed in terms of their implications for seasonality, SAD, serotonin, food preference, sleep, and circadian rhythms.","subset":"pubmed_abstract"} +{"meta":{"pmid":33996360,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Synchronous occurrence of breast cancer and refractory diffuse large B-cell abdominal lymphoma: Management and review of the literature.\nThe synchronous occurrence of primary breast cancer and lymphoid tissue malignant tumors has been rarely reported in the literature. We present an exceedingly rare case of synchronous breast invasive ductal carcinoma with an abdominal diffuse large B-cell lymphoma (DLBCL). A 78-year-old woman who was diagnosed with a luminal A invasive breast cancer on core biopsy, and complaint of progressively worsening low back pain. An abdominal computed tomography (CT) scan that was performed as part of the preoperative staging showed a large abdominal mass measuring 10.5 \u00d7 4.8 \u00d7 9.5 cm surrounding the lower part of the abdominal aorta, the right common iliac, right external, right internal iliac, and the left internal iliac arteries. A CT-guided fine-needle aspiration biopsy (FNAB) of the abdominal mass was then performed, to exclude the possibility of being an abdominal tumor metastasis of the known primary breast cancer. Histopathological findings were suggestive of DLBCL. Following a multidisciplinary team discussion, chemotherapy was initiated for DLBCL. The tumor however was refractory to multiple chemotherapy regimens and exhibited a highly aggressive clinical course. The diagnostic evaluation and management of the patient are discussed, along with a review of the relevant literature. This case underscores the fact that the presence of synchronous malignancies may pose both diagnostic and treatment challenges. Accurate staging of both malignancies and multidisciplinary team discussion is of utmost importance to guide an optimal therapeutic approach. Histopathological evaluation is essential for both tumors, for the second malignancy not to be misinterpreted as a secondary deposit of the primary one.","subset":"pubmed_abstract"} +{"meta":{"pmid":24477946,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":17}}},"text":"Molecular dynamics simulations of apocupredoxins: insights into the formation and stabilization of copper sites under entatic control.\nCupredoxins perform copper-mediated long-range electron transfer (ET) in biological systems. Their copper-binding sites have evolved to force copper ions into ET-competent systems with decreased reorganization energy, increased reduction potential, and a distinct electronic structure compared with those of non-ET-competent copper complexes. The entatic or rack-induced state hypothesis explains these special properties in terms of the strain that the protein matrix exerts on the metal ions. This idea is supported by X-ray structures of apocupredoxins displaying \"closed\" arrangements of the copper ligands like those observed in the holoproteins; however, it implies completely buried copper-binding atoms, conflicting with the notion that they must be exposed for copper loading. On the other hand, a recent work based on NMR showed that the copper-binding regions of apocupredoxins are flexible in solution. We have explored five cupredoxins in their \"closed\" apo forms through molecular dynamics simulations. We observed that prearranged ligand conformations are not stable as the X-ray data suggest, although they do form part of the dynamic landscape of the apoproteins. This translates into variable flexibility of the copper-binding regions within a rigid fold, accompanied by fluctuations of the hydrogen bonds around the copper ligands. Major conformations with solvent-exposed copper-binding atoms could allow initial binding of the copper ions. An eventual subsequent incursion to the closed state would result in binding of the remaining ligands, trapping the closed conformation thanks to the additional binding energy and the fastening of noncovalent interactions that make up the rack.","subset":"pubmed_abstract"} +{"meta":{"pmid":36774324,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Acute effects of deep brain stimulation on brain function in obsessive-compulsive disorder.\nDeep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. We explored how DBS doses between 3-5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs). We focused on theta power\/ phase-stability, given their previously established role in DBS for OCD. Cortical theta power and theta phase-stability did not increase significantly with DBS voltage. DBS-induced theta power peaks were seen at the previously defined individualized therapeutic voltage. Although LFP power generally increased with DBS voltages, this occurred mostly in frequency peaks that overlapped with stimulation artifacts limiting its interpretability. Though highly idiosyncratic, three subjects showed significant acute DBS effects on electroencephalogram theta power and four subjects showed significant carry-over effects (pre-vs post DBS, unstimulated) on LFP and electroencephalogram theta power. Our findings challenge the presence of a consistent dose-response relationship between stimulation voltage and brain activity. Theta power may be investigated further as a neurophysiological marker to aid personalized DBS voltage optimization in OCD.","subset":"pubmed_abstract"} +{"meta":{"pmid":18371191,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":13}}},"text":"Hypothesis testing for evaluating a multimodal pattern recognition framework applied to speaker detection.\nSpeaker detection is an important component of many human-computer interaction applications, like for example, multimedia indexing, or ambient intelligent systems. This work addresses the problem of detecting the current speaker in audio-visual sequences. The detector performs with few and simple material since a single camera and microphone meets the needs. A multimodal pattern recognition framework is proposed, with solutions provided for each step of the process, namely, the feature generation and extraction steps, the classification, and the evaluation of the system performance. The decision is based on the estimation of the synchrony between the audio and the video signals. Prior to the classification, an information theoretic framework is applied to extract optimized audio features using video information. The classification step is then defined through a hypothesis testing framework in order to get confidence levels associated to the classifier outputs, allowing thereby an evaluation of the performance of the whole multimodal pattern recognition system. Through the hypothesis testing approach, the classifier performance can be given as a ratio of detection to false-alarm probabilities. Above all, the hypothesis tests give means for measuring the whole pattern recognition process efficiency. In particular, the gain offered by the proposed feature extraction step can be evaluated. As a result, it is shown that introducing such a feature extraction step increases the ability of the classifier to produce good relative instance scores, and therefore, the performance of the pattern recognition process. The powerful capacities of hypothesis tests as an evaluation tool are exploited to assess the performance of a multimodal pattern recognition process. In particular, the advantage of performing or not a feature extraction step prior to the classification is evaluated. Although the proposed framework is used here for detecting the speaker in audiovisual sequences, it could be applied to any other classification task involving two spatio-temporal co-occurring signals.","subset":"pubmed_abstract"} +{"meta":{"pmid":10371567,"dup_signals":{"dup_doc_count":49,"dup_dump_count":33,"dup_details":{"curated_sources":2,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":2,"2016-18":2,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":1,"2014-23":3,"2014-15":4,"2018-13":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening.\nThe Edinburgh randomised trial of breast-cancer screening recruited women aged 45-64 years from 1978 to 1981 (cohort 1), and those aged 45-49 years during 1982-85 (cohorts 2 and 3). Results based on 14 years of follow-up and 270,000 woman-years of observation are reported. Breast-cancer mortality rates in the intervention group (28,628 women offered screening) were compared with those in the control group (26,026) with adjustment for socioeconomic status (SES) of general medical practices. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years. Analyses were by intention to treat. Initial unadjusted results showed a difference of just 13% in breast-cancer mortality rates between the intervention and control groups (156 deaths [5.18 per 10,000] vs 167 [6.04 per 10,000]; rate ratio 0.87 [95% CI 0.70-1.06]), but the results were influenced by differences in SES by trial group. After adjustment for SES, the rate ratio was 0.79 (95% CI 0.60-1.02). When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 (0.53-0.95). There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit (rate ratio 0.70 [0.41-1.20]). No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years. Other-cause mortality rates did not differ by trial group when adjusted for SES. Our findings confirm results from randomised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality. Similar results are reported by the UK geographical comparison, UK Trial of Early Detection of Breast Cancer. The results for younger women suggest benefit from introduction of screening before 50 years of age.","subset":"pubmed_abstract"} +{"meta":{"pmid":29132779,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":2,"2020-40":1,"2020-29":1,"2023-23":1}}},"text":"Reliability assessment of bioreactor landfills using Monte Carlo simulation and coupled hydro-bio-mechanical model.\nThe performance of a bioreactor landfill is highly influenced by the simultaneous interactions of several coupled processes that occur within the landfill. In addition, the high uncertainty and spatial variability in the geotechnical properties of municipal solid waste (MSW) poses significant challenge in accurately predicting the performance of bioreactor landfills. In this study, a 2D coupled hydro-bio-mechanical (CHBM) model was employed to predict the behavior of MSW in bioreactor landfills. The numerical model integrated a two-phase flow hydraulic model, a plane-strain formulation of Mohr-Coulomb constitutive model, and a first order decay biodegradation model. The statistical ranges (mean and standard deviation) of some of the major influential MSW properties were derived from the published studies. Random fields of spatially variable MSW properties were generated following the log-normal distribution. Reliability-based analysis was carried out by performing several realizations of Monte-Carlo simulations and the statistical response of the output results including the moisture distribution, pore fluid pressures, landfill settlement, and interface shear response of the composite liner system were quantified. The results clearly indicate the importance of considering spatial variability of the geotechnical MSW properties and its influence on the performance of bioreactor landfills during leachate injection operations. A comparison of the results with the deterministic analysis was performed to evaluate the relative benefits and to emphasize the need for reliability-based analysis for effective design of bioreactor landfills.","subset":"pubmed_abstract"} +{"meta":{"pmid":32567552,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Platelet parameters in Chinese older adults with metabolic syndrome.\nWe aimed to examine the associations of platelet parameters with the presence of metabolic syndrome in community-dwelling older Chinese adults. Study sample was from the Weitang Geriatric Diseases Study, which included 4338 individuals aged 60 years or above. The mean age of the participants was 68 years. Metabolic syndrome was defined based on the Adult Treatment Panel III criteria. Platelet parameters were assessed using an automated hematology analyzer. Multiple logistic regression models were fitted to examine relationships between the platelet parameters and the presence of metabolic syndrome after adjusting for potential confounders. The adjusted odds ratio (95% CI) of metabolic syndrome for the highest quartile of platelet parameters (platelet count, mean platelet volume, plateletcrit, platelet distribution width, platelet larger cell ratio) when compared to the lowest quartile were 1.32 (1.06, 1.64), 1.00 (0.81, 1.24), 1.37 (1.10, 1.71), 1.45 (1.14, 1.83), 1.11 (0.89, 1.39), respectively. Hypertension and diabetes modified the relationship between platelet distribution width and metabolic syndrome with the associations being significant in hypertensive and non-diabetic groups. The levels of platelet distribution width increased with the risk of metabolic syndrome in men but not in women. The levels of platelet count, plateletcrit and platelet distribution width increased in older adults with metabolic syndrome, suggesting that these parameters may be useful biomarkers for further risk appraisal of metabolic syndrome in aged population.","subset":"pubmed_abstract"} +{"meta":{"pmid":3030901,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Irritable bowel-type symptoms in spontaneous and induced constipation.\nThe prevalence and severity of irritable bowel symptoms was assessed by systematic questioning in 44 constipated volunteers, most of whom had documented slow intestinal transit. All but two had one or more of the following: passage of mucus, rectal dissatisfaction, bloating, and abdominal pain relieved by defecation. All the symptoms were more prevalent than in 17 normal volunteers or in 301 apparently healthy people studied previously. When 12 normal subjects were made constipated with loperamide all developed one or more irritable bowel symptoms. When 24 constipated subjects received effective laxative treatment the prevalence and severity of these symptoms fell markedly. The findings suggest that in some subjects the slowing down of intestinal transit is associated with irritable bowel symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":26053344,"dup_signals":{"dup_doc_count":24,"dup_details":{"curated_sources":2,"unknown":22}}},"text":"Number of deployments, relationship satisfaction and perpetration of partner violence among U.S. Navy members.\nThe present brief report examined whether number of deployments, relationship satisfaction, and the interaction between number of deployments and relationship satisfaction predicted Navy members' reports of perpetrating physical partner violence. Participants were 80 U.S. Navy members assigned to an Arleigh Burke-class destroyer anticipating an 8-month deployment after Operation Enduring Freedom\/Operation Iraqi Freedom. The effect that the number of deployments had on perpetrating physical partner violence diminished as relationship satisfaction increased. Results suggest the importance of designing domestic violence intervention and treatment efforts toward those who report high levels of deployment and low relationship satisfaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":11817724,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Chiral separation of enantiomeric 1,2-diamines using molecular imprinting method and selectivity enhancement by addition of achiral primary amines into eluents.\nThe imprinted polymers based on a transient complex formation between methacrylic acid and template molecules were prepared by using methacrylic acid and ethylene dimethacrylate as a cross-linking agent. The template molecules used were (R,R)-cyclohexanediamine (1), (S,S)-1,2-diphenylethylenediamine (2) and (S)-1,1'-binaphthyl-2,2'-diamine (3). Another group of templates were those in which the amino group of these templates had been substituted by the hydroxy group: (R,R)-1,2-cyclohexanediol (4) and (S,S)-hydrobenzoin (5). Racemic 2 was separated by the polymer prepared with template 2 (P2) and that with template 1 (P1). Template 2 is larger than template 1 in steric bulkiness, but P1 was effective for the enantiomer separation of racemic 2. P1 was not effective for the separation of racemic 4. Enantioselectivity observed in racemic 2 in P2 was higher than that in racemic 1 in P1. P2 has no definite predetermined shape for solute 1, but it was capable of separating racemic 1. This separation should be thus ascribed to the orientation of at least two carbonyl groups reflecting the conformation of template 2 in P2 cavity. Racemic 5, having the same configuration of the two bulky phenyl groups as that of solute 2, was separated in P2. When the primary amines such as propylamine, cyclohexylamine and 1-adamantanamine were added into the acetic acid-methanol mixtures as eluents, both enantioselectivity and retentivity for racemic 2 were enhanced along with the remarkable peak tailing.","subset":"pubmed_abstract"} +{"meta":{"pmid":16676038,"dup_signals":{"dup_doc_count":24,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":3,"2016-30":3,"2016-22":2,"2016-18":1,"2016-07":3,"2015-40":1,"2015-32":1,"2015-27":1,"2015-22":2,"2017-39":1}}},"text":"Absolute measurement of F2-laser power at 157 nm.\nWe report a comparison of laser power measurements at the F2-laser wavelength of 157 nm made at two facilities of the Physikalisch-Technische Bundesanstalt (PTB), the German national metrology institute. At the PTB laboratory at the electron storage ring BESSY II in Berlin, the scale for laser power was directly traced to a cryogenic radiometer operating at 157 nm, whereas at the PTB laser radiometry facility in Braunschweig the calibration of transfer detectors was performed with a newly developed standard for laser power at 157 nm, which is traceable in several steps to a cryogenic radiometer operating at 633 nm. The comparison was performed under vacuum conditions with laser pulse energies of approximately 10 microJ, however with different average powers because different primary standard radiometers were used. The relative deviation for the responsivity of the transfer detector was 4.8% and thus within the combined standard uncertainty.","subset":"pubmed_abstract"} +{"meta":{"pmid":2500708,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Activation of salivary secretion: coupling of cell volume and [Ca2+]i in single cells.\nHigh-resolution differential interference contrast microscopy and digital imaging of the fluorescent calcium indicator dye fura-2 were performed simultaneously in single rat salivary gland acinar cells to examine the effects of muscarinic stimulation on cell volume and cytoplasmic calcium concentration ([Ca2+]i). Agonist stimulation of fluid secretion is initially associated with a rapid tenfold increase in [Ca2+]i as well as a substantial cell shrinkage. Subsequent changes of cell volume in the continued presence of agonist are tightly coupled to dynamic levels of [Ca2+]i, even during [Ca2+]i oscillations. Experiments with Ca2+ chelators and ionophores showed that physiological elevations of [Ca2+]i are necessary and sufficient to cause changes in cell volume. The relation between [Ca2+]i and cell volume suggests that the latter reflects the secretory state of the acinar cell. Agonist-induced changes in [Ca2+]i, by modulating specific ion permeabilities, result in solute movement into or out of the cell. The resultant cell volume changes may be important in modulating salivary secretion.","subset":"pubmed_abstract"} +{"meta":{"pmid":19062317,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2022-21":1,"2021-17":1,"2020-05":1,"2019-39":1,"2018-51":1,"2018-30":1,"2018-09":1,"2017-47":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-23":1,"2017-13":1}}},"text":"Expression of costimulatory ligand CD70 on steady-state dendritic cells breaks CD8+ T cell tolerance and permits effective immunity.\nSteady-state dendritic cells (DCs) maintain peripheral T cell tolerance, whereas mature DCs generate immunity. CD70 is a costimulatory ligand acquired upon DC maturation. To determine its impact on T cell fate, we have generated mice that constitutively express CD70 in conventional DCs (cDCs). In these mice, naive CD4+ and CD8+ T cells spontaneously convert into effector cells. Administration of peptide without adjuvant, which is ordinarily tolerogenic, elicited tumor-eradicating CD8+ T cell responses and robust CD4+ T cell-independent memory. CD70 was also constitutively expressed in cDCs that inducibly present viral epitopes. In this case, tolerance induction was prevented as well. The antigen-presenting DCs generated protective immunity to virus infection and broke a pre-existing state of CD8+ T cell tolerance. Thus, the sole expression of CD70 by otherwise immature cDCs sufficed to convert CD8+ T cell tolerance into immunity, defining the importance of CD27-CD70 interactions at the interface between T cell and DC.","subset":"pubmed_abstract"} +{"meta":{"pmid":21749249,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers.\nA cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.","subset":"pubmed_abstract"} +{"meta":{"pmid":22711759,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"A longer interval without GH replacement and female gender are associated with lower bone mineral density in adults with childhood-onset GH deficiency: a KIMS database analysis.\nChildhood-onset GH deficiency (COGHD) is associated with low bone mineral density (BMD). Adults with persistent COGHD may be at risk for insufficient bone accrual or bone loss during adulthood. The purpose of this study was to identify BMD predictors and to characterize the effects of GH replacement on BMD in COGHD adults with persistent GHD. Retrospective analysis of the KIMS database. Variables predicting standardized BMD (sBMD) were identified. The effect of GH replacement (3 years) on BMD was examined. Three hundred and fourteen COGHD adults (148 women, 166 men; 62 non-na\u00efve, 178 semi-na\u00efve, and 74 true na\u00efve, depending on length and timing of previous GH replacement), who had BMD measured in lumbar spine (LS) and femoral neck (FN) at study entry. In semi-na\u00efve subjects, a longer gap in GH replacement between childhood and adulthood was predictive of lower sBMD in the FN (r=-0.18, P=0.038). TSH deficiency predicted lower sBMD in the LS (r=-0.16, P=0.052). In true na\u00efve patients, a longer gap between onset of pituitary disease and study entry (r=-0.35, P=0.012), and female gender (r=-0.27, P=0.043) independently predicted lower sBMD in the FN. There were no differences in BMD increases between non-na\u00efve, semi-na\u00efve, and true na\u00efve subjects on GH replacement. In semi-na\u00efve subjects a longer interval off GH replacement was associated with lower sBMD in the FN. Among true na\u00efve patients, a longer gap between the onset of pituitary disease and GH replacement, and female gender predicted lower sBMD in the FN.","subset":"pubmed_abstract"} +{"meta":{"pmid":29056421,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Structure-Guided Development of a Potent and Selective Non-covalent Active-Site Inhibitor of USP7.\nDeubiquitinating enzymes (DUBs) have garnered significant attention as drug targets in the last 5-10 years. The excitement stems in large part from the powerful ability of DUB inhibitors to promote degradation of oncogenic proteins, especially proteins that are challenging to directly target but which are stabilized by DUB family members. Highly optimized and well-characterized DUB inhibitors have thus become highly sought after tools. Most reported DUB inhibitors, however, are polypharmacological agents possessing weak (micromolar) potency toward their primary target, limiting their utility in target validation and mechanism studies. Due to a lack of high-resolution DUB\u22c5small-molecule ligand complex structures, no structure-guided optimization efforts have been reported for a mammalian DUB. Here, we report a small-molecule\u22c5ubiquitin-specific protease (USP) family DUB co-structure and rapid design of potent and selective inhibitors of USP7 guided by the structure. Interestingly, the compounds are non-covalent active-site inhibitors.","subset":"pubmed_abstract"} +{"meta":{"pmid":21337521,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium.\nThe telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGF\u03b2 on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":10400768,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The resistance of retroviral vectors produced from human cells to serum inactivation in vivo and in vitro is primate species dependent.\nThe ability to deliver genes as therapeutics requires an understanding of the vector pharmacokinetics similar to that required for conventional drugs. A first question is the half-life of the vector in the bloodstream. Retroviral vectors produced in certain human cell lines differ from vectors produced in nonhuman cell lines in being substantially resistant to inactivation in vitro by human serum complement (F. L. Cosset, Y. Takeuchi, J. L. Battini, R. A. Weiss, and M. K. Collins, J. Virol. 69:7430-7436, 1995). Thus, use of human packaging cell lines (PCL) may produce vectors with longer half-lives, resulting in more-efficacious in vivo gene therapy. However, survival of human PCL-produced vectors in vivo following systemic administration has not been explored. In this investigation, the half-lives of retroviral vectors packaged by either canine D17 or human HT1080 PCL were measured in the bloodstreams of macaques and chimpanzees. Human PCL-produced vectors exhibited significantly higher concentrations of circulating biologically active vector at the earliest time points measured (>1, 000-fold in chimpanzees), as well as substantially extended half-lives, compared to canine PCL-produced vectors. In addition, the circulation half-life of human PCL-produced vector was longer in chimpanzees than in macaques. This was consistent with in vitro findings which demonstrated that primate serum inactivation of vector produced from human PCL increased with increasing phylogenetic distance from humans. These results establish that in vivo retroviral vector half-life correlates with in vitro resistance to complement. Furthermore, these findings should influence the choice of animal models used to evaluate retroviral-vector-based therapies.","subset":"pubmed_abstract"} +{"meta":{"pmid":10616945,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"unknown":10}}},"text":"Autobiographical memory and dissociation in borderline personality disorder.\nThis study investigated whether individuals with borderline personality disorder (BPD) tend to be overgeneral in their autobiographical recall and whether the extent of their overgeneral recall covaries with their susceptibilities to dissociative experiences, as expected on theoretical grounds. Twenty-three patients with BPD and 23 matched controls completed the Autobiographical Memory Test (AMT) and self-report measures of depression, anxiety, trait anger and dissociative experiences. Participants with BPD scored significantly higher than the control group on the measures of depression, anxiety, trait anger, and dissociative experiences and also retrieved significantly more general memories on the AMT. The number of general memories retrieved by the BPD group correlated significantly with their dissociation scores but not with their scores on mood measures. Patients with BPD have difficulties in recalling specific autobiographical memories. These difficulties are related to their tendency to dissociate and may help them to avoid episodic information that would evoke acutely negative affect.","subset":"pubmed_abstract"} +{"meta":{"pmid":22222953,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2023-40":1,"2023-06":1,"2021-39":1,"2021-31":2,"2021-21":1,"2019-18":1,"2018-47":1,"2018-39":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2023-50":1,"2024-18":1}}},"text":"Investigation of the origin and spread of a Mammalian transposable element based on current sequence diversity.\nAlmost half the human genome consists of mobile DNA elements, and their analysis is a vital part of understanding the human genome as a whole. Many of these elements are ancient and have persisted in the genome for tens or hundreds of millions of years, providing a window into the evolution of modern mammals. The Golem family have been used as model transposons to highlight computational analyses which can be used to investigate these elements, particularly the use of molecular dating with large transposon families. Whole-genome searches found Golem sequences in 20 mammalian species. Golem A and B subsequences were only found in primates and squirrel. Interestingly, the full-length Golem, found as a few copies in many mammalian genomes, was found abundantly in horse. A phylogenetic profile suggested that Golem originated after the eutherian-metatherian divergence and that the A and B subfamilies originated at a much later date. Molecular dating based on sequence diversity suggests an early age, of 175 Mya, for the origin of the family and that the A and B lineages originated much earlier than expected from their current taxonomic distribution and have subsequently been lost in some lineages. Using publically available data, it is possible to investigate the evolutionary history of transposon families. Determining in which organisms a transposon can be found is often used to date the origin and expansion of the families. However, in this analysis, molecular dating, commonly used for determining the age of gene sequences, has been used, reducing the likelihood of errors from deleted lineages.","subset":"pubmed_abstract"} +{"meta":{"pmid":24037626,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Heritable forms of pulmonary arterial hypertension.\nTremendous progress has been made in understanding the genetics of heritable pulmonary arterial hypertension (HPAH) since its description in the 1950s. Germline mutations in the gene coding bone morphogenetic receptor type 2 (BMPR2) are detectable in the majority of cases of HPAH, and in a small proportion of cases of idiopathic pulmonary arterial hypertension (IPAH). Recent advancements in gene sequencing methods have facilitated the discovery of additional genes with mutations among those with and without familial PAH (CAV1, KCNK3). HPAH is an autosomal dominant disease characterized by reduced penetrance, variable expressivity, and female predominance. These characteristics suggest that genetic and nongenetic factors modify disease expression, highlighting areas of active investigation. The reduced penetrance makes genetic counseling complex, as the majority of carriers of PAH-related mutations will never be diagnosed with the disease. This issue is increasingly important, as clinical testing for BMPR2 and other mutations is now available for the evaluation of patients and their at-risk kin. The possibilities to avoid mutation transmission, such as the rapidly advancing field of preimplantation genetic testing, highlight the need for all clinicians to understand the genetic features of PAH risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":20959563,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The Arabidopsis dynamin-related protein2 family is essential for gametophyte development.\nClathrin-mediated membrane trafficking is critical for multiple stages of plant growth and development. One key component of clathrin-mediated trafficking in animals is dynamin, a polymerizing GTPase that plays both regulatory and mechanical roles. Other eukaryotes use various dynamin-related proteins (DRP) in clathrin-mediated trafficking. Plants are unique in the apparent involvement of both a family of classical dynamins (DRP2) and a family of dynamin-related proteins (DRP1) in clathrin-mediated membrane trafficking. Our analysis of drp2 insertional mutants demonstrates that, similar to the DRP1 family, the DRP2 family is essential for Arabidopsis thaliana development. Gametophytes lacking both DRP2A and DRP2B were inviable, arresting prior to the first mitotic division in both male and female gametogenesis. Mutant pollen displayed a variety of defects, including branched or irregular cell plates, altered Golgi morphology and ectopic callose deposition. Ectopic callose deposition was also visible in the pollen-lethal drp1c-1 mutant and appears to be a specific feature of pollen-defective mutants with impaired membrane trafficking. However, drp2ab pollen arrested at earlier stages in development than drp1c-1 pollen and did not accumulate excess plasma membrane or display other gross defects in plasma membrane morphology. Therefore, the DRP2 family, but not DRP1C, is necessary for cell cycle progression during early gametophyte development. This suggests a possible role for DRP2-dependent clathrin-mediated trafficking in the transduction of developmental signals in the gametophyte.","subset":"pubmed_abstract"} +{"meta":{"pmid":1708089,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Regulation of dopamine D2 receptors in a novel cell line (SUP1).\nA prolactin-secreting cell line, SUP1, has been established from rat pituitary tumor 7315a. In radioligand binding experiments, the D2 receptor antagonist (S)-(-)-3-[125I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamide ([125I]IBZM) labeled a single class of sites in homogenates of SUP1 cells (Kd = 0.6 nM; Bmax = 45 fmol\/mg of protein). The sites displayed a pharmacological profile consistent with that of D2 receptors. Inhibition of the binding of [125I]IBZM by dopamine was sensitive to GTP, suggesting that D2 receptors in SUP1 cells are coupled to guanine nucleotide-binding protein(s). In the presence of isobutylmethylxanthine, dopamine decreased the level of cAMP accumulation in SUP1 cells. Dopamine also inhibited prolactin secretion from SUP1 cells. Both the inhibition of cAMP accumulation and the inhibition of prolactin secretion were blocked by D2 receptor antagonists, suggesting that these effects of dopamine were mediated by an interaction with D2 receptors. The regulation of D2 receptors in SUP1 cells by D2 receptor agonists was investigated. Exposure of SUP1 cells to dopamine or to the D2 receptor agonist N-propylnorapomorphine led to increased expression of D2 receptors, with no change in the affinity of the receptors for [125I]IBZM. An increase in the density of D2 receptors in SUP1 cells was evident within 7 hr of exposure to dopamine. Spiroperidol, a D2 receptor antagonist, blocked the effect of dopamine on receptor density. These results suggest that exposure of D2 receptors in SUP1 cells to agonists leads to an up-regulation of D2 receptors. Dopamine retained the ability to inhibit cAMP accumulation in SUP1 cells exposed to dopamine for 24 hr, suggesting that D2 receptors in SUP1 cells are not desensitized by prolonged exposure to agonist. SUP1 cells should be a useful model system for future studies of the regulation of the expression and function of D2 receptors in cultured cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":11095728,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"An autocatalytic mechanism of protein nitrosylation.\nNitros(yl)ation is a widespread protein modification that occurs during many physiological and pathological processes. It can alter both the activity and function of a protein. Nitric oxide (( small middle dot)NO) has been implicated in this process, but its mechanism remained uncertain. ( small middle dot)NO is unable to react with nucleophiles under oxygen-free conditions, suggesting that its higher oxides, such as N(2)O(3), were actually nitrosylating agents. However, low concentrations and short lifespans of these species in vivo raise the question of how they could efficiently locate target proteins. Here we demonstrate that at physiological concentrations of ( small middle dot)NO, N(2)O(3) forms inside protein-hydrophobic cores and causes nitrosylation within the protein interior. This mechanism of protein modification has not been characterized, because all previously described mechanisms (e.g., phosphorylation, acetylation, ADP-ribosylation, etc.) occur via attack on a protein by an external modification agent. Oxidation of ( small middle dot)NO to N(2)O(3) is facilitated by micellar catalysis, which is mediated by the hydrophobic phase of proteins. Thus, a target protein seems to be a catalyst of its own nitrosylation. One of the applications of this finding, as we report here, is the design of specific hydrophobic compounds whose cooperation with ( small middle dot)NO and O(2) allows the rapid inactivation of target enzymes to occur.","subset":"pubmed_abstract"} +{"meta":{"pmid":18944624,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Mechanism of broccoli-mediated verticillium wilt reduction in cauliflower.\nABSTRACT Broccoli is resistant to Verticillium dahliae infection and does not express wilt symptoms. Incorporation of broccoli residues reduces soil populations of V. dahliae. The effects of broccoli residue were tested on the colonization of roots by V. dahliae, plant growth response, and disease incidence of both broccoli and cauliflower in soils with different levels of V. dahliae inoculum and with or without fresh broccoli residue amendments. The three soils included a low-Verticillium soil, a high-Verticillium soil, and a broccoli-rotation soil (soil from a field after two broccoli crops) with an average of 13, 38, and below-detectable levels of microsclerotia per g of soil, respectively. Cauliflower plants in broccoli-amended high-Verticillium soil had significantly (P <\/= 0.05) lower wilt incidence and severity than did plants in unamended soil. An immunohistochemical staining assay utilizing a monoclonal antibody specific to V. dahliae was used to determine colonization of the root cortex. Despite the absence of wilt symptoms, broccoli roots were colonized by V. dahliae. In high-Verticillium soil, the broccoli residue amendment caused a marked reduction in colonization rate of V. dahliae per unit of inoculum on both cauliflower and broccoli roots. In addition to its detrimental effects on the viability of microsclerotia in soil, broccoli residue may also have an inhibitory effect on the root-colonizing potential of surviving microsclerotia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28282858,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The Impact of Shiftwork on Skeletal Muscle Health.\n(1) Background: About one in four workers undertake shift rosters that fall outside the traditional 7 a.m.-6 p.m. scheduling. Shiftwork alters workers' exposure to natural and artificial light, sleep patterns, and feeding patterns. When compared to the rest of the working population, shiftworkers are at a greater risk of developing metabolic impairments over time. One fundamental component of metabolic health is skeletal muscle, the largest organ in the body. However, cause-and-effect relationships between shiftwork and skeletal muscle health have not been established; (2) Methods: A critical review of the literature was completed using online databases and reference lists; (3) Results: We propose a conceptual model drawing relationships between typical shiftwork consequences; altered light exposure, sleep patterns, and food and beverage consumption, and drivers of skeletal muscle health-protein intake, resistance training, and hormone release. At present, there is no study investigating the direct effect of shiftwork on skeletal muscle health. Instead, research findings showing that acute consequences of shiftwork negatively influence skeletal muscle homeostasis support the validity of our model; (4) Conclusion: Further research is required to test the potential relationships identified in our review, particularly in shiftwork populations. Part of this testing could include skeletal muscle specific interventions such as targeted protein intake and\/or resistance-training.","subset":"pubmed_abstract"} +{"meta":{"pmid":27466198,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":14}}},"text":"Analysis with the exome array identifies multiple new independent variants in lipid loci.\nIt has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.","subset":"pubmed_abstract"} +{"meta":{"pmid":16129477,"dup_signals":{"dup_doc_count":11}},"text":"Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats.\nThe purpose of this study is to investigate the effects of flavonoid, isolated from aerial parts of Scutellaria baicalensis Georgi (SSF), on memory deficits, neuronal degeneration and abnormal energy metabolism induced by permanent global ischemia in rats. The global ischemia was produced in female Sprague-Dawley rats by permanent occlusion of the bilateral common carotid arteries. The permanent global ischemia in rats resulted in a significantly increased latency of the rat to find the hidden platform and a decreased swimming distance from the target quadrant in the Morris water maze task. The pathological changes in the neurons of ischemic rats, observed in the hippocampus and cerebral cortex, included neuron loss, neuron swelling, nuclear shrinkage or disappearance, neuronophagia and reduced density of Nissl bodies in the neuron. Moreover, the levels of lactate and ATPase activity in ischemic rats were notably increased and decreased, respectively, in the hippocampus and cerebral cortex as compared with sham-operated rats. Daily oral administration of SSF (35 mg\/kg, 19-20 days) dramatically reduced the decrease in learning and memory, attenuated neuronal injury and improved abnormality of energy metabolites in rats induced by global ischemia. These findings suggest that SSF may be beneficial for the treatment of vascular dementia.","subset":"pubmed_abstract"} +{"meta":{"pmid":27904879,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":15}}},"text":"The Establishment and Diversification of Epidemic-Associated Serogroup W Meningococcus in the African Meningitis Belt, 1994 to 2012.\nEpidemics of invasive meningococcal disease (IMD) caused by meningococcal serogroup A have been eliminated from the sub-Saharan African so-called \"meningitis belt\" by the meningococcal A conjugate vaccine (MACV), and yet, other serogroups continue to cause epidemics. Neisseria meningitidis serogroup W remains a major cause of disease in the region, with most isolates belonging to clonal complex 11 (CC11). Here, the genetic variation within and between epidemic-associated strains was assessed by sequencing the genomes of 92 N. meningitidis serogroup W isolates collected between 1994 and 2012 from both sporadic and epidemic IMD cases, 85 being from selected meningitis belt countries. The sequenced isolates belonged to either CC175 (n = 9) or CC11 (n = 83). The CC11 N. meningitidis serogroup W isolates belonged to a single lineage comprising four major phylogenetic subclades. Separate CC11 N. meningitidis serogroup W subclades were associated with the 2002 and 2012 Burkina Faso epidemics. The subclade associated with the 2012 epidemic included isolates found in Burkina Faso and Mali during 2011 and 2012, which descended from a strain very similar to the Hajj (Islamic pilgrimage to Mecca)-related Saudi Arabian outbreak strain from 2000. The phylogeny of isolates from 2012 reflected their geographic origin within Burkina Faso, with isolates from the Malian border region being closely related to the isolates from Mali. Evidence of ongoing evolution, international transmission, and strain replacement stresses the importance of maintaining N. meningitidis surveillance in Africa following the MACV implementation. IMPORTANCE Meningococcal disease (meningitis and bloodstream infections) threatens millions of people across the meningitis belt of sub-Saharan Africa. A vaccine introduced in 2010 protects against Africa's then-most common cause of meningococcal disease, N. meningitidis serogroup A. However, other serogroups continue to cause epidemics in the region-including serogroup W. The rapid identification of strains that have been associated with prior outbreaks can improve the assessment of outbreak risk and enable timely preparation of public health responses, including vaccination. Phylogenetic analysis of newly sequenced serogroup W strains isolated from 1994 to 2012 identified two groups of strains linked to large epidemics in Burkina Faso, one being descended from a strain that caused an outbreak during the Hajj pilgrimage in 2000. We find that applying whole-genome sequencing to meningococcal disease surveillance collections improves the discrimination among strains, even within a single nation-wide epidemic, which can be used to better understand pathogen spread.","subset":"pubmed_abstract"} +{"meta":{"pmid":30860839,"dup_signals":{"dup_doc_count":22,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-30":2,"2024-22":1,"2024-18":1,"2024-10":1,"unknown":15}}},"text":"Learning from Failure: Predicting Electronic Structure Calculation Outcomes with Machine Learning Models.\nHigh-throughput computational screening for chemical discovery mandates the automated and unsupervised simulation of thousands of new molecules and materials. In challenging materials spaces, such as open shell transition metal chemistry, characterization requires time-consuming first-principles simulation that often necessitates human intervention. These calculations can frequently lead to a null result, e.g., the calculation does not converge or the molecule does not stay intact during a geometry optimization. To overcome this challenge toward realizing fully automated chemical discovery in transition metal chemistry, we have developed the first machine learning models that predict the likelihood of successful simulation outcomes. We train support vector machine and artificial neural network classifiers to predict simulation outcomes (i.e., geometry optimization result and degree of \u27e8 S2\u27e9 deviation) for a chosen electronic structure method based on chemical composition. For these static models, we achieve an area under the curve of at least 0.95, minimizing computational time spent on nonproductive simulations and therefore enabling efficient chemical space exploration. We introduce a metric of model uncertainty based on the distribution of points in the latent space to systematically improve model prediction confidence. In a complementary approach, we train a convolutional neural network classification model on simulation output electronic and geometric structure time series data. This dynamic model generalizes more readily than the static classifier by becoming more predictive as input simulation length increases. Finally, we describe approaches for using these models to enable autonomous job control in transition metal complex discovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":27913147,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-16":1,"2019-09":1,"2018-47":1,"2018-26":1,"2018-13":1,"2017-43":1,"2017-34":1,"2021-43":1}}},"text":"Electro-kinetically driven peristaltic transport of viscoelastic physiological fluids through a finite length capillary: Mathematical modeling.\nAnalytical solutions are developed for the electro-kinetic flow of a viscoelastic biological liquid in a finite length cylindrical capillary geometry under peristaltic waves. The Jefferys' non-Newtonian constitutive model is employed to characterize rheological properties of the fluid. The unsteady conservation equations for mass and momentum with electro-kinetic and Darcian porous medium drag force terms are reduced to a system of steady linearized conservation equations in an axisymmetric coordinate system. The long wavelength, creeping (low Reynolds number) and Debye-H\u00fcckel linearization approximations are utilized. The resulting boundary value problem is shown to be controlled by a number of parameters including the electro-osmotic parameter, Helmholtz-Smoluchowski velocity (maximum electro-osmotic velocity), and Jefferys' first parameter (ratio of relaxation and retardation time), wave amplitude. The influence of these parameters and also time on axial velocity, pressure difference, maximum volumetric flow rate and streamline distributions (for elucidating trapping phenomena) is visualized graphically and interpreted in detail. Pressure difference magnitudes are enhanced consistently with both increasing electro-osmotic parameter and Helmholtz-Smoluchowski velocity, whereas they are only elevated with increasing Jefferys' first parameter for positive volumetric flow rates. Maximum time averaged flow rate is enhanced with increasing electro-osmotic parameter, Helmholtz-Smoluchowski velocity and Jefferys' first parameter. Axial flow is accelerated in the core (plug) region of the conduit with greater values of electro-osmotic parameter and Helmholtz-Smoluchowski velocity whereas it is significantly decelerated with increasing Jefferys' first parameter. The simulations find applications in electro-osmotic (EO) transport processes in capillary physiology and also bio-inspired EO pump devices in chemical and aerospace engineering.","subset":"pubmed_abstract"} +{"meta":{"pmid":32794798,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":15}}},"text":"Many-Body Resonance in a Correlated Topological Kagome Antiferromagnet.\nWe use scanning tunneling microscopy to elucidate the atomically resolved electronic structure in the strongly correlated kagome Weyl antiferromagnet Mn_{3}Sn. In stark contrast to its broad single-particle electronic structure, we observe a pronounced resonance with a Fano line shape at the Fermi level resembling the many-body Kondo resonance. We find that this resonance does not arise from the step edges or atomic impurities but the intrinsic kagome lattice. Moreover, the resonance is robust against the perturbation of a vector magnetic field, but broadens substantially with increasing temperature, signaling strongly interacting physics. We show that this resonance can be understood as the result of geometrical frustration and strong correlation based on the kagome lattice Hubbard model. Our results point to the emergent many-body resonance behavior in a topological kagome magnet.","subset":"pubmed_abstract"} +{"meta":{"pmid":29073132,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Patterns, factors associated and morbidity burden of asthma in India.\nAsthma is a non-curable but preventable disease, responsible for higher morbidity worldwide. According to recent WHO report, nearly 235 million people are suffering from asthma leading to 383000 deaths in 2015. The burden of asthma morbidity is higher in developed countries and is increasing in developing countries. The present study was aimed at studying the change in prevalence rate of asthma, associated risk factors and estimation of morbidity burden and avoidable cases of asthma in India. The second round of Indian Human Development Survey (IHDS-II), 2011-12, was used for the study. For the present study, asthma was defines as ever diagnosed with asthma or having cough with short breath. Multiple-logistic regression was used to identify the possible risk factors associated with prevalence of reporting asthma. Population attributable fractions (PAFs) were computed to estimate the overall and risk factors specific burden of morbidity due to asthma using the extrapolated population of year 2015 using 2011 census. Overall prevalence rate of asthma increased from 41.9 (per 1000 population) in 2004-05 to 54.9 (per 1000 population) in 2011-12. The prevalence rate of reporting asthma was higher in poorer states compared to richer states, and also varied by sub-geographies, with higher prevalence rate in northern states of the country and lower rates in north-eastern states of the country. The odds of reporting asthma was higher for younger and older ages, individual with fewer years of schooling (OR: 1.41; 95% CI: 1.21-1.64) for individual with zero years of schooling compared to those with 11 or more years of schooling, individual from lower economic status, individual living in household using unclean fuels (OR:1.21; 95% CI: 1.08-1.34) and smokers (OR: 1.34; 95% CI: 1.17-1.55) compared to their counterparts. In the year 2015, the overall morbidity burden of asthma was estimated at nearly 65 million and more than 82 thousand deaths were attributed due to asthma. The burden was highest among individuals living in households using solid fuels (firewood~80%, Kerosene~78%). One-third of the cases could be eliminated by minimising the use of any solid fuels. Around 17% of all the asthma cases in population could be attributed to underweight. Eliminating the modifiable risk factors could help reduce in huge amount of asthma cases for example by providing education, cessation in smoking, and schemes like Pradhan Mantri Ujjwala Yojana (PMUY), by providing clean fuel (LPG) to poor and vulnerable households.","subset":"pubmed_abstract"} +{"meta":{"pmid":33152801,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Action mechanism of Roman chamomile in the treatment of anxiety disorder based on network pharmacology.\nAnxiety disorder is a common psychiatric disease. Roman chamomile as medicine or tea has long been used as a mild tranquilizer to reduce anxiety, but the mechanism is unclear. This research is based on network pharmacology combined with database mining to find the ingredients, action pathways and key targets of Roman chamomile for the treatment of anxiety. About 126 common targets related to chamomile and anxiety were obtained, and these targets were involved in 56 KEGG pathways. GEO screened LRRK2 as a key protein, and molecular docking showed that the protein could stably bind to drug components. Roman chamomile has the characteristics of multi-target and multi-pathway in the treatment of anxiety disorder. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as neuroactive ligand-receptor interaction, serotonin synapse, and cAMP signaling pathway. LRRK2 may be an important gene for Roman chamomile in the treatment of anxiety disorder. PRACTICAL APPLICATIONS: Roman chamomile is well known for its use in medicine and tea making. It contains many nutrients, which can relieve people's anxiety, help sleep, antibacterial and anti-inflammatory. In this article, through network pharmacology combined with Gene Expression Omnibus data mining and molecular docking, the target and mechanism of Roman chamomile in the treatment of anxiety were discussed, and its efficacy was verified by model animals, which not only clarified its mechanism at the systematic level, but also proved to be effective at the biological level. It provides a reference for the further development and utilization of Roman chamomile.","subset":"pubmed_abstract"} +{"meta":{"pmid":30394134,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Assessment of endoscopic Doppler to guide hemostasis in high risk peptic ulcer bleeding.\nRebleeding or emergency surgery in failed endoscopic therapy of peptic ulcer bleeding are associated with high rates of morbidity and mortality. The clinical benefit of an endoscopic Doppler (ED) examination prior to endoscopic injection therapy was evaluated in high risk ulcer patients for rebleeding episode. Standard injection therapy (non-Doppler (ND)) was compared with targeted injection therapy after examination of the supplying vessel in the ulcer base by the ED. Sixty patients with peptic ulcer bleeding (Forrest Ia-IIa; Rockall score of 5 or higher) were included in the study. Patients were assigned to ED or ND group with conventional therapy by chance. In the ND group injection was directed by the visual aspect of the ulcer, whereas in ED therapy was directed by ED. Thirty-five patients were allocated to the ED group, and 25 to the ND group, respectively. No significant differences in patient or ulcer characteristics were observed regarding ulcer size, localization, Forrest classification or endoscopic treatment. Recurrent bleeding was observed in 7\/35 (20%) in the ED group and in 13\/25 (52%) of patients in the ND group (p = .013). Fewer ED patients needed surgery for rebleeding (1\/35 vs. 6\/25; p = .017). Bleeding related, but not all-cause mortality was significantly lower in the ED group (1\/35 vs. 6\/25, p = .017). In this comparative analysis, use of ED to guide hemostatic therapy was associated with a significant reduction in recurrence of bleeding, surgical intervention and bleeding associated mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":15601020,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Rapid and localized electron internal-transport-barrier formation during shear inversion in fully noninductive TCV discharges.\nClear evidence is reported for the first time of a rapid localized reduction of core electron energy diffusivity during the formation of an electron internal-transport barrier. The transition occurs rapidly (approximately = 3 ms), during a slow (approximately = 200 ms) self-inductive evolution of the magnetic shear. This crucial observation, and the correlation of the transition with the time and location of the magnetic shear reversal, lend support to models attributing the reduced transport to the local properties of a zero-shear region, in contrast to models predicting a gradual reduction due to a weak or negative shear.","subset":"pubmed_abstract"} +{"meta":{"pmid":2161367,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Immunodeficiency as primary phenotype of diabetes mutation db. Studies with coxsackievirus B4.\nRestriction of food intake (R) in the C57BL\/KsJ db\/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (AL) results in spontaneous diabetes. Previous results showed that coxsackievirus B4 (CB4)-infected genetically identical db\/db mice with and without diabetes could be distinguished by the levels of CB4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cells. Our results show that the diabetic genotype db\/db R was deficient in total spleen lymphocytes and lymphocyte subsets and was unable to produce agglutinating antibody to sheep erythrocytes (SRBCs) or specific antibody to noninfectious CB4. The db\/db AL mutant expressing the diabetic phenotype was not as deficient in spleen cell parameters. The response to noninfectious CB4 was delayed but substantial. The db\/db AL mouse was also unique with its higher agglutinating antibody levels after virus infection than its uninfected control or the infected or uninfected db\/db R mouse. In vitro SRBC immunization of spleen lymphocytes determined that this enhanced response was largely dependent on the diabetic milieu and was not a property of the cells. Genetic predisposition to diabetes is characterized by immunodeficiency as evident from inadequate levels of antibodies to infectious or noninfectious antigens and absolute and relative deficiency in spleen lymphocyte subsets and total numbers of spleen cells. Phenotypic expression of diabetes results in partial amelioration of the immunodeficiency evident in diabetic genotype db\/db R without disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":23305085,"dup_signals":{"dup_doc_count":11}},"text":"The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro-oesophageal reflux disease.\nObese patients have an increased risk of gastro-oesophageal reflux disease; however, the mechanism underlying this association is uncertain. To test the hypothesis that mechanical effects of obesity on oesophageal function increase acid exposure and symptoms. Height, weight and waist circumference (WC) were measured in patients with typical reflux symptoms referred for manometry and 24 h ambulatory pH studies. Symptom severity was assessed by questionnaire. The association between obesity [WC, body mass index (BMI)], oesophageal function, acid exposure and reflux symptoms was assessed. Physiological measurements were obtained from 582 patients (median age 48, 56% female) of whom 406 (70%) completed symptom questionnaires. The prevalence of general obesity was greater in women (BMI \u2265 30 kg\/m(2) ; F 23%:M 16%; P = 0.056), however more men had abdominal obesity (WC \u2265 99 cm (M 41%:F 28%; P = 0.001)). Oesophageal acid exposure increased with obesity (WC: R = 0.284, P < 0.001) and was associated also with lower oesophageal sphincter (LOS) pressure, reduced abdominal LOS length and peristaltic dysfunction (all P < 0.001). Univariable regression showed a negative association of WC with both LOS pressure and abdominal LOS length (R = -0.221 and -0.209 respectively; both P < 0.001). However, multivariable analysis demonstrated that the effects of increasing WC on oesophageal function do not explain increased acid reflux in obese patients. Instead, independent effects of obesity and oesophageal dysfunction on acid exposure were present. Reflux symptoms increased with acid exposure (R = 0.300; P < 0.001) and this association explained increased symptom severity in obese patients. Abdominal obesity (waist circumference) is associated with oesophageal dysfunction, increased acid exposure and reflux symptoms; however, this analysis does not support the mechanical hypothesis that the effects of obesity on oesophageal function are the cause of increased acid exposure in obese patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":26034134,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Knockout of RP2 decreases GRK1 and rod transducin subunits and leads to photoreceptor degeneration in zebrafish.\nRetinitis pigmentosa (RP) affects about 1.8 million individuals worldwide. X-linked retinitis pigmentosa (XLRP) is one of the most severe forms of RP. Nearly 85% of XLRP cases are caused by mutations in the X-linked retinitis pigmentosa 2 (RP2) and RPGR. RP2 has been considered to be a GTPase activator protein for ARL3 and to play a role in the traffic of ciliary proteins. The mechanism of how RP2 mutations cause RP is still unclear. In this study, we generated an RP2 knockout zebrafish line using transcription activator-like effector nuclease technology. Progressive retinal degeneration could be observed in the mutant zebrafish. The degeneration of rods' outer segments (OSs) is predominant, followed by the degeneration of cones' OS. These phenotypes are similar to the characteristics of RP2 patients, and also partly consistent with the phenotypes of RP2 knockout mice and morpholino-mediated RP2 knockdown zebrafish. For the first time, we found RP2 deletion leads to decreased protein levels and abnormal retinal localizations of GRK1 and rod transducin subunits (GNAT1 and GNB1) in zebrafish. Furthermore, the distribution of the total farnesylated proteins in zebrafish retina is also affected by RP2 ablation. These molecular alterations observed in the RP2 knockout zebrafish might probably be responsible for the gradual loss of the photoreceptors' OSs. Our work identified the progression of retinal degeneration in RP2 knockout zebrafish, provided a foundation for revealing the pathogenesis of RP caused by RP2 mutations, and would help to develop potential therapeutics against RP in further studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":21799824,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Interleukin-4 alters early phagosome phenotype by modulating class I PI3K dependent lipid remodeling and protein recruitment.\nPhagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (M\u03a6s) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-term IL-4 exposure (1 hour) during phagocytosis of IgG-opsonized yeast particles by M\u03a6s. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K\/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomal membranes provide topological constraints to signaling molecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell.","subset":"pubmed_abstract"} +{"meta":{"pmid":28253385,"dup_signals":{"dup_doc_count":27,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":3,"2024-26":1,"unknown":20}}},"text":"Association of Steroid 5\u03b1-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.\nSteroid 5\u03b1-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation. Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature. To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features. Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing. Developmental and systemic findings were also recorded. Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative. Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant. Biochemical profiling was conducted to confirm a CDG type I defect. Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016. Detailed clinical phenotypes as well as genetic and biochemical results. The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity. Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family. Detailed ocular phenotyping identified early-onset (aged \u22643 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20\/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus. Six of the 7 patients had learning difficulties and psychomotor delay. Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested. Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment. SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild. Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":9534836,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2015-11":1,"2015-18":1,"unknown":11}}},"text":"Placebo-controlled trial of moclobemide in social phobia.\nMoclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia. Seventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks. Intention-to-treat sample response rates at week 8 were 7\/40 (17.5%) for the moclobemide group and 5\/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated. Moclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.","subset":"pubmed_abstract"} +{"meta":{"pmid":15528729,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2021-04":1,"2020-40":1,"2020-16":1,"2019-43":1,"2019-35":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2022-27":1}}},"text":"The cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human populations.\nThe cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":21996072,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Does coronary artery calcium scoring add to the predictive value of coronary computed tomography angiography for adverse cardiovascular events in low-risk chest pain patients?\nCoronary angiography calcium score (CACS) is included for patients who receive coronary computed tomography angiography (CTA) as part of diagnostic testing for low-risk chest pain. Both tests add radiation exposure, and it is unclear whether the combination provides more information than either test alone. The objective was to asses if CACS = 0 determines freedom from coronary artery disease (CAD) and whether the addition of CACS to coronary CT angiography provides additional risk stratification information or helps predict 30-day cardiovascular outcomes. This was a secondary analysis of a prospective cohort study at an urban university hospital emergency department (ED), of patients with symptoms suggestive of potential acute coronary syndrome (ACS) and low Thrombolysis in Myocardial Infarction (TIMI) risk scores who received coronary CTA. Data collected included demographics and medical history. The main outcome was CAD, defined as the presence of a maximal stenosis >50% on coronary CTA, stratified by CACS results. The secondary outcome was cardiovascular events including death, myocardial infarction, or revascularization at 30 days. Data were analyzed with standard descriptive techniques and relative risks (RR) with 95% confidence intervals (CIs). A total of 1,049 patients were enrolled (median age = 48.1 years; interquartile range [IQR] = 42.4 to 53.3 years); 55% were female, and 63% were black or African American. Of these, 17 of 795 (2.1%) with CACS of 0 had CAD, 16 of 169 patients (9.5%) with CACS of 0.1 to 99 had CAD, 53.3% (32 of 60) with CACS between 100 and 399 had CAD, and 10 of 23 (43.5%) with CACS \u2265 400 had CAD. There was a higher likelihood of significant CAD with increased CACS. Patients who had a calcium score of 0 but still had CAD were more likely to be young (50 years old or less; RR = 1.73, 95% CI = 1.01 to 2.96). For the secondary outcome, there were 15 cardiovascular events within 30 days: one patient with CACS = 0 and no CAD (1 of 733; 0.1%), one patient with CACS > 0 and no CAD (1 of 182; 0.5%), four patients with CACS = 0 and CAD (4 of 17; 23.5%), and nine patients with CACS > 0 and CAD (9 of 58; 15.5%), with a net reclassification index of -0.001 (p = 0.32). In the study sample, elevated CACS was associated with a higher likelihood of underlying CAD on coronary CTA, but the addition of CACS to coronary CTA did not help predict 30-day cardiovascular events.","subset":"pubmed_abstract"} +{"meta":{"pmid":11454272,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Reflection and dialogue for HIV prevention among young gay men.\nConsiderable interest has been expressed in young gay men's enhanced vulnerability to HIV-related risk. Relatively little research has, however, been conducted into the circumstances in which risk may be greatest and the strategies young gay men can use to reduce their vulnerability. This paper reports on findings from a recent exploratory in-depth study conducted in Norway. Twenty young gay men participated in repeated dialogic and reflective interviews in which situations of real and potential risk were discussed. Central among the factors enhancing vulnerability were found also to be general social codes such as configurations of 'reciprocity', as well as context-specific factors and individual biographic variables. A mode of intervention is described that seeks to empower young men more fully in sexual communication and negotiation. Such an approach has been operationalized in 'man-to-man dialogues' facilitated by members of the Norwegian Gay Health Committee.","subset":"pubmed_abstract"} +{"meta":{"pmid":29208114,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2024-10":1,"unknown":5}}},"text":"Epidemiological and virological assessment of influenza activity in Europe, during the 2004-2005 winter.\nThe 2004-2005 influenza season in Europe started in late December 2004 and the first influenza activity occurred in the west and southwest (Spain, United Kingdom and Ireland). Influenza activity then moved gradually east across Europe during January and early February 2005, and from late February until late March, most movement was south to north. The intensity of clinical influenza activity in ten out of 23 countries was higher than during the 2003-2004 season, and lower or equal to the 2003-2004 season in the other 13 countries. The highest consultation rates were generally observed among children aged 0-14 years. However, the peak consultation rates due to influenza-like illness or acute respiratory infection were not especially high when compared with historical data. The predominant virus strain was influenza A (83% of total detections) of the H3 subtype (85% of H-subtyped A viruses), with fewer influenza B (17% of total detections) or A(H1) viruses (15 % of H-subtyped A viruses) detected. The vast majority of A(H3) viruses were similar to the reference strains A\/Wellington\/1\/2004 (H3N2) and, subsequently, A\/California\/7\/2004 (H3N2) that are closely related drift variants of the A\/Fujian\/411\/2002 (H3N2) prototype vaccine strain. The B viruses co-circulated with A viruses during the whole influenza season in 11 out of 24 countries. Seven of these were located in the northeast of Europe and in these countries the proportion of B viruses was higher (range: 31-60%) than in the rest of Europe (range: 6-26%). In 13 out of 24 countries the B viruses circulated relatively late in the season. About 43% of all antigenically characterised B viruses were B\/Hong Kong\/330\/2001-like (B\/Victoria\/2\/87 lineage), a strain that is distinguishable from the vaccine influenza B strain, which was a B\/Yamagata\/16\/88 lineage virus. Based on the viruses detected worldwide until February 2005, the World Health Organization modified the composition of the 2005-2006 influenza vaccine from the 2004-2005 season vaccine to include a new A(H3N2) component: an A\/California\/7\/2004 (H3N2)-like virus.","subset":"pubmed_abstract"} +{"meta":{"pmid":3125997,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Carcinogen-induced unscheduled DNA synthesis in xenotransplanted human tracheobronchial epithelium: comparison with rat tracheal epithelium.\nExtrapolation from rodent genotoxicity data to humans is complicated by variables such as interspecies differences in carcinogen metabolism and DNA repair. A xenograft system containing human bronchial epithelial cells was used to assess the induction of unscheduled DNA synthesis (UDS) by carcinogens and to compare the response with that of rat tracheal epithelium. Cells from human bronchus were grown in explant culture, inoculated into de-epithelialized rat tracheas and implanted subcutaneously into nude mice. Within six weeks, a differentiated mucociliary epithelium lined the xenografted tracheas. Fresh rat tracheas and human xenografts were cut into rings and incubated in media containing [3H]thymidine and either the direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 3-1000 microM), or a carcinogen requiring metabolic activation, 4-nitroquinoline-1-oxide (4-NQO, 3-100 microM). Tissues were then fixed, sectioned, processed for autoradiography and the number of nuclear grains (NG) determined for 100 epithelial cells lining the trachea in each section. A time- and concentration-dependent increase in NG was observed in both human xenografts and rat tracheas after treatment with MNNG or 4-NQO, indicating induction of UDS by these agents. The UDS response to MNNG in the human xenografts was similar to that observed in the rat tracheas, whereas the response to 4-NQO was greater in rat tracheas. These studies indicate that the human xenograft system should have applications for the study of carcinogen-induced damage in normal bronchial epithelial cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":8969511,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2021-17":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-09":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2017-13":1}}},"text":"Physical mapping of Mycobacterium bovis BCG pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from M. bovis.\nA Dral restriction map of the approximately 4.35 Mb circular chromosome of the vaccine strain Mycobacterium bovis BCG Pasteur was constructed by linking all 21 Dral fragments, ranging in size from 6 to 820 kb, using specific clones that spanned the Dral recognition sites as hybridization probes. The positions of 20 known genes were also established. Comparison of the resultant genome map with that of the virulent tubercle bacillus Mycobacterium tuberculosis H37Rv revealed extensive global conservation of the genomes of these two members of the M. tuberculosis complex. Possible sites of evolutionary rearrangements were localized on the chromosome of M. bovis BCG Pasteur by comparing the Asnl restriction profile with that of M. tuberculosis H37Rv. When selected cosmids from the corresponding areas of the genome of M. tuberculosis H37Rv were used as hybridization probes to examine different BCG strains, wild-type M. bovis and M. tuberculosis H37Rv, a number of deletions up to 10 kb in size, insertions and other polymorphisms were detected. In addition to the known deletions covering the genes for the protein antigens ESAT-6 and mpt64, other genetic loci exhibiting polymorphisms or rearrangements were detected in M. bovis BCG Pasteur.","subset":"pubmed_abstract"} +{"meta":{"pmid":15367842,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Congenital heart disease never goes away, even when it has been 'treated': the adult with congenital heart disease.\nAs the specialties of pediatrics and pediatric cardiology continue to forge ahead with better diagnoses, medical care, and surgical results, an expanding population of patients with congenital heart disease (CHD) outgrows the pediatric age group, yet does not quite graduate to routine adult cardiology or general medicine. The adult with congenital heart disease (ACHD) faces medical, surgical, and psychosocial issues that are unique to this population and must be addressed as such. This review attempts to discuss and highlight some of the important advances and controversies brought up in the past year, in the care and management of these patients. The past five to 10 years have seen dynamic interest in understanding sequelae of corrected, uncorrected, or palliated congenital heart disease. The search for the ideal surgery, optimal prosthesis, and a smooth transition to adult care continues and is reflected in the vast amount of academic work and publications in this field. Of particular interest, conduit reoperations and single ventricle pathway modifications are still an art and a science in evolution. While all are agreed that there is a pressing need to focus on the delivery of care to the adult with congenital heart disease, this essentially requires a clearer understanding of late sequelae of CHD. The sheer heterogeneity of anatomy, age, surgery, and institutional management protocols can make it difficult to develop clear guidelines. This review attempts to give an up-to-date perspective on some of the new findings related to the more common lesions and problems faced in this group.","subset":"pubmed_abstract"} +{"meta":{"pmid":21516219,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"The Early Development of the Autonomic Nervous System Provides a Neural Platform for Social Behavior: A Polyvagal Perspective.\nWe present a biobehavioral model that explains the neurobiological mechanisms through which measures of vagal regulation of the heart (e.g., respiratory sinus arrhythmia) are related to infant self-regulatory and social engagement skills. The model describes the sequential development of the neural structures that provide a newborn infant with the ability to regulate physiological state in response to a dynamically changing postpartum environment. Initially, the newborn uses primitive brainstem-visceral circuits via ingestive behaviors as the primary mechanism to regulate physiological state. However, as cortical regulation of the brainstem improves during the first year of life, reciprocal social behavior displaces feeding as the primary regulator of physiological state. The model emphasizes two sequential phases in neurophysiological development as the fetus transitions to postpartum biological and social challenges: 1) the development of the myelinated vagal system during the last trimester, and 2) the development of cortical regulation of the brainstem areas regulating the vagus during the first year postpartum.","subset":"pubmed_abstract"} +{"meta":{"pmid":10457018,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Successive patterns of clonal cell dispersion in relation to neuromeric subdivision in the mouse neuroepithelium.\nWe made use of the laacz procedure of single-cell labelling to visualize clones labelled before neuromere formation, in 12.5-day mouse embryos. This allowed us to deduce two successive phases of cell dispersion in the formation of the rhombencephalon: an initial anterior-posterior (AP) cell dispersion, followed by an asymmetrical dorsoventral (DV) cell distribution during which AP cell dispersion occurs in territories smaller than one rhombomere. We conclude that the general arrest of AP cell dispersion precedes the onset of morphological segmentation and is not imposed by the interface between adjacent rhombomeres. This demonstrates a major change in the mode of epithelial growth that precedes or accompanies the formation of neuromeres. We also deduced that the period of DV cell dispersion in the neuroepithelium is followed by a coherent growth phase. These results suggest a cell organization on a Cartesian grid, the coordinates of which correspond to the AP and DV axis of the neural tube. A similar sequence of AP cell dispersion followed by an arrest of AP cell dispersion, a preferential DV cell dispersion and then by a coherent neuroepithelial growth, is also observed in the spinal cord and mesencephalon. This demonstrates that a similar cascade of cell events occurs in these different domains of the CNS. In the prosencephalon, differences in spatial constraints may explain the variability in the orientation of cell clusters. Genetic and clonal patterning in the AP and DV dimensions follow the same spatial sequence. An interesting possibility is that these successive patterns of cell growth facilitate the acquisition of positional information.","subset":"pubmed_abstract"} +{"meta":{"pmid":20671890,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-10":1,"2014-10":2,"2013-20":1,"2024-30":1,"unknown":7}}},"text":"Problematic Internet use: an overview.\nThere is wide agreement that the Internet can serve as a tool that enhances well-being. It is more difficult, however, to find consensus around the issue of problematic Internet use. That may be in part because scientific investigation has lagged far behind technological advances and media attention. The diagnostic schemas that have been proposed since 1996, and the screening tools that have been developed, stress similarities with substance use, impulse control disorders, and obsessive-compulsive disorder. Prevalence figures vary as a function of the diagnostic definition used, the age group studied, and whether the surveys were conducted online. Studies suggest high comorbidity rates with mood disorders and, among younger individuals, attention-deficit\/hyperactivity disorder. Treatment should address any comorbid conditions present, as those may be causing, or exacerbating, problematic Internet use. Interventions that may specifically target problematic Internet use include cognitive behavioral therapy and selective serotonin reuptake inhibitors, but detailed guidelines must await further studies. For a medium that has so radically changed how we conduct our lives, the Internet's effects on our psychology remain understudied. More research is needed into the pathophysiology, epidemiology, natural course, and treatment of problematic Internet use. In addition, the more subtle psychological changes, such as disinhibition, that seem to characterize people's online behavior also deserve attention, even if they cannot be seen as necessarily pathological.","subset":"pubmed_abstract"} +{"meta":{"pmid":28851812,"dup_signals":{"dup_doc_count":26,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":23}}},"text":"A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer.\nTWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. Given the potential of TWIST1 as a therapeutic target, a chemical-bioinformatic approach using connectivity mapping (CMAP) analysis was used to identify TWIST1 inhibitors. Characterization of the top ranked candidates from the unbiased screen revealed that harmine, a harmala alkaloid, inhibited multiple TWIST1 functions, including single-cell dissemination, suppression of normal branching in 3D epithelial culture, and proliferation of oncogene driver-defined NSCLC cells. Harmine treatment phenocopied genetic loss of TWIST1 by inducing oncogene-induced senescence or apoptosis. Mechanistic investigation revealed that harmine targeted the TWIST1 pathway through its promotion of TWIST1 protein degradation. As dimerization is critical for TWIST1 function and stability, the effect of harmine on specific TWIST1 dimers was examined. TWIST1 and its dimer partners, the E2A proteins, which were found to be required for TWIST1-mediated functions, regulated the stability of the other heterodimeric partner posttranslationally. Harmine preferentially promoted degradation of the TWIST1-E2A heterodimer compared with the TWIST-TWIST1 homodimer, and targeting the TWIST1-E2A heterodimer was required for harmine cytotoxicity. Finally, harmine had activity in both transgenic and patient-derived xenograft mouse models of KRAS-mutant NSCLC. These studies identified harmine as a first-in-class TWIST1 inhibitor with marked anti-tumor activity in oncogene-driven NSCLC including EGFR mutant, KRAS mutant and MET altered NSCLC.Implications: TWIST1 is required for oncogene-driven NSCLC tumorigenesis and EMT; thus, harmine and its analogues\/derivatives represent a novel therapeutic strategy to treat oncogene-driven NSCLC as well as other solid tumor malignancies. Mol Cancer Res; 15(12); 1764-76. \u00a92017 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":9468365,"dup_signals":{"dup_doc_count":20,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":1,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2,"unknown":7}}},"text":"Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir\/3TC\/ZDV Study Group.\nTriple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)\/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies\/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies\/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies\/g at baseline, was markedly reduced with at least 2.1 log10 copies\/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue.","subset":"pubmed_abstract"} +{"meta":{"pmid":32608978,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":6}}},"text":"Single-Photon Ionization Mass Spectrometry Using a Vacuum Ultraviolet Femtosecond Laser.\nThe wavelength of a femtosecond Ti:sapphire laser (TS, 800 nm) was converted into the ultraviolet (UV, 200 nm) using three \u03b2-barium borate crystals (\u03b2-BaB2O4) for frequency doubling and subsequent mixing. The UV pulse was further converted into the vacuum ultraviolet (VUV, 185 nm) based on four-wave Raman mixing, in which a two-color pump beam consisting of the fundamental beam (800 nm) of the TS and the signal beam of an optical parametric amplifier (1200 nm) pumped by the TS was focused onto a capillary waveguide filled with hydrogen gas for molecular phase modulation and the single-color UV probe beam (200 nm) was then focused onto the waveguide for frequency modulation to generate anti-Stokes and high-order Stokes Raman sidebands at wavelengths of 185 and 218-267 nm, respectively. The efficiency of conversion from the UV (200 nm) to the VUV (185 nm) was 6%. The ionization energy was calculated for 13 amino polycyclic aromatic hydrocarbons using density functional theory, since they are associated with the development of occupational bladder cancers. The values calculated by the B3LYP\/cc-pVDZ and \u03c9B97Xd\/cc-pVTZ methods were 6.24-7.14 eV (199-174 nm) and 6.41-7.35 eV (194-169 nm), respectively. A sample containing a mixture of 9-aminoanthracene, 3-aminofluoranthene, and 1-aminopyrene was separated by gas chromatography (GC), and the eluents were ionized with the VUV pulse (0.015 \u03bcJ) in mass spectrometry (MS). The analytes were observed on a two-dimensional display of GC\/MS, and the detection limit obtained by single-photon ionization of 3-aminofluoranthene was 1 ng\/\u03bcL.","subset":"pubmed_abstract"} +{"meta":{"pmid":35264479,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":7}}},"text":"Identification of Aerotaxis Receptor Proteins Involved in Host Plant Infection by Pseudomonas syringae pv. tabaci 6605.\nPseudomonas syringae pv. tabaci 6605 (Pta6605) is a foliar plant pathogen that causes wildfire disease on tobacco plants. It requires chemotaxis to enter plants and establish infection. While chemotactic signals appear to be the main mechanism by which Pta6605 performs directional movement, the involvement of aerotaxis or energy taxis by this foliar pathogen is currently unknown. Based on domain structures and similarity with more than 50 previously identified putative methyl-accepting chemotaxis proteins (MCPs), the genome of Pta6605 encodes three potential aerotaxis transducers. We identified AerA as the main aerotaxis transducer and found that it possesses a taxis-to-serine-and-repellent (Tsr)-like domain structure that supports a periplasmic 4HB-type ligand-binding domain (LBD). The secondary aerotaxis transducer, AerB, possesses a cytosolic PAS-type LBD, similar to the Aer of Escherichia coli and Pseudomonas aeruginosa. Aerotaxis ability by single and double mutant strains of aerA and aerB was weaker than that by wild-type Pta6605. On the other hand, another cytosolic PAS-type LBD containing MCP did not make a major contribution to Pta6605 aerotaxis in our assay system. Furthermore, mutations in aerotaxis transducer genes did not affect surface motility or chemotactic attraction to yeast extract. Single and double mutant strains of aerA and aerB showed less colonization in the early stage of host plant infection and lower biofilm production than wild-type Pta6605. These results demonstrate the presence of aerotaxis transducers and their contribution to host plant infection by Pta6605.","subset":"pubmed_abstract"} +{"meta":{"pmid":31385927,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.\nWe have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes. Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem. At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 \u00b1 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 \u00b1 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 \u00b1 7.5 mm Hg (day 0) and 89 \u00b1 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20 B cells, CD4 and CD8 T cells, and CD14 macrophages increased consistent with a mild foreign body reaction. The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.","subset":"pubmed_abstract"} +{"meta":{"pmid":33116912,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Anomalies and Clinical Significance of Mylohyoid Nerve: A Review.\nThe mylohyoid nerve is a branch of the inferior alveolar nerve (IAN), which is a branch of the posterior division of the mandibular nerve (MN). It is the source of motor nerve supply to the mylohyoid and anterior belly of the digastric muscle. At times, it provides sensory innervation to the mandibular teeth and skin below the chin. Since the location, anatomical variation and communications of the mylohyoid nerve are varied, it becomes clinically important to have an in-depth knowledge when treating patients for dental and maxillofacial procedures. Such anatomical variations of the mylohyoid nerve innervations may account for failure of the nerve blocks and hence, knowledge is very important for the practitioner. A thorough literature search was done using the key words mandibular nerve, communications of the mylohyoid nerve, inferior alveolar nerve, lingual nerve, failure of dental anaesthesia, mylohyoid nerve and dental implants \"from the Databases - PubMed, Scopus Embase and Web of Science (years 1952-2020)\". The mylohyoid nerve may contain motor and sensory fibres, it may pass through the mylohyoid groove or canal and communicate with other nerves, which is clinically significant. Such anatomical variations may be one of the reasons for the failure of the inferior alveolar nerve block. Awareness of these variations is very significant in planning treatment and avoiding any unnecessary steps. The most frequently encountered anatomic variation of the mylohyoid nerve was innervation of the submental skin and the anterior teeth.","subset":"pubmed_abstract"} +{"meta":{"pmid":18538025,"dup_signals":{"dup_doc_count":16,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-06":2,"2014-10":2,"2013-48":3,"2013-20":2,"2015-11":1,"unknown":5}}},"text":"Environment And Genetics in Lung cancer Etiology (EAGLE) study: an integrative population-based case-control study of lung cancer.\nLung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency\/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.","subset":"pubmed_abstract"} +{"meta":{"pmid":1539753,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Brugia malayi: ivermectin inhibits the exsheathment of microfilariae.\nBrugia malayi-infected microfilaremic jirds (Meriones unguiculatus) were treated with ivermectin at a single dose of 200 micrograms\/kg of body weight injected subcutaneously. Susceptible Aedes aegypti mosquitoes were fed on treated jirds 24 hours later. Mosquitoes fed on untreated jirds served as controls. Infected mosquitoes were dissected at 1, 3, 24, 48, 72, and 96 hr after the blood meal, and differential counts of sheathed microfilariae, exsheathed microfilariae, and cast sheaths were performed using fluoresceinated wheat germ agglutinin. Microfilariae failed to exsheath in mosquitoes fed on ivermectin-treated jirds. Microfilariae from ivermectin-treated jirds also did not exsheath in vitro in the presence of 10 mM CaCl2, whereas 85-90% of sheathed microfilariae from untreated jirds exsheathed in vitro. In addition, sheathed microfilariae from untreated jirds, when pretreated in vitro with ivermectin at 0.25, 0.5, or 1 microgram\/ml, lost their ability to exsheath in vitro in the presence of 10 mM CaCl2. However, ivermectin treatment had no effect on exsheathing of microfilariae when incubated with papaya protease. Thus, ivermectin appears to inhibit the intrinsic exsheathing process of microfilariae in the mosquito host, thereby blocking their development and further transmission of infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":24477758,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Cu(I)-based delafossite compounds as photocathodes in p-type dye-sensitized solar cells.\nThe research of p-type dye-sensitized solar cells (p-DSSCs) has attracted growing attention because of the potential for integration with conventional n-type DSSCs (n-DSSCs) into the more efficient tandem-DSSCs. However, to date the performance of p-DSSCs is lagging behind that of n-DSSCs. One main reason is the lack of optimal photocathode materials. This article reviews the most recent progress in utilizing Cu(I)-based delafossite compounds, CuMO2 (M = Al, Ga or Cr), as photocathodes in p-DSSCs. As alternative materials to the commonly used NiO, the CuMO2 compounds have their intrinsic advantages such as lower valence band edge, larger optical bandgap and higher conductivity. By providing an insight into these materials and their applications in p-DSSCs, this perspective aims to stimulate more exciting research in the development of p-DSSCs as well as of tandem-DSSCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":22563904,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Indium tri(isopropoxide)-catalyzed selective Meerwein-Ponndorf-Verley reduction of aliphatic and aromatic aldehydes.\nIndium tri(isopropoxide)-catalyzed Meerwein-Ponndorf-Verley reduction of aliphatic and aromatic aldehydes in 2-propanol gave selectively the corresponding primary alcohols in good to excellent yields at room temperature. A wide range of functional groups including alkene, ether, ketone, ester, nitrile, and nitro were tolerated under the optimum reaction conditions. Chemoselective reductions were also achieved not only between aromatic aldehyde, aromatic ketone, and epoxide but also between aliphatic aldehyde and alkene.","subset":"pubmed_abstract"} +{"meta":{"pmid":28167700,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"The Transcription Factor MYB29 Is a Regulator of ALTERNATIVE OXIDASE1a.\nPlants sense and integrate a variety of signals from the environment through different interacting signal transduction pathways that involve hormones and signaling molecules. Using ALTERNATIVE OXIDASE1a (AOX1a) gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, MYB DOMAIN PROTEIN29 (MYB29) was identified as a negative regulator (regulator of alternative oxidase1a 7 [rao7] mutant) in a genetic screen of Arabidopsis (Arabidopsis thaliana). rao7\/myb29 mutants have increased levels of AOX1a transcript and protein compared to wild type after induction with antimycin A. A variety of genes previously associated with the mitochondrial stress response also display enhanced transcript abundance, indicating that RAO7\/MYB29 negatively regulates mitochondrial stress responses in general. Meta-analysis of hormone-responsive marker genes and identification of downstream transcription factor networks revealed that MYB29 functions in the complex interplay of ethylene, jasmonic acid, salicylic acid, and reactive oxygen species signaling by regulating the expression of various ETHYLENE RESPONSE FACTOR and WRKY transcription factors. Despite an enhanced induction of mitochondrial stress response genes, rao7\/myb29 mutants displayed an increased sensitivity to combined moderate light and drought stress. These results uncover interactions between mitochondrial retrograde signaling and the regulation of glucosinolate biosynthesis, both regulated by RAO7\/MYB29. This common regulator can explain why perturbation of the mitochondrial function leads to transcriptomic responses overlapping with responses to biotic stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":21318028,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2015-18":1,"unknown":12}}},"text":"An integrated approach for assessing aquatic ecological carrying capacity: a case study of Wujin District in the Tai Lake Basin, China.\nAquatic ecological carrying capacity is an effective method for analyzing sustainable development in regional water management. In this paper, an integrated approach is employed for assessing the aquatic ecological carrying capacity of Wujin District in the Tai Lake Basin, China. An indicator system is established considering social and economic development as well as ecological resilience perspectives. While calculating the ecological index, the normalized difference vegetation index (NDVI) is extracted from Moderate Resolution Imaging Spectroradiometer (MODIS) time-series images, followed by spatial and temporal analysis of vegetation cover. Finally, multi-index assessment of aquatic ecological carrying capacity is carried out for the period 2000 to 2008, including both static and dynamic variables. The results reveal that aquatic ecological carrying capacity presents a slight upward trend in the past decade and the intensity of human activities still exceeded the aquatic ecological carrying capacity in 2008. In terms of human activities, population has decreased, GDP has quadrupled, and fertilizer application and industrial wastewater discharge have declined greatly in the past decade. The indicators representing aquatic ecosystem conditions have the lowest scores, which are primarily attributed to the water eutrophication problem. Yet the terrestrial ecosystem is assessed to be in better condition since topographic backgrounds and landscape diversity are at higher levels. Based on the work carried out, it is suggested that pollutant emission be controlled to improve water quality and agricultural development around Ge Lake (the largest lake in Wujin District) be reduced.","subset":"pubmed_abstract"} +{"meta":{"pmid":2538841,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Microbial glycolipids: possible virulence factors that scavenge oxygen radicals.\nTwo important pathogens of developing countries, Mycobacterium leprae, the etiologic agent of leprosy, and Leishmania donovani, the protozoal parasite that causes kalaazar, persist in the human host primarily in mononuclear phagocytes. The mechanisms by which they survive in these otherwise highly cytocidal cells are presently unknown. Since the best understood cytocidal mechanism of these cells is the oxygen-dependent system that provides lethal oxidants including the superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH), and singlet oxygen (1O2), we sought specific microbial products of these organisms that might enable them to elude oxidative cytocidal mechanisms. Phenolic glycolipid I of M. leprae and lipophosphoglycan of L. donovani are unique cell-wall-associated glycolipids produced in large amounts by the organisms. In this study, phenolic glycolipid I derivatives and lipophosphoglycan were examined for their ability to scavenge potentially cytocidal oxygen metabolites in vitro. Electron spin resonance and spin-trapping indicate that phenolic glycolipid I derivatives and lipophosphoglycan are highly effective in scavenging hydroxyl radicals and superoxide anions. The results suggest that complex glycolipids and carbohydrates of intracellular pathogens that can scavenge oxygen radicals may contribute to their pathogenicity and virulence.","subset":"pubmed_abstract"} +{"meta":{"pmid":14962625,"dup_signals":{"dup_doc_count":26,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-24":1,"2019-51":1,"2019-47":1,"2019-35":1,"2019-26":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-30":1,"2017-22":1,"2023-23":1,"2017-13":1}}},"text":"A possible association between fetal\/neonatal exposure to radiofrequency electromagnetic radiation and the increased incidence of autism spectrum disorders (ASD).\nRecently disclosed epidemiological data indicate a dramatic increase in the incidence of autism spectrum disorders. Previously, the incidence of autism has been reported as 4-5 per 10000 children. The most recent evidence indicates an increased incidence of about 1 per 500 children. However, the etiology of autism is yet to be determined. The recently disclosed data suggest a possible correlation between autism incidence and a previously unconsidered environmental toxin. It is generally accepted in the scientific community that radiofrequency (RF) radiation is a biologically active substance. It is also readily acknowledged that human exposures to RF radiation have become pervasive during the past 20 years, whereas such exposures were uncommon prior to that time. It is suggested that fetal or neo-natal exposures to RF radiation may be associated with an increased incidence of autism.","subset":"pubmed_abstract"} +{"meta":{"pmid":28661933,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"PYR-41, A Ubiquitin-Activating Enzyme E1 Inhibitor, Attenuates Lung Injury in Sepsis.\nDuring sepsis, systemic inflammation is observed and is associated with multiple organ failure. Activation of NF-\u03baB is crucial for inducing inflammation, which is controlled by degradation of inhibitor molecules (I\u03baB). The ubiquitination proteasome pathway is responsible for the regulation of protein turnover. In this study, we hypothesized that administration of 4[4-(5-nitro-furan-2-ylmethylene)-3, -dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR-41), an inhibitor of ubiquitination, could reduce inflammation and organ injury in septic mice. PYR-41 prevented the reduction of I\u03baB protein levels and inhibited release of tumor necrosis factor (TNF)-\u03b1 in mouse macrophage RAW264.7 cells at 4 h after lipopolysaccharide stimulation dose-dependently. Male C57BL\/6 mice were subjected to cecal ligation and puncture (CLP) to induce sepsis. PYR-41 (5 mg\/kg) or dimethyl sulfoxide in saline (vehicle) was injected intravenously immediately after CLP. At 20 h after CLP, PYR-41 treatment significantly decreased serum levels of proinflammatory cytokines (TNF-\u03b1, interleukin [IL]-1\u03b2, and IL-6) and organ injury markers (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). PYR-41 significantly improved microscopic structure, and reduced myeloperoxidase activity, number of apoptotic cells and caspase-3 degradation in the lungs of septic mice. The reduced protein levels of I\u03baB in the lungs after CLP were restored by PYR-41 treatment. PYR-41 inhibited the expression of cytokines (IL-1\u03b2 and IL-6), chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein 2), and inflammatory mediators (cyclooxygenase-2 and inducible nitric oxide synthase) in the lungs of septic mice. Importantly, PYR-41 significantly increased 10-day survival in septic mice from 42% to 83%. Therefore, targeting ubiquitination by PYR-41 to inhibit NF-\u03baB activation may represent a potential strategy of sepsis therapeutics.","subset":"pubmed_abstract"} +{"meta":{"pmid":2969319,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":13}}},"text":"Atrial natriuretic peptide and total exchangeable body sodium: relationships in rats with chronic myocardial infarction.\n1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially. 2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P less than 0.01). The decrease was the same in rats with infarction as in controls. 3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P less than 0.01). 4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium. 5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.","subset":"pubmed_abstract"} +{"meta":{"pmid":28419759,"dup_signals":{"dup_doc_count":20}},"text":"Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB.\nKnowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (\u03c354), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high c-di-GMP levels. Our findings imply that the production of biofilm exopolysaccharide in B. cenocepacia is regulated through a cascade involving two consecutive transcription events that are both activated by c-di-GMP. This type of regulation may allow tight control of the expenditure of cellular resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":24013445,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Characterisation of platinum-based fuel cell catalyst materials using 195Pt wideline solid state NMR.\nThis study demonstrates the utility of the novel Field Sweep Fourier Transform (FSFT) method for acquiring wideline (195)Pt NMR data from various sized Pt nanoparticles, Pt-Sn intermetallics\/bimetallics used to catalyse oxidative processes in fuel cell applications, and various other related Pt3X alloys (X = Al, Sc, Nb, Ti, Hf and Zr) which can facilitate oxygen reduction catalysis. The (195)Pt and (119)Sn NMR lineshapes measured from the PtSn intermetallic and Pt3Sn bimetallic systems suggest that these are more ordered than other closely related bimetallic alloys; this observation is supported by other characterisation techniques such as XRD. From these reconstructed spectra the mean number of atoms in a Pt nanoparticle can be accurately determined, along with detailed information regarding the number of atoms present effectively in each layer from the surface. This can be compared with theoretical predictions of the number of Pt atoms in these various layers for cubo-octahedral nanoparticles, thereby providing an estimate of the particle size. A comparison of the common NMR techniques used to acquire wideline data from the I = 1\/2 (195)Pt nucleus illustrates the advantages of the automated FSFT technique over the Spin Echo Height Spectroscopy (SEHS) (or Spin Echo Integration Spectroscopy (SEIS)) approach that dominates the literature in this area of study. This work also presents the first (195)Pt NMR characterisation of novel small Pt13 nanoclusters which are diamagnetic and thus devoid of metallic character. This unique system provides a direct measure of an isotropic chemical shift for these Pt nanoparticles and affords a better basis for determining the actual Knight shift when compared to referencing against the primary IUPAC shift standard (1.2 M Na2PtCl6(aq)) which has a very different local chemical environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":18541705,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":7}}},"text":"The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA.\nInvadopodia are actin-based membrane protrusions formed at contact sites between invasive tumor cells and the extracellular matrix with matrix proteolytic activity. Actin regulatory proteins participate in invadopodia formation, whereas matrix degradation requires metalloproteinases (MMPs) targeted to invadopodia. In this study, we show that the vesicle-tethering exocyst complex is required for matrix proteolysis and invasion of breast carcinoma cells. We demonstrate that the exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. Interaction between IQGAP1 and the exocyst is necessary for invadopodia activity because enhancement of matrix degradation induced by the expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We further show that the exocyst and IQGAP1 are required for the accumulation of cell surface membrane type 1 MMP at invadopodia. Based on these results, we propose that invadopodia function in tumor cells relies on the coordination of cytoskeletal assembly and exocytosis downstream of Rho guanosine triphosphatases.","subset":"pubmed_abstract"} +{"meta":{"pmid":34100773,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Relation between micro- and nanostructure features and biological properties of the decellularized rat liver.\nOrgan decellularization is one of the promising technologies of regenerative medicine, which allows obtaining cell-free extracellular matrix (ECM), which provide preservation of the composition, architecture, vascular network and biological activity of the ECM. The method of decellularization opens up wide prospects for its practical application not only in the field of creating full-scale bioengineered structures, but also in the manufacture of vessels, microcarriers, hydrogels, and coatings. The main goal of our work was the investigation of structure and biological properties of lyophilized decellularized Wistar rat liver fragments (LDLFs), as well as we assessed the regenerative potential of the obtained ECM. We obtained decellularized liver of a Wistar rat, the vascular network and the main components of the ECM of tissue were preserved. H&E staining of histological sections confirmed the removal of cells. DNA content of ECM is equal to 0.7% of native tissue DNA content. Utilizing scanning probe nanotomogrphy method, we showed sinuous, rough topography and highly nanoporous structure of ECM, which provide high level of mouse 3T3 fibroblast and Hep-G2cells biocompatibility. Obtained LDLF had a high regenerative potential, which we studied in an experimental model of a full-thickness rat skin wound healing: we observed the acceleration of wound healing by 2.2 times in comparison with the control.","subset":"pubmed_abstract"} +{"meta":{"pmid":18830237,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":10}}},"text":"Involvement of amygdala dopamine and nucleus accumbens NMDA receptors in ethanol-seeking behavior in mice.\nAlthough progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens core. However, specific mechanisms within these nuclei are unknown. In the present experiments, we used site-specific microinfusions of dopamine and NMDA receptor antagonists to examine the roles of accumbens and amygdala in the expression of ethanol conditioned place preference (CPP) in mice. In experiments 1 and 2, a D1\/D2\/D3 receptor antagonist (flupenthixol) was infused into accumbens or amygdala before testing, whereas experiment 3 used pretest infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens NMDA receptors. Dopamine antagonism of accumbens was without effect, but intra-amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect was dependent upon dopamine antagonism within the basolateral nucleus but not the central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also blocked CPP expression. The present findings suggest that expression of the ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA receptors. These are the first studies in any species to show a role for amygdala dopamine receptors and the first studies in mice to implicate accumbens NMDA receptors in ethanol-induced conditioned effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":18250764,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Polarization-controlled multistage switch based on polarization-selective computer-generated holograms.\nWe describe a polarization-controlled free-space optical multistage interconnection network based on polarization-selective computer-generated holograms: optical elements that are capable of imposing arbitrary, independent phase functions on horizontally and vertically polarized monochromatic light. We investigate the design of a novel nonblocking space-division photonic switch architecture. The multistage-switch architecture uses a fan-out stage, a single stage of 2 x 2 switching elements, and a fan-in stage. The architecture is compatible with several control strategies that use 1 x 2 and 2 x 2 polarization-controlled switches to route the input light beams. One application of the switch is in a passive optical network in which data is optically transmitted through the switch with a time-of-flight delay but without optical-to-electrical conversions at each stage. We have built and characterized a proof-of-principle 4 x 4 free-space switching network using three cascaded stages of arrayed birefringent computer-generated holographic elements. Data modulated at 20 MHz\/channel were transmitted through the network to demonstrate transparent operation.","subset":"pubmed_abstract"} +{"meta":{"pmid":19487029,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2022-05":1,"2021-17":2,"2021-10":1,"2021-04":1,"2020-34":1,"2020-05":1,"2019-30":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-30":1,"2018-13":1,"2023-06":1}}},"text":"Methodologies to assess blood flow in cerebral aneurysms: current state of research and perspectives.\nWith intracranial aneurysms disease bringing a weakened arterial wall segment to initiate, grow and potentially rupture an aneurysm, current understanding of vessel wall biology perceives the disease to follow the path of a dynamic evolution and increasingly recognizes blood flow as being one of the main stakeholders driving the process. Although currently mostly morphological information is used to decide on whether or not to treat a yet unruptured aneurysm, among other factors, knowledge of blood flow parameters may provide an advanced understanding of the mechanisms leading to further aneurismal growth and potential rupture. Flow patterns, velocities, pressure and their derived quantifications, such as shear and vorticity, are today accessible by direct measurements or can be calculated through computation. This paper reviews and puts into perspective current experimental methodologies and numerical approaches available for such purposes. In our view, the combination of current medical imaging standards, numerical simulation methods and endovascular treatment methods allow for thinking that flow conditions govern more than any other factor fate and treatment in cerebral aneurysms. Approaching aneurysms from this perspective improves understanding, and while requiring a personalized aneurysm management by flow assessment and flow correction, if indicated.","subset":"pubmed_abstract"} +{"meta":{"pmid":19114980,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":18}}},"text":"Roles and mechanisms of copper transporting ATPases in cancer pathogenesis.\nCopper (Cu) is an essential trace element for cell metabolism as a cofactor to many key metabolic enzymes. Numerous physiological processes rely on the adequate and timely transport of copper ions mediated by copper-transporting ATPases (Cu-ATPases), which are essential for human cell growth and development. Inherited gene mutations of ATP7A and ATP7B result in clinical diseases related to damage in the multiple organ systems. Increased expression of these genes has been recently observed in some human cancer specimens, and may be associated with tumorigenesis and chemotherapy resistance. However, underlying mechanisms of Cu-ATPases in human cancer progression and treatment are largely unknown. In this review, we summarize current progress on the copper transport system, the structural and functional properties of the Cu-ATPases, ATP7A and ATP7B, in copper homeostasis, and their roles in anti-tumor drug resistance and cancer metastasis. This review provides valuable information for clinicians and researchers who want to recognize the newest advances in this new field and identify possible lines of investigation in copper transport as important mediators in human physiology and cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":33193010,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The Prevalence of Migraine With Anxiety Among Genders.\nObjective: The aims of the present systematic review were to explore the prevalence of migraine with anxiety exclusively and determine if and why there are likely to be differences across genders. Introduction: Migraine is a very common neurological disorder and cause of productive disability worldwide that is more frequent in women of childbearing age than males. Previous studies have frequently demonstrated comorbidity of migraine and other psychiatric disorders. Although the prevalence of migraine across gender is well-established there are few if any systematic reviews on the prevalence of migraine comorbidity with anxiety cross-genders. Methods: The present systematic review included prevalence studies, clinic-based and cohort studies that reported the frequency of migraine with anxiety within the study sample. Eleven studies were included in the review after screening by two independent reviewers. Studies included participants who were 16 years and older diagnosed with migraine. Results: The main findings of this review indicated that anxiety is a major comorbidity of migraine worldwide, with a wide range (16-83%) of prevalence and a mean of ~43% of patients experiencing comorbid symptoms. Subjective anxiety symptoms appear to be greater among males with migraine than females which could be attributable to both environmental and\/or hormonal and genetic predispositions. Conclusions: The results reemphasize the high prevalence of migraine and comorbid anxiety symptoms worldwide while showing that although migraine is far more prevalent among women in general co-morbidity of migraine with anxiety unfolds a different gender difference. The results highlight the significance of exploring the impact of existing and pre-existing comorbid conditions of patients with migraines and further consideration into their diagnostic and treatment strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":34697901,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":2,"2024-10":1,"unknown":11}}},"text":"The association between visual display terminal use and dry eye: a review.\nDry eye disease (DED) is a multifactorial disease of the tear film and ocular surface. It causes ocular symptoms, reduced quality of life and a considerable economic burden on society. Prolonged use of visual display terminals (VDTs) has been suggested as an important risk factor for DED. This review aims to study the association between DED and VDT use with an emphasis on the prevalence of DED among VDT users and harmful daily duration of VDT use. A PubMed search was conducted and yielded 57 relevant articles based on a set of inclusion and exclusion criteria. The studies were subclassified according to study design. The far majority of the studies showed an association between VDT use and DED or DED-related signs and symptoms. The prevalence of definite or probable DED in VDT and office workers ranged from 26% to 70%, with as few as 1-2 hr of VDT exposure per day being associated with DED. VDT use is strongly associated with DED. VDT-associated DED is prevalent, but the exact prevalence needs to be further elucidated using standardized DED diagnosis criteria. Furthermore, a safe lower limit of daily VDT use has yet to be established. More research is needed on the effect of digitalization and digital transformation, which are particularly high during the time of the COVID-19 pandemic.","subset":"pubmed_abstract"} +{"meta":{"pmid":1756347,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2017-22":1,"2017-09":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2017-39":1,"2015-11":1,"2015-18":1}}},"text":"Dhat syndrome--a useful diagnostic entity in Indian culture.\nIn a prospective study of 144 consecutive male patients with psychosexual disorders, comprising 93 with Dhat syndrome with or without impotence or premature ejaculation, 21 with premature ejaculation, and 30 suffering only impotence, the commonest associated psychiatric illness was neurotic depression (39%) followed by anxiety neurosis (21%), while 31% did not receive a psychiatric diagnosis. The common presenting a symptoms of Dhat syndrome were weakness (71%), fatigue (69%), palpitations (69%), and sleeplessness (62%). After random allocation into groups, four types of treatment were given: an anti-anxiety drug, an antidepressant, a placebo, or counselling. The best response was seen with the anti-anxiety and antidepressant drugs. Twenty-one patients dropped out of treatment; 15 of whom were from the counselling group.","subset":"pubmed_abstract"} +{"meta":{"pmid":28737291,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Nucleoside reverse transcriptase inhibitor-reducing strategies in HIV treatment: assessing the evidence.\nAntiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, \"NRTI-reducing\" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI-sparing strategies, for example an integrase strand transfer inhibitor (INSTI) plus a ritonavir-boosted protease inhibitor (PI\/r) or PI\/r + lamivudine (3TC), in both na\u00efve and switch regimes. Of 10 key studies in treatment-na\u00efve adults assessing five NRTI-reducing strategies, only four studies demonstrated noninferiority vs. SOC [GARDEL, NEAT 001, AIDS Clinical Trials Group 5142 and PROGRESS]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI-reducing arm was shown in six of 10 studies (ATLAS-M, SALT, DUAL, OLE, LATTE-2 and SWORD). In general, NRTI-reducing therapy did not always result in an improvement in short- or long-term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI-reducing strategies has been compared against a single-pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety\/tolerability, and a favourable cost-efficacy ratio, preferably in a single pill, will eventually match the current SOC of triple ARV therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":32565898,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":11}}},"text":"Tumour-infiltrating Langerhans cells in non-melanoma skin cancer, a clinical and immunohistochemical study.\nNon-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represents 78.5% of all skin malignant tumours in Egypt. Dendritic cells can be found in almost all human tumours, they play an important role in antitumour immunity. The aim of the present study was to evaluate the percentage of Langerhans cells using CD1a in non-melanoma skin cancer, including BCC and SCC and to correlate this percentage with their clinicopathological features. The current study was performed on surgically excised specimens of 41 patients presented with non-melanoma skin cancer (26 BCC and 15 SCC) and 16 healthy volunteer control subjects. The mean and median percentage of Langerhans cells were higher in normal epidermis of control compared to malignant tumour tissue (p < 0.0001) and adjacent epidermis overlying malignant tumour tissue (p = 0.007). Langerhans cells were significantly seen in BCC cases more than SCC (p = 0.035) and they were seen in facial lesions more than those arising from other sites (p = 0.007). The reduction of Langerhans cells is a way for non-melanoma skin cancer to develop and progress. Marked reduction of Langerhans cells in SCC compared to BCC could refer to their role as a barrier against metastasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":23297615,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"[Iodine and thyroid gland with or without nuclear catastrophe].\nIodine, as a trace element, is a necessary and limiting substrate for thyroid gland hormone synthesis. It is an essential element that enables the thyroid gland to produce thyroid hormones thyroxine (T4) and triiodothyronine (T3). Synthesis of Thyroid Hormones and Iodine Metabolism. Three iodine molecules are added to make triiodothyronine, and four for thyroxine - the two key hormones produced by the thyroid gland. Iodine deficiency The proper daily amount of iodine is required for optimal thyroid function. Iodine deficiency can cause hypothyroidism, developmental brain disorders and goiter. Iodine deficiency is the single most common cause of preventable mental retardation and brain damage in the world. It also decreases child survival, causes goiters, and impairs growth and development. Iodine deficiency disorders in pregnant women cause miscarriages, stillbirths, and other complications. Children with iodine deficiency disorders can grow up stunted, apathetic, mentally retarded, and incapable of normal movements, speech or hearing. Excessive Iodine Intake. Excessive iodine intake, which can trigger a utoimmune thyroid disease and dysfunction. is on the other side. Iodine use in Case of Nuclear Catastrophe. In addition to other severe consuquences of radioactivity, high amount of radioactive iodine causes significant increase in incidence of thyroid gland carcinoma after some of the nuclear catastrophes (Hiroshima, Nagasaki, Chernobyl, Fukushima). The incidence of thyroid carcinoma was increased mostly in children. This paper was aimed at clarifying some of the possibilities of prevention according to the recommendations given by the World Health Organization.","subset":"pubmed_abstract"} +{"meta":{"pmid":23110990,"dup_signals":{"dup_doc_count":31,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":3,"2015-11":1,"2015-06":2,"2014-10":3,"2013-48":4,"2013-20":3,"unknown":14}}},"text":"Morphological, compositional, structural, and optical properties of Si-nc embedded in SiOx films.\nStructural, compositional, morphological, and optical properties of silicon nanocrystal (Si-nc) embedded in a matrix of non-stoichiometric silicon oxide (SiOx) films were studied. SiOx films were prepared by hot filament chemical vapor deposition technique in the 900 to 1,400\u00b0C range. Different microscopic and spectroscopic characterization techniques were used. The film composition changes with the growth temperature as Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy reveal. High-resolution transmission electron microscopy supports the existence of Si-ncs with a diameter from 1 to 6.5 nm in the matrix of SiOx films. The films emit in a wide photoluminescent spectrum, and the maximum peak emission shows a blueshift as the growth temperature decreases. On the other hand, transmittance spectra showed a wavelength shift of the absorption border, indicating an increase in the energy optical bandgap, when the growth temperature decreases. A relationship between composition, Si-nc size, energy bandgap, PL, and surface morphology was obtained. According to these results, we have analyzed the dependence of PL on the composition, structure, and morphology of the Si-ncs embedded in a matrix of non-stoichiometric SiOx films.","subset":"pubmed_abstract"} +{"meta":{"pmid":27263326,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Physiotherapy as a first point of contact in general practice: a solution to a growing problem?\nAim To evaluate the clinical effectiveness, patient satisfaction and economic efficacy of a physiotherapy service providing musculoskeletal care, as an alternative to GP care. There is a growing demand on general practice resources. A novel '1st Line Physiotherapy Service' was evaluated in two GP practices (inner city practice, university practice). Physiotherapy, as a first point of contact, was provided as an alternative to GP care for patients with musculoskeletal complaints. Participants A convenience cohort sample of over 500 patients with a musculoskeletal complaint was assessed within the physiotherapy service. For the economic evaluation a cohort of 100 GP patients was retrospectively reviewed. Clinical outcome measures were collected at assessment, one and six months following assessment. Patient satisfaction was collected at assessment. An economic evaluation was undertaken on the physiotherapy cohort of patients and compared to a retrospective cohort of patients (n=100) seen by a GP. This evaluation considered only the health care perspective (primary and secondary care). Societal issues such as absence from employment were not considered. There were no adverse events associated with the physiotherapy service. Patients reported high levels of satisfaction with the physiotherapy service. Patients managed within the 1st Line Physiotherapy Service demonstrated clinical improvements (EQ-5D-5L, Global Rating of Change) at the six-month point. There was a statistically significant difference in favour of the physiotherapy groups using a non-parametric bootstrap test; inner city practice, mean difference in costs=\u00a3538.01 (P =0.006; 95% CI; \u00a3865.678, \u00a3226.98), university practice mean difference in costs=\u00a3295.83 (P=0.044; 95% CI; \u00a3585.16, \u00a383.69). The limitations of this pragmatic service evaluation are acknowledged. Nevertheless, the physiotherapy service appears to provide a safe and efficacious service. The service is well received by patients. There appear to be potential financial implications to the health economy. Physiotherapists, as a first point of contact for patients with musculoskeletal-related complaints, could contribute to the current challenges faced in primary care.","subset":"pubmed_abstract"} +{"meta":{"pmid":21896847,"dup_signals":{"dup_doc_count":11}},"text":"Identification of a novel locus for autosomal dominant primary open angle glaucoma on 4q35.1-q35.2.\nPrimary open angle glaucoma is the most prevalent type of glaucoma and the leading cause of irreversible blindness worldwide. The genetic basis is poorly understood. Of 14 loci associated with this disease, only two genes have been identified, accounting for approximately 4% of cases. The authors investigated the genetic cause of primary open angle glaucoma in a large four-generation family with an apparent autosomal dominant mode of inheritance. Twenty-three family members underwent comprehensive phenotyping by a single ophthalmologist, and the MYOC gene was sequenced in all affected family members for whom DNA was available. Parametric genomewide linkage analysis was performed on 10 affected family members and one unaffected family member. Within the critical region, mutation analysis of candidate genes LRP2BP, CYP4V2, and UFSP2 was carried out by direct sequencing. No mutations were identified in MYOC. Genomewide linkage analysis generated one significant LOD score of 3.1 (maximum affected-only LOD score of 2.8) centered on chromosome 4 at 4q35.1-q35.2, a critical region that does not contain any of the previously reported primary open angle glaucoma loci. A 1.866-Mb (7.2 cM) region was identified containing 17 known or hypothetical genes. No mutations were identified in the candidate genes LRPB2BP, CYP4V2, and UFSP2. This study identifies a new primary open angle glaucoma locus, GLC1Q, in a region on chromosome 4 not previously associated with glaucoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":18200247,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":2,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-27":1,"2015-18":1}}},"text":"Optical absorption by randomly oriented carbon spheroids.\nThe optical properties of carbon spheroids are compared with those of carbon spheres for all size regimes. In general, the absorption cross section\/unit volume is increased by axial elongation, particularly away from the resonance region. The results are specific to carbon since the effect of shape change in a given size regime can depend crucially on the value of the refractive index.","subset":"pubmed_abstract"} +{"meta":{"pmid":31920906,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Superior Frontal Sulcus Focal Cortical Dysplasia Type II: An MRI, PET, and Quantified SEEG Study.\nPurpose: The superior frontal sulcus (SFS), located in the prefrontal and premotor cortex, is considered as one of the common locations of focal cortical dysplasia (FCD). However, the characteristics of seizures arising from this area are incompletely known. The primary purpose of this study was to investigate the clinical features and the epileptic networks of seizures originating from the SFS. Methods: We included seventeen patients with type II FCD within the SFS. SFS was identified both visually and automatically. Semiological features were evaluated and grouped. Interictal 18FDG-PET imaging in all patients was compared to controls using statistical parametric mapping (SPM-PET). In those subjects with stereoelectroencephalography (SEEG), two different quantitative intracranial electroencephalography analyses were applied. Finally, the locations of the SFS-related hypometabolic regions and epileptogenic zones (EZs) were transformed into standard space for group analysis. Results: We identified two semiological groups. Group 1 (9\/17) showed elementary motor signs (head version and tonic posturing), while group 2 (8\/17) exhibited complex motor behavior (fear, hypermotor, and ictal pouting). Based on SPM-PET, an SFS-supplementary motor area (SMA) epileptic propagation network was found in group 1, and an SFS-middle cingulate cortex (MCC)-pregenual anterior cingulate cortex (pACC) propagation network was discovered in group 2. Intracranial EEG analysis suggested similar affected structures with high epileptogenicity. The SFS-related hypometabolic regions and EZs in these groups showed a posterior-anterior spatial relationship. Conclusions: Even though originating from the spatially restricted cortex, SFS seizures can be divided into two groups based on semiological features. The SFS-SMA and SFS-MCC-pACC epileptic propagation networks may play pivotal roles in the generation of different semiologies. The posterior-anterior spatial relationship of both hypometabolic regions and EZs provides potentially useful information for distinguishing different types of SFS seizures and surgical evaluation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21745412,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-21":1,"2021-10":1,"2015-48":1,"2015-40":1,"2015-27":1,"2015-22":2,"2014-52":1,"2014-41":1,"2014-23":1,"2021-31":1,"2024-10":1,"2015-18":2,"2014-10":1,"2024-30":1}}},"text":"Topical haemostatic agents for skin wounds: a systematic review.\nVarious agents and techniques have been introduced to limit intra-operative blood loss from skin lesions. No uniformity regarding the type of haemostasis exists and this is generally based on the surgeon's preference. To study the effectiveness of haemostatic agents, standardized wounds like donor site wounds after split skin grafting (SSG) appear particularly suitable. Thus, we performed a systematic review to assess the effectiveness of haemostatic agents in donor site wounds. We searched all randomized clinical trials (RCTs) on haemostasis after SSG in Medline, Embase and the Cochrane Library until January 2011. Two reviewers independently assessed trial relevance and quality and performed data analysis. Primary endpoint was effectiveness regarding haemostasis. Secondary endpoints were wound healing, adverse effects, and costs. Nine relevant RCTs with a fair methodological quality were found, comparing epinephrine, thrombin, fibrin sealant, alginate dressings, saline, and mineral oil. Epinephrine achieved haemostasis significantly faster than thrombin (difference up to 2.5 minutes), saline or mineral oil (up to 6.5 minutes). Fibrin sealant also resulted in an up to 1 minute quicker haemostasis than thrombin and up to 3 minutes quicker than placebo, but was not directly challenged against epinephrine. Adverse effects appeared negligible. Due to lack of clinical homogeneity, meta-analysis was impossible. According to best available evidence, epinephrine and fibrin sealant appear superior to achieve haemostasis when substantial topical blood loss is anticipated, particularly in case of (larger) SSGs and burn debridement.","subset":"pubmed_abstract"} +{"meta":{"pmid":9020169,"dup_signals":{"dup_doc_count":12}},"text":"Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein.\nDrosophila single-minded, which acts as a positive master gene regulator in central nervous system midline formation in Drosophila, its two mouse homologs SIM1 and SIM2, and the mammalian aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins are members of the basic-helix-loop-helix.PAS family of transcription factors. In the yeast two-hybrid system, we demonstrate strong constitutive interaction of ARNT with SIM1 and SIM2 and fully ligand-dependent interaction of ARNT with AHR. Both the helix-loop-helix and the PAS regions of SIM1 and of ARNT are required for efficient heterodimerization. SIM1 and SIM2 do not form homodimers, and they do not interact with AHR. We also failed to detect homodimerization of ARNT. The interaction of ARNT with SIM1 was confirmed with in vitro synthesized proteins. Like AHR, in vitro synthesized SIM1 associates with the 90-kDa heat shock protein. SIM1 inhibits binding of the AHR.ARNT dimer to the xenobiotic response element in vitro. Introduction of SIM1 into hepatoma cells inhibits transcriptional transactivation by the endogenous AHR.ARNT dimer. The mouse SIM1. ARNT dimer binds only weakly to a proposed DNA target for the Drosophila SIM.ARNT dimer. In adult mice mRNA for SIM1 was expressed in lung, skeletal muscle, and kidney, whereas the mRNA for SIM2 was found in the latter two. ARNT is also expressed in these organs. Thus mouse SIM1 and SIM2 are novel heterodimerization partners for ARNT in vitro, and they may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism.","subset":"pubmed_abstract"} +{"meta":{"pmid":17329382,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Ethical challenges in voluntary blood donation in Kerala, India.\nThe National Blood Policy in India relies heavily on voluntary blood donors, as they are usually assumed to be associated with low levels of transfusion-transmitted infections (TTIs). In India, it is mandatory to test every unit of blood collected for hepatitis B, hepatitis C, HIV\/AIDS, syphilis and malaria. Donors come to the blood bank with altruistic intentions. If donors test positive to any of the five infections, their blood is discarded. Although the blood policy advocates disclosure of TTI status, donors are not, in practice, informed about their results. The onus is on the donor to contact the blood bank. Out of approximately 16 000 donations in the past 2 years, 438 tested positive for TTI, including 107 for HIV. Only 20% of the donors contacted the blood bank; none of them were HIV positive. Disclosure by blood banks of TTI status by telephone or mail has resulted in serious consequences for some donors. Health providers face an ethical dilemma, in the absence of proper mechanisms in place for disclosure of test results, regarding notification to donors who may test positive but remain ignorant of their TTI status. Given the high cost of neglecting to notify infected donors, the authors strongly recommend the use of rapid tests before collecting blood, instead of the current practice, which takes 3 h to obtain results, and disclosure of results directly to the donor by a counsellor, to avoid dropouts and to ensure confidentiality.","subset":"pubmed_abstract"} +{"meta":{"pmid":27587472,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.\nIn addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1\u00d710-4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5\u00d710-8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":23585609,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Patient poverty and workload in primary care: study of prescription drug benefit recipients in community health centres.\nTo determine if patient poverty is associated with increased workload for primary care providers (PCPs). Linkage of administrative data identifying patient poverty and comorbidity with survey data about the organizational structure of community health centres (CHCs). Ontario's 73 CHCs. A total of 64 CHC sites (N=63 included in the analysis). Patient poverty was determined in 2 different ways: based on receipt of Ontario Drug Benefits (identifying recipients of welfare, provincial disability support, and low-income seniors' benefits) or residence in low-income neighbourhoods. Patient comorbidities were determined through administrative diagnostic data from the CHCs and the Institute for Clinical Evaluative Sciences. Primary care workload was determined by examining PCP panel size (the number of patients cared for by a full-time-equivalent PCP during a 2-year interval). The CHCs with higher proportions of poor patients had smaller panel sizes. The smaller panel sizes were entirely explained by the medical comorbidity profile of the poor patients. Poor patients generate a higher workload for PCPs in CHCs; however, this is principally because they are sicker than higher-income patients are. Further information is required about the spectrum of services used by poor patients in CHCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":15925091,"dup_signals":{"dup_doc_count":25,"dup_dump_count":24,"dup_details":{"curated_sources":1,"2022-33":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2023-50":1}}},"text":"Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor.\nSeveral endpoints of different molecular complexity were studied in the Hershberger assay in order to evaluate the specificity and suitability of this test as a broad screening model. Androgen and estrogen receptors were activated or blocked, and expression of typical estrogen- or androgen responsive genes (complement C3, ERalpha, ERbeta, AR, TRPM-2, PBP C3, ODC, and IGF-1 mRNA) was analyzed in rat ventral prostate by real time RT-PCR. Administration of estradiol benzoate (EB) to castrated testosterone-treated rats had no effect on reproductive organ weights or gene expression levels and the anti-estrogen, ICI 182780, only affected ODC expression. Therefore, estrogenic or anti-estrogenic compounds would not be expected to seriously affect the outcome of a Hershberger test. However, EB given alone to castrated rats resulted in various effects. EB increased seminal vesicle weight, an effect reversed by ICI 182780, and affected TRPM-2, PBP C3, ODC, IGF-1, AR, and ERalpha mRNA levels. AR expression in the prostate seemed to be under regulation of both estrogens and androgens, as ICI 182780 inhibited the testosterone-induced AR expression, and flutamide inhibited the EB-induced AR expression. These data indicate that estrogens have various effects in castrated male rats and that expression of several genes is under multi-hormonal control in the ventral prostate. However, interactions between estrogens and androgens do not play a major role in the Hershberger assay, as simultaneous TP administration abolished the effects of EB. First choice of gene expression profiles in the Hershberger assay to study androgenic or anti-androgenic effects would be the traditional, TRPM-2 and PBP C3, supplemented with the new complement C3.","subset":"pubmed_abstract"} +{"meta":{"pmid":27495127,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Interspecific interference competition at the resource patch scale: do large herbivores spatially avoid elephants while accessing water?\nAnimals may anticipate and try to avoid, at some costs, physical encounters with other competitors. This may ultimately impact their foraging distribution and intake rates. Such cryptic interference competition is difficult to measure in the field, and extremely little is known at the interspecific level. We tested the hypothesis that smaller species avoid larger ones because of potential costs of interference competition and hence expected them to segregate from larger competitors at the scale of a resource patch. We assessed fine-scale spatial segregation patterns between three African herbivore species (zebra Equus quagga, kudu Tragelaphus strepsiceros and giraffe Giraffa camelopardalis) and a megaherbivore, the African elephant Loxodonta africana, at the scale of water resource patches in the semi-arid ecosystem of Hwange National Park, Zimbabwe. Nine waterholes were monitored every two weeks during the dry season of a drought year, and observational scans of the spatial distribution of all herbivores were performed every 15 min. We developed a methodological approach to analyse such fine-scale spatial data. Elephants increasingly used waterholes as the dry season progressed, as did the probability of co-occurrence and agonistic interaction with elephants for the three study species. All three species segregated from elephants at the beginning of the dry season, suggesting a spatial avoidance of elephants and the existence of costs of being close to them. However, contrarily to our expectations, herbivores did not segregate from elephants the rest of the dry season but tended to increasingly aggregate with elephants as the dry season progressed. We discuss these surprising results and the existence of a trade-off between avoidance of interspecific interference competition and other potential factors such as access to quality water, which may have relative associated costs that change with the time of the year.","subset":"pubmed_abstract"} +{"meta":{"pmid":32858804,"dup_signals":{"dup_doc_count":50,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2023-50":4,"2023-40":2,"2023-23":1,"2023-14":3,"2022-49":3,"2022-33":2,"2022-27":4,"2022-21":1,"2022-05":2,"2021-49":1,"2021-39":3,"2021-31":1,"2021-25":1,"2021-21":2,"2021-17":4,"2021-10":3,"2020-50":3,"2024-26":2,"2024-22":3,"2024-18":1,"2024-30":1}}},"text":"Chikungunya E2 Protein Produced in E. coli and HEK293-T Cells-Comparison of Their Performances in ELISA.\nChikungunya virus (CHIKV) is a mosquito-borne pathogen that causes a disease characterized by the acute onset of fever accompanied by arthralgia and intense joint pain. Clinical similarities and cocirculation of this and other arboviruses in many tropical countries highlight the necessity for efficient and accessible diagnostic tools. CHIKV envelope proteins are highly conserved among alphaviruses and, particularly, the envelope 2 glycoprotein (CHIKV-E2) appears to be immunodominant and has a considerable serodiagnosis potential. Here, we investigate how glycosylation of CHIKV-E2 affects antigen\/antibody interaction and how this affects the performance of CHIKV-E2-based Indirect ELISA tests. We compare two CHIKV-E2 recombinant antigens produced in different expression systems: prokaryotic-versus eukaryotic-made recombinant proteins. CHIKV-E2 antigens are expressed either in E. coli BL21(DE3)-a prokaryotic system unable to produce post-translational modifications-or in HEK-293T mammalian cells-a eukaryotic system able to add post-translational modifications, including glycosylation sites. Both prokaryotic and eukaryotic recombinant CHIKV-E2 react strongly to anti-CHIKV IgG antibodies, showing accuracy levels that are higher than 90%. However, the glycan-added viral antigen presents better sensitivity and specificity (85 and 98%) than the non-glycosylated antigen (81 and 71%, respectively) in anti-CHIKV IgM ELISA assays.","subset":"pubmed_abstract"} +{"meta":{"pmid":22479170,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Collective dynamics differentiates functional divergence in protein evolution.\nProtein evolution is most commonly studied by analyzing related protein sequences and generating ancestral sequences through Bayesian and Maximum Likelihood methods, and\/or by resurrecting ancestral proteins in the lab and performing ligand binding studies to determine function. Structural and dynamic evolution have largely been left out of molecular evolution studies. Here we incorporate both structure and dynamics to elucidate the molecular principles behind the divergence in the evolutionary path of the steroid receptor proteins. We determine the likely structure of three evolutionarily diverged ancestral steroid receptor proteins using the Zipping and Assembly Method with FRODA (ZAMF). Our predictions are within ~2.7 \u00c5 all-atom RMSD of the respective crystal structures of the ancestral steroid receptors. Beyond static structure prediction, a particular feature of ZAMF is that it generates protein dynamics information. We investigate the differences in conformational dynamics of diverged proteins by obtaining the most collective motion through essential dynamics. Strikingly, our analysis shows that evolutionarily diverged proteins of the same family do not share the same dynamic subspace, while those sharing the same function are simultaneously clustered together and distant from those, that have functionally diverged. Dynamic analysis also enables those mutations that most affect dynamics to be identified. It correctly predicts all mutations (functional and permissive) necessary to evolve new function and ~60% of permissive mutations necessary to recover ancestral function.","subset":"pubmed_abstract"} +{"meta":{"pmid":34513866,"dup_signals":{"dup_doc_count":24,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":17}}},"text":"Slowed Saccadic Reaction Times in Seemingly Normal Parts of Glaucomatous Visual Fields.\nPurpose: In eye movement perimetry, peripheral stimuli are confirmed by goal-directed eye movements toward the stimulus. The saccadic reaction time (SRT) is regarded as an index of visual field responsiveness, whereas in standard automated perimetry (SAP), the visual field sensitivity is tested. We investigated the relation between visual field sensitivity and responsiveness in corresponding locations of the visual field in healthy controls and in patients with mild, moderate and advanced glaucoma. Materials and Methods: Thirty-four healthy control subjects and 42 glaucoma patients underwent a 54-point protocol in eye movement perimetry (EMP) and a 24-2 SITA standard protocol in a Humphrey Field Analyzer. The visual field points were stratified by total deviation sensitivity loss in SAP into 6 strata. A generalized linear mixed model was applied to determine the influence of the various factors. Results: The generalized linear mixed model showed that the mean SRT increased with increasing glaucoma severity, from 479 ms in the control eyes to 678 ms in the eyes of patients with advanced glaucoma (p < 0.001). Mean SRTs significantly increased with increasing SAP sensitivity loss. Even at the locations where no sensitivity loss was detected by SAP (total deviation values greater or equal than 0 dB), we found lengthened SRTs in mild, moderate and advanced glaucoma compared to healthy controls (p < 0.05) and in moderate and advanced glaucoma compared to mild glaucoma (p < 0.05). At locations with total deviation values between 0 and -3 dB, -3 and -6 dB and -6 and -12 dB, we found similar differences. Conclusions: The lengthened SRT in areas with normal retinal sensitivities in glaucomatous eyes, i.e., planning and execution of saccades to specific locations, precede altered sensory perception as assessed with SAP. Better understanding of altered sensory processing in glaucoma might allow earlier diagnosis of emerging glaucoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":24844132,"dup_signals":{"dup_doc_count":54,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2023-40":3,"2023-23":1,"2023-14":3,"2023-06":1,"2022-49":3,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-17":2,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":2,"2020-34":1,"2019-47":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":2,"2018-47":2,"2018-43":2,"2018-34":2,"2018-30":2,"2018-22":2,"2018-17":1,"2018-13":1,"2024-30":2,"2024-18":3,"2024-10":1}}},"text":"Diagnostic sensitivity of radiography, ultrasonography, and magnetic resonance imaging for detecting shoulder osteochondrosis\/osteochondritis dissecans in dogs.\nRadiography, magnetic resonance imaging (MRI), and ultrasonography are commonly used for diagnosis of shoulder osteochondrosis and osteochondritis dissecans (OC\/OCD) in dogs, however there is a lack of published information on the relative diagnostic sensitivities of these modalities. The purpose of this prospective study was to compare diagnostic sensitivities of these modalities for detecting shoulder OC\/OCD in a group of dogs, using arthroscopy as the reference standard. Inclusion criteria were history and clinical findings consistent with osteochondrosis and\/or osteochondritis dissecans involving at least one shoulder. With informed client consent, both shoulders for all included dogs were examined using standardized radiography, ultrasonography, MRI, and arthroscopy protocols. One of three veterinary surgeons recorded clinical and arthroscopic findings without knowledge of diagnostic imaging findings. One of two veterinary radiologists recorded diagnostic imaging findings without knowledge of clinical and arthroscopic findings. Eighteen client-owned dogs (n = 36 shoulders) met inclusion criteria. Diagnostic sensitivity, specificity, and accuracy (correct classification rate) values for detecting presence or absence of shoulder osteochondrosis\/osteochondritis dissecans were as follows: radiography (88.5%, 90%, 88.9%), ultrasonography (92%, 60%, 82.6%), and MRI (96%, 88.9%, 94.4%). Odds of a correct diagnosis for MRI were 3.2 times more than ultrasonography and two times more than radiography. For MRI detection of lesions, the sagittal T2 or PD-FAT SAT sequences were considered to be most helpful. For radiographic detection of lesions, the additional supinated-mediolateral and pronated-mediolateral projections were considered to be most helpful. Findings from the current study support more evidence-based diagnostic imaging recommendations for dogs with clinically suspected shoulder osteochondrosis or osteochondritis dissecans.","subset":"pubmed_abstract"} +{"meta":{"pmid":32261692,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Antifouling performances of macro- to micro- to nano-copper materials for the inhibition of biofouling in its early stages.\nCopper has been known to possess antimicrobial properties since as far back as the Phoenician era where ship hulls were copper sheathed to prevent the inevitable effects of biofouling. As a consequence of evolving scientific research and development, the realisation of novel materials and agents has enabled new scientific branches - such as nanotechnology. In this paper we investigate the performance of different forms of copper (macro, micro and nano) for application as antifouling materials. Samples are deployed in SmartBay Ireland for four weeks and analysed for evidence of biofouling. It was found that copper in its nano form, produced the greatest antifouling effectiveness in both PDMS and sol-gel matrices.","subset":"pubmed_abstract"} +{"meta":{"pmid":8164693,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Transcriptional activation by herpes simplex virus type 1 VP16 in vitro and its inhibition by oligopeptides.\nVP16 is a herpes simplex virus (HSV)-encoded transcriptional activator protein that is essential for efficient viral replication and as such may be a target for novel therapeutic agents directed against viral gene expression. We have reconstituted transcriptional activation by VP16 in an in vitro system that is dependent on DNA sequences from HSV immediate-early gene promoters and on protein-protein interactions between VP16 and Oct-1 that are required for VP16 activation in vivo. Activation increased synergistically with the number of TAATGARAT elements (the cis-acting element for VP16 activation in vivo) upstream of the core promoter, and mutations of this element that reduce Oct-1 or VP16 DNA binding reduced transactivation in vitro. A VP16 insertion mutant unable to interact with Oct-1 was inactive, but, surprisingly, a deletion mutant lacking the activation domain was approximately 65% as active as the full-length protein. The activation domains of Oct-1 were necessary for activation in reactions containing the VP16 deletion mutant, and they contributed significantly to activation by full-length VP16. Addition of a GA-rich element present in many HSV immediate-early gene enhancers synergistically stimulated VP16-activated transcription. Finally, oligopeptides that are derived from a region of VP16 thought to contact a cellular factor known as HCF (host cell factor) and that inhibit efficient VP16 binding to the TAATGARAT element also specifically inhibited VP16-activated, but not basal, transcription. Amino acid substitutions in one of these peptides identified three residues that are absolutely required for inhibition and presumably for interaction of VP16 with HCF.","subset":"pubmed_abstract"} +{"meta":{"pmid":26100591,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":4,"2024-30":1,"unknown":2}}},"text":"Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil.\nHuman rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterize the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. Nasopharyngeal aspirates were collected from 630 children <5 years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analyzed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia, and asthma\/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma\/EVW, RV-C was detected relatively more frequently than RV-A (23% vs. 5%; P = 0.04). Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV-A and C species were detected. However, RV-C was more frequently found in children with asthma\/EVW than RV-A.","subset":"pubmed_abstract"} +{"meta":{"pmid":22363301,"dup_signals":{"dup_doc_count":25,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2017-13":1,"unknown":21}}},"text":"Adaptation to antifaces and the perception of correct famous identity in an average face.\nPrevious experiments have examined exposure to anti-identities (faces that possess traits opposite to an identity through a population average), finding that exposure to antifaces enhances recognition of the plus-identity images. Here we examine adaptation to antifaces using famous female celebrities. We demonstrate: that exposure to a color and shape transformed antiface of a celebrity increases the likelihood of perceiving the identity from which the antiface was manufactured in a composite face and that the effect shows size invariance (experiment 1), equivalent effects are seen in internet and laboratory-based studies (experiment 2), adaptation to shape-only antifaces has stronger effects on identity recognition than adaptation to color-only antifaces (experiment 3), and exposure to male versions of the antifaces does not influence the perception of female faces (experiment 4). Across these studies we found an effect of order where aftereffects were more pronounced in early than later trials. Overall, our studies delineate several aspects of identity aftereffects and support the proposal that identity is coded relative to other faces with special reference to a relatively sex-specific mean face representation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22023232,"dup_signals":{"dup_doc_count":17}},"text":"Exploring the relationship between resilience and diabetes outcomes in African Americans.\nThe purpose of this descriptive, correlational study is to describe the relationship between resilience scores and glycosylated hemoglobin (HbA1c) levels in African-American women with type 2 diabetes. Demographic data were collected from a voluntary sample of 71 African-American women who received care for type 2 diabetes at a federally qualified health center in southern Connecticut. The Wagnild and Young Resilience Scale was used to measure resilience scores in each participant. HbA1c levels were obtained at time of enrollment in the study. The majority of the women were resilient with over half the sample scoring in the high resilience range. Only nine participants had resilience scores that were considered low. Interestingly, HbA1c levels and resilience scores had a significant negative correlation, as individuals scored high on the resilience scale, HbA1c levels went down, suggesting that resilience may influence glycemic control in this sample. Nurse practitioners (NPs) have an opportunity to consider resilience in the care of minority populations with a chronic illness such as type 2 diabetes. High levels of resilience were significantly related to lower HbA1c levels indicating better glycemic control. Clinical implications based on the findings of this study included preventing complications of poorly controlled diabetes. NPs need to recognize holistic approaches to care that integrate not only the physiological aspects of care but also the psychological aspect of the person, including interventions to help build individual resilience.","subset":"pubmed_abstract"} +{"meta":{"pmid":14872066,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":3,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-11":1,"unknown":4}}},"text":"Biomedical conflicts of interest: a defence of the sequestration thesis-learning from the cases of Nancy Olivieri and David Healy.\nNo discussion of academic freedom, research integrity, and patient safety could begin with a more disquieting pair of case studies than those of Nancy Olivieri and David Healy. The cumulative impact of the Olivieri and Healy affairs has caused serious self examination within the biomedical research community. The first part of the essay analyses these recent academic scandals. The two case studies are then placed in their historical context-that context being the transformation of the norms of science through increasingly close ties between research universities and the corporate world. After a literature survey of the ways in which corporate sponsorship has biased the results of clinical drug trials, two different strategies to mitigate this problem are identified and assessed: a regulatory approach, which focuses on managing risks associated with industry funding of university research, and a more radical approach, the sequestration thesis, which counsels the outright elimination of corporate sponsorship. The reformist approach is criticised and the radical approach defended.","subset":"pubmed_abstract"} +{"meta":{"pmid":28841230,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2022-49":1,"2022-33":2,"2022-05":1,"2021-43":2,"2021-31":1,"2021-17":1,"2021-10":2,"2020-45":1,"2020-16":1,"2023-23":1}}},"text":"Rationale and design of the Drug-Eluting Stents vs Bare-Metal Stents in Saphenous Vein Graft Angioplasty (DIVA) Trial.\nVA Cooperative Studies Program #571 (DIVA) was designed to evaluate the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure when compared with bare-metal stents (BMS) in participants undergoing stenting of de novo SVG lesions. Participants undergoing clinically indicated stenting of de novo SVG lesions were randomized in a 1:1 ratio to DES or BMS. Randomization was stratified by presence\/absence of diabetes mellitus and the number of target SVG lesions (1 vs \u22652) within each participating site. At sites that did not routinely administer 12-months of dual antiplatelet therapy after SVG stenting participants without acute coronary syndromes received 1 month of open-label clopidogrel, followed by 11 months of clopidogrel for those assigned to DES and 11 months of placebo for those assigned to BMS. The primary endpoint was the 12-month incidence of target-vessel failure (defined as the composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). Secondary endpoints included the incidence of other clinical endpoints and the incremental cost-effectiveness of DES relative to BMS. Due to lower-than-anticipated target-vessel failure rates, target enrollment was increased from 519 to 762. The study had randomized 599 participants when recruitment ended in December 2015. The DIVA trial will provide clarity on the appropriate stent type for de novo SVG lesions.","subset":"pubmed_abstract"} +{"meta":{"pmid":22239332,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":17}}},"text":"A longitudinal integrated placement and medical students' intentions to practise rurally.\nIntegrated longitudinal rural placements are designed to promote favourable student attitudes towards and facilitate return to rural practice upon graduation. We explored the impact of an integrated placement on medical students' attitudes towards rural practice. Data were available from interviews with 10 medical students, 15 clinical supervisors and teachers, three community health staff, and focus groups made up of medical students. Socio-cognitive career theory gave insight into the personal, contextual and experiential factors, as well as the career barriers, that influence students' rural practice intentions. Framework analysis was used to develop a thematic framework illustrating the key findings. The longitudinal placement enabled students to achieve personal goals, and enhanced self-efficacy beliefs and orientation towards the complex personal and professional demands of rural practice. The informal curriculum, including multifaceted interactions with patients and their families, clinical teachers and other health care staff, was a vital experiential component. Students assimilated these rich experiences into their practice and evolving notions of professional identity as rural practitioners. Some students had little intention of practising rurally, partly as a result of contextual barriers such as geographic isolation, family and relationship needs, restricted postgraduate training opportunities and limited opportunities for specialist practice. The richness of the informal curriculum in a longitudinal rural placement powerfully influenced students' intentions to practise rurally. It provided an important context for learning and evolving notions of professionalism and rural professional identity. This richness could be reinforced by developing formal curricula using educational activities based around service-led and interprofessional learning. To overcome the contextual barriers, the rural workforce development model needs to focus on socialising medical students into rural and remote medicine. More generic issues include student selection, further expansion of structured vocational training pathways that vertically integrate with longitudinal rural placements and the maintenance of rurally focused support throughout postgraduate training.","subset":"pubmed_abstract"} +{"meta":{"pmid":8627573,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Preclinical pharmacology of CB30900, a novel dipeptide inhibitor of thymidylate synthase, in mice.\nCB30900 is a novel, potent thymidylate synthase inhibitor which can not be polyglutamated and may be active in cancers expressing low or defective folylpolyglutamate synthetase. Pharmacokinetics were studied in mouse tumors and tissues after bolus or infusion protocols. Elimination was triphasic after 100 mg kg-1 i.v. (T 1\/2 alpha, 2.8 min; T 1\/2 beta, 19.1 min and T 1\/2 gamma, 4.1 hr). Peak concentrations were 716 microM; clearance, 1.19 ml g-1 hr-1; and area under the curve (AUC 0-2 hr), 131 microM hr. Biphasic elimination occurred after i.p. administration and was comparable to the i.v. route giving complete i.p. bioavailability. Kidney concentrations were similar to plasma (AUC 0-2 hr, 84.3 microM hr). CB30900 concentrations in the gut increased steadily with time (AUC 0-2 hr, 645 microM hr) and liver drug concentrations were 7-fold greater than plasma (AUC 0-2 hr, 847 microM hr). Peak tumor concentrations occurred at 30 min and were 27% of plasma concentrations, but tumor drug clearance was markedly slower than for plasma (T 1\/2, 51 +\/- 8.2 min, mean +\/- S.E.). CB30900 was remarkably stable in vivo with 93% of an administered dose recovered unchanged after 48 hr. Plasma drug binding was concentration-dependent, ranging from 93.3 to 76% over 1 to 500 microM. During 24 hr infusion (50 mg kg-1 s.c.), steady-state plasma concentrations were 3 microM, giving an AUC 0-24 hr of 71 microM hr. Kidney drug levels were similar to plasma but liver concentrations were elevated 7-fold. By contrast, tumor drug concentrations were about 0.5 microM (AUC 0-24 hr, 14.6 microM hr). However, these low plasma drug concentrations are growth inhibitory in vitro (24-hr exposure).","subset":"pubmed_abstract"} +{"meta":{"pmid":6363217,"dup_signals":{"dup_doc_count":13,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2024-30":1,"unknown":5}}},"text":"Bacteriuria and primary biliary cirrhosis.\nSignificant bacteriuria was found in 19% of 87 women with primary biliary cirrhosis, whereas in 89 women with other types of chronic liver disease bacteriuria was present in only 7%. In 74 women with rheumatoid arthritis 8% were bacteriuric. Midstream urine specimens obtained from 144 consecutive women with primary biliary cirrhosis attending hospital over a two year period showed that 50 (35%) developed bacteriuria during 12 months of follow up. Bacteriuria was unrelated to age, raised serum bilirubin, drug therapy or urinary pH but was more common in patients with late stage (fibrotic) disease as judged by histological criteria. Fifty seven per cent of bacteriuric primary biliary cirrhosis patients suffered more than one urinary infection. Fifty nine per cent of the 156 bacteriuric episodes were asymptomatic. The types of organism isolated, the antibiotic sensitivity patterns and cure rate were similar to those reported in bacteriuric women without other underlying disease. The reinfection rate (34%), however, was double that reported for bacteriuric episodes in 'problem' women with recurrent bacteriuria, indicating a special susceptibility to urinary infection. The most common isolates were E coli (70%), which did not show abnormal adhesiveness to uroepithelial or buccal cells of normal women, or to those of primary biliary cirrhosis patients. Patients with primary biliary cirrhosis have not been reported to be more susceptible to infection in general. Bacteriuria, however, was common throughout all clinical stages of primary biliary cirrhosis. Thus there may be a unique association between bacteriuria and primary biliary cirrhosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":16984220,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Stratus not altocumulus: a new view of the yeast protein interaction network.\nSystems biology approaches can reveal intermediary levels of organization between genotype and phenotype that often underlie biological phenomena such as polygenic effects and protein dispensability. An important conceptualization is the module, which is loosely defined as a cohort of proteins that perform a dedicated cellular task. Based on a computational analysis of limited interaction datasets in the budding yeast Saccharomyces cerevisiae, it has been suggested that the global protein interaction network is segregated such that highly connected proteins, called hubs, tend not to link to each other. Moreover, it has been suggested that hubs fall into two distinct classes: \"party\" hubs are co-expressed and co-localized with their partners, whereas \"date\" hubs interact with incoherently expressed and diversely localized partners, and thereby cohere disparate parts of the global network. This structure may be compared with altocumulus clouds, i.e., cotton ball-like structures sparsely connected by thin wisps. However, this organization might reflect a small and\/or biased sample set of interactions. In a multi-validated high-confidence (HC) interaction network, assembled from all extant S. cerevisiae interaction data, including recently available proteome-wide interaction data and a large set of reliable literature-derived interactions, we find that hub-hub interactions are not suppressed. In fact, the number of interactions a hub has with other hubs is a good predictor of whether a hub protein is essential or not. We find that date hubs are neither required for network tolerance to node deletion, nor do date hubs have distinct biological attributes compared to other hubs. Date and party hubs do not, for example, evolve at different rates. Our analysis suggests that the organization of global protein interaction network is highly interconnected and hence interdependent, more like the continuous dense aggregations of stratus clouds than the segregated configuration of altocumulus clouds. If the network is configured in a stratus format, cross-talk between proteins is potentially a major source of noise. In turn, control of the activity of the most highly connected proteins may be vital. Indeed, we find that a fluctuation in steady-state levels of the most connected proteins is minimized.","subset":"pubmed_abstract"} +{"meta":{"pmid":23382925,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2017-13":1,"2013-20":1,"2024-22":1,"unknown":4}}},"text":"Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.\nThe Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":14660618,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":12}}},"text":"The mitotic chromosome is an assembly of rigid elastic axes organized by structural maintenance of chromosomes (SMC) proteins and surrounded by a soft chromatin envelope.\nThe structure of mitotic chromosomes is still poorly understood. Here we describe the use of a novel approach based on elasticity measurements of a single chromosome for studying the organization of these objects. The data reveal that mitotic chromosomes exhibit a non-homogenous structure consisting of rigid elastic axes surrounded by a soft chromatin envelope. The chemical continuity of DNA, but not RNA, was required for the maintenance of these axes. The axes show a modular structure, and the structural maintenance of chromosomes (SMC) proteins participate in their organization. Topoisomerase II was not involved in either the organization of the axes or the maintenance of the mitotic chromosomes. A model for the assembly and the structure of the mitotic chromosome is proposed. According this model, the chromosome axes are dynamic structures that assemble at the onset and disassemble the end of mitosis, respectively. The SMC proteins, in addition to maintaining axis elasticity, are essential for the determination of the rod-like chromosome shape. The extreme compaction of mitotic chromosomes is determined mainly by the high amount of bivalent ions bound to DNA at mitosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24852954,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":17}}},"text":"Multidisciplinary investigation of a multicountry outbreak of Salmonella Stanley infections associated with turkey meat in the European Union, August 2011 to January 2013.\nBetween August 2011 and January 2013, an outbreak of Salmonella enterica serovar Stanley (S. Stanley) infections affected 10 European Union (EU) countries, with a total of 710 cases recorded. Following an urgent inquiry in the Epidemic Intelligence Information System for food- and waterborne diseases (EPIS-FWD) on 29 June 2012, an international investigation was initiated including EU and national agencies for public health, veterinary health and food safety. Two of three local outbreak investigations undertaken by affected countries in 2012 identified turkey meat as a vehicle of infection. Furthermore, routine EU monitoring of animal sources showed that over 95% (n=298) of the 311 S. Stanley isolates reported from animal sampling in 2011 originated from the turkey food production chain. In 2004\u201310, none had this origin. Pulsed-field gel electrophoresis (PFGE) profile analysis of outbreak isolates and historical S. Stanley human isolates revealed that the outbreak isolates had a novel PFGE profile that emerged in Europe in 2011. An indistinguishable PFGE profile was identified in 346 of 464 human, food, feed, environmental and animal isolates from 16 EU countries: 102 of 112 non-human isolates tested were from the turkey production chain. On the basis of epidemiological and microbiological evidence, turkey meat was considered the primary source of human infection, following contamination early in the animal production chain.","subset":"pubmed_abstract"} +{"meta":{"pmid":20215436,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data.\nDeciphering transcription factor networks from microarray data remains difficult. This study presents a simple method to infer the regulation of transcription factors from microarray data based on well-characterized target genes. We generated a catalog containing transcription factors associated with 2720 target genes and 6401 experimentally validated regulations. When it was available, a distinction between transcriptional activation and inhibition was included for each regulation. Next, we built a tool (www.tfacts.org) that compares submitted gene lists with target genes in the catalog to detect regulated transcription factors. TFactS was validated with published lists of regulated genes in various models and compared to tools based on in silico promoter analysis. We next analyzed the NCI60 cancer microarray data set and showed the regulation of SOX10, MITF and JUN in melanomas. We then performed microarray experiments comparing gene expression response of human fibroblasts stimulated by different growth factors. TFactS predicted the specific activation of Signal transducer and activator of transcription factors by PDGF-BB, which was confirmed experimentally. Our results show that the expression levels of transcription factor target genes constitute a robust signature for transcription factor regulation, and can be efficiently used for microarray data mining.","subset":"pubmed_abstract"} +{"meta":{"pmid":11375363,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Off-loading the diabetic foot wound: a randomized clinical trial.\nTo compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes. In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day). The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1-26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 +\/- 320.0 daily steps) compared with the half-shoe (1,461.8 +\/- 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 +\/- 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15). The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe.","subset":"pubmed_abstract"} +{"meta":{"pmid":17982582,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":12}}},"text":"Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward.\nThis review will introduce the concept of toll-like receptor (TLR)-mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward). Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference) and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine) level of analysis. Moreover, a novel antagonism of TLR4 by (+)- and (-)-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia) and unwanted (tolerance, dependence, and reward) actions of opioids, thereby improving the safety and efficacy of their use.","subset":"pubmed_abstract"} +{"meta":{"pmid":29642181,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Associations between serum vitamin D and the risk of female reproductive tumors: A meta-analysis with trial sequential analysis.\nFemale reproductive tumors are common with high morbidity and mortality worldwide; however, the association between gynecological tumors and serum vitamin D is controversial. The aim of this meta-analysis was to evaluate the relationship between insufficiency of serum vitamin D and the occurrence of benign and malignant gynecological tumors. Studies from inception to June 2017 were searched in the electronic databases: National Library of Medicine (PubMed), Web of Science (Clerivate), and Cochrane Database of Systematic Reviews (Cochrane Library, CDSR) by 2 investigators independently. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. STATA 12.0 Software and Trial Sequential Analysis (TSA) software were applied for data analyses. Overall, 8 studies (including 2391 patients and 5798 patients with and without female reproductive tumors, respectively) were eligible for the present meta-analysis. In the subsequent meta-analysis, the occurrence of vitamin D deficiency in the case and control groups were 52.36% and 48.70%, respectively; women with female reproductive benign and malignant tumors were 55.57% and 50.59%, respectively. Although, no conclusive association was found between vitamin D deficiency and female reproductive tumors (OR, 1.05; 95% CI, 0.85-1.31); vitamin D deficiency may be a risk factor of malignant female reproductive neoplasm, as shown by the pooled OR (95% CI):1.17 (1.02-1.33). Furthermore, based on the OR values, association of vitamin D insufficiency with disease type, study location, number of patients, and methods for detecting CLA was observed. Similar results in the sensitivity analysis were observed. TSA showed that the cumulative Z-curve crossed the traditional boundary line, rather than crossing the trial sequential monitoring boundary. However, the cumulative information failed to reach the required information size. Currently, vitamin D deficiency appears to be a common issue in females, and there may be an urgent need to improve the level of vitamin D. Furthermore, vitamin D deficiency may be a non-negligible risk factor of malignant female reproductive neoplasm. Undoubtedly, more trials are required in the future according to TSA.","subset":"pubmed_abstract"} +{"meta":{"pmid":23289611,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2021-49":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2022-05":1,"2024-18":1}}},"text":"Charge-pairing interactions control the conformational setpoint and motions of the FMN domain in neuronal nitric oxide synthase.\nThe NOS (nitric oxide synthase; EC 126.96.36.199) enzymes contain a C-terminal flavoprotein domain [NOSred (reductase domain of NOS)] that binds FAD and FMN, and an N-terminal oxygenase domain that binds haem. Evidence suggests that the FMN-binding domain undergoes large conformational motions to shuttle electrons between the NADPH\/FAD-binding domain [FNR (ferredoxin NADP-reductase)] and the oxygenase domain. Previously we have shown that three residues on the FMN domain (Glu762, Glu816 and Glu819) that make charge-pairing interactions with the FNR help to slow electron flux through nNOSred (neuronal NOSred). In the present study, we show that charge neutralization or reversal at each of these residues alters the setpoint [Keq(A)] of the NOSred conformational equilibrium to favour the open (FMN-deshielded) conformational state. Moreover, computer simulations of the kinetic traces of cytochrome c reduction by the mutants suggest that they have higher conformational transition rates (1.5-4-fold) and rates of interflavin electron transfer (1.5-2-fold) relative to wild-type nNOSred. We conclude that the three charge-pairing residues on the FMN domain govern electron flux through nNOSred by stabilizing its closed (FMN-shielded) conformational state and by retarding the rate of conformational switching between its open and closed conformations.","subset":"pubmed_abstract"} +{"meta":{"pmid":25566368,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"The impact of early life factors on cognitive function in old age: The Hordaland Health Study (HUSK).\nPrevious studies have shown that adverse conditions during fetal and early life are associated with lower performance on neurocognitive tests in childhood, adolescence and adult life. There is, however, a paucity in studies investigating these associations into old age. The aim was to investigate the impact of early life factors on cognitive function in old age by taking advantage of the potential for a linkage between a community survey and historical birth records. A historical cohort study employing a linkage between a community survey of people aged 72-74 years with the participants' birth records (n=346). Early life factors included anthropometric measures taken at birth, birth complications, parental socioeconomic status, and maternal health status. The main outcome was a z-scored composite cognitive score, based on test scores from Kendrick Object Learning Test, Trail Making Test A, a modified version of the Digit Symbol Test, Block Design, a modified version of Mini-Mental State Examination and an abridged version of the Controlled Oral Word Association Test (COWAT). The separate cognitive tests were also individually analysed in relation to measures identified at birth. Higher parental socioeconomic status (SES; based on father's occupation) was associated with a higher value on the composite cognitive score (by 0.25 SD, p=0.0146) and higher Digit Symbol and Trail Making Test A performance. Higher head circumference at birth was associated with higher COWAT and Trail Making Test A performance. Both higher parental SES and head circumference at birth predicted cognitive function in old age independently of each other. There were no other consistent associations. In general we found little evidence for a substantial role of early life factors on late-life cognitive function. However, there was some evidence for an association with parental SES status and head circumference on certain cognitive domains.","subset":"pubmed_abstract"} +{"meta":{"pmid":7981396,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A sample-size-optimal Bayesian procedure for sequential pharmaceutical trials.\nConsider a pharmaceutical trial where the consequences of different decisions are expressed on a financial scale. The efficacy of the new drug under consideration has a prior distribution obtained from the underlying biological process, animal experiments, clinical experience, and so forth. Berry and Ho (Biometrics 44, 219-227) show how these components are used to establish an optimal (Bayes) sequential testing procedure, assuming a known constant sample size at each decision point. We show in this article how it is also possible to optimize further, with respect to the sample-size rule. This component of the design, which is missing from most sequential procedures, has the potential to yield considerably larger expected net gains (equivalently, considerably smaller Bayes risks).","subset":"pubmed_abstract"} +{"meta":{"pmid":31081016,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Overexpression of amyA and glaA substantially increases glucoamylase activity in Aspergillus niger.\nThe purpose of this study was to obtain an engineered Aspergillus niger strain with high glucoamylase activity by overexpressing the glucoamylase gene glaA and \u03b1-amylase gene amyA in A. niger CICC2462. Three recombinant strains containing a single copy of amyA (1A), containing two copies of amyA (2A), and coexpressing amyA and glaA (AG), respectively, were constructed. The transcript levels of amyA in 1A and 2A were increased by 2.95 folds and 3.09 folds, respectively. The levels of amyA and glaA in AG were increased by 1.21 folds and 2.86 folds, but the maximum extracellular glucoamylase activities did not differ significantly. In addition, after 1% casein phosphopeptides (CPPs) was added to the fermentation medium, the maximum extracellular glucoamylase activities for strains 1A, 2A, and AG were 35,200, 37,300, and 40,710 U\/ml, respectively, which were significantly higher than that of the parental strain CICC2462 (28,250 U\/ml), while CPPs alone had no effect on the parental strain CICC2462. We demonstrate that overexpression of amyA and glaA substantially increases the expression and secretion of glucoamylase in A. niger, and CPPs effectively improves the yield of glucoamylase in recombinant A. niger strains overexpressing amyA and glaA. The newly developed strains and culture methods may have extensive industrial applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":32536334,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Methylenedioxymethamphetamine-like discriminative stimulus effects of pyrrolidinyl cathinones in rats.\nSynthetic cathinone derivatives are used as alternatives both for stimulant drugs such as cocaine and methamphetamine and for club drugs such as 3,4-methylenedioxymethamphetamine (MDMA), but little is known about their MDMA-like subjective effects. In order to determine their similarity to MDMA, the discriminative stimulus effects of 10 pyrrolidinyl cathinones (\u03b1-pyrrolidinopropiophenone, 4'-methyl-\u03b1-pyrrolidinopropiophenone (4'-MePPP), \u03b1-pyrrolidinobutiophenone, 3',4'-methylenedioxy-\u03b1-pyrrolidinobutyrophenone (MD-PBP), \u03b1-pyrrolidinovalerophenone, 3,4-methylenedioxy-pyrovalerone (MDPV), \u03b1-pyrrolidinopentiothiophenone, napthylpyrovalerone (naphyrone), \u03b1-pyrrolidinohexiophenone, and 4'-methyl-\u03b1-pyrrolidinohexiophenone (4'-MePHP)) were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg\/kg racemic \u00b1-MDMA from vehicle. Compounds with no substitutions on the phenyl ring and the thiophene produced 44-67% MDMA-appropriate responding. In contrast, the substituted pyrrolidinyl cathinones produced a range of MDMA-appropriate responding dependent upon the length of the alpha side chain. 4'-MePPP, with a single carbon on the alpha position, produced 99.8% MDMA-appropriate responding, MD-PBP (two carbons) produced 83%, naphyrone (three carbons) produced 71%, MDPV (three carbons) produced, 66%, and 4'-MePHP (four carbons) produced 47%. Many cathinone compounds have discriminative stimulus effects similar to those of MDMA. However, the pyrrolidine substitution appears to reduce serotonergic effects, with a commensurate decrease in MDMA-like effects. Substitutions on the phenyl ring appear to be able to restore MDMA-like responding, but only in compounds with short alpha side chains. These findings agree with earlier findings of increasing dopaminergic effects and stronger reinforcing effects with increasing side chain. Assessment of more compounds is necessary to establish the replicability\/robustness of this phenomenon. These findings may be of use in predicting which compounds will have MDMA\/club drug-like effects versus psychostimulant-like effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":14960290,"dup_signals":{"dup_doc_count":60,"dup_dump_count":53,"dup_details":{"curated_sources":2,"2022-49":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-10":1,"2020-45":1,"2020-34":1,"2020-05":1,"2019-39":1,"2019-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":1,"2014-23":2,"2014-15":2,"2023-14":1,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1}}},"text":"Exposure to postnatal depression predicts elevated cortisol in adolescent offspring.\nAnimal research shows that early adverse experience results in altered glucocorticoid levels in adulthood, either raised basal levels or accentuated responses to stress. If a similar phenomenon operates in humans, this suggests a biological mechanism whereby early adversity might transmit risk for major depression, glucocorticoid elevations being associated with the development of this disorder. We measured salivary cortisol at 8:00 am and 8:00 pm over 10 days in 13-year-old adolescents who had (n = 48) or had not (n = 39) been exposed to postnatal maternal depression. Maternal postnatal depression was associated with higher, more variable morning cortisol in offspring, a pattern previously found to predict major depression. Early adverse experiences might alter later steroid levels in humans. Because maternal depression confers added risk for depression to children, these alterations might provide a link between early events and later psychopathology.","subset":"pubmed_abstract"} +{"meta":{"pmid":28942435,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":14}}},"text":"Re-examining the arterial cord blood gas pH screening criteria in neonatal encephalopathy.\nScreening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH \u22647.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate\/severe encephalopathy. Infants born at a single centre between 2008 and 2015, who were \u226536 weeks, had no congenital anomalies and had a cABG pH \u22647.10 were identified for a retrospective cohort study. Maternal\/perinatal and patient factors were collected. 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35\/85 infants with pH <7.00 and 34\/327 infants with pH between 7.00 and 7.10 had moderate\/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5\/35 and 13\/34 infants in the two pH groups, respectively.A cABG pH threshold of \u22647.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate\/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate\/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods. Universal cord blood gas screening with a pH threshold \u22647.10 and mandatory encephalopathy examination results in greater detection of infants with moderate\/severe encephalopathy and timely initiation of therapeutic hypothermia.","subset":"pubmed_abstract"} +{"meta":{"pmid":27764591,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"Improving the Incoherence of a Learned Dictionary via Rank Shrinkage.\nThis letter considers the problem of dictionary learning for sparse signal representation whose atoms have low mutual coherence. To learn such dictionaries, at each step, we first update the dictionary using the method of optimal directions (MOD) and then apply a dictionary rank shrinkage step to decrease its mutual coherence. In the rank shrinkage step, we first compute a rank 1 decomposition of the column-normalized least squares estimate of the dictionary obtained from the MOD step. We then shrink the rank of this learned dictionary by transforming the problem of reducing the rank to a nonnegative garrotte estimation problem and solving it using a path-wise coordinate descent approach. We establish theoretical results that show that the rank shrinkage step included will reduce the coherence of the dictionary, which is further validated by experimental results. Numerical experiments illustrating the performance of the proposed algorithm in comparison to various other well-known dictionary learning algorithms are also presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":18264109,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":14}}},"text":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens.\nInfections by attaching and effacing (A\/E) bacterial pathogens, such as Escherichia coli O157:H7, pose a serious threat to public health. Using a mouse A\/E pathogen, Citrobacter rodentium, we show that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium. Infection of IL-22 knockout mice results in increased intestinal epithelial damage, systemic bacterial burden and mortality. We also find that IL-23 is required for the early induction of IL-22 during C. rodentium infection, and adaptive immunity is not essential for the protective role of IL-22 in this model. Instead, IL-22 is required for the direct induction of the Reg family of antimicrobial proteins, including RegIIIbeta and RegIIIgamma, in colonic epithelial cells. Exogenous mouse or human RegIIIgamma substantially improves survival of IL-22 knockout mice after C. rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A\/E bacterial pathogens.","subset":"pubmed_abstract"} +{"meta":{"pmid":18292986,"dup_signals":{"dup_doc_count":35,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-23":2,"2023-14":2,"2022-49":1,"2022-40":2,"2022-21":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-10":1,"2019-43":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-26":2,"2024-22":1,"2024-18":1,"2024-10":2}}},"text":"Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies.\nThe aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders. After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies. Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p < 0.001). There was little evidence of heterogeneity between studies (p = 0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p = 0.01). This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.","subset":"pubmed_abstract"} +{"meta":{"pmid":27655820,"dup_signals":{"dup_doc_count":11}},"text":"Photoreception and vision in the ultraviolet.\nUltraviolet (UV) light occupies the spectral range of wavelengths slightly shorter than those visible to humans. Because of its shorter wavelength, it is more energetic (and potentially more photodamaging) than 'visible light', and it is scattered more efficiently in air and water. Until 1990, only a few animals were recognized as being sensitive to UV light, but we now know that a great diversity, possibly even the majority, of animal species can visually detect and respond to it. Here, we discuss the history of research on biological UV photosensitivity and review current major research trends in this field. Some animals use their UV photoreceptors to control simple, innate behaviors, but most incorporate their UV receptors into their general sense of vision. They not only detect UV light but recognize it as a separate color in light fields, on natural objects or living organisms, or in signals displayed by conspecifics. UV visual pigments are based on opsins, the same family of proteins that are used to detect light in conventional photoreceptors. Despite some interesting exceptions, most animal species have a single photoreceptor class devoted to the UV. The roles of UV in vision are manifold, from guiding navigation and orientation behavior, to detecting food and potential predators, to supporting high-level tasks such as mate assessment and intraspecific communication. Our current understanding of UV vision is restricted almost entirely to two phyla: arthropods and chordates (specifically, vertebrates), so there is much comparative work to be done.","subset":"pubmed_abstract"} +{"meta":{"pmid":30611159,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Impactful publishing: the Journal of Neurosurgery and its diamond anniversary (1944-2019).\nWith this landmark issue of the Journal of Neurosurgery (JNS), we celebrate the 75th anniversary of continuous publication of articles in neurosurgery. It is likely not a coincidence that the diamond anniversary of the JNS coincides precisely with the 150th anniversary of the birth of Harvey Cushing. It is possible that some events in life are inextricably and cosmically tied together, such as the birth of the founding father of our specialty, the society named after him that ultimately became the American Association of Neurological Surgeons (AANS), and the journal of this organization-the JNS.","subset":"pubmed_abstract"} +{"meta":{"pmid":2975503,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Risk of recurrence of occupational back pain over three year follow up.\nA random sample including 2342 cases representative of all occupational back injuries in Quebec (1981) was followed up prospectively over three years to assess the recurrence rate of back problems (lumbar, thoracic, and cervical). Each medical and accident report was reviewed to obtain the site of symptoms and occupation. Age, sex, industrial sector, and number of episodes of absence from work were abstracted from the computerised Quebec Compensation Board files. The recurrence rate was 20.0% at one year follow up and 36.3% at three years. A multivariate analysis using a Poisson regression, was performed to model the risk of recurrence over time. Men had a higher chance of recurrence (risk ratio = 1.85, 95% CI = 1.50-2.27) but among recurrent cases, the average total number of episodes was comparable between men and women. Age showed a protective effect on the probability of recurrence (10 years: RR = 0.93, 95% CI = 0.88-0.98) due to the lower recurrence rate in the 45-64 year old group (31.8%). Cervical and lumbar symptoms had identical recurrence profiles whereas thoracic symptoms had a significantly lower recurrence rate. Drivers had the highest recurrence rate (42.1%) and nurses had the highest average number of recurrences (2.03) among recurrent cases. Both occupations had statistically significant excesses after controlling for the other variables.","subset":"pubmed_abstract"} +{"meta":{"pmid":2841237,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[A hepatitis non-A, non-B-associated substance in the feces--identification and cloning of a partially double-stranded circular DNA].\nBy means of a radioimmunoassay a substance excreted in feces could be detected in patients with hepatitis non-A,non-B (HNANB). Feces extracts of patients with sporadic and posttransfusion HNANB as well as of healthy persons were precipitated with PEG, digested with RNase and DNase and separated on CsCl. In HNANB-patients a RIA-positive material with a density of 1.3 g\/ml CsCl could be detected which contained a partially double-stranded circular DNA. Cloning of this DNA in lambda-phase resulted in DNA of about 5 Kb, which hybridized with feces DNA under stringent conditions. The 5 Kb-DNA were mapped with different restriction enzymes. A 1.5 Kb EcoRi-fragment cross-hybridizes with HBV-DNA. No hybridization and sequence homologies were found with human, viral and procaryotic DNA as well as with plasmid and phage DNA (data base EMBL, Heidelberg). It is assumed that the DNA excreted in feces of HNANB-patients represents a viral genome not detected so far.","subset":"pubmed_abstract"} +{"meta":{"pmid":29386252,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":10}}},"text":"Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.\nGermline pathogenic variants in SDHB\/SDHC\/SDHD are the most frequent causes of inherited phaeochromocytomas\/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB\/SDHC\/SDHD mutation carriers. A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma\/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB\/SDHC\/SDHD (n=673\/43\/160). Tumour risks were correlated with in silico structural prediction analyses. Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371\/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB\/SDHC\/SDHD mutation carriers.","subset":"pubmed_abstract"} +{"meta":{"pmid":2317008,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34.\nIdiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and\/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non-Jewish kindred was located on chromosome 9q32-34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32-34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine-beta-hydroxylase. The same gene may be responsible for ITD both in the non-Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":24998618,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2022-33":1,"2022-27":1,"2021-10":1,"2021-04":1,"2019-22":1,"2018-51":2,"2018-39":1,"2018-30":1,"2018-17":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2023-40":1,"2024-26":1}}},"text":"An ice-templated, pH-tunable self-assembly route to hierarchically porous graphene nanoscroll networks.\nPorous graphene nanostructures are of great interest for applications in catalysis and energy storage. However, the fabrication of three-dimensional (3D) macroporous graphene nanostructures with controlled morphology, porosity and surface area still presents significant challenges. Here we introduce an ice-templated self-assembly approach for the integration of two-dimensional graphene nanosheets into hierarchically porous graphene nanoscroll networks, where the morphology of porous structures can be easily controlled by varying the pH conditions during the ice-templated self-assembly process. We show that freeze-casting of reduced graphene oxide (rGO) solution results in the formation of 3D porous graphene microfoam below pH 8 and hierarchically porous graphene nanoscroll networks at pH 10. In addition, we demonstrate that graphene nanoscroll networks show promising electrocatalytic activity for the oxygen reduction reaction (ORR).","subset":"pubmed_abstract"} +{"meta":{"pmid":29307296,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Dietary fatty acids and susceptibility to multiple sclerosis.\nThe gut microbiome as well as dietary habits have recently been established as environmental contributors to the pathogenesis of multiple sclerosis (MS), a T-cell-mediated autoimmune disease of the central nervous system (CNS). To summarize recent findings on the Janus-faced effects of dietary short-chain fatty acids (SCFAs) and long-chain fatty acids (LCFAs) on T-cell immunity with a special focus on the gut and the microbiome as an interface linking diet and T-cell responses during MS. Review article. The autoimmune basis of MS most likely stems from an imbalance between pro-inflammatory T helper cell (Th)1 and Th17 cells and anti-inflammatory or regulatory mechanisms including regulatory T cells (Treg). Hence, the rationale of currently available therapeutic interventions is to either suppress pathogenic Th1\/Th17 and\/or to foster Treg responses. Dietary fatty acids are often discussed for their detrimental role in MS. However, recent studies investigating saturated fatty acids in animal models of MS revealed harmful as well as beneficial effects depending on their aliphatic chain length. Dietary SCFAs constitute interesting candidates as safe and potent add-on therapy in the immunomodulatory treatment armamentarium for relapsing-remitting MS.","subset":"pubmed_abstract"} +{"meta":{"pmid":27264466,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2019-09":1,"2018-51":2,"2018-43":2,"2018-34":1,"2018-22":2,"2018-09":2,"2019-22":1}}},"text":"Effect of Sialic Acid on Platelet Cryopreservation.\nSialic acid is a molecule which is responsible for the net negative surface charge of platelets. We investigated the effect of sialic acid on fresh and cryopreserved platelets. Platelet samples were obtained by platelet apheresis from 8 healthy donors. Platelet suspensions with different sialic acid concentrations (0, 1, 2 and 4 mg\/mL) were studied for ADP and ristocetin induced platelet aggregation, basal and ADP induced P-selectin and glycoprotein- Ib\/IX expression. Then platelet samples were cryopreserved in 5% DMSO with or without 4 mg\/mL sialic acid. After thawing, P-selectin expression was compared with the control group. Six samples were also washed after thawing and P-selectin expression was again compared to unwashed samples. Sialic acid suppressed ADP induced platelet aggregation and P-selectin expression in a dose dependent manner. In cryopreserved samples, P-selectin expression of 4 mg\/mL sialic acid containing group was found significantly higher than the control group (p< 0.001). In cryopreserved control group, P-selectin expression of thawedwashed group was significantly higher than thawed-unwashed group (p< 0.05). Our results indicate that sialic acid is not a good cryoprotective agent. Washing procedure after thawing to eliminate DMSO causes significant platelet activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29243200,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":18}}},"text":"The Cascading Effects of Multiple Dimensions of Implementation on Program Outcomes: a Test of a Theoretical Model.\nThis study tests a theoretical cascade model in which multiple dimensions of facilitator delivery predict indicators of participant responsiveness, which in turn lead to improvements in targeted program outcomes. An effectiveness trial of the 10-session New Beginnings Program for divorcing families was implemented in partnership with four county-level family courts. This study included 366 families assigned to the intervention condition who attended at least one session. Independent observers provided ratings of program delivery (i.e., fidelity to the curriculum and process quality). Facilitators reported on parent attendance and parents' competence in home practice of program skills. At pretest and posttest, children reported on parenting and parents reported child mental health. We hypothesized effects of quality on attendance, fidelity and attendance on home practice, and home practice on improvements in parenting and child mental health. Structural Equation Modeling with mediation and moderation analyses were used to test these associations. Results indicated quality was significantly associated with attendance, and attendance moderated the effect of fidelity on home practice. Home practice was a significant mediator of the links between fidelity and improvements in parent-child relationship quality and child externalizing and internalizing problems. Findings provide support for fidelity to the curriculum, process quality, attendance, and home practice as valid predictors of program outcomes for mothers and fathers. Future directions for assessing implementation in community settings are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":7515853,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions.\nThree isozymes of nitric oxide (NO) synthase (EC 22.214.171.124) have been identified and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells) are encoded for by three different genes located on chromosomes 12, 17, and 7, respectively. The deduced amino acid sequences of the human isozymes show less than 59% identity. Across species, amino acid sequences for each isoform are well conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use L-arginine and molecular oxygen as substrates and require the cofactors NADPH, 6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin mononucleotide. They all bind calmodulin and contain heme. Isoform I is constitutively present in central and peripheral neuronal cells and certain epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves. It has also been implicated in neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase can be induced with lipopolysaccharide and cytokines in a multitude of different cells. Based on sequencing data there is no evidence for more than one inducible isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large amounts of NO that has cytostatic effects on parasitic target cells by inhibiting iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is involved in the pathophysiology of autoimmune diseases and septic shock. Isoform III of NO synthase has been found mostly in endothelial cells. It is constitutively expressed, but expression can be enhanced, eg, by shear stress. Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps blood vessels dilated, prevents the adhesion of platelets and white cells, and probably inhibits vascular smooth muscle proliferation.","subset":"pubmed_abstract"} +{"meta":{"pmid":19643763,"dup_signals":{"dup_doc_count":52,"dup_dump_count":31,"dup_details":{"curated_sources":3,"2023-50":2,"2023-40":1,"2023-23":2,"2023-14":1,"2023-06":1,"2022-49":3,"2022-40":2,"2022-27":1,"2022-21":2,"2022-05":1,"2021-49":2,"2021-43":4,"2021-39":1,"2021-31":2,"2021-21":2,"2021-17":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":2,"2018-26":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-30":3,"2024-26":1,"2024-22":1,"2024-18":3,"2024-10":1}}},"text":"Genealogical typing of Neisseria meningitidis.\nDespite the increasing popularity of multilocus sequence typing (MLST), the most appropriate method for characterizing bacterial variation and facilitating epidemiological investigations remains a matter of debate. Here, we propose that different typing schemes should be compared on the basis of their power to infer clonal relationships and investigate the utility of sequence data for genealogical reconstruction by exploiting new statistical tools and data from 20 housekeeping loci for 93 isolates of the bacterial pathogen Neisseria meningitidis. Our analysis demonstrated that all but one of the hyperinvasive isolates established by multilocus enzyme electrophoresis and MLST were grouped into one of six genealogical lineages, each of which contained substantial variation. Due to the confounding effect of recombination, evolutionary relationships among these lineages remained unclear, even using 20 loci. Analyses of the seven loci in the standard MLST scheme using the same methods reproduced this classification, but were unable to support finer inferences concerning the relationships between the members within each complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":16684099,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":10}}},"text":"A single-run, real-time PCR for detection and identification of Borrelia burgdorferi sensu lato species, based on the hbb gene sequence.\nLyme borreliosis is the most important vector-borne disease caused by spirochetes within the Borrelia burgdorferi sensu lato (B. burgdorferi sl) complex. There is strong evidence that different species of this group of genetically diverse spirochetes are involved in distinct clinical manifestations of the disease. In order to differentiate species within this bacterial complex, we developed a real-time-PCR protocol, which targets the hbb gene. We designed a fluorescein-labeled probe specific of a region of this gene harboring a polymorphism linked to species. An internally Red640 labeled primer allowed a fluorescence resonance energy transfer to occur. The sensitivity of this method was in the range of 10 bacteria per assay. After amplification, a melting curve was generated for genotyping. Analysis of these melting curves clearly allowed the distinction between the main European species of B. burgdorferi sl. One hundred seventy tick extracts were analysed by this hbb-based method and in parallel by amplification of the 5S-23S intergenic spacer and RFLP analyses. There was a good correlation between these two methods. We conclude that this hbb-based real-time-PCR is suitable for epidemiological studies on field-collected ticks, although rare mutations in the genomic sequence spanned by the probe could lead to misidentification.","subset":"pubmed_abstract"} +{"meta":{"pmid":22573319,"dup_signals":{"dup_doc_count":67,"dup_dump_count":43,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":2,"2023-23":4,"2023-14":1,"2022-49":2,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2020-10":1,"2020-05":1,"2019-39":2,"2019-35":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-47":2,"2018-39":3,"2018-30":1,"2018-26":2,"2018-22":1,"2018-17":1,"2018-13":2,"2018-09":1,"2017-51":3,"2017-43":3,"2017-34":3,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2024-22":2,"2017-13":1,"2024-26":1}}},"text":"Defining requirements for collagenase cleavage in collagen type III using a bacterial collagen system.\nDegradation of fibrillar collagens is important in many physiological and pathological events. These collagens are resistant to most proteases due to the tightly packed triple-helical structure, but are readily cleaved at a specific site by collagenases, selected members of the matrix metalloproteinases (MMPs). To investigate the structural requirements for collagenolysis, varying numbers of GXY triplets from human type III collagen around the collagenase cleavage site were inserted between two triple helix domains of the Scl2 bacterial collagen protein. The original bacterial CL domain was not cleaved by MMP-1 (collagenase 1) or MMP-13 (collagenase 3). The minimum type III sequence necessary for cleavage by the two collagenases was 5 GXY triplets, including 4 residues before and 11 residues after the cleavage site (P4-P11'). Cleavage of these chimeric substrates was not achieved by the catalytic domain of MMP-1 or MMP-13, nor by full-length MMP-3. Kinetic analysis of the chimeras indicated that the rate of cleavage by MMP-1 of the chimera containing six triplets (P7-P11') of collagen III was similar to that of native collagen III. The collagenase-susceptible chimeras were cleaved very slowly by trypsin, a property also seen for native collagen III, supporting a local structural relaxation of the triple helix near the collagenase cleavage site. The recombinant bacterial-human collagen system characterized here is a good model to investigate the specificity and mechanism of action of collagenases.","subset":"pubmed_abstract"} +{"meta":{"pmid":14740701,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effects of calcium administration during post-ischemic reperfusion on myocardial contractility, stiffness, edema, and ultrastructure.\nPrevious investigators have suggested that calcium may play a role in the pathogenesis of myocardial cell damage following ischemia and reperfusion. Twenty-six in-situ blood perfused isovolumic canine preparations were divided into four groups. Group I dogs were maintained normocalcemic during 45 min of reperfusion following 45 min of hypothermic (27 degrees C) ischemic arrest; Group II dogs received CaCl2 (7 mg\/kg) after 15 min of reperfusion; Group III dogs received citrate solution (0.8 ml\/kg citrate-phosphate-dextrose [CPD]) after 15 min of reperfusion; Group IV dogs received 7 mg\/kg of CaCl2 at 5 min after receiving the same citrate dose as Group III after 15 min of reperfusion. In Group II hearts, calcium improved the left ventricular contractility (P < 0.05 vs Group I) without causing additional cellular or subcellular injury. Calcium also appeared to increase myocardial stiffness (alpha(n)) compared to Group I hearts (P < 0.01). In Group III hearts, citrate reduced contractility (P < 0.01 vs Group I) and increased myocardial edema (P < 0.005 vs Group I) without any apparent improvement in cellular or subcellular preservation. In Group IV hearts, calcium reversed the depression of contractility caused by citrate, resulted in no additional morphologic injury, increased myocardial stiffness compared to Group I or Group III (P < 0.005), and minimized myocardial edema (P < 0.005 vs Group I or III). These results suggest that calcium administered after 15 min of reperfusion improves the depression of contractility that follows hypothermic ischemic arrest without causing additional myocardial damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":23020257,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"The baric probe: a novel long-term implantable intracranial pressure monitor with ultrasound-based interrogation.\nPrompt diagnosis of shunt malfunction is critical in preventing neurological morbidity and death in individuals with hydrocephalus; however, diagnostic methods for this condition remain limited. For several decades, investigators have sought a long-term, implantable intracranial pressure (ICP) monitor to assist in the diagnosis of shunt malfunction, but efforts have been impeded by device complexity, marked measurement drift, and limited instrumentation lifespan. In the current report, the authors introduce an entirely novel, simple, compressible gas design that addresses each of these problems. The device described herein, termed the \"baric probe,\" consists of a subdural fluid bladder and multichannel indicator that monitors the position of an air-fluid interface (AFI). A handheld ultrasound probe is used to interrogate the baric probe in vivo, permitting noninvasive ICP determination. To assess the function of device prototypes, ex vivo experiments were conducted using a water column, and short- and long-term in vivo experiments were performed using a porcine model with concurrent measurements of ICP via a fiberoptic monitor. Following a toe region of approximately 2 cm H(2)O, the baric probe's AFI demonstrated a predictable linear relationship to ICP in both ex vivo and in vivo models. After a 2-week implantation of the device, this linear relationship remained robust and reproducible. Further, changes in ICP were observed with the baric probe, on average, 3 seconds in advance of the fiberoptic ICP monitor reading. The authors demonstrate \"proof-of-concept\" and feasibility for the baric probe, a long-term implantable ICP monitor designed to facilitate the prompt and accurate diagnosis of shunt malfunction. The baric probe showed a consistent linear relationship between ICP and the device's AFI in ex vivo and short- and long-term in vivo models. With a low per-unit cost, a reduced need for radiography or CT, and an indicator that can be read with a handheld ultrasound probe that interfaces with any smart phone, the baric probe promises to simplify the care of patients with shunt-treated hydrocephalus throughout both the developed and the developing world.","subset":"pubmed_abstract"} +{"meta":{"pmid":14653902,"dup_signals":{"dup_doc_count":22,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2024-22":6,"2024-18":3,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"unknown":5}}},"text":"The association between socioeconomic development at the town level and the distribution of dental caries in Brazilian children.\nTo investigate the association between dental caries among children in the state of S\u00e3o Paulo, Brazil, and town-level indices of socioeconomic development. We examined 15 385 oral-examination records from children aged 5 or 6 years old from 129 towns and cities in the state of S\u00e3o Paulo. We studied two outcomes: (1) the mean number of decayed, missing, and filled deciduous teeth (dmft index) and (2) the care index, which is the proportion of decayed teeth that have already been filled. The explanatory variables were the child development index, human development index, illiteracy rate among subjects older than 20 years, household income, Gini coefficient, insufficient income, fluoridated water supply, number of dentists per 10 000 inhabitants, number of dentists in the public service per 10 000 inhabitants, and number of weekly hours of dentist work in the public service per 10 000 inhabitants. Multiple linear regression models were fitted to the two outcome variables (dmft index and care index). The multiple linear regression analysis showed that a higher dmft index was associated with a low child development index, a high illiteracy rate, and an unfluoridated water supply. The child development index was significantly associated with the care index, and the number of dentists in the public service per 10 000 inhabitants showed borderline statistical significance. Our results indicate that town-level indices of socioeconomic status are significantly correlated with caries indices. Our results also emphasize the beneficial effect that fluoridating water has on reducing the prevalence of dental caries and the fact that strategies for treating and preventing oral diseases should be emphasized within the context of overall health promotion for children.","subset":"pubmed_abstract"} +{"meta":{"pmid":24851372,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"[Idiopathic environmental intolerance: 2 disabling entities to recognize].\nIdiopathic environmental intolerance is characterized by a variety of non-specific symptoms involving several organs within the same individual, and attributed to the exposure to chemical odors (multiple chemical sensitivities) or to the exposure to electromagnetic fields (electromagnetic hypersensitivity). Symptoms occur following an exposure to agents generally regarded as harmless due to the low levels of exposure, and they do not answer to any definition of organic diseases. The lack of established etiology renders treatment difficult. It is important for practitioner to recognize such disorders and assess the social and professional impact so as to improve patients' quality of life.","subset":"pubmed_abstract"} +{"meta":{"pmid":18470947,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":2,"unknown":10}}},"text":"Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion and duplication events revealed by microsatellite analysis.\nThe human Y chromosome shows frequent structural variants, some of which are selectively neutral, while others cause impaired fertility due to the loss of spermatogenic genes. The large-scale use of multiple Y-chromosomal microsatellites in forensic and population genetic studies can reveal such variants, through the absence or duplication of specific markers in haplotypes. We describe Y chromosomes in apparently normal males carrying null and duplicated alleles at the microsatellite DYS448, which lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and made up of \"ampliconic\" repeats that act as substrates for nonallelic homologous recombination (NAHR). Physical mapping in 26 DYS448 deletion chromosomes reveals that only three cases belong to a previously described class, representing independent occurrences of an approximately 1.5-Mb deletion mediated by recombination between the b1 and b3 repeat units. The remainder belong to five novel classes; none appears to be mediated through homologous recombination, and all remove some genes, but are likely to be compatible with normal fertility. A combination of deletion analysis with binary-marker and microsatellite haplotyping shows that the 26 deletions represent nine independent events. Nine DYS448 duplication chromosomes can be explained by four independent events. Some lineages have risen to high frequency in particular populations, in particular a deletion within haplogroup (hg) C(*)(xC3a,C3c) found in 18 Asian males. The nonrandom phylogenetic distribution of duplication and deletion events suggests possible structural predisposition to such mutations in hgs C and G.","subset":"pubmed_abstract"} +{"meta":{"pmid":28650053,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"In situ crystal growth of gold nanocrystals on upconversion nanoparticles for synergistic chemo-photothermal therapy.\nA multifunctional cancer therapy nanocomposite was proposed and synthesized by linking the pH-responsive SH-PEG-DOX prodrug onto gold nanocrystals that were grown in situ on the surface of upconversion nanoparticles (UCNPs). In the structure of the SH-PEG-DOX prodrug, a hydrazone bond was utilized for subsequent pH-responsive drug release in the intracellular acidic microenvironment of cancer cells. This innovative assembly method is facile and mild, and can be used to obtain nanocomposites of UCNPs and gold, which show excellent photostability and biocompatibility. The final UCNPs@Au-DOX nanocomposites offer efficient treatment effects in vitro under irradiation with an 808 nm laser due to the synergistic effect of chemotherapy and photothermal therapy. In addition, the UCNPs@Au-DOX nanocomposites show excellent intracellular locating ability via upconversion luminescence (UCL) imaging with Er3+ ions and magnetic resonance imaging (MRI) with Gd3+ ions, indicating that they have potential as a visual tracking agent in cancer treatment. Therefore, the presented bioimaging-guided multifunctional synergistic therapy nanocomposites are promising tools for imaging-guided cancer therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":21856737,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":2,"unknown":21}}},"text":"Comparative analysis of algorithms for next-generation sequencing read alignment.\nThe advent of next-generation sequencing (NGS) techniques presents many novel opportunities for many applications in life sciences. The vast number of short reads produced by these techniques, however, pose significant computational challenges. The first step in many types of genomic analysis is the mapping of short reads to a reference genome, and several groups have developed dedicated algorithms and software packages to perform this function. As the developers of these packages optimize their algorithms with respect to various considerations, the relative merits of different software packages remain unclear. However, for scientists who generate and use NGS data for their specific research projects, an important consideration is choosing the software that is most suitable for their application. With a view to comparing existing short read alignment software, we develop a simulation and evaluation suite, Seal, which simulates NGS runs for different configurations of various factors, including sequencing error, indels and coverage. We also develop criteria to compare the performances of software with disparate output structure (e.g. some packages return a single alignment while some return multiple possible alignments). Using these criteria, we comprehensively evaluate the performances of Bowtie, BWA, mr- and mrsFAST, Novoalign, SHRiMP and SOAPv2, with regard to accuracy and runtime. We expect that the results presented here will be useful to investigators in choosing the alignment software that is most suitable for their specific research aims. Our results also provide insights into the factors that should be considered to use alignment results effectively. Seal can also be used to evaluate the performance of algorithms that use deep sequencing data for various purposes (e.g. identification of genomic variants). Seal is available as open source at http:\/\/compbio.case.edu\/seal\/. email@example.com Supplementary data are available at Bioinformatics online.","subset":"pubmed_abstract"} +{"meta":{"pmid":22364300,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":3,"2023-14":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-21":1,"2021-04":1,"2020-50":2,"2020-40":1,"2020-29":1,"2020-24":1,"2023-40":1}}},"text":"Effect of high saturated free fatty acids feeding on progression of renal failure in rat model of experimental nephrotoxicity.\nThe current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFD)received an experimental high fat diet rich in palm kernel oil (40% of Calories as fat) for the same period. The third group (HFDG) was given 80 mg\/kg (body weight)\/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":26077475,"dup_signals":{"dup_doc_count":13}},"text":"Emergency Department Visits for Self-Inflicted Injuries in Adolescents.\nTo describe emergency department (ED) visits for self-inflicted injury (SII) among adolescents, examine trends in SII mechanisms, and identify factors associated with increased risk. Analyses included patients aged 10 to 18 years from the National Trauma Data Bank, years 2009 to 2012. We used Cochran-Armitage trend tests to examine change over time and generalized linear models to identify risk factors for SII. We examined 286,678 adolescent trauma patients, 3664 (1.3%) of whom sustained an SII. ED visits for SII increased from 2009 to 2012 (1.1% to 1.6%, P for trend \u2264 .001), whereas self-inflicted firearm visits decreased (27.3% to 21.9%, P for trend = .02). The most common mechanism in males was firearm (34.4%), and in females, cut\/pierce (48.0%). Odds of SII were higher in females (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.13-1.77), older adolescents (OR 2.73, 95% CI 2.38-3.14), adolescents with comorbid conditions (OR 1.64; 95% CI 1.49-1.80), and Asian adolescents (OR 1.67, 95% CI 1.35-2.08) and lower in African American adolescents (OR 0.78, 95% CI 0.70-0.87). Adolescents in the public or self-pay insurance category had higher odds of SII (OR 1.44, 95% CI 1.27-1.64) than those in the private insurance category (OR 1.15, 95% CI 1.01-1.31). Adolescents with an SII had higher odds of death than those with other injuries (OR 12.9, 95% CI 6.78-24.6). We found a significant increase in the number of SIIs by adolescents that resulted in ED visits from 2009 to 2012. Although SIIs increased, we found a significant decrease in the percentage of adolescents who self-injured with a firearm. SIIs reflect a small percentage of ED visits, but these patients have dramatically higher odds of death.","subset":"pubmed_abstract"} +{"meta":{"pmid":22241050,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Deletion of the murein hydrolase CbpD reduces transformation efficiency in Streptococcus thermophilus.\nRecently it has been shown that Streptococcus thermophilus is competent for natural genetic transformation. This property is widespread among streptococci and may include all members of the genus. Upon entering the competent state, streptococci start transcribing a number of competence-specific genes whose products are required for binding, uptake and processing of transforming DNA. In addition to the core competence genes, competent streptococci express a number of accessory genes that are dispensable for transformation in the laboratory, but presumably play an important role under natural conditions. In Streptococcus pneumoniae, one of these accessory genes encodes a competence-specific murein hydrolase termed CbpD. Experimental evidence indicates that pneumococcal CbpD is part of a predatory mechanism that lyses noncompetent sister cells or members of closely related species in order to release homologous DNA that can be taken up by the competent attacker cells. Competent S. thermophilus LMG18311 cells produce a CbpD-like protein, Stu0039, which might have the same or a similar function. In the present study we have characterized this protein and shown that it is a murein hydrolase with a novel type of cell surface-binding domain. Furthermore, we show that Stu0039 is rapidly inactivated by H(2)O(2) produced during aerobic growth of S. thermophilus. We propose that this inactivation mechanism has evolved for self-protection purposes to prevent extensive autolysis in a competent population. Interestingly, in contrast to pneumococcal CbpD, which does not affect the transformation properties of the producer strain, deletion of Stu0039 reduces the transformability of S. thermophilus.","subset":"pubmed_abstract"} +{"meta":{"pmid":19012814,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Obsessive and compulsive symptoms in prediagnosed Huntington's disease.\nObsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease. The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non-gene-expanded controls from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as \"near-to-onset\" (< 9 estimated years to onset), \"mid-to-onset\" (9-15 years to onset), and \"far-to-onset\" (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender. All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying. Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status.","subset":"pubmed_abstract"} +{"meta":{"pmid":16944950,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":2,"unknown":12}}},"text":"Investigating the dynamic nature of the interactions between nuclear proteins and histones upon DNA damage using an immobilized peptide chemical proteomics approach.\nAs a result of the complexity and dynamic range of the cellular proteome, including mutual interactions and interactions with other molecules, focused proteomic approaches are important to study subsets of physiologically important proteins. In one such approach, a small molecule or part of a protein is immobilized on a solid phase and used as bait to fish out interacting proteins from complex mixtures such as cellular lysates. Here, such a chemical proteomics experiment is presented to explore the range of proteins that interact with the N-terminal tail of core histones. Therefore, a core histone consensus N-terminal tail (NTT) peptide was synthesized and immobilized on agarose. Interactions between histone NTTs and proteins are extremely important as they regulate chromatin structure, which is important in many DNA-related processes, like transcription and DNA repair. Induction of DNA damage, like DNA double strand breaks, is known to trigger chromatin remodeling events through interactions between histone NTTs and so-called histone chaperones. Therefore, we set out to investigate specific changes in interactions of nuclear proteins before and shortly after DNA double strand break induction. Over 700 proteins were found to bind specifically to the NTT peptide, which makes our study the most comprehensive proteomic survey of the broad spectrum of nuclear proteins interacting with the NTT of core histones in nucleosomes. Apart from a few exceptions, the abundance of the majority of NTT binding proteins was found to be unchanged following DNA damage. However, an in-depth analysis of protein phosphorylation (we detected more than 90 unique sites in about 60 proteins) revealed that the phosphorylation status of several proteins involved in chromatin remodeling changes upon DNA damage. We observed that in these differentially phosphorylated chaperones are part of closely interacting protein complexes involved in regulatory mechanisms at the crossroads of nucleosome assembly, DNA replication, transcription, and the early onset of DNA damage repair.","subset":"pubmed_abstract"} +{"meta":{"pmid":22580295,"dup_signals":{"dup_doc_count":12}},"text":"Radium dial watches, a potentially hazardous legacy?\nThis study re-examines the risk to health from radium ((226)Ra) dial watches. Ambient dose equivalent rates have been measured for fifteen pocket watches giving results of up to 30 \u03bcSv h(-1) at a distance of 2 cm taken with a series 1000 mini-rad from the front face (arithmetic mean ambient dose equivalent for pocket watches being 13.2 \u03bcSv h(-1)). A pocket compass gave rise to a similar ambient dose equivalent rate, of 20 \u03bcSv h(-1), to the pocket watches, with its cover open. Eighteen wristwatches have also been assessed, but their dose rates are generally much lower (the arithmetic mean being 3.0 \u03bcSv h(-1)), although the highest ambient dose equivalent rate noted was 20 \u03bcSv h(-1). A phantom experiment using a TLD suggested an effective dose equivalent of 2.2 mSv\/y from a 1 \u03bcCi (37 kBq) radium dial worn for 16 h\/day throughout the year (dose rate 0.375 \u03bcSv h(-1)). For this condition we estimated maximum skin dose for our pocket watches as 16 mSv per year, with effective doses of 5.1 mSv and 1.169 mSv when worn in vest and trouser pockets respectively. This assumes exposure from the back of the watch which is generally around 60-67% of that from the front. The maximum skin dose from a wristwatch was 14 mSv, with 4.2 mSv effective dose in vest pocket. Radium ((226)Ra) decays to the radioactive gas radon ((222)Rn), and atmospheric radon concentration measurements taken around a pocket watch in a small sealed glass sphere recorded 18,728 B qm(-3). All watches were placed in a room with a RAD7 real-time radon detector. Radon concentration average was 259\u00b19 Bq m(-3) over 16 h, compared to background average over 24h of 1.02 Bq m(-3). Over 6 weeks highs of the order of 2000 Bq m(-3) were routinely recorded when the heating\/ventilation system in the room was operating at reduced rates, peaking at over 3000 Bq m(-3) on several occasions. Estimates of the activity of (226)Ra in the watches ranged from 0.063 to 1.063 \u03bcCi (2.31 to 39.31 kBq) for pocket watches and from 0.013 to 0.875 \u03bcCi (0.46 to 32.38 kBq) for wrist watches. The risk from old watches containing radium appears to have been largely forgotten today. This paper indicates a health risk, particular to collectors, but with knowledge and appropriate precautions the potential risks can be reduced.","subset":"pubmed_abstract"} +{"meta":{"pmid":12224751,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Constructing scientific authorities: issue framing of chlorinated disinfection byproducts in public health.\nThe practice of chlorine disinfection of drinking water to reduce microbial risks provides substantial benefits to public health. However, increasing concern around potential risks of cancer associated with exposure to chlorinated disinfection byproducts confuses this issue. This article examines the science agenda regarding chlorinated disinfection byproducts (CDBP) and cancer in Canada and the United States, focusing on the social construction of scientific knowledge claims and evidence. Data for this analysis were obtained from published documents as well as from in-depth interviews with epidemiologists and toxicologists centrally involved with the issue in both countries. Results of the analysis suggest that toxicological scientists want to close the door on the \"chloroform issue\" due to increasing evidence that chloroform is safe at low doses, because epidemiological scientists can no longer move forward the cancer science until significant improvements can be made in assessing human exposures, and because the scientific foci of research on DBP have shifted accordingly. Further, a distinction emerges in terms of how scientific uncertainties are interpreted when they cross-cut disciplines in the context of human health risk assessment. We suggest this tension reflects a balance of how uncertainty and authorities are managed in a mandated science-policy domain. Sufficient evidence was provided to keep the DBP issue on the regulatory agenda and to generate additional research, yet authorities and concomitant interpretations of uncertainty were contested. Such science generation and contestation inevitably influences complex risk assessment processes with respect to what water-related health risks are addressed and how.","subset":"pubmed_abstract"} +{"meta":{"pmid":26968875,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2023-50":1}}},"text":"Adjacent segment degeneration after lumbar spinal fusion compared with motion-preservation procedures: a meta-analysis.\nThis meta-analysis aimed to evaluate the efficacy of motion-preservation procedures to prevent the adjacent segment degeneration (ASDeg) or adjacent segment disease (ASDis) compared with fusion in lumbar spine. PubMed, Embase and the Cochrane Library were comprehensively searched and a meta-analysis was performed of all randomized controlled trials and well designed prospective or retrospective comparative cohort studies assessing the lumbar fusion and motion-preservation procedures. We compared the ASDeg and ASDis rate, reoperation rate, operation time, blood loss, length of hospital stay, visual analogue scale (VAS) and oswestry disability index (ODI) improvement of the two procedures. A total of 15 studies consisting of 1474 patients were included in this study. The meta-analysis indicated that the prevalence of ASDeg, ASDis and reoperation rate on the adjacent level were lower in motion-preservation procedures group than in the fusion group (P = 0.001; P = 0.0004; P < 0.0001). Moreover, shorter length of hospital stay was found in motion-preservation procedures group (P < 0.0001). No difference was found in terms of operation time (P = 0.57), blood loss (P = 0.27), VAS (P = 0.76) and ODI improvement (P = 0.71) between the two groups. The present evidences indicated that the motion-preservation procedures had an advantage on reducing the prevalence of ASDeg, ASDis and the reoperation rate due to the adjacent segment degeneration compared with the lumbar fusion. And the clinical outcomes of the two procedures are similar.","subset":"pubmed_abstract"} +{"meta":{"pmid":17900379,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Multiple functions of cation-chloride cotransporters in the fish retina.\nA GABA- or glycine-induced increase in Cl(-) permeability can produce either a depolarization or hyperpolarization, depending on the Cl(-) equilibrium potential. It has been shown that retinal neurons express the chloride cotransporters, Na-K-2Cl (NKCC) and K-Cl (KCC), the primary molecular mechanisms that control the intracellular Cl(-) concentration. We thus studied (1) the localization of these cotransporters in the fish retina, and (2) how suppression of cotransporter activity in the fish retina affects function. Specific antibodies against NKCC and KCC2 revealed that both cotransporters were expressed in the outer and inner plexiform layers, and colocalized in many putative amacrine cells and in cells of the ganglion cell layer. However, the somata of putative horizontal cells displayed only NKCC immunoreactivity and many bipolar cells were only immunopositive for KCC2. In the outer retina, application of bumetanide, a specific inhibitor of NKCC activity, (1) increased the steady-state extracellular concentration of K+ ([K+](o)) and enhanced the light-induced decrease in the [K+](o), (2) increased the sPIII photoreceptor-dependent component of the ERG, and (3) reduced the extracellular space volume. In contrast, in the outer retina, application of furosemide, a specific inhibitor of KCC activity, decreased sPIII and the light-induced reduction in [K+](o), but had little effect on steady-state [K+](o). In the inner retina, bumetanide increased the sustained component of the light-induced increase in [K+](o). These findings thus indicate that NKCC and KCC2 control the [K+](o) and extracellular space volume in the retina in addition to regulating GABA- and glycine-mediated synaptic transmission. In addition, the anatomical and electrophysiological results together suggest that all of the major neuronal types in the fish retina are influenced by chloride cotransporter activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":22346143,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Surface fragmented QRS in a patient with hypertrophic cardiomyopathy and malignant arrhythmias: Is there an association?\nAn 18- year old woman with hypertrophic cardiomyopathy, aborted sudden cardiac death and implanted with an implantable cardioverter defibrillator (ICD), developed progressive fragmentation of her surface 12-lead electrocardiogram (ECG). During the follow-up, she presented with multiple appropriate ICD discharges. Here, we discuss the possible association between surface fragmented ECG and the risk of ventricular arrhythmias in patients with hypertrophic cardiomyopathy.","subset":"pubmed_abstract"} +{"meta":{"pmid":27572143,"dup_signals":{"dup_doc_count":28,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-50":2,"2021-25":1,"2020-34":1,"2019-22":1,"2019-18":2,"2019-09":2,"2018-30":2,"2018-13":2,"2017-51":4,"2017-43":2,"2017-34":2,"2024-26":2,"2024-30":1}}},"text":"Economic Burden of Mental Illnesses in Pakistan.\nThe economic consequences of mental illnesses are much more than health consequences. In Low and Middle Income Countries (LMIC) the economic impact of mental illnesses is rarely analyzed. This paper attempts to fill the gap in research on economics of mental health in LMIC. We provide economic burden of mental illness in Pakistan that can serve as an argument for reorienting health policy, resource allocation and priority settings. To estimate economic burden of mental illnesses in Pakistan. The study used prevalence based cost of illnesses approach using bottom-up costing methodology. We used Aga Khan University Hospital, Psychiatry department data set (N = 1882) on admission and ambulatory care for the year 2005-06. Healthcare cost data was obtained from finance department of the hospital. Productivity losses, caregiver and travel cost were estimated using socio-economic features of patients in the data set and data of national household survey. We used stratified random sampling and methods of ordinary least square multiple linear regressions to estimate cost on medicines for ambulatory care. All estimates of cost are based on 1000 bootstrap samples by ICD-10 disease classification. Prevalence data on mental illnesses from Pakistan and regional countries was used to estimate economic burden. The economic burden of mental illnesses in Pakistan was Pakistan Rupees (PKR) 250,483 million (USD 4264.27 million) in 2006. Medical care costs and productivity losses contributed 37% and 58.97% of the economic burden respectively. Tertiary care admissions costs were 70% of total medical care costs. The average length of stay (LOS) for admissions care was around 8 days. Daily average medical care cost of admitted patients was PKR 3273 (USD 55.72). For ambulatory care, on average a patient visited the clinic twice a year. The estimated average yearly cost for all mental illnesses was PKR 81,922 (USD 1394.65) and PKR 19,592 (USD 333.54) for admissions and ambulatory care respectively. In the sensitivity analysis productivity losses showed high variability (from USD 1022.17 million to USD 4007.01 million). Assuming a gate keeping role of primary healthcare (PHC) demonstrated a saving of USD 1577.19 million in total economic burden. This study set out to generate evidence using a low cost innovative approach relevant to many LMICs. In Pakistan, like many LMICs, patients access tertiary care directly, even for illness that can be efficiently managed at PHC level. In economic terms the non-medical consequences of mental illnesses are far greater than medical consequences. Based on these finding we recommend, firstly, that mental illnesses should be prioritized equally as other illnesses in health policy and secondly there needs to be integration of mental health in primary health care in Pakistan.","subset":"pubmed_abstract"} +{"meta":{"pmid":8110529,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-10":1,"2024-30":1}}},"text":"The epidemiology of vertebral fractures. European Vertebral Osteoporosis Study Group.\nVertebral fractures are recognised as a hallmark of osteoporosis, yet little is known of their epidemiology. This deficiency limits accurate characterisation of the public health importance of osteoporosis. Assessment of the impact of vertebral fractures has been hampered by the absence of formal criteria for identifying fractures on a thoracolumbar radiograph. Initial methods relying upon subjective radiological assessments have given way to morphometric measurements of vertebral heights, with deformities defined according to various algorithms. These methods have been used in a series of studies performed in Rochester, MN, to determine the incidence, outcome, and time trends of vertebral deformities. The results suggest a prevalence rate of vertebral deformity of 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), with an estimated incidence of 17.8 per 1,000 person-years. The incidence of clinically diagnosed vertebral fractures among women in the same population was 5.3 per 1,000 person-years, suggesting that around 30% of such deformities in women receive clinical attention. Morphometric measurement on the radiographs of women with clinically diagnosed fractures revealed that 80% had grade 2 ( > 4 SD) deformities. Comparable data on the occurrence and health impact of vertebral deformities throughout Europe are urgently required. The European Vertebral Osteoporosis Study (EVOS) is a multicentre epidemiological study that aims to address this issue. It is designed as a radiographic prevalence study in 34 European centres.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":29790876,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Novel chemiluminescent immunochromatographic assay using a dual-readout signal probe for multiplexed detection of pesticide residues.\nA novel immunochromatographic assay (ICA) using a dual-readout signal probe was developed for multiplexed detection of pesticide residues by adopting methyl parathion and fenpropathrin as model analytes. Luminol-reduced Au nanoparticles (LRAuNPs) were synthesized and utilized in the proposed ICA platform as a colorimetric\/chemiluminescent (CL) dual-readout probe. The methyl parathion antibody and fenpropathrin antibody were tagged with the prepared LRAuNPs to conduct spatially-resolved multiplexed detection. After the occurrence of two immunoreactions on the test strip, the probes were captured by the immobilized antigens on the two test zones. The red color resulting from the accumulation of captured LRAuNPs was adopted as the visual and semi-quantitative readout. For the sensitive quantitative detection of the analytes, the CL signals caused by the luminophore in the LRAuNPs were collected after triggering the luminol-H2O2 CL reaction. Under the optimal conditions, the detection limits for methyl parathion and fenpropathrin were 0.17 ng mL-1 and 0.10 ng mL-1 (S\/N = 3), respectively. The whole procedure for ICA was completed within 15 min. The present ICA protocol was successfully applied for detection of pesticide residues in spiked traditional Chinese medicine samples. This dual-readout ICA platform showed merits such as low cost, time efficiency, easy operation and high sensitivity. Its application potential has been demonstrated in the rapid screening and field detection of multiple pesticide residues.","subset":"pubmed_abstract"} +{"meta":{"pmid":15824132,"dup_signals":{"dup_doc_count":28,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":1,"2015-06":1,"2017-13":1,"unknown":21}}},"text":"Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.\nDegradation of specific protein substrates by the anaphase-promoting complex\/cyclosome (APC) is critical for mitotic exit. We have identified the protein Xenopus nuclear factor 7 (Xnf7) as a novel APC inhibitor able to regulate the timing of exit from mitosis. Immunodepletion of Xnf7 from Xenopus laevis egg extracts accelerated the degradation of APC substrates cyclin B1, cyclin B2, and securin upon release from cytostatic factor arrest, whereas excess Xnf7 inhibited APC activity. Interestingly, Xnf7 exhibited intrinsic ubiquitin ligase activity, and this activity was required for APC inhibition. Unlike other reported APC inhibitors, Xnf7 did not associate with Cdc20, but rather bound directly to core subunits of the APC. Furthermore, Xnf7 was required for spindle assembly checkpoint function in egg extracts. These data suggest that Xnf7 is an APC inhibitor able to link spindle status to the APC through direct association with APC core components.","subset":"pubmed_abstract"} +{"meta":{"pmid":9451501,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Temperature titration: a new approach to the thermodynamics of oxygen binding to hemoglobin.\nA cell was constructed in order to study hemoglobin's reaction with gaseous ligands. The temperature of the hemoglobin sample is systematically altered within a given temperature range (275-310 degrees K), while the percentage of oxygen in the equilibrating gas is kept constant. The equilibration time of the sample at each temperature step depends on sample concentration, ligand affinity, and absolute temperature; in most cases, the equilibration time is on the order of minutes. The construction of the optical compartment allows the experimenter to vary the optical pathlength using specially designed spacers, thus making it possible to study hemoglobin-ligand interactions over a wide range of protein concentrations (0.1-200 mg\/ml). Optical glass is used in the construction of the cuvette in order to optimize its optical stability over a long period of time. At equilibrium the absorption spectrum of the sample is collected and decomposed into the relative contributions of oxy-Hb, deoxy-Hb, and ferric-Hb, thus revealing the fraction of oxyhemoglobin as well as any baseline drifts and protein degradation. Temperature steps of 1 degree K are already sufficient to change the absorption spectra in a significant way. This type of setup is also advantageous in that the experimenter can change the sample at any point (temperature) without having to restart the entire experiment. This makes it possible to study the oxygen binding characteristics of unstable hemoglobins. Analyses of the binding curves obtained with this technique immediately yield the overall oxygen binding constants beta i together with the respective standard enthalpies delta H(i).","subset":"pubmed_abstract"} +{"meta":{"pmid":26864502,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Improved chemical and mechanical stability of peptoid nanosheets by photo-crosslinking the hydrophobic core.\nPeptoid nanosheets can be broadly functionalized for a variety of applications. However, they are susceptible to degradation when exposed to chemical or mechanical stress. To improve their strength, photolabile monomers were introduced in order to crosslink the nanosheet interior. Photo-crosslinking produced a more robust material that can survive sonication, lyophilization, and other biochemical manipulations.","subset":"pubmed_abstract"} +{"meta":{"pmid":11843445,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-20":1,"2017-13":1,"unknown":9}}},"text":"Fracture resistance of all-ceramic and metal-ceramic inlays.\nMetal-ceramic inlay designs were developed to determine if the esthetic qualities of all-ceramic inlays could be duplicated and at the same time improve their strength and stability. The objectives of this study were to: (1) compare the fracture resistance of metal-ceramic inlays with that of all-ceramic inlays; (2) determine the correlation between the degree of preparation taper and fracture resistance; and (3) determine the correlation between marginal gap width and fracture resistance. Inlay preparations were made on 60 Dentoform teeth, with 30 teeth allocated for metal-ceramic inlays and 30 teeth for all-ceramic inlays. Each group was further subdivided into 5-, 10-, and 20-degree taper preparations. Metal-ceramic inlays were fabricated using Goldtech Bio 2000 metal and Ceramco porcelain extending to the margin, while all-ceramic inlays were made from Empress II ceramic. Marginal gap widths were measured at six critical areas after fabrication. The load at failure was measured using an Instron Universal Testing Machine. The mean fracture load for all-ceramic inlays and metal-ceramic inlays at 5, 10, and 20 degrees was 70+\/-40 N, 48+\/-37 N, 33+\/-7 N, and 40+\/-23 N, 29+\/-22 N, and 14+\/-4 N, respectively. The mean gap width was 105 microm and 126 microm for all-ceramic and metal-ceramic inlays, respectively. The mean fracture load for Empress inlays was significantly higher than that for metal-ceramic inlays. Inlays with a 5-degree taper were significantly more fracture resistant than those with a 20-degree taper. There was no relation between marginal gap width and fracture resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":19285616,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Changing patterns of bridging to heart transplantation in children.\nMechanical support as a bridge to cardiac transplantation in children is an accepted treatment. With improved devices and increasing experience, the length of time that children can be supported has increased. Donor organs remain scarce and there is significant associated morbidity. Retrospective review of all children offered mechanical support as a bridge to heart transplant over 10 years in one of the two UK pediatric heart transplant centers. Outcomes during the years 1998 to 2002 were compared with outcomes during the years 2003 to 2007. Forty children in 41 separate patient episodes received mechanical support as a bridge to transplantation or, in 1 case, to recovery. Survival to transplant or recovery was achieved in 29 of 41 (71%); 26 of 40 children (63%) survived to hospital discharge. Devices used were extracorporeal membrane oxygenation (ECMO), the Medos HIAA, the Berlin Heart (from November 2005) and the Levitronix ventricular assist device (VAD) from 2007. All 3 children supported with the Levitronix survived to transplant (median duration of support 10 days). Ten of 13 children (77%) supported by the Berlin Heart survived to transplant or recovery (median duration of support 44 days). Four of 7 (57%) children supported using the Medos device survived to transplant (median duration of support 7 days). Neurologic events were the most common cause of death in both eras (1998 to 2002 and 2003 to 2008). Waiting times to pediatric cardiac transplant in the UK have increased. The Berlin Heart allows children to be bridged to transplant over long periods. Neurologic morbidity remains as a major concern.","subset":"pubmed_abstract"} +{"meta":{"pmid":19828083,"dup_signals":{"dup_doc_count":27,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2018-47":1,"2018-39":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-43":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2019-04":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-11":1}}},"text":"XML-based approaches for the integration of heterogeneous bio-molecular data.\nThe today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":28983617,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":4,"unknown":9}}},"text":"CREB1 and Smad3 mediate TGF\u2011\u03b23\u2011induced Smad7 expression in rat hepatic stellate cells.\nTransforming growth factor (TGF)\u2011\u03b23 has previously been reported to antagonize hepatic fibrosis in vivo and in vitro. The present study aimed to investigate the mechanism underlying the involvement of TGF\u2011\u03b23 in hepatic fibrosis. Short hairpin (sh)RNA\u2011cAMP-responsive element binding protein (CREB) 1 and small interfering (si)RNA\u2011Smad3 were utilized to silence the expression of CREB1 and Smad3 in hepatic stellate cells (HSCs), whereas the vector pRSV\u2011CREB1 was used to induce CREB1 overexpression in HSCs. Cells were treated with or without exogenous TGF\u2011\u03b23 or TGF\u2011\u03b21, and mRNA and protein expression levels were assessed using reverse transcription\u2011quantitative polymerase chain reaction and western blot analysis. Untreated cells served as the control group. Exogenous TGF\u2011\u03b23 increased Smad7 mRNA and protein expression levels in rat HSCs, and CREB1 and Smad3 appeared to be implicated in the mechanism of Smad7. CREB1 knockdown inhibited the TGF\u2011\u03b23\u2011induced upregulation of Smad7, whereas its overexpression potentiated the Smad7 upregulation in HSCs; conversely, CREB1 manipulations had no effect on Smad7 expression under basal conditions. In addition, TGF\u2011\u03b23\u2011induced Smad7 upregulation was blocked when the activity of p38, a kinase upstream of CREB1, was inhibited. Furthermore, silencing Smad3 resulted in decreased Smad7 expression under basal conditions and in TGF\u2011\u03b23\u2011stimulated cells. Notably, Smad7 expression appeared to also be induced by exogenous TGF\u2011\u03b21, independent of CREB1. The present study demonstrated that TGF\u2011\u03b23 increased Smad7 expression in HSCs, whereas CREB1 and Smad3 appeared to participate in the mechanism of induction. Smad3 is the key regulator whereas CREB\u20111 acts as a co\u2011regulator. These results suggested that this mechanism may underlie the antagonizing effects of TGF\u2011\u03b23 on hepatic fibrosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":23399313,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-06":1,"2022-40":2,"2022-21":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-34":1,"2020-24":1,"2023-50":1}}},"text":"Factor structure and construct validity of the psychopathic personality inventory in a forensic sample.\nA wealth of research has underscored the strong relationship between PCL-R scores and recidivism. However, mounting criticism cites the PCL-R's cumbersome administration procedures and failure to adequately measure core features associated with the construct of psychopathy (Skeem, Polaschek, Patrick, & Lilienfeld, 2011). In light of these concerns, this study examined the PPI and the PPI-R, which were designed to measure core personality features associated with psychopathy (Lilienfeld & Andrews, 1996; Lilienfeld & Widows, 2005). Study one examined the PPI relative to the PCL-R and examined its factor structure. The instruments shared few significant correlations and neither the PCL-R nor the PPI significantly predicted recidivism. Study two examined the PPI-R relative to the PCL-R, the PPI, both history of violence and future criminal activity and measure of related constructs. The PPI-R was significantly correlated with measures of empathy and criminal thinking and the factors were related to a history of violence and predicted future violent criminal behavior.","subset":"pubmed_abstract"} +{"meta":{"pmid":28791869,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Study of Compression-Induced Supramolecular Nanostructures of an Imidazole Derivative by Langmuir-Blodgett Technique.\nIn this communication, we report the design and synthesis as well as the supramolecular assembly behavior of a 2,4,5-triaryl imidazole derivative (compound 1) at the air-water interface and in thin films using Langmuir-Blodgett (LB) technique. The main idea for such a chemical structure is that the long alkyl chain and N-H of the imidazole core may help to form supramolecular architecture through the hydrophobic-hydrophobic interaction and hydrogen bonding, respectively. Accordingly, the interfacial behavior as well as morphology of 1 in thin films were studied through a series of characterization methods such as surface pressure-area (\u03c0-A) isotherm, hysteresis analysis, ultraviolet-visible (UV-vis) absorption and steady-state fluorescence spectroscopies, Fourier transform infrared, X-ray diffraction, Brewster angle microscopy (BAM), and atomic force microscopy (AFM) measurements, and so forth. Pressure-area isotherm is an indication toward the formation of supramolecular nanostructures instead of an ideal monolayer at the air-water interface. This has been confirmed by the hysteresis analysis and BAM measurement at the air-water interface. AFM images of 1 in the LB monolayer exhibits the formation of supramolecular nanowires as well as nanorods. By controlling different film-forming parameters, it becomes possible to manipulate these nanostructures. With the passage of time, the nanowires come close to each other and become straight. Similarly, nanorods come close to each other and form bundles of several rods in the LB films. H-bonding, J-aggregation, as well as compression during film formation might play a key role in the formation of such nanostructures. Electrical switching behavior of compound 1 was also observed because of the presence of an electron donor-acceptor system in 1. This type of organic switching behavior may be promising for next-generation organic electronics.","subset":"pubmed_abstract"} +{"meta":{"pmid":29223929,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-14":1,"2023-06":1,"2021-04":1,"2020-45":1,"2019-18":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2023-50":1}}},"text":"The minimum monitoring signal-to-noise ratio for off-axis signals and its implications for directional hearing aids.\nThe signal-to-noise ratio (SNR) benefit of hearing aid directional microphones is dependent on the angle of the listener relative to the target, something that can change drastically and dynamically in a typical group conversation. When a new target signal is significantly off-axis, directional microphones lead to slower target orientation, more complex movements, and more reversals. This raises the question of whether there is an optimal design for directional microphones. In principle an ideal microphone would provide the user with sufficient directionality to help with speech understanding, but not attenuate off-axis signals so strongly that orienting to new signals was difficult or impossible. We investigated the latter part of this question. In order to measure the minimal monitoring SNR for reliable orientation to off-axis signals, we measured head-orienting behaviour towards targets of varying SNRs and locations for listeners with mild to moderate bilateral symmetrical hearing loss. Listeners were required to turn and face a female talker in background noise and movements were tracked using a head-mounted crown and infrared system that recorded yaw in a ring of loudspeakers. The target appeared randomly at \u00b1 45, 90 or 135\u00b0 from the start point. The results showed that as the target SNR decreased from 0 dB to -18 dB, first movement duration and initial misorientation count increased, then fixation error, and finally reversals increased. Increasing the target angle increased movement duration at all SNRs, decreased reversals (above -12 dB target SNR), and had little to no effect on initial misorientations. These results suggest that listeners experience some difficulty orienting towards sources as the target SNR drops below -6 dB, and that if one intends to make a directional microphone that is usable in a moving conversation, then off-axis attenuation should be no more than 12 dB.","subset":"pubmed_abstract"} +{"meta":{"pmid":30845509,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Morphological, Pathogenic, and Genetic Comparisons of Colletotrichum graminicola Isolates from Poaceae.\nIsolates of Colletotrichum graminicola from annual blue grass and creeping bent grass were investigated for their morphological characteristics, host specificity, and genetic relatedness. One isolate from maize and one from sorghum (C. sublineolum) were included for comparison. Recently isolated cultures of C. graminicola from annual blue grass were readily distinguished from those isolated from creeping bent grass on the basis of pigmentation. Differences in appressoria size and shape were found only between the turf grass isolates and those from maize and sorghum. Spore length varied significantly between host groups. Differences in host range and virulence were also apparent. In general, isolates from creeping bent grass incited disease on both creeping bent grass and annual blue grass, while those from annual blue grass essentially were limited to host. Random amplified polymorphic DNA (RAPD) marker analysis of C. graminicola isolates from turf grass revealed that a high degree of genetic similarity exists among isolates recovered from the same host, but exceptions were found. Therefore, an absolute distinction between isolates recovered from two turf grass hosts could not be made based on RAPD markers.","subset":"pubmed_abstract"} +{"meta":{"pmid":21427169,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"RNA-induced silencing complex-bound small interfering RNA is a determinant of RNA interference-mediated gene silencing in mice.\nDeeper knowledge of pharmacokinetic and pharmacodynamic (PK\/PD) concepts for RNA therapeutics is important to streamline the drug development process and for rigorous selection of best performing drug candidates. Here we characterized the PK\/PD relationship for small interfering RNAs (siRNAs) targeting luciferase by examining siRNA concentration in plasma and liver, the temporal RNA-induced silencing complex binding profiles, mRNA reduction, and protein inhibition measured by noninvasive bioluminescent imaging. A dose-dependent and time-related decrease in bioluminescence was detected over 25 days after a single treatment of a lipid nanoparticle-formulated siRNA targeting luciferase messenger RNA. A direct relationship was observed between the degree of in vivo mRNA and protein reduction and the Argonaute2 (Ago2)-bound siRNA fraction but not with the total amount of siRNA found in the liver, suggesting that the Ago2-siRNA complex is the key determinant of target inhibition. These observations were confirmed for an additional siRNA that targets endogenously expressed Sj\u00f6gren syndrome antigen B (Ssb) mRNA, indicating that our observations are not limited to a transgenic mouse system. Our data provide detailed information of the temporal regulation of siRNA liver delivery, Ago2 loading, mRNA reduction, and protein inhibition that are essential for the rapid and cost-effective clinical development of siRNAs therapeutics.","subset":"pubmed_abstract"} +{"meta":{"pmid":1429275,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2019-30":1,"2019-26":1,"2019-09":1,"2019-04":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-17":1,"2017-09":1,"2021-21":1,"2017-13":1}}},"text":"Differences in heritability estimates from multiple-trait and repeated-records models.\nAnalyses of ovulation rates in consecutive estrous cycles with multiple-trait and repeated-records animal models resulted in different estimates of heritability. The estimate from the repeated-records model was seen to be approximately the product of the average genetic correlation and the average heritability from the multiple-trait procedure. A simple model is used to show algebraically that such a result is expected, particularly if the environmental correlations are small among records of the same animal. Comparison of results of the two types of analyses of 10 replications of 10 combinations of underlying heritabilities and genetic correlations confirms this explanation.","subset":"pubmed_abstract"} +{"meta":{"pmid":30645333,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Different measures of speckle and coherence at the output of a multimode optical fiber.\nExcitation of a multimode fiber with a focused spatially coherent light of finite bandwidth results in a partially coherent light at the output of the fiber. Here we study the properties of speckle and classical coherence of such light with analytical theory, numerical modeling, and experimentally. Of particular interest is the relationship between measures of coherence and speckle and their dependence on input source bandwidth and fiber length. Speckle contrast is easy to measure experimentally and there exist at least two different methods to generate ensembles of random speckles. We show that speckle contrast evaluated over the ensemble of external diffusers is related to the number of effective modes-one of the characteristics of beam global coherence. The other speckle contrast measure evaluated over the ensemble of random bends and twists of the fiber is related to residual coherence, which is the pedestal on the average modulus of the complex degree of the coherence function on the output endface of the fiber.","subset":"pubmed_abstract"} +{"meta":{"pmid":24998179,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Setting-up an in vitro model of rat blood-brain barrier (BBB): a focus on BBB impermeability and receptor-mediated transport.\nThe blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and characterize a highly reproducible rat syngeneic in vitro model of the BBB using co-cultures of primary rat brain endothelial cells (RBEC) and astrocytes to study receptors involved in transcytosis across the endothelial cell monolayer. Astrocytes were isolated by mechanical dissection following trypsin digestion and were frozen for later co-culture. RBEC were isolated from 5-week-old rat cortices. The brains were cleaned of meninges and white matter, and mechanically dissociated following enzymatic digestion. Thereafter, the tissue homogenate was centrifuged in bovine serum albumin to separate vessel fragments from nervous tissue. The vessel fragments underwent a second enzymatic digestion to free endothelial cells from their extracellular matrix. The remaining contaminating cells such as pericytes were further eliminated by plating the microvessel fragments in puromycin-containing medium. They were then passaged onto filters for co-culture with astrocytes grown on the bottom of the wells. RBEC expressed high levels of tight junction (TJ) proteins such as occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. The transendothelial electrical resistance (TEER) of brain endothelial monolayers, indicating the tightness of TJs reached 300 ohm x cm(2) on average. The endothelial permeability coefficients (Pe) for lucifer yellow (LY) was highly reproducible with an average of 0.26 \u00b1 0.11 x 10(-3) cm\/min. Brain endothelial cells organized in monolayers expressed the efflux transporter P-glycoprotein (P-gp), showed a polarized transport of rhodamine 123, a ligand for P-gp, and showed specific transport of transferrin-Cy3 and DiILDL across the endothelial cell monolayer. In conclusion, we provide a protocol for setting up an in vitro BBB model that is highly reproducible due to the quality assurance methods, and that is suitable for research on BBB transporters and receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":37551712,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":13,"unknown":2}}},"text":"A combination of metformin and galantamine exhibits synergistic benefits in the treatment of sarcopenia.\nAge-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1-\/-). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01-treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28812915,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Kardiovize Brno 2030, a prospective cardiovascular health study in Central Europe: Methods, baseline findings and future directions.\nBackground Atherosclerotic cardiovascular disease is highly prevalent in Eastern and Central Europe, where the incidence is the highest in the world. The Kardiovize Brno 2030 study was designed as a prospective cohort study to investigate the complex relationships of cardiovascular disease and outcomes with a range of biological, psychosocial, environmental, behavioral, and economic factors in an urban population of the Czech Republic. Methods We randomly selected a 1% sample of the city of Brno residents aged 25-64 years stratified by sex and age. The study assessed traditional and novel cardiovascular disease risk factors, including sociodemographic and smoking status, physical activity, diet, depression, stress, body fat, cardio-ankle vascular index, and intima media thickness, complemented by blood tests; biological samples were stored for future analyses. Results The study enrolled 2160 participants (54.8% women), with a mean age of 47 \u00b1 11.3 years. They were mostly full-time employed (75.6%) and married (62.1%). Hyperlipidemia was highly prevalent (70.7% in men, and 67.1% in women, NS). Hypertension and diabetes mellitus were more prevalent in men than in women (54.3% vs. 38.7% and 7.1% vs. 3.5%, respectively, P < 0.001 for both). A total of 25.3% of men and 21.9% of women smoked, whereas 20.0% and 43.0% of men and 18.1% and 26.6% of women were obese and overweight, respectively. Conclusions Cardiovascular risk factors are highly prevalent in the city of Brno, an urban population from Central Europe. The Kardiovize Brno 2030 study will provide unique multidimensional and longitudinal cardiovascular health data from a region where epidemiological studies are scarce.","subset":"pubmed_abstract"} +{"meta":{"pmid":29154033,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":1,"2022-21":3,"2021-43":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":2,"2021-04":1,"2020-45":1,"2023-23":1,"2024-10":1,"2024-18":1}}},"text":"Measuring preschool learning engagement in the laboratory.\nLearning engagement is a critical factor for academic achievement and successful school transitioning. However, current methods of assessing learning engagement in young children are limited to teacher report or classroom observation, which may limit the types of research questions one could assess about this construct. The current study investigated the validity of a novel assessment designed to measure behavioral learning engagement among young children in a standardized laboratory setting and examined how learning engagement in the laboratory relates to future classroom adjustment. Preschool-aged children (N = 278) participated in a learning-based Tangrams task and Story sequencing task and were observed based on seven behavioral indicators of engagement. Confirmatory factor analysis supported the construct validity for a behavioral engagement factor composed of six of the original behavioral indicators: attention to instructions, on-task behavior, enthusiasm\/energy, persistence, monitoring progress\/strategy use, and negative affect. Concurrent validity for this behavioral engagement factor was established through its associations with parent-reported mastery motivation and pre-academic skills in math and literacy measured in the laboratory, and predictive validity was demonstrated through its associations with teacher-reported classroom learning behaviors and performance in math and reading in kindergarten. These associations were found when behavioral engagement was observed during both the nonverbal task and the verbal story sequencing tasks and persisted even after controlling for child minority status, gender, and maternal education. Learning engagement in preschool appears to be successfully measurable in a laboratory setting. This finding has implications for future research on the mechanisms that support successful academic development.","subset":"pubmed_abstract"} +{"meta":{"pmid":16113242,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2023-23":3,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2023-40":1,"2024-10":1,"2024-18":1}}},"text":"Isolation of a small molecule inhibitor of DNA base excision repair.\nThe base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic\/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":27611569,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-49":1,"2022-27":1,"2021-43":1,"2021-17":1,"2020-40":1,"2020-24":1,"2019-30":1,"2019-22":1,"2019-18":1,"2019-04":1,"2023-50":1}}},"text":"Epidemiology and outcomes of out-of-hospital cardiac arrest in Qatar: A nationwide observational study.\nOut-of-hospital cardiac arrest (OHCA) studies from the Middle East and Asian region are limited. This study describes the epidemiology, emergency health services, and outcomes of OHCA in Qatar. This was a prospective nationwide population-based observational study on OHCA patients in Qatar according to Utstein style guidelines, from June 2012 to May 2013. Data was collected from various sources; the national emergency medical service, 4 emergency departments, and 8 public hospitals. The annual crude incidence of presumed cardiac OHCA attended by EMS was 23.5 per 100,000. The age-sex standardized incidence was 87.8 per 100,000 population. Of the 447 OHCA patients included in the final analysis, most were male (n=360, 80.5%) with median age of 51years (IQR=39-66). Frequently observed nationalities were Qatari (n=89, 19.9%), Indian (n=74, 16.6%) and Nepalese (n=52, 11.6%). Bystander cardiopulmonary resuscitation (CPR) was carried out in 92 (20.6%) OHCA patients. Survival rate was 8.1% (n=36) and multivariable logistic regression indicated that initial shockable rhythm (OR 13.4, 95% CI 5.4-33.3, p=0.001) was associated with higher odds of survival while male gender (OR 0.27, 95% CI 0.1-0.8, p=0.01) and advanced cardiac life support (ACLS) (OR 0.15, 95% CI 0.04-0.5, p=0.02) were associated with lower odds of survival. Standardized incidence and survival rates were comparable to Western countries. Although expatriates comprise more than 80% of the population, Qataris contributed 20% of the total cardiac arrests observed. There are significant opportunities to improve outcomes, including community-based CPR and defibrillation training.","subset":"pubmed_abstract"} +{"meta":{"pmid":16217711,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Atypical MRI findings in Canavan disease: a patient with a mild course.\nCanavan disease is a severe, progressive leukodystrophy with an autosomal recessive inheritance, caused by aspartoacylase (ASPA) deficiency. The characteristic MRI features include diffuse, symmetrical white matter degeneration in the subcortical areas, with bilateral involvement of the globus pallidus. Proton magnetic resonance spectroscopy of the brain shows an increase in the concentration of N-acetylaspartic acid (NAA). The altered NAA metabolism has been traced to mutations in the gene encoding ASPA, located on chromosome 17 (17p13-ter). We present here a patient with a mild form of Canavan disease confirmed with the absent ASPA activity, atypical MRI findings, related to compound heterozygosity for a missense mutation, p.Tyr288Cys, and the known pan-European mutation, the p.Ala305Glu.","subset":"pubmed_abstract"} +{"meta":{"pmid":28959367,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Elacridar, a third-generation ABCB1 inhibitor, overcomes resistance to docetaxel in non-small cell lung cancer.\nDocetaxel is a third-generation chemotherapeutic drug that is widely used in the treatment of patients with non-small cell lung cancer (NSCLC). However, the majority of patients with NSCLC eventually acquire resistance to the treatment. In the present study, the mechanism of acquired resistance to docetaxel treatment in lung cancer cells was investigated. The three NSCLC cell lines, H1299 with wild-type epidermal growth factor receptor (EGFR), EGFR-mutant HCC4006 and HCC827, and experimentally established docetaxel-resistant (DR) cells, H1299-DR, HCC827-DR, and HCC4006-DR were used with stepwise increases in concentrations of docetaxel. It was demonstrated that the established cell lines showed resistance to docetaxel and EGFR-tyrosine kinase inhibitors (TKIs). Molecular analysis revealed that all of the resistant cell lines highly expressed ATP binding cassette subfamily B member 1 (ABCB1), which is also known as P-glycoprotein or MDR1. Furthermore, HCC827-DR and HCC4006-DR cells exhibited a cancer stem cell-like marker and epithelial-to-mesenchymal transition features, respectively. Elacridar (GF120918), a third-generation inhibitor of ABCB1, was able to overcome resistance to docetaxel. Additionally, knockdown of ABCB1 using small interfering RNA (si)-ABCB1 recovered sensitivity to docetaxel. However, elacridar and si-ABCB1 could not recover sensitivity to EGFR-TKIs in established resistant cells. The results of the present study revealed that docetaxel-resistant NSCLC cells also acquired cross-resistance to EGFR-TKI therapy through mechanisms other than ABCB1, that ABCB1 serves an important role in acquired resistance to docetaxel in lung cancer, and that combination therapy with elacridar can overcome ABCB1-mediated docetaxel resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":19655487,"dup_signals":{"dup_doc_count":11,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":2}}},"text":"Biologic height-width ratio of the buccal supra-implant mucosa.\nRecently, esthetic implant dentistry has focused on changes in buccal implant mucosal height. The purpose of this article was to investigate the relationship between the height and width of buccal supra-implant mucosa based on the physiologic mucosal form surrounding the implant. Fourteen patients who had buccal supra-implant mucosal heights of more than 1.5 mm and keratinized mucosa 1 year or more after superstructure placement (average period: 3 years 5 months) were studied. Silicone impressions were taken immediately after superstructures and abutments were removed. The study model used for the measurement process was manufactured using improved dental stone. The height and width of the buccal supra-implant mucosa were measured using digital slide calipers, and the ratio of the height and width was investigated. In all cases, the widths were greater than the heights. The average height of the buccal supra-implant mucosa was 2.17 mm, while the average width was 3.44 mm. The average biologic height-width ratio was 1:1.58. The width was larger in the posterior region than in the anterior. There were no differences in the biologic height-width ratio in terms of the diameter of the implant. These findings indicate that peri-implant soft tissue augmentation procedures resulting in an average biologic height-width ratio of 1:1.5 may provide a stable buccal cervical line around the implant superstructure, even for thin periodontal biotypes.","subset":"pubmed_abstract"} +{"meta":{"pmid":25561395,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-14":1,"2022-49":1,"2022-27":1,"2021-49":1,"2021-21":1,"2020-45":1,"2020-24":1,"2020-05":1,"2019-22":1,"2023-50":1,"2024-18":1,"2024-10":2,"2024-30":1}}},"text":"Co-registration of magnetic resonance spectroscopy and transcranial magnetic stimulation.\nTranscranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain activity, that is thought to interact primarily with excitatory and inhibitory neurotransmitter systems. Neurotransmitters such as glutamate and GABA can be measured by magnetic resonance spectroscopy (MRS). An important prerequisite for studying the relationship between MRS neurotransmitter levels and responses to TMS is that both modalities should examine the same regions of brain tissue. However, co-registration of TMS and MRS has been little studied to date. This study reports on a procedure for the co-registration and co-visualization of MRS and TMS, successfully localizing the hand motor cortex, as subsequently determined by its functional identification using TMS. Sixteen healthy subjects took part in the study; in 14 of 16 subjects, the TMS determined location of motor activity intersected the (2.5cm)(3) voxel selected for MRS, centered on the so called 'hand knob' of the precentral gyrus. It is concluded that MRS voxels placed according to established anatomical landmarks in most cases agree well with functional determination of the motor cortex by TMS. Reasons for discrepancies are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":6365203,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Diminished activity of a chemotactic inhibitor in synovial fluids from patients with familial Mediterranean fever.\nSynovial fluids from patients with osteoarthritis contain a chemotactic inhibitor that acts by antagonizing the complement-derived chemotactic anaphylotoxin, C5a. The activity of this inhibitor in synovial fluids from patients with several forms of inflammatory arthritis (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and gout) were comparable to the activity present in osteoarthritic synovial fluids. In contrast, levels of inhibitory activity in synovial fluids from 9 patients with familial Mediterranean fever were decreased to less than 20% of those found in osteoarthritis fluids. The possibility was considered that the diminished inhibitory activity in fluids from patients with familial Mediterranean fever plays a part in the pathogenesis of the inflammatory attacks characteristic of this disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":27042763,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2022-49":1,"2022-21":2,"2021-39":2,"2021-21":1,"2021-17":1,"2020-45":1,"2020-29":1,"2020-24":1,"2023-40":1}}},"text":"Abnormalities in Diffusional Kurtosis Metrics Related to Head Impact Exposure in a Season of High School Varsity Football.\nThe purpose of this study was to determine whether the effects of cumulative head impacts during a season of high school football produce changes in diffusional kurtosis imaging (DKI) metrics in the absence of clinically diagnosed concussion. Subjects were recruited from a high school football team and were outfitted with the Head Impact Telemetry System (HITS) during all practices and games. Biomechanical head impact exposure metrics were calculated, including: total impacts, summed acceleration, and Risk Weighted Cumulative Exposure (RWE). Twenty-four players completed pre- and post-season magnetic resonance imaging, including DKI; players who experienced clinical concussion were excluded. Fourteen subjects completed pre- and post-season Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). DKI-derived metrics included mean kurtosis (MK), axial kurtosis (K axial), and radial kurtosis (K radial), and white matter modeling (WMM) parameters included axonal water fraction, tortuosity of the extra-axonal space, extra-axonal diffusivity (De axial and radial), and intra-axonal diffusivity (Da). These metrics were used to determine the total number of abnormal voxels, defined as 2 standard deviations above or below the group mean. Linear regression analysis revealed a statistically significant relationship between RWE combined probability (RWECP) and MK. Secondary analysis of other DKI-derived and WMM metrics demonstrated statistically significant linear relationships with RWECP after covariate adjustment. These results were compared with the results of DTI-derived metrics from the same imaging sessions in this exact same cohort. Several of the DKI-derived scalars (Da, MK, K axial, and K radial) explained more variance, compared with RWECP, suggesting that DKI may be more sensitive to subconcussive head impacts. No significant relationships between DKI-derived metrics and ImPACT measures were found. It is important to note that the pathological implications of these metrics are not well understood. In summary, we demonstrate a single season of high school football can produce DKI measurable changes in the absence of clinically diagnosed concussion.","subset":"pubmed_abstract"} +{"meta":{"pmid":21897668,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2018-26":1,"2017-13":1}}},"text":"Patient-physician Communication Barrier: A Pilot Study Evaluating Patient Experiences.\nThis study aims to identify the patient-physician communication barriers in the primary healthcare setting in Pulau Penang, Malaysia. A cross-sectional study was designed to attain the objectives of the study. A self-developed 17-item study tool was used to explore respondent's perception about the barriers they have faced while communicating with physician. The reliability scale was applied and internal consistency of the study tool was estimated on the basis of Cronbach's alpha (\u03b1 = 0.58). The data analysis was conducted using statistical package for social sciences students SPSS 13(\u00ae). Chi Square test was used to test the difference between proportions. A total of n = 69 patients responded to this survey. A higher participation was seen by the male respondents, 39 (56.5%). About 52 (76.5%) of the respondents were satisfied with the information provided by the physician. In an effort to identify the patient-physician barriers, a poor understanding among the patients and physician was revealed. 16 (23.5%) respondents disclosed lack of satisfaction from the information provided to them. Overall, it is seen that lack of physician-patient understanding was the main reason that result hindrance in the affective communication. Moreover, there is a possibility that a low level of health literacy among the patients and inability of the physician to affectively listen to patients may be the other factors that result in a deficient communication.","subset":"pubmed_abstract"} +{"meta":{"pmid":22924582,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases.\nThis international retrospective study of 593 Splenic Marginal Zone Lymphoma (SMZL) patients aimed to identify factors that determine treatment initiation and influence lymphoma-specific survival (LSS). Logistic regression was used to identify the factors associated with treatment. A Cox regression was used to analyse LSS in a derivation cohort of 366 patients. This produced a prognostic index (PI) and enabled the identification of three risk groups. The resulting stratification was validated in another cohort of 227 patients and compared with the Interguppo Italiano Linfomi (IIL) score in the group of 450 patients for whom all the required data were available using an extension of the net reclassification improvement. Haemoglobin concentration (Hb), extrahilar lymphadenopathy and hepatitis C virus status were associated with the initiation of treatment. Hb, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy were independently associated with LSS. Three risk groups with significantly different five-year LSS (94%, 78% and 69%, respectively) were identified. This stratification (named HPLL on the basis of determinant factors) had a better discriminative power than the IIL score. This system is useful for stratifying SMZL patients into risk groups and may help in the selection of risk-tailored treatment approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":27799469,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Plant Reactome: a resource for plant pathways and comparative analysis.\nPlant Reactome (http:\/\/plantreactome.gramene.org\/) is a free, open-source, curated plant pathway database portal, provided as part of the Gramene project. The database provides intuitive bioinformatics tools for the visualization, analysis and interpretation of pathway knowledge to support genome annotation, genome analysis, modeling, systems biology, basic research and education. Plant Reactome employs the structural framework of a plant cell to show metabolic, transport, genetic, developmental and signaling pathways. We manually curate molecular details of pathways in these domains for reference species Oryza sativa (rice) supported by published literature and annotation of well-characterized genes. Two hundred twenty-two rice pathways, 1025 reactions associated with 1173 proteins, 907 small molecules and 256 literature references have been curated to date. These reference annotations were used to project pathways for 62 model, crop and evolutionarily significant plant species based on gene homology. Database users can search and browse various components of the database, visualize curated baseline expression of pathway-associated genes provided by the Expression Atlas and upload and analyze their Omics datasets. The database also offers data access via Application Programming Interfaces (APIs) and in various standardized pathway formats, such as SBML and BioPAX.","subset":"pubmed_abstract"} +{"meta":{"pmid":10952892,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression.\nPrevious work has shown that heterozygocity for a null mutation of the VEGF-A gene, resulting in a 50% reduction in VEGF-A expression, is embryonic lethal at embroyonic day (E) 9.5 in mice. We now show that two- to threefold overexpression of VEGF-A from its endogenous locus results in severe abnormalities in heart development and embryonic lethality at E12.5-E14. The mutant embryos displayed an attenuated compact layer of myocardium, overproduction of trabeculae, defective ventricular septation and abnormalities in remodeling of the outflow track of the heart. In addition, aberrant coronary development was characterized by formation of oversized epicardial vessels, apparently through vasculogenesis. We infer that embryonic survival requires a narrow window of VEGF-A expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":27905907,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2019-13":1,"2019-09":1,"2018-51":2,"2018-39":1,"2018-30":1,"2018-22":1,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":2,"2019-18":1,"2017-13":1}}},"text":"Addressing asthma and obesity in children with community health workers: proof-of-concept intervention development.\nThe objective of this study was to design and test the feasibility and impact of a community health worker (CHW) intervention for comorbid asthma and obesity. Using a proof of concept study design, we collected pre\/post outcomes from a single intervention cohort of urban low-income in a single community area. A community-based participatory research approach was employed. Forty-six children and their caregivers were recruited. Children were 5-12 years old with physician-diagnosed asthma and body mass index (BMI) > 85%. Families were offered 12 home visits from CHWs that integrated asthma and obesity core curriculums. The primary asthma outcome was asthma control, measured via the Childhood Asthma Control Test (cACT). The primary obesity outcome was child body mass index (BMI). Families received a median of 10 out of the 12 home visits over 1 year. At 1 year, there was a significant improvement in the number of children with controlled asthma as measured via cACT (85.7% at 1 year compared to 61.9% at baseline, p = 0.01). Activity limitations and emergency utilization were reduced while inhaler technique improved (p < 0.01 for all). Child BMI z-score was reduced: mean = 1.97 (SD 0.79) at 1 year compared to mean = 2.13 (SD 0.40) at baseline, p < 0.01. No association was seen between change in child BMI and change in asthma control. Worse baseline child depression scores were associated with less improvement in asthma control (p = 0.003) and higher baseline caregiver post-traumatic stress disorder scores were associated with increased child BMI (p = 0.012). The CHW intervention has promise for improving asthma and weight outcomes in high-risk children with comorbid asthma and obesity; this model warrants further development and investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":15943217,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"A model of standardized training in basic life support skills of emergency medicine residents.\nThis intervention study was designed to determine the current level of basic life support knowledge and skills of residents in a university-based emergency medicine residency program, and to investigate the potential benefit derived by these residents from a standardized theoretical and practical training session. All residents underwent tests before and after the training session. The residents were asked to perform basic life support on a recording cardiopulmonary resuscitation mannequin. Assessments were made using a 10-item checklist, with the highest score being 17. Each step performed by the resident was scored by an emergency physician for accuracy and effectiveness. Twenty-eight residents participated in the study. According to the modified Berden scale, the pretest and posttest scores were 11.2 +\/- 2.9 and 15.6 +\/- 1.0, respectively, and the mean difference was 4.36 +\/- 2.9 (t test, P<.001). Only 11 residents (39.3%) were rated as \"good\" or \"very good\" in the pretest, whereas the corresponding figure in the posttest was 27 (96.4%) (P<.001). Skills, such as checking the airway patency (P<.001), checking breathing (P<.001), appropriate compression rate (P<.003), and delivering 2 effective breaths (P<.001), improved significantly. Depth of chest compression (P<.023) was improved significantly only in residents with fewer than 2 years of experience. The training process should comprise standardized courses to facilitate acquisition of the desired skills.","subset":"pubmed_abstract"} +{"meta":{"pmid":29789716,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.\nMany tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.","subset":"pubmed_abstract"} +{"meta":{"pmid":22718172,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":9}}},"text":"A cross-sectional study of cutaneous drug reactions in a private dental college and government medical college in eastern India.\nCutaneous drug reactions are a common impediment in therapy, the incidence ranging from 2% to 8%. This cross-sectional study was designed to compare different trends of cutaneous drug reaction in two different socio-economic groups of patients in the same region. The aim was to evaluate common drugs implicated in causing reactions, describe the adverse cutaneous drug reactions, study the characteristics of patients presenting with the reactions. This is an observational study of cross-sectional type. The study was carried out in the department of Oral and Maxillofacial surgery in a Private dental College and department of General Medicine in a Medical College only on outdoor basis for 3 years. Out of 2000 patients observed in each college for their necessary treatment 75 patients in the dental College and 200 patients in the Medical College were reported to have various types of cutaneous drug reactions. Diagnosis was based on detailed history including temporal correlation between drug intake and onset of rash and thorough clinical examination Apart from history of drug intake, information regarding associated other allergy, comorbidity and severity (whether hospitalization was required or not) was recorded. Rechallenge with the drug was not possible due to ethical problem. Out of 2000 patients observed in each college 75 patients in dental College and 200 patients in Medical College were documented to have different kinds of cutaneous drug reactions. A total of 30 were male and 45 female in dental college whereas 90 male and 110 female patients were enrolled in Medical College. The age group of the patients in both the colleges ranged from 18 to 75 years. Common culprits observed in this study were antibiotics and NSAIDs. They had contributed 53% and 40% of the total skin reactions respectively in dental college and 47.5% and 45% in Medical College. We encountered 6 patients of systemic lupus erythematosus (SLE), 20 patients with allergic rhinitis and 12 patients with bronchial asthma in the whole proceedings. The duration of drug intake varied from 15 minutes to 2 weeks. The most common reaction noted was maculopapular rash 37 (50.5%), urticaria 15 (20%), fixed drug eruption (FDR) 15 (20%), angioedema 6 (8%) in dental College whereas a little different trend was observed in the medical college. Hospitalization was required in two cases of Steven--Johnson syndrome caused by NSAIDS in the dental College whereas 11 patients were hospitalized for the same indication in the medical College. Except for maculopapular rash, all other skin reactions were observed more frequently with NSAIDS in dental College whereas Steven--Johnson syndrome is predominantly observed in Medical College with anticonvulsants. In all the cases causative drugs were withdrawn. A total 40% of the patients required only antihistaminic, 35% required antihistaminic and topical corticosteroid and rest required a combination of antihistaminic, oral and topical corticosteroids. Commonest drugs causing drug reactions are antibiotics mainly beta lactams and quinolones. Severe reactions were seen in our series with anticonvulsants and NSAIDS. Association with other diseases could not be inferred due to this modest patient pool.","subset":"pubmed_abstract"} +{"meta":{"pmid":24348655,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Analysis of anxiety scale and related elements in endodontic patients.\nAnxiety of patients is one of the problems in dentistry which are considered in recent years, and it prevents them from having a treatment out of stress. This study was conducted to specify anxiety prevalence and related elements among endodontic patients. The study was conducted on 150 patients referred to Endodontic department of dental school of Islamic Azad University, using a cross sectional descriptive method in 2006. Using background characteristics, the patients were classified as a matter of age, sex, education and related factors such as previous dental visit, unfavorable experience in dental office, and the most prevalent cause of referring to dentist. In this regard, Dental Fear Survey (DFS), questionnaire was used and patients were divided in three groups of anxiety level. The results were analyzed using Chi-square and Fisher exact tests. The findings showed highest anxiety scales among dental office referents were statistically significant for age group of 20-30, women, and under diploma education (P<0.05). Improving the knowledge about causes of anxiety and its preventive methods are suggested to dentists. They should also provide treatments without annoyance and trauma.","subset":"pubmed_abstract"} +{"meta":{"pmid":25555046,"dup_signals":{"dup_doc_count":24,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2019-30":1,"2019-26":2,"2019-04":1,"2018-43":2,"2018-30":1,"2018-17":1,"2018-13":1,"2017-39":1,"2017-30":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2021-25":1,"2024-18":2,"2017-13":1}}},"text":"Inkjet printed nanohydrogel coated carbon nanotubes electrodes for matrix independent sensing.\nPolyacrylamide (PA) based hydrogels are used in several applications including polyacrylamide gel electrophoresis and sensing devices. Homogeneous and compact PA films can be prepared based on chemical or photopolymerization processes. However, the accurate and reproducible coating of substrates with nanohydrogel patterns is challenging due to the in situ polymerization and deposition requirements. Herein, we report an inkjet printing (IJP) concept with simultaneously performed UV photopolymerization of a specifically prepared acrylamide\/N,N'-methylenebis(acrylamide) containing ink. A prepolymerization step of the hydrogel precursor molecules was implemented in the ink formulation protocol to adjust the viscosity of the ink and to enhance the rate of polymerization during printing. After the optimization of the printing parameters, a nanometer thin PA hydrogel coating with well distributed nanopores was achieved on top of a stand-alone carbon nanotubes (CNTs) pattern. Batches of fully inkjet printed PA\/CNT modified electrodes were prepared that showed outstanding improvements for the electrochemical detection of antioxidants in complex matrices such as untreated orange juice and red wine samples thanks to the properties of the PA coating.","subset":"pubmed_abstract"} +{"meta":{"pmid":24134608,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":9}}},"text":"The effect of statin therapy withdrawal on monocyte subsets.\nThree functionally distinct monocyte subsets have been identified. Statins are of undoubted effect in atherosclerosis and have numerous pleiotropic effects that contribute to their clinical success, but the effect of these drugs on monocyte subsets is unclear. We hypothesised a beneficial effect of statins on key receptor expression by monocyte subsets. Effects of temporal (2 weeks) cessation of statin therapy by 66 patients with stable coronary artery disease on monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)], their aggregates with platelets and their expression of a number of receptors involved in inflammation (IL-6 receptor), adhesion [vascular cell adhesion molecule (VCAM)], angiogenesis [vascular endothelial growth factor (VEGF)] and repair were assessed by flow cytometry. Statin cessation did not lead to any significant changes in absolute numbers of monocyte subsets or the degree of their aggregation with platelets. All monocyte subsets showed significant downregulation of expression of vascular endothelial factor receptor 2, Tie2 and Toll-like receptor-4 (TLR4; all changes P < 0\u00b701). Expression of CXCR4 was only reduced in Mon1 cells (P = 0\u00b7013). There was no significant change in the expression of CD14, CD16, CCR4, IL6 receptor and VCAM (all P = NS). Statin withdrawal does not affect counts of any of monocyte subsets, but leads to downregulation of expression of TLR4 and receptors related to angiogenesis on all subsets, as well as a decrease in density of CXCR4 expression on 'classical' Mon1. These data provide further support of pleiotropic effects of statins and their effects on monocyte pro-angiogenic and proreparative characteristics.","subset":"pubmed_abstract"} +{"meta":{"pmid":29787684,"dup_signals":{"dup_doc_count":39,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2023-50":2,"2023-23":1,"2023-14":2,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":3,"2021-31":2,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-16":2,"2020-10":1,"2020-05":1,"2019-35":1,"2019-26":1,"2019-22":2,"2019-18":2,"2019-04":1,"2018-43":2,"2018-34":2,"2024-22":1}}},"text":"Trends and variation in prescribing of low-priority treatments identified by NHS England: a cross-sectional study and interactive data tool in English primary care.\nObjectives NHS England recently announced a consultation seeking to discourage the use of treatments it considers to be low-value. We set out to produce an interactive data resource to show savings in each NHS general practice and to assess the current use of these treatments, their change in use over time, and the extent and reasons for variation in such prescribing. Design Cross-sectional analysis. Setting English primary care. Participants English general practices. Main outcome measures We determined the cost per 1000 patients for prescribing of each of 18 treatments identified by NHS England for each month from July 2012 to June 2017, and also aggregated over the most recent year to assess total cost and variation among practices. We used mixed effects linear regression to determine factors associated with cost of prescribing. Results Spend on low-value treatments was \u00a3153.5 m in the last year, across 5.8 m prescriptions (mean, \u00a326 per prescription). Among individual treatments, liothyronine had the highest prescribing cost at \u00a329.6 m, followed by trimipramine (\u00a320.2 m). Over time, the overall total number of low-value prescriptions decreased, but the cost increased, although this varied greatly between treatments. Three treatment areas increased in cost and two increased in volume, all others reduced in cost and volume. Annual practice level spending varied widely (median, \u00a32262 per thousand patients; interquartile range \u00a31439 to \u00a33298). Proportion of patients over 65 was strongly associated with low-value prescribing, as was Clinical Commissioning Group. Our interactive data tool was deployed to OpenPrescribing.net where monthly updated figures and graphs can be viewed. Conclusions Prescribing of low-value treatments is extensive but varies widely by treatment, geographic area and individual practice. Despite a fall in prescription numbers, the overall cost of prescribing for low-value items has risen. Prescribing behaviour is clustered by Clinical Commissioning Group, which may represent variation in the optimisation efficiency of medicines, or in some cases access inequality.","subset":"pubmed_abstract"} +{"meta":{"pmid":22681057,"dup_signals":{"dup_doc_count":26,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2021-17":1,"2021-04":1,"2018-47":2,"2018-43":1,"2018-34":2,"2018-30":1,"2018-22":4,"2018-13":1,"2018-09":3,"2017-51":5,"2016-44":3,"2021-49":1}}},"text":"Search for scalar bottom quark pair production with the ATLAS detector in pp collisions at sqrt[s]=7 TeV.\nThe results of a search for pair production of the scalar partners of bottom quarks in 2.05 fb(-1) of pp collisions at sqrt[s]=7 TeV using the ATLAS experiment are reported. Scalar bottom quarks are searched for in events with large missing transverse momentum and two jets in the final state, where both jets are identified as originating from a bottom quark. In an R-parity conserving minimal supersymmetric scenario, assuming that the scalar bottom quark decays exclusively into a bottom quark and a neutralino, 95% confidence-level upper limits are obtained in the b(1) - \u03c7(1)(0) mass plane such that for neutralino masses below 60 GeV scalar bottom masses up to 390 GeV are excluded.","subset":"pubmed_abstract"} +{"meta":{"pmid":31929593,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":17}}},"text":"Description and characterization of the artisanal elasmobranch fishery on Guatemala's Caribbean coast.\nSmall-scale shark and ray fisheries are conducted throughout Central America's Caribbean coast. Yet, there is limited information regarding catch composition and diversity of these fisheries, especially in Guatemala. Surveys of catch landings were conducted in two of Guatemala's primary Caribbean coastal shark and ray fishing communities, El Quetzalito and Livingston, between January 2015 and July 2017. Biological data from 688 landed chondrichthyans were collected, with 31 species (24 sharks, six rays and one chimaera) identified. The four most frequently captured species included Carcharhinus falciformis (30.2%), Sphyrna lewini (12.7%), Hypanus guttatus (12%) and Rhizoprionodon spp. (6.7%). Landed sharks contained most size classes with a high proportion of juveniles of species with low productivity. The large-bodied species C. falciformis and S. lewini were often recorded at sizes below known maturity; 96.6% and 85.1%, of the captured individuals were immature, respectively. This study can serve as a baseline to determine future trends in the elasmobranch fisheries conducted by Guatemala's Caribbean coastal communities and support assessments on the persistence of the fisheries.","subset":"pubmed_abstract"} +{"meta":{"pmid":15865474,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-39":1,"2020-50":1,"2020-45":1,"2020-29":1,"2020-10":1,"2019-43":1,"2019-13":1,"2014-15":2,"2022-21":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1}}},"text":"Development of a questionnaire measuring student attitudes to working and living in rural areas.\nStudent attachments in rural locations have been instigated, in part to foster positive attitudes to rural practice and encourage rural recruitment. Based on medical and allied health literature, it was hypothesised that students' attitudes to rural practice and rural life encompasses the following three dimensions: (1) community and social issues; (2) family and personal issues; and (3) professional issues. However, there are limited studies assessing attitudinal change before and after rural placement and no valid and reliable tools which examine change across all three dimensions. This article reports on the development, reliability and validity of such a tool to fill this gap in the rural health research literature. Students who undertook a rural placement in South Australia or a rural placement organised by the Mt Isa Centre for Rural and Remote Health in Queensland, Australia, during 2001 were invited to complete a pre- and post-placement questionnaire (n = 243). The response rate for the pre-placement questionnaire was 74.9% (n = 182) and 50.2% (n = 122) for the post-placement questionnaire. A literature review informed the content of the initial questionnaire, which consisted of a series of statements to which respondents were instructed to indicate how strongly they agreed or disagreed on a Likert scale of one to six. The assessment of validity and reliability of the questionnaire involved three main processes. Content validity was assessed by discussion and rating by academics and students, resulting in 18 questionnaire items. Exploratory factor analysis was used to provide evidence of construct validity. The internal consistency reliability of the questionnaire was assessed using Cronbach's alpha. The Cronbach's alpha coefficient for the post-questionnaire was 0.68, acceptable for newly developed scales. Exploratory factor analysis and varimax rotation was conducted for pre- and post-placement (n = 110) questionnaires. The pre-placement questionnaire did not lend itself to logical interpretation, probably due to the diverse attitudes students may have pre-rural placement. However the factors on the post-placement questionnaire were interpretable. The Scree Plot indicated four factors, explaining 60.82% of the total variance. The factors were rotated using the normalised varimax rotation method. The factors extracted were: (1) friendliness and support in rural areas; (2) isolation and socialisation problems associated with living and working in rural areas; (3) enjoyable aspects of living in a rural area; and (4) opportunities that working in a rural area provides. Analysis of the Student Attitudes to Rural Practice and Life Questionnaire provides evidence of validity. The study identified four factors associated with student attitudes to living and working in rural areas, which differ from those hypothesised. The main deviation was Factor 2, grouping all the negative aspects of isolation and socialisation in a rural area. The resulting factors provide a more integrated reflection of the rural experience, rather than the rigid categorisation of professional, social and personal issues. Reliability was found to be adequate. The questionnaire is able to measure student attitudes to rural practice and rural life, and may be used to evaluate the impact of rural placement on student attitudes.","subset":"pubmed_abstract"} +{"meta":{"pmid":24865601,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":14}}},"text":"Speciation and demographic history of Atlantic eels (Anguilla anguilla and A. rostrata) revealed by mitogenome sequencing.\nProcesses leading to speciation in oceanic environments without obvious physical barriers remain poorly known. European and American eel (Anguilla anguilla and A. rostrata) spawn in partial sympatry in the Sargasso Sea. Larvae are advected by the Gulf Stream and other currents towards the European\/North African and North American coasts, respectively. We analyzed 104 mitogenomes from the two species along with mitogenomes of other Anguilla and outgroup species. We estimated divergence time between the two species to identify major events involved in speciation. We also considered two previously stated hypotheses: one where the ancestral species was present in only one continent but was advected across the Atlantic by ocean current changes and another where population declines during Pleistocene glaciations led to increasing vicariance, facilitating speciation. Divergence time was estimated to \u223c3.38 Mya, coinciding with the closure of the Panama Gateway that led to reinforcement of the Gulf Stream. This could have advected larvae towards European\/North African coasts, in which case American eel would be expected to be the ancestral species. This scenario could, however, not be unequivocally confirmed by analyses of dN\/dS, nucleotide diversity and effective population size estimates. Extended bayesian skyline plots showed fluctuations of effective population sizes and declines during glaciations, and thus also lending support to the importance of vicariance during speciation. There was evidence for positive selection at the ATP6 and possibly ND5 genes, indicating a role in speciation. The findings suggest an important role of ocean current changes in speciation of marine organisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":24766389,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Biparental care in insects: paternal care, life history, and the function of the nest.\nThe evolution of parental care is a complex process, and many evolutionary pathways have been hypothesized. Maternal care is common, but paternal care is not. High confidence of paternity should favor the evolution of paternal attendance in caring for young; biparental care is rare because paternity assurance is typically low compared to maternity. Biparental care in insects has evolved several times and has high diversity. To evaluate the conditions for the evolution of biparental care, a comparison across taxa is suitable. In this review, common traits of biparental species are discussed in order to evaluate previous models of biparental care and the life history of insects. It will be shown that nesting is a common feature in biparental insects. Nest structure limits extra-pair copulations, contributing to the evolution of biparental care.","subset":"pubmed_abstract"} +{"meta":{"pmid":24202006,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Experimental and theoretical investigation of correlated fine structure branching ratios arising from state-selected predissociation of BrO (A2\u03a03\/2).\nWe present results for the v'-dependent predissociation dynamics of the BrO (A(2)\u03a03\/2) state using velocity map ion imaging. Correlated fine structure branching ratios, Br((2)P(J)) + O((3)P(J)), have been measured for v' = 5-16 states. The experimental branching ratios are non-statistical and strongly dependent on the initial vibronic state. The current measurements represent an extensive dataset containing rich information about the predissociation dynamics of this system and should provide a stringent test for modern theory. New high level ab initio excited state potentials are presented and have been optimized using experimental v'-dependent predissociation lifetimes and calculated coupling constants. Comparisons between the experimental branching ratios and the predictions based on diabatic and adiabatic limiting models are presented. We find that the adiabatic model is most consistent with the observed trends in the correlated branching ratios, in contrast to previous studies on the related ClO system.","subset":"pubmed_abstract"} +{"meta":{"pmid":1295734,"dup_signals":{"dup_doc_count":14,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2021-10":3,"2021-04":1,"2019-43":1,"2019-30":1,"2019-22":1,"2018-26":1,"2017-47":1,"2016-40":1}}},"text":"A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm.\nPattern formation in the hindbrain and paraxial mesoderm of vertebrates occurs by the formation of a series of repeated segments. These processes of segmentation appear different at the morphological level, since hindbrain segments, the rhombomeres, form by the subdivision of the neural epithelium into compartments, whereas the mesodermal somites form by the sequential aggregation of mesenchymal cells into epithelial balls. Previous studies have implicated genes encoding transcription factors in the development of hindbrain segments, but nothing is known of genes involved in the formation of somites. Cellular interactions and signal transduction must be an important aspect of hindbrain segmentation, so we have screened for tyrosine kinases expressed in rhombomere-restricted patterns in the developing mouse embryo. We have identified a receptor protein tyrosine kinase, Sek, that has high relative levels of expression in rhombomeres 3 and 5. This alternating pattern is established coincidentally, both spatially and temporally, with the expression of Krox-20, a zinc-finger gene expressed prior to the morphological formation of rhombomeres. In addition, Sek expression occurs in several other developing tissues, including a dynamic regulation in the developing forebrain, spinal cord, early mesoderm and anterior presomitic mesoderm (segmental plate). The latter expression occurs in two stripes that correlate with, and presage, the formation of somites. Sek expression initially occurs throughout the presumptive somite, then becomes restricted anteriorly, and finally is down-regulated as the definitive somite is formed. These data suggest that despite the morphological differences in the segmentation of the hindbrain and mesoderm, Sek is involved in the segmental patterning of both of these tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":32395525,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A profiling analysis on the receptor ACE2 expression reveals the potential risk of different type of cancers vulnerable to SARS-CoV-2 infection.\nThe new coronavirus pneumonia (NCP) is now causing a severe public health emergency. The novel coronavirus 2019 (2019-nCoV) infected individuals by binding human angiotensin converting enzyme II (ACE2) receptor. ACE2 is widely expressed in multiple organs including respiratory, cardiovascular, digestive and urinary systems in healthy individuals. These tissues with high expression level of ACE2 seemed to be more vulnerable to SARS-CoV-2 infection. Recently, it has been reported that patients with tumors were likely to be more susceptible to SARS-CoV-2 infection and indicated poor prognosis. The tissue atlas database and the blood atlas were used to analyze the distribution of ACE2 in human tissues or organs of cancers and normal samples. Starbase dataset was applied to predict the prognosis of cancers according to expression level of ACE2. In this study, we demonstrated a landscape profiling analysis on expression level of ACE2 in pan-cancers and showed the risky of different type of cancers to SARS-CoV-2 according to the expression level of ACE2. In addition, we found that ACE2 was both differential expression and related to the prognosis only in liver hepatocellular carcinoma (LIHC). Relative high expression of ACE2 indicated a favorable prognosis in LIHC, but they might be more susceptible to SARS-CoV-2. We indeed emphasized that LIHC patients with high expression level of ACE2 should be more cautious of the virus infection. Our study might provide a potential clue for preventing infection of SARS-CoV-2 in cancers.","subset":"pubmed_abstract"} +{"meta":{"pmid":11889273,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The National Birth Defects Prevention Study.\nThe National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7,470 cases and 3,821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nation's leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.","subset":"pubmed_abstract"} +{"meta":{"pmid":11247695,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"2014-10":1,"2013-48":1,"2013-20":1,"unknown":6}}},"text":"Thoracic computed tomography in patients with suspected malignant pleural effusions.\nTo assess the role of contrast-enhanced computed tomography (CT) prospectively in patients with suspected malignant pleural effusions. Forty consecutive patients referred for the investigation of a suspected malignant pleural effusion had contrast-enhanced thoracic CT, thoracoscopy, thoraco-centesis and pleural biopsy, either percutaneously or at thoracoscopy. Final diagnoses were based on histopathological or cytological analysis (n = 30), autopsy findings (n = 3) or clinical follow-up (n = 7). The pleural surfaces were classified at contrast-enhanced CT as normal or abnormal and, if abnormal, as benign or malignant in appearance using previously established CT criteria for malignant pleural thickening by two observers unaware of the pathological diagnosis. Pleural effusions were malignant in 32 patients and benign in eight patients. Pleural surfaces assessed at CT showed features of malignancy in 27 out of 32 patients with a malignant effusion (sensitivity 84%, specificity 100%). Overall, CT appearances indicated the presence of malignancy in 28 of 32 (87%) patients. All eight patients with benign pleural disease were correctly diagnosed by CT. Contrast-enhanced CT is of value in patients with suspected malignant pleural effusions. The previously established criteria for malignant pleural thickening of nodularity, irregularity and pleural thickness >1 cm are reliable in the presence of a pleural effusion.","subset":"pubmed_abstract"} +{"meta":{"pmid":2999784,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Direct mapping of adeno-associated virus capsid proteins B and C: a possible ACG initiation codon.\nThe three major capsid proteins of adeno-associated virus type 2 (AAV2) virions are designated A, B, and C and have molecular sizes of 90, 72, and 60 kDa, respectively. These proteins are related, and genetic studies have shown they are encoded by a long open reading frame located in the right half of the genome. The coding capacity distal to the first ATG in this reading frame is only 503 amino acids (i.e., a protein about the size of protein C), but an open frame sequence devoid of ATG codons extends upstream for an additional 184 codons. Although the amino terminus of the C capsid protein is blocked, partial amino acid sequence analyses of peptides from C have confirmed that it is encoded within the portion of the reading frame distal to the first ATG at nucleotide (nt) location 2810. The amino terminus of the B capsid protein is not blocked, and its sequence begins with alanine. The triplet encoding this alanine lies 64 codons upstream from the initiation site for protein C and is immediately preceded by the threonine codon, ACG, at nt 2615. This ACG codon lies in the most favorable sequence context for protein synthesis initiation. All three AAV2 capsid proteins are labeled in vitro with formyl[35S]methionyl-tRNAf, indicating that synthesis of each protein is initiated independently. Our data suggest that the nt 2615 ACG codon directs the methionyl-tRNA-dependent initiation of the AAV2 B capsid protein. Proteins B and C may be synthesized from the same mRNA species and their relative abundance could be determined by the efficiencies of their respective initiation codons.","subset":"pubmed_abstract"} +{"meta":{"pmid":26913169,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2022-27":2,"2021-43":1,"2021-39":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-10":1,"2019-43":1,"2019-30":1,"2018-47":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-13":1,"2024-26":1,"2024-18":1,"2024-30":1}}},"text":"Speeding up biomolecular interactions by molecular sledding.\nNumerous biological processes involve association of a protein with its binding partner, an event that is preceded by a diffusion-mediated search bringing the two partners together. Often hindered by crowding in biologically relevant environments, three-dimensional diffusion can be slow and result in long bimolecular association times. Similarly, the initial association step between two binding partners often represents a rate-limiting step in biotechnologically relevant reactions. We demonstrate the practical use of an 11-a.a. DNA-interacting peptide derived from adenovirus to reduce the dimensionality of diffusional search processes and speed up associations between biological macromolecules. We functionalise binding partners with the peptide and demonstrate that the ability of the peptide to one-dimensionally diffuse along DNA results in a 20-fold reduction in reaction time. We also show that modifying PCR primers with the peptide sled enables significant acceleration of standard PCR reactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":23672284,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Modified graphene\/polyimide nanocomposites: reinforcing and tribological effects.\nBy taking advantage of design and construction of strong graphene-matrix interfaces, we have prepared modified graphene\/polyimide (MG\/PI) nanocomposites via a two-stage process consisting of (a) surface modification of graphene and (b) in situ polymerization. The 2 wt % MG\/PI nanocomposites exhibited a 20-fold increase in wear resistance and a 12% reduction in friction coefficient, constituting a potential breakthrough for future tribological application. Simultaneously, MG also enhanced thermal stability, electrical conductivity, and mechanical properties, including tensile strength, Young's modulus, storage modulus, and microhardness. Excellent thermal stability and compatibility of interface, strong covalent adhesion interaction and mechanical interlocking at the interface, as well as homogeneous and oriented dispersion of MG were achieved here, contributing to the enhanced properties observed here. The superior wear resistance is ascribed to (a) tribological effect of MG, including suppression effect of MG in the generation of wear debris and protective effect of MG against the friction force, and (b) the increase in mechanical properties. In light of the relatively low cost and the unique properties of graphene, the results of this study highlight a pathway to expand the engineering applications of graphene and solve wear-related mechanical failures of polymer parts.","subset":"pubmed_abstract"} +{"meta":{"pmid":28795294,"dup_signals":{"dup_doc_count":18}},"text":"How Long Does Antimycobacterial Antibiotic-loaded Bone Cement Have In Vitro Activity for Musculoskeletal Tuberculosis?\nAntibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. However, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking. (1) In antibiotic-loaded cement, is there effective elution of streptomycin and Augmentin\u00ae (amoxicillin and clavulanic acid) individually and in combination? (2) What is the antibacterial activity duration for streptomycin- and amoxicillin and clavulanic acid -loaded cement? Six different types of bone cement discs were created by mixing 40 g bone cement with 1 or 2 g streptomycin only, 0.6 g or 1.2 g Augmentin\u00ae (amoxicillin and clavulanic acid) only, and a combination of 1 g streptomycin plus 0.6 g amoxicillin and clavulanic acid and 2 g streptomycin plus 1.2 g amoxicillin and clavulanic acid. Five bone discs of each type were incubated in phosphate buffered saline for 30 days with renewal of the phosphate buffered saline every day. The quantity of streptomycin and\/or amoxicillin and clavulanic acid in eluates were measured by a liquid chromatography-mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv, were calculated by comparing the minimal inhibitory concentration of each eluate with that of tested drugs using broth dilution assay on microplate. Streptomycin was detected in eluates for 30 days (in 1 g and 2 g discs), whereas 1.2 g amoxicillin and clavulanate eluted until Day 7 and 0.6 g amoxicillin and clavulanate until Day 3. All eluates in streptomycin-containing discs (streptomycin only, and in combination with amoxicillin and clavulanic acid) had effective antimycobacterial activity for 30 days, while amoxicillin and clavulanate-only preparations were only active until Day 14. The antimycobacterial activity of eluates of 2 g streptomycin plus 1.2 g amoxicillin and clavulanate were higher than those of discs containing 1 g streptomycin plus 0.6 g amoxicillin and clavulanate until Day 3, without differences (Day 3, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 17.5 \u00b1 6.85 ug\/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 32.5 \u00b1 16.77 ug\/mL; p = 0.109). After Day 7, however, values of the two combinations remained no different than that of Day 30 (Day 30, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 0.88 \u00b1 0.34 ug\/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 0.59 \u00b1 0.94 ug\/mL; p = 0.107). Streptomycin, in the form of antibiotic-loaded bone cement, had effective elution characteristics and antimycobacterial effects during a 30-day period, whereas amoxicillin and clavulanate only had effective elution and antimycobacterial characteristics during the early period of this study. The two drugs did not interfere with each other during the elution test. This research revealed that combinations of streptomycin and amoxicillin and clavulanate mixed with bone cement are effective for 30 days. Further trials to determine various different combinations of drugs are necessary to improve the effectiveness of treatments for musculoskeletal tuberculosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":21213198,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-33":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2019-39":1,"2019-04":1,"2018-39":1,"2018-22":1,"2018-05":1,"2023-23":1,"2024-18":1}}},"text":"The pleura in health and disease.\nA wide variety of local, regional, and systemic diseases may have pleural manifestations. The scope of this pathology encompasses a wide spectrum ranging from minimal inflammatory changes to highly malignant neoplasms. An overview of the normal structure of the pleura is provided, along with the diseases that may be encountered. Pleural specimens from patients with pneumothorax are rarely encountered by pathologists. In contrast, pathologists frequently receive pleural specimens showing evidence of inflammation, repair, or neoplasm. In these circumstances, an awareness of less common (and often clinically highly important) conditions such as epithelioid hemangioendothelioma and primary pleural malignant mesothelioma is essential. Knowledge of the clinical setting (e.g., disease tempo) and radiological picture (e.g., laterality) is often of great value to the pathologist in arriving at a correct diagnosis. Similarly, knowledge of the normal anatomical considerations and familiarity with the expected pleural histopathology for the most clinically relevant pleural diseases are critical assets for pulmonary physicians in providing optimal care for their patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":22689716,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":14}}},"text":"Risk of acute coronary syndrome in elderly users of antipsychotic drugs: a nested case-control study.\nTo examine the association between antipsychotic use and the risk of acute coronary syndrome (ACS) in elderly de novo users of antipsychotics. A community-based nested case-control study. Pharmacy dispensing records from community pharmacies in The Netherlands were linked to hospital discharge records of 950,000 community-dwelling residents from 1998 to 2008. Cases were 2803 patients aged 60 years or older, with a first hospital admission for ACS identified within a cohort of 26,157 elderly persons with at least one antipsychotic prescription (de novo users). For each case, four controls with no hospitalisation for ACS (n=11,024) were randomly selected from the same cohort, matched by age, gender and duration of registration in the database. Relative risks, expressed as ORs, for ACS associated with antipsychotic drug use adjusted for comorbidity. Current exposure to antipsychotics was associated with a decreased risk of hospitalisation for ACS compared with past users (adjusted OR 0.5, 95% CI 0.5 to 0.6). Cumulative use up to 100 Defined Daily Doses was also associated with a decreased risk of hospitalisation (OR 0.7, CI 0.6 to 0.8). No differences in risk were found between typical and atypical antipsychotics, current dosage or different degrees of serotonergic, histaminergic or adrenergic affinity of the antipsychotic. A decreased risk of hospitalisation for ACS in elderly patients currently using antipsychotics was found. Further research is needed to confirm our results and to determine whether there is a cardioprotective effect or a high non-referral rate in elderly antipsychotic users with ACS.","subset":"pubmed_abstract"} +{"meta":{"pmid":20454661,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"IsiA is required for the formation of photosystem I supercomplexes and for efficient state transition in synechocystis PCC 6803.\nIron deficiency and other stress conditions strongly impact photosynthetic apparatus in photosynthetic organisms. Two novel chlorophyll (Chl)-containing supercomplexes (F4 and F5) in addition to the photosystem (PS) I trimers (F3) were observed by sucrose gradient ultracentrifugation in Synechocystis PCC 6803 under extensive iron starvation. 77K fluorescence and Western blot analyses of these supercomplexes revealed that they all contained IsiA. The F4 was identified as an IsiA-PSI-PSII supercomplex, while the F5 was assigned as an IsiA-PSI supercomplex. Deletion of isiA resulted in diminishing the PSI trimers (including the PSI trimers in iron-replete cells) and the two novel PSI supercomplexes (F4 and F5), and a significant reduction in the saturated whole-chain electron transport rate. However, the maximum PSII activities remained at levels similar to those of the wild type under various light conditions. The isiA(-) mutant was defective in state transition and sensitive to high light. The sensitivity of the isiA(-) mutant to high light was correlated with a higher level of membrane peroxidation. These results demonstrated that IsiA is required for the formation of PSI trimers and other higher complexes, and that IsiA is critical for efficient state transition.","subset":"pubmed_abstract"} +{"meta":{"pmid":2589463,"dup_signals":{"dup_doc_count":11}},"text":"Effects of systemic administration of indomethacin on ovulation, luteinization, and steroidogenesis in the rabbit ovary.\nIndomethacin blocks ovulation in human chorionic gonadotropin-stimulated rabbits. Experiments were done with an in vitro ovarian perfusion system to investigate whether indomethacin affects luteinization and steroidogenesis. Indomethacin (10 mg\/kg) was administered in combination with human chorionic gonadotropin (100 IU) via a marginal ear vein, and a second dose of indomethacin was given 8 hours later. Control animals received vehicle in place of indomethacin. Laparotomy was performed 24 hours after the initial treatment. The presence of unruptured follicles and corpora lutea was recorded and the ovaries were perfused in vitro for 3 hours. Progesterone, prostaglandin F2 alpha, prostaglandin E2, and 6-keto-prostaglandin F1 alpha were measured in samples obtained at 0, 30, 60, 120, and 180 minutes from the circulating perfusion medium entering and exiting the ovary. At the end of the perfusion all ovaries (12 treated and 10 controls) were fixed for histologic analysis. Ovulation occurred in all control ovaries but in none of the indomethacin-treated ovaries. The mean number of unruptured follicles per ovary in the treated group was not significantly different from the number of corpora lutea plus unruptured follicles per ovary in the controls. Cells in both groups were qualitatively similar in ultrastructure; abundant lipid droplets, smooth endoplasmic reticulum, and mitochondria were seen. Secretion rates of progesterone and prostaglandin did not differ between the two groups during the 3-hour perfusion period. These results suggest that transformation of granulosa cells into fully functional luteal cells can occur in the absence of follicular rupture.","subset":"pubmed_abstract"} +{"meta":{"pmid":21884533,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":12}}},"text":"C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study.\nThe placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U\/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert\u00ae; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U\/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. A single dose of 20 U\/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.","subset":"pubmed_abstract"} +{"meta":{"pmid":24996851,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":18}}},"text":"Capacity building efforts and perceptions for wildlife surveillance to detect zoonotic pathogens: comparing stakeholder perspectives.\nThe capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats. The PREDICT project, a component of United States Agency for International Development's Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global 'hot spot' regions where zoonotic disease emergence is likely to occur. Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program. A survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife. Both stakeholder groups identified some human-animal interfaces (i.e. areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance. Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%). However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists). A One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife. This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps. Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":30139713,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"\u03b11L-adrenoceptors mediate contraction of human erectile tissue.\n\u03b11-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly \u03b11A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the \u03b11L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3H]tamsulosin) binding assays, were used to determine the \u03b11-adrenoceptor population. A61603, a \u03b11A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The \u03b11A- and \u03b11D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD = 9.7 \u00b1 0.3), whilst BMY7378 (100 nM) (\u03b11D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD = 8.2 \u00b1 0.1) and RS17053 (pKD = 6.9 \u00b1 0.2), antagonists which discriminate between the \u03b11A- and \u03b11L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD = 10.3 \u00b1 0.1) with a receptor density of 28.1 \u00b1 1.4 fmol mg-1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pKi = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the \u03b11L-adrenoceptor.","subset":"pubmed_abstract"} +{"meta":{"pmid":8623928,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bcl-2-deficient mice.\nRenal development in bcl-2-deficient mice was monitored to examine the temporal and spatial function of this gene during nephrogenesis in vivo. Extensive apoptosis occurred during abnormal nephrogenesis in bcl-2-deficient mice. In embryos and newborn mice, the sequence of morphological events was monitored by morphology in conjunction with morphometry, and bcl-2 -\/-, bcl-2 +\/-, and bcl-2 +\/+ mice were compared. In bcl-2 -\/- mice, initial induction of nephrons was detected by embryonic day 13 (E-13) as normal. Then, apoptotic cells became five times more frequent at E-13 to E-16 with a significant reduction (1\/5) in nephron number at E-17 to E-19 in bcl-2 -\/- mice compared with bcl-2 +\/+ mice. No morphological difference was evident between bcl-2 +\/- mice and bcl-2 +\/+ mice by morphometry. Apoptotic cells were found mainly among the mesenchyme and less frequently in tubuli. Little apoptosis among ureteric buds was noted. In bcl-2 -\/- mice at E-17 to E-19, inactive branching and insufficient convolution of ureteric buds were accompanied by fulminant apoptosis in the mesenchyme. Neonatal bcl-2 -\/- mice lacked the nephrogenic zone, exhibiting renal hypoplasia. Thus, bcl-2 seems to inhibit apoptosis in renal stem cells during the induction of nephrons in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":9521337,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Randomized, double-blind, placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure.\nReduced cGMP production caused by increased superoxide has been proposed as a mechanism of nitrate tolerance during continuous nitrate therapy. This study was designed to evaluate the effects of ascorbate, an antioxidant, on the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure. Twenty patients with congestive heart failure were randomized to receive intravenous infusion of nitroglycerin concomitantly with placebo (placebo group, n=10) or intravenous ascorbate (vitamin C group, n=10). After baseline measurements were obtained, dose titration was started by the infusion of nitroglycerin at a rate of 0.5 microg\/kg per minute (titration period). Measurements of hemodynamic parameters and blood sampling were performed serially at 0, 6, 12, 18, and 24 hours after the titration period. At baseline, mean pulmonary artery pressure (MPAP, mm Hg), mean pulmonary capillary wedge pressure (PCWP, mm Hg), plasma vitamin E level (micromol\/L), and platelet cGMP level (pmol\/10[9] platelets) were comparable in the two groups (placebo group: MPAP, 48+\/-6; PCWP, 24+\/-4; cGMP, 0.76+\/-0.12; vitamin E, 18.2+\/-1.2; vitamin C: MPAP, 49+\/-7; PCWP, 24+\/-4; cGMP, 0.71+\/-0.16; vitamin E, 18.6+\/-1.3). In both groups, at 6 hours after the titration period, MPAP and PCWP were significantly decreased (placebo group: MPAP, 26+\/-5; PCWP, 15+\/-4; vitamin C: MPAP, 26+\/-4; PCWP, 16+\/-4), and platelet cGMP was significantly increased (placebo group: 2.42+\/-0.24; vitamin C: 2.26+\/-0.26). However, at 18 hours after titration, in the placebo group, MPAP (44+\/-5) and PCWP (23+\/-4) were increased, and platelet cGMP (0.85+\/-0.20) and plasma vitamin E levels (12.4+\/-1.4) were significantly decreased. In contrast, in the vitamin C group, MPAP (31+\/-6), PCWP (17+\/-5), platelet cGMP (2.49+\/-0.23), and plasma vitamin E levels (17.6+\/-1.4) were maintained for 18 hours after the titration period. These findings indicate that ascorbate, an antioxidant, may prevent the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":23589155,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":3,"2024-18":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Improved adjuvanting of seasonal influenza vaccines: preclinical studies of MVA-NP+M1 coadministration with inactivated influenza vaccine.\nLicensed seasonal influenza vaccines induce antibody (Ab) responses against influenza hemagglutinin (HA) that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia Ankara (MVA) virus encoding NP and M1 (MVA-NP+M1) is designed to boost preexisting T-cell responses in adults in order to elicit a cross-protective immune response. We examined the coadministration of HA protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Ab responses postimmunization were measured by ELISA and pseudotype neutralization assays. Here, we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing Ab responses to HA while simultaneously inducing potent T-cell responses to conserved internal Ags. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and Ab responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations.","subset":"pubmed_abstract"} +{"meta":{"pmid":2106931,"dup_signals":{"dup_doc_count":15,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-22":3,"2024-18":2,"2017-13":2,"2013-48":1,"2024-30":1,"unknown":4}}},"text":"Analysis of serial measurements in medical research.\nIn medical research data are often collected serially on subjects. The statistical analysis of such data is often inadequate in two ways: it may fail to settle clinically relevant questions and it may be statistically invalid. A commonly used method which compares groups at a series of time points, possibly with t tests, is flawed on both counts. There may, however, be a remedy, which takes the form of a two stage method that uses summary measures. In the first stage a suitable summary of the response in an individual, such as a rate of change or an area under a curve, is identified and calculated for each subject. In the second stage these summary measures are analysed by simple statistical techniques as though they were raw data. The method is statistically valid and likely to be more relevant to the study questions. If this method is borne in mind when the experiment is being planned it should promote studies with enough subjects and sufficient observations at critical times to enable useful conclusions to be drawn. Use of summary measures to analyse serial measurements, though not new, is potentially a useful and simple tool in medical research.","subset":"pubmed_abstract"} +{"meta":{"pmid":18937341,"dup_signals":{"dup_doc_count":35,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2017-13":1,"2024-26":1,"unknown":30}}},"text":"Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects.\nNeural tube defects (NTDs), including spina bifida and anencephaly, are the second most common birth defect with an incidence of 1\/1000. Genetic factors are believed to contribute to NTD risk and family-based studies can be useful for identifying such risk factors. We ascertained 1066 NTD families (1467 affected patients), including 307 multiplex NTD families. We performed pedigree analysis to describe the inheritance patterns, pregnancy outcomes, and recurrence risks to relatives of various types. Myelomeningocele or spina bifida (66.9%) and cranial defects (17.7%) were the most common NTD subtypes observed. The overall male:female ratio for affected individuals was 0.82, and there were even fewer males among individuals with an upper level NTD (0.62). Among twins, 2 of the 5 monozygotic twins and only 3 of 35 dizygotic twins were concordant, while 27% of the same sex twins were concordant, but none of the different sex twins. The estimated 6.3% recurrence risk to siblings (CI 0.04-0.08) is consistent with previous reports. Families with two or more affected individuals show a higher proportion of female transmitters (p = 0.0002). Additionally, the number of affected relatives in maternal compared to paternal lineages was more than double (p = 0.006). There were significantly more miscarriages, infant deaths, and stillborn pregnancies of the maternal aunts and uncles (p < 0.0001) and of first cousins (p = 0.04). Our data provide several lines of evidence consistent with a maternal effect, as well as a sex-influenced effect, in the etiology of NTDs.","subset":"pubmed_abstract"} +{"meta":{"pmid":23299895,"dup_signals":{"dup_doc_count":15}},"text":"Mid-infrared optical frequency combs at 2.5 \u03bcm based on crystalline microresonators.\nThe mid-infrared spectral range (\u03bb~2-20 \u03bcm) is of particular importance as many molecules exhibit strong vibrational fingerprints in this region. Optical frequency combs--broadband optical sources consisting of equally spaced and mutually coherent sharp lines--are creating new opportunities for advanced spectroscopy. Here we demonstrate a novel approach to create mid-infrared optical frequency combs via four-wave mixing in a continuous-wave pumped ultra-high Q crystalline microresonator made of magnesium fluoride. Careful choice of the resonator material and design made it possible to generate a broadband, low-phase noise Kerr comb at \u03bb=2.5 \u03bcm spanning 200 nm (\u224810 THz) with a line spacing of 100 GHz. With its distinguishing features of compactness, efficient conversion, large mode spacing and high power per comb line, this novel frequency comb source holds promise for new approaches to molecular spectroscopy and is suitable to be extended further into the mid-infrared.","subset":"pubmed_abstract"} +{"meta":{"pmid":23750859,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-30":1,"unknown":16}}},"text":"Health related quality of life across the perinatal period among Australian women.\nTo investigate the significant features in health-related quality of life and to examine the changes over time during the perinatal period. Health-related quality of life during the perinatal period is significant for women. Screening or surveillance during the perinatal period is inconsistent and often not part of continued assessment. Prospective. Setting involved antenatal clinics at three public hospitals in metropolitan Brisbane, Australia. A total of 363 participants out of a cohort of 605 women completed all items of the Short Form-12 Health Survey in late pregnancy and again at 6 and 12 weeks postpartum. There was a significant difference across the three perinatal time periods in all the health-related quality-of-life subscales. Significant improvements were noted from late pregnancy to 6 weeks following childbirth and again at 12 weeks particularly in physical health, role physical, bodily pain, vitality, role emotional and mental health. Even when confounding variables such as maternal ages, partner status, parity, delivery type and ethnicity were introduced, significant improvements were noted. Maternal distress significantly related to almost all quality-of-life factors over time even when all possible confounding factors were controlled. Significant changes occur in health-related quality of life across the perinatal period. All dimensions of health-related quality of life except for social functioning and maternal distress showed marked improvement following childbirth. During this period, maternal distress was negatively related to health-related quality of life. Nurses need to be mindful of the broader view of health as encompassed in health-related quality-of-life measures and the potential these have for alerting health professionals when providing care. More rigorous health assessment for mothers at risk is useful so that appropriate support and follow-up can be given.","subset":"pubmed_abstract"} +{"meta":{"pmid":22023668,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep, and hormone levels in rhesus monkeys.\nDopamine transporter (DAT) inhibitors have been developed as a promising treatment approach for cocaine dependence. However, the stimulant effects of DAT inhibitors have the potential to disrupt sleep patterns, and the influence of long-term treatment on dopamine neurochemistry is still unknown. The objectives of this study were to (1) explore the stimulant-related effects of chronic DAT inhibitor (RTI-336) treatment on motor activity and sleep-like measures in male rhesus monkeys (Macaca mulatta; n = 4) and (2) to determine the effect of drug treatment on prolactin and cortisol levels. Subjects were fitted with a collar-mounted activity monitor to evaluate their motor activity, with 4 days of baseline recording preceding 21 days of daily saline or RTI-336 (1 mg\/kg\/day; intramuscular) injections. Blood samples were collected immediately prior to and following chronic treatment to assess hormone levels. RTI-336 produced a significant increase in locomotor activity at the end of the daytime period compared to saline administration. During the 3-week treatment period, sleep efficiency was decreased and the fragmentation index and latency to sleep onset were significantly increased. Hormone levels were not changed throughout the study. Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":10394363,"dup_signals":{"dup_doc_count":13}},"text":"Synip: a novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes.\nInsulin-stimulated glucose transport and GLUT4 translocation require regulated interactions between the v-SNARE, VAMP2, and the t-SNARE, syntaxin 4. We have isolated a novel syntaxin 4-binding protein, Synip, which specifically interacts with syntaxin 4. Insulin induces a dissociation of the Synip:syntaxin 4 complex due to an apparent decrease in the binding affinity of Synip for syntaxin 4. In contrast, the carboxyterminal domain of Synip does not dissociate from syntaxin 4 in response to insulin stimulation but inhibits glucose transport and GLUT4 translocation. These data implicate Synip as an insulin-regulated syntaxin 4-binding protein directly involved in the control of glucose transport and GLUT4 vesicle translocation.","subset":"pubmed_abstract"} +{"meta":{"pmid":11085649,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":2,"2013-20":2,"unknown":7}}},"text":"Changing the heme ligation in flavocytochrome b2: substitution of histidine-66 by cysteine.\nSubstitution by cysteine of one of the heme iron axial ligands (His66) of flavocytochrome b2 (L-lactate:cytochrome c oxidoreductase from Saccharomyces cerevisiae) has resulted in an enzyme (H66C-b2) which remains a competent L-lactate dehydrogenase (kcat 272+\/-6 s(-1), L-lactate KM 0.60+\/-0.06 mM, 25 degrees C, I 0.10, Tris-HCl, pH 7.5) but which has no cytochrome c reductase activity. As a result of the mutation, the reduction potential of the heme was found to be -265+5 mV, over 240 mV more negative than that of the wild-type enzyme, and therefore unable to be reduced by L-lactate. Surface-enhanced resonance Raman spectroscopy indicates similarities between the heme of H66C-b2 and those of cytochromes P450, with a nu4 band at 1,345 cm(-1) which is indicative of cysteine heme-iron ligation. In addition, EPR spectroscopy yields g-values at 2.33, 2.22 and 1.94, typical of low-spin ferric cytochromes P450, optical spectra show features between 600 and 900 nm which are characteristic of sulfur coordination of the heme iron, and MCD spectroscopy shows a blue-shifted NIR CT band relative to the wild-type, implying that the H66C-b2 heme is P450-like. Interestingly, EPR evidence also suggests that the second histidine heme-iron ligand (His43) is displaced in the mutant enzyme.","subset":"pubmed_abstract"} +{"meta":{"pmid":29078570,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2019-39":1,"2019-30":1,"2019-26":1,"2019-13":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-09":1,"2020-10":1,"2017-13":1}}},"text":"Robotic technological aids in esophageal surgery.\nRobotic technology is an emerging technology that has been developed in order to overcome some limitations of the standard laparoscopic approach, offering a stereoscopic three-dimensional visualization of the surgical field, increased maneuverability of the surgical tools with consequent increased movement accuracy and precision and improved ergonomics. It has been used for the surgical treatment of most benign esophageal disorders. More recently, it has been proposed also for patients with operable esophageal cancer. The current evidence shows that there are no real benefits of the robotic technology over conventional laparoscopy in patients undergoing a fundoplication for gastroesophageal reflux disease (GERD), hiatal closure for giant hiatal hernia, or Heller myotomy for achalasia. A few small studies suggest potential advantages in patients undergoing redo surgery for failed fundoplication or Heller myotomy, but large comparative studies are needed to better clarify the role of the robotic technology in these patients. Robot-assisted esophagectomy seems to be safe and effective in selected patients; however, there are no data showing superiority of this approach over both conventional laparoscopic and open surgery. The short-term and long-term oncologic results of ongoing randomized controlled trials (RCTs) are awaited to validate this approach for the treatment of esophageal cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":30829475,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Origin and Fate of Vanadium in the Hazeltine Creek Catchment following the 2014 Mount Polley Mine Tailings Spill in British Columbia, Canada.\nResults from the analysis of aqueous and solid-phase V speciation within samples collected from the Hazeltine Creek catchment affected by the August 2014 Mount Polley mine tailings dam failure in British Columbia, Canada, are presented. Electron microprobe and X-ray absorption near-edge structure (XANES) analysis found that V is present as V3+ substituted into magnetite and V3+ and V4+ substituted into titanite, both of which occur in the spilled Mount Polley tailings. Secondary Fe oxyhydroxides forming in inflow waters and on creek beds have V K-edge XANES spectra exhibiting E1\/2 positions and pre-edge features consistent with the presence of V5+ species, suggesting sorption of this species on these secondary phases. PHREEQC modeling suggests that the stream waters mostly contain V5+ and the inflow and pore waters contain a mixture of V3+ and V5+. These data, and stream, inflow, and pore water chemical data, suggest that dissolution of V(III)-bearing magnetite, V(III)- and V(IV)-bearing titanite, V(V)-bearing Fe(-Al-Si-Mn) oxhydroxides, and V-bearing Al(OH)3 and\/or clay minerals may have occurred. In the circumneutral pH environment of Hazeltine Creek, elevated V concentrations are likely naturally attenuated by formation of V(V)-bearing secondary Fe oxyhydroxide, Al(OH)3, or clay mineral colloids, suggesting that the V is not bioavailable. A conceptual model describing the origin and fate of V in Hazeltine Creek that is applicable to other river systems is presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":18461212,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Effects of a 12-week exercise training programme on aerobic fitness, body composition, blood lipids and C-reactive protein in adolescents with obesity.\nDeveloping effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact. In this study, the effects of a 12-week twice weekly additional exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises, in additional to typical physical education sessions, on aerobic fitness, body composition and serum C-reactive protein (CRP) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group. Both the exercise group (EG, n = 12) and control group (CG, n = 12) participated in the typical 2 sessions of 40-minute physical education (PE) per week in schools, but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65% to 85% maximum heart rate (HRmax = 220 - age). Body composition was measured using dual energy X-ray absorptiometry (DEXA). Fasting serum CRP and blood lipids were analysed pre- and postexercise programme. Aerobic fitness was measured by an objective laboratory submaximal exercise test, PWC170 (Predicted Work Capacity at HR 170 bpm). Exercise training significantly improved lean muscle mass, body mass index, fitness, resting HR, systolic blood pressure and triglycerides in EG. Serum CRP concentrations were elevated at baseline in both groups, but training did not result in a change in CRP levels. In the CG, body weight increased significantly at the end of the 12-week period. This study supports the value of an additional exercise training programme, beyond the typical twice weekly physical education classes, to produce physiological benefits in the management of obesity in adolescents, including prevention of weight gain.","subset":"pubmed_abstract"} +{"meta":{"pmid":18456391,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":13}}},"text":"Characterization of ultrasound propagation through ex-vivo human temporal bone.\nAdjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke. The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.03 and 2.00-MHz ultrasound transducers to identify optimal ultrasound parameters that would maximize penetration and minimize aberration of the beam. To achieve this goal, in vitro experiments were conducted on five human skull specimens. In a water-filled tank, two unfocused transducers (0.12 and 1.03 MHz) and one focused transducer (2.00 MHz) were consecutively placed near the right temporal bone of each skull. A hydrophone, mounted on a micropositioning system, was moved to an estimated location of the middle cerebral artery (MCA) origin, and measurements of the surrounding acoustic pressure field were performed. For each measurement, the distance from the position of maximum acoustic pressure to the estimated origin of the MCA inside the skulls was quantified. The -3 dB depth-of-field and beamwidth in the skull were also investigated as a function of the three frequencies. Results show that the transducer alignment relative to the skull is a significant determinant of the detailed behavior of the acoustic field inside the skull. For optimal penetration, insonation normal to the temporal bone was needed. The shape of the 0.12-MHz intracranial beam was more distorted than those at 1.03 and 2.00 MHz because of the large aperture and beamwidth. However, lower ultrasound pressure reduction was observed at 0.12 MHz (22.5%). At 1.03 and 2.00 MHz, two skulls had an insufficient temporal bone window and attenuated the beam severely (up to 96.6% pressure reduction). For all frequencies, constructive and destructive interference patterns were seen near the contralateral skull wall at various elevations. The 0.12-MHz ultrasound beam depth-of-field was affected the most when passing through the temporal bone and showed a decrease in size of more than 55% on average. The speed of sound in the temporal bone of each skull was estimated at 1.03 MHz and demonstrated a large range (1752.1 to 3285.3 m\/s). Attenuation coefficients at 1.03 and 2.00 MHz were also derived for each of the five skull specimens. This work provides needed information on ultrasound beam shapes inside the human skull, which is a necessary first step for the development of an optimal transcranial ultrasound-enhanced thrombolysis device.","subset":"pubmed_abstract"} +{"meta":{"pmid":28579178,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-49":1,"2022-33":1,"2022-27":1,"2021-39":1,"2020-10":2,"2019-47":1,"2019-43":1,"2019-35":2,"2019-18":1,"2019-09":1,"2018-34":1,"2018-13":1,"2017-43":1,"2023-50":1,"2024-26":1}}},"text":"Waste biorefineries: Enabling circular economies in developing countries.\nThis paper aims to examine the potential of waste biorefineries in developing countries as a solution to current waste disposal problems and as facilities to produce fuels, power, heat, and value-added products. The waste in developing countries represents a significant source of biomass, recycled materials, chemicals, energy, and revenue if wisely managed and used as a potential feedstock in various biorefinery technologies such as fermentation, anaerobic digestion (AD), pyrolysis, incineration, and gasification. However, the selection or integration of biorefinery technologies in any developing country should be based on its waste characterization. Waste biorefineries if developed in developing countries could provide energy generation, land savings, new businesses and consequent job creation, savings of landfills costs, GHG emissions reduction, and savings of natural resources of land, soil, and groundwater. The challenges in route to successful implementation of biorefinery concept in the developing countries are also presented using life cycle assessment (LCA) studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":24473232,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Protective effect of resveratrol on biomarkers of oxidative stress induced by iron\/ascorbate in mouse spermatozoa.\nResveratrol (RVT) is a polyphenolic compound found mainly in the grape and attributed with various pharmacological properties, among them their antioxidant activity. In the present study, we assess the antioxidant activity of resveratrol on oxidative damage induced by ferrous iron\/ascorbate (100 \u00b5M\/150 \u00b5M) in sperm of CD1+ mice. We evaluated several parameters in spermatozoa treated with or without resveratrol: (i) sperm quality analysis; (ii) mitochondrial transmembrane potential (\u0394\u0471m); (iii) ROS generation; (iv) superoxide dismutase (SOD) activity; (v) glutathione peroxidase (GPX) activity; (vi) lipid peroxidation; (vii) and in vitro fertilization (IVF) capability. Spermatozoa treated with RVT (15 \u00b5g\/mL) before ferrous iron\/ascorbate treatment exhibited: a significant increase in motility (8-fold), a significant increase in viability (2-fold), a significant increase in \u0394\u0471m (1.15-fold), accompanied with a significant decrease in the generation of ROS (4.96-fold), a significant decrease in GPX activity (1.32-fold), and a significant decrease in lipid peroxidation concentration (10.29-fold) relative to spermatozoa treated with ferrous iron\/ascorbate; however, no changes in SOD activity were observed. Finally, spermatozoa treated with RVT before ferrous iron\/ascorbate treatment showed a significant increase in oocyte fertilization (1.2-fold), relative to spermatozoa treated with ferrous iron\/ascorbate. These results suggest that RVT possesses antioxidant properties that may prevent the deleterious effects produced by oxidative damage on spermatozoa, resulting in the maintenance of fertility.","subset":"pubmed_abstract"} +{"meta":{"pmid":30699573,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Dianthus barbatus-A New Host of Stolbur Phytoplasma in Serbia.\nSweet William (Dianthus barbatus, Caryophyllaceae) is a biennial or short-lived perennial plant native to southern Europe, from the Pyrenees to the Carpathians and the Balkans. During the summers of 2012 and 2013, phytoplasma-like symptoms were observed on D. barbatus plants on a Serbian plantation (Pancevo, 44\u00b051'49\u2033 N, 20\u00b039'33\u2033 E, 80 m ASL). Only seven symptomatic plants were observed in the summer of 2012. Disease incidence in 2013 was estimated to be less than 1% but increased during 2014 to 4%. Affected plants, showing symptoms of leaf reddening, malformation, and proliferation; flower bud deficiency; and abnormal shoot production, were tested for phytoplasmas. Samples were collected from seven symptomatic and three symptomless plants each year (20 samples), and total nucleic acid was extracted from midrib tissue using a method that includes a phytoplasma enrichment step and DNA purification by chloroform\/phenol (3). Oligonucleotide primers specific to the phytoplasma 16S to 23S rRNA intergenic spacer region were used in polymerase chain reaction (PCR) assays on DNA extracted from Sweet William plants (1,3). Using phytoplasma universal primer pairs P1\/P7 and P1\/16S-Sr, phytoplasma-specific 1.8- and 1.5-kb amplicons were obtained from four and six symptomatic plants collected in 2012 and 2013, respectively. Nested PCR with R16F2n\/R2 primers yielded ~1.2-kb amplicons from DNAs of all symptomatic plants (1). No amplicon was generated in PCRs conducted with DNA templates from symptomless plants. Restriction fragment length polymorphism (RFLP) analysis of amplified 1.2-kb fragments was performed using four endonucleases (AluI, Tru1I, HhaI, and HpaII). Comparative analysis was done using RFLP patterns of Stolbur (Stol), Aster Yellows (AY), Flavescence Doree-C (FD-C), Poinsettia Branch-Inducing (PoiBI), and Clover Yellow Edge (CYE) phytoplasmas. PCR-RFLP patterns from tested samples were identical to those of the Stol reference strain, indicating that diseased Sweet William was affected by phytoplasma belonging to the 16SrXII-A (Stolbur) group. The sequence of a 1.2-kb rDNA PCR product derived from sample Tk9 (deposited under accession number KM401436 in NCBI GenBank) showed the closest identity (100%) to those of Bulgarian corn (KF907506.1), Iranian 'Bois Noir' (KJ637208.1), and two Serbian phytoplasmas (KJ174507.1 from Calendula officinalis and KF614623.1 from Paeonia tenuifolia), all belonging to the 'Candidatus Phytoplasma solani' Stolbur subgroup. Previously, Aster Yellows Phytoplasma (16SrI) had been detected in two Dianthus species: D. barbatus (Sweet William) and D. caryophyllus (carnation) (2). This is the first record of the 16SrXII-A phytoplasma subgroup being associated with yellowing and reddening of D. barbatus in Serbia. The Stolbur phytoplasma occurrence on Sweet William is significant for the management of the disease in Serbia. References: (1) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (2) P. Northover et al. http:\/\/www.umanitoba.ca\/faculties\/afs\/MAC_proceedings\/proceedings\/ 2007\/Philip_Northover.pdf , 2007. (3) J. P. Prince et al. Phytopathology 83:1130, 1993.","subset":"pubmed_abstract"} +{"meta":{"pmid":21035147,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Ataxia in posterior circulation stroke: clinical-MRI correlations.\nAtaxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input\/outputs in causing ataxia. Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH\/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH\/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P<0.001) and less severe (P<0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns. In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":16832617,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: subanalysis of a double-blind randomized controlled study.\nRecent studies have shown that normalization of the lactulose breath test (LBT) with neomycin leads to a significant reduction in irritable bowel syndrome (IBS) symptoms. This subanalysis was done on the constipation-predominant IBS subgroup of patients (C-IBS) to test the ability of neomycin to improve constipation and its correlation with the elimination of methane on breath test. IBS subjects underwent LBT in a blinded fashion. They were then randomly allocated to neomycin or placebo groups. For the purpose of this analysis, only the C-IBS subjects were identified. They were then evaluated for global improvement, abdominal pain, and constipation severity. The ability of neomycin to eliminate methane and its associated improvement in constipation was also determined. One hundred eleven subjects meeting Rome I criteria for IBS were included in the study. Thirty-nine of these had C-IBS. Of these, 20 received placebo and 19 received neomycin. With neomycin, a global improvement of 36.7+\/-7.9% was seen, compared to 5.0+\/-3.2% for placebo (P < .001) in the intention-to-treat analysis. Constipation was improved by 32.6+\/-9.9% with neomycin compared to 18.7+\/-7.2% for placebo (P=.26). Of the original 111 subjects, 12 demonstrated methane on breath test. All 12 of these patients were constipation predominant. In the methane producers receiving neomycin or placebo, improvement in constipation was significantly greater in those receiving neomycin (44.0+\/-12.3%) compared to placebo (5.0+\/-5.1%) (P < .05). Treatment with neomycin improves constipation in C-IBS. This improvement depends on the presence and elimination of methane on breath test.","subset":"pubmed_abstract"} +{"meta":{"pmid":27068686,"dup_signals":{"dup_doc_count":38,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":2,"2022-49":1,"2022-27":2,"2022-21":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-24":1,"2020-10":1,"2020-05":1,"2019-39":1,"2019-13":1,"2018-51":1,"2018-47":2,"2018-39":1,"2018-34":2,"2018-30":1,"2018-22":2,"2018-17":1,"2018-09":3,"2017-51":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries.\nAs malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. However, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-Saharan Africa. A quantitative survey of human movement patterns was conducted in four countries in sub-Saharan Africa: Mali, Burkina Faso, Zambia, and Tanzania, with three to five survey locations chosen in each country. Questions were included on demographic and trip details, malaria risk behaviour, children accompanying travellers, and mobile phone usage to enable phone signal data to be better correlated with movement. A total of 4352 individuals were interviewed and 6411 trips recorded. A cluster analysis of trips highlighted two distinct traveller groups of relevance to malaria transmission: women travelling with children (in all four countries) and youth workers (in Mali). Women travelling with children were more likely to travel to areas of relatively high malaria prevalence in Mali (OR = 4.46, 95% CI = 3.42-5.83), Burkina Faso (OR = 1.58, 95% CI = 1.23-1.58), Zambia (OR = 1.50, 95% CI = 1.20-1.89), and Tanzania (OR = 2.28, 95% CI = 1.71-3.05) compared to other travellers. They were also more likely to own bed nets in Burkina Faso (OR = 1.77, 95% CI = 1.25-2.53) and Zambia (OR = 1.74, 95% CI = 1.34 2.27), and less likely to own a mobile phone in Mali (OR = 0.50, 95% CI = 0.39-0.65), Burkina Faso (OR = 0.39, 95% CI = 0.30-0.52), and Zambia (OR = 0.60, 95% CI = 0.47-0.76). Malian youth workers were more likely to travel to areas of relatively high malaria prevalence (OR = 23, 95% CI = 17-31) and for longer durations (mean of 70 days cf 21 days, p < 0.001) compared to other travellers. Women travelling with children were a remarkably consistent traveller group across all four countries surveyed. They are expected to contribute greatly towards spatial malaria transmission because the children they travel with tend to have high parasite prevalence. Youth workers were a significant traveller group in Mali and are expected to contribute greatly to spatial malaria transmission because their movements correlate with seasonal rains and hence peak mosquito densities. Interventions aimed at interrupting spatial transmission of parasites should consider these traveller groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":27241201,"dup_signals":{"dup_doc_count":24,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-10":2,"2020-45":2,"2020-29":1,"2020-16":1,"2020-10":1,"2019-51":1,"2019-35":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-47":1,"2023-23":1,"2024-30":2}}},"text":"Left inferior parietal lobe engagement in social cognition and language.\nSocial cognition and language are two core features of the human species. Despite distributed recruitment of brain regions in each mental capacity, the left parietal lobe (LPL) represents a zone of topographical convergence. The present study quantitatively summarizes hundreds of neuroimaging studies on social cognition and language. Using connectivity-based parcellation on a meta-analytically defined volume of interest (VOI), regional coactivation patterns within this VOI allowed identifying distinct subregions. Across parcellation solutions, two clusters emerged consistently in rostro-ventral and caudo-ventral aspects of the parietal VOI. Both clusters were functionally significantly associated with social-cognitive and language processing. In particular, the rostro-ventral cluster was associated with lower-level processing facets, while the caudo-ventral cluster was associated with higher-level processing facets in both mental capacities. Contrarily, in the (less stable) dorsal parietal VOI, all clusters reflected computation of general-purpose processes, such as working memory and matching tasks, that are frequently co-recruited by social or language processes. Our results hence favour a rostro-caudal distinction of lower- versus higher-level processes underlying social cognition and language in the left inferior parietal lobe.","subset":"pubmed_abstract"} +{"meta":{"pmid":28158441,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":2,"2024-30":1,"unknown":8}}},"text":"Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative.\nThe role of symptomatic patients who are toxigenic strain positive (TS+) but fecal toxin negative (FT-) in transmission of Clostridium difficile is currently unknown. We investigated the contribution of symptomatic TS+\/FT- and TS+\/FT+ patients in C. difficile transmission in 2 UK regions. From 2-step testing, all glutamate dehydrogenase (GDH)-positive specimens, regardless of fecal toxin result, from Oxford (April 2012 through April 2013) and Leeds (July 2012 through April 2013) microbiology laboratories underwent culture and whole-genome sequencing (WGS), using WGS to identify toxigenic strains. Plausible sources for each TS+\/FT+ case, including TS+\/FT- and TS+\/FT+ patients, were determined using WGS, with and without hospital admission data. A total of 1447 of 12772 (11%) fecal samples were GDH positive, 866 of 1447 (60%) contained toxigenic C. difficile, and fecal toxin was detected in 511 of 866 (59%), representing 235 Leeds and 191 Oxford TS+\/FT+ cases. TS+\/FT+ cases were 3 times more likely to be plausibly acquired from a previous TS+\/FT+ case than a TS+\/FT- patient. Fifty-one of 265 (19%) TS+\/FT+ cases diagnosed >3 months into the study were genetically related (\u22642 single-nucleotide polymorphisms) to \u22651 previous TS+\/FT+ case or TS+\/FT- patient: 27 (10%) to only TS+\/FT+ cases, 9 (3%) to only TS+\/FT- patients, and 15 (6%) to both. Only 10 of 265 (4%) were genetically related to a previous TS+\/FT+ or TS+\/FT- patient and shared the same ward simultaneously or within 28 days. Symptomatic TS+\/FT- patients were a source of C. difficile transmission, although they accounted for less onward transmission than TS+\/FT+ cases. Although transmission from symptomatic patients with either fecal toxin status accounted for a low overall proportion of new cases, both groups should be infection control targets.","subset":"pubmed_abstract"} +{"meta":{"pmid":18942980,"dup_signals":{"dup_doc_count":20,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":11}}},"text":"Characterization of colletotrichum isolates from tamarillo, passiflora, and mango in Colombia and identification of a unique species from the genus.\nABSTRACT This study was conducted to identify the species of Colletotrichum infecting tamarillo, mango, and passiflora in Colombia and to assess whether cross-infection between host species is occurring. Isolates of Colletotrichum spp. from tamarillo (n = 54), passiflora (n = 26), and mango (n = 15) were characterized by various molecular methods and by morphological criteria. Morphological characterization grouped the tamarillo isolates as C. acutatum and the passiflora and mango isolates as C. gloeosporioides. Species-specific primer analysis was reliable and confirmed grouping of the tamarillo isolates (besides Tom-6) as C. acutatum and the mango isolates (besides Man-76) as C. gloeosporioides. However, DNA of the passiflora isolates was not amplified by either C. acutatum- or C. gloeosporioides-specific primers, but reacted with a new primer, Col1, designed according to the internal transcribed spacer (ITS) 1 region of these isolates. Isolates Tom-6 and Man-76 also reacted positively with the Col1 primer. All the isolates reacting with the C. acutatum- and C. gloeosporioides-specific primers failed to react with primer Col1. Isolate Pass-35 from passiflora did not react with any of the taxon-specific primers. Arbitrarily primed polymerase chain reaction (ap-PCR), random amplified polymerase DNA (RAPD)-PCR, and A+T-rich DNA analyses delineated representative isolates into subgroups within the designated species. Molecular analyses indicated that the C. acutatum tamarillo isolates were uniform or clonal, whereas the C. gloeosporioides mango isolates and Colletotrichum passiflora isolates were heterogeneous. Likewise, sequence analysis of the complete ITS (ITS1-5.8S-ITS2) region identified certain isolates to their respective species: tamarillo isolates as C. acutatum; mango isolates as C. gloeosporioides; passiflora, Tom-6, and Man-76 isolates as a Colletotrichum sp. as yet undefined; and the Pass-35 isolate as an additional undefined Colletot-richum sp. Molecular analyses of the population of Colletotrichum isolates from passiflora, Tom-6 from tamarillo, and Man-76 from mango indicate that this population may not be host specific.","subset":"pubmed_abstract"} +{"meta":{"pmid":29651103,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Versatile and efficient chromatin pull-down methodology based on DNA triple helix formation.\nThe goal of present paper is to develop a reliable DNA-based method for isolation of protein complexes bound to DNA (Isolation of DNA Associated Proteins: IDAP). We describe a robust and versatile procedure to pull-down chromatinized DNA sequences-of-interest by formation of a triple helix between a sequence tag present in the DNA and a complementary triple helix forming oligonucleotide (TFO) coupled to a desthiobiotin residue. Following optimization to insure efficient recovery of native plasmids via TFO probe in vitro, the procedure is shown to work under various experimental situations. For instance, it allows capture proteins associated to plasmids hosted in E. coli, and is also successfully applied to recovering nucleosomes in vitro opening many possibilities to study post translational modifications of histones in a genuine nucleosome context. Incubation in human nuclear extracts of a plasmid carrying a NF-\u03baB model promoter is shown to pull-down a specific transcription factor. Finally, isolation of a specific locus from human genomic chromatin has been successfully achieved (Chromatin-of-Interest Fragment Isolation: CoIFI). In conclusion, the methodology can be implemented for capturing proteins that specifically bind to any sequence-of-interest, DNA adduct or secondary structure provided a short sequence tag for triple helix formation is located nearby.","subset":"pubmed_abstract"} +{"meta":{"pmid":11442215,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight.\nPrevention of placental malaria through administration of antimalarial medications to pregnant women in disease-endemic areas decreases the risk of delivery of low birth weight (LBW) infants. In areas of high Plasmodium falciparum transmission, two intermittent presumptive treatment doses of sulfadoxine-pyrimethamine (SP) during the second and third trimesters of pregnancy are effective in decreasing the prevalence of placental malaria in human immunodeficiency virus (HlV)-negative women, while HIV-positive women may require a monthly SP regimen to reduce their prevalence of placental parasitemia. A decision-analysis model was used to compare the cost-effectiveness of three different presumptive SP treatment regimens with febrile case management with SP in terms of incremental cost per case LBW prevented. Factors considered included HIV seroprevalence, placental malaria prevalence, LBW incidence, the cost of SP, medical care for LBW infants, and HIV testing. For a hypothetical cohort of 10,000 pregnant women, the monthly SP regimen would always be the most effective strategy for reducing LBW associated with malaria. The two-dose SP and monthly SP regimens would prevent 172 and 229 cases of LBW, respectively, compared with the case management approach. At HIV seroprevalence rates greater than 10%, the monthly SP regimen is the least expensive strategy. At HIV seroprevalence rates less than 10%, the two-dose SP regimen would be the less expensive option. When only antenatal clinic costs are considered, the two-dose and monthly SP strategies cost US $11 and $14, respectively, well within the range considered cost effective. Presumptive treatment regimens to prevent LBW associated with malaria and the subsequent increased risk of mortality during the first year of life are effective and cost effective strategies in areas with both elevated HIV prevalence and malaria transmission rates.","subset":"pubmed_abstract"} +{"meta":{"pmid":18955671,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy.\nSudden cardiac death remains a leading cause of mortality despite advances in medical treatment for the prevention of ischemic heart disease and heart failure. Recent studies showed a benefit of implantable cardioverter defibrillator implantation, but appropriate shocks for ventricular tachyarrhythmias were noted only in a minority of patients during 4 to 5 years of follow-up. Accordingly, better risk stratification is needed to optimize patient selection. In this regard, microvolt T-wave alternans (TWA) has emerged as a potentially useful measure of arrhythmia vulnerability, but it has not been evaluated previously in a prospective, randomized trial of implantable cardioverter defibrillator therapy. This investigation was a prospective substudy of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) that included 490 patients at 37 clinical sites. TWA tests were classified by blinded readers as positive (37%), negative (22%), or indeterminate (41%) by standard criteria. The composite primary end point was the first occurrence of any of the following events: sudden cardiac death, sustained ventricular tachycardia\/fibrillation, or appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 30 months, no significant differences in event rates were found between TWA-positive or -negative patients (hazard ratio 1.24, 95% confidence interval 0.60 to 2.59, P=0.56) or TWA-negative and nonnegative (positive and indeterminate) subjects (hazard ratio 1.28, 95% confidence interval 0.65 to 2.53, P=0.46). Similar results were obtained with the inclusion or exclusion of patients randomized to amiodarone in the analyses. TWA testing did not predict arrhythmic events or mortality in SCD-HeFT, although a small reduction in events (20% to 25%) among TWA-negative patients cannot be excluded given the sample size of this study. Accordingly, these results suggest that TWA is not useful as an aid in clinical decision making on implantable cardioverter defibrillator therapy among patients with heart failure and left ventricular systolic dysfunction.","subset":"pubmed_abstract"} +{"meta":{"pmid":30930963,"dup_signals":{"dup_doc_count":11}},"text":"A dietary isothiocyanate-enriched moringa (Moringa oleifera) seed extract improves glucose tolerance in a high-fat-diet mouse model and modulates the gut microbiome.\nMoringa oleifera (moringa) has been traditionally used for the treatment of diabetes and in water purification. We previously showed that moringa seed extract (MSE), standardized to its primary bioactive isothiocyanate (MIC-1), modulated inflammatory and antioxidant signaling pathways in vitro. To understand the efficacy and mechanisms of action of MSE in vivo, we incorporated MSE into the diets of normal and obese C57Bl\/6J male mice fed a standard low-fat diet or a very high-fat diet for 12 wk, respectively. MSE supplementation resulted in reduced body weight, decreased adiposity, improved glucose tolerance, reduced inflammatory gene expression, and increased antioxidant gene expression. 16S rRNA gene sequencing and quantitative PCR of fecal\/cecal samples showed major modulation of the gut microbial community and a significantly reduced bacterial load, similar to an antibiotic response. This suggests that MSE improves metabolic health by its intracellular anti-inflammatory and antioxidant activities, and\/or its antibiotic-like restructuring of the gut microbiota.","subset":"pubmed_abstract"} +{"meta":{"pmid":23959902,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2019-43":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-22":1,"2017-39":1,"2020-16":1}}},"text":"Sight over sound in the judgment of music performance.\nSocial judgments are made on the basis of both visual and auditory information, with consequential implications for our decisions. To examine the impact of visual information on expert judgment and its predictive validity for performance outcomes, this set of seven experiments in the domain of music offers a conservative test of the relative influence of vision versus audition. People consistently report that sound is the most important source of information in evaluating performance in music. However, the findings demonstrate that people actually depend primarily on visual information when making judgments about music performance. People reliably select the actual winners of live music competitions based on silent video recordings, but neither musical novices nor professional musicians were able to identify the winners based on sound recordings or recordings with both video and sound. The results highlight our natural, automatic, and nonconscious dependence on visual cues. The dominance of visual information emerges to the degree that it is overweighted relative to auditory information, even when sound is consciously valued as the core domain content.","subset":"pubmed_abstract"} +{"meta":{"pmid":17124315,"dup_signals":{"dup_doc_count":66,"dup_dump_count":41,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":2,"2022-27":1,"2022-05":1,"2021-49":1,"2021-43":2,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":2,"2019-39":3,"2019-35":1,"2018-47":1,"2018-26":1,"2018-22":1,"2018-17":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":4,"2017-34":1,"2017-30":2,"2017-22":3,"2017-17":2,"2017-09":1,"2017-04":1,"2016-50":2,"2016-44":2,"2016-40":3,"2016-36":3,"2016-30":2,"2016-22":2,"2016-18":1,"2016-07":2,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2023-40":1,"2017-13":1,"2024-26":1}}},"text":"What is natural? The need for a long-term perspective in biodiversity conservation.\nEcosystems change in response to factors such as climate variability, invasions, and wildfires. Most records used to assess such change are based on short-term ecological data or satellite imagery spanning only a few decades. In many instances it is impossible to disentangle natural variability from other, potentially significant trends in these records, partly because of their short time scale. We summarize recent studies that show how paleoecological records can be used to provide a longer temporal perspective to address specific conservation issues relating to biological invasions, wildfires, climate change, and determination of natural variability. The use of such records can reduce much of the uncertainty surrounding the question of what is \"natural\" and thereby start to provide important guidance for long-term management and conservation.","subset":"pubmed_abstract"} +{"meta":{"pmid":30580097,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Temporal stability and specificity of high bipolar electrogram entropy regions in sustained atrial fibrillation: Implications for mapping.\nThe potential utility of entropy (En) for atrial fibrillation (AF) mapping has been demonstrated in previous studies by multiple groups, where an association between high bipolar electrogram (EGM) entropy and the pivot of rotors has been shown. Though En is potentially attractive new approach to ablation, no studies have examined its temporal stability and specificity, which are critical to the application of entropy to clinical ablation. In the current study, we sought to objectively measure the temporal stability and specificity of bipolar EGM entropy in medium to long term recordings using three studies: i) a human basket catheter AF study, ii) a tachypaced sheep AF study and iii) a computer simulation study. To characterize the temporal dynamics and specificity of Approximate, Sample and Shannon entropy (ApEn\/SampEn\/ShEn) in human (H), sheep (S), and computer simulated AF. 64-electrode basket bi-atria sustained AF recordings (H:15 min; S:40 min) were separated into 5 s segments. ShEn\/ApEn\/SampEn were computed, and co-registered with NavX 3D maps. Temporal stability was determined in terms of: (i) global pattern stability of En and (ii) the relative stability the top 10% of En regions. To provide mechanistic insights into underlying mechanisms, stability characteristics were compared to models depicting various propagation patterns. To verify these results, cross-validation was performed across multiple En algorithms, across species, and compared with dominant frequency (DF) temporal characteristics. The specificity of En was also determined by looking at the association of En to rotors and areas of wave cross propagation. Episodes of AF were analysed (H:26 epochs, 6040 s; S:15 epochs, 14,160 s). The global pattern of En was temporally unstable (CV- H:13.42% \u00b1 4.58%; S:14.13% \u00b1 8.13%; Friedman- H: p > 0.001; S: p > 0.001). However, within this dynamic flux, the top 10% of ApEn\/SampEn\/ShEn regions were relatively temporally stable (Kappa >0.6) whilst the top 10% of DF regions were unstable (Kappa <0.06). In simulated AF scenarios, the experimental data were optimally reproduced in the context of an AF pattern with stable rotating waves surrounded by wavelet breakup (Kappa: 0.610; p < 0.0001). En shows global temporal instability, however within this dynamic flux, the top 10% regions exhibited relative temporal stability. This suggests that high En regions may be an appealing ablation target. Despite this, high En was associated with not just the pivot of rotors but also with areas of cross propagation, which suggests the need for future work before clinical application is possible.","subset":"pubmed_abstract"} +{"meta":{"pmid":18948493,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-26":1,"2017-13":1}}},"text":"The short-term effects of prescribed burning on biomass removal and the release of nitrogen and phosphorus in a treatment wetland.\nNutrient removal by constructed wetlands can decline over time due to the accumulation of organic matter. A prescribed burn is one of many management strategies used to remove detritus in macrophyte-dominated systems. We quantified the short-term effects on effluent water quality and the amount of aboveground detritus removed from a prescribed burn event. Surface water outflow concentrations were approximately three times higher for P and 1.5 times higher for total Kjeldhal nitrogen (TKN) following the burn event when compared to the control. The length of time over which the fire effect was significant (P < 0.05), 3 d for TKN and up to 23 d for P fractions. Over time, the concentration of soluble reactive phosphorus (SRP) in the effluent decreased, but was compensated with increases in dissolved organic phosphorus (DOP) and particulate phosphorus (PP), such that net total P remained the same. Total aboveground biomass decreased by 68.5% as a result of the burn, however, much of the live vegetation was converted to standing dead material. These results demonstrate that a prescribed burn can significantly decrease the amount of senescent organic matter in a constructed wetland. However, short-term nutrient releases following the burn could increase effluent nutrient concentrations. Therefore, management strategies should include hydraulically isolating the burned area immediately following the burn event to prevent nutrient export.","subset":"pubmed_abstract"} +{"meta":{"pmid":23032355,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"National newspaper portrayal of nursing homes: tone of coverage and its correlates.\nThe mass media can exert considerable influence over the relative saliency of different public policy concerns. Because emotional resonance can have a strong impact on how the general public and policy makers perceive specific issues, the purpose of this study is to characterize the tone of nursing home coverage in the national media. Keyword searches of LexisNexis were used to identify 1562 articles published in 4 national newspapers from 1999 to 2008. The content of each article was analyzed and tone, themes, prominence, focal entity, and geographic focus assessed. Multinomial logit was used to examine the correlates of tone. Most articles were negative (49.2%) or neutral (40.3%); few were positive (10.5%). Both positive and negative articles were considerably more likely than neutral articles (>10 times) to be an opinion piece. Negative articles were three quarters more likely to be on the front page and two thirds more likely to focus on industry actors. Positive articles were 10 times more likely to be about community actors and two and three quarters more likely to be about local issues. Positive articles were considerably more likely to be about quality; negative articles about negligence\/fraud and natural disasters. Findings suggest that negative reporting predominates and its impact on public perceptions and government decision making may be reinforced by its prominence and focus on industry interests\/behavior. The adverse impact of media coverage on the industry's reputation has likely influenced consumer care choices, particularly in light of growing competition from the home-based and community-based and assisted living sectors.","subset":"pubmed_abstract"} +{"meta":{"pmid":22925506,"dup_signals":{"dup_doc_count":36,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2020-34":1,"2020-05":1,"2019-39":1,"2019-35":1,"2019-30":3,"2019-26":1,"2019-22":1,"2019-18":2,"2019-13":1,"2019-09":3,"2019-04":2,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-26":1,"2023-50":1,"2024-26":1}}},"text":"Specific morphogenetic events in mouse external genitalia sex differentiation are responsive\/dependent upon androgens and\/or estrogens.\nThe objective of this study was to perform a comprehensive morphologic analysis of developing mouse external genitalia (ExG) and to determine specific sexual differentiation features that are responsive to androgens or estrogens. To eliminate sex steroid signaling postnatally, male and female mice were gonadectomized on the day of birth, and then injected intraperitoneally every other day with DES (200 ng\/g), DHT (1 \u03bcg\/g), or oil. On day-10 postnatal male and female ExG were dissected, fixed, embedded, serially sectioned and analyzed. We identified 10 sexually dimorphic anatomical features indicative of normal penile and clitoral differentiation in intact mice. Several (but not all) penile features were impaired or abolished as a result of neonatal castration. Those penile features remaining after neonatal castration were completely abolished with attendant clitoral development in androgen receptor (AR) mutant male mice (X(Tfm)\/Y and X\/Y AR-null) in which AR signaling is absent both pre- and postnatally. Administration of DHT to neonatally castrated males restored development of all 10 masculine features to almost normal levels. Neonatal ovariectomy of female mice had little effect on clitoral development, whereas treatment of ovariectomized female mice with DHT induced partial masculinization of the clitoris. Administration of DES to neonatally gonadectomized male and female mice elicited a spectrum of development abnormalities. These studies demonstrate that the presence or absence of androgen prenatally specifies penile versus clitoral identity. Differentiated penile features emerge postnatally and are sensitive to and dependent upon prenatal or pre- and postnatal androgen. Emergence of differentiated clitoral features occurs postnatally in either intact or ovariectomized females. It is likely that each penile and clitoral feature has a unique time-course of hormonal dependency\/sensitivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":33704072,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Attitudes Toward the Use of Voice-Assisted Technologies Among People With Parkinson Disease: Findings From a Web-Based Survey.\nSpeech problems are common in people living with Parkinson disease (PD), limiting communication and ultimately affecting their quality of life. Voice-assisted technology in health and care settings has shown some potential in small-scale studies to address such problems, with a retrospective analysis of user reviews reporting anecdotal communication effects and promising usability features when using this technology for people with a range of disabilities. However, there is a need for research to establish users' perspectives on the potential contribution of voice-assisted technology for people with PD. This study aims to explore the attitudes toward the use of voice-assisted technology for people with PD. A survey was approved for dissemination by a national charity, Parkinson's UK, to be completed on the web by people living with the condition. The survey elicited respondent demographics, PD features, voice difficulties, digital skill capability, smart technology use, voice-assisted technology ownership and use, confidentiality, and privacy concerns. Data were analyzed using descriptive statistics and summative content analysis of free-text responses. Of 290 participants, 79.0% (n=229) indicated that they or others had noticed changes in their speech or voice because of the symptoms of their condition. Digital skills and awareness were reported on 11 digital skills such as the ability to find a website you have visited before. Most participants (n=209, 72.1%) reported being able to perform at least 10 of these 11 tasks. Similarly, of 70.7% (n=205) participants who owned a voice-assisted device, most of them (166\/205, 80.9%) used it regularly, with 31.3% (52\/166) reporting that they used the technology specifically to address the needs associated with their PD. Of these 166 users, 54.8% (n=91) sometimes, rarely, or never had to repeat themselves when using the technology. When asked about speech changes since they started using it, 25% (27\/108) of participants noticed having to repeat themselves less and 14.8% (16\/108) perceived their speech to be clearer. Of the 290 respondents, 90.7% (n=263) were not concerned, or only slightly concerned, about privacy and confidentiality. Having been added to the homes of Western society, domestic voice assist devices are now available to assist those with communication problems. People with PD reported a high digital capability, albeit those who responded to a web-based survey. Most people have embraced voice-assisted technology, find it helpful and usable, and some have found benefit to their speech. Speech and language therapists may have a virtual ally that is already in the patient's home to support future therapy provision.","subset":"pubmed_abstract"} +{"meta":{"pmid":29315858,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Understanding successful and unsuccessful landings of aerial maneuver variations in professional surfing.\nAlthough performing aerial maneuvers can increase wave score and winning potential in competitive surfing, the critical features underlying successful aerial performance have not been systematically investigated. This study aimed to analyze highly skilled aerial maneuver performance and to identify the critical features associated with successful or unsuccessful landing. Using video recordings of the World Surf League's Championship Tour, every aerial performed during the quarterfinal, semifinal, and final heats from the 11 events in the 2015 season was viewed. From this, 121 aerials were identified with the Frontside Air (n = 15) and Frontside Air Reverse (n = 67) being selected to be qualitatively assessed. Using chi-squared analyses, a series of key critical features, including landing over the center of the surfboard (FS Air \u03c72 = 14.00, FS Air Reverse \u03c72 = 26.61; P < .001) and landing with the lead ankle in dorsiflexion (FS Air \u03c72 = 3.90, FS Air Reverse \u03c72 = 13.64; P < .05), were found to be associated with successful landings. These critical features help surfers land in a stable position, while maintaining contact with the surfboard. The results of this study provide coaches with evidence to adjust the technique of their athletes to improve their winning potential.","subset":"pubmed_abstract"} +{"meta":{"pmid":18944522,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Genetic Diversity of Panicum mosaic virus Satellite RNAs in St. Augustinegrass.\nABSTRACT St. Augustine decline is a viral disease caused by Panicum mosaic virus (PMV) alone or in combination with a satellite virus (SPMV) and\/or satellite RNAs (satRNAs). A ribonuclease protection assay (RPA) was used to evaluate the genetic diversity of PMV satRNAs isolated from 100 naturally infected St. Augustinegrass plants (Stenotaphrum secundatum). Distinctive satRNA RPA profiles were observed for 40 of 52 samples from College Station (CS) and 37 of 48 samples from Corpus Christi (CC), Texas. A dendrogram constructed from the RPA data revealed that satRNAs were grouped in two distinct clusters based on their place of origin. From 100 samples, only 4 satRNAs from CS were placed in the CC group, and only 2 satRNAs from CC were placed in the CS group. The data show that there is genetic variability in PMV satRNAs in naturally occurring infections, and distinct geographically separate populations can be identified from CC and CS.","subset":"pubmed_abstract"} +{"meta":{"pmid":32098995,"dup_signals":{"dup_doc_count":56,"dup_dump_count":19,"dup_details":{"curated_sources":1,"2023-40":2,"2023-23":3,"2023-14":4,"2023-06":2,"2022-49":2,"2022-40":4,"2022-27":3,"2022-21":2,"2022-05":4,"2021-49":1,"2021-43":4,"2021-39":1,"2021-31":5,"2021-25":1,"2021-21":1,"2021-17":4,"2021-10":1,"2021-04":6,"2020-45":5}}},"text":"Supervised deep learning for real-time quality monitoring of laser welding with X-ray radiographic guidance.\nLaser welding is a key technology for many industrial applications. However, its online quality monitoring is an open issue due to the highly complex nature of the process. This work aims at enriching existing approaches in this field. We propose a method for real-time detection of process instabilities that can lead to defects. Hard X-ray radiography is used for the ground truth observations of the sub-surface events that are critical for the quality. A deep artificial neural network is applied to reveal the unique signatures of those events in wavelet spectrograms from the laser back-reflection and acoustic emission signals. The autonomous classification of the revealed signatures is tested on real-life data, while the real-time performance is reached by means of parallel computing. The confidence of the quality classification ranges between 71% and 99%, with a temporal resolution down to 2 ms and a computation time per classification task as low as 2 ms. This approach is a new paradigm in the digitization of industrial processes and can be exploited to provide feedbacks in a closed-loop quality control system.","subset":"pubmed_abstract"} +{"meta":{"pmid":22003360,"dup_signals":{"dup_doc_count":30,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2023-50":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":2,"2021-39":3,"2021-31":1,"2021-25":1,"2021-21":1,"2021-10":3,"2021-04":1,"2020-45":2,"2024-26":3,"2024-22":1}}},"text":"Towards a family-centered approach to HIV treatment and care for HIV-exposed children, their mothers and their families in poorly resourced settings.\nThis article provides a summary of emerging psychosocial evidence relevant to the success of comprehensive family-centered approaches to HIV prevention, treatment, care and support programs in poorly resourced settings. This report synthesizes current evidence on maternal, paternal and family experiences of HIV prevention, diagnosis, treatment, adherence and disclosure, with special focus on HIV-infected mothers and HIV-exposed children. Taking a developmental approach, we explore the current challenges and opportunities towards a family-centered approach within the continuum of HIV treatment and care, beginning in pregnancy and following the course of childhood. The discussion is limited to early and middle childhood and excludes discussion of special issues emergent in adolescence, which would warrant discussion outside the scope of this article. Attention is drawn to the complexity of problems arising within the family context and the need for improvements in the integration of aspects of treatment, care and support. While this article focuses on examples from sub-Saharan Africa, the lessons learnt and future challenges outlined are applicable to most low- and middle-income countries, and to poorly resourced contexts in higher-income countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":9799664,"dup_signals":{"dup_doc_count":12,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":2}}},"text":"Expressions and activities of cell cycle regulatory molecules during the transition from myocyte hyperplasia to hypertrophy.\nThe role of cell cycle dependent molecules in controlling the switch from cardiac myocyte hyperplasia to hypertrophy remains unclear, although in the rat this process occurs between day 3 and 4 after birth. In this study we have determined (1) cell cycle profiles by fluorescence activated cell sorting (FACS); and (2) expressions, co-expressions and activities of a number of cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and in vitro kinase assays in freshly isolated rat cardiac myocytes obtained from 2, 3, 4 and 5-day-old animals. The percentage of myocytes found in the S phase of the cell cycle decreased significantly during the transition from hyperplasia to hypertrophy (5.5, 3.5, 2.3 and 1.9% of cells in 2-, 3-, 4- and 5-day-old myocytes, respectively,P<0.05), concomitant with a significant increase in the percentage of G0\/G1 phase cells. At the molecular level, the expressions and activities of G1\/S and G2\/M phase acting cyclins and CDKs were downregulated significantly during the transition from hyperplasia to hypertrophy, whereas the expressions and activities of G1 phase acting cyclins and CDKs were upregulated significantly during this transition. In addition, p21(CIP1)- and p27(KIP1)- associated CDK kinase activities remained relatively constant when histone H1 was used as a substrate, whereas phosphorylation of the retinoblastoma protein was upregulated significantly during the transition from hyperplasia to hypertrophy. Thus, there is a progressive and significant G0\/G1 phase blockade during the transition from myocyte hyperplasia to hypertrophy. Whilst CDK2 and cdc2 may be pivotal in the withdrawal of cardiac myocytes from the cell cycle, CDK4 and CDK6 may be critical for maintaining hypertrophic growth of the myocyte during development.","subset":"pubmed_abstract"} +{"meta":{"pmid":23287831,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Concurrent training in elite male runners: the influence of strength versus muscular endurance training on performance outcomes.\nMuch recent attention has been given to the compatibility of combined aerobic and anaerobic training modalities. However, few of these studies have reported data related to well-trained runners, which is a potential limitation. Therefore, because of the limited evidence available for this population, the main aim was to determine which mode of concurrent strength-endurance training might be the most effective at improving running performance in highly trained runners. Eighteen well-trained male runners (age 23.7 \u00b1 1.2 years) with a maximal oxygen consumption (VO2max) more than 65 ml\u00b7kg(-1)\u00b7min(-1) were randomly assigned into 1 of the 3 groups: Endurance-only Group (n = 6), who continued their usual training, which included general strength training with Thera-band latex-free exercise bands and endurance training; Strength Group (SG; n = 6) who performed combined resistance and plyometric exercises and endurance training; Endurance-SG (ESG; n = 6) who performed endurance-strength training with loads of 40% and endurance training. The study comprised 12 weeks of training in which runners trained 8 times a week (6 endurance and 2 strength sessions) and 5 weeks of detraining. The subjects were tested on 3 different occasions (countermovement jump height, hopping test average height, 1 repetition maximum, running economy (RE), VO2max, maximal heart rate [HRmax], peak velocity (PV), rating of perceived exertion, and 3-km time trial were measured). Findings revealed significant time \u00d7 group interaction effects for almost all tests (p < 0.05). We can conclude that concurrent training for both SG and ESG groups led to improved maximal strength, RE, and PV with no significant effects on the VO2 kinetics pattern. The SG group also seems to show improvements in 3-km time trial tests.","subset":"pubmed_abstract"} +{"meta":{"pmid":33767283,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Age-stratified comparison of clinical outcomes between medical and surgical treatments in patients with unilateral primary aldosteronism.\nAlthough adrenalectomy (ADX) is an established treatment for unilateral primary aldosteronism (uPA), the influence of age on the surgical outcomes is poorly understood. Therefore, we aimed to elucidate how age affects the clinical outcomes after treatments. We analyzed 153 older (\u2265 65 years) and 702 younger patients (< 65 years) with uPA, treated either with ADX or mineralocorticoid receptor antagonist (MRA) in the Japan PA Study, and compared the estimated glomerular filtration rate (eGFR) or blood pressure over a 36-month period after treatments. ADX-treated patients showed severer biochemical indicators than MRA-treated patients. During 6 and 36 months, the eGFR decreased more prominently in older but not in younger patients with ADX than in those with MRA, which remained significant after adjustment with the inverse probability of treatment weighting (IPTW). There was a significant interaction between the age-groups and the treatment choices in the change of the eGFR with IPTW-adjusted analysis. The post-treatment dose of antihypertensive medication was lower in younger and higher in older patients with ADX than those with MRA. The clinical benefit of ADX differed between younger and older patients with uPA. These findings indicate the need for further validation on whether ADX can benefit older patients with uPA.","subset":"pubmed_abstract"} +{"meta":{"pmid":25003366,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma.\nSeveral treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)\/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p = 0.024). High miR-200c (p = 0.0004) and miR-141 (p = 0.009) expression correlated with shorter OS in adenocarcinoma - but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p = 0.033) and in adenocarcinoma patients (OR, 10.649; p = 0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p = 0.04; A-549, p = 0.03; HCC-44, p = 0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001). High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":16760892,"dup_signals":{"dup_doc_count":55,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2023-06":1,"2022-40":1,"2022-21":1,"2021-39":2,"2021-21":1,"2020-45":1,"2020-34":1,"2020-16":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":4,"2018-26":1,"2018-17":1,"2018-13":3,"2018-09":2,"2017-51":5,"2017-43":5,"2017-34":5,"2017-26":5,"2023-50":1,"2024-22":1}}},"text":"Mold prevention strategies and possible health effects in the aftermath of hurricanes and major floods.\nExtensive water damage after major hurricanes and floods increases the likelihood of mold contamination in buildings. This report provides information on how to limit exposure to mold and how to identify and prevent mold-related health effects. Where uncertainties in scientific knowledge exist, practical applications designed to be protective of a person's health are presented. Evidence is included about assessing exposure, clean-up and prevention, personal protective equipment, health effects, and public health strategies and recommendations. The recommendations assume that, in the aftermath of major hurricanes or floods, buildings wet for <48 hours will generally support visible and extensive mold growth and should be remediated, and excessive exposure to mold-contaminated materials can cause adverse health effects in susceptible persons regardless of the type of mold or the extent of contamination. For the majority of persons, undisturbed mold is not a substantial health hazard. Mold is a greater hazard for persons with conditions such as impaired host defenses or mold allergies. To prevent exposure that could result in adverse health effects from disturbed mold, persons should 1) avoid areas where mold contamination is obvious; 2) use environmental controls; 3) use personal protective equipment; and 4) keep hands, skin, and clothing clean and free from mold-contaminated dust. Clinical evaluation of suspected mold-related illness should follow conventional clinical guidelines. In addition, in the aftermath of extensive flooding, health-care providers should be watchful for unusual mold-related diseases. The development of a public health surveillance strategy among persons repopulating areas after extensive flooding is recommended to assess potential health effects and the effectiveness of prevention efforts. Such a surveillance program will help CDC and state and local public health officials refine the guidelines for exposure avoidance, personal protection, and clean-up and assist health departments to identify unrecognized hazards.","subset":"pubmed_abstract"} +{"meta":{"pmid":21802659,"dup_signals":{"dup_doc_count":44,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":2,"2022-49":1,"2022-40":1,"2022-21":1,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":1,"2021-04":1,"2020-34":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-13":2,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":2,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":1,"2023-50":1,"2024-30":2,"2024-26":1,"2024-18":1,"2017-13":1}}},"text":"Should neonates sleep alone?\nMaternal-neonate separation (MNS) in mammals is a model for studying the effects of stress on the development and function of physiological systems. In contrast, for humans, MNS is a Western norm and standard medical practice. However, the physiological impact of this is unknown. The physiological stress-response is orchestrated by the autonomic nervous system and heart rate variability (HRV) is a means of quantifying autonomic nervous system activity. Heart rate variability is influenced by level of arousal, which can be accurately quantified during sleep. Sleep is also essential for optimal early brain development. To investigate the impact of MNS in humans, we measured HRV in 16 2-day-old full-term neonates sleeping in skin-to-skin contact with their mothers and sleeping alone, for 1 hour in each place, before discharge from hospital. Infant behavior was observed continuously and manually recorded according to a validated scale. Cardiac interbeat intervals and continuous electrocardiogram were recorded using two independent devices. Heart rate variability (taken only from sleep states to control for level of arousal) was analyzed in the frequency domain using a wavelet method. Results show a 176% increase in autonomic activity and an 86% decrease in quiet sleep duration during MNS compared with skin-to-skin contact. Maternal-neonate separation is associated with a dramatic increase in HRV power, possibly indicative of central anxious autonomic arousal. Maternal-neonate separation also had a profoundly negative impact on quiet sleep duration. Maternal separation may be a stressor the human neonate is not well-evolved to cope with and may not be benign.","subset":"pubmed_abstract"} +{"meta":{"pmid":12374320,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2015-06":1,"unknown":8}}},"text":"Exact frequency-domain reconstruction for thermoacoustic tomography--II: Cylindrical geometry.\nMicrowave-induced thermoacoustic tomography (TAT) in a cylindrical configuration is developed to image biological tissue. Thermoacoustic signals are acquired by scanning a flat ultrasonic transducer. Using a new expansion of a spherical wave in cylindrical coordinates, we apply the Fourier and Hankel transforms to TAT and obtain an exact frequency-domain reconstruction method. The effect of discrete spatial sampling on image quality is analyzed. An aliasing-proof reconstruction method is proposed. Numerical and experimental results are included.","subset":"pubmed_abstract"} +{"meta":{"pmid":11951377,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Death from hypovolemic shock caused by perforation of duodenal ulcer in a patient with angiosarcoma of the scalp.\nWe report a case of an 86-year-old woman with angiosarcoma on the scalp, who died from hypovolemic shock caused by perforation of a duodenal ulcer. A purple-red macule was first noticed on her left temporal scalp, and over a 1-month period this macule rapidly grew to a 6 cm purple-red indurated plaque with hematomas. The diagnosis of angiosarcoma was made based on the clinical features and histopathological finding of the lesional skin. Perilesional injections of recombinant interleukin 2 (rIL-2) were followed by surgical resection of the lesion and graft repair. However, 5 months later, new hematomas appeared and increased in number and size to cover her cheek, left temporal scalp and around the grafted area. Electron-beam radiotherapy showed only a temporary effect and the skin lesions with spontaneous severe bleeding extended rapidly again toward a wide region of the left half of the scalp and cheek. The patient died of hypovolemic shock after acute abdominal pain with intestinal hemorrhage. The surgical pathology revealed the presence of a perforated duodenal ulcer which might have been the direct cause of hypovolemic shock.","subset":"pubmed_abstract"} +{"meta":{"pmid":16752583,"dup_signals":{"dup_doc_count":47,"dup_dump_count":26,"dup_details":{"curated_sources":4,"2016-40":1,"2016-36":1,"2016-30":2,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":2,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":2,"2014-49":2,"2014-42":7,"2014-41":4,"2014-35":1,"2014-23":4,"2014-15":2,"2016-44":1,"2015-11":1,"2015-06":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Clinical comparison of a novel breast DXA technique to mammographic density.\nWe compare mammography breast density (BD(MD)) to the measure of breast composition using a clinical dual energy absorptiometry (DXA) system (BD(DXA)) calibrated to measure breast density. A DXA scanning protocol was developed to scan breasts isolated in the DXA scan field in either a prone pendulous or decubitus mediolateral position. A total of 17 participants were recruited among women undergoing clinical mammography examinations. Each participant had duplicate DXA scans and duplicate craniocaudal-view mammograms of their right breast with repositioning between each scan and one DXA and one craniocaudal-view mammogram of their left breast. The in vivo repeatability (RMS SD) of BD(DXA) and BD(MD) on duplicate scans was found to be 1.2% for BD(DXA) and 1.4% for BD(MD) when repeat BD(MD) measures were made on the same day. When repeat BD(MD) measures of the same breast were made more than 50 days apart, the repeatability decreased to 5.5%. Left and right breast measurements were highly correlated with both techniques at r2 = 0.98 for BD(DXA) and r2 = 0.86 for BD(MD). Moderate correlation (r2 = 0.52) was found between BD(DXA) and BD(MD) measurements. However, after recalibrating the DXA system to mammography reference materials, negative percent fibroglandular values were measured for the most fatty breasts. Thus, our results are reproducible and accurate to common mammography tissue standards, but did not accurately reflect true percent fibroglandular levels and further development of phantom standards are necessary. We conclude that breast composition can be precisely evaluated and assessed with clinical DXA densitometers at a lower dose than with mammographic breast density methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":17246135,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Nullisomic Tetrahymena. II. a Set of Nullisomics Define the Germinal Chromosomes.\nCrosses of a diploid Tetrahymena thermophila to a strain with a haploid germinal nucleus result in chromosome loss during meiosis in the haploid. The resulting monosomics can be made nullisomic by a special cross that induces homozygosis of a meiotic product of the germinal nucleus, but retention of the parental somatic nucleus. The creation and testing of single nullisomics for three of the five chromosome pairs and a triple nullisomic missing another pair is presented. Taken together, these strains make possible a series of crosses in which all but one of the chromosomes is missing in one parent. This set of nullisomics can, therefore, be used to map any mutation in Tetrahymena to a specific chromosome.","subset":"pubmed_abstract"} +{"meta":{"pmid":10880457,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Isolation and characterization of Tn7 transposase gain-of-function mutants: a model for transposase activation.\nTn7 transposition has been hypothesized to require a heteromeric transposase formed by two Tn7-encoded proteins, TnsA and TnsB, and accessory proteins that activate the transposase when they are associated with an appropriate target DNA. This study investigates the mechanism of Tn7 transposase activation by isolation and analysis of transposase gain-of-function mutants that are active in the absence of these accessory proteins. This work shows directly that TnsA and TnsB are essential and sufficient components of the Tn7 transposase and also provides insight into the signals that activate the transposase. We also describe a protein-protein interaction between TnsA and TnsC, a regulatory accessory protein, that is likely to be critical for transposase activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":24583693,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-39":1,"2020-05":1,"2019-09":1,"2019-04":1,"2018-39":1,"2018-26":1,"2018-17":2,"2017-51":1,"2017-43":1,"2023-23":1}}},"text":"Direct biosensor detection of botulinum neurotoxin endopeptidase activity in sera from patients with type A botulism.\nBotulinum neurotoxin A (BoNT\/A) has intrinsic endoprotease activity specific for SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation of SNAP-25 by BoNT\/A underlies botulism, a rare but potentially fatal disease. There is a crucial need for a rapid and sensitive in vitro serological test for BoNT\/A to replace the current in vivo mouse bioassay. Cleavage of SNAP-25 by BoNT\/A generates neo-epitopes which can be detected by binding of a monoclonal antibody (mAb10F12) and thus measured by surface plasmon resonance (SPR). We have explored two SPR assay formats, with either mAb10F12 or His6-SNAP-25 coupled to the biosensor chip. When BoNT\/A was incubated with SNAP-25 in solution and the reaction products were captured on a mAb-coated chip, a sensitivity of 5 fM (0.1LD50\/ml serum) was obtained. However, this configuration required prior immunoprecipitation of BoNT\/A. A sensitivity of 0.5 fM in 10% serum (0.1 LD50\/ml serum) was attained when SNAP-25 was coupled directly to the chip, followed by sequential injection of BoNT\/A samples and mAb10F12 into the flow system to achieve on-chip cleavage and detection, respectively. This latter format detected BoNT\/A endoprotease activity in 50-100 \u00b5l serum samples from all patients (11\/11) with type A botulism within 5h. No false positives occurred in sera from healthy subjects or patients with other neurological diseases. The automated chip-based procedure has excellent specificity and sensitivity, with significant advantages over the mouse bioassay in terms of rapidity, required sample volume and animal ethics.","subset":"pubmed_abstract"} +{"meta":{"pmid":7644510,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"14-3-3 proteins associate with cdc25 phosphatases.\nThe cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein have been isolated in this screening. 14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that were originally isolated in mammalian brain preparations and that possess diverse biochemical activities related to signal transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins physically interact both in vitro and in vivo. 14-3-3 protein does not, however, affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. 14-3-3 protein, however, has no effect on the cdc25A-kinase activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with Raf-1 in vivo, participating in the linkage between mitogenic signaling and the cell cycle machinery.","subset":"pubmed_abstract"} +{"meta":{"pmid":27572833,"dup_signals":{"dup_doc_count":38,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":3,"2020-45":1,"2020-34":2,"2020-24":1,"2020-05":1,"2019-51":2,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-40":1,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"Global microbialization of coral reefs.\nMicrobialization refers to the observed shift in ecosystem trophic structure towards higher microbial biomass and energy use. On coral reefs, the proximal causes of microbialization are overfishing and eutrophication, both of which facilitate enhanced growth of fleshy algae, conferring a competitive advantage over calcifying corals and coralline algae. The proposed mechanism for this competitive advantage is the DDAM positive feedback loop (dissolved organic carbon (DOC), disease, algae, microorganism), where DOC released by ungrazed fleshy algae supports copiotrophic, potentially pathogenic bacterial communities, ultimately harming corals and maintaining algal competitive dominance. Using an unprecedented data set of >400 samples from 60 coral reef sites, we show that the central DDAM predictions are consistent across three ocean basins. Reef algal cover is positively correlated with lower concentrations of DOC and higher microbial abundances. On turf and fleshy macroalgal-rich reefs, higher relative abundances of copiotrophic microbial taxa were identified. These microbial communities shift their metabolic potential for carbohydrate degradation from the more energy efficient Embden-Meyerhof-Parnas pathway on coral-dominated reefs to the less efficient Entner-Doudoroff and pentose phosphate pathways on algal-dominated reefs. This 'yield-to-power' switch by microorganism directly threatens reefs via increased hypoxia and greater CO2 release from the microbial respiration of DOC.","subset":"pubmed_abstract"} +{"meta":{"pmid":21321148,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2021-10":1,"2020-40":1,"2019-13":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2022-49":1,"2017-13":1,"2024-22":1}}},"text":"Impact of dose de-escalation and escalation on daptomycin's pharmacodynamics against clinical methicillin-resistant Staphylococcus aureus isolates in an in vitro model.\nDe-escalation and escalation therapeutic strategies are commonly employed by clinicians on the basis of susceptibility results and patient response. Since no in vitro or in vivo data are currently available to support one strategy over the other for daptomycin, we attempted to evaluate the effects of dose escalation and de-escalation on daptomycin activity against methicillin-resistant Staphylococcus aureus (MRSA) isolates using an in vitro pharmacokinetic\/pharmacodynamic (PK\/PD) model with simulated endocardial vegetations. Three clinical MRSA isolates, including one heterogeneous vancomycin-intermediate S. aureus (hVISA) isolate and one vancomycin-intermediate S. aureus (VISA) isolate, were exposed to daptomycin at 10 or 6 mg\/kg of body weight\/day for 8 days using a starting inoculum of \u223c10(9) CFU\/g of vegetations, with dose escalation and de-escalation initiated on the fourth day. Daptomycin MIC values ranged from 0.5 to 1 \u03bcg\/ml. In the PK\/PD model, high-dose daptomycin (10 mg\/kg\/day) and de-escalation simulation (10 to 6 mg\/kg\/day) appeared to be the most efficient regimens against the three tested isolates, exhibiting the fastest bactericidal activity (4 to 8 h) compared to that of the standard regimen of 6 mg\/kg\/day and the escalation therapy of 6 to 10 mg\/kg\/day. The differences in the numbers of CFU\/g observed between dose escalation and de-escalation were significant for the hVISA strain, with the de-escalation simulation exhibiting a better killing effect than the escalation simulation (P<0.024). Although our results need to be carefully considered, the use of high-dose daptomycin up front demonstrated the most efficient activity against the tested isolates. Different therapeutic scenarios including isolates with higher MICs and prolonged drug exposures are warranted to better understand the outcomes of escalation and de-escalation strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":11234499,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[Chronic diarrhea as late complication of partial gastrectomy].\nThe authors present a clinical case of a forty-nine-year-old man admitted to hospital because of a seven month history of diarrhoea. The patient had been submitted to partial gastrectomy twenty-two years ago due to peptic ulcer. The analytic study was compatible with malabsorption syndrome. The colonoscopic and radiological studies revealed the existence of two fistulas between the gastric-stump, the small intestine and the colon. The patient was submitted to surgery with resection of the fistulas and re-gastrectomy with trunk vagotomy and Roux-en-Y reanastomosis. The follow-up twelve months after surgery showed an asymptomatic subject with weight recovery who had resumed his professional activities without limitations.","subset":"pubmed_abstract"} +{"meta":{"pmid":24044030,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Use of Ultrasonic Bone Surgery (Piezosurgery) to Surgically Treat Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ). A Case Series Report with at Least 1 Year of Follow-Up.\nThis preliminary work documents the use of a powerful piezosurgery device to treat biphosphonate-related osteonecrosis of the jaw (BRONJ) in combination with classical medication therapy. Eight patients presenting 9 BRONJ sites were treated, 2 in the maxilla and 7 in the mandible. Reason for biphosphonate (BiP) intake was treatment of an oncologic disease for 5 patients and osteoporosis for 3. The oncologic and osteoporosis patients were diagnosed with BRONJ after 35-110 months and 80-183 months of BiP treatment, respectively. BRONJ 2 and 3 was found in 4 patients. Resection of the bone sequestrae was performed with a high power ultrasonic (piezo) surgery and antibiotics were administrated for 2 weeks. Soft tissue healing was incomplete at the 2-week control but it was achieved within 1 month. At the 1-year control, soft tissue healing was maintained at all patients, without symptom recurrence. One patient with paraesthesia had abated; of the 2 pa-tients with trismus, one was healed, severity of the second trismus abated. This case report series suggests that bone resection performed with a high power ultrasonic surgery device combined with antibiotics might lead to BRONJ healing. More patients are warranted to confirm the present findings and assess this treatment approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":26079616,"dup_signals":{"dup_doc_count":40,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2022-27":1,"2022-21":2,"2021-43":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":2,"2019-35":2,"2019-26":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-47":1,"2018-30":1,"2018-22":2,"2018-13":2,"2017-47":2,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-09":2,"2017-04":2,"2022-49":1,"2017-13":1,"2024-26":1}}},"text":"Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation.\nIn 2013, the Follow-up and Active Surveillance of Trivalent Influenza Vaccine in Mums (FASTMum) program began using short message service (SMS) to collect adverse event information in pregnant women who recently received trivalent influenza vaccine (TIV). This study was designed to compare data collected via SMS and telephone for the purposes of monitoring vaccine safety. A number of 344 women who received TIV were randomly assigned to a telephone interview group. They were telephoned seven days post-vaccination and administered a standard survey soliciting any adverse events following immunisation (AEFI) they experienced. They were matched by brand of vaccine, age group, and residence to 344 women who were sent a SMS seven days post-vaccination. The SMS solicited similar information. AEFI reported by SMS and telephone interview were compared by calculating risk ratios. Response rate was higher to SMS compared to telephone interview (90.1% vs. 63.9%). Women who were surveyed by SMS were significantly less likely to report an AEFI compared to women who were surveyed by telephone (RR: 0.41; 95% CI: 0.29-0.59). The greatest discrepancies between SMS and telephone interview were for self-reported injection site reactions (3.1% vs. 16.8%) and unsolicited (or \"other\") events (11.4% vs. 4.1%). Data collected by SMS was significantly timelier. Data collection by SMS results in significantly improved response rates and timeliness of vaccine safety data. Systems which incorporate SMS could be used to more rapidly detect safety signals and promote more rapid public health response to vaccine quality issues.","subset":"pubmed_abstract"} +{"meta":{"pmid":18452726,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-10":2,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2023-50":1,"2024-22":1}}},"text":"A comparison of the physiologic effects of acute whole-body vibration exercise in young and older people.\nTo examine the acute physiologic effects of acute whole-body vibration (WBV) exercise in young and older people. Every participant performed 9 conditions in a static squat position, consisting of no vibration and WBV at 30Hz and 3 loads corresponding to (1) no load (0% body mass), (2) load of 20% body mass, and (3) load of 40% body mass. A Jendrassik voluntary contraction was also performed with no vibration and WBV at 30Hz with no load and 20% body mass. Laboratory facilities at a university in the United Kingdom. Healthy young people (n=12; 6 men, 6 women; mean age, 21.5y) and 12 healthy older people (6 men, 6 women; mean age, 69.2y) from the local community. Not applicable. The Physical Activity Questionnaire, anthropometric measures, counter-movement jump, and isometric maximal voluntary contraction with the Jendrassik maneuver were assessed in both groups. Oxygen uptake (Vo2), blood pressure, heart rate, and rating of perceived exertion (RPE) were recorded during WBV and load conditions as the outcome of the study. Both vibration and load were associated with an increase (P<.001) in Vo2 for older and young groups. WBV elicited the equivalent of a .35 metabolic equivalent (MET) increase in Vo2, with additional loads of 20% and 40% body mass increasing Vo2 by 0.8 and 1.2 METs, respectively. Additionally, there was an interaction effect of vibration and group in which the WBV-related Vo2 increase was less in the old compared with the young. Both vibration and load caused an increase in heart rate, blood pressure, and RPE (all P<.001); however, there were no significant group differences between young and older groups. The Jendrassik maneuver elicited an increase in Vo2 by 27.6% for the old and 33% for the young group (P<.001); however, there was no significant difference between groups. Vo2 significantly increased in both the older and young people with vibration and additional load and when the Jendrassik maneuver was superimposed with vibration and load. However, the elicited increase in Vo2 (1.2mL x kg(-1).min(-1)) from WBV may be an insufficient stimulus to improve cardiovascular fitness.","subset":"pubmed_abstract"} +{"meta":{"pmid":9795762,"dup_signals":{"dup_doc_count":36,"dup_dump_count":20,"dup_details":{"curated_sources":3,"2023-23":3,"2023-14":1,"2022-27":1,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":2,"2021-25":1,"2021-17":2,"2021-10":2,"2021-04":3,"2020-45":1,"2020-40":2,"2020-29":2,"2019-51":2,"2019-47":1,"2023-50":1,"2024-22":2,"2024-18":1}}},"text":"Cytotoxic T-lymphocyte escape viral variants: how important are they in viral evasion of immune clearance in vivo?\nAlthough viral variants which are not recognized by epitope-specific cytotoxic T lymphocytes (CTL) have been shown to arise during a number of persistent virus infections, in many cases their significance remains controversial: it has been argued that the immune response is sufficiently plastic to contain their replication. In this review, we describe the mechanisms by which amino acid changes in viral proteins may affect epitope recognition by virus-specific CTL, and discuss the viral and immunological basis for the emergence of viral variants bearing such amino acid changes during infection. We then consider the impact that viral variation may have on the host CTL response and its ability to contain virus replication. We argue that the emergence of a viral variant demonstrates that it must have an in vivo replicative advantage, and that as such, the variant must tip the balance between virus replication and immune control somewhat in favor of the virus. Further, we suggest that although the immune response can evolve to recognize new viral epitopes, the CTL generated following such evolution frequently have a reduced ability to contain virus replication. We conclude that this escape mechanism likely does make a significant contribution to persistence\/pathogenesis during a number of different virus infections.","subset":"pubmed_abstract"} +{"meta":{"pmid":19579895,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[Metabolic study results of 54 patients with high risk of recurrent urolitiasis].\nUrolithiasis is a metabolic disorder with a tendency to relapse. The aim of this study was to assess the prevalence of metabolic abnormalities in patients at high risk and the impact of sex and age. Descriptive study of 54 patients (37 men and 17 women), with lithiasic pathology at high risk of recurrence. The metabolic study included the measurement of calcemia, uricemia, fosfemia, parathormone, calciuria\/24 h, uricosuria\/24 h, fosfaturia\/24 h, oxalaturia\/24 h, citraturia\/24 h and creatinine\/24 h. The values obtained were corrected according to weight and creatinine. The test used for statistical analysis was t-student (STATA 7.0). It was considered significant p<0.05. In 64,8% (35\/54) of the cases a metabolic abnormality was observed and in 27,7% (15\/54) there was 2 or more alterations present. The metabolic disorders most frequently observed were hypercalciuria (15\/54) 27,7%, hypocitraturia (15\/54) 27,7%, hyperuricemia (8\/54) 14,8%. and hyperoxaluria (8\/54) 14,8%. There was no significant difference in age or sex between the groups with and without metabolic abnormality. Most patients with recurrent lithiasic pathology or at high-risk display one or more metabolic disorders, being hypercalciuria and hypocitraturia the most frecuently encountered. In this study, there was no difference between sexes in most of the metabolic disorders, nor in its age distribution. These results demonstrate the need for metabolic studies in high-risk patients, since there are tools that allow therapeutic medical management of metabolic disorders and thus reduce the recurrence of lithiasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":2829217,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Inoculation of newborn SWR\/J females with an ecotropic murine leukemia virus can produce transgenic mice.\nEndogenous ecotropic murine leukemia proviruses that were not present in the parental stock are acquired by the progeny of some SWR\/J X RF\/J hybrid females. We have made a stock of an ecotropic murine leukemia virus produced by such a hybrid female and inoculated newborn SWR\/J females with it. We show that upon crossing of the inoculated females to SWR\/J males, some of their progeny acquire ecotropic proviruses. Although most of these proviruses appear to be distributed in somatic tissues in a mosaic way, some are transmitted through the germ line. Thus an exogenous infection is able to mimic the phenomenon observed in SWR\/J X RF\/J hybrid mice. Available evidence suggests that this infection occurs during oogenesis in the recipient female. Our results document the conversion of an exogenous infectious ecotropic murine leukemia virus to an endogenous provirus without any manipulation of either eggs or embryos.","subset":"pubmed_abstract"} +{"meta":{"pmid":19041589,"dup_signals":{"dup_doc_count":17}},"text":"Lifecourse social conditions and racial disparities in incidence of first stroke.\nSome previous studies found excess stroke rates among black subjects persisted after adjustment for socioeconomic status (SES), fueling speculation regarding racially patterned genetic predispositions to stroke. Previous research was hampered by incomplete SES assessments, without measures of childhood conditions or adult wealth. We assess the role of lifecourse SES in explaining stroke risk and stroke disparities. Health and Retirement Study participants age 50+ (n = 20,661) were followed on average 9.9 years for self- or proxy-reported first stroke (2175 events). Childhood social conditions (southern state of birth, parental SES, self-reported fair\/poor childhood health, and attained height), adult SES (education, income, wealth, and occupational status) and traditional cardiovascular risk factors were used to predict first stroke onset using Cox proportional hazards models. Black subjects had a 48% greater risk of first stroke incidence than whites (95% confidence interval, 1.33-1.65). Childhood conditions predicted stroke risk in both blacks and whites, independently of adult SES. Adjustment for both childhood social conditions and adult SES measures attenuated racial differences to marginal significance (hazard ratio, 1.13; 95% CI, 1.00-1.28). Childhood social conditions predict stroke risk in black and White American adults. Additional adjustment for adult SES, in particular wealth, nearly eliminated the disparity in stroke risk between black and white subjects.","subset":"pubmed_abstract"} +{"meta":{"pmid":33149832,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Unexamined Diversity: Disability Policies and Practices in US Graduate Medical Education Programs.\nGraduate medical education (GME) institutions must ensure equal access for trainees with disabilities through appropriate and reasonable accommodations and policies. To date, no comprehensive review of the availability and inclusiveness of GME policies for residents with disabilities exists. We examined institutions' compliance with Accreditation Council for Graduate Medical Education (ACGME) requirements and alignment with Association of American Medical Colleges (AAMC) policy considerations. Between June and August 2019, we conducted a directed content analysis of GME institutional policies using the AAMC report on disability considerations and the ACGME institutional requirements as a framework. Of the 47 GME handbooks available for review, 32 (68%) included a disability policy. Forty-one of the 47 (87%) handbooks maintained a nondiscrimination statement that included disability. Twelve of the 32 (38%) handbooks included a specific disability policy and language that encouraged disclosure, and 17 (53%) included a statement about the confidential documentation used to determine reasonable accommodations. Nineteen of the 32 (59%) maintained a clear procedure for disclosing disabilities and requesting accommodations. While disability policies are present in many of the largest GME institutions, it is not yet a standardized practice. For institutions maintaining a disability policy, many lack key elements identified as best practices in the AAMC considerations.","subset":"pubmed_abstract"} +{"meta":{"pmid":23371555,"dup_signals":{"dup_doc_count":33,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2017-34":3,"2017-22":1,"2017-09":3,"2016-50":2,"2016-44":1,"2016-40":2,"2016-36":4,"2016-30":4,"2016-26":1,"2016-22":1,"2016-18":3,"2016-07":3,"2024-18":1,"2013-20":1,"2024-30":1}}},"text":"Living crystals of light-activated colloidal surfers.\nSpontaneous formation of colonies of bacteria or flocks of birds are examples of self-organization in active living matter. Here, we demonstrate a form of self-organization from nonequilibrium driving forces in a suspension of synthetic photoactivated colloidal particles. They lead to two-dimensional \"living crystals,\" which form, break, explode, and re-form elsewhere. The dynamic assembly results from a competition between self-propulsion of particles and an attractive interaction induced respectively by osmotic and phoretic effects and activated by light. We measured a transition from normal to giant-number fluctuations. Our experiments are quantitatively described by simple numerical simulations. We show that the existence of the living crystals is intrinsically related to the out-of-equilibrium collisions of the self-propelled particles.","subset":"pubmed_abstract"} +{"meta":{"pmid":29057629,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Impacts of Influenza Infection and Vaccination on Exacerbation of Myasthenia Gravis.\nUpper respiratory infection (URI), including influenza, may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune disease that causes muscle weakness. There is also concern that the influenza vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of influenza infection and vaccination on symptom severity in MG patients. Patients diagnosed with MG were enrolled from 10 university-affiliated hospitals between March and August 2015. Subjects completed a questionnaire at the first routine follow-up visit after enrolling in the study. The patient history was obtained to determine whether a URI had been experienced during the previous winter, if an influenza vaccination had been administered before the previous winter, and whether their MG symptoms were exacerbated during or following either a URI or vaccination. Influenza-like illness (ILI) was defined and differentiated from the common cold as a fever of \u226538\u00b0C accompanied by a cough and\/or a sore throat. Of the 258 enrolled patients [aged 54.1\u00b115.2 years (mean\u00b1SD), 112 men, and 185 with generalized MG], 133 (51.6%) had received an influenza vaccination and 121 (46.9%) had experienced a common cold (96 patients) or ILI (25 patients) during the analysis period. MG symptoms were aggravated in 10 (40%) patients after ILI, whereas only 2 (1.5%) experienced aggravation following influenza vaccination. The rate of symptom aggravation was significantly higher in patients experiencing an ILI (10\/25, 40%) than in those with the common cold (15\/96, 15.6%, p=0.006). The results of this study suggest that the potential risk of aggravating autoimmune disease is higher for ILI than for influenza vaccination, which further suggests that influenza vaccination can be offered to patients with MG.","subset":"pubmed_abstract"} +{"meta":{"pmid":27206457,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"The Changing Nature of Guilt in Family Caregivers: Living Through Care Transitions of Parents at the End of Life.\nOlder adults cared for at home by family members at the end of life are at risk for care transitions to residential and institutional care settings. These transitions are emotionally distressing and fraught with suffering for both families and the older adult. A theoretical model titled \"The Changing Nature of Guilt in Family Caregivers: Living Through Care Transitions of Parents at the End of Life\" was developed using the method of grounded theory. When a dying parent cannot remain at home to die, family members experience guilt throughout the transition process. Findings indicated that guilt surrounding transfers escalated during the initial stages of the transfer but was mitigated by achieving what family members deemed as a \"good\" death when relatives were receiving hospice care. The findings of this interpretative approach provide new insights into family-focused perspectives in care transfers of the dying.","subset":"pubmed_abstract"} +{"meta":{"pmid":17090668,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Life-history evolution under a production constraint.\nThe recently formulated metabolic theory of ecology has profound implications for the evolution of life histories. Metabolic rate constrains the scaling of production with body mass, so that larger organisms have lower rates of production on a mass-specific basis than smaller ones. Here, we explore the implications of this constraint for life-history evolution. We show that for a range of very simple life histories, Darwinian fitness is equal to birth rate minus death rate. So, natural selection maximizes birth and production rates and minimizes death rates. This implies that decreased body size will generally be favored because it increases production, so long as mortality is unaffected. Alternatively, increased body size will be favored only if it decreases mortality or enhances reproductive success sufficiently to override the preexisting production constraint. Adaptations that may favor evolution of larger size include niche shifts that decrease mortality by escaping predation or that increase fecundity by exploiting new abundant food sources. These principles can be generalized to better understand the intimate relationship between the genetic currency of evolution and the metabolic currency of ecology.","subset":"pubmed_abstract"} +{"meta":{"pmid":10326131,"dup_signals":{"dup_doc_count":25,"dup_dump_count":24,"dup_details":{"curated_sources":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-10":1,"2019-51":1,"2019-47":1,"2019-39":1,"2019-35":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2021-43":1}}},"text":"Off-axis monochromatic aberrations estimated from double pass measurements in the human eye.\nOff-axis monochromatic aberrations in the human eye impose limits on peripheral vision. However, the magnitude of the aberrations off-axis, and in particular coma, has not been yet completely determined. We have developed a procedure to estimate third order aberrations in the periphery of the human eye. The technique is based on recording series of double pass retinal images with unequal entrance and exit pupil diameters (Artal, Iglesias, L\u00f3pez-Gil & Green (1995b). J. Opt. Soc. Am. A, 12, 2358-2366.) which allows the odd asymmetries in the retinal image be assessed. The procedure that is described provides accurate estimates of the main off-axis aberrations: astigmatism, defocus and coma. We have measured these aberrations in four normal subjects. For a given eccentricity, the measured amount of coma and astigmatism are relatively similar among subjects, because the angular distance from the axis is the dominant factor in determining the magnitude of these aberrations. However, we found considerable variability in the values of peripheral defocus, probably due to a complicate combination of off-axis aberrations and fundus shape. The final off-axis optical performance of the eye for a given object location is determined by a particular mixture of defocus, astigmatism, coma and higher order aberrations.","subset":"pubmed_abstract"} +{"meta":{"pmid":8603700,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":2,"2024-18":1,"unknown":11}}},"text":"Transcriptional repression by methylation: cooperativity between a CpG cluster in the promoter and remote CpG-rich regions.\nCytosine methylation of binding sites for transcription factors is a straightforward mechanism to prevent transcription, while data on an indirect mechanism, by methylation outside of the factor binding sites, are still scarce. We have studied the latter effect using a model promoter construct. For this, a 69 bp G + C rich DNA segment with a cluster of 14 CpG sites was inserted between upstream lexA sites and the TATA box. Transcription was measured in transient transfection assays with lexA-VP16 as an activating factor. When the entire plasmid was methylated at all CpGs before transfection, transcription was blocked (to 3% residual activity), whereas transcription was only mildly inhibited (to 60%) by methylation of a control plasmid that lacked the 69 bp CpG cluster. However, the effect could not simply be attributed to methylation of the CpG cluster: neither a methylated CpG cluster in an otherwise methylation-free reporter gene plasmid, nor the methylated plasmid with an unmethylated CpG cluster, inhibited transcription considerably (69% and 44% remaining activity, respectively). The data presented here suggest that a minimal length of methylated DNA in the promoter is required for repression, and imply that concomitant methylation of CpGs in the promoter region and in remote sequences can cooperatively block transcription, without the need to methylate any binding sites for transcription factors. We also note that the cooperation for a negative effect described here bears an analogy to transcriptional activation, where a promoter often cooperates with a remote enhancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":9391886,"dup_signals":{"dup_doc_count":28,"dup_dump_count":20,"dup_details":{"curated_sources":8,"2019-43":1,"2019-04":1,"2018-26":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-18":1,"2016-07":1,"2014-41":1,"2014-15":1,"2023-50":1,"2013-48":1,"2015-06":1}}},"text":"Prader-Willi syndrome.\nPrader-Willi syndrome is a complex disorder affecting multiple systems with many manifestations relating to hypothalamic insufficiency. Major findings include infantile hypotonia, developmental delay and mental retardation, behaviour disorder, characteristic facial appearance, obesity, hypogonadism, and short stature. Obesity and the behavioural problems are the major causes of morbidity and mortality. Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process. Diagnostic identification of all causes has become available in recent years, permitting early detection and institution of appropriate management. This testing has permitted recent identification of some phenotypic differences among affected subjects of different race and between those with deletions and uniparental disomy as a cause.","subset":"pubmed_abstract"} +{"meta":{"pmid":29210226,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":11}}},"text":"Fire severity and tree regeneration following bark beetle outbreaks: the role of outbreak stage and burning conditions.\nThe degree to which recent bark beetle (Dendroctonus ponderosae) outbreaks may influence fire severity and postfire tree regeneration is of heightened interest to resource managers throughout western North America, but empirical data on actual fire effects are lacking. Outcomes may depend on burning conditions (i.e., weather during fire), outbreak severity, or intervals between outbreaks and subsequent fire. We studied recent fires that burned through green-attack\/red-stage (outbreaks <3 years before fire) and gray-stage (outbreaks 3\u201315 years before fire) subalpine forests dominated by lodgepole pine (Pinus contorta var. latifolia) in Greater Yellowstone, Wyoming, USA, to determine if fire severity was linked to prefire beetle outbreak severity and whether these two disturbances produced compound ecological effects on postfire tree regeneration. With field data from 143 postfire plots that burned under different conditions, we assessed canopy and surface fire severity, and postfire tree seedling density against prefire outbreak severity. In the green-attack\/red stage, several canopy fire-severity measures increased with prefire outbreak severity under moderate burning conditions. Under extreme conditions, few fire-severity measures were related to prefire outbreak severity, and effect sizes were of marginal biological significance. The percentage of tree stems and basal area killed by fire increased with more green-attack vs. red-stage trees (i.e., the earliest stages of outbreak). In the gray stage, by contrast, most fire-severity measures declined with increasing outbreak severity under moderate conditions, and fire severity was unrelated to outbreak severity under extreme burning conditions. Postfire lodgepole pine seedling regeneration was unrelated to prefire outbreak severity in either post-outbreak stage, but increased with prefire serotiny. Results suggest bark beetle outbreaks can affect fire severity in subalpine forests under moderate burning conditions, but have little effect on fire severity under extreme burning conditions when most large wildfires occur in this system. Thus, beetle outbreak severity was moderately linked to fire severity, but the strength and direction of the linkage depended on both endogenous (outbreak stage) and exogenous (fire weather) factors. Closely timed beetle outbreak and fire did not impart compound effects on tree regeneration, suggesting the presence of a canopy seedbank may enhance resilience to their combined effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":28636392,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-10":1,"unknown":12}}},"text":"Hybrid CPU\/GPU Integral Engine for Strong-Scaling Ab Initio Methods.\nWe present a parallel integral algorithm for two-electron contributions occurring in Hartree-Fock and hybrid density functional theory that allows for a strong scaling parallelization on inhomogeneous compute clusters. With a particular focus on graphic processing units, we show that our approach allows an efficient use of CPUs and graphics processing units (GPUs) simultaneously, although the different architectures demand conflictive strategies in order to ensure efficient program execution. Furthermore, we present a general strategy to use large basis sets like quadruple-\u03b6 split valence on GPUs and investigate the balance between CPUs and GPUs depending on l-quantum numbers of the corresponding basis functions. Finally, we present first illustrative calculations using a hybrid CPU\/GPU environment and demonstrate the strong-scaling performance of our parallelization strategy also for pure CPU-based calculations.","subset":"pubmed_abstract"} +{"meta":{"pmid":33229772,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Clinicopathologic Features and the Association with Short-Term Outcome of Primary Membranous Nephropathy in Children: A Single-Center Study from Pakistan.\nMembranous nephropathy (MN) is an uncommon cause of steroid-resistant nephrotic syndrome in children. Our study aimed to determine the clinicopathologic features of primary MN in children and their association with short-term outcome. This observational study was conducted from January 2009 to June 2017 at the Pediatric Nephrology Department. A total of 50 children were diagnosed with primary MN. Their clinical, laboratory, and histopathological findings on renal biopsy were recorded. The minimum follow-up was for six months. Clinicopathologic features were correlated with the outcome at the last follow-up. Data analysis was done using IBM SPSS Statistics for Windows software version 20.0. The mean age at onset was 10.92 \u00b1 3.08 years (range: 4-17 years). The male-to-female ratio was 3:1. The serum albumin of \u22642.5 g\/dL was seen in 40 patients (80%), hypertension was present in 38 (76%), and heavy proteinuria was seen in 32 children (70%). The mean estimated glomerular filtration rate (eGFR) at presentation was 178.71 \u00b1 0.78 mL\/min\/1.73 m2. At the initial visit, nine children (18.4%) were in chronic kidney disease stage 2 and one (2%) in stage 4. Phospholipase A2 receptor antibody was present in five (15%) of 32 children tested. At the last follow-up (28 interquartile range: 25.5 months), 11 children (26%) were in complete remission and 25 (66%) had achieved partial remission. The mean eGFR had reduced to 145.84 \u00b1 78.05 mL\/min\/1.73 m2. Patients with normal initial eGFR were more likely to go into remission (P = 0.001). The short-term outcome of childhood primary MN is relatively good in our setup. A multicenter collaborative study is required to determine prognostic factors and to standardize treatment in this uncommon nephropathy.","subset":"pubmed_abstract"} +{"meta":{"pmid":10604478,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2016-44":1,"2015-18":1}}},"text":"The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors.\nThe rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.","subset":"pubmed_abstract"} +{"meta":{"pmid":27926847,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2018-47":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-47":2,"2017-39":1,"2018-51":1}}},"text":"Probing Lipid Bilayers under Ionic Imbalance.\nBiological membranes are normally under a resting transmembrane potential (TMP), which originates from the ionic imbalance between extracellular fluids and cytosols, and serves as electric power storage for cells. In cell electroporation, the ionic imbalance builds up a high TMP, resulting in the poration of cell membranes. However, the relationship between ionic imbalance and TMP is not clearly understood, and little is known about the effect of ionic imbalance on the structure and dynamics of biological membranes. In this study, we used coarse-grained molecular dynamics to characterize a dipalmitoylphosphatidylcholine bilayer system under ionic imbalances ranging from 0 to \u223c0.06 e charges per lipid (e\/Lip). We found that the TMP displayed three distinct regimes: 1) a linear regime between 0 and 0.045 e\/Lip, where the TMP increased linearly with ionic imbalance; 2) a yielding regime between \u223c0.045 and 0.060 e\/Lip, where the TMP displayed a plateau; and 3) a poration regime above \u223c0.060 e\/Lip, where we observed pore formation within the sampling time (80 ns). We found no structural changes in the linear regime, apart from a nonlinear increase in the area per lipid, whereas in the yielding regime the bilayer exhibited substantial thinning, leading to an excess of water and Na+ within the bilayer, as well as significant misalignment of the lipid tails. In the poration regime, lipid molecules diffused slightly faster. We also found that the fluid-to-gel phase transition temperature of the bilayer dropped below the normal value with increased ionic imbalances. Our results show that a high ionic imbalance can substantially alter the essential properties of the bilayer, making the bilayer more fluid like, or conversely, depolarization of a cell could in principle lead to membrane stiffening.","subset":"pubmed_abstract"} +{"meta":{"pmid":15756637,"dup_signals":{"dup_doc_count":37,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-10":1,"unknown":29}}},"text":"Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.\nHarlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":10759860,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":20}}},"text":"Combining phage display and molecular modeling to map the epitope of a neutralizing antitoxin antibody.\nCrotoxin is a potent presynaptic neurotoxin from the venom of the rattlesnake Crotalus durissus terrificus. It is composed of the noncovalent and synergistic association of a weakly toxic phospholipase A2, CB, and a nontoxic three-chain subunit, CA, which increases the lethal potency of CB. The A-56.36 mAb is able to dissociate the crotoxin complex by binding to the CA subunit, thereby neutralizing its toxicity. Because A-56.36 and CB show sequence homology and both compete for binding to CA, we postulated that A-56.36 and CB had overlapping binding sites on CA. By screening random phage-displayed libraries with the mAb, phagotopes bearing the (D\/S)GY(A\/G) or AAXI consensus motifs were selected. They all bound A-56.36 in ELISA and competed with CA for mAb binding, although with different reactivities. When mice were immunized with the selected clones, polyclonal sera reacting with CA were induced. Interestingly, the raised antibodies retained the crotoxin-dissociating effect of A-56.36, suggesting that the selected peptides may be used to produce neutralizing antibodies. By combining these data with the molecular modeling of CA, it appeared that the functional epitope of A-56.36 on CA was conformational, one subregion being discontinuous and corresponding to the first family of peptides, the other subregion being continuous and composed of amino acids of the second family. Phage-displayed peptides corresponding to fragments of the two identified regions on CA reacted with A-56.36 and with CB. Our data support the hypothesis that A-56.36 and CB interact with common regions of CA, and highlight residues which are likely to be critical for CA-CB complex formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28944394,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Buckling-driven self-assembly of self-similar inspired micro\/nanofibers for ultra-stretchable electronics.\nSelf-similar structures are capable of highly enhancing the deformability of stretchable electronics. We presented a self-assembly method based on the tunable buckling of serpentine fiber-based interconnects (FiberBIs), which are deposited using our presented helix electrohydrodynamic printing (HE-printing) technique, to fabricate self-similar structures with enhanced stretchability (up to 250%). It provides a low-cost, printing-based approach for the generation of large-scale self-similar FiberBIs. Distinct buckling behaviors and modes occur under specific conditions. To elucidate the mechanics governing this phenomenon, we present detailed experimental and theoretical studies of the buckling mechanics of serpentine microfibers on compliant substrates. Firstly, the effect of the magnitude and direction of prestrain on the buckling behavior of a fiber-on-substrate is discussed. Secondly, the critical geometry of a serpentine fiber as a key parameter for fabricating uniform self-similar fibers is also figured out. Finally, the cross-sectional geometry of the fiber as a judgment criterion for determining the in-surface or out-of-surface buckling of the fiber is established. The investigation can guide the fabrication process of large-scale self-similar structures for high-performance electronic devices with extreme stretchability.","subset":"pubmed_abstract"} +{"meta":{"pmid":12573761,"dup_signals":{"dup_doc_count":17,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2023-40":1,"2024-18":3,"2024-10":1}}},"text":"Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy.\nTo investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low alpha\/beta ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high alpha\/beta ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors.","subset":"pubmed_abstract"} +{"meta":{"pmid":16552002,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Improved detection of metastatic melanoma by T2*-weighted imaging.\nThe imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2*-weighted signal intensity loss. We hypothesized that T2*-weighted images would improve detection of metastatic melanoma. The T2* and T1 characteristics of 120 newly detected metastatic brain lesions from 31 patients with malignant melanoma were compared with those of 120 brain metastases from 23 patients with lung cancer. Melanoma metastases were 5 times more likely to demonstrate prominent T2*-related signal intensity loss (susceptibility effect) than were lung metastases (42% vs 8%; P < .01), and 4.5 times more likely to demonstrate T1 hyperintensity (55% vs 12%; P < .01). Patients with melanoma had lesions that were either hypointense on T2*-weighted images, hyperintense on T1 images, or both, in 71% (85\/120), compared with 19% (23\/120) of lung carcinoma metastases (P < .01). Melanoma lesions were 16 times more likely than lung cancer lesions to show combined T2* related signal intensity loss and T1 hyperintensity (P < .01). Remarkably, 8 melanoma lesions (7%) in 3 patients were detectable principally on the T2*-weighted sequences, whereas no lung cancer lesion was detected solely on susceptibility images. We found a direct correlation between melanin content and T1 hyperintensity but no correlation between T2* intensity and melanin. T2*-weighted images improve lesion detection in patients with melanoma metastases, and in conjunction with T1-weighted sequences, can suggest melanoma as the etiology of an intracranial mass. This sequence should be employed for evaluation of possible brain metastasis in patients without a known primary malignancy and in studies for melanoma staging.","subset":"pubmed_abstract"} +{"meta":{"pmid":17009876,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evidence for diversity in transcriptional profiles of single hematopoietic stem cells.\nHematopoietic stem cells replenish all the cells of the blood throughout the lifetime of an animal. Although thousands of stem cells reside in the bone marrow, only a few contribute to blood production at any given time. Nothing is known about the differences between individual stem cells that dictate their particular state of activation readiness. To examine such differences between individual stem cells, we determined the global gene expression profile of 12 single stem cells using microarrays. We showed that at least half of the genetic expression variability between 12 single cells profiled was due to biological variation in 44% of the genes analyzed. We also identified specific genes with high biological variance that are candidates for influencing the state of readiness of individual hematopoietic stem cells, and confirmed the variability of a subset of these genes using single-cell real-time PCR. Because apparent variation of some genes is likely due to technical factors, we estimated the degree of biological versus technical variation for each gene using identical RNA samples containing an RNA amount equivalent to that of single cells. This enabled us to identify a large cohort of genes with low technical variability whose expression can be reliably measured on the arrays at the single-cell level. These data have established that gene expression of individual stem cells varies widely, despite extremely high phenotypic homogeneity. Some of this variation is in key regulators of stem cell activity, which could account for the differential responses of particular stem cells to exogenous stimuli. The capacity to accurately interrogate individual cells for global gene expression will facilitate a systems approach to biological processes at a single-cell level.","subset":"pubmed_abstract"} +{"meta":{"pmid":30580204,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2020-10":2,"2019-51":1,"2019-47":1,"2019-39":1,"2019-35":1,"2019-26":3,"2019-22":1,"2019-13":2,"2019-04":2,"2020-16":1}}},"text":"Manuscript prepared for submission to environmental toxicology and pharmacology pollution in drinking water source areas: Microplastics in the Danjiangkou Reservoir, China.\nAs the source of water for the South-to-North Water Diversion Project of China, the water quality of the Danjiangkou Reservoir (DJKR) is related to the safety of drinking water for billions of residents. Consequently, microplastics in surface water and sediment samples of the DJKR were investigated in this study. Microplastics were observed in all water and sediment samples with abundances varying from 467 to 15,017 n\/m3 and 15 to 40 n\/kg wet weight, respectively. Microplastics were rich in colour and dominated by fibrous items. Small-sized particles (< 2 mm) were more frequently observed than other sizes. Analysis by micro-Raman spectroscopy showed that polypropylene was the major polymer type. These systematic results demonstrated that the DJKR is suffering from the pollution of microplastics, which should be paid more attention based on its potential threat to the aquatic organisms and residents impacted by the drinking water source pollution.","subset":"pubmed_abstract"} +{"meta":{"pmid":23388627,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Validation of global rating scale and checklist instruments for the infant lumbar puncture procedure.\nThe Patient Outcomes in Simulation Education network has developed tools for the assessment of competency to perform the infant lumbar puncture (ILP) procedure. The objective of this study was to evaluate the validity and reliability of these tools in a simulated setting. We developed a 4-point anchored global rating scale (GRS) and 15-item dichotomous checklist instrument to assess ILP performance in a simulated environment. Video recordings of 60 subjects performing an unsupervised lumbar puncture on an infant bench top simulator were collected prospectively; 20 performed by subjects in each of 3 categories (beginner, intermediate experienced, or expert). Three blinded, expert raters independently scored each subject's video recording using the GRS and checklist instruments. The final version of the scoring instruments is presented. Across all subject groups, higher GRS scores were found with advancing level of experience (P < 0.01). Total checklist scores were similar between the expert and intermediate experienced groups (P = 0.54). Both groups scored higher than the beginner group on the checklist instrument (P < 0.01). For each rater, a significant positive correlation was found between GRS scores and total checklist scores (median \u03c1 = 0.75, P < 0.01). Cronbach \u03b1 coefficient for the checklist was 0.77. The intraclass correlation coefficients between raters for the GRS and total checklist scores were 0.71 and 0.52, respectively. This study provides some initial evidence to support the validity and reliability of the ILP-anchored GRS. Acceptable internal consistency was found for the checklist instrument. The GRS instrument outperformed the checklist in its discriminant ability and interrater agreement.","subset":"pubmed_abstract"} +{"meta":{"pmid":28002586,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Correlation between TRAIL and caspase-8 expression and their relationship with cell proliferation and apoptosis in human osteosarcoma.\nOsteosarcoma is a common malignant bone tumor that mainly affects children and adolescents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily. Caspase-8 appears in the upstream of apoptosis signaling pathway among caspases. We investigated TRAIL and caspase-8 levels in osteosarcoma patients to determine their correlation with cell proliferation and apoptosis. Osteosarcoma and osteochondroma patients receiving surgery in our hospital were selected. TRAIL and caspase-8 expression levels in tissue were determined by immunohistochemistry, and protein levels in cells were evaluated by western blotting. Human osteosarcoma cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The osteosarcoma and osteochondroma cell cycles and apoptosis were investigated by flow cytometry. Correlation analysis was applied to TRAIL and caspase-8 levels during cell apoptosis. Positive TRAIL and caspase-8 expression rates in osteosarcoma tissue were significantly lower than in the controls (P < 0.05). TRAIL (0.114 \u00b1 0.002) and caspase-8 (0.352 \u00b1 0.124) levels in experimental cells were obviously lower than in the controls (P < 0.05). Osteosarcoma cells in the experimental group demonstrated higher proliferation and lower apoptosis at 24, 48, and 72 h (P < 0.05). The experimental cell number increased in the G1 stage and decreased in the S stage (P < 0.05). TRAIL and caspase-8 proteins showed positive correlation with apoptosis in osteosarcoma (P < 0.05). Human osteosarcoma presented reduced TRAIL and caspase-8 levels with enhanced cell proliferation and reduced apoptosis. TRAIL and caspase-8 expression levels were positively correlated with apoptosis in osteosarcoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":11009413,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Technique for enhanced rare earth separation\nA process is demonstrated for the efficient separation of rare earth elements, using a combination of selective reduction and vacuum distillation of halides. The large differences in the redox chemistry of the rare earth elements and in the vapor pressures of rare earth di- and trihalides are exploited for separation. Experimental proof of concept is provided for the binary systems praseodymium-neodymium and neodymium-samarium. This process enhances the separation factor for the isolation of samarium and neodymium from their mixture by more than an order of magnitude.","subset":"pubmed_abstract"} +{"meta":{"pmid":24572042,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":2,"2015-18":1,"unknown":7}}},"text":"Social stimulation and corticolimbic reactivity in premenstrual dysphoric disorder: a preliminary study.\nPremenstrual dysphoric disorder (PMDD), characterized by luteal phase-induced negative affect and loss of impulse control, often results in compromised social interactions. Although amygdala activation is generally linked to negative affect, increased amygdala reactivity to aversive stimuli in the luteal phase has not been consistently reported in PMDD. We tested the hypothesis that amygdala hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked to socially relevant stimuli. Blood oxygenation level dependent signal changes during exposure to negative images with social and non-social content were evaluated in the mid-follicular and late luteal phase of the menstrual cycle. Fourteen women with PMDD and 13 healthy controls participated. When compared with healthy controls, women with PMDD in the luteal phase had enhanced reactivity to social stimuli compared to non-social stimuli in the amygdala and insula, but attenuated reactivity in the anterior cingulate cortex. Functional couplings between emotion processing and controlling areas were significantly different, being positive in women with PMDD and negative in healthy controls. Changes in progesterone levels in women with PMDD correlated positively with altered amygdala reactivity. Socially relevant aversive stimulation elicited enhanced activity in affective processing brain regions that were functionally coupled to compromised activity in cognitive control areas. Because increased reactivity correlated positively with alterations in ovarian steroid levels, data preliminary support the hypothesis that enhanced progesterone sensitivity in PMDD affects corticolimbic processing of social emotions.","subset":"pubmed_abstract"} +{"meta":{"pmid":8988886,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":11}}},"text":"Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators.\nRandomized trials comparing coronary angioplasty with bypass surgery in patients with multivessel coronary disease have shown no significant differences in overall rates of death and myocardial infarction. We compared quality of life, employment, and medical care costs during five years of follow-up among patients treated with angioplasty or bypass surgery. A total of 934 of the 1829 patients enrolled in the randomized Bypass Angioplasty Revascularization Investigation participated in this study. Detailed data on quality of life were collected annually, and economic data were collected quarterly. During the first three years of follow-up, functional-status scores on the Duke Activity Status Index, which measures the ability to perform common activities of daily living, improved more in patients assigned to surgery than in those assigned to angioplasty (P<0.05). Other measures of quality of life improved equally in both groups throughout the follow-up period. Patients in the angioplasty group returned to work five weeks sooner than did patients in the surgery group (P<0.001). The initial mean cost of angioplasty was 65 percent that of surgery ($21,113 vs. $32,347, P<0.001), but after five years the total medical cost of angioplasty was 95 percent that of surgery ($56,225 vs. $58,889), a difference of $2,664 (P = 0.047). The five-year cost of angioplasty was significantly lower than that of surgery among patients with two-vessel disease ($52,930 vs. $58,498, P<0.05), but not among patients with three-vessel disease ($60,918 vs. $59,430). After five years of follow-up, surgery had an overall cost-effectiveness ratio of $26,117 per year of life added, but unacceptable ratios of $100,000 or more per year of life added could not be excluded (P=0.13). Surgery appeared particularly cost effective in treating diabetic patients because of their significantly improved survival. In patients with multivessel coronary disease, coronary-artery bypass surgery is associated with a better quality of life for three years than coronary angioplasty, after the initial morbidity caused by the procedure. Coronary angioplasty has a lower five-year cost than bypass surgery only in patients with two-vessel coronary disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":11446884,"dup_signals":{"dup_doc_count":11}},"text":"Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.\nSeveral studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg\/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg\/kg Infliximab, 71.4% in the group receiving 3 mg\/kg, 80.0% in the group receiving 5 mg\/kg, and 85.7% in the group receiving 10 mg\/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg\/kg groups compared with the 1 and 3 mg\/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.","subset":"pubmed_abstract"} +{"meta":{"pmid":24074217,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2019-47":1,"2019-39":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-39":2,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2023-50":1,"2024-22":1}}},"text":"Monitoring and benchmarking population diet quality globally: a step-wise approach.\nINFORMAS (International Network for Food and Obesity\/non-communicable diseases Research, Monitoring and Action Support) aims to monitor and benchmark the healthiness of food environments globally. In order to assess the impact of food environments on population diets, it is necessary to monitor population diet quality between countries and over time. This paper reviews existing data sources suitable for monitoring population diet quality, and assesses their strengths and limitations. A step-wise framework is then proposed for monitoring population diet quality. Food balance sheets (FBaS), household budget and expenditure surveys (HBES) and food intake surveys are all suitable methods for assessing population diet quality. In the proposed 'minimal' approach, national trends of food and energy availability can be explored using FBaS. In the 'expanded' and 'optimal' approaches, the dietary share of ultra-processed products is measured as an indicator of energy-dense, nutrient-poor diets using HBES and food intake surveys, respectively. In addition, it is proposed that pre-defined diet quality indices are used to score diets, and some of those have been designed for application within all three monitoring approaches. However, in order to enhance the value of global efforts to monitor diet quality, data collection methods and diet quality indicators need further development work.","subset":"pubmed_abstract"} +{"meta":{"pmid":7476958,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-33":1,"2021-43":1,"2021-31":1,"2021-17":1,"2020-34":1,"2020-24":1,"2020-05":1,"2019-35":1,"2019-22":1,"2022-49":1,"2024-10":1,"2024-26":1}}},"text":"[Use of thermostable DNA polymerase from Thermus thermophilus KTP in a combined reverse transcription and amplification reaction of detecting interleukin 2alpha RNA and determining expression of the multidrug resistance gene (MDR-1)].\nAccording to our data native Tth DNA polymerase displays higher reverse transcription activity than Taq DNA polymerase. This allows one to use Tth DNA polymerase in the complete reaction of reverse transcription and amplification (RT\/PCR). We used this enzyme to synthesize the interleukine (IL-2 alpha) RNA template synthesized by the RT\/PCR method in vitro. The conditions for RNA IL-2 alpha detection were optimized. The maximum yield of the specific product was obtained at pH 8.5-9.0. The influence of bivalent cations on the efficiency of RT reaction of coupled RT\/PCR can be expressed as: Mn2+ > or = Cu2+ > Mg2+ > Cd2+ >> Co2+. The optimal ratio is 1.25-1.88 for Mn2+\/dNTPs and 1.88-2.5 for Cu2+\/dNTPs and Cd2+\/dNTPs. The maximum yield of the RT\/PCR product is found at Mg2+\/dNTPs = 3.75. When Mn2+ is used instead of Mg2+ in the PCR reaction the efficiency of RT\/PCR decreases. The RT\/PCR method embracing thermostable Tth DNA-polymerase provides detection of 10(3) copies of RNA IL-2 alpha. An efficient method of the express-diagnostics of MDR-1 gene expression by coupled RT\/PCR using Tth DNA polymerase is described.","subset":"pubmed_abstract"} +{"meta":{"pmid":9834255,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Recombinant CD40L treatment protects allogeneic murine bone marrow transplant recipients from death caused by herpes simplex virus-1 infection.\nPosttransplant infection associated with host immune deficiency is the major cause of nonrelapse mortality of human bone marrow transplant recipients. In a new murine model of posttransplant infection, allogeneic bone marrow transplant recipients were infected with herpes simplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks after transplantation. Allogeneic transplant recipients with graft-versus-host disease (GVHD) had significantly increased mortality from HSV-1 encephalitis, with deficiencies of both specific anti-HSV-1 antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokine profile (increased interleukin-4 [IL-4] and decreased interferon-gamma) and decreased lipopolysaccharide (LPS) responses, suggesting that both T-cell and B-cell defects contributed to the impaired production of antibody. Because passive transfer of hyperimmune serum protected mice from HSV-1 infection, we hypothesized that CD40 ligand (CD40L), which induces B-cell maturation, would protect mice from HSV-1 infection. CD40L-treated GVHD mice showed elevated IgG2a levels and increased survival compared with vehicle-treated transplant recipients.","subset":"pubmed_abstract"} +{"meta":{"pmid":19216767,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-40":1,"2023-06":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2019-26":1,"2019-18":1,"2018-51":1,"2018-43":1,"2018-22":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-22":1,"2024-18":1,"2024-26":1}}},"text":"The extent of population genetic subdivision differs among four co-distributed shark species in the Indo-Australian archipelago.\nThe territorial fishing zones of Australia and Indonesia are contiguous to the north of Australia in the Timor and Arafura Seas and in the Indian Ocean to the north of Christmas Island. The area surrounding the shared boundary consists of a variety of bio-diverse marine habitats including shallow continental shelf waters, oceanic trenches and numerous offshore islands. Both countries exploit a variety of fisheries species, including whaler (Carcharhinus spp.) and hammerhead sharks (Sphyrna spp.). Despite their differences in social and financial arrangements, the two countries are motivated to develop complementary co-management practices to achieve resource sustainability. An essential starting point is knowledge of the degree of population subdivision, and hence fisheries stock status, in exploited species. Populations of four commercially harvested shark species (Carcharhinus obscurus, Carcharhinus sorrah, Prionace glauca, Sphyrna lewini) were sampled from northern Australia and central Indonesia. Neutral genetic markers (mitochondrial DNA control region sequence and allelic variation at co-dominant microsatellite loci) revealed genetic subdivision between Australian and Indonesian populations of C. sorrah. Further research is needed to address the possibility of genetic subdivision among C. obscurus populations. There was no evidence of genetic subdivision for P. glauca and S. lewini populations, but the sampling represented a relatively small part of their distributional range. For these species, more detailed analyses of population genetic structure is recommended in the future. Cooperative management between Australia and Indonesia is the best option at present for P. glauca and S. lewini, while C. sorrah and C. obscurus should be managed independently. On-going research on these and other exploited shark and ray species is strongly recommended. Biological and ecological similarity between species may not be a predictor of population genetic structure, so species-specific studies are recommended to provide new data to assist with sustainable fisheries management.","subset":"pubmed_abstract"} +{"meta":{"pmid":19882205,"dup_signals":{"dup_doc_count":11}},"text":"Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events.\nBesides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain. We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan-Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25-0.5 microg\/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox's proportional hazards analysis. The mean follow-up period was 55.1 +\/- 38.9 months in the alfacalcidol treatment group and 41.9 +\/- 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin-angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone. These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.","subset":"pubmed_abstract"} +{"meta":{"pmid":24789204,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2019-43":1,"2019-13":1,"2018-39":1,"2018-34":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-23":1,"2024-10":1}}},"text":"Esophageal reflexes modulate frontoparietal response in neonates: Novel application of concurrent NIRS and provocative esophageal manometry.\nCentral and peripheral neural regulation of swallowing and aerodigestive reflexes is unclear in human neonates. Functional near infrared spectroscopy (NIRS) is a noninvasive method to measure changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD). Pharyngoesophageal manometry permits evaluation of aerodigestive reflexes. Modalities were combined to investigate feasibility and to test neonatal frontoparietal cortical changes during pharyngoesophageal (visceral) stimulation and\/or swallowing. Ten neonates (45.6 \u00b1 3.0 wk postmenstrual age, 4.1 \u00b1 0.5 kg) underwent novel pharyngoesophageal manometry concurrent with NIRS. To examine esophagus-brain interactions, we analyzed cortical hemodynamic response (HDR) latency and durations during aerodigestive provocation and esophageal reflexes. Data are presented as means \u00b1 SE or percent. HDR rates were 8.84 times more likely with basal spontaneous deglutition compared with sham stimuli (P = 0.004). Of 182 visceral stimuli, 95% were analyzable for esophageal responses, 38% for HDR, and 36% for both. Of analyzable HDR (n = 70): 1) HbO concentration (\u03bcmol\/l) baseline 1.5 \u00b1 0.7 vs. 3.7 \u00b1 0.7 poststimulus was significant (P = 0.02), 2) HbD concentration (\u03bcmol\/l) between baseline 0.1 \u00b1 0.4 vs. poststimulus -0.5 \u00b1 0.4 was not significant (P = 0.73), and 3) hemispheric lateralization was 21% left only, 29% right only, and 50% bilateral. During concurrent esophageal and NIRS responses (n = 66): 1) peristaltic reflexes were present in 74% and HDR in 61% and 2) HDR was 4.75 times more likely with deglutition reflex vs. secondary peristaltic reflex (P = 0.016). Concurrent NIRS with visceral stimulation is feasible in neonates, and frontoparietal cortical activation is recognized. Deglutition contrasting with secondary peristalsis is related to cortical activation, thus implicating higher hierarchical aerodigestive protective functional neural networks.","subset":"pubmed_abstract"} +{"meta":{"pmid":21502280,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Survey of physicians' practices in the control of cardiovascular risk factors: the EURIKA study.\nTo assess the practices of physicians in 12 European countries in the primary prevention of cardiovascular disease (CVD). In 2009, 806 physicians from 12 European countries answered a questionnaire, delivered electronically or by post, regarding their assessment of patients with cardiovascular risk factors, and their use of risk calculation tools and clinical practice guidelines (ClinicalTrials.gov number: NCT00882336). Approximately 60 physicians per country were selected (participation rate varied between 3.1% in Sweden and 22.8% in Turkey). Among participating physicians, 85.2% reported using at least one clinical guideline for CVD prevention. The most popular were the ESC guidelines (55.1%). Reasons for not using guidelines included: the wide choice available (47.1%), time constraints (33.3%), lack of awareness of guidelines (27.5%), and perception that guidelines are unrealistic (23.5%). Among all physicians, 68.5% reported using global risk calculation tools. Written charts were the preferred method (69.4%) and the most commonly used was the SCORE equation (35.4%). Reasons for not using equations included time constraints (59.8%), not being convinced of their usefulness (21.7%) and lack of awareness (19.7%). Most physicians (70.8%) believed that global risk-equations have limitations; 89.8% that equations overlook important risk factors, and 66.5% that they could not be used in elderly patients. Only 46.4% of physicians stated that their local healthcare framework was sufficient for primary prevention of CVD, while 67.2% stated that it was sufficient for secondary prevention of CVD. A high proportion of physicians reported using clinical guidelines for primary CVD prevention. However, time constraints, lack of perceived usefulness and inadequate knowledge were common reasons for not using CVD prevention guidelines or global CVD risk assessment tools.","subset":"pubmed_abstract"} +{"meta":{"pmid":15804822,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Staining human lymphocytes and onion root cell nuclei with madder root.\nWe performed staining experiments on cells using natural dyes and different mordants using techniques that are used for wool and silk dyeing. The natural dye sources were madder root, daisy, corn cockle and yellow weed. Ferrous sulfate, copper sulfate, potassium tartrate, urea, potassium aluminum sulfate and potassium dichromate were used as mordants. Distilled water, distilled water plus ethanol, heptane, and distilled water plus methanol were used as solvents. All dye-mordant-solvent combinations were studied at pH 2.4, 3.2 and 4.2. The generic staining procedure was to boil 5-10 onion roots or stimulated human lymphocyte (SHL) preparations in a dye bath on a hot plate. Cells were examined at every half hour. For multicolor staining, madder-dyed lymphocytes were decolorized, then stained with Giemsa. The AgNOR technique was performed following the decolorization of Giemsa stained lymphocytes. Good results were obtained for both onion root cells and lymphocytes that were boiled for 3 h in a dye bath that included 4 g madder root, 4 g ferrous sulfate as mordant in 50 ml of 1:1 (v\/v) methanol:distilled water. The pH was adjusted to 4.2 with 6 ml acetic acid. We conclude that madder root has potential as an alternative dye for staining biological materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":19011910,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Response of endangered plant species to inoculation with arbuscular mycorrhizal fungi and soil bacteria.\nThree endangered plant species, Plantago atrata and Pulsatilla slavica, which are on the IUCN red list of plants, and Senecio umbrosus, which is extinct in the wild in Poland, were inoculated with soil microorganisms to evaluate their responsiveness to inoculation and to select the most effective microbial consortium for application in conservation projects. Individuals of these taxa were cultivated with (1) native arbuscular mycorrhizal fungi (AMF) isolated from natural habitats of the investigated species, (2) a mixture of AMF strains available in the laboratory, and (3) a combination of AMF lab strains with rhizobacteria. The plants were found to be dependent on AMF for their growth; the mycorrhizal dependency for P. atrata was 91%, S. umbrosus-95%, and P. slavica-65%. The applied inocula did not significantly differ in the stimulation of the growth of P. atrata and S. umbrosus, while in P. slavica, native AMF proved to be the less efficient. We therefore conclude that AMF application can improve the ex situ propagation of these three threatened taxa and may contribute to the success of S. umbrosus reintroduction. A multilevel analysis of chlorophyll a fluorescence transients by the JIP test permitted an in vivo evaluation of plant vitality in terms of biophysical parameters quantifying photosynthetic energy conservation, which was found to be in good agreement with the results concerning physiological parameters. Therefore, the JIP test can be used to evaluate the influence of AMF on endangered plants, with the additional advantage of being applicable in monitoring in a noninvasive way the acclimatization of reintroduced species in nature.","subset":"pubmed_abstract"} +{"meta":{"pmid":35120348,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Diurnal Variation in Straylight in Patients With Fuchs Endothelial Corneal Dystrophy and Controls.\nThe goal of this study was to investigate diurnal changes in intraocular straylight in relation to other corneal parameters and subjective complaints in patients with Fuchs endothelial dystrophy and healthy controls. This is a prospective study conducted in 2 tertiary care hospitals in Germany and the Netherlands. Patients with Fuchs endothelial dystrophy (n = 71) and healthy controls (n = 34) were included. Patients with Fuchs dystrophy were grouped by the presence of subjective complaints and measured over multiple time points during the day. Measurements included intraocular straylight using the C-Quant and corneal thickness and backscatter using a Scheimpflug camera. A separate group of healthy controls was measured intensively with repeated straylight measurements directly after waking. An exponential decay model was used to model the diurnal change. Healthy controls showed an average straylight baseline of 1.17 log(s) with an increase in straylight after waking of 0.22 log(s). In the repeated measurements subgroup, the increase in morning straylight lasted for 22 minutes. Patients with Fuchs dystrophy showed a morning increase in straylight of 0.21 log(s) present up to 4 hours after waking before reaching an average baseline of 1.30 log(s). Straylight was positively correlated with anterior corneal backscatter, r = 0.21, P = 0.022, and corneal thickness, r = 0.46, P < 0.01. Healthy eyes experience a diurnal straylight increase similar to patients with Fuchs dystrophy in intensity. However, in Fuchs dystrophy, the resolution of increased straylight is prolonged over multiple hours compared with minutes in healthy eyes. This suggests pathological exacerbation of a physiological diurnal change. This mechanism can play a role in subjective complaints experienced by patients with Fuchs dystrophy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28848712,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Burkholderia pseudomallei Evades Nramp1 (Slc11a1)- and NADPH Oxidase-Mediated Killing in Macrophages and Exhibits Nramp1-Dependent Virulence Gene Expression.\nBacterial survival in macrophages can be affected by the natural resistance-associated macrophage protein 1 (Nramp1; also known as solute carrier family 11 member a1 or Slc11a1) which localizes to phagosome membranes and transports divalent cations, including iron. Little is known about the role of Nramp1 in Burkholderia infection, in particular whether this differs for pathogenic species like Burkholderia pseudomallei causing melioidosis or non-pathogenic species like Burkholderia thailandensis. Here we show that transfected macrophages stably expressing wild-type Nramp1 (Nramp1+) control the net replication of B. thailandensis, but not B. pseudomallei. Control of B. thailandensis was associated with increased cytokine responses, and could be abrogated by blocking NADPH oxidase-mediated production of reactive oxygen species but not by blocking generation of reactive nitrogen species. The inability of Nramp1+ macrophages to control B. pseudomallei was associated with rapid escape of bacteria from phagosomes, as indicated by decreased co-localization with LAMP1 compared to B. thailandensis. A B. pseudomallei bipB mutant impaired in escape from phagosomes was controlled to a greater extent than the parent strain in Nramp1+ macrophages, but was also attenuated in Nramp1- cells. Consistent with reduced escape from phagosomes, B. thailandensis formed fewer multinucleated giant cells in Nramp1+ macrophages at later time points compared to B. pseudomallei. B. pseudomallei exhibited elevated transcription of virulence-associated genes of Type VI Secretion System cluster 1 (T6SS-1), the Bsa Type III Secretion System (T3SS-3) and the bimA gene required for actin-based motility in Nramp1+ macrophages. Nramp1+ macrophages were found to contain decreased iron levels that may impact on expression of such genes. Our data show that B. pseudomallei is able to evade Nramp1- and NADPH oxidase-mediated killing in macrophages and that expression of virulence-associated genes by pathogenic B pseudomallei is enhanced in macrophages expressing wild-type compared to non-functional Nramp1. B. thailandensis has been proposed as surrogate for B. pseudomallei in the study of melioidosis however our study highlights important differences in the interaction of these bacteria with macrophages.","subset":"pubmed_abstract"} +{"meta":{"pmid":28265522,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":13}}},"text":"P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice.\nAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterised by the accumulation of aggregated proteins, microglia activation and motor neuron loss. The mechanisms underlying neurodegeneration and disease progression in ALS are unknown, but the ATP-gated P2X7 receptor channel is implicated in this disease. Therefore, the current study aimed to examine P2X7 in the context of neurodegeneration, and investigate whether the P2X7 antagonist, Brilliant Blue G (BBG), could alter disease progression in a murine model of ALS. Human SOD1G93A transgenic mice, which normally develop ALS, were injected with BBG or saline, three times per week, from pre-onset of clinical disease (62-64 days of age) until end-stage. During the course of treatment mice were assessed for weight, clinical score and survival, and motor coordination, which was assessed by rotarod performance. Various parameters from end-stage mice were assessed as follows. Motor neuron loss and microgliosis were assessed by immunohistochemistry. Relative amounts of lumbar spinal cord SOD1 and P2X7 were quantified by immunoblotting. Serum monocyte chemoattractant protein-1 was measured by ELISA. Splenic leukocyte populations were assessed by flow cytometry. Relative expression of splenic and hepatic P2X7 mRNA was measured by quantitative real-time PCR. Lumbar spinal cord SOD1 and P2X7 were also quantified by immunoblotting in untreated female SOD1G93A mice during the course of disease. BBG treatment reduced body weight loss in SOD1G93A mice of combined sex, but had no effect on clinical score, survival or motor coordination. BBG treatment reduced body weight loss in female, but not male, SOD1G93A mice. BBG treatment also prolonged survival in female, but not male, SOD1G93A mice, extending the mean survival time by 4.3% in female mice compared to female mice treated with saline. BBG treatment had no effect on clinical score or motor coordination in either sex. BBG treatment had no major effect on any end-stage parameters. Total amounts of lumbar spinal cord SOD1 and P2X7 in untreated female SOD1G93A mice did not change over time. Collectively, this data suggests P2X7 may have a partial role in ALS progression in mice, but additional research is required to fully elucidate the contribution of this receptor in this disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":24588839,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":12}}},"text":"\"Blurred lines?\" Sexual aggression and barroom culture.\nMeeting potential sexual\/romantic partners for mutual pleasure is one of the main reasons young adults go to bars. However, not all sexual contacts are positive and consensual, and aggression related to sexual advances is a common experience. Sometimes such aggression is related to misperceptions in making and receiving sexual advances while other times aggression reflects intentional harassment or other sexually aggressive acts. This study uses objective observational research to assess quantitatively gender of initiators and targets and the extent that sexual aggression involves intentional aggression by the initiator, the nature of responses by targets, and the role of third parties and intoxication. We analyzed 258 aggressive incidents involving sexual advances observed as part of a larger study on aggression in large capacity bars and clubs, using variables collected as part of the original research (gender, intoxication, intent) and variables coded from narrative descriptions (invasiveness, persistence, targets' responses, role of third parties). Hierarchical linear modeling analyses were used to account for nesting of incidents in evening and bars. Ninety percent of incidents involved male initiators and female targets, with almost all incidents involving intentional or probably intentional aggression. Targets mostly responded nonaggressively, usually using evasion. Staff rarely intervened; patron third parties intervened in 21% of incidents, usually to help the target but sometimes to encourage the initiator. initiators' level of invasiveness was related to intoxication of the targets, but not their own intoxication, suggesting intoxicated women were being targeted. Sexual aggression is a major problem in bars often reflecting intentional sexual invasiveness and unwanted persistence rather than misperceptions in sexual advances. Prevention needs to focus on addressing masculinity norms of male patrons and staff who support sexual aggression and better management of the highly sexualized and sexist environments of most bars.","subset":"pubmed_abstract"} +{"meta":{"pmid":20579406,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":8}}},"text":"Dietary patterns and colorectal cancer in a Japanese population: the Fukuoka Colorectal Cancer Study.\nFew studies have addressed the relation between dietary patterns and colorectal cancer in Japan. We investigated dietary patterns in relation to colorectal cancer risk in a community-based case-control study. The association with dietary patterns was also examined for different sites of colorectal cancer. Data were derived from the Fukuoka Colorectal Cancer Study, including 800 cases and 775 controls interviewed from September 2000 to December 2003. The cases were admitted to one of the participating hospitals for the first surgical treatment during this period. We identified dietary patterns using principal component analysis of intakes of twenty-nine items of food groups and specific foods. Quartile categories of each dietary pattern were used, and non-dietary lifestyle factors and total energy intake were adjusted for in the analysis. We identified three dietary patterns: prudent, high-fat and light-meal patterns. The prudent dietary pattern characterised by high intakes of vegetables, fruits, seafoods and soya foods showed a nearly significant protective association with the overall risk of colorectal cancer (trend P = 0.054), and it was statistically significantly related to a decreased risk of distal colon cancer (trend P = 0.002), but not to that of either proximal colon or rectal cancer. The high-fat and light-meal dietary patterns were not materially related to the overall or site-specific risk of colorectal cancer. In summary, a prudent dietary pattern was associated with a decreased risk of colorectal cancer, especially with that of distal colon cancer, in a fairly large case-control study in Japan.","subset":"pubmed_abstract"} +{"meta":{"pmid":31216102,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Accuracy of five self-report screening instruments for substance use in pregnancy.\nThe accuracy of current screening instruments for identification of substance use in pregnancy is unclear, particularly given methodological shortcomings in existing research. This diagnostic accuracy study compared five existing instruments for ability to identify illicit drug, opioid and alcohol use, under privacy expectations consistent with applied practice and using a gold standard incorporating toxicological analysis. Prospective cross-sectional screening accuracy study. Three sites encompassing four prenatal care clinics in the United States. Convenience sample of 1220 racially, ethnically and socio-economically diverse pregnant women aged 18 years and over. In Phase I, participants completed the five screening instruments in counterbalanced order. Instruments included the Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT (acronym for five-item screener with items related to car, relax, alone, forget, friends and trouble), 5Ps (parents, peers, partner, pregnancy, past), Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (NIDA) Quick Screen. In Phase II, participants provided a urine sample and completed a calendar recall-based interview regarding substance use. These screeners were tested, using receiver operating characteristic (ROC) analysis and accuracy statistics, against a reference standard consisting of substance use in three classes (illicit drugs, opioids and alcohol), considered positive if use was evident via 30-day calendar recall or urine analysis. Three hundred and fifteen of 1220 participants (26.3%) met reference standard criteria for positivity. The single-item screening questions from the NIDA Quick Screen showed high specificity (0.99) for all substances, but very poor sensitivity (0.10-0.27). The 5Ps showed high sensitivity (0.80-0.88) but low specificity (0.35-0.37). The CRAFFT, SURP-P and 5Ps had the highest area under the curve (AUC) for alcohol (0.67, 0.66 and 0.62, respectively), and the WIDUS had the highest AUC for illicit drugs and opioids (0.70 and 0.69, respectively). Performance of all instruments varied significantly with race, site and economic status. Of five screening instruments for substance use in pregnancy tested (Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT, 5Ps, Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (Quick Screen), none showed both high sensitivity and high specificity, and area under the curve was low for nearly all measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":29764756,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2022-40":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-10":1,"2019-43":1,"2019-35":1,"2019-30":1,"2019-22":1,"2019-13":1,"2023-40":1}}},"text":"Straightforward hit identification approach in fragment-based discovery of bromodomain-containing protein 4 (BRD4) inhibitors.\nA combination approach of a fragment screening and \"SAR by catalog\" was used for the discovery of bromodomain-containing protein 4 (BRD4) inhibitors. Initial screening of 3695-fragment library against bromodomain 1 of BRD4 using thermal shift assay (TSA), followed by initial hit validation, resulted in 73 fragment hits, which were used to construct a follow-up library selected from available screening collection. Additionally, analogs of inactive fragments, as well as a set of randomly selected compounds were also prepared (3 \u00d7 3200 compounds in total). Screening of the resulting sets using TSA, followed by re-testing at several concentrations, counter-screen, and TR-FRET assay resulted in 18 confirmed hits. Compounds derived from the initial fragment set showed better hit rate as compared to the other two sets. Finally, building dose-response curves revealed three compounds with IC50 = 1.9-7.4 \u03bcM. For these compounds, binding sites and conformations in the BRD4 (4UYD) have been determined by docking.","subset":"pubmed_abstract"} +{"meta":{"pmid":17945180,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-27":1,"2021-25":1,"2020-24":1,"2020-05":1,"2019-51":1,"2019-35":1,"2019-22":1,"2019-13":1,"2023-14":1,"2024-10":1,"2024-26":1}}},"text":"Tobacco proliferating cell nuclear antigen binds directly and stimulates both activity and processivity of ddNTP-sensitive mungbean DNA polymerase.\nPCNA is well known as a component of DNA replication system and plays important roles in multiple cellular pathways in addition to replication and repair. In this work we have demonstrated the physical and functional interaction between tobacco PCNA and mungbean ddNTP-sensitive DNA polymerase which shares many physicochemical properties with family X-DNA polymerases except with the moderately processive mode of nucleotide incorporation. We have shown here that recombinant PCNA binds directly to mungbean DNA polymerase as revealed in affinity chromatography, pull-down and co-immunoprecipitation approaches. In vitro DNA polymerase activity assay and processivity analyses indicated recombinant PCNA specifically stimulates both activity and processivity of mungbean DNA polymerase. These observations lead to interesting speculation about the functional significance of the ddNTP-sensitive enzyme in replication event in higher plants since the enzyme has been shown to be active and expressed at an elevated level during the endoreduplication stages in developing mungbean seeds.","subset":"pubmed_abstract"} +{"meta":{"pmid":28338769,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"IQ, the Urban Environment, and Their Impact on Future Schizophrenia Risk in Men.\nExposure to an urban environment during early life and low IQ are 2 well-established risk factors for schizophrenia. It is not known, however, how these factors might relate to one another. Data were pooled from the North Jutland regional draft board IQ assessments and the Danish Conscription Registry for men born between 1955 and 1993. Excluding those who were followed up for less than 1 year after the assessment yielded a final cohort of 153170 men of whom 578 later developed a schizophrenia spectrum disorder. We found significant effects of having an urban birth, and also experiencing an increase in urbanicity before the age of 10 years, on adult schizophrenia risk. The effect of urban birth was independent of IQ. However, there was a significant interaction between childhood changes in urbanization in the first 10 years and IQ level on the future adult schizophrenia risk. In short, those subjects who moved to more or less urban areas before their 10th birthday lost the protective effect of IQ. When thinking about adult schizophrenia risk, the critical time window of childhood sensitivity to changes in urbanization seems to be linked to IQ. Given the prediction that by 2050, over 80% of the developed world's population will live in an urban environment, this represents a major future public health issue.","subset":"pubmed_abstract"} +{"meta":{"pmid":29458725,"dup_signals":{"dup_doc_count":46,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":2,"2023-14":1,"2023-06":2,"2022-49":1,"2022-40":2,"2022-33":2,"2022-27":1,"2022-21":3,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":2,"2021-04":2,"2020-45":4,"2020-40":2,"2020-24":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-22":1,"2024-26":3,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Molecular Basis and Genetic Modifiers of Thalassemia.\nThalassemia is a disorder of hemoglobin characterized by reduced or absent production of one of the globin chains in human red blood cells with relative excess of the other. Impaired synthesis of \u03b2-globin results in \u03b2-thalassemia, whereas defective synthesis of \u03b1-globin leads to \u03b1-thalassemia. Despite being a monogenic disorder, thalassemia exhibits remarkable clinical heterogeneity that is directly related to the intracellular imbalance between \u03b1- and \u03b2-like globin chains. Novel insights into the genetic modifiers have contributed to the understanding of the correlation between genotype and phenotype and are being explored as therapeutic pathways to cure this life-limiting disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":26111824,"dup_signals":{"dup_doc_count":91,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":3,"2023-23":5,"2023-14":3,"2023-06":3,"2022-49":4,"2022-40":3,"2022-33":2,"2022-27":4,"2022-21":2,"2022-05":4,"2021-43":3,"2021-39":4,"2021-31":4,"2021-25":1,"2021-21":4,"2021-17":3,"2021-10":3,"2021-04":3,"2020-50":2,"2020-45":6,"2020-40":3,"2018-22":1,"2018-17":1,"2018-05":1,"2017-51":1,"2017-43":2,"2017-34":2,"2024-22":1,"2024-18":4,"2024-10":4,"2024-26":1}}},"text":"Time dependency of foamy virus evolutionary rate estimates.\nIt appears that substitution rate estimates co-vary very strongly with their timescale of measurement; the shorter the timescale, the higher the estimated value. Foamy viruses have a long history of co-speciation with their hosts, and one of the lowest estimated rates of evolution among viruses. However, when their rate of evolution is estimated over short timescales, it is more reminiscent of the rapid rates seen in other RNA viruses. This discrepancy between their short-term and long-term rates could be explained by the time-dependency of substitution rate estimates. Several empirical models have been proposed and used to correct for the time-dependent rate phenomenon (TDRP), such as a vertically-translated exponential rate decay model and a power-law rate decay model. Nevertheless, at present, it is still unclear which model best describes the rate dynamics. Here, we use foamy viruses as a case study to empirically describe the phenomenon and to determine how to correct rate estimates for its effects. Four empirical models were investigated: (i) a vertically-translated exponential rate decay model, (ii) a simple exponential rate decay model, (iii) a vertically-translated power-law rate decay model, and (iv) a simple power-law rate decay model. Our results suggest that the TDRP is likely responsible for the large discrepancy observed in foamy virus short-term and long-term rate estimates, and the simple power-law rate decay model is the best model for inferring evolutionary timescales. Furthermore, we demonstrated that, within the Bayesian phylogenetic framework, currently available molecular clocks can severely bias evolutionary date estimates, indicating that they are inadequate for correcting for the TDRP. Our analyses also suggest that different viral lineages may have different TDRP dynamics, and this may bias date estimates if it is unaccounted for. As evolutionary rate estimates are dependent on their measurement timescales, their values must be used and interpreted under the context of the timescale of rate estimation. Extrapolating rate estimates across large timescales for evolutionary inferences can severely bias the outcomes. Given that the TDRP is widespread in nature but has been noted only recently the estimated timescales of many viruses may need to be reconsidered and re-estimated. Our models could be used as a guideline to further improve current phylogenetic inference tools.","subset":"pubmed_abstract"} +{"meta":{"pmid":2522833,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"The pH of spontaneously beating cultured rat heart cells is regulated by an ATP-calmodulin-dependent Na+\/H+ antiport.\nWe investigated the mechanisms by which spontaneously beating cultured rat ventricular cells regulate intracellular pH (pHi). Specifically, the relative contributions of the Na+\/H+ antiport, Cl-\/HCO3- exchange, ATP, and calmodulin-dependent processes in regulating the pHi of cells loaded with the intracellular fluorescent pH indicator BCECF were investigated. The pHi of ventricular cells bathed in HEPES-buffered medium averaged 7.30 +\/- 0.02. Subsequent exposure of the cells to CO2-HCO3- -buffered medium resulted in intracellular acidification followed by recovery to pHi levels approximately 0.1 pH units lower than in controls. Recovery was inhibited by the Na+\/H+ antiport inhibitor 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The recovery from intracellular acidification, induced by a 15-mM ammonium chloride prepulse, was also dependent solely upon activation of the Na+\/H+ antiport. Recovery was dependent upon extracellular sodium, was completely inhibited by EIPA, and could be modulated by changes in extracellular pH (pHo). At low pHo values (6.3) the recovery of pHi was greatly attenuated, while at high pHo (8.0) the recovery process was accelerated. The final pHi to which the cells recovered was also dependent upon pHo. Preincubation of the cells with 2-deoxy-D-glucose to deplete cellular ATP levels reduced pHi by approximately 0.2 pH units and greatly impaired the cells' ability to recover from 15-mM ammonium chloride-induced acid load. Similarly, preincubation of cells with the calmodulin inhibitors W-7 and trifluoperazine also impaired their ability to recover from the acid load. The Cl- -HCO3- exchange played no role in the cells' ability to recover from intracellular acidosis. However, the presence of HCO3- significantly increased the resistance of myocardial cells to changes in pHi by approximately doubling their buffer capacity. These results demonstrated that a Na+\/H+ antiport is the major pHi-regulating system in spontaneously beating rat ventricular cells. The ability of the Na+\/H+ antiport to regulate myocardial pHi is dependent upon the cells' ability to maintain adequate levels of ATP. The antiport's dependency on ATP, in conjunction with its dependency on calmodulin, suggests that activation of the antiport in ventricular cells involves phosphorylation processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19884424,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":3,"2013-20":2,"2014-10":1,"unknown":11}}},"text":"Predisposing factors for recurrent shoulder dislocation after arthroscopic treatment.\nArthroscopic repair of anterior dislocation of the shoulder can fail. We hypothesized that patients who are at higher risk for redislocation following repair could be recognized preoperatively on the basis of their clinical history. The purpose of the present study was to identify the risk factors for recurrence in a community-based population of patients with traumatic unidirectional instability that was treated with a single arthroscopic technique. From January 2000 to December 2003, 625 patients with anterior unidirectional instability were managed with an arthroscopic Bankart technique, and 385 met the criteria for inclusion in the study. Demographic data were collected, and clinical follow-up was performed at three, six, twelve, twenty-four, and thirty-six months. At thirty-six months, thirty-one patients (8.1%) had experienced a redislocation; the rate was 13.3% among patients who were twenty-two years of age and younger and 6.3% among older patients. Age at the time of the first dislocation, male sex, and the time from the first dislocation until surgery were significant risk factors for recurrence (p < 0.05 for all). Patients who are more likely to have a redislocation following arthroscopic repair of an anterior shoulder dislocation can be identified preoperatively on the basis of sex, age, and the time from the first dislocation to surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":19065210,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":9}}},"text":"Light propagation from a fluorescent particle embedded in a photonic cluster of micrometer-sized dielectric spheres.\nIn self-assembled multilayer arrays of micrometer-sized spheres that include small amounts of fluorescent particles, unique six-dot-triangular and seven-dot-hexagonal patterns have been known to appear in the fluorescence microscopic images. Although it has been suggested that these two types of patterns correspond to local domain structures, i.e., face centered cubic (fcc) or hexagonal closed packed (hcp), no conclusive evidence has been provided to support this claim. In this study, we systematically investigated the relationship between the propagation patterns and the arrangement of the particles. Through a cross-check between an experiment using well-defined clusters fabricated by a micromanipulation technique and a rigorous calculation based on the expansion of vector spherical harmonics, we confirmed that the six-dot-triangular and seven-dot-hexagonal patterns correspond to the fcc and hcp domains, respectively. Further, we also found that the propagation patterns depend on the size of the clusters. As a result of a quantitative discussion on the light propagation in clusters with various sizes, it was clarified that a sufficient domain size is necessary for the appearance of clear triangular or hexagonal patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":29199746,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":3,"2018-43":3,"2018-30":3,"2018-17":2,"2018-13":2,"2018-05":3,"2017-51":3}}},"text":"Ultrafast interfacial energy transfer and interlayer excitons in the monolayer WS2\/CsPbBr3 quantum dot heterostructure.\nThe idea of fabricating artificial solids with band structures tailored to particular applications has long fascinated condensed matter physicists. Heterostructure (HS) construction is viewed as an effective and appealing approach to engineer novel electronic properties in two dimensional (2D) materials. Different from common 2D\/2D heterojunctions where energy transfer is rarely observed, CsPbBr3 quantum dots (0D-QDs) interfaced with 2D materials have become attractive HSs for exploring the physics of charge transfer and energy transfer, due to their superior optical properties. In this paper, a new 0D\/2D HS is proposed and experimentally studied, making it possible to investigate both light utilization and energy transfer. Specifically, this HS is constructed between monolayer WS2 and CsPbBr3 QDs, and exhibits a hybrid band alignment. The dynamics of energy transfer within the investigated 0D\/2D HS is characterized by femtosecond transient absorption spectrum (TAS) measurements. The TAS results reveal that ultrafast energy transfer caused by optical excitation is observed from CsPbBr3 QDs to the WS2 layer, which can increase the exciton fluence within the WS2 layer up to 69% when compared with pristine ML WS2 under the same excitation fluence. Moreover, the formation and dynamics of interlayer excitons have also been investigated and confirmed in the HS, with a calculated recombination time of 36.6 ps. Finally, the overall phenomenological dynamical scenario for the 0D\/2D HS is established within the 100 ps time region after excitation. The techniques introduced in this work can also be applied to versatile optoelectronic devices based on low dimensional materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":32611864,"dup_signals":{"dup_doc_count":17,"dup_dump_count":10,"dup_details":{"curated_sources":3,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":2,"2020-40":2,"2020-29":2,"2022-49":1}}},"text":"In vivo evaluation of zinc oxide-propolis mixture as root canal filling material in the primary molars: A 24-month follow-up randomized controlled trial.\nPulpectomy is a routine practice in children with pulpal and periapical infections, the success of which depends on the elimination of bacteria from the root canals. Propolis, a natural product with proven antibacterial and anti-inflammatory properties when mixed with zinc oxide powder as root canal filling material, it could provide good success in endodontic therapy of primary teeth. The aim was to evaluate and compare the clinical effectiveness of zinc oxide-propolis mixture with zinc oxide eugenol (ZOE) as root canal filling material in nonvital primary molars. This was a 2-arm, parallel group randomized controlled trial with blinded outcome assessment. Forty primary molars from children aged 4-8 years requiring pulpectomy treatment were randomly allocated into two groups according to the obturating material used: zinc oxide-propolis mixture (test group) and ZOE (control group). All the pulpectomy treated teeth were finally restored with stainless steel crowns, and the children were recalled at 6, 12, and 24 months for postoperative clinical and radiographic evaluation. Chi-square test was used to analyze the data. The overall success rate of pulpectomy with zinc oxide-propolis mixture and ZOE was found to be 95% and 70%, respectively, and the difference was statistically significant (P = 0.037). Zinc oxide-propolis mixture has shown a success rate of 100% at 6 months and 95% at 12 and 24 months follow-up, whereas ZOE has shown 80% success rate at 6 and 12 months, and it declined to 70% at 24-month follow-up. Zinc oxide-propolis mixture demonstrated good clinical and radiographic success at the end of 24 months, and hence, it can be considered as an alternate root canal filling material in the primary teeth.","subset":"pubmed_abstract"} +{"meta":{"pmid":25588366,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":11}}},"text":"The improvement of the dissolution rate of ziprasidone free base from solid oral formulations.\nThis work aims at increasing solubility and dissolution rate of ziprasidone free base-Biopharmaceutics Classifaction System (BCS) class II compound. The authors describe a practical approach to amorphization and highlight problems that may occur during the development of formulations containing amorphous ziprasidone, which was obtained by grinding in high-energy planetary ball mills or cryogenic mills. The release of ziprasidone free base from the developed formulations was compared to the reference drug product containing crystalline ziprasidone hydrochloride-Zeldox\u00ae hard gelatin capsules. All preparations were investigated using compendial tests (USP apparatuses II and IV) as well as novel, biorelevant dissolution tests. The novel test methods simulate additional elements of mechanical and hydrodynamic stresses, which have an impact on solid oral dosage forms, especially during gastric emptying. This step may prove to be particularly important for many formulations of BCS class II drugs that are often characterized by narrow absorption window, such as ziprasidone. The dissolution rate of the developed ziprasidone free base preparations was found to be comparable or even higher than in the case of the reference formulation containing ziprasidone hydrochloride, whose water solubility is about 400 times higher than its free base.","subset":"pubmed_abstract"} +{"meta":{"pmid":30639904,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Exposure to traffic and mortality risk in the 1991-2011 Canadian Census Health and Environment Cohort (CanCHEC).\nThere is evidence that local traffic density and living near major roads can adversely affect health outcomes. We aimed to assess the relationship between local road length, proximity to primary highways, and cause-specific mortality in the 1991 Canadian Census Health and Environment Cohort (CanCHEC). In this long-term study of 2.6 million people, based on completion of the long-form census in 1991 and followed until 2011, we used annual residential addresses to determine the total length of local roads within 200 m of postal code representative points and the postal code's distance to primary highways. The association between exposure to traffic and cause-specific non-accidental mortality was estimated using Cox proportional hazards models, adjusting for individual covariates and contextual factors, including census division-level proportion in high school, the percentage of recent immigrants, and neighborhood income. We performed sensitivity analyses, including adjustment for exposure to PM2.5, NO2, or O3, restricting to subjects in core urban areas, and spatial variation by climatic zone. The hazard ratio (HR) for all non-accidental mortality associated with an interquartile increase in length of local roads was 1.05 (95% CI 1.04, 1.05), while for an interquartile range increase in proximity to primary highways, the HR was 1.03 (95% CI 1.02, 1.04). HRs by traffic quartile increased with increasing lengths of local roads, as well as with closer proximity to primary highways, for all mortality causes. The associations were stronger within subjects' resident in urban core areas, attenuated by adjustment for PM2.5, and HRs showed limited spatial variation by climatic zone. In the CanCHEC cohort, exposure to higher road density and proximity to major traffic roads was associated with increased mortality risk from cerebrovascular and cardiovascular disease, ischemic heart disease, COPD, respiratory disease, and lung cancer, with unclear results for diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":32719521,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"Distinct and temporary-restricted epigenetic mechanisms regulate human \u03b1\u03b2 and \u03b3\u03b4 T cell development.\nThe development of TCR\u03b1\u03b2 and TCR\u03b3\u03b4 T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics show clear stage specificity and reveal that human T cell-lineage commitment is marked by GATA3- and BCL11B-dependent closing of PU.1 sites. A temporary increase in H3K27me3 without open chromatin modifications is unique for \u03b2-selection, whereas emerging \u03b3\u03b4 T cells, which originate from common precursors of \u03b2-selected cells, show large chromatin accessibility changes due to strong T cell receptor (TCR) signaling. Furthermore, we unravel distinct chromatin landscapes between CD4+ and CD8+ \u03b1\u03b2-lineage cells that support their effector functions and reveal gene-specific mechanisms that define mature T cells. This resource provides a framework for studying gene regulatory mechanisms that drive normal and malignant human T cell development.","subset":"pubmed_abstract"} +{"meta":{"pmid":38071848,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Endogenous CO imaging in bacterial pneumonia with a NIR fluorescent probe.\nBacterial pneumonia is a serious respiratory illness that poses a great threat to human life. Rapid and precise diagnosis of bacterial pneumonia is crucial for symptomatic clinical treatment. Endogenous carbon monoxide (CO) is regarded as a significant indicator of bacterial pneumonia; herein, we developed a near-infrared (NIR) probe for fluorescence and photoacoustic (PA) dual-mode imaging of endogenous CO in bacterial pneumonia. NO2-BODIPY could rapidly and specifically react with CO to produce strong NIR fluorescence as well as ratiometric PA signals. NO2-BODIPY has outstanding features including fast response, fluorescence\/PA dual mode signals, good specificity, and a low limit of detection (LOD = 20.3 nM), which enables it to image endogenous CO in cells and bacterial pneumonia mice with high sensitivity and high contrast ratio. In particular, NO2-BODIPY has two-photon excited (1340 nm, \u03c31 = 1671 GM) NIR fluorescence and has been utilized to image endogenous CO in bacterial pneumonia mice with deep tissue penetration. NO2-BODIPY has been demonstrated a good capability of fluorescence\/PA dual-mode imaging of CO in bacterial pneumonia mice, providing a precise manner to diagnose bacterial pneumonia.","subset":"pubmed_abstract"} +{"meta":{"pmid":24755550,"dup_signals":{"dup_doc_count":45,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":2,"2023-06":1,"2022-40":3,"2022-27":1,"2022-21":2,"2021-43":2,"2021-31":2,"2021-21":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-29":2,"2020-16":2,"2020-05":1,"2019-47":1,"2019-39":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-26":1,"2024-22":1,"2024-30":1}}},"text":"Fetal growth and risk of stillbirth: a population-based case-control study.\nStillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings. Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary.","subset":"pubmed_abstract"} +{"meta":{"pmid":28785263,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Similarities in the Metabolic Reprogramming of Immune System and Endothelium.\nCellular metabolism has been known for its role in bioenergetics. In recent years, much light has been shed on the reprogrammable cellular metabolism underlying many vital cellular processes, such as cell activation, proliferation, and differentiation. Metabolic reprogramming in immune and endothelial cells (ECs) is being studied extensively. These cell compartments are implicated in inflammation and pathogenesis of many diseases but their similarities in metabolic reprogramming have not been analyzed in detail. One of the most notable metabolic reprogramming is the Warburg-like effect, famously described as one of the hallmarks of cancer cells. Immune cells and ECs can display this phenotype that is characterized by a metabolic switch favoring glycolysis over oxidative phosphorylation (OXPHOS) in aerobic conditions. Though energy-inefficient, aerobic glycolysis confers many benefits to the respiring cells ranging from higher rate of adenosine triphosphate production to maintaining redox homeostasis. Chemical and biological regulators either promote or perturb this effect. In this review, nitric oxide, hypoxia-inducible factor, and adenosine monophosphate-activated protein kinase have been discussed for their common involvement in metabolic reprogramming of both systems. From in vitro and animal studies, various discrepancies exist regarding the effects of those regulators on metabolic switch. However, it is generally accepted that glycolysis favors inflammatory reactions while OXPHOS favors anti-inflammatory processes. The reasons for such observation are currently subject of intense studies and not completely understood. Finally, metabolic reprogramming in immune cells and ECs does not limit to the physiological state in health but can also be observed in pathological states, such as atherosclerosis and cancer. These new insights provide us with a better understanding of the similarities in metabolic reprogramming across a number of cell types, which could pave the way for future research and possible metabolic-based therapeutics.","subset":"pubmed_abstract"} +{"meta":{"pmid":18817188,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Comparison of heat shock response in Brucella abortus and Brucella melitensis.\nHeat shock protein (hsp) is highly conserved, that serves a wide range of function in protein folding and transport. It protect from various type of stress including heat shocks. However, it is well known that the virulence of B. melitensis is more than B. abortus, but there is not any strong evidence to verify it. For this purpose, in refer to potent antigenicity of hsps in various infectious as well as some hsp molecules act as potent activator of macrophage (danger signal), we hypothesized that difference in virulence between B. abortus and B. melitensis may be originated from difference in pattern of response to heat shock induced by high degree of fever that usually present in brucellosis. To this end, five B. abortus and five B. melitensis strains isolated from cows and human, were subjected to 39, 40 and 42 degrees C heat shocks. The bacterial whole cell proteins were extracted and resolved by SDS-PAGE. Western blotting was used to detect antibody production against the extracted bacterial proteins especially hsp60 in both control and patient sera. SDS-PAGE gels revealed protein bands mainly in the range of 10-100 kDa. The amounts of a 60 kDa protein band (hsp60) was significantly enhanced following heat shock at 42 degrees C in relation to the unheated cells in both bacterial species. The heat shock responses in B. abortus and B. melitensis point to the higher production of a 60 kDa protein (hsp60) in both bacterial species, especially in B. abortus. It seems that, lower hsp60 production by B. melitensis would induce a relatively much lower immune response against the bacterium leading to its greater virulence potentials; the sera from Brucellosis patients reacted with several of these cell derived protein bands in western blots, none of which were reactive with sera from healthy individuals. The western blot protein bands showed striking differences. This observation points to the immunogenic properties of hsps, specially the overwhelming response to hsp-60. Therefore, hsp-60 can be a good antigenic candidate for engineering subunit vaccine against Brucella, as well as for ELISA test development.","subset":"pubmed_abstract"} +{"meta":{"pmid":22257915,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Cardiovascular involvement in psoriatic arthritis.\nPsoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.","subset":"pubmed_abstract"} +{"meta":{"pmid":6658364,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Selenium levels in whole blood of Finnish volunteers before and during organic and inorganic selenium supplementation.\nHigh selenium barley biscuits containing 1 mumol (70 micrograms) organic Se were administered to healthy male volunteers for 5 weeks at doses of 2.1 mumol Se (group A) or 6.4 mumol (group B). In addition, 2 mg Na-selenate capsules (5.4 mumol Se) were given to two other groups at daily doses of 2 mg (group C) or 8 mg (group D). Groups A, B and C each comprised eight healthy men and group D eight healthy women and three men. The initial median concentration of whole blood selenium (B-Se for groups A, B and C were 1.0-1.1 mumol\/l (range 0.7-1.7) and for group D 1.3 mumol\/l (range 0.9-1.8). In 1-2 weeks time the B-Se concentrations rose to 1.6 mumol\/l for groups A and C, to 1.8 mumol\/l for group B, and to 2.2 mumol\/l for group D. There was no decrease 1 week after the Se intake ceased. As expected, the level of B-Se increased more (in relation to dose) in those given organic Se than in those given inorganic Se. Groups A, B and C, however, had rather moderate increases. The daily dose required to raise the B-Se of Finns up to the North American level (2.2 mumol\/l) was as high as 8 mg Na-selenate (21.5 mumol or 1700 micrograms Se), but the dose of organic Se which would be required to achieve this level is not yet known.","subset":"pubmed_abstract"} +{"meta":{"pmid":12904075,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"A comparison of phosphonothioic acids with phosphonic acids as phosphatase inhibitors.\nPhosphorothioates, analogues of phosphate esters in which a sulfur replaces an oxygen atom in the phosphoryl group, are competent surrogate substrates for a number of phosphatases. In some cases the thio analogues show similar binding (as estimated by K(m)) while other phosphatases show quite different K(m) values for phosphate compared to phosphorothioate esters. On this basis it was hypothesized that there might be different inhibitory tendencies by the nonhydrolyzable analogues, phosphonothioic acids compared with phosphonic acids. A series of phosphonothioic acids and corresponding phosphonic acids were synthesized and their inhibitory properties were compared toward human placental and E. coli alkaline phosphatases, the protein-tyrosine phosphatase from Yersinia, and the serine\/threonine protein phosphatases PP2C and lambda. Sulfur substitution for oxygen gives the phosphonothioic acids pK(a) values that are close to those of phosphate esters, in contrast to the higher pK(a) values typical of phosphonic acids. Despite different steric requirements and differences in charge distribution in the anions of phosphonothioic acids compared with phosphonic acids, it was found that, with some exceptions, differences in inhibitory properties were modest.","subset":"pubmed_abstract"} +{"meta":{"pmid":19088517,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Influenza vaccine: awareness and barriers to immunization in families of children with chronic medical conditions other than asthma.\nChildren with chronic medical conditions (CMCs) are considered to be at increased risk for influenza and its related complications. Despite this, influenza immunization rates in the United States for children with CMCs in the primary care setting remain between 7-10%. This was a survey study looking at the barriers to influenza immunization among children with CMCs other than asthma. We examined caregiver knowledge and perceptions regarding influenza vaccine in addition to assessing other barriers, such as availability and perceived safety of the vaccine. The study was conducted during the fall-winter influenza seasons of 2002-2003 and 2003-2004 at five academic institutions across the southeastern US. Convenience samples of 100-150 families attending pediatric subspecialty clinics were surveyed. A total of 794 surveys were completed. Controlling for disease, failure to recommend vaccination was significantly associated with failure to get the vaccine (P < 0.0001). Of the children who did not receive the vaccine, 61% of their parents believed that the vaccine itself could give influenza, 54% cited other safety concerns, and 30% thought it did not work. Among vaccine recipients, 163 (43%) reported that the primary care provider had given the vaccine, whereas 171 (45%) reported that the vaccine had been given at the subspecialty clinic. This study highlights the importance of physician recommendation, as well as parental education, as some of the key elements crucial to the receipt of influenza vaccination in children with CMCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":28078623,"dup_signals":{"dup_doc_count":30,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2021-10":3,"2020-16":4,"2020-10":1,"2019-47":5,"2019-43":1,"2019-35":3,"2019-30":10,"2019-26":1,"2019-13":1}}},"text":"Identification of Host Fruit Volatiles from Snowberry (Symphoricarpos albus), Attractive to Rhagoletis zephyria Flies from the Western United States.\nA mixture of behaviorally active volatiles was identified from the fruit of snowberry, Symphoricarpos albus laevigatus, for Rhagoletis zephyria flies reared from snowberry fruit. A nine-component blend containing 3-methylbutan-1-ol (3%), dimethyl trisulfide (1%), 1-octen-3-ol (40%), myrcene (8%), nonanal (9%), linalool (13%), (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT, 6%), decanal (15%), and \u03b2-caryophyllene (5%) was identified that gave consistent electroantennogram activity and was behaviorally active in flight tunnel tests. In other flight tunnel assays, snowberry flies from two sites in Washington state, USA, displayed significantly greater levels of upwind oriented flight to sources with the snowberry volatile blend compared with previously identified volatile blends from domestic apple (Malus domestica) and downy hawthorn (Crataegus mollis) fruit from the eastern USA, and domestic apple, black hawthorn (C. douglasii) and ornamental hawthorn (C. monogyna) from Washington state. Selected subtraction assays showed that whereas removal of DMNT or 1-octen-3-ol significantly reduced the level of upwind flight, removal of myrcene and \u03b2-caryophyllene, or dimethyl trisulfide alone did not significantly affect the proportion of upwind flights. Our findings add to previous studies showing that populations of Rhagoletis flies infesting different host fruit are attracted to unique mixtures of volatile compounds specific to their respective host plants. Taken together, the results support the hypothesis that differences among flies in their behavioral responses to host fruit odors represent key adaptations involved in sympatric host plant shifts, contributing to host specific mating and generating prezygotic reproductive isolation among members of the R. pomonella sibling species complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":29131728,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":6,"2022-49":1,"2022-21":1,"2021-25":1,"2021-04":2,"2020-50":1,"2020-40":1,"2020-34":1,"2023-40":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Yoga practice is associated with superior motor imagery performance.\nYoga is an activity that aims to integrate physical, mental and spiritual elements and is an increasingly popular approach to enhancing physical fitness. The integration of imagery within yoga practice is considered an important component and may be critical in contributing to the benefits of yoga that have been reported. In this study, we tested whether individuals who practice yoga demonstrate superior performance on an objective measure of implicit motor imagery. Thirty-six participants (18 yoga, 18 non-yoga) matched for age, sex and handedness, undertook the hand laterality recognition task; an objective measure of implicit motor imagery performance. Accuracy and response times were gathered and analysed to determine any group differences as well as any differences relating to the typical hallmarks of imagery (i.e. dominance and awkwardness effects) on the task. Response Times (RTs) in the yoga group were significantly faster than controls (p < 0.05) and there was also a trend towards greater accuracy for the Yoga group (p = 0.073). Dominance effects (faster responses to images corresponding with the dominant limb) and Awkwardness effects (faster responses to images corresponding with natural compared with awkward postures) were evident across groups, supporting the participants' use of motor imagery in undertaking the task. Additionally, a Group \u00d7 Awkwardness interaction (p < 0.05) revealed that the enhanced imagery performance for the yoga group was most pronounced for awkward postures. This is the first study to show that yoga practice is associated with superior motor imagery performance; an association that may be important in explaining the established rehabilitative value of yoga for chronic pain.","subset":"pubmed_abstract"} +{"meta":{"pmid":21550123,"dup_signals":{"dup_doc_count":34,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2020-29":2,"2020-05":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-30":2,"2018-22":1,"2017-43":2,"2017-34":2,"2017-26":2,"2017-17":2,"2017-09":2,"2023-40":1,"2024-10":1,"2017-13":2,"2013-48":1,"2024-26":1}}},"text":"N4 component responses to pre-pulse startle stimuli in young adults: relationship to alcohol dependence.\nBoth physiological and behavioral studies provide evidence to suggest that deficits in frontal cortical control circuits may contribute to the risk for developing alcohol dependence. Event-related potential (ERP) and eye blink responses to startle and short delay prepulse-plus-startle stimuli, and psychiatric diagnoses were investigated in young adult (age 18-30 years) men (n=135) and women (n=205) Mexican Americans. Women displayed a significant increase in the amplitude of the eye blink response to both the startle and pre-pulse-plus-startle stimuli. None of the psychiatric diagnoses were associated with differences in eye blink responses. ERP responses to the startle and prepulse-plus startle stimuli included a negative polarity wave at approximately 400 ms that was of the highest amplitude in the frontal leads (N4S). Women were found to have significantly higher amplitude N4S responses than men. Participants with alcohol dependence demonstrated significantly less inhibition and more facilitation of the N4S component by the pre-pulse stimuli. This finding was not associated with a diagnosis of: any other drug dependence disorder (including nicotine), anxiety or affective disorder, or conduct\/antisocial personality disorder. The present study suggests that gender and a lifetime diagnosis of alcohol dependence may selectively contribute to this frontal late wave electrophysiological response to prepulse-plus-startle stimuli.","subset":"pubmed_abstract"} +{"meta":{"pmid":23746529,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":2,"2024-10":1,"2017-13":1,"unknown":8}}},"text":"Translational cross talk in gene networks.\nIt has been shown experimentally that competition for limited translational resources by upstream mRNAs can lead to an anticorrelation between protein counts. Here, we investigate a stochastic model for this phenomenon, in which gene transcripts of different types compete for a finite pool of ribosomes. Throughout, we utilize concepts from the theory of multiclass queues to describe a qualitative shift in protein count statistics as the system transitions from being underloaded (ribosomes exceed transcripts in number) to being overloaded (transcripts exceed ribosomes in number). The exact analytical solution of a simplified stochastic model, in which the numbers of competing mRNAs and ribosomes are fixed, exhibits weak positive correlations between steady-state protein counts when total transcript count slightly exceeds ribosome count, whereas the solution can exhibit strong negative correlations when total transcript count significantly exceeds ribosome count. Extending this analysis, we find approximate but reasonably accurate solutions for a more realistic model, in which abundances of mRNAs and ribosomes are allowed to fluctuate randomly. Here, ribosomal fluctuations contribute positively and mRNA fluctuations contribute negatively to correlations, and when mRNA fluctuations dominate ribosomal fluctuations, a strong anticorrelation extremum reliably occurs near the transition from the underloaded to the overloaded regime.","subset":"pubmed_abstract"} +{"meta":{"pmid":22693337,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2022-05":1,"2021-17":1,"2020-16":1,"2020-10":1,"2019-43":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2022-33":1,"2024-18":1}}},"text":"The role of motion streaks in the perception of the kinetic Zollner illusion.\nIn classic geometric illusions such as the Zollner illusion, vertical lines superimposed on oriented background lines appear tilted in the direction opposite to the background. In kinetic forms of this illusion, an object moving over oriented background lines appears to follow a titled path, again in the direction opposite to the background. Existing literature does not proffer a complete explanation of the effect. Here, it is suggested that motion streaks underpin the illusion; that the effect is a consequence of interactions between detectors tuned to the orientation of background lines and those sensing the motion streaks that arise from fast object motion. This account was examined in the present study by measuring motion-tilt induction under different conditions in which the strength or salience of motion streaks was attenuated: by varying object speed (Experiment 1), contrast (Experiment 2), and trajectory\/length by changing the element life-time within the stimulus (Experiment 3). It was predicted that, as motion streaks become less available, background lines would less affect the perceived direction of motion. Consistent with this prediction, the results indicated that, with a reduction in object speed below that required to generate motion streaks (< 1.12\u00b0\/s), Weber contrast (< 0.125) and motion streak length (two frames) reduced or extinguished the motion-tilt-induction effect. The findings of the present study are consistent with previous reports and computational models that directly combine form and motion information to provide an effective determinant of motion direction.","subset":"pubmed_abstract"} +{"meta":{"pmid":30943202,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2022-27":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-05":1,"2019-39":1,"2023-40":1,"2024-10":1}}},"text":"Application of long read sequencing to determine expressed antigen diversity in Trypanosoma brucei infections.\nAntigenic variation is employed by many pathogens to evade the host immune response, and Trypanosoma brucei has evolved a complex system to achieve this phenotype, involving sequential use of variant surface glycoprotein (VSG) genes encoded from a large repertoire of ~2,000 genes. T. brucei express multiple, sometimes closely related, VSGs in a population at any one time, and the ability to resolve and analyse this diversity has been limited. We applied long read sequencing (PacBio) to VSG amplicons generated from blood extracted from batches of mice sacrificed at time points (days 3, 6, 10 and 12) post-infection with T. brucei TREU927. The data showed that long read sequencing is reliable for resolving variant differences between VSGs, and demonstrated that there is significant expressed diversity (449 VSGs detected across 20 mice) and across the timeframe of study there was a clear semi-reproducible pattern of expressed diversity (median of 27 VSGs per sample at day 3 post infection (p.i.), 82 VSGs at day 6 p.i., 187 VSGs at day 10 p.i. and 132 VSGs by day 12 p.i.). There was also consistent detection of one VSG dominating expression across replicates at days 3 and 6, and emergence of a second dominant VSG across replicates by day 12. The innovative application of ecological diversity analysis to VSG reads enabled characterisation of hierarchical VSG expression in the dataset, and resulted in a novel method for analysing such patterns of variation. Additionally, the long read approach allowed detection of mosaic VSG expression from very few reads-the earliest in infection that such events have been detected. Therefore, our results indicate that long read analysis is a reliable tool for resolving diverse gene expression profiles, and provides novel insights into the complexity and nature of VSG expression in trypanosomes, revealing significantly higher diversity than previously shown and the ability to identify mosaic gene formation early during the infection process.","subset":"pubmed_abstract"} +{"meta":{"pmid":19004388,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":14}}},"text":"Justice and justiciability: advancing solidarity and justice through South Africans' right to health jurisprudence.\nThe South African Constitutional Court's jurisprudence provides a path-breaking illustration of the social justice potential of an enforceable right to health. It challenges traditional objections to social rights by showing that their enforcement need not be democratically unsound or make zero-sum claims on limited resources. Indeed the South African experience suggests that enforcing health rights may in fact contribute to greater degrees of collective solidarity and justice as the Court has sought to ensure that the basic needs of the poor are not unreasonably restricted by competing public and private interests. This approach has seen the Court adopt a novel fights paradigm which locates individual civil and social rights within a communitarian framework drawing from the traditional African notion of'ubuntu', denoting collective solidarity, humaneness and mutual responsibilities to recognize the respect, dignity and value of all members of society. Yet this jurisprudence also illustrates the limits of litigation as a tool of social transformation, and of social rights that remain embedded in ideological baggage even where they have been constitutionally entrenched and enforced. This paper explores the Constitutional Court's unfolding jurisprudence on the right to health, providing background to the constitutional entrenchment of a justiciable right to health; exploring early Constitutional Court jurisprudence on this right; turning to the forceful application of this right in relation to government policy on AIDS treatment; and concluding with thoughts about the strengths and limits of this jurisprudence in light of subsequent case-law.","subset":"pubmed_abstract"} +{"meta":{"pmid":18202164,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Population based epidemiology and prognosis of mesothelioma in Leeds, UK.\nMalignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK. Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients' hospital records and the Trust histology database were reviewed, as well as coroner's reports on all patients with a post mortem diagnosis of mesothelioma. Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110\/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery\/cutting CT biopsies or chest drains. 73\/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92\/146 (63%) had a performance status of 2 or better at diagnosis but only 54\/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery. This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.","subset":"pubmed_abstract"} +{"meta":{"pmid":16221733,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Project quality rating by experts and practitioners: experience with Preffi 2.0 as a quality assessment instrument.\nPreffi 2.0 is an evidence-based Dutch quality assessment instrument for health promotion interventions. It is mainly intended for both planning and assessing one's own projects but can also be used to assess other people's projects (external use). This article reports a study on the reliability of Preffi as an external quality assessment instrument. Preffi is used to assess quality at three levels: (i) specific criteria, (ii) clusters of criteria and (iii) entire projects. The study compared Preffi-based assessments of 20 projects by three practitioners with their intuitive assessments of the same projects and with assessments by three experts, which were to be used as external criteria. The intuitive assessments only related to the cluster and project levels. Our main hypothesis was that intuitive assessments by practitioners would be less reliable and accurate than their Preffi-based assessments and the experts' assessments. On the whole, we failed to confirm this hypothesis: the experts' assessments proved less reliable and accurate than the practitioners' intuitive and Preffi-based assessments and differed too much from each other to be used as external criteria. The Preffi-based assessments by the practitioners had an acceptable generalizability coefficient (G) and accuracy (standard error of measurement). At the level of the entire project, two assessors are needed to produce sufficiently reliable and accurate assessments, whereas three are needed for assessment at cluster level. The study also showed that different assessors use different perspectives and base their assessment on a variety of aspects. This was regarded as inevitable and even useful by the assessors themselves. Discussions between assessors are important to achieve consensus. The article suggests some improvements to Preffi to further increase its reliability.","subset":"pubmed_abstract"} +{"meta":{"pmid":29517258,"dup_signals":{"dup_doc_count":34,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":1,"2023-14":4,"2023-06":1,"2022-40":1,"2022-33":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-24":1,"2019-30":2,"2019-22":2,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2024-30":1}}},"text":"The moral standing of animals: Towards a psychology of speciesism.\nWe introduce and investigate the philosophical concept of 'speciesism' -the assignment of different moral worth based on species membership -as a psychological construct. In five studies, using both general population samples online and student samples, we show that speciesism is a measurable, stable construct with high interpersonal differences, that goes along with a cluster of other forms of prejudice, and is able to predict real-world decision-making and behavior. In Study 1 we present the development and empirical validation of a theoretically driven Speciesism Scale, which captures individual differences in speciesist attitudes. In Study 2, we show high test-retest reliability of the scale over a period of four weeks, suggesting that speciesism is stable over time. In Study 3, we present positive correlations between speciesism and prejudicial attitudes such as racism, sexism, homophobia, along with ideological constructs associated with prejudice such as social dominance orientation, system justification, and right-wing authoritarianism. These results suggest that similar mechanisms might underlie both speciesism and other well-researched forms of prejudice. Finally, in Studies 4 and 5, we demonstrate that speciesism is able to predict prosociality towards animals (both in the context of charitable donations and time investment) and behavioral food choices above and beyond existing related constructs. Importantly, our studies show that people morally value individuals of certain species less than others even when beliefs about intelligence and sentience are accounted for. We conclude by discussing the implications of a psychological study of speciesism for the psychology of human-animal relationships. (PsycINFO Database Record (c) 2019 APA, all rights reserved).","subset":"pubmed_abstract"} +{"meta":{"pmid":2824913,"dup_signals":{"dup_doc_count":36,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2018-05":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":1,"2014-41":1,"2014-35":1,"2014-23":2,"2014-15":1,"2021-10":1,"2015-11":1,"2015-06":1,"2013-48":1,"2015-18":1}}},"text":"Opioid receptors and endogenous opioids in diverse human and animal cancers.\nReceptor binding studies demonstrated specific high-affinity, saturable binding of a number of opioid ligands to a wide variety of neural and nonneural human and animal tumors. Radioimmunoassays revealed the presence of beta-endorphin and methionine-enkephalin in these tumors. Both methionine- and leucine-enkephalin were detected in tumor tissue by immunocytochemistry, with immunoreactivity related to the cortical cytoplasm of tumor cells, but not to cell nuclei. Endogenous opioids and receptors were found in benign and malignant tumors representative of ectodermal, mesodermal, and endodermal origin. Receptors and endogenous opioid peptides were present in tumors from many different species, including those transplanted into nude mice. These results suggest that opioid receptors and endogenous opioids are fundamental features of human and animal cancers.","subset":"pubmed_abstract"} +{"meta":{"pmid":27575626,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"The Use of \"Optimal Cytoreduction\" Nomenclature in Ovarian Cancer Literature: Can We Move Toward a More Optimal Classification System?\nThe objective of this study is to explore how cytoreductive surgical outcomes such as residual disease (RD) and use of the term \"optimal cytoreduction\" (OCR) have changed over time in the ovarian cancer literature. We identified all English-language publications referring to ovarian cancer cytoreduction for a 12-year period. Publications were evaluated for how the diameter of RD was categorized and whether OCR was defined. In addition, the use of RD and OCR terminology trends over time and associations between terminology and the region of corresponding author, study type, and journal impact factor were explored. Of the 772 publications meeting inclusion criteria, the RD stratification points used to demarcate patient groups were as follows: 0 mm (45%), 5 mm (3.6%), 10 mm (65%), and 20 mm (24%). The use of 0-mm RD (odds ratio [OR], 1.1; 95% confidence interval, 1.05-1.15) and 10-mm RD (OR, 1.1; 95% confidence interval, 1.09-1.20) to delineate patient outcomes increased over time. The use of OCR terminology did not change over time but was more commonly used in clinical studies as well as those from North America. Many studies (70%) defined OCR as less than or equal to 10-mm RD, whereas 30% defined OCR differently or not at all. Optimal cytoreduction terminology remains ambiguous and inconsistently used in the ovarian cancer surgical literature. On the basis of this literature review, we propose a novel classification system to categorize RD without reference to OCR while accurately and succinctly identifying meaningful clinical subgroups and minimizing bias.","subset":"pubmed_abstract"} +{"meta":{"pmid":34782484,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":1,"2024-10":1,"unknown":9}}},"text":"External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland.\nThe QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland. We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020. Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively. Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":27252462,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Prosthetic Vascular Graft Infections: Bacterial Cultures from Negative-Pressure-Wound-Therapy Foams Do Not Improve Diagnostics.\nWe analyzed the diagnostic value of microorganisms cultured from negative-pressure-wound-therapy (NPWT) foam samples compared to that of microorganisms cultured from deep tissue samples from patients with vascular graft infections. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 58%, 86%, 81%, and 66%, respectively. The diagnostic value of microbiological cultures from NPWT foams was poor.","subset":"pubmed_abstract"} +{"meta":{"pmid":32682459,"dup_signals":{"dup_doc_count":12}},"text":"A vulnerability index for the management of and response to the COVID-19 epidemic in India: an ecological study.\nCOVID-19 is spreading rapidly in India and other parts of the world. Despite the Indian Government's efforts to contain the disease in the affected districts, cases have been reported in 627 (98%) of 640 districts. There is a need to devise a tool for district-level planning and prioritisation and effective allocation of resources. Based on publicly available data, this study reports a vulnerability index for identification of vulnerable regions in India on the basis of population and infrastructural characteristics. We computed a composite index of vulnerability at the state and district levels based on 15 indicators across the following five domains: socioeconomic, demographic, housing and hygiene, epidemiological, and health system. We used a percentile ranking method to compute both domain-specific and overall vulnerability and presented results spatially with number of positive COVID-19 cases in districts. A number of districts in nine large states-Bihar, Madhya Pradesh, Telangana, Jharkhand, Uttar Pradesh, Maharashtra, West Bengal, Odisha, and Gujarat-located in every region of the country except the northeast, were found to have high overall vulnerability (index value more than 0\u00b775). These states also had high vulnerability according to most of the five domains. Although our intention was not to predict the risk of infection for a district or a state, we observed similarities between vulnerability and the current concentration of COVID-19 cases at the state level. However, this relationship was not clear at the district level. The vulnerability index presented in this paper identified a number of vulnerable districts in India, which currently do not have large numbers of COVID-19 cases but could be strongly impacted by the epidemic. Our index aims to help planners and policy makers effectively prioritise regions for resource allocation and adopt risk mitigation strategies for better preparedness and responses to the COVID-19 epidemic. None.","subset":"pubmed_abstract"} +{"meta":{"pmid":29039370,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"De-Identification of Medical Narrative Data.\nMaintaining data security and privacy in an era of cybersecurity is a challenge. The enormous and rapidly growing amount of health-related data available today raises numerous questions about data collection, storage, analysis, comparability and interoperability but also about data protection. The US Health Portability and Accountability Act (HIPAA) of 1996 provides a legal framework and a guidance for using and disclosing health data. Practically, the approach proposed by HIPAA is the de-identification of medical documents by removing certain Protected Health Information (PHI). In this work, a rule-based method for the de-identification of French free-text medical data using Natural Language Processing (NLP) tools will be presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":28258167,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":13}}},"text":"Locomotion Induces Stimulus-Specific Response Enhancement in Adult Visual Cortex.\nThe responses of neurons in the visual cortex (V1) of adult mammals have long been thought to be stable over long periods. Here, we investigated whether repeated exposure to specific stimuli would enhance V1 visual responses in mice using intrinsic signal imaging through the intact skull and two-photon imaging of calcium signals in single neurons. Mice ran on Styrofoam balls floating on air while viewing one of three different, high-contrast visual stimuli. V1 responses to the stimuli that were viewed by the animal were specifically enhanced, while responses to other stimuli were unaffected. Similar exposure in stationary mice or in mice in which NMDA receptors were partially blocked did not significantly enhance responses. These findings indicate that stimulus-specific plasticity in the adult visual cortex depends on concurrent locomotion, presumably as a result of the high-gain state of the visual cortex induced by locomotion.SIGNIFICANCE STATEMENT We report a rapid and persistent increase in visual cortical responses to visual stimuli presented during locomotion in intact mice. We first used a method that is completely noninvasive to image intrinsic signals through the intact skull. We then measured the same effects on single neurons using two-photon calcium imaging and found that the increase in response to a particular stimulus produced by locomotion depends on how well the neuron is initially driven by the stimulus. To our knowledge, this is the first time such enhancement has been described in single neurons or using noninvasive measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":15456867,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":7,"unknown":7}}},"text":"beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1.\nbeta-arrestin-1 is an adaptor protein that mediates agonist-dependent internalization and desensitization of G-protein-coupled receptors (GPCRs) and also participates in the process of heterologous desensitization between receptor tyrosine kinases and GPCR signaling. In the present study, we determined whether beta-arrestin-1 is involved in insulin-induced insulin receptor substrate 1 (IRS-1) degradation. Overexpression of wild-type (WT) beta-arrestin-1 attenuated insulin-induced degradation of IRS-1, leading to increased insulin signaling downstream of IRS-1. When endogenous beta-arrestin-1 was knocked down by transfection of beta-arrestin-1 small interfering RNA, insulin-induced IRS-1 degradation was enhanced. Insulin stimulated the association of IRS-1 and Mdm2, an E3 ubiquitin ligase, and this association was inhibited to overexpression of WT beta-arrestin-1, which led by decreased ubiquitin content of IRS-1, suggesting that both beta-arrestin-1 and IRS-1 competitively bind to Mdm2. In summary, we have found the following: (i) beta-arrestin-1 can alter insulin signaling by inhibiting insulin-induced proteasomal degradation of IRS-1; (ii) beta-arrestin-1 decreases the rate of ubiquitination of IRS-1 by competitively binding to endogenous Mdm2, an E3 ligase that can ubiquitinate IRS-1; (iii) dephosphorylation of S412 on beta-arrestin and the amino terminus of beta-arrestin-1 are required for this effect of beta-arrestin on IRS-1 degradation; and (iv) inhibition of beta-arrestin-1 leads to enhanced IRS-1 degradation and accentuated cellular insulin resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":8093239,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2020-50":1,"2020-34":3,"2020-29":1,"2019-43":3,"2019-35":1,"2021-21":1}}},"text":"Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12.\nThe phase variation of type 1 fimbriation in Escherichia coli is associated with the inversion of a short DNA element. This element (switch) acts in cis to control transcription of fimA, the major fimbrial subunit gene. Thus, fimA is transcribed when the switch is in one orientation (the on orientation) but not the other (the off orientation). The fim inversion requires either fimB (on-to-off or off-to-on inversion) or fimE (on-to-off inversion only), as well as integration host factor, and is also influenced by the abundant DNA-binding protein H-NS. Here we report that an additional gene, lrp, a factor known to influence the expression of both Pap and K99 fimbriae, is also required for normal activity of the fim switch. The frequencies of both fimB-promoted and fimE-promoted inversions, and consequently the phase variation of type 1 fimbriation, are lower in lrp mutants. Lrp affects slightly the transcription of both fimB (which is increased) and fimE (which is decreased). We believe that these alterations in fimB and fimE transcription alone are unlikely to account for the sharp reduction in switching found in lrp mutants.","subset":"pubmed_abstract"} +{"meta":{"pmid":21852500,"dup_signals":{"dup_doc_count":32,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2017-13":4,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"unknown":19}}},"text":"Rapid range shifts of species associated with high levels of climate warming.\nThe distributions of many terrestrial organisms are currently shifting in latitude or elevation in response to changing climate. Using a meta-analysis, we estimated that the distributions of species have recently shifted to higher elevations at a median rate of 11.0 meters per decade, and to higher latitudes at a median rate of 16.9 kilometers per decade. These rates are approximately two and three times faster than previously reported. The distances moved by species are greatest in studies showing the highest levels of warming, with average latitudinal shifts being generally sufficient to track temperature changes. However, individual species vary greatly in their rates of change, suggesting that the range shift of each species depends on multiple internal species traits and external drivers of change. Rapid average shifts derive from a wide diversity of responses by individual species.","subset":"pubmed_abstract"} +{"meta":{"pmid":30442909,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-21":1,"2021-10":1,"2020-45":1,"2020-29":1,"2019-51":1,"2019-43":1,"2019-30":1,"2019-22":1,"2023-50":1,"2024-26":1}}},"text":"Mycobiome diversity: high-throughput sequencing and identification of fungi.\nFungi are major ecological players in both terrestrial and aquatic environments by cycling organic matter and channelling nutrients across trophic levels. High-throughput sequencing (HTS) studies of fungal communities are redrawing the map of the fungal kingdom by hinting at its enormous - and largely uncharted - taxonomic and functional diversity. However, HTS approaches come with a range of pitfalls and potential biases, cautioning against unwary application and interpretation of HTS technologies and results. In this Review, we provide an overview and practical recommendations for aspects of HTS studies ranging from sampling and laboratory practices to data processing and analysis. We also discuss upcoming trends and techniques in the field and summarize recent and noteworthy results from HTS studies targeting fungal communities and guilds. Our Review highlights the need for reproducibility and public data availability in the study of fungal communities. If the associated challenges and conceptual barriers are overcome, HTS offers immense possibilities in mycology and elsewhere.","subset":"pubmed_abstract"} +{"meta":{"pmid":19801241,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2022-05":1,"2021-17":1,"2020-05":1,"2019-30":1,"2018-26":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2023-06":1,"2024-22":1}}},"text":"Acoustic hypochlorite activation in simulated curved canals.\nIt was the goal of this study to compare different NaOCl activation schemes regarding a desired and an untoward outcome. Ultrasonic tips and a currently marketed sonic system were used in conjunction with a 2.5% sodium hypochlorite solution. Necrotic pulp tissue dissolution in simulated accessory canals and transportation of the main canal were assessed. Epoxy resin models (10 per group) with a curved simulated main root canal and two simulated accessory canals filled with necrotic bovine pulp tissue were irrigated passively with one of three ultrasonic setups (straight stainless steel files, prebent stainless steel files, or nickel-titanium tips) or a sonic device in conjunction with a plastic tip. Activation was performed four times for 30 seconds with replenishment of the NaOCl solution in between. All the files\/tips had a 2% taper and a 0.15-mm tip diameter according to the manufacturer. Data from superimposing and analyzing digital photos before and after treatment were statistically analyzed using one-way analysis of variance followed by Bonferroni's correction for multiple comparisons (alpha < 0.05). Passive ultrasonic irrigation (PUI) in all the groups dissolved significantly more tissue than sonic activation (p < 0.05). No detectable canal transportation with sonic activation was observed. The difference in this outcome was not significant compared with ultrasonically activated nickel-titanium tips, whereas the straight stainless steel files caused significantly more ledging compared with these setups (p < 0.05). Under the current conditions, PUI with a nickel-titanium tip promoted superior tissue-dissolving effects over sonic irrigant activation while maintaining simulated canal anatomy.","subset":"pubmed_abstract"} +{"meta":{"pmid":31651579,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":9}}},"text":"Long-term impact of adolescent chronic pain on young adult educational, vocational, and social outcomes.\nDespite evidence of broad impact on daily functioning in adolescence, little is known regarding the life course effects of childhood chronic pain. This is the first nationally representative study to characterize the disruptive impact of chronic pain in adolescence on key educational, vocational, and social outcomes in young adulthood (12 years later). Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were used, including 3174 youth with chronic pain and 11,610 without chronic pain. Multivariate regression analyses controlling for sociodemographic factors and adolescent depression found that chronic pain in adolescence was associated with long-term risk of a constellation of impairments indicative of socioeconomic disparities. Specifically, adolescent chronic pain was subsequently associated with reduced educational attainment (eg, lower odds of attaining a high school diploma and bachelor's degree), poor vocational functioning (eg, lower odds of receiving employer-provided benefits and higher odds of receiving public aid), and social impairments (eg, early parenthood, lower self-reported romantic relationship quality) in young adulthood. These findings provide a window into the future of adolescents with chronic pain, contributing to the limited knowledge base of the scope of adverse long-term outcomes during the transition to adulthood. However, several questions remain. Increased research attention is needed to understand the life course impact of pediatric chronic pain, including early risk factors and underlying mechanisms that drive adverse outcomes as they unfold across the lifespan.","subset":"pubmed_abstract"} +{"meta":{"pmid":15007725,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":14}}},"text":"Plant responses to precipitation in desert ecosystems: integrating functional types, pulses, thresholds, and delays.\nThe 'two-layer' and 'pulse-reserve' hypotheses were developed 30 years ago and continue to serve as the standard for many experiments and modeling studies that examine relationships between primary productivity and rainfall variability in aridlands. The two-layer hypothesis considers two important plant functional types (FTs) and predicts that woody and herbaceous plants are able to co-exist in savannas because they utilize water from different soil layers (or depths). The pulse-reserve model addresses the response of individual plants to precipitation and predicts that there are 'biologically important' rain events that stimulate plant growth and reproduction. These pulses of precipitation may play a key role in long-term plant function and survival (as compared to seasonal or annual rainfall totals as per the two-layer model). In this paper, we re-evaluate these paradigms in terms of their generality, strengths, and limitations. We suggest that while seasonality and resource partitioning (key to the two-layer model) and biologically important precipitation events (key to the pulse-reserve model) are critical to understanding plant responses to precipitation in aridlands, both paradigms have significant limitations. Neither account for plasticity in rooting habits of woody plants, potential delayed responses of plants to rainfall, explicit precipitation thresholds, or vagaries in plant phenology. To address these limitations, we integrate the ideas of precipitation thresholds and plant delays, resource partitioning, and plant FT strategies into a simple 'threshold-delay' model. The model contains six basic parameters that capture the nonlinear nature of plant responses to pulse precipitation. We review the literature within the context of our threshold-delay model to: (i) develop testable hypotheses about how different plant FTs respond to pulses; (ii) identify weaknesses in the current state-of-knowledge; and (iii) suggest future research directions that will provide insight into how the timing, frequency, and magnitude of rainfall in deserts affect plants, plant communities, and ecosystems.","subset":"pubmed_abstract"} +{"meta":{"pmid":26048139,"dup_signals":{"dup_doc_count":17,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2017-13":1,"2024-30":1,"unknown":11}}},"text":"Carboxybetaine Modified Interface for Electrochemical Glycoprofiling of Antibodies Isolated from Human Serum.\nImpedimetric lectin biosensors capable of recognizing two different carbohydrates (galactose and sialic acid) in glycans attached to antibodies isolated from human serum were prepared. The first step entailed the modification of a gold surface by a self-assembled monolayer (SAM) deposited from a solution containing a carboxybetaine-terminated thiol applied to the subsequent covalent immobilization of lectins and to resist nonspecific protein adsorption. In the next step, Sambucus nigra agglutinin (SNA) or Ricinus communis agglutinin (RCA) was covalently attached to the SAM, and the whole process of building a bioreceptive layer was optimized and characterized using a diverse range of techniques including electrochemical impedance spectroscopy, cyclic voltammetry, quartz crystal microbalance, contact angle measurements, zeta-potential assays, X-ray photoelectron spectroscopy, and atomic force microscopy. In addition, the application of the SNA-based lectin biosensor in the glycoprofiling of antibodies isolated from the human sera of healthy individuals and of patients suffering from rheumatoid arthritis (RA) was successfully validated using an SNA-based lectin microarray. The results showed that the SNA lectin, in particular, is capable of discriminating between the antibodies isolated from healthy individuals and those from RA patients based on changes in the amount of sialic acid present in the antibodies. In addition, the results obtained by the application of RCA and SNA biosensors indicate that the abundance of galactose and sialic acid in antibodies isolated from healthy individuals is age-related.","subset":"pubmed_abstract"} +{"meta":{"pmid":15810081,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-30":1,"unknown":14}}},"text":"Value of CT in the diagnosis and management of gallstone ileus.\nTo retrospectively establish the diagnostic criteria of gallstone ileus on CT, and to prospectively apply these criteria to determine the diagnostic accuracy of CT to confirm or exclude gallstone ileus in patients who presented with acute small bowel obstruction (SBO). Another purpose was to ascertain whether the size of ectopic gallstones would affect treatment strategy. Fourteen CT scans in cases of proved gallstone ileus were evaluated retrospectively by two radiologists for the presence or absence of previously reported CT findings to establish the diagnostic criteria. These criteria were applied in a prospective contrast enhanced CT study of 165 patients with acute SBO, which included those 14 cases of gallstone ileus. The hard copy images of 165 CT studies were reviewed by a different group of two radiologists but without previous knowledge of the patient's final diagnosis. All CT data were further analyzed to determine the diagnostic accuracy of gallstone ileus when using CT in prospective evaluation of acute SBO. The size of ectopic gallstone on CT was correlated with the clinical course. The diagnostic criteria of gallstone ileus on CT were established retrospectively, which included: (1) SBO; (2) ectopic gallstone; either rim-calcified or total-calcified; (3) abnormal gall bladder with complete air collection, presence of air-fluid level, or fluid accumulation with irregular wall. Prospectively, CT confirmed the diagnosis in 13 cases of gallstone ileus with these three criteria. Only one false negative case could be identified. The remaining 151 patients are true negative cases and no false positive case could be disclosed. The overall sensitivity, specificity and accuracy of CT in diagnosing gallstone ileus were 93%, 100%; and 99%, respectively. Surgical exploration was performed in 13 patients of gallstone ileus with ectopic stones sized larger than 3 cm. One patient recovered uneventfully following conservative treatment with an ectopic stone sized 2 cm in the long axis. Contrast enhanced CT imaging offered crucial evidence not only for the diagnosis of gallstone ileus but also for decision making in management strategy.","subset":"pubmed_abstract"} +{"meta":{"pmid":8969918,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2017-13":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":9}}},"text":"Effects of ecstasy on aldosterone secretion in the rat in vivo and in vitro.\nThis study investigated the effects of Methylenedioxymethamphetamine (MDMA) on aldosterone and renin secretion via, (1) acute administration of MDMA to conscious Wistar rats, and (2) superfusion of whole rat adrenal capsules with 1 microM and 10 microM MDMA, in the presence of 5-HT. In study 1 basal aldosterone levels increased significantly from 3.490 +\/- 1.1 nmol\/l to 12.099 +\/- 2 nmol\/l after administration of MDMA (P < 0.05). Control rats showed no significant increase in aldosterone secretion. Basal plasma renin activity (PRA) was 6.86 +\/- 1.65 ng\/ml\/hr in the MDMA treated animals increasing to 228.56 +\/- 34.1 ng\/ml\/hr after administration (P < 0.05). In study 2 the aldosterone response to 5-HT was potentiated by 1 microM and 10 microM MDMA. No consistent stimulation of aldosterone was observed by MDMA alone. In conclusion, acute administration of MDMA to conscious rats causes activation of the renin-angiotensin-aldosterone system. In addition, MDMA can potentiate the direct action of 5-HT on aldosterone secretion in vitro by a mechanism which could be associated with the 5-HT transporter.","subset":"pubmed_abstract"} +{"meta":{"pmid":19218310,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Usability and acceptability of a website that provides tailored advice on falls prevention activities for older people.\nThis article presents the usability and acceptability of a website that provides older people with tailored advice to help motivate them to undertake physical activities that prevent falls. Views on the website from interviews with 16 older people and 26 sheltered housing wardens were analysed thematically. The website was well received with only one usability difficulty with the action plan calendar. The older people selected balance training activities out of interest or enjoyment, and appeared to carefully add them into their current routine. The wardens were motivated to promote the website to their residents, particularly those who owned a computer, had balance problems, or were physically active. However, the participants noted that currently a minority of older people use the Internet. Also, some older people underestimated how much activity was enough to improve balance, and others perceived themselves as too old for the activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":21849469,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Epithelial protein-tyrosine phosphatase 1B contributes to the induction of mammary tumors by HER2\/Neu but is not essential for tumor maintenance.\nProtein-tyrosine phosphatase 1B (PTP1B), a well-established metabolic regulator, plays an important role in breast cancer. Using whole-body PTP1B knockout mice, recent studies have shown that PTP1B ablation delays HER2\/Neu-induced mammary cancer. Whether PTP1B plays a cell-autonomous or a noncell-autonomous role in HER2\/Neu-evoked tumorigenesis and whether it is involved in tumor maintenance was unknown. We generated mice expressing HER2\/Neu and lacking PTP1B specifically in the mammary epithelium. We found that mammary-specific deletion of PTP1B delays the onset of HER2\/Neu-evoked mammary tumors, establishing a cell autonomous role for PTP1B in such neoplasms. We also deleted PTP1B in established mouse mammary tumors or depleted PTP1B in human breast cancer cell lines grown as xenografts. PTP1B inhibition did not affect tumor growth in either model showing that neither epithelial nor stromal PTP1B is necessary for tumor maintenance. Taken together, our data show that despite the PTP1B contribution to tumor onset, it is not essential for tumor maintenance. This suggests that PTP1B inhibition could be effective in breast tumor prevention.","subset":"pubmed_abstract"} +{"meta":{"pmid":19103601,"dup_signals":{"dup_doc_count":23,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2019-35":1,"2019-30":1,"2019-26":2,"2019-22":1,"2019-13":2,"2019-09":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-34":2,"2018-26":2,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2020-40":1}}},"text":"Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086.\nLP2086 is a family of outer membrane lipoproteins from Neisseria meningitidis, which elicits bactericidal antibodies and are currently undergoing human clinical trials in a bivalent formulation where each antigen represents one of the two known LP2086 subfamilies. Here we report the NMR structure of the recombinant LP2086 variant B01, a representative of the LP2086 subfamily B. The structure reveals a novel fold composed of two domains: a \"taco-shaped\" N-terminal beta-sheet and a C-terminal beta-barrel connected by a linker. The structure in micellar solution is consistent with a model of LP2086 anchored to the outer membrane bilayer through its lipidated N terminus. A long flexible chain connects the folded part of the protein to the lipid anchor and acts as spacer, making both domains accessible to the host immune system. Antibodies broadly reactive against members from both subfamilies have been mapped to the N terminus. A surface of subfamily-defining residues was identified on one face of the protein, offering an explanation for the induction of subfamily-specific bactericidal antibodies.","subset":"pubmed_abstract"} +{"meta":{"pmid":16751775,"dup_signals":{"dup_doc_count":26,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2023-14":2,"2022-40":2,"2022-21":2,"2021-49":2,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases.\nAlthough understanding of the function and specificity of many natural killer (NK) cell receptors is increasing, the molecular mechanisms regulating their expression during late development of NK cells remain unclear. Here we use representational difference analysis to identify molecules required for late NK cell differentiation. Axl protein tyrosine kinase, together with the structurally related receptors Tyro3 and Mer, were essential for NK cell functional maturation and normal expression of inhibitory and activating NK cell receptors. Also, all three receptors were expressed in maturing NK cells, the ligands of these receptors were produced by bone marrow stromal cells, and recombinant versions of these ligands drove NK cell differentiation in vitro. These results collectively suggest that Axl, Tyro3 and Mer transmit signals that are essential for the generation of a functional NK cell repertoire.","subset":"pubmed_abstract"} +{"meta":{"pmid":23860639,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":2,"2017-22":1,"2017-17":1,"2018-51":1}}},"text":"Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation.\nThe advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care.","subset":"pubmed_abstract"} +{"meta":{"pmid":31488492,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":13}}},"text":"Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.\nPaget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08\/S0501\/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. ISRCTN11616770.","subset":"pubmed_abstract"} +{"meta":{"pmid":17045716,"dup_signals":{"dup_doc_count":24,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":1,"2024-10":2,"2017-13":1,"2024-30":1,"unknown":18}}},"text":"Social capital and mental health: a comparative analysis of four low income countries.\nWomen and the poor are disproportionately affected by common mental disorders (CMD), and women in low income countries are particularly at risk. Social capital may explain some of the geographical variation in CMD, but the association between social capital and CMD in low income countries has rarely been studied. This paper aims to explore the relationship between individual and ecological measures of social capital and maternal CMD in four low income countries. Cross-sectional data from the Young Lives (YL) study with information across 234 communities in Peru, Ethiopia, Vietnam and Andhra Pradesh (India) were used. The mental health of mothers of one-year-old children (n=6909), and the individual cognitive and structural social capital of all respondents was assessed. Ecological social capital was calculated by aggregating individual responses to the community level. Multi-level modelling was used to explore the association between individual and ecological (community level) social capital and maternal CMD in each of the four countries, adjusting for a wide range of individual and community level confounders. The analysis shows that individual cognitive social capital is associated with reduced odds of CMD across all four countries. The results for structural social capital are more mixed and culturally specific, with some aspects associated with increased odds of CMD. This suggests that structural social capital has context-specific effects and cognitive social capital more universal effects on maternal CMD.","subset":"pubmed_abstract"} +{"meta":{"pmid":27440003,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction.\nPatients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2\u00b0P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death\/MI\/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (\u22653 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease\/MI\/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. URL: https:\/\/www.clinicaltrials.gov. Unique identifier: NCT00526474.","subset":"pubmed_abstract"} +{"meta":{"pmid":29750653,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-40":2,"2022-49":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-24":1,"2023-50":1}}},"text":"Risk of hypoglycemia in youth with type 2 diabetes on insulin.\nThe objective of this study was to ascertain the risk of hypoglycemia among youth with type 2 diabetes (T2D) on insulin therapy. Twenty-two youth with T2D on insulin therapy (M=12, F=10, age=14.4\u00b14.0 years) were enrolled from a single pediatric endocrine practice. They were followed-up for 3 months with weekly phone calls and monthly in-person visits to review blood glucose logs and document any signs or symptoms of hypoglycemia (defined as finger stick glucose of \u226470 mg\/dL). Episodes of hypoglycemia were categorized into five categories: severe, documented symptomatic, asymptomatic, probable symptomatic and relative hypoglycemia. In addition to examining the risk of hypoglycemia, the degree to which hypoglycemia was associated with patient demographics (e.g. age, gender and body mass index [BMI]) or clinical factors (i.e. duration of diabetes, duration of insulin treatment, glycemic control or insulin dose and regimen) was determined. Nine hypoglycemic events occurred during the study period in five patients with an incidence rate of nine events per 5.3 patient-years. Of the hypoglycemic events, five were symptomatic and four were asymptomatic. No severe hypoglycemic events occurred. Hypoglycemia was not associated with age, ethnicity, duration of insulin treatment, insulin dose or initial hemoglobin (HbA1c). However, a significant difference in BMI was noted, with T2D youth who experienced hypoglycemia having a lower BMI than those who did not experience hypoglycemia. The results of this study suggest that the risk of hypoglycemia in youth with T2D on insulin therapy is low.","subset":"pubmed_abstract"} +{"meta":{"pmid":28295106,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-18":1,"unknown":9}}},"text":"Structure, electrocatalysis and dynamics of immobilized cytochrome PccH and its microperoxidase.\nGeobacter sulfurreducens cells have the ability to exchange electrons with conductive materials, and the periplasmic cytochrome PccH plays an essential role in the direct electrode-to-cell electron transfer in this bacterium. It has atypically low redox potential and unique structural features that differ from those observed in other c-type cytochromes. We report surface enhanced resonance Raman spectroscopic and electrochemical characterization of the immobilized PccH, together with molecular dynamics simulations that allow for the rationalization of experimental observations. Upon attachment to electrodes functionalized with partially or fully hydrophobic self-assembled monolayers, PccH displays a distribution of native and non-native heme spin configurations, similar to those observed in horse heart cytochrome c. The native structural and thermodynamic features of PccH are preserved upon attachment mixed hydrophobic (-CH3\/-NH2) surfaces, while pure -OH, -NH2 and -COOH surfaces do not provide suitable platforms for its adsorption, indicating that its still unknown physiological redox partner might be membrane integrated. Neither of the employed immobilization strategies results in electrocatalytically active PccH capable of the reduction of hydrogen peroxide. Pseudoperoxidase activity is observed in immobilized microperoxidase, which is enzymatically produced from PccH and spectroscopically characterized. Further improvement of PccH microperoxidase stability is required for its application in electrochemical biosensing of hydrogen peroxide.","subset":"pubmed_abstract"} +{"meta":{"pmid":14641053,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"The irony of manganese superoxide dismutase.\nThe manganese and iron SODs (superoxide dismutases) form a superfamily of closely related antioxidant defence metalloenzymes. MnSOD requires Mn (not Fe) for activity. However, when MnSOD is expressed in Escherichia coli grown in medium supplemented with ferrous salts, Fe substitutes for Mn in the active site, reflecting relatively indiscriminate uptake of either Mn or Fe and a surprisingly low selectivity for the identity of the bound metal ion. X-ray crystallographic studies on Fe-substituted MnSOD show that the substrate access channel is blocked by solvent (hydroxide), providing a structural explanation for the observed metal specificity of the catalytic activity. The mechanism of metal binding has been investigated in vitro using recombinant thermophilic SODs. The thermophilic Thermus thermophilus MnSOD expressed in E. coli was isolated as the metal-free apoprotein when heat treatment was eliminated from the purification procedure. While incubation of the purified MnSOD apoprotein with metal salts at ambient temperatures did not restore SOD activity, re-activation could be achieved by heating the protein with Mn salts at elevated temperatures. This in vitro thermally triggered metal uptake is non-specific for the metal ion; both Mn and Fe bind, but only Mn restores catalytic activity. Formation of the metal complex is essentially irreversible under these conditions. The metallation process is strongly temperature-dependent, suggesting that there are substantial activation barriers to metal uptake at ambient temperatures that are overcome by a transition in the apoprotein structure under physiological conditions. Two mechanisms may be proposed for SOD metallation: one involving subunit dissociation and another involving domain separation. Thermally triggered metal binding by thermophilic SODs is providing new insight into the metallation mechanism of the SOD apoprotein, which is likely to be conserved over this family of enzymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":30035015,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2021-21":1,"2021-04":2,"2020-45":2,"2019-43":1,"2019-30":1,"2019-04":1,"2018-51":1,"2018-43":1,"2018-34":1,"2023-50":1,"2024-22":1}}},"text":"Hippocampal metabolites in asthma and their implications for cognitive function.\nEmerging research indicates that individuals with asthma have an increased risk of cognitive impairment, yet the associations of asthma with neural correlates of memory remain relatively unknown. The hippocampus is the predominant neural structure involved in memory, and alterations in the hippocampal metabolic profile are observed in individuals with mild cognitive impairment. We therefore hypothesized that individuals with asthma may have altered hippocampal metabolites compared to healthy controls. Structural magnetic resonance imaging (sMRI) and proton magnetic resonance spectroscopy (1H-MRS) were used to compare hippocampal volume and metabolites of otherwise healthy adults with and without asthma (N = 40), and to study the association of these measures with cognitive function and asthma-related variables. Participants underwent 3-Tesla sMRI and 1H-MRS, with the volume of interest placed in the left hippocampus to measure levels of N-acetylaspartate (NAA), glutamate (Glu), creatine (Cr), and myo-inositol (MI), as indicators of neuronal viability, cellular activity, cellular energy reserve, as well as glial activation. Individuals with asthma had lower hippocampal NAA compared to healthy controls. For all participants, poorer cognitive function was associated with reduced NAA and Glu. For individuals with asthma, poorer cognitive function was associated with reduced disease control. Additionally, short-acting rescue bronchodilator use was associated with significantly lower NAA, and Glu, whereas inhaled corticosteroid use was related to significantly higher Cr and in tendency higher NAA and Glu. All findings controlled for left hippocampal volume, which was not different between groups. These findings highlight that asthma and\/or its treatment may affect hippocampal chemistry. It is possible that the observed reductions in hippocampal metabolites in younger individuals with asthma may precede cognitive and hippocampal structural deficits observed in older individuals with asthma.","subset":"pubmed_abstract"} +{"meta":{"pmid":30931360,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Management of Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitor Therapy: a Minireview of Current Clinical Guidelines.\nSuccessful targeting and inhibition of the cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death-1 protein\/programmed cell death ligand 1 immune checkpoint pathways has led to a rapidly expanding repertoire of immune checkpoint inhibitors for the treatment of various cancers. The approved agents now include ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab. In addition to antitumor responses, immune checkpoint inhibition can lead to activation of autoreactive T-cells resulting in unique immune-related adverse events (irAEs). Therefore, it is imperative that oncology nurses, and other clinicians involved in the care of cancer patients, are familiar with the management of irAEs which differ significantly from the management of adverse events from cytotoxic chemotherapy. Herein, we review the mechanisms of irAEs and strategies for management of irAEs and highlight similarities as well as differences among clinical guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology, Society for Immunotherapy of Cancer, and European Society for Medical Oncology. Understanding these similarities and key differences will facilitate the development and implementation of a practice site-specific plan for the management of irAEs.","subset":"pubmed_abstract"} +{"meta":{"pmid":31461091,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Hamiltonian formalism of spin-orbit Jahn-Teller and pseudo-Jahn-Teller problems in trigonal and tetragonal symmetries.\nA formalism for expansions of all bimodal spin-orbit Jahn-Teller and pseudo-Jahn-Teller Hamiltonian operators in trigonal and tetragonal symmetries is presented. With the formalism, we can easily obtain expansion formulas of the Hamiltonian matrix elements in symmetry-adapted vibrational coordinates up to arbitrary order. The formalism is presented as a set of generic matrices and lookup tables, which are convenient to use even without understanding the derivation of the formalism. Three examples are used to demonstrate the correctness, completeness, and conciseness of the formalism. One of the examples is also used to demonstrate how to obtain expansion formulas in more than two vibrational modes by using the bimodal formalism. This work lays a foundation for deriving a unified formalism for spin-orbit and non-spin-orbit (pseudo-)Jahn-Teller Hamiltonians in general axial symmetries.","subset":"pubmed_abstract"} +{"meta":{"pmid":1540947,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Frequent association of p53 gene mutation in invasive bladder cancer.\nStructural alterations of the p53 gene were investigated to elucidate the molecular biological difference between superficial and invasive bladder cancer by polymerase chain reaction single-strand conformation polymorphism analysis. In 25 bladder cancers obtained from 23 patients, p53 gene mutations were investigated in exon regions 4 to 11. Twenty-four were transitional cell carcinomas, and the remaining one was a squamous cell carcinoma. Only one of 13 superficial bladder cancers, including pTis, pTa, and pT1, was found to have p53 gene mutation. However, of 12 invasive bladder cancers with pT2, pT3, and pT4, six primary carcinomas, including a squamous cell carcinoma and one metastatic carcinoma, were found to have p53 gene mutations. The number of cancers examined in Grades 1, 2, and 3 was three, seven, and 15, respectively. p53 gene mutation was not found in any of the ten cancers with Grades 1 and 2, while eight of 15 bladder cancers with Grade 3 were found to have p53 gene mutation. The results indicated that the incidence of p53 gene mutations appeared to be much higher in invasive-type and high-grade bladder cancers than in superficial and low-grade ones. Our results are compatible with the recently published results by Sidransky et al. [Science (Washington DC), 252: 706-709, 1991] showing that p53 gene mutations were frequently found in invasive bladder cancers by sequence analysis on polymerase chain reaction amplified products corresponding to exons 5 to 9. Our results are also compatible with previously reported results by Olumi et al. (Cancer Res., 50: 7081-7083, 1990) showing that the loss of chromosome 17p, revealed by analysis with restriction fragment length polymorphism, was frequent in high-grade bladder cancers. In this study, p53 gene mutations were often found in exon 4 as well as in other exons. Therefore, this region should also be examined for screening of mutations of this gene in bladder cancer. There appeared to be no consistent mutation sites in exons 4 to 11 of the p53 gene and no specific patterns of the mutation in bladder cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":31364446,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults.\nBackground Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-\u03b54 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-\u03b54 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73\u00b17 years, 42% female) underwent echocardiography to determine cardiac output (L\/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and \u03b54 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race\/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-\u03b54 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output\u00d7APOE-\u03b54 status interaction and again stratified by \u03b54 carrier status. Cardiac output\u00d7APOE-\u03b54 status related to naming (\u03b2=0.91, P=0.0009), category fluency (\u03b2=1.2, P=0.01), information processing speed (\u03b2=-5.4, P=0.001), visuospatial skill (\u03b2=0.85, P=0.003), and executive function performances (\u03b2=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-\u03b54 carriers. Conclusions APOE-\u03b54 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the \u03b54 allele. These findings add to increasing evidence that APOE-\u03b54 carrier status has important implications for associations between vascular and brain health in aging adults.","subset":"pubmed_abstract"} +{"meta":{"pmid":9059266,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":7}}},"text":"Retrobulbar pressures measured during surgical decompression of the orbit.\nIn Graves' ophthalmopathy the increase in volume of intraocular muscles and fat will cause elevated intraorbital pressure. In order to investigate the pressure levels involved, intraorbital pressure, or retrobulbar pressure (RBP) was measured continuously in orbits of patients with Graves' ophthalmopathy during surgical decompression. Retrobulbar pressure was measured before and during surgical decompression using an intraorbitally applied pressure transducer. In eight patients with dysthyroid optic neuropathy (DON) RBPs between 17 and 40 mm Hg were recorded. At the end of the surgical procedure the mean RBP was reduced from 28.7 mm Hg to 18.7 mm Hg, the decrease ranging from 8 to 12 mm Hg, which showed a high correlation with the starting pressures (p < 0.001). In two cases without DON, pressures were 11 and 9 mm Hg. Forces exerted by spatula manipulation usually resulted in a RBP level of more than 70 mm Hg. This study shows that RBPs are markedly elevated in Graves' ophthalmopathy and that surgical decompression can result in a significant reduction in the intraorbital pressure. Optic nerve dysfunction in Graves' ophthalmopathy may not be caused exclusively by the direct pressure of swollen extraocular muscles upon the optic nerve, but also by a raised RBP. It is hypothesised that the damage inflicted upon the optic nerve can be caused in consequence by RBP induced incarceration of the nerve, compressed by surrounding periosteal lined orbital fat bulging posteriorly into the entrance of the optic canal.","subset":"pubmed_abstract"} +{"meta":{"pmid":19875653,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Heritabilities of ocular biometrical traits in two croatian isolates with extended pedigrees.\nTo assess the effects of body stature and years of education, in addition to age and sex, on six oculometric traits and to estimate the heritabilities of these quantitative traits in two Croatian cross-population studies. Adult subjects living on the two Croatian islands of Vis and Korcula were recruited for a large epidemiologic and genetic study that included eye biometry, keratometry, and autorefraction. Effects and heritabilities were estimated by using general linear mixed models for axial length (AL), anterior chamber depth (ACD), corneal curvature (CC), corneal thickness (CT), lens thickness (LT), and spherical equivalent refraction (SER). Both cohorts were genotyped with dense SNP arrays, allowing the use of kinship coefficients derived from genotypic data (realized kinship) rather than from pedigree information (expected kinship). Across cohorts, body mass index (BMI) did not consistently influence any of the ocular traits adjusted for age and\/or sex, whereas height and years in education (YrEd) did, explaining up to an additional 5% of the variance (in CC). CT was the trait least influenced by covariates. Estimated heritabilities in Vis and Korcula, respectively, were 84% and 52% for CC, 75% and 71% for CT, 37% and 32% for LT, 59% and 45% for ACD, 37% and 74% for AL, and 0% and 17% for SER. While heritabilities of CT and CC seemed uniformly high across studies of Caucasian datasets, estimates for SER varied widely and were at the lower end of the spectrum of published observations in our study.","subset":"pubmed_abstract"} +{"meta":{"pmid":2507623,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":4,"2018-43":3,"2018-30":1,"2018-17":2,"2018-13":1,"2017-51":3}}},"text":"Case-mix payment for nursing home care: lessons from Maryland.\nEven before Medicare adopted case-based payments for hospitals, some state Medicaid programs employed case-mix payment systems for nursing home care. Their purpose was less to promote cost containment than to improve access to nursing homes for the most costly patients. This paper evaluates one such system, adopted by the state of Maryland in 1983 as part of an overall reimbursement reform. Using data on nursing home patient characteristics, costs, and staffing, as well as interviews with officials and various providers of care, the article shows that Maryland's system was successful in shifting nursing home service away from light-care and toward heavy-care patients. Furthermore, the shift occurred without inducing readily measurable declines in quality of care and with little additional administrative cost (partly because the state built its case-mix system on preexisting patient review activities). Although states could learn from and improve upon Maryland's experience--most notably in offering incentives to improve quality of care and in targeting community care on the light-care patients that nursing homes become less willing to serve--Maryland demonstrates that case-mix payment can change nursing home behavior in desired directions without substantial negative consequences.","subset":"pubmed_abstract"} +{"meta":{"pmid":26197536,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"The Lignan-containing Extract of Schisandra chinensis Berries Inhibits the Growth of Chlamydia pneumonia.\nThe purpose of this study was to investigate the effect and selectivity of an extract of Schisandra chinensis berries against Chlamydia pneumoniae and C. trachomatis. Among the ethnopharmacological uses of the extract from Schisandrae fructus are cough and pneumonia. Therefore we focused on respiratory pathogens. The extract completely inhibited the growth of C. pneumoniae strain CV6 at 250 \u03bcg\/mL concentration. The inhibition of C. pneumoniae and C. trachomatis growth was dose dependent and established with three different strains. The extract inhibited C. pneumoniae production of infectious progeny in a dose dependent manner. Chlamydia selectivity was elucidated with growth inhibition measurements of three other respiratory bacterial species. A pure compound found in Schisandra chinensis berries, schisandrin B at 20.0 \u03bcg\/mL concentration inhibited the growth of both C. pneumoniae and C. trachomatis. The extract was found to be non-toxic to the human host cells. These findings highlight the potential of the extract from Schisandra chinensis berries as a source for antichlamydial compounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":18991499,"dup_signals":{"dup_doc_count":35,"dup_dump_count":11,"dup_details":{"curated_sources":5,"2021-49":1,"2021-43":1,"2021-04":1,"2020-45":1,"2020-40":5,"2020-34":1,"2020-10":1,"2019-43":15,"2019-39":2,"2019-13":1,"2022-40":1}}},"text":"Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging.\nNormal pressure hydrocephalus (NPH) represents a treatable form of dementia. Recent estimates of the incidence of this condition are in the region of 5% of patients with dementia. The symptoms of NPH can vary among individuals and may be confused with those of patients with multi-infarct dementia, dementia of the Alzheimer type, or even Parkinson disease. Traditionally the diagnosis of NPH could only be confirmed postoperatively by a favorable outcome to surgical diversion of CSF. The object of this literature review was to examine the role of structural and functional imaging in providing biomarkers of favorable surgical outcome. A Medline search was undertaken for the years 1980-2006, using the following terms: normal pressure hydrocephalus, adult hydrocephalus, chronic hydrocephalus, imaging, neuroimaging, imaging studies, outcomes, surgical outcomes, prognosis, prognostic value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The query revealed 16 studies that correlated imaging with surgical outcomes offering accuracy results. Three studies fulfilled the statistical criteria of a biomarker. A dementia Alzheimer-type pattern on SPECT in patients with idiopathic NPH, the presence of CSF flow void on MR imaging, and the N-acetylaspartate\/choline ratio in patients with the secondary form are able to predict surgical outcomes with high accuracy. There is at present Level A evidence for using MR spectroscopy in patients with secondary NPH, and Level B evidence for using SPECT and phase-contrast MR imaging to select patients with idiopathic NPH for shunt placement. The studies, however, need to be repeated by other groups. The current work should act as a platform to design further studies with larger sample sizes.","subset":"pubmed_abstract"} +{"meta":{"pmid":15843386,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Evaluation of photo-mutagenicity and photo-cytotoxicity of food coloring agents.\nPigments extracted from natural products are widely used for food coloration in Japan. An investigation concerning the photo-mutagenicity and photo-carcinogenicity of frequently used colorants in Japan was performed. Colorants examined were from Laccifer lacca (lac-color), Coccus cacti (cochineal-color), Carthamus tinctorius (carthamus yellow), Gardenia augusta (gardenia yellow and gardenia blue), Monascus anka and Monascus purpureus (monascus red), the skin of Vitis vinifera and Vitis labrusca (grape-skin color), Tamarindus indica (tamarind brown) and Beta vulgaris (beet red). No significant increase in bacterial mutation was found when Salmonella typhimurium TA98, TA100 and TA102 were simultaneously treated with colorants and subjected to UVA irradiation for 30 min. When colorant solutions were subjected to UVA irradiation for 4 h, irradiated solutions containing lac-color became slightly mutagenic toward S.typhimurium TA98 without metabolic activation. A decrease in cell survival resulted when WTK-1 cells were subjected to UVA irradiation for 60 min in the presence of purpurin at 1 mg\/ml. Delayed cytotoxicity was also observed following 24 h incubation in fresh medium of samples that were subjected to UVA irradiation for 60 min in the presence of colorant (carthamus yellow, grape-skin color, gardenia blue, cochineal-color, monascus red or purpurin).","subset":"pubmed_abstract"} +{"meta":{"pmid":9048755,"dup_signals":{"dup_doc_count":24,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":1,"2023-06":2,"2022-49":1,"2022-40":1,"2022-33":1,"2022-27":4,"2022-05":1,"2024-30":2,"2024-26":1,"2024-18":3,"2024-10":2}}},"text":"Differential regulation by methylenedioxymethamphetamine of 5-hydroxytryptamine1A receptor density and mRNA expression in rat hippocampus, frontal cortex, and brainstem: the role of corticosteroids.\nThe present study examined the effects of repeated administration to rats of 3,4-methylenedioxymethamphetamine (MDMA, \"Ecstasy\") on 5-hydroxytryptamine1A (5-HT1A) receptor density and mRNA expression in the hippocampus, frontal cortex, and brainstem. As expected, 7 days after subacute MDMA administration (20 mg\/kg i.p. twice daily for 4 consecutive days) 5-HT content was markedly reduced (-70%) in the hippocampus and the frontal cortex. 5-HT1A receptor density was increased in the frontal cortex by 23% and decreased in the hippocampus and the brainstem by 25%. These changes correlated with an enhanced or diminished 5-HT1A receptor mRNA expression in the three regions studied. To examine the influence of corticosteroids on these changes, adrenalectomized (ADX) rats received the same dosage regimen as above. Adrenalectomy by itself did not modify 5-HT content in the brain regions examined and increased 5-HT1A receptor density in the hippocampus (+20%) but produced no change in the frontal cortex and brainstem. Adrenalectomy also prevented MDMA-induced changes in receptor number in the hippocampus and brainstem but not in the frontal cortex. Dexamethasone (1 mg\/kg\/day i.p.) administered for 7 consecutive days reversed the effects of adrenalectomy in the hippocampus but not in the frontal cortex. In the brainstem, MDMA no longer reduced 5-HT1A receptor number in ADX rats, but a significant reduction was restored when ADX animals received the glucocorticoid treatment. The present data show that MDMA may affect 5-HT1A receptors in a regionally dependent manner, notably through a drug effect on corticosterone release, which attenuates 5-HT1A receptor gene transcription selectively in the hippocampus.","subset":"pubmed_abstract"} +{"meta":{"pmid":22521004,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"[Intra-gastric ballon in the treatment of morbid obesity].\nIntragastric balloon is a temporary treatment for weight loss with proven safety and efficacy when associated with lifestyle intervention. It is indicated in the super--obese who are candidates for bariatric surgery to lose weight and to reduce their high surgical risk. Our aim was to retrospectively evaluate the results of the patients in whom this device was inserted during a three-year period from the beginning of this practice in the Hospital de Santa Maria. Data from the medical records in what concerns bioanthropometric characteristics in the beginning and following balloon removal were reviewed and submitted to descriptive analysis. Fifty-seven patients underwent intragastric balloon placement, of whom 46 female and 11 male, with median age 44,2 \u00b1 11,77 years. Median body mass index (BMI) 51,6 \u00b1 9,45 kg\/m(2). Five patients were lost to follow-up. The balloon was inserted for a median time of 206 \u00b1 62,62 days, during which there was a median weight loss of 17,2 \u00b1 9,46 kg, a reduction of 6,7 \u00b1 3,73 kg\/m(2) in BMI and a mean excessive weight loss of 26,7 \u00b1 16,99%. There were 5 patients in whom serious complications occurred, one of which died. One half of the patients went on to bariatric surgery. The median time between balloon removal and surgery was 241,6 \u00b1 243,66 days in which there was a median weight variation of + 3,5 \u00b1 11,69 kg. The remaining patients: 15 dropped out further treatment, 5 patients are under medical therapy and have no invasive procedure scheduled, 4 patients are to be submitted to another balloon insertion and 2 patients were submitted to the insertion of a second balloon during the time this article refers to. Our findings are similar to some previously described. Intragastric balloon is a temporary and efficacious option in the treatment of morbid obesity. However, it is very important to strictly select the patients and to have a good coordination with the Surgical department so that results can be optimized.","subset":"pubmed_abstract"} +{"meta":{"pmid":9527835,"dup_signals":{"dup_doc_count":18,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-27":1,"2022-21":3,"2021-39":1,"2020-34":1,"2020-24":1,"2019-30":1,"2019-22":1,"2019-13":1,"2022-33":1,"2024-30":3}}},"text":"Neural processing in the subsecond time range in the temporal cortex.\nThe hypothesis that cortical processing of the millisecond time range is performed by latency competition between the first spikes produced by neuronal populations is analyzed. First, theorems that describe how the mechanism of latency competition works in a model cortex are presented. The model is a sequence of cortical areas, each of which is an array of neuronal populations that laterally inhibit each other. Model neurons are integrate-and-fire neurons. Second, the model is applied to the ventral pathway of the temporal lobe, and neuronal activity of the superior temporal sulcus of the monkey is reproduced with the model pathway. It consists of seven areas: V1, V2\/V3, V4, PIT, CIT, AIT, and STPa. Neural activity predicted with the model is compared with empirical data. There are four main results: (1) Neural responses of the area STPa of the model showed the same fast discrimination between stimuli that the corresponding responses of the monkey did: both were significant within 5 ms of the response onset. (2) The hypothesis requires that the response latency of cortical neurons should be shorter for stronger responses. This requirement was verified by both the model simulation and the empirical data. (3) The model reproduced fast discrimination even when spontaneous random firing of 9 Hz was introduced to all the cells. This suggests that the latency competition performed by neuronal populations is robust. (4) After the first few competitions, the mechanism of latency competition always detected the strongest of input activations with different latencies.","subset":"pubmed_abstract"} +{"meta":{"pmid":8968385,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":13}}},"text":"Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: effect of 5-fluorouracil.\nPrevious studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-1) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but also in the cytosolic cellular compartment, as indicated by the results of Western blot analysis. Northern blot analysis of total RNA extracted from 5-FU-treated HT-29 or C22.20 cells shows an increase in the steady-state levels of CEA and CEA-related transcripts (e.g., biliary glycoprotein). Moreover 5-FU-mediated augmentation of the CEA transcript appears to be attributable mainly to enhanced transcription rather than to increased mRNA stability. It is concluded that induction of enhanced CEA protein expression in cancer cells treated with 5-FU could be of clinical interest for the development of immunochemotherapeutic protocols based on CEA protein as the target molecule.","subset":"pubmed_abstract"} +{"meta":{"pmid":17638044,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2020-29":1,"2020-16":1,"2023-40":1,"2024-18":1,"2024-30":1}}},"text":"Posttreatment tree mortality after forest ecological restoration, Arizona, United States.\nPine-oak forests are of high ecological importance worldwide, but many are threatened by uncharacteristically severe wildfire. Forest restoration treatments, including the reintroduction of a surface fire regime, are intended to decrease fire hazard and emulate historic ecosystem structure and function. Restoration has recently received much management attention and short-term study, but little is known about longer-term ecosystem responses. We remeasured a replicated experimental restoration site in the southwestern United States 5 years after treatments. Basal area, tree density, and canopy cover decreased in the treated units at a faster rate than in controls. Delayed mortality, not evident right after treatment, decreased density modestly (13% in treated units and 10% in controls) but disproportionately affected large trees (\"large\" ponderosa pines were those with diameter at breast height [dbh] > or =37.5 cm; other species dbh > or =20 cm). In treated units, 10.9 large trees ha(-1) died, whereas 6.2 trees ha(-1) died in control units. Compared with reference conditions, the experimental blocks remained higher in pine density and, in three of the four blocks, in basal area. Pine trees grew significantly faster in treated units than in controls, enough to reach the reference level of basal area in 6 years. Although mortality of large trees is a concern, the treated units have vigorous growth and low density, indicating that they will be relatively resistant to future drought and fire events. Similar treatments may be beneficial in many areas of the United States and in related pine-oak ecosystems elsewhere.","subset":"pubmed_abstract"} +{"meta":{"pmid":16838605,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"[Usefulness of bcl-2 expression as a new basal cell marker in prostatic pathology].\nThe diagnosis of invasive adenocarcinoma of the prostate is often difficult in needle prostatic cores, where, additionally, the assessment of the presence of basal cells has demonstrated to be of paramount importance. Currently, the immunohistochemical expression of 34betaE12 antigen and p63 protein are the most utilized markers. In our study, we analyzed comparatively the expression of 34betaE12, p63, bcl-2 and alpha-methylacyl-CoA racemase in order to evaluate the usefulness of bcl-2 as a new marker of the basal cells in prostatic pathology. This study comprises radical prostatectomy specimens from 48 patients which were studied in order to determine the lack of staining of basal cells in invasive tumor areas together with the expression of racemase. Likewise, the presence of basal cells in areas of atrophy, hyperplasia, adenosis, and high-grade prostatic intraepithelial neoplasia (PIN) was also examined. Within the areas of adenosis and PIN a discontinuous pattern of basal cell expression was found in some cases. In 2 out of 48 cases (4,2%) of invasive carcinoma a weak bcl-2 expression without a basal cell distribution was found. Moreover, the expression of bcl-2 in the stromal lymphocytes appeared to be essential as an internal positive control of the technique. In addition to classical markers, we demonstrated the diagnostic value of bcl-2 as a new basal cell marker.","subset":"pubmed_abstract"} +{"meta":{"pmid":23447369,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":18}}},"text":"A quantitative approach for understanding small-scale human mesenchymal stem cell culture - implications for large-scale bioprocess development.\nHuman mesenchymal stem cell (hMSC) therapies have the potential to revolutionise the healthcare industry and replicate the success of the therapeutic protein industry; however, for this to be achieved there is a need to apply key bioprocessing engineering principles and adopt a quantitative approach for large-scale reproducible hMSC bioprocess development. Here we provide a quantitative analysis of the changes in concentration of glucose, lactate and ammonium with time during hMSC monolayer culture over 4 passages, under 100% and 20% dissolved oxgen (dO2 ), where either a 100%, 50% or 0% growth medium exchange was performed after 72h in culture. Yield coefficients, specific growth rates (h(-1) ) and doubling times (h) were calculated for all cases. The 100% dO2 flasks outperformed the 20% dO2 flasks with respect to cumulative cell number, with the latter consuming more glucose and producing more lactate and ammonium. Furthermore, the 100% and 50% medium exchange conditions resulted in similar cumulative cell numbers, whilst the 0% conditions were significantly lower. Cell immunophenotype and multipotency were not affected by the experimental culture conditions. This study demonstrates the importance of determining optimal culture conditions for hMSC expansion and highlights a potential cost savings from only making a 50% medium exchange, which may prove significant for large-scale bioprocessing.","subset":"pubmed_abstract"} +{"meta":{"pmid":22726308,"dup_signals":{"dup_doc_count":21,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-06":1,"2014-10":1,"2013-48":4,"2013-20":2,"2015-11":1,"unknown":11}}},"text":"Comparison of communication skills between medical students admitted after interviews or on academic merits.\nSelection of the best medical students among applicants is debated and many different methods are used. Academic merits predict good academic performance, but students admitted by other pathways need not be less successful. The aim of this study, was to compare communication skills between students admitted to medical school through interviews or on academic merits, respectively. A retrospective cohort study. Communication skills at a surgical OSCE in 2008 were assessed independently by two observers using an evaluative rating scale. Correlations, t-tests and multivariate analyses by logistic regressions were employed. Academic merits were defined as upper secondary school grade point average (GPA) or scores from the Swedish Scholastic Assessment Test (SweSAT). The risk of showing unsatisfactory communicative performance was significantly lower among the students selected by interviews (OR 0.32, CI95 0.12-0.83), compared to those selected on the basis of academic merits. However, there was no significant difference in communication skills scores between the different admission groups; neither did the proportion of high performers differ. No difference in the result of the written examination was seen between groups. Our results confirm previous experience from many medical schools that students selected in different ways achieve comparable results during the clinical semesters. However, selection through interview seems to reduce the number of students who demonstrate inferior communication skills at 4th year of medical school.","subset":"pubmed_abstract"} +{"meta":{"pmid":29038726,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Knowledge, attitudes and practices toward prevention of hepatitis B virus infection among medical students at Northern Border University, Arar, Kingdom of Saudi Arabia.\nHealth care workers' risk of occupational exposure to HBV is a chief concern, particularly with young students in the health profession. This study was carried out to assess the knowledge regarding symptoms, risk factors and prevention of hepatitis B virus infection among medical students. A cross-sectional study was carried out from November 01, 2016 to May 30, 2017 on medical students at the Northern Border University (Arar, Kingdom of Saudi Arabia). Data were collected from 200 students from all academic years using pre-designed questionnaire which included questions designed to fulfill the study objectives. Regarding students' knowledge about hepatitis B infection, 81% of them knew that carriers could transmit infection, 89.5% of them knew that it could not be spread by casual contact, 80% by contact with open wound, 96.5% by contaminated blood and body fluids, 92.5% by unsterilized syringe, needle and surgical instruments and 79.5% by unsafe sex. In total, 86.5% of students knew that a vaccine could prevent HBV infection, 95% knew it had been laboratory tested, 64% knew HBV had post exposure prophylaxis and only 55% knew that it could be cured. In all, 75.5% of students knew that HBV caused liver cancer. Regarding attitude, 23% of students said they had no concern of being infected with HBV, 86.5% agreed that HBV vaccine was safe and effective and 90% believed that following infection, control guidelines would protect them from being infected by HBV at work. Regarding practice, only 56.5% of students had screened for HBV infection 22% had had a needle prick injury but 68% would report that injury. Furthermore, 69.5% have received HBV vaccine but only 38% of them had received 3 doses. The students' knowledge of the hepatitis B virus was found to be good. We recommend improving knowledge, attitude and practice of the public as well as students, through health education campaigns and settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":14663336,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-26":1,"unknown":10}}},"text":"Activation systems for latent matrix metalloproteinase-2 are upregulated immediately after focal cerebral ischemia.\nDuring focal cerebral ischemia, matrix metalloproteinase-2 (MMP-2) can contribute to the loss of microvessel integrity within ischemic regions by degrading the basal lamina. MMP-2 is secreted in latent form (pro-MMP-2), but the activation of pro-MMP-2 in the ischemic territory has not been shown. Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP-2, MT1-MMP and MT3-MMP, and the indirect activation system tissue plasminogen activator, urokinase (u-PA), its receptor (u-PAR), and its inhibitor PAI-1 after middle cerebral artery occlusion\/reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons. The expressions of all three MMPs, u-PA, u-PAR, and PA1-1, but not tissue plasminogen activator, were increased from 1 hour after middle cerebral artery occlusion in the ischemic core. mRNA transcripts confirmed the increases in latent MMP-2, u-PA, u-PAR, and PAI-1 antigen very early after middle cerebral artery occlusion. The expression patterns are consistent with secretion of pro-MMP-2 and its activators in the ischemic core, perhaps from separate cell compartments. The rapid and coordinate appearance of pro-MMP-2 and its activation apparatus suggest that in the primate striatum this protease may participate in matrix injury during focal cerebral ischemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":22950647,"dup_signals":{"dup_doc_count":20,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-18":1,"2015-06":1,"2013-48":1,"2024-10":1,"unknown":15}}},"text":"Segmental dataset and whole body expression data do not support the hypothesis that non-random movement is an intrinsic property of Drosophila retrogenes.\nSeveral studies in Drosophila have shown excessive movement of retrogenes from the X chromosome to autosomes, and that these genes are frequently expressed in the testis. This phenomenon has led to several hypotheses invoking natural selection as the process driving male-biased genes to the autosomes. Metta and Schl\u00f6tterer (BMC Evol Biol 2010, 10:114) analyzed a set of retrogenes where the parental gene has been subsequently lost. They assumed that this class of retrogenes replaced the ancestral functions of the parental gene, and reported that these retrogenes, although mostly originating from movement out of the X chromosome, showed female-biased or unbiased expression. These observations led the authors to suggest that selective forces (such as meiotic sex chromosome inactivation and sexual antagonism) were not responsible for the observed pattern of retrogene movement out of the X chromosome. We reanalyzed the dataset published by Metta and Schl\u00f6tterer and found several issues that led us to a different conclusion. In particular, Metta and Schl\u00f6tterer used a dataset combined with expression data in which significant sex-biased expression is not detectable. First, the authors used a segmental dataset where the genes selected for analysis were less testis-biased in expression than those that were excluded from the study. Second, sex-biased expression was defined by comparing male and female whole-body data and not the expression of these genes in gonadal tissues. This approach significantly reduces the probability of detecting sex-biased expressed genes, which explains why the vast majority of the genes analyzed (parental and retrogenes) were equally expressed in both males and females. Third, the female-biased expression observed by Metta and Schl\u00f6tterer is mostly found for parental genes located on the X chromosome, which is known to be enriched with genes with female-biased expression. Fourth, using additional gonad expression data, we found that autosomal genes analyzed by Metta and Schl\u00f6tterer are less up regulated in ovaries and have higher chance to be expressed in meiotic cells of spermatogenesis when compared to X-linked genes. The criteria used to select retrogenes and the sex-biased expression data based on whole adult flies generated a segmental dataset of female-biased and unbiased expressed genes that was unable to detect the higher propensity of autosomal retrogenes to be expressed in males. Thus, there is no support for the authors' view that the movement of new retrogenes, which originated from X-linked parental genes, was not driven by selection. Therefore, selection-based genetic models remain the most parsimonious explanations for the observed chromosomal distribution of retrogenes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27522177,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-49":1,"2018-13":1,"2018-05":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2022-49":1,"2017-13":1,"2024-18":1}}},"text":"The protective rate of the feline immunodeficiency virus vaccine: An Australian field study.\nA case-control field study was undertaken to determine the level of protection conferred to client-owned cats in Australia against feline immunodeficiency virus (FIV) using a commercial vaccine. 440 cats with outdoor access from five Australian states\/territories underwent testing, comprising 139 potential cases (complete course of primary FIV vaccinations and annual boosters for three or more years), and 301 potential controls (age, sex and postcode matched FIV-unvaccinated cats). FIV status was determined using a combination of antibody testing (using point-of-care test kits) and nucleic acid amplification, as well as virus isolation in cases where results were discordant and in all suspected FIV-vaccinated\/FIV-infected cats ('vaccine breakthroughs'). Stringent inclusion criteria were applied to both 'cases' and 'controls'; 89 FIV-vaccinated cats and 212 FIV-unvaccinated cats ultimately satisfied the inclusion criteria. Five vaccine breakthroughs (5\/89; 6%), and 25 FIV-infected controls (25\/212; 12%) were identified, giving a vaccine protective rate of 56% (95% CI -20 to 84). The difference in FIV prevalence rates between the two groups was not significant (P=0.14). Findings from this study raise doubt concerning the efficacy of Fel-O-Vax FIV\u00ae under field conditions. Screening for FIV infection may be prudent before annual FIV re-vaccination and for sick FIV-vaccinated cats. Owners should not rely on vaccination alone to protect cats against the risk of acquiring FIV infection; other measures such as cat curfews, the use of 'modular pet parks' or keeping cats exclusively indoors, are recommended.","subset":"pubmed_abstract"} +{"meta":{"pmid":17327407,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":13}}},"text":"Dynamic regulation of Gata factor levels is more important than their identity.\nThree Gata transcription factors (Gata1, -2, and -3) are essential for hematopoiesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythroid cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gata1, -2, and -3 transgenes driven by beta-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements.","subset":"pubmed_abstract"} +{"meta":{"pmid":33439330,"dup_signals":{"dup_doc_count":14}},"text":"I fear COVID but diabetic foot (DF) is worse: a survey on patients' perception of a telemedicine service for DF during lockdown.\nTo evaluate the patients' perceptions of telemedicine visits during COVID-19 lockdown and their level of anxiety about COVID and diabetic foot (DF). In May 2020, we contacted by phone all the patients who underwent in March and April to remote monitoring visits for DF during the lockdown for COVID-19, with a structured interview, focusing on their perceptions about telemedicine service for DF and on the anxiety toward COVID and DF. We analyzed 257 remote monitoring visits in 211 patients. Two hundred and six patients answered the follow-up interview; 177 patients (85.9%) remembered the monitoring visit, 140 (67.9%) the health care professional and 181 patients (87.9%) the reason of contact; 169 patients were alone during the visit, 37 with a relative. Patients judged useful both the monitoring during pandemic (4.35 \u00b1 0.28 on a maximum of five) and the possibility to continue after the lockdown (4.34 \u00b1 0.23 on a maximum of five). Eventually, we observed that DF patients were more worried by DF than by COVID on a scale from 0 (not fear at all) to 5 (terrified) (4.79 \u00b1 0.05 vs. 3.27 \u00b1 1.03, p < 0.05). This difference was higher in previously ulcerated patients (4.84 \u00b1 0.03 vs. 3.03 \u00b1 1.13, p < 0.05) and even more in amputees (4.93 \u00b1 0.03 vs. 2.73 \u00b1 1.21, p < 0.05). DF patients appreciated televisits during lockdown and the continuation of this service after its end. In this context DF prevails on COVID in the worries of patients, especially if they are recurrent ones.","subset":"pubmed_abstract"} +{"meta":{"pmid":11349192,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"The relationship of pregnancy to the use of highly active antiretroviral therapy.\nPublic health agencies have recommended that the criteria for the use of highly active antiretroviral therapy should not be modified because of pregnancy. However, little information has been published with regard to the degree to which these recommendations are being followed. We report here the frequency of highly active antiretroviral therapy use among pregnant women in the Women's Interagency HIV Study and compare the frequencies of its use by pregnant women meeting published criteria for implementing highly active antiretroviral therapy and its use by nonpregnant women meeting the same criteria. From October 1994 through November 1995, a total of 2059 human immunodeficiency virus type 1-seropositive women were enrolled in a cohort study. Participants were evaluated at baseline and at 6-month intervals with standardized interview instruments. In addition to a general physical examination at each visit, patients had a urine pregnancy test performed and were asked about current pregnancies, pregnancies since the last visit, and which antiretroviral medications they had used since the last visit. Highly active antiretroviral therapy was defined according to 1997 National Institutes of Health guidelines. At each calendar interval after October 1996, a greater proportion of nonpregnant women than pregnant women reported the use of highly active antiretroviral therapy. The use of monotherapy declined for both groups during the course of multiple calendar periods (P <.01), although the use of monotherapy remained higher among the pregnant women. In any given calendar period, pregnant women meeting published criteria for highly active antiretroviral therapy use were slightly less likely than similar nonpregnant women to receive highly active antiretroviral therapy (odds ratio, 0.28-0.98). Because of the sample size these differences reached significance in only one calendar period (P =.02). With time pregnant women did demonstrate an increase in the percentage receiving highly active antiretroviral therapy. In nearly all calendar periods a larger percentage of pregnant than nonpregnant women were receiving a regimen that included zidovudine. Highly active antiretroviral therapy is being received by an increasing percentage of women who meet published criteria for its use, and pregnancy is a relatively small impediment to its use. Further efforts are needed to bolster the use of highly active antiretroviral therapy by all appropriate candidates and to ensure equal access to this therapy for pregnant women. Because of the increasingly frequent use of highly active antiretroviral therapy during pregnancy, ongoing efforts are needed to monitor any long-term effects of in utero exposure to multiple antiretroviral agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":28831072,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-22":1,"unknown":17}}},"text":"Working memory accuracy for multiple targets is driven by reward expectation and stimulus contrast with different time-courses.\nThe richness of sensory input dictates that the brain must prioritize and select information for further processing and storage in working memory. Stimulus salience and reward expectations influence this prioritization but their relative contributions and underlying mechanisms are poorly understood. Here we investigate how the quality of working memory for multiple stimuli is determined by priority during encoding and later memory phases. Selective attention could, for instance, act as the primary gating mechanism when stimuli are still visible. Alternatively, observers might still be able to shift priorities across memories during maintenance or retrieval. To distinguish between these possibilities, we investigated how and when reward cues determine working memory accuracy and found that they were only effective during memory encoding. Previously learned, but currently non-predictive, color-reward associations had a similar influence, which gradually weakened without reinforcement. Finally, we show that bottom-up salience, manipulated through varying stimulus contrast, influences memory accuracy during encoding with a fundamentally different time-course than top-down reward cues. While reward-based effects required long stimulus presentation, the influence of contrast was strongest with brief presentations. Our results demonstrate how memory resources are distributed over memory targets and implicates selective attention as a main gating mechanism between sensory and memory systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":10408262,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":12}}},"text":"Attempted suicide and major public holidays in Europe: findings from the WHO\/EURO Multicentre Study on Parasuicide.\nThe aim of the study was to examine the relationship between suicide attempts and major public holidays in Europe. The analysis was based on data on 24 388 suicide attempts by persons aged 15 years or older in the period 1989-1996. Data from 13 centres (representing 11 countries) participating in the WHO\/EURO Multicentre Study on Parasuicide were analysed. The analysis of the fluctuation of suicide attempts around public holidays was based on the daily number of suicide attempts for each centre. For each day in the period under examination a mean number of suicide attempts (mu) was calculated. The analysis was based on the assumption that the data followed a Poisson distribution. The observed number of daily suicide attempts was compared with the expected number of attempts. A multiplicative model for the expected number in each centre was developed. Before Christmas there were fewer suicide attempts than expected, and after Christmas there were approximately 40% more attempts than expected. In addition, more attempts than expected were registered on New Year's Day. In countries where people have the day off work on Whit Monday there were significantly fewer attempts during the 3 days before, but where Whit Monday is a normal working day significantly fewer attempts occurred on the Monday to Wednesday after Whit Sunday. There appears to be a transposition of a significant number of suicide attempts from before (and during) a major public holiday until after it. The division of holidays into non-working and working days showed that a 'holiday effect' could only be found around major public holidays, particularly Christmas, Easter and Whitsun. These findings support the theory of the 'broken-promise effect' for major public holidays.","subset":"pubmed_abstract"} +{"meta":{"pmid":28082514,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":11}}},"text":"Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.\nDrug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M2-receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side effect is one of the main reasons that limit clinical application of muscarinic agonists. Herein we show that dualsteric (orthosteric\/allosteric) agonists induce less cardiac depression ex vivo and in vivo than conventional full agonists. Exploration of the underlying mechanism in living cells employing cellular dynamic mass redistribution identified context-sensitive agonism of these dualsteric agonists. They translate elevation of intracellular cAMP into a switch from full to partial agonism. Designed context-sensitive agonism opens an avenue toward postreceptor pharmacologic selectivity, which even works in target tissues operated by the same subtype of pharmacologic receptor.","subset":"pubmed_abstract"} +{"meta":{"pmid":23312015,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"FRET and FRAP imaging: approaches to characterise tau and stathmin interactions with microtubules in cells.\nMicrotubules (MTs) are involved in many crucial processes such as cell morphogenesis, mitosis and motility. These dynamic structures resulting from the complex assembly of tubulin are tightly regulated by stabilising MT-associated proteins (MAPs) such as tau and destabilising proteins, notably stathmin. Because of their key role, these MAPs and their interactions have been extensively studied using biochemical and biophysical approaches, particularly in vitro. Nevertheless, numerous questions remain unanswered and the mechanisms of interaction between MT and these proteins are still unclear in cells. Techniques coupling cell imaging and fluorescence methods, such as F\u00f6rster resonance energy transfer and fluorescence recovery after photobleaching, are excellent tools to study these interactions in situ. After describing these methods, we will present emblematic data from the literature and unpublished experimental results from our laboratory concerning the interactions between MTs, tau and stathmin in cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":28982751,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":6}}},"text":"Clinical Significance of Histologic Variants of Bladder Cancer.\nPathologists have identified many \"histologic variants\" of bladder cancer (BCA): histologic patterns that differ from conventional urothelial carcinoma (transitional cell carcinoma). Several of these are biologically aggressive, and their identification may aid in clinical decision-making. This article reviews several histologic variants and their value in deciding management of cT1 disease and predicting response to neoadjuvant chemotherapy (NAC). Diagnostic issues are also addressed, such as interobserver variability among pathologists. For example, although stage cT1 conventional urothelial carcinoma is usually managed conservatively, cT1 micropapillary carcinoma has high mortality following conservative management, and early cystectomy may reduce mortality. Similarly, plasmacytoid and small cell cancers are remarkably aggressive, and those diagnosed as stage cT1 at transurethral resection are likely understaged; conservative management thus greatly risks undertreatment. As an example of response, NAC dramatically reduces mortality in patients with small cell BCA, and is thus the standard of care, even in stage cT1 disease. Although identification of histologic variants may inform on optimal management, diagnostic issues challenge their incorporation into clinical practice. For example, interobserver reproducibility is only moderate for the diagnosis of micropapillary BCA. Studies have identified specific histologic issues underlying this diagnostic irreproducibility, and ongoing work aims to remedy this issue. In summary, histologic variants are emerging as potentially useful biomarkers in the management of BCA. Although issues remain unresolved, pathologists and treating physicians will benefit from understanding these variants and their prognostic and therapeutic implications.","subset":"pubmed_abstract"} +{"meta":{"pmid":31251903,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Specific inhibition of DPY30 activity by ASH2L-derived peptides suppresses blood cancer cell growth.\nDPY30 facilitates H3K4 methylation by directly binding to ASH2L in the SET1\/MLL complexes and plays an important role in hematologic malignancies. However, the domain on DPY30 that regulates cancer growth is not evident, and the potential of pharmacologically targeting this chromatin modulator to inhibit cancer has not been explored. Here we have developed a peptide-based strategy to specifically target DPY30 activity. We have designed cell-penetrating peptides derived from ASH2L that can either bind to DPY30 or show defective or enhanced binding to DPY30. The DPY30-binding peptides specifically inhibit DPY30's activity in interacting with ASH2L and enhancing H3K4 methylation. Treatment with the DPY30-binding peptides significantly inhibited the growth of MLL-rearranged leukemia and other MYC-dependent hematologic cancer cells. We also revealed subsets of genes that may mediate the effect of the peptides on cancer cell growth, and showed that the DPY30-binding peptide sensitized leukemia to other types of epigenetic inhibitors. These results strongly support a critical role of the ASH2L-binding groove of DPY30 in promoting blood cancers, and demonstrate a proof-of-principle for the feasibility of pharmacologically targeting the ASH2L-binding groove of DPY30 for potential cancer inhibition.","subset":"pubmed_abstract"} +{"meta":{"pmid":31054630,"dup_signals":{"dup_doc_count":38,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":3,"2023-23":2,"2023-14":1,"2023-06":2,"2022-49":1,"2022-40":2,"2022-27":2,"2022-21":3,"2021-49":1,"2021-43":2,"2021-31":3,"2021-17":3,"2024-30":2,"2024-26":1,"2024-22":1,"2024-18":2,"2024-10":1}}},"text":"Other Potential CKD Hotspots in the World: The Cases of Mexico and the United States.\nHotspots of chronic kidney disease of unknown etiology (CKDu) have been identified throughout the globe, of which the Mesoamerican nephropathy in Central America is the most conspicuous example. It affects mainly agricultural workers, heat exposure during extenuating shifts leading to sudden dehydration and subsequent acute kidney injury (AKI) episodes is the main hypothesis, with other factors such as environmental and social determinants playing an underlying role. Recent reports have suggested that Mexico and the United States may have newly identified CKDu hotspots. Studies from Tierra Blanca, a rural region in Mexico, have shown that the prevalence of probable CKD is high (25%) among the population, of which almost half of the identified cases had no known risk factor (such as diabetes or hypertension). Studies in Hispanic agricultural workers from California and Florida have shown that heat stress and dehydration is frequent and is correlated with AKI episodes after a work shift (33% of workers in one shift). Because recurrent AKI is an established risk factor for CKD, these studies strengthen the evidence that suggests an association between this occupational exposure and CKD. Whether the etiology responsible for the entities described is the same as in other CKDu hotspots in the world remains unknown. The development of preventative and intervention strategies is the most urgent priority to address this issue.","subset":"pubmed_abstract"} +{"meta":{"pmid":24817864,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Bacteriophages of leuconostoc, oenococcus, and weissella.\nLeuconostoc (Ln.), Weissella, and Oenococcus form a group of related genera of lactic acid bacteria, which once all shared the name Leuconostoc. They are associated with plants, fermented vegetable products, raw milk, dairy products, meat, and fish. Most of industrially relevant Leuconostoc strains can be classified as either Ln. mesenteroides or Ln. pseudomesenteroides. They are important flavor producers in dairy fermentations and they initiate nearly all vegetable fermentations. Therefore, bacteriophages attacking Leuconostoc strains may negatively influence the production process. Bacteriophages attacking Leuconostoc strains were first reported in 1946. Since then, the majority of described Leuconostoc phages was isolated from either dairy products or fermented vegetable products. Both lytic and temperate phages of Leuconostoc were reported. Most of Leuconostoc phages examined using electron microscopy belong to the Siphoviridae family and differ in morphological details. Hybridization and comparative genomic studies of Leuconostoc phages suggest that they can be divided into several groups, however overall diversity of Leuconostoc phages is much lower as compared to, e.g., lactococcal phages. Several fully sequenced genomes of Leuconostoc phages have been deposited in public databases. Lytic phages of Leuconostoc can be divided into two host species-specific groups with similarly organized genomes that shared very low nucleotide similarity. Phages of dairy Leuconostoc have rather limited host-ranges. The receptor binding proteins of two lytic Ln. pseudomesenteroides phages have been identified. Molecular tools for detection of dairy Leuconostoc phages have been developed. The rather limited data on phages of Oenococcus and Weissella show that (i) lysogeny seems to be abundant in Oenococcus strains, and (ii) several phages infecting Weissella cibaria are also able to productively infect strains of other Weissella species and even strains of the genus Lactobacillus.","subset":"pubmed_abstract"} +{"meta":{"pmid":26511928,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"CRISPR\/Cas9-mediated mutagenesis in the sea lamprey Petromyzon marinus: a powerful tool for understanding ancestral gene functions in vertebrates.\nLamprey is one of only two living jawless vertebrates, a group that includes the first vertebrates. Comparisons between lamprey and jawed vertebrates have yielded important insights into the origin and evolution of vertebrate physiology, morphology and development. Despite its key phylogenetic position, studies of lamprey have been limited by their complex life history, which makes traditional genetic approaches impossible. The CRISPR\/Cas9 system is a bacterial defense mechanism that was recently adapted to achieve high-efficiency targeted mutagenesis in eukaryotes. Here we report CRISPR\/Cas9-mediated disruption of the genes Tyrosinase and FGF8\/17\/18 in the sea lamprey Petromyzon marinus, and detail optimized parameters for producing mutant F0 embryos. Using phenotype and genotype analyses, we show that CRISPR\/Cas9 is highly effective in the sea lamprey, with a majority of injected embryos developing into complete or partial mutants. The ability to create large numbers of mutant embryos without inbred lines opens exciting new possibilities for studying development in lamprey and other non-traditional model organisms with life histories that prohibit the generation of mutant lines.","subset":"pubmed_abstract"} +{"meta":{"pmid":7915439,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Dynamic transcranial Doppler assessment of positional vertebrobasilar ischemia.\nA hemodynamic as opposed to an embolic origin of vertebrobasilar ischemia may be suspected when symptoms are brief and triggered by changes in the position of the head or neck. It may be difficult, and not without risk, to reproduce the symptoms and to prove the short-lived hemodynamic changes during angiography. If transcranial Doppler sonography (TCD) could detect these changes, it would be useful as a noninvasive screening method to select patients for further diagnostic evaluation. TCD monitoring of the P1 segments of both posterior cerebral arteries was performed during different head movements in 14 patients referred for evaluation of suspected hemodynamic vertebrobasilar ischemia and in 10 healthy control subjects with a two-channel, 2-MHz, computerized Doppler system. Patients' symptoms were correlated with the Doppler findings. Four patients with stereotypical symptoms had a severe drop in posterior cerebral artery blood flow velocities (BFVs) to 20% of baseline (mean; SD, 14.3; range, 0% to 48%) and subsequent reactive hyperemia with an increase in BFV to 149% (mean; SD, 20.6; range, 110% to 186%) dependent on head rotation to one side (group 1). Compared with the values found in group 2 patients and in control subjects, these drops were significant (P = .0001 for both). Symptoms together with BFV changes could be reproduced several times. Angiography confirmed severe vertebral artery obstruction during head rotation and the presence of anomalies in the posterior circulation. In 10 patients (group 2), symptoms were not short-lived, stereotyped, or clearly dependent on head movements and could not be reproduced during TCD testing. Their BFVs dropped to 88% (mean; SD, 9.0; range, 64% to 102%) of baseline values during maximal head rotation, to 86% (mean; SD, 10.3; range, 64% to 100%) during flexion, and to 88% (mean; SD, 6.7; range, 75% to 103%) during extension. In the 10 control subjects, BFVs dropped to 86% (mean; SD, 8.8; range, 61% to 98%) of baseline values during rotation, to 90% (mean; SD, 10.3; range, 74% to 107%) during flexion, and to 76% (mean; SD, 17.1; range, 54% to 104%) during extension. Monitoring posterior cerebral artery BFV during head movements is a simple, noninvasive method to document a hemodynamic etiology of symptoms in patients with suspected positional vertebrobasilar ischemia. The correlation of symptoms to the hemodynamic findings proved a useful screening method to identify those patients with true position-evoked hemodynamic insufficiency in the posterior circulation. These patients should be selected for angiographic evaluation to identify the source and site of arterial compression.","subset":"pubmed_abstract"} +{"meta":{"pmid":36525271,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"COVID-19 Pandemic Experiences and Symptoms of Pandemic-Associated Traumatic Stress Among Mothers in the US.\nThe primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown. To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms. This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022. The primary exposures were pandemic-associated changes in mothers' health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators. The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure. The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic\/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences-one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster. In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":16216855,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":15}}},"text":"Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy.\nTo determine the range of survival rates of patients with hypertrophic cardiomyopathy (HCM) by comparing and contrasting the natural history of a cohort of patients seen between 1988 and 2002 with that of other published series. 956 adult (> or = 16 years old) patients with HCM (572 men, mean (SD) age 42 (15) years, range 16-88) were evaluated by ECG, Holter, exercise testing, and echocardiography. Patient characteristics and survival data were compared with those in natural history studies from referral and non-referral centres published between 1960 and January 2003. The duration of follow up was 69 (45) months. 120 (12.6%) patients died or underwent cardiac transplantation. Sudden cardiac death (n = 48) was the most common mode of death. The annual rate of sudden death or implantable cardioverter-defibrillator discharge was 1.02 (95% confidence interval (CI) 0.76 to 1.26). Annual rates for heart failure death or transplantation and stroke related death were 0.55% (95% CI 0.37% to 0.78%) and 0.07% (95% CI 0.02% to 0.19%), respectively. When studies published within the last 10 years of the study period were compared with earlier reports, the size of individual study cohorts was larger (309 (240.6) v 136.5 (98.8), p = 0.058) and the proportion with severe functional limitation NYHA class III\/IV lower (12.4% v 24.8%, p < 0.0001), and fewer patients underwent septal myotomy-myectomy (5.2% v 18.7%, p < 0.0001). Published sudden death rates over the last 10 years were lower than previously published figures (median 1.0% (range 0.1-1.7) v 2.0% (0-3.5)). Published survival rates in HCM cohorts have improved progressively over the past 40 years. In the modern era the prevalence of disease related complications is similar in all reporting centres.","subset":"pubmed_abstract"} +{"meta":{"pmid":26346065,"dup_signals":{"dup_doc_count":24,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":21}}},"text":"Improvement in emotional eating associated with an enhanced body image in obese women: mediation by weight-management treatments' effects on self-efficacy to resist emotional cues to eating.\nTo assess effects of cognitive-behavioural weight-loss treatments on self-efficacy to control emotionally cued eating and whether those changes mediate relationships between body satisfaction and emotional eating. Emotional eating is common, especially in women with obesity. A better understanding of relationships of its psychosocial correlates might benefit behavioural weight-loss treatments. A field-based, quantitative study incorporated two theoretically derived weight-loss treatments using repeated measures analyses that employed validated surveys. Women with obesity volunteered for a community-based weight-loss study and were assigned to either a treatment of a manual plus phone support (n = 47), or in-person contacts emphasizing self-regulation (n = 48), over 6 months. Both emphasized physical activity, healthy eating and building self-efficacy for enabling the health-behaviour changes. Data were collected between 2013-2014. Multiple regression analyses assessed predictors of self-efficacy change. Mixed-model analysis of variances assessed treatment differences in psychosocial changes. Mediation analyses assessed mediation of the relationships between body satisfaction and emotional eating changes. Changes in Overall mood and Self-regulation significantly predicted change in Self-efficacy to control emotionally cued eating. Changes in Body satisfaction, Emotional eating, Mood, Self-regulating eating and Self-efficacy were significant overall, and each significantly greater in the in-person treatment. Self-efficacy significantly mediated the relationship between changes in Body satisfaction and Emotional eating total (and Emotional eating when depressed or anxious, but not when frustrated\/angry). Results clarified mediation of the dynamic relationship between body satisfaction and emotional eating, which might enable behavioural weight-loss treatments to better-address emotional eating.","subset":"pubmed_abstract"} +{"meta":{"pmid":16230383,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Gene expression profiling of human sarcomas: insights into sarcoma biology.\nSarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray. Remarkably, 2,766 probes differentially expressed across this sample set clearly delineated the various tumor classes. Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes. We also identified subgroups of tumors within the liposarcomas, leiomyosarcomas, and malignant fibrous histiocytomas. We found significant gene ontology correlates for each tumor group and identified similarity to normal tissues by Gene Set Enrichment Analysis. Mutation analysis done on 275 tumor samples revealed that the high expression of epidermal growth factor receptor (EGFR) in certain tumors was not associated with gene mutations. Finally, to further the investigation of human sarcoma biology, we have created an online, publicly available, searchable database housing the data from the gene expression profiles of these tumors (http:\/\/watson.nhgri.nih.gov\/sarcoma), allowing the user to interactively explore this data set in depth.","subset":"pubmed_abstract"} +{"meta":{"pmid":15537976,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":4,"2024-10":1,"unknown":8}}},"text":"Artifacts in CT: recognition and avoidance.\nArtifacts can seriously degrade the quality of computed tomographic (CT) images, sometimes to the point of making them diagnostically unusable. To optimize image quality, it is necessary to understand why artifacts occur and how they can be prevented or suppressed. CT artifacts originate from a range of sources. Physics-based artifacts result from the physical processes involved in the acquisition of CT data. Patient-based artifacts are caused by such factors as patient movement or the presence of metallic materials in or on the patient. Scanner-based artifacts result from imperfections in scanner function. Helical and multisection technique artifacts are produced by the image reconstruction process. Design features incorporated into modern CT scanners minimize some types of artifacts, and some can be partially corrected by the scanner software. However, in many instances, careful patient positioning and optimum selection of scanning parameters are the most important factors in avoiding CT artifacts.","subset":"pubmed_abstract"} +{"meta":{"pmid":26808452,"dup_signals":{"dup_doc_count":14,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":3,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"The potential of imogolite nanotubes as (co-)photocatalysts: a linear-scaling density functional theory study.\nWe report a linear-scaling density functional theory (DFT) study of the structure, wall-polarization absolute band-alignment and optical absorption of several, recently synthesized, open-ended imogolite (Imo) nanotubes (NTs), namely single-walled (SW) aluminosilicate (AlSi), SW aluminogermanate (AlGe), SW methylated aluminosilicate (AlSi-Me), and double-walled (DW) AlGe NTs. Simulations with three different semi-local and dispersion-corrected DFT-functionals reveal that the NT wall-polarization can be increased by nearly a factor of four going from SW-AlSi-Me to DW-AlGe. Absolute vacuum alignment of the NT electronic bands and comparison with those of rutile and anatase TiO2 suggest that the NTs may exhibit marked propensity to both photo-reduction and hole-scavenging. Characterization of the NTs' band-separation and optical properties reveal the occurrence of (near-)UV inside-outside charge-transfer excitations, which may be effective for electron-hole separation and enhanced photocatalytic activity. Finally, the effects of the NTs' wall-polarization on the absolute alignment of electron and hole acceptor states of interacting water (H2O) molecules are quantified and discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":10409711,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2016-44":1,"2015-18":1}}},"text":"Characterization of mouse dishevelled (Dvl) proteins in Wnt\/Wingless signaling pathway.\nThe dishevelled (dsh) gene family encodes cytoplasmic proteins that have been implicated in Wnt\/Wingless (Wg) signaling. To demonstrate functional conservation of Dsh family proteins, two mouse homologs of Drosophila Dsh, Dvl-1 and Dvl-2, were biochemically characterized in mouse and Drosophila cell culture systems. We found that treatment with a soluble Wnt-3A leads to hyperphosphorylation of Dvl proteins and a concomitant elevation of the cytoplasmic beta-catenin levels in mouse NIH3T3, L, and C57MG cells. This coincides well with our finding in a Drosophila wing disc cell line, clone-8, that Wg treatment induced hyperphosphorylation of Dsh (Yanagawa, S., van Leeuwen, F., Wodarz, A., Klingensmith, J., and Nusse, R. (1995) Genes Dev. 9, 1087-1097). Furthermore, we showed that mouse Dvl proteins affect downstream components of Drosophila Wg signaling as Dsh does; overexpression of Dvl proteins in clone-8 cells results in elevation of Armadillo (Drosophila homolog of beta-catenin) and Drosophila E-cadherin levels, hyperphosphorylation of Dvl proteins themselves, and inhibition of Zeste-White3 kinase-mediated phosphorylation of a microtubule-binding protein, Tau. In addition, casein kinase II was shown to coimmunoprecipitate with Dvl proteins, and Dvl proteins were phosphorylated in these immune complexes. These results are direct evidence that Dsh family proteins mediate a set of conserved biochemical processes in the Wnt\/Wg signaling pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":17559107,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Emergence of homochirality in far-from-equilibrium systems: mechanisms and role in prebiotic chemistry.\nSince the model proposed by Frank (Frank FC, Biochem Biophys Acta 1953;11:459-463), several alternative models have been developed to explain how an asymmetric non-racemic steady state can be reached by a chirally symmetric chemical reactive system. This paper explains how a stable non-racemic regime can be obtained as a symmetry breaking occurring in a far-from-equilibrium reactive system initiated with an initial imbalance. Departing from the variations around the original Frank's model that are commonly described in the literature, i.e. open-flow systems of direct autocatalytic reactions, we discuss recent developments emphasizing both an active recycling of components and an autocatalytic network of simple reactions. We will present our APED model as the most natural realization of such thermodynamic openness and non-equilibrium, of recycling and of network autocatalysis, each of these in prebiotic conditions. The different experimental and theoretical models in the literature will be classified according to mechanism. The place and role of such self-structured networks responsible for the presence of homochirality in the primitive Earth will be detailed.","subset":"pubmed_abstract"} +{"meta":{"pmid":30975987,"dup_signals":{"dup_doc_count":28}},"text":"Quantifying economic resilience from input-output susceptibility to improve predictions of economic growth and recovery.\nModern macroeconomic theories were unable to foresee the last Great Recession and could neither predict its prolonged duration nor the recovery rate. They are based on supply-demand equilibria that do not exist during recessionary shocks. Here we focus on resilience as a nonequilibrium property of networked production systems and develop a linear response theory for input-output economics. By calibrating the framework to data from 56 industrial sectors in 43 countries between 2000 and 2014, we find that the susceptibility of individual industrial sectors to economic shocks varies greatly across countries, sectors, and time. We show that susceptibility-based growth predictions that take sector- and country-specific recovery into account, outperform-by far-standard econometric models. Our results are analytically rigorous, empirically testable, and flexible enough to address policy-relevant scenarios. We illustrate the latter by estimating the impact of recently imposed tariffs on US imports (steel and aluminum) on specific sectors across European countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":34784769,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Testosterone amplifies the negative valence of an agonistic gestural display by exploiting receiver perceptual bias.\nMany animals communicate by performing elaborate displays that are incredibly extravagant and wildly bizarre. So, how do these displays evolve? One idea is that innate sensory biases arbitrarily favour the emergence of certain display traits over others, leading to the design of an unusual display. Here, we study how physiological factors associated with signal production influence this process, a topic that has received almost no attention. We focus on a tropical frog, whose males compete for access to females by performing an elaborate waving display. Our results show that sex hormones like testosterone regulate specific display gestures that exploit a highly conserved perceptual system, evolved originally to detect 'dangerous' stimuli in the environment. Accordingly, testosterone makes certain gestures likely to appear more perilous to rivals during combat. This suggests that hormone action can interact with effects of sensory bias to create an evolutionary optimum that guides how display exaggeration unfolds.","subset":"pubmed_abstract"} +{"meta":{"pmid":15941807,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2015-18":1,"unknown":10}}},"text":"Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally.\nThe United Nations Millennium Development Goals (MDGs) are stimulating more rigorous evaluations of the impact of DOTS (the WHO-recommended approach to tuberculosis control based on 5 essential elements) and other possible strategies for tuberculosis (TB) control. To evaluate the prospects for detecting 70% of new sputum smear-positive cases and successfully treating 85% of these by the end of 2005, for reducing TB incidence, and for halving TB prevalence and deaths globally between 1990 and 2015, as specified by the MDGs. TB case notifications (1980-2003) from DOTS and non-DOTS programs and cohort treatment outcomes (1994-2002) reported annually to the World Health Organization (WHO) by up to 200 countries, TB death registrations, and prevalence surveys of infection and disease. Case notification series that reflect trends in incidence, treatment outcomes from DOTS cohorts, death statistics from countries with WHO-validated vital registration systems, and national prevalence surveys of infection and disease. Case reports, treatment outcomes, prevalence surveys, and death registrations from WHO's global TB database covering 1990-2003 to estimate TB incidence, prevalence, and death rates through 2015 for 9 epidemiologically different world regions. TB incidence increased globally in 2003, but incidence, prevalence, and death rates were approximately stable or decreased in 7 of 9 regions. The exceptions were regions of Africa with low (<4% in adults 15-49 years) and high rates (> or =4%) of HIV infection. The global detection rate of new smear-positive cases by DOTS programs increased from 11% in 1995 to 45% in 2003 (with the lowest case-detection rates in Eastern Europe and the highest rates in the Western Pacific) and could reach 60% by 2005. More than 17 million patients were treated in DOTS programs between 1994 and 2003, with overall treatment success rates more than 80% since 1998. In 2003, overall reported treatment success was 82%, with much variation among regions. The highest rates were reported in the Western Pacific region (89%) and lowest rates in African countries with high and low HIV infection rates (71% and 74%, respectively), in established market economies (77%), and in Eastern Europe (75%). To halve the prevalence rate by 2015, TB control programs must reach global targets for detection (70%) and treatment success (85%) and also reduce the incidence rate by at least 2% annually. To halve the death rate, incidence must decrease more steeply, by at least 5% to 6% annually. Reduction of TB incidence, prevalence, and deaths by 2015 could be achieved in most of the world, but the challenge will be greatest in Africa and Eastern Europe.","subset":"pubmed_abstract"} +{"meta":{"pmid":8598111,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Measurement of sugar probes in serum: an alternative to urine measurement in intestinal permeability testing.\nThe percentage dose of lactulose and mannitol excreted in urine after oral ingestion is used as a noninvasive method of assessing small intestinal permeability. The collection of incomplete or inaccurately timed urine samples can lead to errors in estimation of sugar probe molecules. We describe an HPLC method for the simultaneous determination of lactulose and mannitol in serum after oral ingestion of test sugars. We applied the test to healthy volunteers and to subjects undergoing jejunal biopsy for suspected gluten-sensitive enteropathy. The ratio of concentrations of lactulose and mannitol in serum discriminated well between subjects with a normal biopsy and those with villous atrophy, discrimination being best at 90 min postdose. The results agree well with lactulose:mannitol ratios determined in urine (r= 0.88), and the two methods can be used interchangeably. The determination of mannitol and lactulose in serum provides an acceptable alternative to urine collection and may be particularly useful in young children. It also reduces the time spent on the investigation from 5 h to 90 min.","subset":"pubmed_abstract"} +{"meta":{"pmid":20854710,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Nucleases: diversity of structure, function and mechanism.\nNucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review, I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely, a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associated with exonucleases producing mononucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion-independent RNases generate 2',3'-cyclic phosphate products, and all metal-ion-independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.","subset":"pubmed_abstract"} +{"meta":{"pmid":24808195,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Ontologies in biological data visualization.\nIn computer science, an ontology is essentially a graph-based knowledge representation in which each node corresponds to a concept and each edge specifies a relation between two concepts. Ontological development in biology can serve as a focus to discuss the challenges and possible research directions for ontologies in visualization. The principle challenges are the dynamic and evolving nature of ontologies, the ever-present issue of scale, the diversity and richness of the relationships in ontologies, and the need to better understand the relationship between ontologies and the data analysis tasks scientists wish to support. Research directions include visualizing ontologies; visualizing semantically or ontologically annotated texts, documents, and corpora; automated generation of visualizations using ontologies; and visualizing ontological context to support search. Although this discussion uses issues of ontologies in biological data visualization as a springboard, these topics are of general relevance to visualization.","subset":"pubmed_abstract"} +{"meta":{"pmid":7505739,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":5}}},"text":"Neuromelanin accumulation with age in catecholaminergic neurons from Macaca fascicularis brainstem.\nNeuromelanin (NM) is an auto-oxidation by-product of catecholamine synthesis which is observed almost exclusively in primates. We have estimated the distribution and the number of NM-positive neurons of the upper brainstem and the degree of their melanization from birth to the onset of senescence in 5 monkeys (Macaca fascicularis) aged 0, 1.5, 3.5, 8 and 13 years. Series of sections taken at 640-microns intervals were examined either unstained to detect unstained NM, stained for NM with Masson silver impregnation or processed by tyrosine hydroxylase (TH) immunohistochemistry to analyze catecholaminergic neurons. The proportion of NM-containing cells among TH-positive neurons varied from one catecholaminergic region to another: low in the hypothalamus and central gray substance (cgs); moderate in the cell group A8, and high in the ventral tegmental area (VTA), locus coeruleus (LC) and substantia nigra (SN). TH-positive neurons were detected in the SN, VTA, catecholaminergic cell group A8, LC, cgs and hypothalamus. At birth, although no unstained NM-positive neurons were detected, Masson-stained cells were observed, though only in the LC. At 1.5 and 3.5 years, Masson-positive neurons were observed despite the absence of visible pigment. At 8 and 13 years, unstained NM was present in Masson-positive neurons. The number of unstained NM-positive neurons and Masson-positive neurons and the amount of NM per neuron increased with age in each subregion studied. Nevertheless, some TH-positive neurons were found to be without NM. The data indicate a differential increased NM content with age in the neurons of midbrain catecholaminergic cell groups. However, its functional significance remains to be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":24847688,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Reduced nephron endowment in the neonates of Indigenous Australian peoples.\nRates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.","subset":"pubmed_abstract"} +{"meta":{"pmid":22004148,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Preference for place of death in Germany.\nDying in the preferred place is considered a key requirement for a \"good death.\" The aims of our study were to explore preferred places of death of deceased people and their bereaved relatives in Rhineland-Palatinate (Germany). We further wanted to assess the congruence between preferred and actual place of death. The cross-sectional study was based on a random sample of 5000 inhabitants of Rhineland-Palatinate (Germany) who died between May 25 and August 24, 2008. Relatives of these deceased persons were interviewed by a written survey. After removing duplicates, 4967 questionnaires were sent out, 3832 delivered, and 1378 completed, yielding a response rate of 36.0%. Regarding the deceased, 93.8% wanted to die at home, 0.7% in a hospital, 2.8% in palliative care, 2.4% in a nursing home, and 0.3% elsewhere. The figures for the relatives were 80.7%, 4.3%, 7.5%, 7.1%, and 0.5%, respectively. Of the deceased 58.9% and of the relatives 59.1% had their wish fulfilled. Logistic regression analysis revealed that living in a rural municipality (adjusted odds ratio [aOR]: 1.88; 95% confidence interval [CI]: 1.02-3.43), rural town (aOR: 2.30; 95% CI: 1.17-4.49) or small town (aOR: 1.95; 95% CI: 1.04-3.68), having a nonworking relative (aOR: 1.79; 95% CI: 1.16-2.76), and living together with a relative (aOR: 2.28; 95% CI:1.57-3.32) increases the probability to die in the preferred place. Because the availability of a relative was the most important factor to die in the preferred place, relatives of dying people should be supported in providing informal care. The introduction of palliative home care teams should allow more people to die in their preferred place by easing the burden of informal carers.","subset":"pubmed_abstract"} +{"meta":{"pmid":38008919,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":4,"2024-26":1,"2024-30":1,"unknown":5}}},"text":"Analysis of Forensic Death Statistics From 2013 to 2022 and Autopsy Practices in T\u00fcrkiye.\nAutopsy rates are significantly lower that what they should be worldwide. Additionally, autopsy practices vary between countries. To examine the autopsy rates, the distribution and temporal changes of forensic autopsy cases, so as to identify the areas in the death investigation system that require improvement in T\u00fcrkiye. Cross-sectional study. \"Forensic Death Examination Statistics\" of the Council of Forensic Medicine (CFM) and \"Death Statistics\" of the Turkish Statistical Institute were compared and analyzed for the years 2013-2022 in Turkey. The number of forensic death cases sent to the CFM has increased over time. For all causes of deaths, the autopsy rate is approximately 3.6-4.8%. The cause-specific mortality rates for deaths due to sharp instrument trauma, blunt trauma, occupational accident, undetermined, and poisoning have increased over the years. \"The percentage of \"undetermined\" deaths, which are important to demonstrate negative autopsies, was 14.2% in 2021. Although the autopsy rates have slightly increased in a volatile trend over time in Turkey, they are still not at the desired level. Thus, it is essential to further raise awareness among all professionals involved in death investigations about the importance of autopsies.","subset":"pubmed_abstract"} +{"meta":{"pmid":25884696,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"Understanding feedback report uptake: process evaluation findings from a 13-month feedback intervention in long-term care settings.\nLong-term care settings provide care to a large proportion of predominantly older, highly disabled adults across the United States and Canada. Managing and improving quality of care is challenging, in part because staffing is highly dependent on relatively non-professional health care aides and resources are limited. Feedback interventions in these settings are relatively rare, and there has been little published information about the process of feedback intervention. Our objectives were to describe the key components of uptake of the feedback reports, as well as other indicators of participant response to the intervention. We conducted this project in nine long-term care units in four facilities in Edmonton, Canada. We used mixed methods, including observations during a 13-month feedback report intervention with nine post-feedback survey cycles, to conduct a process evaluation of a feedback report intervention in these units. We included all facility-based direct care providers (staff) in the feedback report distribution and survey administration. We conducted descriptive analyses of the data from observations and surveys, presenting this in tabular and graphic form. We constructed a short scale to measure uptake of the feedback reports. Our analysis evaluated feedback report uptake by provider type over the 13 months of the intervention. We received a total of 1,080 survey responses over the period of the intervention, which varied by type of provider, facility, and survey month. Total number of reports distributed ranged from 103 in cycle 12 to 229 in cycle 3, although the method of delivery varied widely across the period, from 12% to 65% delivered directly to individuals and 15% to 84% left for later distribution. The key elements of feedback uptake, including receiving, reading, understanding, discussing, and reporting a perception that the reports were useful, varied by survey cycle and provider type, as well as by facility. Uptake, as we measured it, was consistently high overall, but varied widely by provider type and time period. We report detailed process data describing the aspects of uptake of a feedback report during an intensive, longitudinal feedback intervention in long-term care facilities. Uptake is a complex process for which we used multiple measures. We demonstrate the feasibility of conducting a complex longitudinal feedback intervention in relatively resource-poor long-term care facilities to a wider range of provider types than have been included in prior feedback interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":23038283,"dup_signals":{"dup_doc_count":42,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":4,"2016-36":4,"2016-30":4,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":4,"2015-40":1,"2015-35":5,"2015-32":3,"2015-27":2,"2015-22":4,"2015-18":1}}},"text":"Lens based adaptive optics scanning laser ophthalmoscope.\nWe present an alternative approach for an adaptive optics scanning laser ophthalmoscope (AO-SLO). In contrast to other commonly used AO-SLO instruments, the imaging optics consist of lenses. Images of the fovea region of 5 healthy volunteers are recorded. The system is capable to resolve human foveal cones in 3 out of 5 healthy volunteers. Additionally, we investigated the capability of the system to support larger scanning angles (up to 5\u00b0) on the retina. Finally, in order to demonstrate the performance of the instrument images of rod photoreceptors are presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":29059417,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Brief Web-Based Interventions for Young Adult Smokers With Severe Mental Illnesses: A Randomized, Controlled Pilot Study.\nAbout 50% of young adults with schizophrenia, bipolar disorder, and other severe mental illnesses smoke tobacco, but few studies have evaluated interventions for this group. We conducted a randomized pilot study among 58 young adult smokers with severe mental illnesses comparing a brief interactive web-based motivational tool, Let's Talk About Smoking, to computerized standard education from the National Cancer Institute. An additional 23 subjects received minimal tobacco assessment at baseline and no intervention, providing a comparison condition for naturalistic cessation behavior. All participants (total n = 81) were assessed for smoking and breath carbon monoxide at baseline and 14 weeks and had access to standard cessation treatments. The 81 participants were stable outpatients ages 18-30 (mean 24.8 years): 43.2% were diagnosed with schizophrenia-spectrum disorders, the remainder with severe mood and anxiety disorders. They smoked 14.6 \u00b1 10.2 cigarettes per day. All participants completed their assigned intervention; 83.4% of Let's Talk About Smoking users and 71.4% of standard education users rated their intervention \"good\" or \"very good.\" At 14 weeks, less than 15% of participants in all conditions had used additional cessation treatment. Let's Talk About Smoking users were more likely to have biologically verified abstinence at 14 weeks than standard education users (14.8% vs. 0%; X2 = 3.7, p = .05). None of the participants in the naturalistic comparison condition were abstinent at 14 weeks. Interactive, web-based motivational interventions are feasible and promising for smoking cessation among young smokers with severe mental illnesses. Such interventions warrant further study among this group of smokers. Young adult smokers with severe mental illnesses are a vulnerable population that, without intervention, goes on to experience disparate morbidity and mortality. Brief, easily disseminable interventions are needed to facilitate cessation in this group. This pilot research indicates that brief, technology-delivered, motivational interventions that are tailored for this group may be able to activate a significant number to quit without additional cessation intervention.","subset":"pubmed_abstract"} +{"meta":{"pmid":29373581,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":13}}},"text":"MUMmer4: A fast and versatile genome alignment system.\nThe MUMmer system and the genome sequence aligner nucmer included within it are among the most widely used alignment packages in genomics. Since the last major release of MUMmer version 3 in 2004, it has been applied to many types of problems including aligning whole genome sequences, aligning reads to a reference genome, and comparing different assemblies of the same genome. Despite its broad utility, MUMmer3 has limitations that can make it difficult to use for large genomes and for the very large sequence data sets that are common today. In this paper we describe MUMmer4, a substantially improved version of MUMmer that addresses genome size constraints by changing the 32-bit suffix tree data structure at the core of MUMmer to a 48-bit suffix array, and that offers improved speed through parallel processing of input query sequences. With a theoretical limit on the input size of 141Tbp, MUMmer4 can now work with input sequences of any biologically realistic length. We show that as a result of these enhancements, the nucmer program in MUMmer4 is easily able to handle alignments of large genomes; we illustrate this with an alignment of the human and chimpanzee genomes, which allows us to compute that the two species are 98% identical across 96% of their length. With the enhancements described here, MUMmer4 can also be used to efficiently align reads to reference genomes, although it is less sensitive and accurate than the dedicated read aligners. The nucmer aligner in MUMmer4 can now be called from scripting languages such as Perl, Python and Ruby. These improvements make MUMer4 one the most versatile genome alignment packages available.","subset":"pubmed_abstract"} +{"meta":{"pmid":11099414,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":16}}},"text":"Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis.\nMany apoptotic molecules relocate subcellularly in cells undergoing apoptosis. The pro-apoptotic protein BID underwent posttranslational (rather than classic cotranslational) N-myristoylation when cleavage by caspase 8 caused exposure of a glycine residue. N-myristoylation enabled the targeting of a complex of p7 and myristoylated p15 fragments of BID to artificial membranes bearing the lipid composition of mitochondria, as well as to intact mitochondria. This post-proteolytic N-myristoylation serves as an activating switch, enhancing BID-induced release of cytochrome c and cell death.","subset":"pubmed_abstract"} +{"meta":{"pmid":30563959,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"A Prospective Study to Compare Superb Microvascular Imaging with Grayscale Ultrasound and Color Doppler Flow Imaging of Vascular Distribution and Morphology in Thyroid Nodules.\nBACKGROUND This study aimed to compare superb microvascular imaging (SMI) with grayscale ultrasound (US) and color Doppler flow imaging (CDFI) to evaluate vascular distribution and morphology to distinguish between benign and malignant thyroid nodules. MATERIAL AND METHODS Seventy-one patients with 76 thyroid nodules underwent grayscale US, CDFI, and SMI thyroid imaging. CDFI and SMI assessed vascular quantity, morphology, and distribution, and was graded according to Adler's method, as absent (grade 0), minimal (grade 1), moderate (grade 2), or marked (grade 3). The detection of malignancy was compared between the following imaging groups, grayscale US alone, US combined with CDFI, and US combined with SMI. RESULTS SMI was significantly more accurate in identifying malignant thyroid nodules (79.3%) compared with CDFI (55.2%) (P<0.001). In malignant thyroid nodules, penetrating blood vessels were identified by SMI in 62.1% and by CDFI in 41.4%; there was no significant difference in vascular distribution between SMI (P=0.835) and CDFI (P=0.806). Grayscale US with SMI resulted in the greatest diagnostic sensitivity, accuracy, and specificity (86.21%, 85.53%, and 85.11%) compared with grayscale US with CDFI (75.86%, 82.89%, and 87.23%). Receiver operating characteristic (ROC) area under the curve (AUC) values of US with SMI, US with CDFI, and US alone were 0.918 (95% CI, 0.856-0.979), 0.911 (95% CI, 0.849-0.973), and 0.847 (95% CI, 0.762-0.932), respectively (P<0.001). CONCLUSIONS SMI as an adjunct to grayscale US provided significantly more information on vascularity associated with malignancy in thyroid nodules, when compared with grayscale US or with US and CDFI.","subset":"pubmed_abstract"} +{"meta":{"pmid":35608369,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":7}}},"text":"'He called me out of the blue': An ethnographic exploration of contrasting temporalities in a social prescribing intervention.\nSocial prescribing, a way of connecting patients to local services, is central to the NHS Personalised Care agenda. This paper employs ethnographic data, generated with 19 participants between November 2018 and July 2020, to explore the socio-temporal relations shaping their experiences of a local social prescribing intervention. Our focus is on the ways in which the intervention synchronised with the multitude of shifting, complex and often contradictory 'timespaces' of our participants. Our focus on the temporal rhythms of everyday practice allows us to trace a tension between the linearity and long horizon of the intervention and the oft contrasting timeframes of participants, sometimes leading to a mismatch that limited the intervention's impact. Further, we observed an interventional 'drift' from continuity towards unsupported signposting and 'out-of-the-blue' contacts which favour the temporality of the intervention. We demonstrate a need for intervention planning to be flexible to multiple, often conflicting, temporalities. We argue that health interventions must account for the temporal relations lived by the people they seek to support.","subset":"pubmed_abstract"} +{"meta":{"pmid":23033998,"dup_signals":{"dup_doc_count":32,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2022-21":2,"2021-49":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2020-29":2,"2020-16":2,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-47":1}}},"text":"Comparison of the effects of e-cigarette vapor and cigarette smoke on indoor air quality.\nElectronic cigarettes (e-cigarettes) have earned considerable attention recently as an alternative to smoking tobacco, but uncertainties about their impact on health and indoor air quality have resulted in proposals for bans on indoor e-cigarette use. To assess potential health impacts relating to the use of e-cigarettes, a series of studies were conducted using e-cigarettes and standard tobacco cigarettes. Four different high nicotine e-liquids were vaporized in two sets of experiments by generic 2-piece e-cigarettes to collect emissions and assess indoor air concentrations of common tobacco smoke by products. Tobacco cigarette smoke tests were conducted for comparison. Comparisons of pollutant concentrations were made between e-cigarette vapor and tobacco smoke samples. Pollutants included VOCs, carbonyls, PAHs, nicotine, TSNAs, and glycols. From these results, risk analyses were conducted based on dilution into a 40 m\u00b3 room and standard toxicological data. Non-cancer risk analysis revealed \"No Significant Risk\" of harm to human health for vapor samples from e-liquids (A-D). In contrast, for tobacco smoke most findings markedly exceeded risk limits indicating a condition of \"Significant Risk\" of harm to human health. With regard to cancer risk analysis, no vapor sample from e-liquids A-D exceeded the risk limit for either children or adults. The tobacco smoke sample approached the risk limits for adult exposure. For all byproducts measured, electronic cigarettes produce very small exposures relative to tobacco cigarettes. The study indicates no apparent risk to human health from e-cigarette emissions based on the compounds analyzed.","subset":"pubmed_abstract"} +{"meta":{"pmid":27540412,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":2,"2024-26":1,"unknown":7}}},"text":"Determination of diclofenac concentrations in human plasma using a sensitive gas chromatography mass spectrometry method.\nA gas chromatography mass spectrometry (GCMS) method for the determination of diclofenac in human plasma has been developed and validated. This method utilizes hexane which is a relatively less toxic extraction solvent compared to heptane and benzene. In addition, phosphoric acid and acetone were added to the samples as deproteination agents, which increased the recovery of diclofenac. These revised processes allow clean extraction and near-quantitative recovery of analyte (approx. 89-95 %). Separation was achieved on a BP-1 column with helium as carrier gas. The molecular ion peaks of the indolinone derivatives of diclofenac ion (m\/z 277) and the internal standard, 4-hydroxydiclofenac ion (m\/z 439) were monitored by a mass-selective detector using selected ion monitoring (SIM) mode. The linear range for the newly developed and highly sensitive assay was between 0.25-50 ng\/mL. The detection and lower quantifiable limits were 0.125 and 0.25 ng\/mL, respectively. The inter-day and intra-day coefficients of variation for high, medium and low quality control concentrations were less than 9 %. The robustness and efficacy of this sensitive GCMS method was further demonstrated by using it for a pharmacokinetic study of an oral dosage form of diclofenac, 100 mg of modified-release capsules (Rhumalgan XL), in human plasma. This method is rapid, sensitive, specific, reproducible and robust, and offers improved sensitivity over previous methods. This method has considerable potential to be used for detailed pharmacokinetics, pharmacodynamics and bioequivalence studies of diclofenac in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":16840830,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":11}}},"text":"Two novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.\nMultiple endocrine neoplasia type 1 (MEN1) is characterized by parathyroid, enteropancreatic endocrine and pituitary adenomas as well as germline mutation of the MEN1 gene. We describe 2 families with MEN1 with novel mutations in the MEN1 gene. One family was of Turkish origin, and the index patient had primary hyperparathyroidism (PHPT) plus a prolactinoma; three relatives had PHPT only. The index patient in the second family was a 46-yr-old woman of Chinese origin living in Taiwan. This patient presented with a complaint of epigastric pain and watery diarrhea over the past 3 months, and had undergone subtotal parathyroidectomy and enucleation of pancreatic islet cell tumor about 10 yr before. There was also a prolactinoma. Sequence analysis of the MEN1 gene from leukocyte genomic DNA revealed heterozygous mutations in both probands. The Turkish patient and her affected relatives all had a heterozygous A to G transition at codon 557 (AAG-->GAG) of exon 10 of MEN1 that results in a replacement of lysine by glutamic acid. The Chinese index patient and one of her siblings had a heterozygous mutation at codon 418 of exon 9 (GAC-->TAT) that results in a substitution of aspartic acid by tyrosine. In conclusion, we have identified 2 novel missense mutations in the MEN1 gene.","subset":"pubmed_abstract"} +{"meta":{"pmid":2533206,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Brain dynein crossbridges microtubules into bundles.\nCytoplasmic dynein was purified from pig brain, using a modified version of published procedures, in order to study its interaction with microtubules. Since the preparation produces ATP-dependent sliding of taxol-stabilized purified microtubules over glass and runs on SDS-containing gels as a major band exceeding 300,000 Mr plus a medium chain band at about 75,000 Mr, it is assumed to be identical to the mammalian brain dynein (MAP 1C) purified by Vallee and colleagues. When viewed by electron microscopy in negative stain, individual particles show two distinct configurations. Some are clearly similar to the two-headed bouquet structure already shown for MAP 1C. A larger number of molecules in the present preparation appear to have two heads fused together, forming a dimeric globular particle with two separate tails. They are referred to as phiparticles, because of their resemblance to the greek letter phi. A model for the structural relationship between the two molecular forms is presented. The stems of two associated dynein subunits may separate beyond the base, to form a bouquet, or they may remain fused to form the larger tail of a phi-particle. The smaller tail probably represents a combined pair of features equivalent to the 'stalks' shown to emanate from axonemal dynein heads by Goodenough and colleagues. Both tails of a phi-particle can bind to microtubules, even in the presence of ATP, and cause microtubule bundling. These results suggest a complete structural homology between axonemal and cytoplasmic dynein.","subset":"pubmed_abstract"} +{"meta":{"pmid":8182140,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Regulation of hepatic 7 alpha-hydroxylase expression by dietary psyllium in the hamster.\nSoluble fiber consistently lowers plasma total and low density lipoprotein (LDL)-cholesterol concentrations in humans and various animal models including the hamster; however, the mechanism of this effect remains incompletely defined. We performed studies to determine the activity of dietary psyllium on hepatic 7 alpha-hydroxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and LDL receptor expression in the hamster. In animals fed a cholesterol-free semisynthetic diet containing 7.5% cellulose (avicel) as a fiber source, substitution of psyllium for avicel increased hepatic 7 alpha-hydroxylase activity and mRNA levels by 3-4-fold. Comparable effects on 7 alpha-hydroxylase expression were observed with 1% cholestyramine. Psyllium also increased hepatic 7 alpha-hydroxylase activity and mRNA in animals fed a diet enriched with cholesterol and triglyceride. Activation of 7 alpha-hydroxylase was associated with an increase in hepatic cholesterol synthesis that was apparently not fully compensatory since the cholesterol content of the liver declined. Although dietary psyllium did not increase hepatic LDL receptor expression in animals fed the cholesterol-free, very-low-fat diet, it did increase (or at least restore) receptor expression that had been downregulated by dietary cholesterol and triglyceride. Thus, 7.5% dietary psyllium produced effects on hepatic 7 alpha-hydroxylase and LDL metabolism that were similar to those of 1% cholestyramine. Induction of hepatic 7 alpha-hydroxylase activity by dietary psyllium may account, in large part, for the hypocholesterolemic effect of this soluble fiber.","subset":"pubmed_abstract"} +{"meta":{"pmid":16665771,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Characterization of Iron Uptake from Ferrioxamine B by Chlorella vulgaris.\nIron uptake from two Fe(3+)-hydroxamate siderophores, ferrioxamine B and Fe(3+)-rhodotorulate, by iron-stressed Chlorella vulgaris (ATCC strain 11468) was evaluated with some comparison to iron uptake from synthetic and organic acid ferric chelates. Iron-stress induced iron uptake from ferrioxamine B. Dissipation of the electrochemical gradient, via uncouplers, inhibited iron uptake. Respiratory inhibitors gave variable results, an indication that a direct link to respiration was not apparent. Vanadate inhibition of iron uptake indicated that an ATPase or phosphate intermediate could be involved in the uptake mechanism. Divalent cations manifested variable effects dependent on the cation and chelator used. These data confirm that C. vulgaris has an inducible iron-uptake system for Fe(3+)-hydroxamic acid siderophores which may involve a different mechanism than that observed for other chelates.","subset":"pubmed_abstract"} +{"meta":{"pmid":16509050,"dup_signals":{"dup_doc_count":42,"dup_dump_count":2,"dup_details":{"curated_sources":5,"2024-18":1,"2024-26":1,"unknown":35}}},"text":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: long-term treatment of schizophrenia.\nThese guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A-D). This second part of the guidelines covers the long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28024228,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2019-30":1,"2019-22":2,"2019-13":1,"2018-43":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2023-23":1,"2024-26":1}}},"text":"Vector-field statistics for the analysis of time varying clinical gait data.\nIn clinical settings, the time varying analysis of gait data relies heavily on the experience of the individual(s) assessing these biological signals. Though three dimensional kinematics are recognised as time varying waveforms (1D), exploratory statistical analysis of these data are commonly carried out with multiple discrete or 0D dependent variables. In the absence of an a priori 0D hypothesis, clinicians are at risk of making type I and II errors in their analyis of time varying gait signatures in the event statistics are used in concert with prefered subjective clinical assesment methods. The aim of this communication was to determine if vector field waveform statistics were capable of providing quantitative corroboration to practically significant differences in time varying gait signatures as determined by two clinically trained gait experts. The case study was a left hemiplegic Cerebral Palsy (GMFCS I) gait patient following a botulinum toxin (BoNT-A) injection to their left gastrocnemius muscle. When comparing subjective clinical gait assessments between two testers, they were in agreement with each other for 61% of the joint degrees of freedom and phases of motion analysed. For tester 1 and tester 2, they were in agreement with the vector-field analysis for 78% and 53% of the kinematic variables analysed. When the subjective analyses of tester 1 and tester 2 were pooled together and then compared to the vector-field analysis, they were in agreement for 83% of the time varying kinematic variables analysed. These outcomes demonstrate that in principle, vector-field statistics corroborates with what a team of clinical gait experts would classify as practically meaningful pre- versus post time varying kinematic differences. The potential for vector-field statistics to be used as a useful clinical tool for the objective analysis of time varying clinical gait data is established. Future research is recommended to assess the usefulness of vector-field analyses during the clinical decision making process.","subset":"pubmed_abstract"} +{"meta":{"pmid":26576562,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":10}}},"text":"Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.\nTau is a microtubule-associated protein and a key regulator of microtubule stabilization as well as the main component of neurofibrillary tangles-a principle neuropathological hallmark of Alzheimer's disease (AD)-as well as pleomorphic neuronal and glial inclusions in neurodegenerative tauopathies. Cross-sectional studies of neurofibrillary pathology in AD reveal a stereotypic spatiotemporal pattern of neuronal vulnerability that correlates with disease severity; however, the relationship of this pattern to disease progression is less certain and exceptions to the typical pattern have been described in a subset of AD patients. The basis for the selective vulnerability of specific populations of neurons to tau pathology and cell death is largely unknown, although there have been a number of hypotheses based upon shared properties of vulnerable neurons (e.g., degree of axonal myelination or synaptic plasticity). A recent hypothesis for selective vulnerability takes into account the emerging science of functional connectivity based upon resting state functional magnetic resonance imaging, where subsets of neurons that fire synchronously define patterns of degeneration similar to specific neurodegenerative disorders, including various tauopathies. In the past 6 years, the concept of tau propagation has emerged from numerous studies in cell and animal models suggesting that tau moves from cell-to-cell and that this may trigger aggregation and region-to-region spread of tau pathology within the brain. How the spread of tau pathology relates to functional connectivity is an area of active investigation. Observations of templated folding and propagation of tau have prompted comparisons of tau to prions, the pathogenic proteins in transmissible spongiform encephalopathies. In this review, we discuss the most compelling studies in the field, discuss their shortcomings and consider their implications with respect to human tauopathies as well as the controversy that tauopathies may be prion-like disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":7004477,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-18":1,"2015-06":1,"2024-22":1,"unknown":9}}},"text":"Deposition, retention, and clearance of inhaled particles.\nThe relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":28742794,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).\nTo assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. Using a CA125-ROCA cost of \u00a320, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of \u00a391 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to \u00a315, the ICER becomes \u00a377 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of \u00a330 033 per LYG, while Markov modelling produces an ICER of \u00a346 922 per QALY. Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.","subset":"pubmed_abstract"} +{"meta":{"pmid":29313707,"dup_signals":{"dup_doc_count":25,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":2,"2024-30":1,"unknown":19}}},"text":"Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma.\nInflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma. To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma. We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent [VDP]) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated. MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (\u22653%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV1, indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005). In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22272344,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Soft coral Sarcophyton (Cnidaria: Anthozoa: Octocorallia) species diversity and chemotypes.\nResearch on the soft coral genus Sarcophyton extends over a wide range of fields, including marine natural products and the isolation of a number of cembranoid diterpenes. However, it is still unknown how soft corals produce this diverse array of metabolites, and the relationship between soft coral diversity and cembranoid diterpene production is not clear. In order to understand this relationship, we examined Sarcophyton specimens from Okinawa, Japan, by utilizing three methods: morphological examination of sclerites, chemotype identification, and phylogenetic examination of both Sarcophyton (utilizing mitochondrial protein-coding genes MutS homolog: msh1) and their endosymbiotic Symbiodinium spp. (utilizing nuclear internal transcribed spacer of ribosomal DNA: ITS- rDNA). Chemotypes, molecular phylogenetic clades, and sclerites of Sarcophyton trocheliophorum specimens formed a clear and distinct group, but the relationships between chemotypes, molecular phylogenetic clade types and sclerites of the most common species, Sarcophyton glaucum, was not clear. S. glaucum was divided into four clades. A characteristic chemotype was observed within one phylogenetic clade of S. glaucum. Identities of symbiotic algae Symbiodinium spp. had no apparent relation to chemotypes of Sarcophyton spp. This study demonstrates that the complex results observed for S. glaucum are due to the incomplete and complex taxonomy of this species group. Our novel method of identification should help contribute to classification and taxonomic reassessment of this diverse soft coral genus.","subset":"pubmed_abstract"} +{"meta":{"pmid":11883832,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2014-10":1,"2024-10":1,"unknown":11}}},"text":"Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy.\nSpontaneous spinal cerebrospinal fluid (CSF) leaks are increasingly recognized as a cause of postural headaches. The authors examined a group of patients suffering from spontaneous spinal CSF leaks who also had minor skeletal features of Marfan syndrome for abnormalities of fibrillin-containing microfibrils. Patients with spontaneous CSF leaks were evaluated for the clinical characteristics of connective tissue disorders. Skin biopsies were obtained in three patients with skeletal manifestations that constitute part of the Marfan syndrome phenotype. Cultured fibroblasts were studied for fibrillin-1 synthesis and incorporation into the extracellular matrix (ECM) by performing quantitative metabolic labeling and immunohistochemical analysis. Among 20 consecutive patients found to have spinal CSF leaks, four (20%) exhibited minor skeletal features of Marfan syndrome, but lacked any ocular or cardiovascular abnormalities. The mean age of these patients (30 years) was lower than that of the 16 patients without skeletal abnormalities (44 years; p = 0.01). Abnormalities in fibrillin-1 metabolism and immunostaining were detected in all three patients with the skeletal abnormalities who underwent examination, but not in a control patient without these skeletal manifestations. Twenty percent of patients who experience spontaneous spinal CSF leaks have minor skeletal features of Marfan syndrome. The authors demonstrated abnormalities in fibrillin-1 protein deposition in all patients examined, but only one person was found to have a fibrillin-1 abnormality typically found in classic Marfan syndrome. The results indicate that there is a heterogeneous involvement of other components of ECM microfibrils at the basis of this cerebrospinal manifestation. In addition, the authors identified a connective-tissue etiological factor in a group of disorders not previously classified as such.","subset":"pubmed_abstract"} +{"meta":{"pmid":8321111,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"Regulation of central blood volume and cardiac filling in endurance athletes: the Frank-Starling mechanism as a determinant of orthostatic tolerance.\nOrthostatic intolerance may result from either an abnormally large postural decrease in central blood volume, cardiac filling pressures, and stroke volume, or inadequate neurohumoral responses to orthostasis. Endurance athletes have been reported as having a high incidence of orthostatic intolerance, which has been attributed primarily to abnormalities in baroreflex regulation of heart rate and peripheral resistance. In this review, we present evidence that athletes also have structural changes in the cardiovascular system that although beneficial during exercise, lead to an excessively large decrease in stroke volume during orthostasis and contribute to orthostatic intolerance. A unifying hypothesis based on cardiac mechanics that may explain the divergence of findings in conditions such as bed rest or spaceflight, and short- and long-term endurance training is presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":2549964,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Carbachol and histamine stimulation of guanine-nucleotide-dependent phosphoinositide hydrolysis in rat brain cortical membranes.\nGuanine nucleotides have been shown to stimulate phosphoinositide breakdown in brain membranes, but no potentiation of such an effect by agonist was demonstrated. We have studied the effect of carbachol and histamine on guanosine 5'-[gamma-thio]triphosphate (GTP[S]) stimulation of inositol phosphates formation in [3H]inositol-labelled rat brain cortical membranes. In this preparation, GTP[S] enhancement of phosphoinositide hydrolysis required the presence of MgATP and low Ca2+ concentration (100 nM). Carbachol potentiation of the GTP[S] effect was only observed when 1 mM-deoxycholate was also added. Under these conditions, stimulated production of [3H]inositol phosphates was linear for at least 15 min, and [3H]inositol bisphosphate [( 3H]IP2) accounted for approx. 80%, whereas the amount of [3H]inositol trisphosphate [( 3H]IP3) was very low. Stimulation by GTP[S] was concentration-dependent (half-maximal effect at 0.86 microM), and its maximal effect (815% over basal) was increased by 1 mM-carbachol (1.9-fold) and -histamine (1.7-fold). Both agonists decreased the slope index of the GTP[S] concentration\/effect curve to values lower than unity, suggesting the appearance of some heterogeneity in the population of guanine-nucleotide-binding proteins (G-proteins) involved. The carbachol and histamine effects were also concentration-dependent, and were inhibited by atropine and mepyramine respectively. Fluoroaluminate stimulated phosphoinositide hydrolysis to a higher extent than GTP[S] plus carbachol, and these stimulations were not additive, indicating that the same polyphosphoinositide phospholipase C-coupled G-protein mediates both effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":19289594,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"Evidence that stainable bone marrow iron following parenteral iron therapy does not correlate with serum iron studies and may not represent readily available storage iron.\nWe recently reported that parenteral iron therapy is associated with a characteristic pattern of iron staining on bone marrow aspirate smears. We now present clinical information from 6 patients who received parenteral iron and, at one or more points in follow-up, were found to have low or borderline low serum ferritin levels and\/or serum iron levels, even though marrow aspirate smears revealed abundant stainable iron in the pattern characteristic of prior parenteral iron therapy. We conclude that stainable iron seen in this pattern does not correlate with serum iron studies and may not represent functionally available storage iron. This pattern of iron staining should not be used as evidence to withhold further iron therapy in patients who otherwise continue to have features of iron deficiency anemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":12410781,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Community pharmacy services for drug misusers in Scotland: what difference does 5 years make?\nTo assess current levels of participation of community pharmacists in needle exchange provision, assess participation in dispensing any drugs for drug misuse, explore methadone dispensing practice, assess involvement in health promotion for drug misusers, assess levels of training in drug misuse and compare all of the above with data from 5 years previously. A cross-sectional postal questionnaire. All community pharmacies in Scotland (n = 1162). A total of 969 pharmacists managing community pharmacies on a day-to-day basis (response rate 83.4%). Descriptive data were collected on demography, drug misuse services provided and training. Data were combined with a dataset from an identical survey conducted 5 years previously for statistical comparison. Levels of needle exchange provision has not changed significantly (9.7% in 2000 compared to 8.6% in 1995). Of all respondents, 71.5% now dispense drug for the management of drug misuse, 68.9% dispense methadone and 56.7% provide a supervised methadone consumption service. The number of methadone clients receiving methadone through pharmacies has increased from 3387 in 1995 to 8792 in 2000 and the mean number of clients dispensed methadone per pharmacy has increased from 7.3 in 1995 to 13.2 in 2000; 65.1% of all methadone clients now consume their methadone under pharmacist supervision. The proportion of pharmacists dispensing methadone who provide a supervised consumption service has increased significantly from 37% to 82.8%. Considerable changes in pharmacy practice are evident with significant increases in the number of pharmacists who always lay down ground rules, ask for identification on first visits, make up prescriptions in advance and provide verbal advice and leaflets on the management of drug misuse. Training in drug misuse doubled from 31.8% to 66.8%. Community pharmacy involvement with drug misusers has increased dramatically in the last 5 years. However, this increase is largely in methadone dispensing and supervision. Pharmacists appear to be more proactive in providing advice and information, perhaps as a result of greater training.","subset":"pubmed_abstract"} +{"meta":{"pmid":21792751,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-20":1,"2017-13":1,"unknown":20}}},"text":"The neurocritical care research network: NCRN.\nNeurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":17601950,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate by Drosophila melanogaster larvae.\nThe effects of chronic exposure to dietary salicylate on elimination and renal excretion of salicylate by D. melanogaster larvae were evaluated using salicylate-selective microelectrodes. Larvae chronically exposed to dietary salicylate showed 25% less salicylate in the haemolymph compared to the control group after feeding on a salicylate-enriched diet. By 1 h after transfer to a salicylate-free diet the levels of salicylate in the haemolymph of larvae raised on dietary salicylate were 46% lower than in the control group. Salicylate flux increased dramatically across Malpighian tubules but not across midgut or hindgut isolated from larvae chronically exposed to dietary salicylate, relative to the control group. Malpighian tubules isolated from experimental larvae showed a 4.7-fold increase in Kt and a nearly 5-fold increase in Jmax relative to the control. These changes in salicylate transport were accompanied by a 3.2-fold increase in fluid secretion rate. Moreover, the high rates of fluid secretion by the Malpighian tubules isolated from experimental larvae were stimulated 2.1-fold and 2.8-fold when tubules were challenged with 1 mmol l(-1) cAMP and 10 micromol l(-1) leucokinin I, respectively. Taken together, these results indicate that chronic exposure of D. melanogaster larvae to dietary salicylate alters elimination of such toxins from the haemolymph and increases the basal rate of fluid secretion and excretion of salicylate by the Malpighian tubules.","subset":"pubmed_abstract"} +{"meta":{"pmid":19497097,"dup_signals":{"dup_doc_count":44,"dup_dump_count":35,"dup_details":{"curated_sources":2,"2020-45":1,"2019-51":1,"2019-09":1,"2018-47":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2014-42":3,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":2,"2023-23":1,"2013-48":1,"2013-20":2,"2014-10":1}}},"text":"Overexpression and simple purification of the Thermotoga maritima 6-phosphogluconate dehydrogenase in Escherichia coli and its application for NADPH regeneration.\nThermostable enzymes from thermophilic microorganisms are playing more and more important roles in molecular biology R&D and industrial applications. However, over-production of recombinant soluble proteins from thermophilic microorganisms in mesophilic hosts (e.g. E. coli) remains challenging sometimes. An open reading frame TM0438 from a hyperthermophilic bacterium Thermotoga maritima putatively encoding 6-phosphogluconate dehydrogenase (6PGDH) was cloned and expressed in E. coli. The purified protein was confirmed to have 6PGDH activity with a molecular mass of 53 kDa. The kcat of this enzyme was 325 s-1 and the Km values for 6-phosphogluconate, NADP+, and NAD+ were 11, 10 and 380 muM, respectively, at 80 degrees C. This enzyme had half-life times of 48 and 140 h at 90 and 80 degrees C, respectively. Through numerous approaches including expression vectors, hosts, cultivation conditions, inducers, and codon-optimization of the 6pgdh gene, the soluble 6PGDH expression levels were enhanced to ~250 mg per liter of culture by more than 500-fold. The recombinant 6PGDH accounted for >30% of total E. coli cellular proteins when lactose was used as a low-cost inducer. In addition, this enzyme coupled with glucose-6-phosphate dehydrogenase for the first time was demonstrated to generate two moles of NADPH per mole of glucose-6-phosphate. We have achieved a more than 500-fold improvement in the expression of soluble T. maritima 6PGDH in E. coli, characterized its basic biochemical properties, and demonstrated its applicability for NADPH regeneration by a new enzyme cocktail. The methodology for over-expression and simple purification of this thermostable protein would be useful for the production of other thermostable proteins in E. coli.","subset":"pubmed_abstract"} +{"meta":{"pmid":11705950,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Evaluation of cholera vaccines formulated with toxin-coregulated pilin peptide plus polymer adjuvant in mice.\nCholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In addition, polyclonal and several monoclonal antibodies directed against TCP have been shown to provide passive immunity to disease in the infant mouse cholera model. In the present study, synthetic peptides corresponding to portions of the C-terminal disulfide region of TcpA pilin were formulated with polymer adjuvants currently in clinical trials and used to actively immunize adult female CD-1 mice. The experimental vaccine formulations elicited high levels of antigen-specific immunoglobulin G (IgG), including a broad spectrum of subclasses (IgG1, IgG2a, IgG2b, and IgG3), and lower levels of IgA. Infant mice born to the immunized mothers showed 100% protection against a 50% lethal dose (1 LD(50)) challenge and 50% protection against a 10-LD(50) challenge with virulent strain O395. These results indicate that specific regions of TcpA, including those delineated by the peptides used in this study, have the potential to be incorporated into an effective defined subunit vaccine for cholera.","subset":"pubmed_abstract"} +{"meta":{"pmid":32392844,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma \u03b2-cells.\nGlucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to \u03b2-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with \u03b2-cell function in pancreatic \u03b2-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic\/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal \u03b2-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 \u00b5g\/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 \u00b5g\/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 \u00b5g\/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce \u03b2-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":24586559,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":9}}},"text":"Changes in voluntary activation assessed by transcranial magnetic stimulation during prolonged cycling exercise.\nMaximal central motor drive is known to decrease during prolonged exercise although it remains to be determined whether a supraspinal deficit exists, and if so, when it appears. The purpose of this study was to evaluate corticospinal excitability and muscle voluntary activation before, during and after a 4-h cycling exercise. Ten healthy subjects performed three 80-min bouts on an ergocycle at 45% of their maximal aerobic power. Before exercise and immediately after each bout, neuromuscular function was evaluated in the quadriceps femoris muscles under isometric conditions. Transcranial magnetic stimulation was used to assess voluntary activation at the cortical level (VATMS), corticospinal excitability via motor-evoked potential (MEP) and intracortical inhibition by cortical silent period (CSP). Electrical stimulation of the femoral nerve was used to measure voluntary activation at the peripheral level (VAFNES) and muscle contractile properties. Maximal voluntary force was significantly reduced after the first bout (13 \u00b1 9%, P<0.01) and was further decreased (25 \u00b1 11%, P<0.001) at the end of exercise. CSP remained unchanged throughout the protocol. Rectus femoris and vastus lateralis but not vastus medialis MEP normalized to maximal M-wave amplitude significantly increased during cycling. Finally, significant decreases in both VATMS and VAFNES (\u223c 8%, P<0.05 and \u223c 14%, P<0.001 post-exercise, respectively) were observed. In conclusion, reductions in VAFNES after a prolonged cycling exercise are partly explained by a deficit at the cortical level accompanied by increased corticospinal excitability and unchanged intracortical inhibition. When comparing the present results with the literature, this study highlights that changes at the cortical and\/or motoneuronal levels depend not only on the type of exercise (single-joint vs. whole-body) but also on exercise intensity and\/or duration.","subset":"pubmed_abstract"} +{"meta":{"pmid":10803497,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2021-43":1,"2021-39":1,"2020-40":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-22":1,"2017-09":1,"2023-40":1,"2017-13":1,"2024-26":1}}},"text":"Induction of high levels of epitope-specific antibodies by epitope\/peptide candidate vaccines against human immunodeficiency virus type-1 (HIV-1).\nTo test the immunogenicity of GPGRAFY-epitope-based candidate vaccines, a peptide with four repetitive GPGRAFY epitopes, V3-P1 [C-(GPGRAFY)4], and a peptide (PND) of the principal neutralizing domain (V3 loop: amino acid 301-328: C-TRPNNNTRKSIRIQRGPGRAFYTIGKI) on gp120 were synthesized and covalently coupled to a carrier protein BSA. Immunization of BALB\/c mice and New Zealand White Rabbits with these conjugate vaccines engendered strong antibody responses against the PND (mouse serum titer by 1:12,800-25,600; rabbit serum titer by 1:6,400-12,800). Interestingly, the V3-P1-BSA conjugates and the PND-BSA conjugates could induce high levels of GPGRAFY-epitope-specific antibodies in the mice and rabbits (mouse serum titer by 1:25,600; rabbit serum titer by 1:12,800-25,600), while a recombinant gp160 subunit vaccine induced a low level of GPGRAFY-epitope-specific antibodies (serum titer by 1:400-1,600 in mice and rabbits). To confirm the above results, GPGRAFY-epitope-specific antibodies were isolated from rabbit sera induced by V3-P1-BSA, PND-BSA conjugates and rgp160 vaccine. In fact, 23-38 and 13-22 microg epitope-specific antibodies per milliliter serum were isolated from rabbit sera induced by V3-P1-BSA and PND-BSA conjugate, respectively, while 1.34 microg epitope-specific antibodies per milliliter serum were identified in rabbit serum induced by rgp160 vaccine. In the control group, only 0.069 microg proteins per milliliter serum were found in pooled pre-immune serum (normal serum). These results from mouse and rabbit experiments indicate that epitope and peptide vaccines both induce high levels of GPGRAFY-epitope-specific antibodies in comparison with rgp160 subunit vaccine, suggesting that epitope\/peptide vaccines may be a new strategy to induce protective activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28414741,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Effects of music on arousal during imagery in elite shooters: A pilot study.\nBeneficial effects of music on several performance-related aspects of sport have been reported, but the processes involved are not well understood. The purpose of the present study was to investigate effects of relaxing and arousing classical music on physiological indicators and subjective perceptions of arousal during imagery of a sport task. First, appropriate music excerpts were selected. Then, 12 skilled shooters performed shooting imagery while listening to the three preselected music excerpts in randomized order. Participants' galvanic skin response, peripheral temperature, and electromyography were monitored during music played concurrently with imagery. Subjective music ratings and physiological measures showed, as hypothesized, that unfamiliar relaxing music was the most relaxing and unfamiliar arousing music was the most arousing. Researchers should examine the impact of unfamiliar relaxing and arousing music played during imagery on subsequent performance in diverse sports. Practitioners can apply unfamiliar relaxing and arousing music with imagery to manipulate arousal level.","subset":"pubmed_abstract"} +{"meta":{"pmid":27447175,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2018-05":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2018-13":1,"2017-13":1}}},"text":"Targeting the vitamin D endocrine system (VDES) for the management of inflammatory and malignant skin diseases: An historical view and outlook.\nVitamin D represents one of the major driving factors for the development of life on earth and for human evolution. While up to 10-20 % of the human organism's requirements in vitamin D can be obtained by the diet (under most living conditions in the USA and Europe), approximately 90 % of all needed vitamin D has to be photosynthesized in the skin through the action of the sun (ultraviolet-B (UV-B)). The skin represents a key organ of the human body's vitamin D endocrine system (VDES), being both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites. It was shown that human keratinocytes possess the enzymatic machinery (CYP27B1) for the synthesis of the biologically most active natural vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), representing an autonomous vitamin D3 pathway. Cutaneous production of 1,25(OH)2D3 may exert intracrine, autocrine, and paracrine effects on keratinocytes and on neighboring cells. Many skin cells (including keratinocytes, sebocytes, fibroblasts, melanocytes, and skin immune cells) express the vitamin D receptor (VDR), an absolute pre-requisite for the mediation of genomic effects of 1,25(OH)2D3 and analogs. VDR belongs to the superfamily of trans-acting transcriptional regulatory factors, which includes the steroid and thyroid hormone receptors as well as the retinoid X receptors (RXR) and retinoic acid receptors (RAR). Numerous studies, including cDNA microarray analyses of messenger RNAs (mRNAs), indicate that as many as 500-1000 genes may be regulated by VDR ligands that control various cellular functions including growth, differentiation, and apoptosis. The observation that 1,25(OH)2D3 is extremely effective in inducing the terminal differentiation and in inhibiting the proliferation of cultured human keratinocytes has resulted in the use of vitamin D analogs for the treatment of psoriasis. This review gives an historical view and summarizes our present knowledge about the relevance of the VDES for the management of inflammatory and malignant skin diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":24765335,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Forgotten intrauterine device contributing to infertility.\nThe aim of the study is to show that long standing forgotten intrauterine device contributes to infertility, reporting three cases presented at Central Hospital Warri, Nigeria, a government tertiary health center. Three cases of forgotten intrauterine contraceptive device (IUCD) contributing to infertility were seen. Two were inserted for contraceptive reasons while one was inserted while being managed for uterine synechae. Health care providers should ensure proper documentation of all procedures carried out, adequate counseling which should include taking an informed consent and also ensuring both short and long term follow up of their clients. Also all patients being evaluated for infertility and clients with past history of intrauterine device must have a speculum examination and ultrasound scan carried out.","subset":"pubmed_abstract"} +{"meta":{"pmid":29661902,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.\nThe effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health. Participants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg\/d oral conjugated equine estrogen (oCEE); 50 \u03bcg\/d transdermal 17\u03b2-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg\/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68). Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo. The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT.","subset":"pubmed_abstract"} +{"meta":{"pmid":31793548,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"[Peripheral neurostimulation in headache treatment].\nAccording to rough estimates, at least one third of the population in developed countries suffers, to varying degrees, from certain forms of primary headache, the modern pharmacotherapy of which is not always effective and has a number of limitations. The non-pharmacological treatment of headache can be an alternative to the prescription of pharmacological agents and the only possible assistance option for patients developing drug-resistant cephalalgias. This review describes various methods of electrical neuromodulation that are used for the management of primary headaches. The authors provide information on current stages in implementation of implantable and non-invasive equipment into clinical practice, which makes possible electrical stimulations of peripheral nerves and of the sphenopalatine ganglion, as well as allows transcranial magnetic stimulation. Also the appearance and usage of portable electrical devices available on the world market are described, and mechanisms that can underlie anticephalgic action of neuromodulation therapy are discussed. Special attention is paid to the methods that are applied for electrostimulation of the vagus nerve and occipital nerves.","subset":"pubmed_abstract"} +{"meta":{"pmid":24725596,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-05":1,"2019-35":1,"2019-22":1,"2023-40":1,"2024-18":1}}},"text":"Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription.\nAntisense transcription is widespread in many genomes; however, how much is functional is hotly debated. We are investigating functionality of a set of long noncoding antisense transcripts, collectively called COOLAIR, produced at Arabidopsis FLOWERING LOCUS C (FLC). COOLAIR initiates just downstream of the major sense transcript poly(A) site and terminates either early or extends into the FLC promoter region. We now show that splicing of COOLAIR is functionally important. This was revealed through analysis of a hypomorphic mutation in the core spliceosome component PRP8. The prp8 mutation perturbs a cotranscriptional feedback mechanism linking COOLAIR processing to FLC gene body histone demethylation and reduced FLC transcription. The importance of COOLAIR splicing in this repression mechanism was confirmed by disrupting COOLAIR production and mutating the COOLAIR proximal splice acceptor site. Our findings suggest that altered splicing of a long noncoding transcript can quantitatively modulate gene expression through cotranscriptional coupling mechanisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":23519028,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.\nCharcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P). Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.","subset":"pubmed_abstract"} +{"meta":{"pmid":17361207,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2022-05":1,"2020-40":1,"2020-05":1,"2019-39":1,"2019-18":1,"2019-09":1,"2018-34":1,"2018-26":1,"2018-13":1,"2018-05":2,"2017-47":1,"2017-43":1,"2017-39":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-50":1,"2017-13":1}}},"text":"D2-40 and calretinin - a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation.\nAnti-calretinin antibodies are useful to differentiate adenocarcinomas from malignant mesotheliomas of the lung. Therefore, calretinin expression is rarely reported for sarcomatoid mesotheliomas. Anti-podoplanin antibodies (eg D2-40) react with lymphatic endothelia, Kaposi's sarcoma, lymphangioma and mesotheliomas. For the interpretation of spindle cell lesions of the pleura, knowledge of calretinin and D2-40 expression frequencies in sarcomatoid mesothelioma is desirable. To systematically investigate the sensitivity of calretinin and D2-40 antibodies in epithelioid and sarcomatoid areas of malignant mesotheliomas, a tissue microarray with 341 malignant mesotheliomas, including 112 epithelioid, 46 sarcomatoid and 183 biphasic tumors was constructed. Epithelioid and sarcomatoid differentiated tumor areas were clearly separated within the tissue microarray. Expression of calretinin and D2-40 was separately studied in epithelioid and sarcomatoid areas by immunohistochemistry. Calretinin expression was found in 91% of epithelioid and 57% of sarcomatoid tumor areas. D2-40 immunostaining was present in 66% of the epithelioid and 30% of the sarcomatoid tumor areas. A combination of calretinin and D2-40 increased the sensitivity in epithelioid tumor areas to 0.96 and in sarcomatoid tumor areas to 0.66. These data indicate that a combination of calretinin and D2-40 will improve diagnostic accuracy for spindle cell lesions of the pleura, whereas almost all epithelioid mesotheliomas are identified by calretinin alone.","subset":"pubmed_abstract"} +{"meta":{"pmid":29370089,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus.\nRaman microspectra combine information on chemical composition of plant tissues with spatial information. The contributions from the building blocks of the cell walls in the Raman spectra of plant tissues can vary in the microscopic sub-structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root, stem, and leaf tissues of Cucumis sativus, using different spectral contributions from cellulose and lignin in both univariate and multivariate imaging methods. Imaging based on hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicates different substructures in the xylem cell walls of the different tissues. Using specific signals from the cell wall spectra, analysis of the whole set of different tissue sections based on the Raman images reveals differences in xylem tissue morphology. Due to the specifics of excitation of the Raman spectra in the visible wavelength range (532 nm), which is, e.g., in resonance with carotenoid species, effects of photobleaching and the possibility of exploiting depletion difference spectra for molecular characterization in Raman imaging of plants are discussed. The reported results provide both, specific information on the molecular composition of cucumber tissue Raman spectra, and general directions for future imaging studies in plant tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":3618788,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effects of leukotriene D4 on glomerular dynamics in the rat.\nGlomerular micropuncture studies were performed in euvolemic, anesthetized, adult, male Munich-Wistar rats to evaluate the glomerular microcirculatory actions of leukotriene D4 (LTD4). In preliminary experiments, intrarenal arterial administration of LTD4 (1 microgram X kg-1 X min-1) was found to cause a rise in mean systemic arterial pressure, a loss of plasma volume, and a fall in renal blood flow, effects identical to those previously reported for LTC4. To assess the local glomerular actions of LTD4 independently of these systemic effects, glomerular microcirculatory dynamics were assessed during LTD4 infusion while constancy of renal perfusion pressure and plasma volume were maintained by partial aortic constriction and isoncotic plasma infusion, respectively. To ascertain the LTD4 actions that are independent of angiotensin II, saralasin (5 micrograms X kg-1 X min-1 iv) was also given throughout the study. LTD4 caused a significant increase in efferent arteriolar resistance in association with a fall in glomerular plasma flow rate (QA) and a rise in glomerular capillary hydraulic pressure. Despite the latter, single-nephron filtration rate fell due to combined reductions in QA and the glomerular ultrafiltration coefficient. These local glomerular constrictor actions of LTD4 support the possibility that this eicosanoid might play an important intermediary role in the functional impairment accompanying some forms of inflammatory injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":21347346,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"BosR (BB0647) controls the RpoN-RpoS regulatory pathway and virulence expression in Borrelia burgdorferi by a novel DNA-binding mechanism.\nIn Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative \u03c3 factor \u03c3\u2075\u2074 (RpoN) directly activates transcription of another alternative \u03c3 factor, \u03c3(S) (RpoS) which, in turn, controls the expression of virulence-associated membrane lipoproteins. As is customary in \u03c3\u2075\u2074-dependent gene control, a putative NtrC-like enhancer-binding protein, Rrp2, is required to activate the RpoN-RpoS pathway. However, recently it was found that rpoS transcription in Bb also requires another regulator, BosR, which was previously designated as a Fur or PerR homolog. Given this unexpected requirement for a second activator to promote \u03c3\u2075\u2074-dependent gene transcription, and the fact that regulatory mechanisms among similar species of pathogenic bacteria can be strain-specific, we sought to confirm the regulatory role of BosR in a second virulent strain (strain 297) of Bb. Indeed, BosR displayed the same influence over lipoprotein expression and mammalian infectivity for strain Bb 297 that were previously noted for Bb strain B31. We subsequently found that recombinant BosR (rBosR) bound to the rpoS gene at three distinct sites, and that binding occurred despite the absence of consensus Fur or Per boxes. This led to the identification of a novel direct repeat sequence (TAAATTAAAT) critical for rBosR binding in vitro. Mutations in the repeat sequence markedly inhibited or abolished rBosR binding. Taken together, our studies provide new mechanistic insights into how BosR likely acts directly on rpoS as a positive transcriptional activator. Additional novelty is engendered by the facts that, although BosR is a Fur or PerR homolog and it contains zinc (like Fur and PerR), it has other unique features that clearly set it apart from these other regulators. Our findings also have broader implications regarding a previously unappreciated layer of control that can be involved in \u03c3\u2075\u2074-dependent gene regulation in bacteria.","subset":"pubmed_abstract"} +{"meta":{"pmid":26835370,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":8}}},"text":"Autosomal ring chromosomes in human genetic disorders.\nRing chromosomes arise following breakage and rejoining in both chromosome arms. They are heterogeneous with variable size and genetic content and can originate from any chromosome. Phenotypes associated with ring chromosomes are highly variable as apart from any deletion caused by ring formation, imbalances from ring instability can also occur. Of interest is ring chromosome 20 which has a significant association with epilepsy with seizure onset in early childhood. Severe growth deficiency without major malformations is a common finding in the ring chromosome carrier. This phenotype associated with ring behaviour and mitotic instability and independent of the chromosome involved has been termed the \"ring syndrome\". Precise genotype-phenotype correlations for ring chromosomes may not be possible as influencing factors vary depending on the extent of deletion in ring formation, ring instability and the level of mosaicism. Although ring chromosomes usually arise as de novo events, familial transmission of rings from carrier to offspring has been described and prenatal diagnosis for any pregnancies should always be considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":12702722,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Direct interaction of focal adhesion kinase with p190RhoGEF.\nFocal adhesion kinase (FAK) is a protein-tyrosine kinase that associates with multiple cell surface receptors and signaling proteins through which it can modulate the activity of several intracellular signaling pathways. FAK activity can influence the formation of distinct actin cytoskeletal structures such as lamellipodia and stress fibers in part through effects on small Rho GTPases, although the molecular interconnections of these events are not well defined. Here, we report that FAK interacts with p190RhoGEF, a RhoA-specific GDP\/GTP exchange factor, in neuronal cells and in brain tissue extracts by co-immunoprecipitation and co-localization analyses. Using a two-hybrid assay and deletion mutagenesis, the binding site of the FAK C-terminal focal adhesion targeting (FAT) domain was identified within the C-terminal coiled-coil domain of p190RhoGEF. Binding was independent of a LD-like binding motif within p190RhoGEF, yet FAK association was disrupted by a mutation (Leu-1034 to Ser) that weakens the helical bundle structure of the FAK FAT domain. Neuro-2a cell binding to laminin increased endogenous FAK and p190RhoGEF tyrosine phosphorylation, and co-transfection of a dominant-negative inhibitor of FAK activity, termed FRNK, inhibited lamininstimulated p190RhoGEF tyrosine phosphorylation and p21 RhoA GTP binding. Overexpression of FAK in Neuro-2a cells increased both endogenous p190RhoGEF tyrosine phosphorylation and RhoA activity, whereas these events were inhibited by FRNK co-expression. Because insulin-like growth factor 1 treatment of Neuro-2a cells increased FAK tyrosine phosphorylation and enhanced p190RhoGEF-mediated activation of RhoA, our results support the conclusion that FAK association with p190RhoGEF functions as a signaling pathway downstream of integrins and growth factor receptors to stimulate Rho activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":24797265,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"O-Glycosylation of the N-terminal region of the serine-rich adhesin Srr1 of Streptococcus agalactiae explored by mass spectrometry.\nSerine-rich (Srr) proteins exposed at the surface of Gram-positive bacteria are a family of adhesins that contribute to the virulence of pathogenic staphylococci and streptococci. Lectin-binding experiments have previously shown that Srr proteins are heavily glycosylated. We report here the first mass-spectrometry analysis of the glycosylation of Streptococcus agalactiae Srr1. After Srr1 enrichment and trypsin digestion, potential glycopeptides were identified in collision induced dissociation spectra using X! Tandem. The approach was then refined using higher energy collisional dissociation fragmentation which led to the simultaneous loss of sugar residues, production of diagnostic oxonium ions and backbone fragmentation for glycopeptides. This feature was exploited in a new open source software tool (SpectrumFinder) developed for this work. By combining these approaches, 27 glycopeptides corresponding to six different segments of the N-terminal region of Srr1 [93-639] were identified. Our data unambiguously indicate that the same protein residue can be modified with different glycan combinations including N-acetylhexosamine, hexose, and a novel modification that was identified as O-acetylated-N-acetylhexosamine. Lectin binding and monosaccharide composition analysis strongly suggested that HexNAc and Hex correspond to N-acetylglucosamine and glucose, respectively. The same protein segment can be modified with a variety of glycans generating a wide structural diversity of Srr1. Electron transfer dissociation was used to assign glycosylation sites leading to the unambiguous identification of six serines and one threonine residues. Analysis of purified Srr1 produced in mutant strains lacking accessory glycosyltransferase encoding genes demonstrates that O-GlcNAcylation is an initial step in Srr1 glycosylation that is likely required for subsequent decoration with Hex. In summary, our data obtained by a combination of fragmentation mass spectrometry techniques associated to a new software tool, demonstrate glycosylation heterogeneity of Srr1, characterize a new protein modification, and identify six glycosylation sites located in the N-terminal region of the protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":30942775,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Kinetics of photocatalytic removal of imidacloprid from water by advanced oxidation processes with respect to nanotechnology.\nIn this study, the kinetics of photocatalytic removal of imidacloprid, a systemic chloronicotinoid insecticide, from water using two advanced oxidation systems (ZnO(normal)\/H2O2\/artificial sunlight and ZnO(nano)\/H2O2\/artificial sunlight) were investigated. Moreover, the effects of pH, insecticide concentration, catalyst concentration, catalyst particle size, and water type on the photocatalytic removal of imidacloprid were evaluated. Furthermore, total mineralization of imidacloprid under these advanced oxidation systems was evaluated by monitoring the decreases in dissolved organic carbon (DOC) concentrations and formation rate of inorganic ions (Cl- and NO2 -) with irradiation time using total organic carbon (TOC) analysis and ion chromatography to confirm the complete detoxification of imidacloprid in water. The degradation rate of imidacloprid was faster under the ZnO(nano)\/H2O2\/artificial sunlight system than the ZnO(normal)\/artificial sunlight system in both pure and river water. The photocatalytic degradation of imidacloprid under both advanced oxidation systems was affected by pH, catalyst concentration, imidacloprid concentration, and water type. Almost complete mineralization of imidacloprid was only achieved in the ZnO(nano)\/H2O2\/artificial sunlight oxidation system. The photogeneration rate of hydroxyl radicals was higher under the ZnO(nano)\/H2O2\/artificial sunlight system than the ZnO(normal)\/H2O2\/artificial sunlight system. Advanced oxidation processes, particularly those using nanosized zinc oxide, can be regarded as an effective photocatalytic method for imidacloprid removal from water.","subset":"pubmed_abstract"} +{"meta":{"pmid":22745437,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":3,"2024-18":1,"unknown":10}}},"text":"AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation.\nCurrent strategies to help tobacco smokers quit have limited success as a result of the addictive properties of the nicotine in cigarette smoke. We hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector expressing high levels of an anti-nicotine antibody would persistently prevent nicotine from reaching its receptors in the brain. To test this hypothesis, we constructed an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in na\u00efve mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the AAVantiNic vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity. In summary, a single administration of a gene transfer vector expressing a high-affinity anti-nicotine monoclonal antibody elicited persistent (18 weeks), high titers of an anti-nicotine antibody that obviated the physiologic effects of nicotine. If this degree of efficacy translates to humans, AAVantiNic could be an effective preventative therapy for nicotine addiction.","subset":"pubmed_abstract"} +{"meta":{"pmid":17080821,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2015-18":1,"unknown":7}}},"text":"Visualization tools for vorticity transport analysis in incompressible flow.\nVortices are undesirable in many applications while indispensable in others. It is therefore of common interest to understand their mechanisms of creation. This paper aims at analyzing the transport of vorticity inside incompressible flow. The analysis is based on the vorticity equation and is performed along pathlines which are typically started in upstream direction from vortex regions. Different methods for the quantitative and explorative analysis of vorticity transport are presented and applied to CFD simulations of water turbines. Simulation quality is accounted for by including the errors of meshing and convergence into analysis and visualization. The obtained results are discussed and interpretations with respect to engineering questions are given.","subset":"pubmed_abstract"} +{"meta":{"pmid":35248961,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":2,"2024-22":2,"2024-18":1,"2024-10":2,"unknown":8}}},"text":"Environmental levels of carbaryl impair zebrafish larvae behaviour: The potential role of ADRA2B and HTR2B.\nThe insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066-660 ng\/L), zebrafish larvae exhibit impairments in essential behaviours. Interestingly, the observed behavioural effects induced by carbaryl were acetylcholinesterase-independent. To elucidate the molecular initiating event that resulted in the observed behavioural effects, in silico predictions were followed by in vitro validation. We identified two target proteins that potentially interacted with carbaryl, the \u03b12B adrenoceptor (ADRA2B) and the serotonin 2B receptor (HTR2B). Using a pharmacological approach, we then tested the hypothesis that carbaryl had antagonistic interactions with both receptors. Similar to yohimbine and SB204741, which are prototypic antagonists of ADRA2B and HTR2B, respectively, carbaryl increased the heart rate of zebrafish larvae. When we compared the behavioural effects of a 24-h exposure to these pharmacological antagonists with those of carbaryl, a high degree of similarity was found. These results strongly suggest that antagonism of both ADRA2B and HTR2B is the molecular initiating event that leads to adverse outcomes in zebrafish larvae that have undergone 24 h of exposure to environmentally relevant levels of carbaryl.","subset":"pubmed_abstract"} +{"meta":{"pmid":24959865,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Ionizing radiation selectively reduces skin regulatory T cells and alters immune function.\nThe skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth's magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel.","subset":"pubmed_abstract"} +{"meta":{"pmid":9339409,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Anesthetic implications of epilepsy, status epilepticus, and epilepsy surgery.\nEpilepsy is a clinical paroxysmal disorder of recurring seizures, excluding alcohol or drug withdrawal seizures or such recurring exogenous events as repeated insulin-induced hypoglycemia. Epilepsy has a profound impact on each individual diagnosed with this disease. Seizures have been and are thought to arise as a result of abnormalities in (a) neural circuits, (b) excitation\/inhibition balance, (c) potassium, and (d) genetic abnormalities. Therapy for epilepsy is either medical, entailing the use of a variety of antiepileptic drugs, or surgical. An urgent approach to seizure control is indicated when status epilepticus occurs. When all standard therapy fails, general anesthesia can be used to control status epilepticus. Surgery is an option in the treatment of epilepsy and requires extensive preoperative evaluation. The primary concerns for the neuroanesthesiologist anesthetizing the patient with epilepsy are the capacity of anesthetics to modulate or potentiate seizure activity and the interaction of anesthetic drugs with antiepileptic drugs. Proconvulsant and anticonvulsant properties have been reported for nearly every anesthetic. If seizure spikes are to be evoked during seizure surgery, then light anesthesia with a proconvulsant anesthetic is used. Conscious analgesia can be used for awake seizure surgery. However, if electrocorticography is not planned, then a general anticonvulsant anesthetic maintenance regimen is used. The latter technique also may be useful in patients whose anesthetic management is complicated by an incidental history of epilepsy.","subset":"pubmed_abstract"} +{"meta":{"pmid":17855336,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2022-49":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-25":1,"2021-21":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-05":1,"2023-23":1,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"CD4 interacts constitutively with multiple CCR5 at the plasma membrane of living cells. A fluorescence recovery after photobleaching at variable radii approach.\nThe entry of human immunodeficiency virus into target cells requires successive interactions of the viral envelope glycoprotein gp120 with CD4 and the chemokine receptors CCR5 or CXCR4. We previously demonstrated, by F\u00f6rster resonance energy transfer experiments, the constitutive association of CD4 and CCR5 at the surface of living cells. We therefore speculated that this interaction may correlate with compartmentalization of CD4 and CCR5 within the plasma membrane. Here, we characterize the lateral distribution, the dynamics, and the stoichiometry of these receptors in living cells stably expressing CD4 and\/or CCR5 by means of fluorescence recovery after photobleaching at variable radii experiments. We found that (i) these receptors expressed alone are confined into 1-microm-sized domains, (ii) CD4-CCR5 associations occur outside and inside smaller domains, and (iii) these interactions involve multiple CCR5 molecules per CD4.","subset":"pubmed_abstract"} +{"meta":{"pmid":8179965,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Simian immunodeficiency virus SIVsmmPBj 1.9 induces multinucleated giant cell formation in human peripheral blood monocytes.\nSIVsmmPBJ 1.9 is an extremely virulent clone of the simian immunodeficiency virus SIVsmmPBj 14 that causes an acute lethal disease in pigtail macaques, with death occurring 6 to 8 days after infection. The disease is characterized by bloody mucoid diarrhea, lymphoid hyperplasia, and giant cell pneumonia. We have developed an in vitro model for the production of multinucleated giant cells (MGCs) in which peripheral blood monocytes rapidly fuse to form MGCs when cultured in lymphocyte-conditioned medium and antibody against class II MHC. We have tested the effect of SIVsmmPBj on monocytes in our MGC model system. Peripheral blood mononuclear cells (PBMCs) from normal healthy human subjects, when cultured in the presence of anti-class II MHC monoclonal antibody and SIVsmmPBj 1.9, but not either alone, resulted in the formation of MGCs within 4 days. Experiments using Transwell chambers indicated that such MGCs are formed by fusion of monocytes, not by virus-induced fusion of lymphocytes. SIVsmmPBj 1.9 is unique in inducing MGC formation in that other SIV and HIV isolates do not induce MGCs. Whereas SIVsmmPBj 1.9 grown in PBMCs was a potent inducer of MGCs in the presence of anti-class II MHC antibody, SIVsmmPBj 1.9 grown in CEMx174 failed to do so. Antibodies against IFN-gamma and TNF-alpha significantly inhibited SIVsmmPBj\/anti-class II-induced formation of MGCs. These results indicate that cytokines released in response to SIVsmmPBj 1.9, in conjunction with antibodies to class II MHC, caused fusion of monocytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":8078090,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons.\nThe gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 microgram\/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v\/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%.","subset":"pubmed_abstract"} +{"meta":{"pmid":27193800,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Dermoscopic and Immunohistochemical Changes in Acquired Melanocytic Nevi following Narrow-Band Ultraviolet B Therapy.\nAcquired melanocytic nevi (AMN) have been reported to undergo morphological and dermoscopic changes following exposure to narrow-band ultraviolet B (NB-UVB) radiation. To study the morphological, dermoscopic and immunohistochemical changes in AMN following NB-UVB radiation. Suberythemogenic NB-UVB sessions were delivered to 40 patients with AMN. For each patient, a minimum of 2 nevi were selected. One nevus was surgically removed from each patient prior to sessions as control; for the other nevus, dermoscopic images were captured before and after NB-UVB sessions. The images were evaluated for changes. At the end, another nevus was surgically removed for immunohistochemical assessment of Ki-67 and melan-A. Our study showed a statistically significant increase in the size of AMN following NB-UVB radiation. Benign dermoscopic changes were observed. Statistically significant positive correlations were found between some dermoscopic findings and the total cumulative dose of NB-UVB. Immunohistochemical analysis did not show any significant change in the exposed AMN. AMN irradiated with repeated suberythemogenic doses of NB-UVB showed benign morphological and dermoscopic changes, and this was confirmed by our immunohistochemical study.","subset":"pubmed_abstract"} +{"meta":{"pmid":28170441,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":17}}},"text":"Cerebrospinal fluid from patients with amyotrophic lateral sclerosis inhibits sonic hedgehog function.\nSonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterized by selective loss of motor neurons due to poorly understood mechanisms. Evidence indicates that Shh might play an important role in ALS, and that Shh signaling might be also adversely affected in ALS. Since little is known about the functional status of Shh pathway in patients with ALS, we therefore sought to determine whether Shh protein levels or biological activity in cerebrospinal fluid (CSF) was less in ALS patients than controls, and whether these measures could be correlated with ALS disease severity and disease progression, and with other CSF analytes of biological interest in ALS. Comparing Shh levels in the CSF of normal controls (n = 13), neurological controls (n = 12), and ALS patients (n = 9) measured by ELISA, we found that CSF Shh levels were not different between controls and ALS patients. However, when assessing Shh biological activity in CSF using in vitro cell-based assays, which measure Shh activity as inducible Gli-driven luminescence, we found that in the presence of exogenous recombinant Shh or the Shh agonist, purmorphamine, the inducible activity of CSF was significantly augmented in the control groups as expected, but not in the ALS group, suggesting the presence of an inhibitor of Shh signaling in ALS CSF samples. Since purmorphamine acts on Smoothened, downstream of Shh and its receptor Patched, the inhibitory action is downstream of Smoothened. Our results also demonstrated that while the inhibitory effect of ALS CSF on Shh signaling did not correlate significantly with ALS disease characteristics, the levels of IL-1\u03b2 and TNF-\u03b1 did. In addition to being significantly elevated in ALS CSF, these cytokines negatively correlated with the disease duration, whereas GDF11 was a favorable predictor of ALS clinical score. We also found that TNF-\u03b1 significantly inhibited Shh biological activity in vitro, potentially suggesting a novel role of TNF-\u03b1 in ALS pathogenesis. Collectively, this is the first report demonstrating that Shh signaling in CSF of ALS patients is compromised.","subset":"pubmed_abstract"} +{"meta":{"pmid":16912630,"dup_signals":{"dup_doc_count":12}},"text":"Acute rhabdomyolysis complicating status asthmaticus in children: case series and review.\nTo describe a case series of 4 children who developed acute rhabdomyolysis as a complication of acute respiratory failure secondary to status asthmaticus. A retrospective review of all children who were admitted to our pediatric intensive care unit (PICU) with status asthmaticus from November 1998 through July 2004 was performed and all children who developed acute rhabdomyolysis, defined as a 5-fold increase above the upper limit of normal in the serum creatine phosphokinase (CPK) concentration (CPK > or = 1250 IU\/L), were identified. Demographic and clinical data were abstracted from the medical record. During the study period, 108 children with status asthmaticus were admitted to our PICU (3.6% of all admissions). Four children (age 12-19 years) developed acute respiratory failure requiring mechanical ventilation, and all 4 of these children (3.7% of all children with status asthmaticus admitted to the PICU) developed acute rhabdomyolysis. The 4 children who developed acute rhabdomyolysis were older than the children with status asthmaticus, without rhabdomyolysis (median age 15 years vs. 5 years). Acute rhabdomyolysis complicating status asthmaticus may be more common than previously ascertained. We therefore suggest that CPK levels should be followed closely in all children with status asthmaticus and acute respiratory failure. The early presentation of rhabdomyolysis in the current series suggests that factors other than corticosteroids and neuromuscular blockers are potentially involved. Mechanical ventilation and older age seem to be significant risk factors for rhabdomyolysis, perhaps implicating a mechanism similar to the pathogenesis of severe exercise-related rhabdomyolysis. Further clinical study of the incidence and causative factors of rhabdomyolysis in this population is warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":10403250,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2019-39":1,"2019-30":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2021-17":1,"2015-18":1}}},"text":"Mox2 is a component of the genetic hierarchy controlling limb muscle development.\nThe skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate into the limb-bud mesenchyme. Among the genes known to be important for muscle development in mammalian embryos are those encoding the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs; MyoD, Myf5, myogenin and MRF4) and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. Here we show that mice homozygous for a null mutation of Mox2 have a developmental defect of the limb musculature, characterized by an overall reduction in muscle mass and elimination of specific muscles. Mox2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes, as demonstrated by the downregulation of Pax3 and Myf5 but not MyoD in Mox2-deficient limb buds. Our findings show that the MOX2 homeoprotein is an important regulator of vertebrate limb myogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":12795696,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Protein interaction analysis of SCF ubiquitin E3 ligase subunits from Arabidopsis.\nUbiquitin E3 ligases are a diverse family of protein complexes that mediate the ubiquitination and subsequent proteolytic turnover of proteins in a highly specific manner. Among the several classes of ubiquitin E3 ligases, the Skp1-Cullin-F-box (SCF) class is generally comprised of three 'core' subunits: Skp1 and Cullin, plus at least one F-box protein (FBP) subunit that imparts specificity for the ubiquitination of selected target proteins. Recent genetic and biochemical evidence in Arabidopsis thaliana suggests that post-translational turnover of proteins mediated by SCF complexes is important for the regulation of diverse developmental and environmental response pathways. In this report, we extend upon a previous annotation of the Arabidopsis Skp1-like (ASK) and FBP gene families to include the Cullin family of proteins. Analysis of the protein interaction profiles involving the products of all three gene families suggests a functional distinction between ASK proteins in that selected members of the protein family interact generally while others interact more specifically with members of the F-box protein family. Analysis of the interaction of Cullins with FBPs indicates that CUL1 and CUL2, but not CUL3A, persist as components of selected SCF complexes, suggesting some degree of functional specialization for these proteins. Yeast two-hybrid analyses also revealed binary protein interactions between selected members of the FBP family in Arabidopsis. These and related results are discussed in terms of their implications for subunit composition, stoichiometry and functional diversity of SCF complexes in Arabidopsis.","subset":"pubmed_abstract"} +{"meta":{"pmid":19671882,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24: influence on heritable autonomic traits in twin pairs.\nNicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine alpha and four beta subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by alpha3, alpha5, and beta4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced approximately 15 kilobase pairs in 15q24 containing their coding and 5'- and 3'-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.","subset":"pubmed_abstract"} +{"meta":{"pmid":24855453,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2015-48":1,"2015-06":1,"2015-18":1}}},"text":"The synergistic effect of homocysteine and lipopolysaccharide on the differentiation and conversion of raw264.7 macrophages.\nMacrophages play pivotal roles in the progression of atherosclerosis (AS) and their heterogeneous differentiation patterns have been studied extensively. The classical subtype of activated macrophage, M1, promotes the progression of AS. Conversely, the alternative subtype of activated macrophage, M2, is regarded as a repressor of AS. Homocysteine (Hcy) may influence macrophage subtype polarization both in vivo and in vitro. Homocysteinemia (HHcy) is an independent risk factor in coronary heart disease and the effect of Hcy on macrophage differentiation has not been studied until now. Different concentrations of Hcy in combination with a fixed concentration of lipopolysaccharide (LPS, 200 ng\/mL) were used to treat RAW264.7 macrophages. Real-time PCR was used to detect and quantify RNA transcripts indicative of M1 and M2 differentiation. The efficacy and specificity for each chemical stimulant in inducing macrophage differentiation were also investigated. The M2 macrophages (anti-inflammatory subtype) induced using classical methods (IL-4, 10 ng\/mL) were also treated with different concentrations of Hcy complemented with LPS. The synergistic effect of Hcy and LPS in the converting the M2 subtype to M1 was also studied. Macrophages can be induced to differentiate towards M1 by a combination of Hcy with LPS, with the strongest effect observed at an Hcy concentration of 50 \u03bcmol\/L. After inducing macrophages to the M2 subtype using IL-4, treatment with both Hcy and LPS could elicit conversion from the M2 to M1 subtype. Combined treatment with Hcy and LPS can induce the polarization of cultured RAW264.7 macrophages into the pro-inflammatory subtype, as well as promote subtype conversion from anti-inflammatory to pro-inflammatory.","subset":"pubmed_abstract"} +{"meta":{"pmid":8239982,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-18":1,"unknown":6}}},"text":"Gene delivery systems in surgery.\nIncreased understanding of the genetic basis of human disease has led to a number of potential gene-based therapies for various medical and surgical disorders. The development of efficient methods for delivering genes to mammalian cells in vitro has increased the potential clinical utility of gene-based therapies; however, a major focus of research has been more efficient delivery to appropriate target cells, in vivo as well as in vitro, to establish gene therapy as an effective clinical modality for common disorders. Despite substantial progress, a number of critical technical issues to enhance and optimize not only gene transfer but also gene expression must be resolved. These future technological developments will be essential for the widespread clinical implementation of gene-based therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28271234,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Impact of prior biologic use on persistence of treatment in patients with psoriatic arthritis enrolled in the US Corrona registry.\nPsoriatic arthritis (PsA) is a chronic condition characterized by a diverse set of symptoms, from swollen joints to nail disease to skin disease. A variety of treatment options are available, including tumor necrosis factor inhibitors (TNFis). Little is known about treatment persistence in patients with PsA who initiate TNFi therapy, with and without prior biologic use. This study assessed persistence in these subgroups of patients with PsA and identified factors associated with persistence. This retrospective study utilized data from the Corrona registry of patients with PsA-with or without prior biologic experience-who initiated TNFi therapy between October 1, 2002, and March 21, 2013. Kaplan-Meier curves estimated median time to nonpersistence (discontinuation or switch to another biologic). Cox proportional hazards models identified factors associated with TNFi nonpersistence. A total of 1241 TNFi initiations were identified: 549 by biologic-na\u00efve and 692 by biologic-experienced patients. Through 4 years of follow-up, more biologic-na\u00efve than biologic-experienced patients remained persistent. Biologic-na\u00efve patients had a greater mean time to nonpersistence compared with biologic-experienced patients: 32 vs 23 months (p = 0.0002). Moderate and high disease activities based on clinical disease activity index and disease duration were associated with persistence in both biologic-na\u00efve and biologic-experienced patients. Additionally, in the biologic-experienced patients, the number of prior medications and skin disease were associated with persistence. The majority of patients with PsA in this study were persistent with their TNFi therapy; biologic-na\u00efve patients had greater persistence compared with biologic-experienced patients. Predictors of persistence differed slightly between biologic-na\u00efve and biologic-experienced patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":23039995,"dup_signals":{"dup_doc_count":78,"dup_dump_count":38,"dup_details":{"curated_sources":2,"2023-50":8,"2023-40":3,"2023-23":4,"2023-14":4,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":3,"2022-21":2,"2022-05":3,"2021-49":1,"2021-43":1,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":2,"2020-45":3,"2020-16":1,"2019-13":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-30":4,"2018-22":1,"2018-17":1,"2018-13":2,"2018-05":1,"2017-51":2,"2017-43":2,"2017-34":2,"2024-26":3,"2024-22":3,"2024-18":1}}},"text":"Changes in brain morphology in albinism reflect reduced visual acuity.\nAlbinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream.","subset":"pubmed_abstract"} +{"meta":{"pmid":32281954,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Coronary stent embolism to the right posterior cerebral artery.\nA 57-year-old male was admitted to the emergency room with chest pain that has been present for 3 hours. His blood pressure was 70\/50 mmHg and heart rate was 48 bpm. 12-lead surface electrocardiography revealed inferior myocardial infarction and third-degree atrioventricular (AV) block. An emergency coronary angiography showed a 50% stenosis in the middle segment of the left anterior descending artery and 90% in the proximal circumflex (Cx) artery. The right coronary artery was totally occluded. After the predilatation with a 2.0x15 mm compliant balloon at 10 atm, a 3.5x24 mm bare metal stent was implanted. The third-degree AV block improved and a sinus rhythm of 124 bpm was achieved, but hemodynamic stability was not attained. Percutaneous coronary intervention for the Cx artery was performed. Without predilatation, a 3.5x12 mm low profile BMS was easily advanced over the lesion. Just before the stent implantation, asystole developed, followed by convulsions. Blood pressure and heart rate recovered after the administration of 1 mg of atropine. However, during the seizure, the guidewire and coronary stent device fell to the aortic root. Stent struts were not seen on the balloon catheter in a fluoroscopic examination. Fluoroscopic scanning of the vascular system showed that the coronary stent was in the right posterior cerebral artery. There were no symptoms or signs of neurological disorder. Consultant invasive neuroradiologist recommended medical follow-up. Clopidogrel and acetylsalicylic acid were prescribed indefinitely. Two months after the primary PCI, a successful coronary artery bypass graft operation was performed. After 4 years, the patient remained without any symptoms of neurological problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":19821444,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"The impact of conditional cash transfers on health outcomes and use of health services in low and middle income countries.\nConditional cash transfers (CCT) provide monetary transfers to households on the condition that they comply with some pre-defined requirements. CCT programmes have been justified on the grounds that demand-side subsidies are necessary to address inequities in access to health and social services for poor people. In the past decade they have become increasingly popular, particularly in middle income countries in Latin America. To assess the effectiveness of CCT in improving access to care and health outcomes, in particular for poorer populations in low and middle income countries. We searched a wide range of international databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, in addition to development studies and economic databases. We also searched the websites and online resources of numerous international agencies, organisations and universities to find relevant grey literature. The original searches were conducted between November 2005 and April 2006. An updated search in MEDLINE was carried out in May 2009. CCT were defined as monetary transfers made to households on the condition that they comply with some pre-determined requirements in relation to health care. Studies had to include an objective measure of at least one of the following outcomes: health care utilisation, health expenditure, health outcomes or equity outcomes. Eligible study designs were: randomised controlled trial, interrupted time series analysis, or controlled before-after study of the impact of health financing policies following criteria used by the Cochrane Effective Practice and Organisation of Care Group. We performed qualitative analysis of the evidence. We included ten papers reporting results from six intervention studies. Overall, design quality and analysis limited the risks of bias. Several CCT programmes provided strong evidence of a positive impact on the use of health services, nutritional status and health outcomes, respectively assessed by anthropometric measurements and self-reported episodes of illness. It is hard to attribute these positive effects to the cash incentives specifically because other components may also contribute. Several studies provide evidence of positive impacts on the uptake of preventive services by children and pregnant women. We found no evidence about effects on health care expenditure. Conditional cash transfer programmes have been the subject of some well-designed evaluations, which strongly suggest that they could be an effective approach to improving access to preventive services. Their replicability under different conditions - particularly in more deprived settings - is still unclear because they depend on effective primary health care and mechanisms to disburse payments. Further rigorous evaluative research is needed, particularly where CCTs are being introduced in low income countries, for example in Sub-Saharan Africa or South Asia.","subset":"pubmed_abstract"} +{"meta":{"pmid":347958,"dup_signals":{"dup_doc_count":17,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-22":1,"2019-18":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2020-34":1}}},"text":"The influence of acetylator phenotype on the response to sulfalene in individuals with chloroquine-resistant falciparum malaria.\nThe disposition of sulfalene was studied in eight individuals before and during an infection with a chloroquine-resistant strain of Plasmodium falciparum. Isoniazid acetylator phenotype was determined in each individual prior to the administration of sulfalene. Following the administration of sulfalene before infection with malaria, a significant difference in half-life of non-acetylated sulfalene and percent acetylation of sulfalene in plasma was observed between rapid and slow acetylators. When sulfalene was administered during malaria, this difference was no longer apparent. Individuals who did not respond to the therapeutic administration of sulfalene alone were treated with a combination of sulfalene and pyrimethamine. Three individuals were cured by sulfalene without pyrimethamine and one was cured by the drug combination. Three of the four individuals who were not cured by any dose of sulfalene or the drug combination were slow acetylators. There was no distinct correlation between clinical response and maximum levels or half-life of nonacetylated sulfalene. These findings suggest that acetylator phenotype does not influence the therapeutic response of individuals infected with falciparum malaria to sulfalene or to the combination of sulfalene and pyrimethamine. Further information is presented, however, to confirm the importance of an as yet unidentified host factor(s) in determining therapeutic response to these agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":18368624,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Clustering and periodicity of neurofibrillary tangles in the upper and lower cortical laminae in Alzheimer's disease.\nIn Alzheimer's disease (AD), neurofibrillary tangles (NFT) occur within neurons in both the upper and lower cortical laminae. Using a statistical method that estimates the size and spacing of NFT clusters along the cortex parallel to the pia mater, two hypotheses were tested: 1) that the cluster size and distribution of the NFT in gyri of the temporal lobe reflect degeneration of the feedforward (FF) and feedback (FB) cortico-cortical pathways, and 2) that there is a spatial relationship between the clusters of NFT in the upper and lower laminae. In 16 temporal lobe gyri from 10 cases of sporadic AD, NFT were present in both the upper and lower laminae in 11\/16 (69%) gyri and in either the upper or lower laminae in 5\/16 (31%) gyri. Clustering of the NFT was observed in all gyri. A significant peak-to-peak distance was observed in the upper laminae in 13\/15 (87%) gyri and in the lower laminae in 8\/12 (67%) gyri, suggesting a regularly repeating pattern of NFT clusters along the cortex. The regularly distributed clusters of NFT were between 500 and 800 microm in size, the estimated size of the cells of origin of the FF and FB cortico-cortical projections, in the upper laminae of 6\/13 (46%) gyri and in the lower laminae of 2\/8 (25%) gyri. Clusters of NFT in the upper laminae were spatially correlated (in phase) with those in the lower laminae in 5\/16 (31%) gyri. The clustering patterns of the NFT are consistent with their formation in relation to the FF and FB cortico-cortical pathways. In most gyri, NFT clusters appeared to develop independently in the upper and lower laminae.","subset":"pubmed_abstract"} +{"meta":{"pmid":31636508,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-21":1,"2021-17":1,"2020-45":1,"2020-40":2,"2020-29":1,"2020-16":1,"2023-40":1,"2024-10":1,"2024-30":1}}},"text":"Understanding job satisfaction and motivation among nurses in public health facilities of Ethiopia: a cross-sectional study.\nPoor job conditions and limited resources are reducing job satisfaction and motivation among nurses in low-income countries, which may affect the quality of services and attrition rates. The objective of this study was to examine job satisfaction, motivation and associated factors among nurses working in the public health facilities of Ethiopia, with the aim of improving performance and productivity in the health care system. The study employed a cross-sectional two-stage cluster sampling design. From a random sample of 125 health facilities, 424 nurses were randomly selected for face-to-face interviews in all regions of Ethiopia. Nurses responded to questions about their overall job satisfaction and job conditions, including items related to intrinsic and extrinsic motivation, using a 5-point Likert scale. Multilevel analysis was performed to adjust for different clustering effects. Satisfaction levels (percent of respondents who were satisfied) were calculated for individual items, and composite mean scores (range: 1-5) were calculated for motivational factors. Adjusted odds ratios were computed to examine the association of these factors with overall job satisfaction. Overall, 60.8% of nurses expressed satisfaction with their job. Composite mean scores for intrinsic and extrinsic motivational factors were 3.5 and 3.0, respectively. Job satisfaction levels were significantly higher for female nurses (65.6%, p = 0.04), those older than 29 years (67.8%, p = 0.048) and had over 10 years work experiences (68.8%, p = 0.007). Satisfaction with remuneration (AOR = 2.04, 95% CI = 1.36, 3.06), recognition (AOR = 2.21; 95% CI = 1.38, 3.53), professional advancement (AOR = 1.54; 95% CI = 1.06, 2.29), features of the work itself (AOR = 1.65; 95% CI = 1.20, 2.91) and nurses' work experiences from 5 to 10 years (AOR = 0.37, 95% CI = 0.17, 0.79) were significantly associated with overall job satisfaction after controlling for other predictors. The study findings are signals for the Ministry of Health to strengthen the human resource management system and practices to improve nurses' overall job satisfaction and motivation, especially among nurses with 5 to 10 years of experience on the job. Expanded recognition systems and opportunities for advancement are required to increase nurses' job satisfaction and motivation. Equitable salary and fringe benefits are also needed to reduce their dissatisfaction with the job.","subset":"pubmed_abstract"} +{"meta":{"pmid":18297400,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"The study of mentoring in the learning environment (SMILE): a randomized evaluation of the effectiveness of school-based mentoring.\nThe effect of providing youth school-based mentoring (SBM), in addition to other school-based support services, was examined with a sample of 516 predominately Latino students across 19 schools. Participants in a multi-component, school-based intervention program run by a youth development agency were randomly assigned to one of two conditions: (1) supportive services alone or (2) supportive services plus SBM. Compared to community-based mentoring, the duration of the SBM was brief (averaging eight meetings), partly because the agency experienced barriers to retaining mentors. Intent-to-treat (ITT) main effects of SBM were tested using hierarchical linear modeling (HLM) and revealed small, positive main effects of mentoring on self-reported connectedness to peers, self-esteem (global and present-oriented), and social support from friends, but not on several other measures, including grades and social skills. Three-way cross-level interactions of sex and school level (elementary, middle, and high school) revealed that elementary school boys and high school girls benefited the most from mentoring. Among elementary school boys, those in the mentoring condition reported higher social skills (empathy and cooperation), hopefulness, and connectedness both to school and to culturally different peers. Among high school girls, those mentored reported greater connectedness to culturally different peers, self-esteem, and support from friends. Findings suggest no or iatrogenic effects of mentoring for older boys and younger girls. Therefore, practitioners coordinating multi-component programs that include SBM would be wise to provide mentors to the youth most likely to benefit from SBM and bolster program practices that help to support and retain mentors.","subset":"pubmed_abstract"} +{"meta":{"pmid":24191696,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis.\nMultiple sclerosis (MS) is a complex disease influenced by genetic and environmental contributing factors. Endocrine disrupting compounds (EDCs) such as bisphenol A (BPA) affect gene expression and hormone-regulated systems throughout the body. We investigated the effects of BPA on Theiler's-virus induced demyelination (TVID), a mouse model of MS. Perinatal BPA exposure, combined with viral infection, resulted in a decreased level of viral antibodies, accelerated the onset of TVID symptoms, increased inflammation in both the spinal cord and digestive tract, and amplified immune-related gene expression changes induced by viral infection. These results demonstrate the effect of BPA on the trajectory of TVID, and illustrate how multiple factors collectively influence autoimmune disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":19945926,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Type-D personality and body image in men: the role of exercise status.\nThe 'Distressed' or Type-D personality is described by the interaction between high levels of negative affectivity and social inhibition. This study investigated the prevalence of Type-D personality in men of different exercise status, the association between Type-D and body image perceptions, and the moderating effect of exercise status. Participants were 564 British males aged between 18 and 55 years. Of these 200 were classified as sedentary, 148 as active and 216 as weight trainers. Participants completed the DS14 and Multidimensional Body-Self Relations Questionnaire. Results showed that more individuals were classified as Type-D in the sedentary group (45%) than the two active groups, and in the weight training (24.5%) than the active (14.2%) group. Both Type-D and a sedentary lifestyle were associated with a significantly poorer body image. However, exercise mode was not associated with body image differences. Sedentary Type-D men scored significantly lower in Body Areas Satisfaction and higher in Self-Classified Weight than both active groups. Regular exercise might provide a pathway for Type-D men to develop a more positive body image.","subset":"pubmed_abstract"} +{"meta":{"pmid":22033916,"dup_signals":{"dup_doc_count":15,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2019-47":1}}},"text":"Authentication analysis of red fruit (Pandanus Conoideus Lam) oil using FTIR spectroscopy in combination with chemometrics.\nRed fruit (Pandanus conoideus Lam) is endemic plant of Papua, Indonesia and Papua New Guinea. The price of its oil (red fruit oil, RFO) is 10-15 times higher than that of common vegetable oils; consequently, RFO is subjected to adulteration with lower price oils. Among common vegetable oils, canola oil (CaO) and rice bran oil (RBO) have similar fatty acid profiles to RFO as indicated by the score plot of principal component analysis; therefore, CaO and RBO are potential adulterants in RFO. To develop FTIR spectroscopy in combination with chemometrics of partial least square regression (PLSR) and discriminant analysis (DA) for authentication of RFO from CaO and RBO. The presence of CaO in RFO was better determined at frequency regions of 1200-1050 cm\u207b\u00b9; meanwhile, the combined frequency ranges of 1207-1078 and 1747-1600 cm\u207b\u00b9 were exploited for quantitative analysis of RBO with acceptable values of coefficient of determination (R\u00b2) and errors in calibration, prediction and during cross validation. DA based on Mahalanobis distance was able to discriminate between RFO and RFO adulterated with CaO and RBO. FTIR spectroscopy combined with PLSR and DA can be successfully used for quantification and classification of oil adulterants in RFO. The developed method is rapid and environmentally friendly and sample preparation is easy.","subset":"pubmed_abstract"} +{"meta":{"pmid":24111933,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":8}}},"text":"Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force.\nAn international consensus group of clinician-researchers in epilepsy, neurology, neuropsychology, and neuropsychiatry collaborated with the aim of developing clear guidance on standards for the diagnosis of psychogenic nonepileptic seizures (PNES). Because the gold standard of video electroencephalography (vEEG) is not available worldwide, or for every patient, the group delineated a staged approach to PNES diagnosis. Using a consensus review of the literature, this group evaluated key diagnostic approaches. These included: history, EEG, ambulatory EEG, vEEG\/monitoring, neurophysiologic, neurohumoral, neuroimaging, neuropsychological testing, hypnosis, and conversation analysis. Levels of diagnostic certainty were developed including possible, probable, clinically established, and documented diagnosis, based on the availability of history, witnessed event, and investigations, including vEEG. The aim and hope of this report is to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures.","subset":"pubmed_abstract"} +{"meta":{"pmid":32855765,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":9}}},"text":"Mitochondrial and Peroxisomal Alterations Contribute to Energy Dysmetabolism in Riboflavin Transporter Deficiency.\nRiboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by progressive pontobulbar palsy, sensory and motor neuron degeneration, sensorineural hearing loss, and optic atrophy. As riboflavin (RF) is the precursor of FAD and FMN, we hypothesize that both mitochondrial and peroxisomal energy metabolism pathways involving flavoproteins could be directly affected in RTD, thus impacting cellular redox status. In the present work, we used induced pluripotent stem cells (iPSCs) from RTD patients to investigate morphofunctional features, focusing on mitochondrial and peroxisomal compartments. Using this model, we document the following RTD-associated alterations: (i) abnormal colony-forming ability and loss of cell-cell contacts, revealed by light, electron, and confocal microscopy, using tight junction marker ZO-1; (ii) mitochondrial ultrastructural abnormalities, involving shape, number, and intracellular distribution of the organelles, as assessed by focused ion beam\/scanning electron microscopy (FIB\/SEM); (iii) redox imbalance, with high levels of superoxide anion, as assessed by MitoSOX assay accompanied by abnormal mitochondrial polarization state, evaluated by JC-1 staining; (iv) altered immunofluorescence expression of antioxidant systems, namely, glutathione, superoxide dismutase 1 and 2, and catalase, as assessed by quantitatively evaluated confocal microscopy; and (v) peroxisomal downregulation, as demonstrated by levels and distribution of fatty acyl \u03b2-oxidation enzymes. RF supplementation results in amelioration of cell phenotype and rescue of redox status, which was associated to improved ultrastructural features of mitochondria, thus strongly supporting patient treatment with RF, to restore mitochondrial- and peroxisomal-related aspects of energy dysmetabolism and oxidative stress in RTD syndrome.","subset":"pubmed_abstract"} +{"meta":{"pmid":3036998,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription\/translation.\nWe determined the structural basis for the presence of electrophoretically-distinct, antigenically-related forms of invariant chains in Ia oligomers, and established the mechanisms by which they can be expressed from a single gene. S1 nuclease protection assays indicated that, in B cells, transcription of this gene initiates at a minimum of three sites. Thus, unlike previously thought, invariant chain mRNAs have heterogeneous 5' untranslated segments that may differentially affect initiation of translation. Further, restriction mapping and nucleotide sequencing of cDNAs revealed two kinds of invariant chain mRNAs differing by an internal coding segment of 192 bp. This segment represents an alternatively spliced exon, as demonstrated by nucleotide sequencing of corresponding genomic regions. The exon (exon X) encodes a cysteine-rich stretch of 64 amino acids near the COOH terminus that displays a striking and surprising homology to an internal amino acid repeat of thyroglobulin, suggesting an evolutionary mechanism of exon shuffling. Transient expression of cDNAs indicated that both types of alternatively spliced mRNAs contain two in-frame AUGs functioning as alternate start sites for translation. Thus, transfections with exon X-lacking cDNAs resulted in the expression of Mr 33,000 and 31,000 proteins, detected by immunoprecipitation with anti-invariant chain antisera, and identical by two-dimensional gel (2-D) analyses to the B cell invariant-chain forms gamma 1 (Mr 31,000), gamma 2, and gamma 3 (Mr 33,000). Similarly, exon X-containing cDNAs expressed Mr 43,000 and 41,000 proteins, also identical by 2-D migration to Ia-associated proteins. Thus, human Ia molecules contain four forms of invariant chain of closely related but nonidentical primary structure that are generated from a single gene by a complex pattern of alternate transcriptional start, exon splicing, and translational start.","subset":"pubmed_abstract"} +{"meta":{"pmid":3197985,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Effects of morphine on the human sphincter of Oddi.\nThe effects of morphine on intraluminal pressures recorded from the sphincter of Oddi (SO) at endoscopic retrograde cholangiopancreatography in 19 patients who were without evidence of biliary or pancreatic disease were studied. Morphine was given in four successive doses of 2.5, 2.5, 5, and 10 micrograms\/kg iv at five minute intervals. Morphine in subanalgesic doses increased the frequency of SO phasic pressure waves to a maximum of 10-12\/min, caused the phasic waves to occur simultaneously along the sphincter segment, increased phasic wave amplitude from 72 (26) (SE) to 136 (31) mmHg, and increased SO basal pressure from 10 (1) to 29 (9) mmHg (p less than 0.05). The effects of morphine on the SO are mediated by more than one opioid receptor type, as naloxone competitively antagonised the increase in phasic wave frequency induced by morphine, but did not affect the increase in SO basal pressure elicited by morphine. When given after naloxone, morphine decreased phasic wave amplitude, an inhibitory effect that is normally masked by morphine's dominant naloxone sensitive excitatory effect. Mu receptors do not appear to be involved in control of spontaneous SO motor function, as naloxone alone did not affect SO motor activity. The excitatory effects of morphine on the SO are not mediated by cholinergic nerves, as they were not blocked by atropine. Cholinergic nerves, however, may have a role in regulating spontaneous SO motor function because atropine alone depressed phasic wave activity and basal pressure. Although morphine does cause 'spasm' of the human SO, its effects are more complex than is commonly believed.","subset":"pubmed_abstract"} +{"meta":{"pmid":34791187,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Clinician responses to cannabis use during pregnancy and lactation: a systematic review and integrative mixed-methods research synthesis.\nPerinatal cannabis use is increasing, and clinician counselling is an important aspect of reducing the potential harm of cannabis use during pregnancy and lactation. To understand current counselling practices, we conducted a systematic review and integrative mixed-methods synthesis to determine \"how do perinatal clinicians respond to pregnant and lactating patients who use cannabis?\" We searched 6 databases up until 2021-05-31. Eligible studies described the attitudes, perceptions, or beliefs of perinatal clinician about cannabis use during pregnancy or lactation. Eligible clinicians were those whose practice particularly focusses on pregnant and postpartum patients. The search was not limited by study design, geography, or year. We used a convergent integrative analysis method to extract relevant findings for inductive analysis. Thirteen studies were included; describing perspectives of 1,366 clinicians in 4 countries. We found no unified approach to screening and counselling. Clinicians often cited insufficient evidence around the effects of perinatal cannabis use and lacked confidence in counselling about use. At times, this meant clinicians did not address cannabis use with patients. Most counselled for cessation and there was little recognition of the varied reasons that patients might use cannabis, and an over-reliance on counselling focussed on the legal implications of use. Current approaches to responding to cannabis use might result in inadequate counselling. Counselling may be improved through increased education and training, which would facilitate conversations to mitigate the potential harm of perinatal cannabis use while recognizing the benefits patients perceive.","subset":"pubmed_abstract"} +{"meta":{"pmid":23016848,"dup_signals":{"dup_doc_count":13}},"text":"Impact of periictal interventions on respiratory dysfunction, postictal EEG suppression, and postictal immobility.\nSudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Seizure-related respiratory dysfunction (RD), the duration of postictal generalized electroencephalography (EEG) suppression (PGES), and duration of postictal immobility (PI) may be important in the pathophysiology of SUDEP. Periictal interventions may reduce the risk of SUDEP. We assessed the impact of periictal nursing interventions on RD, PGES, and PI duration in patients with localization-related epilepsy and secondarily generalized convulsions (GCs) recorded during video-EEG telemetry in the epilepsy monitoring unit. Video-EEG data were retrospectively reviewed. Interventions including administration of supplemental oxygen, oropharyngeal suction, and patient repositioning were evaluated. Interventions were performed based on nursing clinical judgment at the bedside and were not randomized. The two-sided Wilcoxon rank-sum test was used to compare GCs with and those without intervention. Robust simple linear regression was used to assess the association between timing of intervention and duration of hypoxemia (SaO(2) < 90%), PGES, and PI using data from only the first GC for each patient. Data from 39 patients with 105 GCs were analyzed. PGES >2 s occurred following 31 GCs in 16 patients. There were 21 GCs with no intervention (NOINT) and 84 GC with interventions (INT). In the INT group, the duration of hypoxemia was shorter (p = 0.0014) when intervention occurred before hypoxemia onset (mean duration 53.1 s) than when intervention was delayed (mean duration 132.42 s). Linear regression indicated that in GCs with nursing interventions, earlier intervention was associated with shorter duration of hypoxemia (p < 0.0001) and shorter duration of PGES (p = 0.0012). Seizure duration (p < 0.0001) and convulsion duration (p = 0.0457) were shorter with earlier intervention. PI duration was longer for GCs with PGES than GCs without PGES (p < 0.0001). The mean delay to first active nonrespiratory movement following GCs with PGES was 251.96 s and for GC without PGES was 66.06 s. The duration of PI was positively associated with lower SaO(2) nadir (p = 0.003) and longer duration of oxygen desaturation (p = 0.0026). There was no association between PI duration and seizure duration (p = 0.773), between PI duration and PGES duration (p = 0.758), or between PI duration and the timing of first intervention relative to seizure onset (p = 0.823). PGES did not occur in the NOINT group. The mean duration of desaturation was longer (110.9 vs. 49.9 s) (p < 0.0001), mean SaO(2) nadir was lower (72.8% vs. 79.7%) (p = 0.0086), and mean end-tidal CO(2) was higher (58.6 vs. 50.3 mmHg) (p = 0.0359) in the INT group compared with the NOINT group. The duration of the seizure or of the convulsive component was not significantly different between the INT and NOINT groups. Early periictal nursing intervention was associated with reduced duration of RD and reduced duration of PGES. These findings suggest the possibility that such interventions may be effective in reducing the risk of SUDEP in the outpatient setting. Validation of these preliminary data with a prospective study is needed before definitive conclusions can be reached regarding the efficacy of periictal interventions in reducing the risk of SUDEP.","subset":"pubmed_abstract"} +{"meta":{"pmid":25258516,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Effects on caregiver burden of a donepezil hydrochloride dosage increase to 10 mg\/day in patients with Alzheimer's disease.\nIn this study, we evaluated changes in functioning and caregiver burden in Alzheimer's disease (AD) patients after a dosage increase that was made based on pharmacists' evaluation of AD patients' behavior in daily life. Pharmacists used a checklist, a questionnaire, and the Repetitive Saliva Swallowing Test (RSST) to gather data on the daily life of AD patients taking donepezil 5 mg\/day and their caregivers. In 27 cases, pharmacists suggested a dosage change to 10 mg\/day to AD patients' physicians. Pharmacists then evaluated these patients for 16 weeks after the increase to determine changes in functional assessment staging, caregiver burden, and swallowing function. During the 16-week study, 20 of the 27 patients showed at least one-stage improvement in relation to the five assessed aspects of daily life (time\/place, speech, bathing, dressing, and toileting). The mean score for caregiver burden due to personal strain was significantly lower after the dosage increase than before (5.15\u00b13.76 at baseline; from 3.89\u00b13.42 at week 4 to 3.59\u00b13.90 at week 16; P<0.05), as was the mean score due to role strain (2.19\u00b12.80 at baseline; 1.56\u00b12.64 at week 8; P<0.05). After the dosage increase, the impaired swallowing function that accompanies AD was improved in the patients with swallowing problems, as indicated by a higher mean RSST score (1.22\u00b10.67 at baseline; from 2.78\u00b11.72 at week 4 to 2.78\u00b11.79 at week 16; P<0.05). The dosage increase not only decreased caregiver burden, but also appeared to improve impaired swallowing function. Medication therapy management by pharmacists of AD patients, including the use of a checklist, contributed to the correct use of donepezil and improved quality of life for caregivers.","subset":"pubmed_abstract"} +{"meta":{"pmid":33581728,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-30":1,"unknown":7}}},"text":"Mapping the organizational readiness to change assessment to the Consolidated Framework for Implementation Research.\nImplementation researchers recognize the influential role of organizational factors and, thus, seek to assess these factors using quantitative measurement instruments. However, researchers are hindered by instruments that measure similar constructs but rely on different nomenclature and\/or definitions. The Consolidated Framework for Implementation Research (CFIR) provides a taxonomy of constructs derived from prior frameworks and empirical studies of implementation-related constructs. The CFIR includes constructs based on the original Promoting Action on Research Implementation in Health Services (PARiHS) framework which highlights the key roles of strength of evidence for a specific evidence-based intervention (EBI), favorability of organizational context for change, and capacities to facilitate implementation of the EBI. Although the CFIR is among the most frequently used implementation frameworks, it does not include quantitative measures. The Organizational Resource and Context Assessment (ORCA) is a quantitative measurement instrument that was developed based on PARiHS, assessing its three domains. Factors within these three domains are conceptually similar to constructs in the CFIR but do not match directly. The aim of this work was to map ORCA survey items to CFIR constructs to enable direct comparisons and syntheses of findings across studies using the CFIR and\/or ORCA. Two distinct, independent research teams, each used rigorous constant comparative techniques with deliberation and consensus to map individual items from the ORCA to the five domains and 39 constructs of CFIR. ORCA items were mapped primarily to three of five CFIR domains: Inner Setting, Process, and Intervention Characteristics. The two research teams agreed on 88% of mappings at the higher domain level; at the lower construct level, their mappings aligned for 62.2% of the ORCA items. Mapping results reveal that the ORCA focuses measurement prominently on Inner Setting, Process, and Intervention Characteristics. This mapping guide can help improve consistency in measurement and reporting, enabling more efficient comparison and synthesis of findings that use either the ORCA instrument or the CFIR framework. The guide helps advance implementation science utilizing mixed methods by providing CFIR users with quantitative measures for selected constructs and enables ORCA users to map their findings to CFIR constructs.","subset":"pubmed_abstract"} +{"meta":{"pmid":16643671,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2015-48":1,"2015-40":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-15":2,"2017-22":1,"2015-11":1,"2014-10":1,"2015-18":1}}},"text":"Identification, cloning and functional characterization of novel sperm associated antigen 11 (SPAG11) isoforms in the rat.\nSperm binding proteins and their C-terminal peptides of the Sperm Associated Antigen 11 (SPAG11) family were found to play an important role in epididymal innate immunity in addition to their role in sperm maturation. However, the expression of Spag11 transcripts in rodents is not well documented. Computational analysis was employed to identify novel Spag11 isoforms in the rat. RT-PCR analyses were carried out on RNAs isolated from the male reproductive tract tissues of rat using gene specific primers for Spag11c and Spag11t. The identities of PCR products were confirmed by sequencing. Tissue distribution, developmental expression and androgen regulation of Spag11t and Spag11c were studied using RT-PCR. The antimicrobial activities of recombinant Spag11t and Spag11c were tested against E coli in a colony forming unit assay. In this study, we identified two novel Spag11 transcripts, namely, Spag11t and Spag11c derived from the long arm of chromosome 16 in the rat (Rattus norvegicus), using both in silico and molecular biology approaches. Spag11c is expressed in all three regions of the epididymis, in testis and in ovary but is absent from the seminal vesicle. Spag11t expression is confined to the caput and it is not expressed in the testis, seminal vesicle or ovary. Age dependent expression of Spag11t and Spag11c was observed in the epididymides of rats (10-60 day old). Their expression was found to be most abundant in the adult rat (60 day) suggesting roles in mature reproductive function. Further, both Spag11t and Spag11c expression was down regulated in castrated rat epididymides and the expression was maintained in the testosterone replaced castrated rats. SPAG11C is a potent antibacterial agent. SPAG11T also displayed bactericidal capacity although weaker than SPAG11C and SPAG11E. The abundant expression of Spag11t and Spag11c in the male reproductive tract suggests an important role in male reproductive tract immunity. Their expression is developmentally regulated and androgen dependent. Characterization of novel SPAG11 isoforms will contribute to our understanding of the role of epididymal proteins in sperm maturation and innate immunity.","subset":"pubmed_abstract"} +{"meta":{"pmid":20467572,"dup_signals":{"dup_doc_count":20,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":1,"2014-15":2,"2015-14":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-11":1}}},"text":"Reinforcement Learning with Limited Reinforcement: Using Bayes Risk for Active Learning in POMDPs.\nPartially Observable Markov Decision Processes (POMDPs) have succeeded in planning domains that require balancing actions that increase an agent's knowledge and actions that increase an agent's reward. Unfortunately, most POMDPs are defined with a large number of parameters which are difficult to specify only from domain knowledge. In this paper, we present an approximation approach that allows us to treat the POMDP model parameters as additional hidden state in a \"model-uncertainty\" POMDP. Coupled with model-directed queries, our planner actively learns good policies. We demonstrate our approach on several POMDP problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":26525667,"dup_signals":{"dup_doc_count":13,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2022-27":2,"2021-43":1,"2021-25":2,"2021-10":1,"2020-40":1,"2020-10":1,"2019-43":2,"2019-26":1,"2019-09":1}}},"text":"Dietary extra virgin olive oil attenuates kidney injury in pristane-induced SLE model via activation of HO-1\/Nrf-2 antioxidant pathway and suppression of JAK\/STAT, NF-\u03baB and MAPK activation.\nSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by a widespread organ involvement. Recent studies have suggested that extra virgin olive oil (EVOO) might possess preventive effects on this immunoinflammation-related disease. However, its role in SLE remained unknown. In this work, we evaluated the effects of EVOO diet in a pristane-induced SLE model in mice. Three-month-old mice received an injection of pristane or saline solution and were fed with different experimental diets: sunflower oil diet or EVOO diet. After 24weeks, mice were sacrificed, spleens were collected and kidneys were removed for immunoinflammatory detections. The kidney expression of microsomal prostaglandin E synthase 1, heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf-2), mitogen-activated protein kinases (MAPKs), Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) and nuclear transcription factor-kappa B (NF-\u03baB) pathways were studied by western blotting. In addition to macroscopic and histological analyses, serum matrix metalloproteinase 3 (MMP-3) levels and proinflammatory cytokines production in splenocytes were evaluated by enzyme-linked immunoassay. We have demonstrated that EVOO diet significantly reduced renal damage and decreased MMP-3 serum and PGE2 kidney levels as well as the proinflammatory cytokines production in splenocytes. Our data indicate that Nrf-2 and HO-1 protein expressions were up-regulated in those mice fed with EVOO and the activation of JAK\/STAT, MAPK and NF-\u03baB pathways were drastically ameliorated. These results support the interest of EVOO as a beneficial functional food exerting a preventive\/palliative role in the management of SLE.","subset":"pubmed_abstract"} +{"meta":{"pmid":8320700,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families.\nThe autosomal recessive limb-girdle muscular dystrophies (LGMD) represent a heterogeneous group of diseases which may be characterised by one or more autosomal loci. A gene at 15q has recently been found to be responsible for a mild form of LGMD in a group of families from the isolated island of R\u00e9union, now classified as LGMD2. Based on results of eight out of 11 large Brazilian LGMD families of different racial background (which were informative for the closest available probe to the LGMD2 gene), we confirmed linkage to the LGMD2 gene at 15q in two of these families and exclusion in six others. These data provide the first evidence of genetic heterogeneity for the autosomal recessive limb-girdle muscular dystrophies.","subset":"pubmed_abstract"} +{"meta":{"pmid":30294280,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Investigation of the Syncytial Nature of Detrusor Smooth Muscle as a Determinant of Action Potential Shape.\nUnlike most excitable cells, certain syncytial smooth muscle cells are known to exhibit spontaneous action potentials of varying shapes and sizes. These differences in shape are observed even in electrophysiological recordings obtained from a single cell. The origin and physiological relevance of this phenomenon are currently unclear. The study presented here aims to test the hypothesis that the syncytial nature of the detrusor smooth muscle tissue contributes to the variations in the action potential profile by influencing the superposition of the passive and active signals. Data extracted from experimental recordings have been compared with those obtained through simulations. The feature correlation studies on action potentials obtained from the experimental recordings suggest the underlying presence of passive signals, called spontaneous excitatory junction potentials (sEJPs). Through simulations, we are able to demonstrate that the syncytial organization of the cells, and the variable superposition of the sEJPs with the \"native action potential\", contribute to the diversity in the action potential profiles exhibited. It could also be inferred that the fraction of the propagated action potentials is very low in the detrusor. It is proposed that objective measurements of spontaneous action potential profiles can lead to a better understanding of bladder physiology and pathology.","subset":"pubmed_abstract"} +{"meta":{"pmid":28664701,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Incidence and prevalence of Systemic Sclerosis (SSc) in Poland - differences between rural and urban regions.\n[b] Abstract Introduction.[\/b] Systemic sclerosis (SSc) is a rare and potentially severe connective tissue disease, characterized by skin fibrosis and involvement of internal organs. Because of its rarity and heterogeneous clinical presentation, reliable epidemiological studies on SSc have been particularly difficult to carry out. [b]Objectives[\/b]. The purpose of this study was to present SSc epidemiology among hospitalized patients in Poland. The analysis was based on population-based administrative data, taken from a Polish hospital morbidity study carried out by the National Institute of Public Health between January 2008 - December 2012. [b]Results[\/b]. Analyzed data covered 9,049 hospitalization records. The final sample comprised 3,653 patients with first-time hospitalizations for SSc. The average age of the sample was 53 years (SD 16.2; range 0-91 years); 84% of patients were female and 16% male. Based on hospitalization registers, the average SSc incidence was estimated to be 1.9\/100,000 per year and peak age of incidence was 55 years. The point prevalence was estimated to be 9.4\/100,000 at the end of 2012. SSc was more common in females, with F:M ratio ranging from 6.2:1-4.6:1 depending on the year. Analysis of hospitalization trends revealed that overall numbers of SSc hospitalizations increased, while first-time hospitalizations decreased between 2008-2012. Clusters of higher incidence were observed in more rural regions vs. urban regions. [b]Conclusion[\/b]. Estimated incidence of SSc in Poland was comparable to reported incidence in other European countries. Analysis of demographic factors and reports of clusters of higher incidence may suggest the existence of environmental risk factors for the development of SSc. These observations may require further research.","subset":"pubmed_abstract"} +{"meta":{"pmid":32824654,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"The Absence of C-5 DNA Methylation in Leishmania donovani Allows DNA Enrichment from Complex Samples.\nCytosine C5 methylation is an important epigenetic control mechanism in a wide array of eukaryotic organisms and generally carried out by proteins of the C-5 DNA methyltransferase family (DNMTs). In several protozoans, the status of this mechanism remains elusive, such as in Leishmania, the causative agent of the disease leishmaniasis in humans and a wide array of vertebrate animals. In this work, we showed that the Leishmania donovani genome contains a C-5 DNA methyltransferase (DNMT) from the DNMT6 subfamily, whose function is still unclear, and verified its expression at the RNA level. We created viable overexpressor and knock-out lines of this enzyme and characterized their genome-wide methylation patterns using whole-genome bisulfite sequencing, together with promastigote and amastigote control lines. Interestingly, despite the DNMT6 presence, we found that methylation levels were equal to or lower than 0.0003% at CpG sites, 0.0005% at CHG sites, and 0.0126% at CHH sites at the genomic scale. As none of the methylated sites were retained after manual verification, we conclude that there is no evidence for DNA methylation in this species. We demonstrated that this difference in DNA methylation between the parasite (no detectable DNA methylation) and the vertebrate host (DNA methylation) allowed enrichment of parasite vs. host DNA using methyl-CpG-binding domain columns, readily available in commercial kits. As such, we depleted methylated DNA from mixes of Leishmania promastigote and amastigote DNA with human DNA, resulting in average Leishmania:human enrichments from 62\u00d7 up to 263\u00d7. These results open a promising avenue for unmethylated DNA enrichment as a pre-enrichment step before sequencing Leishmania clinical samples.","subset":"pubmed_abstract"} +{"meta":{"pmid":28555539,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"The independence of the infundibular building blocks in the setting of double-outlet right ventricle.\nIt has long been contentious as to whether the presence of bilateral infundibulums, or conuses, is a prerequisite for the diagnosis of double-outlet right ventricle. As the use of such a criterion would abrogate the so-called \"morphological method\", which correctly states that one variable entity should not be defined on the basis of another entity that is itself variable, it is now accepted that double outlet can exist in the setting of fibrous continuity between the leaflets of the atrioventricular and arterial valves. Although this debate has now been resolved, there are other contentious areas still requiring clarification in the setting of hearts unified because of the presence of this particular ventriculo-arterial connection - for example, it is questionable whether the channel between the ventricles should be described as a \"ventricular septal defect\", whereas it is equally arguable that the mere presence of fibrous continuity between the leaflets of the arterial valves does not necessarily place the channel in a doubly committed location. In this review, we describe a series of autopsied hearts in which the anatomical features serve to illuminate these various topics. We then discuss recent findings regarding cardiac development that point to the individuality of the building blocks of the ventricular outflow tracts, specifically the outlet septum, the inner heart curvature, or ventriculo-infundibular fold, and the septomarginal trabeculation, or septal band.","subset":"pubmed_abstract"} +{"meta":{"pmid":23283095,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-14":1,"2022-33":1,"2021-21":1,"2021-17":2,"2020-45":1,"2020-34":2,"2020-10":1,"2019-51":1,"2023-23":1,"2024-18":1}}},"text":"Impact of functional decline on outcome in elderly patients with acute coronary syndromes.\nManagement of acute coronary syndromes in elderly patients is poorly defined. To assess the impact of functional decline on all-cause mortality in elderly patients with acute coronary syndromes. Clinical data, including the Global Registry of Acute Coronary Events score and assessment of functional status obtained by using the Katz scale, were prospectively collected on 272 patients 70 years or older hospitalized for acute coronary syndromes. All-cause mortality was assessed at 6 months, and longer term outcome data were obtained. Mean age of the patients was 78 years (SD, 6), and 58% were men. A total of 28% had functional decline. Six months after the index hospitalization, 38 patients had died. Another 29 patients died during a median follow-up of 611 days after the initial 6 months. Functional decline was associated with both 6-month (hazards ratio, 3.63; 95% CI, 1.91-6.88; P < .001) and long-term (hazards ratio, 2.69; 95% CI, 1.28-5.64; P = .009) outcomes. Functional decline remained associated with both 6-month and long-term outcomes in multivariate analysis and was systematically selected in the most predictive multivariate models for 6-month and long-term mortality. The multivariate model including the Global Registry of Acute Coronary Events score and functional decline was predictive of 6-month mortality, but the combination of functional decline and biological data was more predictive of long-term mortality than was a model combining functional decline and the Global Registry score. Functional decline in elderly patients with acute coronary syndromes is predictive of poor outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27195143,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Distribution of Genes Encoding Resistance to Macrolides Among Staphylococci Isolated From the Nasal Cavity of Hospital Employees in Khorramabad, Iran.\nEpidemiological data on antibiotic susceptibility of Staphylococcus strains isolated from nasal carriers in each region can be helpful to select appropriate drugs to eradicate carriage states, control nosocomial infections and also treat patients. The current study aimed to investigate the antibiotic resistance profile and the molecular prevalence of the ermA, ermB, ermC and msrA genes among Staphylococcus strains isolated from the anterior nares of hospital employees. In this cross-sectional study, a total of 100 Staphylococcus isolates, 51 Staphylococcus aureus, 49 coagulase-negative staphylococci (CoNS) were isolated from the anterior nares of hospital employees in Khorramabad, Iran. Susceptibility pattern to macrolide antibiotics were determined using the disk diffusion method. The polymerase chain reaction (PCR) assay was applied to determine the major erythromycin-resistant genes (ermA, ermB, ermC and msrA). Fifty-three (53%) isolates were simultaneously resistant to erythromycin, azithromycin and clarithromycin (cross-resistance); while 8 (8%) isolates had variable macrolide susceptibility pattern. Among the S. aureus isolates, the difference in prevalence of resistance to erythromycin between males and females was significant (P = 0.011). The frequency of ermA, ermB, ermC, and msrA genes were 3%, 5%, 33% and 20%, respectively. It was also found that out of 53 isolates resistant to erythromycin, 44 (83%) isolates (eight S. aureus and thirty-six CoNS strains) carried at least one of the four tested genes. Eight (8%) isolates had intermediate phenotype to erythromycin, in which 4 (50%) isolates carried ermB or ermC genes. In addition, out of 39 erythromycin-susceptible isolates, 3 (7.7%) isolates were positive for ermB or ermC genes. No entire association was found between genotype and phenotype methods to detect macrolides-resistant isolates. In addition, distribution of genetically erythromycin-resistant isolates is geographically different among staphylococci. It is recommend removing S. aureus from nasal carriers by proved approaches such as local or systemic administration of effective antibiotics or bacterial interference.","subset":"pubmed_abstract"} +{"meta":{"pmid":21867561,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-18":2,"2015-06":1,"2014-10":1,"2013-48":2,"2013-20":2,"unknown":2}}},"text":"Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs.\nmicroRNAs (miRNA) are short, endogenous transcripts that negatively regulate the expression of specific mRNA targets. miRNAs are found both in tissues and body fluids such as plasma. A major perspective for the use of miRNAs in the clinical setting is as diagnostic plasma markers for neoplasia. While miRNAs are abundant in tissues, they are often scarce in plasma. For quantification of miRNA in plasma it is therefore of importance to use a platform with high sensitivity and linear performance in the low concentration range. This motivated us to evaluate the performance of three commonly used commercial miRNA quantification platforms: GeneChip miRNA 2.0 Array, miRCURY Ready-to-Use PCR, Human panel I+II V1.M, and TaqMan Human MicroRNA Array v3.0. Using synthetic miRNA samples and plasma RNA samples spiked with different ratios of 174 synthetic miRNAs we assessed the performance characteristics reproducibility, recovery, specificity, sensitivity and linearity. It was found that while the qRT-PCR based platforms were sufficiently sensitive to reproducibly detect miRNAs at the abundance levels found in human plasma, the array based platform was not. At high miRNA levels both qRT-PCR based platforms performed well in terms of specificity, reproducibility and recovery. At low miRNA levels, as in plasma, the miRCURY platform showed better sensitivity and linearity than the TaqMan platform. For profiling clinical samples with low miRNA abundance, such as plasma samples, the miRCURY platform with its better sensitivity and linearity would probably be superior.","subset":"pubmed_abstract"} +{"meta":{"pmid":21859475,"dup_signals":{"dup_doc_count":51,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2015-48":2,"2015-40":2,"2015-35":1,"2015-32":2,"2015-27":1,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":4,"2014-42":6,"2014-41":4,"2014-35":3,"2014-23":3,"2014-15":2,"2019-43":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2}}},"text":"Differential patterns of intronic and exonic DNA regions with respect to RNA polymerase II occupancy, nucleosome density and H3K36me3 marking in fission yeast.\nThe generation of mature mRNAs involves interconnected processes, including transcription by RNA polymerase II (Pol II), modification of histones, and processing of pre-mRNAs through capping, intron splicing, and polyadenylation. These processes are thought to be integrated, both spatially and temporally, but it is unclear how these connections manifest at a global level with respect to chromatin patterns and transcription kinetics. We sought to clarify the relationships between chromatin, transcription and splicing using multiple genome-wide approaches in fission yeast. To investigate these functional interdependencies, we determined Pol II occupancy across all genes using high-density tiling arrays. We also performed ChIP-chip on the same array platform to globally map histone H3 and its H3K36me3 modification, complemented by formaldehyde-assisted isolation of regulatory elements (FAIRE). Surprisingly, Pol II occupancy was higher in introns than in exons, and this difference was inversely correlated with gene expression levels at a global level. Moreover, introns showed distinct distributions of histone H3, H3K36me3 and FAIRE signals, similar to those at promoters and terminators. These distinct transcription and chromatin patterns of intronic regions were most pronounced in poorly expressed genes. Our findings suggest that Pol II accumulates at the 3' ends of introns, leading to substantial transcriptional delays in weakly transcribed genes. We propose that the global relationship between transcription, chromatin remodeling, and splicing may reflect differences in local nuclear environments, with highly expressed genes being associated with abundant processing factors that promote effective intron splicing and transcriptional elongation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28857038,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Thermosulfuriphilus ammonigenes gen. nov., sp. nov., a thermophilic, chemolithoautotrophic bacterium capable of respiratory ammonification of nitrate with elemental sulfur.\nAn extremely thermophilic, anaerobic, chemolithoautotrophic bacterium (strain ST65T) was isolated from a deep-sea hydrothermal vent chimney located on the Eastern Lau Spreading Centre in the south-western Pacific Ocean, at a depth of 1870 m. Cells of strain ST65T were non-motile straight or slightly curved short rods, 0.5-0.6 \u00b5m in diameter and 0.8-1.5 \u00b5m in length. The temperature range for growth was 47-75 \u00b0C, with an optimum at 65 \u00b0C. The pH range for growth was 5.5-7.5, with an optimum at pH 6.5. Growth of strain ST65T was observed at NaCl concentrations ranging from 1.5 to 4.5 % (w\/v), with an optimum at 2.0-2.5 %. Strain ST65T grew anaerobically with inorganic carbon as a carbon source and with elemental sulfur as an electron donor and nitrate as an electron acceptor producing sulfate and ammonium. It was also able to grow by disproportionation of elemental sulfur, thiosulfate and sulfite. Sulfate was not utilized as an electron acceptor. Analysis of the 16S rRNA gene sequence revealed that the isolate belongs to a deep lineage in the phylum Thermodesulfobacteria. On the basis of its physiological properties and results of phylogenetic analyses, it is proposed that the isolate represents a novel species of a new genus, Thermosulfuriphilus ammonigenes gen. nov., sp. nov. ST65T (=DSM 102941T=VKM B-2855T) is the type strain of the type species.","subset":"pubmed_abstract"} +{"meta":{"pmid":22050674,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2015-18":1,"2024-18":1,"unknown":15}}},"text":"Identification of common and cell type specific LXXLL motif EcR cofactors using a bioinformatics refined candidate RNAi screen in Drosophila melanogaster cell lines.\nDuring Drosophila development, titers of the steroid ecdysone trigger and maintain temporal and tissue specific biological transitions. Decades of evidence reveal that the ecdysone response is both unique to specific tissues and distinct among developmental timepoints. To achieve this diversity in response, the several isoforms of the Ecdysone Receptor, which transduce the hormone signal to the genome level, are believed to interact with tissue specific cofactors. To date, little is known about the identity of these cofactor interactions; therefore, we conducted a bioinformatics informed, RNAi luciferase reporter screen against a subset of putative candidate cofactors identified through an in silico proteome screen. Candidates were chosen based on criteria obtained from bioinformatic consensus of known nuclear receptor cofactors and homologs, including amino acid sequence motif content and context. The bioinformatics pre-screen of the Drosophila melanogaster proteome was successful in identifying an enriched putative candidate gene cohort. Over 80% of the genes tested yielded a positive hit in our reporter screen. We have identified both cell type specific and common cofactors which appear to be necessary for proper ecdysone induced gene regulation. We have determined that certain cofactors act as co-repressors to reduce target gene expression, while others act as co-activators to increase target gene expression. Interestingly, we find that a few of the cofactors shared among cell types have a reversible roles to function as co-repressors in certain cell types while in other cell types they serve as co-activators. Lastly, these proteins are highly conserved, with higher order organism homologs also harboring the LXXLL steroid receptor interaction domains, suggesting a highly conserved mode of steroid cell target specificity. In conclusion, we submit these cofactors as novel components of the ecdysone signaling pathway in order to further elucidate the dynamics of steroid specificity.","subset":"pubmed_abstract"} +{"meta":{"pmid":32618624,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Machine Learning Applied to Registry Data: Development of a Patient-Specific Prediction Model for Blood Transfusion Requirements During Craniofacial Surgery Using the Pediatric Craniofacial Perioperative Registry Dataset.\nCraniosynostosis is the premature fusion of \u22651 cranial sutures and often requires surgical intervention. Surgery may involve extensive osteotomies, which can lead to substantial blood loss. Currently, there are no consensus recommendations for guiding blood conservation or transfusion in this patient population. The aim of this study is to develop a machine-learning model to predict blood product transfusion requirements for individual pediatric patients undergoing craniofacial surgery. Using data from 2143 patients in the Pediatric Craniofacial Surgery Perioperative Registry, we assessed 6 machine-learning classification and regression models based on random forest, adaptive boosting (AdaBoost), neural network, gradient boosting machine (GBM), support vector machine, and elastic net methods with inputs from 22 demographic and preoperative features. We developed classification models to predict an individual's overall need for transfusion and regression models to predict the number of blood product units to be ordered preoperatively. The study is reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist for prediction model development. The GBM performed best in both domains, with an area under receiver operating characteristic curve of 0.87 \u00b1 0.03 (95% confidence interval) and F-score of 0.91 \u00b1 0.04 for classification, and a mean squared error of 1.15 \u00b1 0.12, R-squared (R) of 0.73 \u00b1 0.02, and root mean squared error of 1.05 \u00b1 0.06 for regression. GBM feature ranking determined that the following variables held the most information for prediction: platelet count, weight, preoperative hematocrit, surgical volume per institution, age, and preoperative hemoglobin. We then produced a calculator to show the number of units of blood that should be ordered preoperatively for an individual patient. Anesthesiologists and surgeons can use this continually evolving predictive model to improve clinical care of patients presenting for craniosynostosis surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":33833897,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":2,"unknown":8}}},"text":"Antioxidant, Cytotoxicity and Cytoprotective Potential of Extracts of Grewia Flava and Grewia Bicolor Berries.\nAccumulation of cellular reactive oxygen species (ROS) leads to oxidative stress. Increased production of ROS, such as superoxide anion, or a deficiency in their clearance by antioxidant defences, mediates cellular pathology. Grewia Spp fruits are a source of bioactive compounds and have notable antioxidant activity. Although the antioxidant capacity of Grewia Spp has been studied, there is very limited evidence that links the antioxidant activities of Grewia bicolor and Grewia flava to the inhibition of free radical formation associated with damage in biological systems. This study evaluated the protective effects of Grewia bicolor and Grewia flava extracts against free radical-induced oxidative stress and the resulting cytotoxicity effect using HeLa cells. Antioxidant properties determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic content (TPC) assays showed significantly higher (p < 0.05) antioxidant activity in Grewia flava (ethanol extract) than Grewia flava (water extract) and Grewia bicolor (ethanol and water extracts). Using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide or MTT assay, cytotoxicity results showed that extracts of Grewia bicolor and Grewia flava were less toxic to HeLa cells at tested concentrations compared to the untreated control. This confirmed the low toxicity of these edible fruits at the tested concentrations in HeLa cells. Furthermore, hydrogen peroxide (H2O2)-induced cell loss was effectively reduced by pre-incubating HeLa cells with Grewia bicolor and Grewia flava extracts, with Grewia flava (ethanol extract) revealing better protection. The effect was speculated to be associated with the higher antioxidant activity of Grewia flava (ethanol extract). Additional studies will warrant confirmation of the mechanism of action of such effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":25561286,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2021-39":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-17":1,"2018-09":1,"2023-14":1}}},"text":"Liposome-Adenoviral hTERT-siRNA Knockdown in Fibroblasts from Keloids Reduce Telomere Length and Fibroblast Growth.\nKeloids, which possess invasive tumor-like behavior, have been clinically challenging to clinicians especially surgeons. Excessive extracellular matrix secreted from fibroblasts is the main histo-pathological feature of keloids. In this study, we transfected hTERT-siRNA into scar fibroblasts by liposome-adenoviral transduction in order to disrupt telomere length homeostasis and influence the cell cycle of fibroblasts. Our results showed that liposome hTERT-siRNA was able to knock down hTERT gene expression in scar fibroblasts. Moreover, the telomerase activity in hTERT-siRNA group was significantly reduced compared with the control groups. And the telomeric length of hTERT-siRNA group was significantly shortened as well. Further, flow cytometry studies and MTT assay demonstrated that apoptosis rate of fibroblasts in liposome hTERT-siRNA group significantly increased. These results indicated that the liposome-mediated hTERT gene transduction could inhibit the growth of fibroblasts in scar tissues suggesting a promising strategy of keloids treatment in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":8603820,"dup_signals":{"dup_doc_count":41,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":1,"2021-39":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-30":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":2,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2023-14":1,"2017-13":1}}},"text":"Cancer-associated mis-sense and deletion mutations impair p16INK4 CDK inhibitory activity.\nThe p16INK4 gene is a candidate tumour-suppressor gene which maps to the genomic locus 9p21, and mutations of this gene are associated with melanoma and other cancers. Biochemical studies suggest that p16INK4 mediates its effects by specifically inhibiting the G1 cyclin-dependent kinases CDK4 and CDK6, thereby regulating the progression through G1 into S phase of the cell cycle. To evaluate the functional effects of mutations in p16INK4 which have been observed in primary cancers and cancer cell lines, we constructed a series of deletion mutants comprising amino acid regions 9-72, 9-131, 73-131 and 73-156; a mis-sense mutation identified in melanoma (Arg87Pro); and the polymorphism Ala48Thr and investigated their ability to inhibit cyclin D1\/CDK4 kinase activity in vitro. Removal of 25 amino acids from the carboxy terminus of p16INIK4 (9-131) had little impact on its inhibitory activity. In contrast, deletion of the 65 N-terminal amino acids comprising the first and second ankyrin repeats of p16INK4 (73-131) abolished its inhibitory activity. The carboxy (73-156) and amino termial (9-72) fragments of p16INK4 also failed to inhibit cyclin D1\/CDK4 activity. These results indicate that the core region (73-131) as well as amino acids N-terminal of this sequence are important, whereas sequences C-terminal of amino acid 131 are less important for the inhibitory activity of this molecule. The melanoma-associated Arg87Pro mutation resulted in loss of inhibitory activity, whereas the Ala148Thr polymorphic variant was as effective as the alanine variant of p16INK4 in inhibiting D1\/CDK4 kinase activity. Binding assays revealed that inhibition was invariably associated with p16INK4 binding to CDK4. Hence, our studies indicate that minor perturbations in p16INK4 primary structure can lead to loss of its inhibitory activity, possibly contributing to oncogenesis in numerous cell types.","subset":"pubmed_abstract"} +{"meta":{"pmid":24068494,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation.\nAlloreactivity of donor lymphocytes leads to graft-versus-host disease (GVHD) contributing to significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Within the past decade, significant progress has been made in elucidating the mechanisms underlying the immunologic dysregulation characteristic of GVHD. The recent discoveries of different cell subpopulations with immune regulatory function has led to a number of studies aimed at understanding their role in allogeneic HCT and possible application for the prevention and treatment of GVHD and a host of other immune-mediated diseases. Preclinical animal modeling has helped define the potential roles of distinct populations of regulatory cells that have progressed to clinical translation with promising early results.","subset":"pubmed_abstract"} +{"meta":{"pmid":26509652,"dup_signals":{"dup_doc_count":53,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":2,"2023-14":2,"2022-49":2,"2022-27":2,"2022-05":2,"2021-39":4,"2021-31":2,"2021-21":2,"2021-10":2,"2020-50":2,"2020-40":2,"2020-29":1,"2020-16":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-26":2,"2018-17":2,"2018-13":1,"2017-51":3,"2017-43":2,"2017-34":1,"2024-22":3,"2024-18":1,"2024-30":1}}},"text":"Bloch-Siegert B1+-mapping for human cardiac (31) P-MRS at 7 Tesla.\nPhosphorus MR spectroscopy ((31) P-MRS) is a powerful tool for investigating tissue energetics in vivo. Cardiac (31) P-MRS is typically performed using surface coils that create an inhomogeneous excitation field across the myocardium. Accurate measurements of B1+ (and hence flip angle) are necessary for quantitative analysis of (31) P-MR spectra. We demonstrate a Bloch-Siegert B1+-mapping method for this purpose. We compare acquisition strategies for Bloch-Siegert B1+-mapping when there are several spectral peaks. We optimize a Bloch-Siegert sensitizing (Fermi) pulse for cardiac (31) P-MRS at 7 Tesla (T) and apply it in a three-dimensional (3D) chemical shift imaging sequence. We validate this in phantoms and skeletal muscle (against a dual-TR method) and present the first cardiac (31) P B1+-maps at 7T. The Bloch-Siegert method correlates strongly (Pearson's r = 0.90 and 0.84) and has bias <25 Hz compared with a multi-TR method in phantoms and dual-TR method in muscle. Cardiac 3D B1+-maps were measured in five normal volunteers. B1+ maps based on phosphocreatine and alpha-adenosine-triphosphate correlated strongly (r = 0.62), confirming that the method is T1 insensitive. The 3D (31) P Bloch-Siegert B1+-mapping is consistent with reference methods in phantoms and skeletal muscle. It is the first method appropriate for (31) P B1+-mapping in the human heart at 7T. Magn Reson Med 76:1047-1058, 2016. \u00a9 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.","subset":"pubmed_abstract"} +{"meta":{"pmid":2835450,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Neurite outgrowth in individual neurons of a neuronal population is differentially regulated by calcium and cyclic AMP.\nIn identified Helisoma neurons, intracellular calcium can regulate neurite elongation and growth cone motility. Neurotransmitters such as 5-HT suppress both neurite elongation and the filopodial and lamellipodial movements of growth cones by causing increases in intracellular calcium (Haydon et al., 1984; Cohan et al., 1987; Mattson and Kater, 1987). Since an additional second messenger, cyclic AMP (cAMP), is known to mediate many physiological effects of neurotransmitters, we tested (1) the possible involvement of cAMP in the regulation of neurite outgrowth from Helisoma buccal neurons and (2) calcium-cAMP interrelationships in the regulation of outgrowth. The cAMP-elevating agents forskolin (5 x 10(-6)-10(-4) M) and dibutyryl cAMP (dbcAMP; 5 x 10(-3)-10(-2) M) suppressed neurite elongation and growth cone movements in identified neurons B19 (5-HT sensitive) and B5 (5-HT insensitive); the suppression was reversible. Exposure of these particular identified neurons to the calcium channel blocker La3+ (10(-5) M) or a culture medium with reduced calcium prevented and reversed the suppressive effects of forskolin and dbcAMP. In order to determine if the results on neurons B5 and B19 were representative of all neurons or only a subset, we examined a larger population of neurons. Calcium ionophore A23187 suppressed outgrowth from all neurons in mass dissociate cultures of buccal neurons, while forskolin or dbcAMP plus IBMX suppressed outgrowth from only one-half of buccal neurons. Finally, we found that 2 subpopulations exist among the neurons whose outgrowth is suppressed by cAMP: One subpopulation requires calcium influx for cAMP to act, while the other does not. Thus, even within the relatively small population of neuronal types comprising the buccal ganglion of Helisoma, second messengers within different neurons can act and interact in different ways to regulate outgrowth.","subset":"pubmed_abstract"} +{"meta":{"pmid":22455989,"dup_signals":{"dup_doc_count":12}},"text":"Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells.\nThis study focused on the characterization of stem cells from human exfoliated deciduous teeth (SHED) in comparison with dental pulp stem cells (DPSCs) to certify SHED as a key element in tissue engineering. In the present study, SHED and DPSCs were assayed for their cell surface antigens and proliferation by measuring the cell cycles, growth rates, Ki67-positive efficiencies, and colony-forming units (CFUs). The evaluation of multi-differentiation was performed using alizarin red and oil red O and real-time PCR in vitro. The mineralization capability of the cells was examined in vivo by implanting with ceramic bovine bone (CBB) into subcutaneous of immunocompromised mice for 8weeks. A three-dimensional pellet cultivation system is proposed for SHED and DPSCs to recreate the biological microenvironment that is similar to that of a regenerative milieu. SHED showed a higher proliferation rate and differentiation capability in comparison with DPSCs in vitro, and the results of the in vivo transplantation suggest that SHED have a higher capability of mineralization than the DPSCs. The mRNA expression levels of inflammatory cytokines, including matrix metalloproteinase-1 (MMP1), tissue inhibitors of metalloproteinase-1 (TIMP1), matrix metalloproteinase-2 (MMP2), tissue inhibitors of metalloproteinase-2 (TIMP2) and interleukin-6 (IL-6) were higher in SHED than that in DPSCs. In addition, the expression levels of Col I and proliferating cell nuclear antigen (PCNA) in SHED sheets were significantly higher than those in DPSCs sheets. This study systematically demonstrated the differences in the growth and differentiation characteristics between SHED and DPSCs. Consequently, SHED may represent a suitable, accessible and potential alternative source for regenerative medicine and therapeutic applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":23041855,"dup_signals":{"dup_doc_count":43,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":6,"2016-36":6,"2016-30":4,"2016-22":3,"2016-18":2,"2016-07":3,"2015-48":4,"2015-40":1,"2015-35":3,"2015-32":2,"2015-27":2,"2015-22":1}}},"text":"Lateral laser speckle contrast analysis combined with line beam scanning illumination to improve the sampling depth of blood flow imaging.\nWe present a lateral laser speckle contrast analysis method combined with line beam scanning illumination to improve the sampling depth of blood flow imaging. Both the phantom and animal experimental results suggest that localized illumination and lateral speckle contrast analysis can significantly enhance the deep blood flow signal to improve the sampling depth of laser speckle contrast imaging compared with the traditional full-field illumination laser speckle contrast analysis method.","subset":"pubmed_abstract"} +{"meta":{"pmid":19293503,"dup_signals":{"dup_doc_count":21,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-18":1,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":15}}},"text":"Electronic medical records in dermatology: practical implications.\nElectronic medical records (EMRs) can be of great use in dermatological data recording. Unfortunately, not many studies have been carried out in this specific area. We attempt to evaluate the use of an EMR system in dermatology, comparing it with a conventional paper-based system. Two hundred patient records of patients attending the dermatology outpatient department were studied over a 3-month period. Half the reports were entered in the conventional paper-based format while the other half was entered in an EMR system. The time taken for each consultation was recorded and the same was carried out for the first subsequent follow-up visit. The average time taken for the completion of the EMR-based consultation for new cases was 19.15 min (range, 10-30 min; standard deviation, 6.47). The paper-based consultation had an average time of 15.70 min (range, 5-25 min; standard deviation, 6.78). The P-value (T-test was used) was 0.002, which was significant. The average time taken for consultations and entering progress notes in the follow-up cases was slightly less than 10 min (9.7) for EMR while it was slightly more than 10 min (10.3) for the paper format. The difference was not statistically significant. The doctors involved also mentioned what they felt were the advantages and disadvantages of the system along with suggestions for improvement. The use of an EMR system in dermatology (or for that matter in any specialty) may overawe most users at the beginning, but once a comfort level is established, EMR is likely to outscore conventional paper recording systems. More time-motion-case studies are required to ascertain the optimal usage of EMR systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":22540038,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Conserved Motifs and Prediction of Regulatory Modules in Caenorhabditis elegans.\nTranscriptional regulation, a primary mechanism for controlling the development of multicellular organisms, is carried out by transcription factors (TFs) that recognize and bind to their cognate binding sites. In Caenorhabditis elegans, our knowledge of which genes are regulated by which TFs, through binding to specific sites, is still very limited. To expand our knowledge about the C. elegans regulatory network, we performed a comprehensive analysis of the C. elegans, Caenorhabditis briggsae, and Caenorhabditis remanei genomes to identify regulatory elements that are conserved in all genomes. Our analysis identified 4959 elements that are significantly conserved across the genomes and that each occur multiple times within each genome, both hallmarks of functional regulatory sites. Our motifs show significant matches to known core promoter elements, TF binding sites, splice sites, and poly-A signals as well as many putative regulatory sites. Many of the motifs are significantly correlated with various types of experimental data, including gene expression patterns, tissue-specific expression patterns, and binding site location analysis as well as enrichment in specific functional classes of genes. Many can also be significantly associated with specific TFs. Combinations of motif occurrences allow us to predict the location of cis-regulatory modules and we show that many of them significantly overlap experimentally determined enhancers. We provide access to the predicted binding sites, their associated motifs, and the predicted cis-regulatory modules across the whole genome through a web-accessible database and as tracks for genome browsers.","subset":"pubmed_abstract"} +{"meta":{"pmid":23801734,"dup_signals":{"dup_doc_count":36,"dup_dump_count":32,"dup_details":{"curated_sources":3,"2023-50":2,"2023-40":1,"2023-23":1,"2023-06":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2024-26":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Defective cerebellar control of cortical plasticity in writer's cramp.\nA large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer's cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients' maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (-40\u00b0 to 40\u00b0) on the direction of movement of the mouse\/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer's cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer's cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer's cramp, but not in healthy subjects, behavioural parameters reflecting their capacity for adapting to the rotation and for washing-out of an earlier adaptation predicted the efficacy of inhibitory cerebellar conditioning to influence sensorimotor plasticity: the better the online adaptation, the smaller the influence of cerebellar inhibitory stimulation on motor cortex plasticity. Altered cerebellar encoding of incoming afferent volleys may result in decoupling the motor component from the afferent information flow, and also in maladjusted sensorimotor calibration. The loss of cerebellar control over sensorimotor plasticity might also lead to building up an incorrect motor program to specific adaptation tasks such as writing.","subset":"pubmed_abstract"} +{"meta":{"pmid":24486943,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Alcoholism, Korsakoff's Syndrome and the Frontal Lobes.\nA subset of the diffuse cerebral changes and psychometric deficits found in chronic alcoholics is similar to that seen in the frontal lobe syndrome. Certain features of alcoholic Korsakoff's syndrome (AKS) also point to cortical involvement, and this may have a basis in alcohol neurotoxicity.Twenty-five patients with AKS and 24 non-Korsakoff alcoholic controls were compared using an automated CT brain scan program. In addition to evidence of their diencephalic lesions (wide third ventricles), AKS patients revealed widespread cerebral damage with greater Sylvian and interhemispheric fissure (IHF) size than alcoholics. Korsakoffs were also inferior to alcoholics in performance on a category sorting test, in which non-perseverative error scores correlated significantly with IHF size.The principle of distinguishing between selective memory decline and global intellectual decline (GID) was applied to 38 patients with AKS. Indices were developed for each type of deficit and much variation found in their distributions. The degree of GID correlated significantly with IHF size, showing similar trends with other cortical measures.These results suggest a cortical substrate for the degree of GID and a frontal substrate for category sorting deficits; with a probable basis in alcohol neurotoxicity rather than thiamine deficiency, which is not known to impair cortical structure. A new model is proposed of the pathophysiology of alcoholic brain damage and AKS which includes recent work on neurotransmitter sources and thalamo-frontal connections.","subset":"pubmed_abstract"} +{"meta":{"pmid":12714508,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion.\nThe CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation with phorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-alpha-converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive. Here we demonstrate a role of the closely related disintegrin-like metalloproteinase 10 (ADAM10) in the constitutive CX3CL1 cleavage. The hydroxamate GW280264X, capable of blocking TACE as well as ADAM10, proved to be an effective inhibitor of the constitutive and the PMA-inducible CX3CL1 cleavage in CX3CL1-expressing ECV-304 cells (CX3CL1-ECV-304), whereas GI254023X, preferentially blocking ADAM10 but not TACE, reduced the constitutive cleavage only. Overexpression of ADAM10 in COS-7 cells enhanced constitutive cleavage of CX3CL1 and, more importantly, in murine fibroblasts deficient of ADAM10 constitutive CX3CL1 cleavage was markedly reduced. Thus, ADAM10 contributes to the constitutive shedding of CX3CL1 in unstimulated cells. Addressing the functional role of CX3CL1 shedding for the adhesion of monocytic cells via membrane-expressed CX3CL1, we found that THP-1 cells adhere to CX3CL1-ECV-304 cells but detach in the course of vigorous washing. Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells. Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers.","subset":"pubmed_abstract"} +{"meta":{"pmid":24204765,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2018-43":1,"2018-34":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":1,"2018-51":1}}},"text":"Racial discrimination & cardiovascular disease risk: my body my story study of 1005 US-born black and white community health center participants (US).\nTo date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD). Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35-64 randomly selected from community health centers in Boston, MA (2008-2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964). Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta = -4.86; 95% CI -9.08, -0.64) and lower Framingham CVD score (beta = -0.36, 95% CI -0.63, -0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score. Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health.","subset":"pubmed_abstract"} +{"meta":{"pmid":1970350,"dup_signals":{"dup_doc_count":26,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":22}}},"text":"Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells.\nCD4+ murine T cell clones, TH1 and TH2, can be distinguished by both functional responses and by their patterns of lymphokine secretion. Recently, a mAb, 23G2, which reacts with a subset of CD45 molecules (CD45R), has been reported to bind differentially to clones of TH1 and TH2 cells. In the present study, normal splenic T cells were analyzed for differences in 23G2-reactivity and were separated into two populations based on their density of CD45R (CD45Rhi and CD45Rlo). The CD45Rhi cells secrete more IL-2 than IL-4 after stimulation in vitro; the reverse is true for the CD45Rlo cells. Because neither population secretes only IL-2 or IL-4, we were unable to classify cells as TH1 or TH2. In vivo and in vitro analyses of the CD45Rhi and CD45Rlo cells suggest a lineage relationship between the two subsets that correlates with the degree of Ag exposure and the state of maturation of the mice. In newborn mice and mice raised under sterile conditions, splenic CD4+ T cells are predominantly CD45Rhi. Under conditions of increased antigenic exposure and maturation of the mice, CD45Rlo cells develop; after long term priming in vivo, the majority of specific Ag-reactive cells are CD45Rlo. Adoptive transfer studies using BALB\/c nu\/nu recipients demonstrate that CD45Rhi cells become CD45Rlo cells and that the recall response (IgG) to specific Ag is mediated by CD45Rlo cells. Taken together, these data indicate that the level of expression of CD45R on CD4+ T cells distinguishes virgin (CD45Rhi) from primed\/memory (CD45Rlo) T cells in normal mice.","subset":"pubmed_abstract"} +{"meta":{"pmid":2836357,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Virulence-associated genetic regions comprising 31 kilobases of the 230-kilobase plasmid in Shigella flexneri 2a.\nBy random transposon Tn5 insertions, we previously identified six virulence-associated SalI fragments, B, D, F, G, H, and P, in the 230-kilobase plasmid pMYSH6000 of Shigella flexneri 2a. In this study, we analyzed the sites of 134 independent Tn5 insertions on four contiguous SalI fragments, B, P, H, and D, of pMYSH6000 and identified five virulence-associated regions; four were associated with inducing a positive Sereny test (Ser), invasion into epithelial cells (Inv), binding to Congo red (Pcr), and inhibition of bacterial growth (Igr), and one was associated with the Ser and Inv but not with the Pcr or Igr phenotypes. Hybridization studies revealed that these virulence-associated DNA regions were highly conserved among 15 other virulence plasmids of four species of Shigella and enteroinvasive Escherichia coli. These data indicate that at least seven separate genetic determinants on the virulence plasmid are required for full expression of the virulence phenotype of shigellae.","subset":"pubmed_abstract"} +{"meta":{"pmid":24496180,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2022-33":2,"2022-27":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-04":2,"2020-50":1,"2020-16":1,"2018-09":1,"2017-39":1,"2017-26":1,"2023-23":1,"2017-13":1,"2024-10":1}}},"text":"Non-invasive mouthguard biosensor for continuous salivary monitoring of metabolites.\nThe present work describes the first example of a wearable salivary metabolite biosensor based on the integration of a printable enzymatic electrode on a mouthguard. The new mouthguard enzymatic biosensor, based on an immobilized lactate oxidase and a low potential detection of the peroxide product, exhibits high sensitivity, selectivity and stability using whole human saliva samples. Such non-invasive mouthguard metabolite biosensors could tender useful real-time information regarding a wearer's health, performance and stress level, and thus hold considerable promise for diverse biomedical and fitness applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":26328312,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Phytoncide, Nanochemicals from Chamaecyparis obtusa, Inhibits Proliferation and Migration of Vascular Smooth Muscle Cells.\nPhytoncide, nanochemicals extracted from Chamaecyparis obtusa (C. obtusa), is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, antioxidant, and antiinflammatory activities. However, the effect of phytoncide in vascuar diseases, especially on the behavior of vascular smooth muscle cells, has not yet been clearly elucidated. Therefore, in the present study, we investigated the effects of 15 kinds of phytoncide by various extraction conditions from C. obtusa on the proliferation and migration in rat aortic smooth muscle cells (RAoSMCs). First of all, we determined the concentration of each extracts not having cytotoxicity by MTT assay. We observed that the proliferation rate measured using BrdU assay was significantly reduced by supercritical fluid, steam distillation, Me-OH, and hexane extraction fraction in order with higher extent, respectively. Moreover, the treatment of above nanofractions inhibit the migration of RAoSMCs by 40%, 60%, and 30%, respectively, both in 2-D wound healing assay and 3-D boyden chamber assay. Immunoblot revealed that the phosphorylated levels of Akt and ERK were significantly reduced in nanofractions treated RAoSMCs. Taken together, these data suggest that phytoncide extracted from C. obtusa inhibits proliferation and migration in RAoSMCs via the modulation of phosphorylated levels of Akt and ERK. Therefore, phytoncide nanomolecules might be a potential therapeutic approach to prevent or treat atheroscrelosis and restenosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":14971250,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Local anti-infective therapy: pharmacological agents. A systematic review.\nIt is well recognized that periodontal diseases are bacterial in nature. An essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing [SRP]), which is time-consuming, difficult, and sometimes ineffective. Over the past 20 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal. This systematic review evaluates literature-based evidence in an effort to determine the efficacy of currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis. In patients with chronic periodontitis, what is the effect of local controlled-release anti-infective drug therapy with or without SRP compared to SRP alone on changes in clinical, patient-centered, and adverse outcomes? MEDLINE, the Cochrane Central Trials Register, and Web of Science were searched. Hand searches were performed of the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. In addition, investigators contacted editors of the above-mentioned journals and companies sponsoring research on these agents for related unpublished data and studies in progress. Studies included randomized controlled clinical trials (RCT), and case-controlled and cohort studies at least 3 months long. Therapeutic interventions had to include 1) SRP alone; 2) local anti-infective drug therapy and SRP; or 3) local anti-infective drug therapy alone. Included studies had to report patient-based mean values and measures of variation for probing depth (PD) and\/or clinical attachment levels (CAL) for both test and control groups. Studies were excluded if they: 1) included data from a previously published article; 2) included daily rinsing with chlorhexidine (CHX); or 3) had unclear descriptions of randomization procedures, examiner masking, or concomitant therapies. For the meta-analysis, PD and CAL were expressed as summary mean effects with 95% confidence intervals (CI) for the effect, and analyzed using a standardized difference between SRP alone and experimental agent groups. The results were assessed with both fixed-effects and random-effects models. Studies were ranked according to the York system. 1. Thirty-two studies were included (28 RCT, 2 cohort, and 2 case-control), incorporating a total patient population of 3,705 subjects. 2. Essentially all studies reported substantial reductions in gingival inflammation and bleeding indices, which were similar in both control and experimental groups. 3. A meta-analysis completed on 19 studies that included SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive PD reduction or CAL gain for minocycline (MINO) gel, microencapsulated MINO, CHX chip and doxycycline (DOXY) gel during SRP compared to SRP alone. 4. Use of antimicrobial irrigants or anti-infective sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events. 1. In some populations, anti-infective agents in a sustained-release vehicle alone can reduce PD and bleeding on probing (BOP) equivalent to that achieved by SRP alone. 2. No evidence was found for an adjunctive effect on reduction of PD and BOP of therapist-delivered CHX irrigation during SRP compared to SRP alone. 3. Additional RCTs are needed which evaluate the effectiveness of these therapies in all forms of periodontitis. 4. The study protocol for future RCTs should include appropriate statistical analyses and complete data sets to facilitate future evidence-based reviews. 5. Alternative surrogate parameters to PD and CAL need to be identified and validated such as microbial, inflammatory, or tissue-destructive markers that could be used in conjunction with clinical parameters to help determine the patient's response to emerging technologies that target the infectious and\/or inflammatory aspects of periodontitis. 6. Future Phase IV clinical trials should be designed that evaluate local anti-infective therapies in conjunction with SRP in a manner consistent with current standards of care and evaluate cost-effectiveness. 7. The use of local anti-infective agents in at-risk patient populations and for the treatment of at-risk disease sites needs to be validated in randomized controlled clinical trials. 8. Several local anti-infective agents combined with SRP appear to provide additional benefits in PD reduction and CAL gain compared to SRP alone. The decision to use local anti-infective adjunctive therapy remains a matter of individual clinical judgment, the phase of treatment, and the patient's status and preferences.","subset":"pubmed_abstract"} +{"meta":{"pmid":36919178,"dup_signals":{"dup_doc_count":16}},"text":"Ability and willingness to work during COVID-19 pandemic:Perspectives of front-line hotel employees.\nThis research note reports the results of a qualitative study exploring front-line hotel employees' views about working during the COVID-19 pandemic in order to identify factors that may influence their ability and willingness to report to work. Findings from online focus-groups reveal that front-line hotel employees generally felt a sense of duty to work during the pandemic. However, there were also a number of perceived barriers to working that impacted on this sense of duty. These emerged as barriers to ability and barriers to willingness, but the distinction is not clear-cut. Instead, most barriers seem to form a continuum ranging from negotiable barriers to insuperable barriers. Following this coneptualisation, the key to reducing absenteeism during the pandemic is likely to take remedial action so that barriers to willingness do not become perceived as barriers to ability to work. Practical implications towards this direction are offered.","subset":"pubmed_abstract"} +{"meta":{"pmid":30708584,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Zebra Chip Disease Development in Relation to Plant Age and Time of 'Candidatus Liberibacter solanacearum' Infection.\nA 2-year field study was conducted to evaluate plant susceptibility to 'Candidatus Liberibacter solanacearum', the putative causal agent of zebra chip disease (ZC). Incubation period of ZC, the rate of symptom progress, and the rate of pathogen population growth were evaluated for individual plants infested on different weeks after emergence. In foliage, incubation period was between 21 and 28 days. The pathogen was detected within leaf tissue in 3 to 4 weeks, regardless of the time of infestation. The rates of foliar symptom progress and pathogen population growth were uniform among all infestations. Although symptoms were observed in only 1.3% of tubers from plants infested 2 weeks before harvest, 74% of these tubers tested positive for the pathogen. There was a positive correlation between symptom severity and titer in the foliage. Within tubers, however, the relationship was negative but nonsignificant. Pathogen titer reached detectable levels some time between 7 to 14 days following infestation. Although yield reduction was significant only in plants infested during early stages of their growth, chemical management of potato psyllids needs to be continued until at least a week before harvest to minimize ZC impact on the tuber quality.","subset":"pubmed_abstract"} +{"meta":{"pmid":31806353,"dup_signals":{"dup_doc_count":14,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":2,"2020-50":1,"2020-40":1,"2023-40":1,"2024-18":1}}},"text":"Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2.\nPolycystin-2 (PC2) is a transient receptor potential (TRP) channel present in ciliary membranes of the kidney. PC2 shares a transmembrane fold with other TRP channels, in addition to an extracellular domain found in TRPP and TRPML channels. Using molecular dynamics (MD) simulations and cryoelectron microscopy we identify and characterize PIP2 and cholesterol interactions with PC2. PC2 is revealed to have a PIP binding site close to the equivalent vanilloid\/lipid binding site in the TRPV1 channel. A 3.0-\u00c5 structure reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are characterized by MD simulations. The two classes of lipid binding sites are compared with sites observed in other TRPs and in Kv channels. These findings suggest PC2, in common with other ion channels, may be modulated by both PIPs and cholesterol, and position PC2 within an emerging model of the roles of lipids in the regulation and organization of ciliary membranes.","subset":"pubmed_abstract"} +{"meta":{"pmid":18236934,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2022-27":1,"2017-13":1}}},"text":"Randomized controlled trials in environmental health research: ethical issues.\nRandomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many ethical challenges, ranging from obtaining informed consent to minimizing risks to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research.","subset":"pubmed_abstract"} +{"meta":{"pmid":26911533,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":20}}},"text":"The possible role of chromosome X variability in hypertensive familiarity.\nFamiliarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67-3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66-3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01-2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87-4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":23043001,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Aquaporin AqpZ is involved in cell volume regulation and sensitivity to osmotic stress in Synechocystis sp. strain PCC 6803.\nThe moderately halotolerant cyanobacterium Synechocystis sp. strain PCC 6803 contains a plasma membrane aquaporin, AqpZ. We previously reported that AqpZ plays a role in glucose metabolism under photomixotrophic growth conditions, suggesting involvement of AqpZ in cytosolic osmolarity homeostasis. To further elucidate the physiological role of AqpZ, we have studied its gene expression profile and its function in Synechocystis. The expression level of aqpZ was regulated by the circadian clock. AqpZ activity was insensitive to mercury in Xenopus oocytes and in Synechocystis, indicating that the AqpZ can be categorized as a mercury-insensitive aquaporin. Stopped-flow light-scattering spectrophotometry showed that addition of sorbitol and NaCl led to a slower decrease in cell volume of the Synechocystis \u0394aqpZ strain than the wild type. The \u0394aqpZ cells were more tolerant to hyperosmotic shock by sorbitol than the wild type. Consistent with this, recovery of oxygen evolution after a hyperosmotic shock by sorbitol was faster in the \u0394aqpZ strain than in the wild type. In contrast, NaCl stress had only a small effect on oxygen evolution. The amount of AqpZ protein remained unchanged by the addition of sorbitol but decreased after addition of NaCl. This decrease is likely to be a mechanism to alleviate the effects of high salinity on the cells. Our results indicate that Synechocystis AqpZ functions as a water transport system that responds to daily oscillations of intracellular osmolarity.","subset":"pubmed_abstract"} +{"meta":{"pmid":32618296,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Highly stable 3D porous HMOF with enhanced catalysis and fine color regulation by the combination of d- and p-ions when compared with those of its monometallic MOFs.\nIn this study, two new monometallic organic frameworks (MOFs), namely {[Zn1.5L(NMP)(H2O)]\u00b7H2O}n (1) and {[Pb2L2(H2O)2]\u00b7H2O}n (2), were synthesized for the first time by a new bifunctional N,O-containing 2-(1H-tetrazol-5-yl)terephthalic acid (H2L) ligand. Then, based on the HSAB principle, another porous Pb-Zn heterometallic organic framework (HMOF), namely {[PbZn0.5L(H2O)]\u00b70.5NMP\u00b7H2O}n (3), was successfully obtained for the first time by combining Pb(ii) and Zn(ii) ions with H2L. The MOFs 1 and 2 are 3D densely packed frameworks, whereas the HMOF 3 is a porous 3D framework (28.9% porosity) with 1D open channels modified by Lewis basic sites (exposed N atoms) and Lewis acidic sites (unsaturated bimetallic sites). The HMOF 3 has a strong boiling water\/acid-base resistance (pH = 2-12) and shows an enhanced high-efficiency catalytic effect for CO2 conversion (98%) under ambient temperature and pressure conditions. In addition, fine color regulations of the MOFs were successfully realized by doping different kinds of metal ions into them. This study aims to provide a new way and field of vision for the construction of HMOFs and their multi-functional materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":7512120,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Molecular cloning and characterization of a murine AIDS virus-related endogenous transcript expressed in C57BL\/6 mice.\nThe murine AIDS (MAIDS) virus has a unique sequence in the gag p12 region, which could be responsible for MAIDS development. RNA preparations from the spleens of normal uninfected C57BL\/6 mice contain a transcript hybridizing with this sequence. Levels of the transcript in the kidney of C57BL\/6 mice were higher than in the spleen, liver or thymus. Although BALB\/c, NFS, DBA\/2 and SL murine strains also contained genomic sequences hybridizing with the MAIDS virus-specific probe, no transcript hybridizing with the probe was detected in these strains of mice. The cDNAs carrying the transcript expressed in C57BL\/6 mice were molecularly cloned. The complete nucleotide sequence of the clone indicates that the transcript is one of the endogenous murine leukaemia virus-related sequences containing large deletions from the R and U5 regions of the 5' long terminal repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the N-terminal region of env p15E, and many short deletions in the 3' LTR U3 region. The nucleotide sequence in the gag p12 region of the transcript was closely similar to that of the MAIDS virus, but the amino acid sequence was less similar because of frameshifting, even when translated. As the MAIDS virus was isolated from C57BL\/6 mice with radiation-induced leukaemia, this transcript may be the progenitor of the MAIDS virus. To determine whether the gag p12 region of the transcript contains a functional sequence, a recombinant virus was generated by replacing the gag p12 region of a replication-competent BM5eco virus with that of the endogenous transcript. The recombinant virus was replication-competent, and the p12 region of the transcript retained the functional sequence present in the BM5eco virus.","subset":"pubmed_abstract"} +{"meta":{"pmid":27775110,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Charge transfer process at the Ag\/MPH\/TiO2 interface by SERS: alignment of the Fermi level.\nA nanoscale metal-molecule-semiconductor assembly (Ag\/4-mercaptophenol\/TiO2) has been fabricated over Au nanoparticle (NP) films as a model to study the interfacial charge transfer (CT) effects involved in Ag\/MPH\/TiO2. Due to the interaction between Au NPs and Ag NPs, some distinct differences occur in the SERS spectra. We also measured the SERS of Ag\/MPH (4-mercaptophenol), Ag\/MPH\/TiO2, and Au\/Ag\/MPH\/TiO2 assemblies at excitation wavelengths of 477, 514, 532, 633, and 785 nm. We found that the changes in the CT process, caused by the introduction of TiO2 and Au, can be reflected in SERS. Then in combination with other detection methods, we proposed a possible CT process involved in the Ag\/MPH, Ag\/MPH\/TiO2, and Au\/Ag\/MPH\/TiO2 assemblies. A Pt\/Ag\/MPH\/TiO2 assembly was also constructed to verify our proposed CT mechanism. This work not only provides more details about CT between metal-molecule-semiconductor interfaces but also aids in constructing nanoscale models to study interfacial problems with the SERS technique.","subset":"pubmed_abstract"} +{"meta":{"pmid":30679040,"dup_signals":{"dup_doc_count":22,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":2,"2024-10":2,"2024-22":1,"unknown":16}}},"text":"Global, regional, and national burden of multiple sclerosis 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.\nMultiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866-2 436 858) globally, which corresponded to a 10\u00b74% (9\u00b71 to 11\u00b78) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164\u00b76, 95% UI, 153\u00b72 to 177\u00b71), western Europe (127\u00b70, 115\u00b74 to 139\u00b76), and Australasia (91\u00b71, 81\u00b75 to 101\u00b77), and the lowest were in eastern sub-Saharan Africa (3\u00b73, 2\u00b79-3\u00b78), central sub-Saharan African (2\u00b78, 2\u00b74 to 3\u00b71), and Oceania (2\u00b70, 1\u00b771 to 2\u00b729). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change -11\u00b75%, 95% UI -35\u00b74 to -4\u00b77), whereas the change in age-standardised DALYs was not significant (-4\u00b72%, -16\u00b74 to 0\u00b78). YLLs due to premature death were greatest in the sixth decade of life (22\u00b705, 95% UI 19\u00b708 to 25\u00b734). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Bill & Melinda Gates Foundation.","subset":"pubmed_abstract"} +{"meta":{"pmid":17932422,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Oct-4 is critical for survival\/antiapoptosis of murine embryonic stem cells subjected to stress: effects associated with Stat3\/survivin.\nUnderstanding survival\/antiapoptosis of murine embryonic stem (ES) cells may enhance their clinical potential. We hypothesized that Oct-4 might be involved in survival of undifferentiated ES cells under stress. The Oct-4 tetracycline conditional knockout cell line ZHBtc4 was used to test this possibility, and apoptosis was induced by either etoposide, heat shock, or UV exposure. Apoptosis in Oct-4 knocked-down ES cells was significantly increased in response to all stress situations compared with parental cells. Oct-4 knockdown was not associated with changes in morphology or expression of Nanog, SSEA-1, KLF-4, or Sox2 within the time frame and culture conditions used, suggesting that enhanced sensitivity of these cells to apoptosis was not due to an overtly differentiated state of the cells. To address potential intracellular mediators, we focused on the inhibitor of apoptosis proteins family member Survivin, an antiapoptosis protein. The Survivin promoter was transfected into ES cells after knockdown of Oct-4. Survivin promoter activity was dramatically decreased in the Oct-4 knockdown cells. Western blots substantiated that Oct-4 knockdown ES cells had decreased Survivin protein expression. Since the Survivin promoter does not have binding sites for Oct-4, this suggested an indirect effect of Oct-4 on expression of Survivin. Leukemia inhibitory factor-induced signal transducer and activator of transcription-3 (STAT3) is responsible for ES cell survival, and STAT3 regulates Survivin expression in breast cancer cells. Western blot analysis showed that downregulated Oct-4 was associated with decreased phosphorylation of STAT3. Our results suggest that Oct-4 is essential for antiapoptosis of ES cells in response to stress, effects that may be mediated through the STAT3\/Survivin pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":18177777,"dup_signals":{"dup_doc_count":16,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1,"unknown":10}}},"text":"Glucose-6-phosphate dehydrogenase deficiency.\nGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community.","subset":"pubmed_abstract"} +{"meta":{"pmid":6643580,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":1,"2013-20":2,"2024-22":1,"unknown":9}}},"text":"Laminin promotes neuritic regeneration from cultured peripheral and central neurons.\nThe ability of axons to grow through tissue in vivo during development or regeneration may be regulated by the availability of specific neurite-promoting macromolecules located within the extracellular matrix. We have used tissue culture methods to examine the relative ability of various extracellular matrix components to elicit neurite outgrowth from dissociated chick embryo parasympathetic (ciliary ganglion) neurons in serum-free monolayer culture. Purified laminin from both mouse and rat sources, as well as a partially purified polyornithine-binding neurite promoting factor (PNPF-1) from rat Schwannoma cells all stimulate neurite production from these neurons. Laminin and PNPF-1 are also potent stimulators of neurite growth from cultured neurons obtained from other peripheral as well as central neural tissues, specifically avian sympathetic and sensory ganglia and spinal cord, optic tectum, neural retina, and telencephalon, as well as from sensory ganglia of the neonatal mouse and hippocampal, septal, and striatal tissues of the fetal rat. A quantitative in vitro bioassay method using ciliary neurons was used to (a) measure and compare the specific neurite-promoting activities of these agents, (b) confirm that during the purification of laminin, the neurite-promoting activity co-purifies with the laminin protein, and (c) compare the influences of antilaminin antibodies on the neurite-promoting activity of laminin and PNPF-1. We conclude that laminin and PNPF-1 are distinct macromolecules capable of expressing their neurite-promoting activities even when presented in nanogram amounts. This neurite-promoting bioassay currently represents the most sensitive test for the biological activity of laminin.","subset":"pubmed_abstract"} +{"meta":{"pmid":27453814,"dup_signals":{"dup_doc_count":24,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2022-49":1,"2021-25":1,"2020-34":1,"2020-05":1,"2019-51":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2023-40":1,"2024-22":1}}},"text":"Allergic Bronchopulmonary Aspergillosis masquerading as recurrent bacterial pneumonia.\nAllergic Bronchopulmonary Aspergillosis (ABPA) can be diagnosed in an asthmatic with suitable radiologic and immunological features. However ABPA is likely to be misdiagnosed with bacterial pneumonia. Here we report a case of ABPA masquerading as recurrent bacterial pneumonia. Treatment with high-dose inhaled corticosteroids was effective. To our best knowledge, this is the first reported case of ABPA in Vietnam.","subset":"pubmed_abstract"} +{"meta":{"pmid":23970097,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-10":2,"unknown":9}}},"text":"Possible role of dynorphins in Alzheimer's disease and age-related cognitive deficits.\nExpression of dynorphin, an endogenous opioid peptide, increases with age and has been associated with cognitive deficits in rodents. Elevated dynorphin levels have been reported in postmortem samples from Alzheimer's disease (AD) patients, and prodynorphin (PDYN) gene polymorphisms might be linked to cognitive function in the elderly. Activation of \u03ba-opioid receptors by dynorphins has been associated with stress-related memory impairments. Interestingly, these peptides can also modulate glutamate neurotransmission and may affect synaptic plasticity underlying memory formation. N-methyl-D-aspartate (NMDA) and \u03b1-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA) ionotropic glutamate receptor levels generally decrease with aging, and their function is impaired in AD. Here, we compared the impact of aging on ionotropic glutamate receptor levels in the hippocampal formation of wild-type (WT) and Pdyn knock-out (KO) mice. We observed a significant reduction in GluR1 and GluR2 AMPA receptor subunits in the hippocampal formation of 18- to 25-month-old WT mice in comparison with 6-month-old mice. Conversely, the GluR1 protein level was maintained in old Pdyn KO mice, and the NMDA NR2B subunit level was increased by 42% when compared to old WT animals. These results suggest that elevated dynorphin expression occurring during aging and AD may mediate cognitive deficits by altering the glutamatergic system integrity.","subset":"pubmed_abstract"} +{"meta":{"pmid":18005689,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":4,"2024-18":3,"unknown":3}}},"text":"A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence.\nStaphylococcus aureus, a bacterium responsible for tremendous morbidity and mortality, exists as a harmless commensal in approximately 25% of humans. Identifying the molecular machinery activated upon infection is central to understanding staphylococcal pathogenesis. We describe the heme sensor system (HssRS) that responds to heme exposure and activates expression of the heme-regulated transporter (HrtAB). Inactivation of the Hss or Hrt systems leads to increased virulence in a vertebrate infection model, a phenotype that is associated with an inhibited innate immune response. We suggest that the coordinated activity of Hss and Hrt allows S. aureus to sense internal host tissues, resulting in tempered virulence to avoid excessive host tissue damage. Further, genomic analyses have identified orthologous Hss and Hrt systems in Bacillus anthracis, Listeria monocytogenes, and Enterococcus faecalis, suggesting a conserved regulatory system by which Gram-positive pathogens sense heme as a molecular marker of internal host tissue and modulate virulence.","subset":"pubmed_abstract"} +{"meta":{"pmid":25259490,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2018-22":1,"2017-13":1}}},"text":"A study of the kinetics and isotherms for Cr(VI) adsorption in a binary mixture of Cr(VI)-Ni(II) using hierarchical porous carbon obtained from pig bone.\nCr(VI) adsorption in a binary mixture Cr(VI)-Ni(II) using the hierarchical porous carbon prepared from pig bone (HPC) was investigated. The various factors affecting adsorption of Cr(VI) ions from aqueous solutions such as initial concentration, pH, temperature and contact time were analyzed. The results showed excellent efficiency of Cr(VI) adsorption by HPC. The kinetics and isotherms for Cr(VI) adsorption from a binary mixture Cr(VI)-Ni(II) by HPC were studied. The adsorption equilibrium described by the Langmuir isotherm model is better than that described by the Freundlich isotherm model for the binary mixture in this study. The maximum adsorption capacity was reliably found to be as high as 192.68 mg\/g in the binary mixture at pH 2. On fitting the experimental data to both pseudo-first- and second-order equations, the regression analysis of the second-order equation gave a better R\u00b2 value.","subset":"pubmed_abstract"} +{"meta":{"pmid":18955467,"dup_signals":{"dup_doc_count":20,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2015-18":1,"unknown":13}}},"text":"Sentinels of safety: service dogs ensure safety and enhance freedom and well-being for families with autistic children.\nChildren with autism might display unpredictable and volatile behavior that places them in considerable physical danger and creates stress for the family. Families of autistic children often have limited freedom and experience difficulty with everyday activities. In this qualitative ethology study, we examined the effect of integrating service dogs into ten families with an autistic child. Data included participant observation, video recordings of family-parent-dog interaction, and semistructured interviews with the parents. The themes were (a) the dog as a sentinel of safety, (b) gaining freedom through enhanced safety, facilitating public outings and family activities, and (c) improving social recognition and status, in which the presence of the dog promoted awareness of autism and affected social interaction. The triadic relationship between parent, autistic child, and service dog constantly evolves. This research provides valuable information for parents interested in having a service dog for their autistic child, and has implications for long-term human-animal companionship for children with special needs and their caregivers.","subset":"pubmed_abstract"} +{"meta":{"pmid":19724005,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":2,"2013-20":2,"unknown":4}}},"text":"Snapping scapula syndrome.\nSnapping scapula syndrome arises from either a soft-tissue or a skeletal anomaly within the scapulothoracic space that creates a cracking sound during scapulothoracic motion that patients associate with pain. Nonoperative measures consisting of supervised physical therapy, anti-inflammatory medications, and therapeutic injections are the mainstay of treatment. Open, arthroscopic, and combined operative approaches have been described for the treatment of refractory cases, with good overall outcomes in many relatively small case series. However, the optimal operative approach has yet to be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":26019191,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-31":1,"2017-13":1}}},"text":"Longitudinal patient-oriented outcomes in neuropathy: Importance of early detection and falls.\nTo evaluate longitudinal patient-oriented outcomes in peripheral neuropathy over a 14-year time period including time before and after diagnosis. The 1996-2007 Health and Retirement Study (HRS)-Medicare Claims linked database identified incident peripheral neuropathy cases (ICD-9 codes) in patients \u226565 years. Using detailed demographic information from the HRS and Medicare claims, a propensity score method identified a matched control group without neuropathy. Patient-oriented outcomes, with an emphasis on self-reported falls, pain, and self-rated health (HRS interview), were determined before and after neuropathy diagnosis. Generalized estimating equations were used to assess differences in longitudinal outcomes between cases and controls. We identified 953 peripheral neuropathy cases and 953 propensity-matched controls. The mean (SD) age was 77.4 (6.7) years for cases, 76.9 (6.6) years for controls, and 42.1% had diabetes. Differences were detected in falls 3.0 years before neuropathy diagnosis (case vs control; 32% vs 25%, p = 0.008), 5.0 years for pain (36% vs 27%, p = 0.002), and 5.0 years for good to excellent self-rated health (61% vs 74%, p < 0.0001). Over time, the proportion of fallers increased more rapidly in neuropathy cases compared to controls (p = 0.002), but no differences in pain (p = 0.08) or self-rated health (p = 0.9) were observed. In older persons, differences in falls, pain, and self-rated health can be detected 3-5 years prior to peripheral neuropathy diagnosis, but only falls deteriorates more rapidly over time in neuropathy cases compared to controls. Interventions to improve early peripheral neuropathy detection are needed, and future clinical trials should incorporate falls as a key patient-oriented outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":3044882,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Diet-induced type II diabetes in C57BL\/6J mice.\nWe investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL\/6J and A\/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A\/J and C57BL\/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A\/J mice, obese C57BL\/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg\/dl and blood insulin levels of greater than 150 microU\/ml. C57BL\/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL\/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19290226,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Effect of Within-field Variation in Soil Texture on Heterodera glycines and Soybean Yield.\nThe influence of soil texture on Soybean yield in the presence of Heterodera glycines was investigated by comparing yields of susceptible cultivars with a resistant cultivar for 2 years. Soybean yield was negatively correlated with increasing sand content (P = 0.05). Yields of susceptible cultivars were suppressed with increasing sand content. Final nematode population densities were lowest in plots with greatest sand content. Soybean infection by SCN, as determined by the number of cysts 30 days after planting, was not consistently related to soil texture over 2 years. Initial nematode population density was positively related to soybean yield the first year and negatively related to soybean yield the second, probably a result of greater yield suppression by H. glycines in plots with greater sand content.","subset":"pubmed_abstract"} +{"meta":{"pmid":21495888,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"The influence of the 2010 World Cup on the Tygerberg Poison Information Centre.\nThe soccer World Cup is one of the biggest sporting events in the world, but data on the effect of sporting events of such a magnitude on the service demand on Poison Information Centres (PICs) are limited. The aim of this study was to determine the influence of the 2010 World Cup on the workload of the Tygerberg Poison Information Centre (TPIC). Data were collected prospectively for three time periods during 2010: (1) 31 days preceding the World Cup (10 May-10 June); (2) 31 days during the World Cup (11 June-11 July); and (3) 31 days after the World Cup (12 July-11 August). The calls received during 2010 were compared to calls received during corresponding time periods in 2008 and 2009. Collected data included date and time, caller's location and medical background, patient's age and gender, intent of exposure, route of exposure and specific toxin class. During the study, 3888 calls related to human poisoning were received (1162 in 2010, 1412 in 2009 and 996 in 2008). The mean daily call volume between 2010 (12.49; 95% CI 11.57-13.42) and 2009 (13.23; 95% CI 12.30-14.15) did not differ significantly (p = 0.25). The mean daily call volume during the World Cup was 11.13 (95% CI 9.59-12.67; n = 345) compared to 14.26 (95% CI 12.71-15.80; n = 442) for the similar period in 2009 (p = 0.08). The mean daily call volume before and after the World Cup was 12.74 (95% CI 11.20-14.29; n = 395) and 13.61 (95% CI 12.07-15.16; n = 422); p = 1.00 and p = 0.39, respectively, when compared with the World Cup period. An unexpected finding of this study was that the hosting of the 2010 World Cup resulted in fewer calls to the TPIC. This decrease could be attributed to the high visibility of policing, an extended school holiday and the positive attitudes of South Africans towards making the World Cup a success. PICs should be consulted during the planning stages of major sporting events. Contingency plans should still be in place to overcome any unexpected rise in call volume.","subset":"pubmed_abstract"} +{"meta":{"pmid":22969327,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Geometric and colour data fusion for outdoor 3D models.\nThis paper deals with the generation of accurate, dense and coloured 3D models of outdoor scenarios from scanners. This is a challenging research field in which several problems still remain unsolved. In particular, the process of 3D model creation in outdoor scenes may be inefficient if the scene is digitalized under unsuitable technical (specific scanner on-board camera) and environmental (rain, dampness, changing illumination) conditions. We address our research towards the integration of images and range data to produce photorealistic models. Our proposal is based on decoupling the colour integration and geometry reconstruction stages, making them independent and controlled processes. This issue is approached from two different viewpoints. On the one hand, given a complete model (geometry plus texture), we propose a method to modify the original texture provided by the scanner on-board camera with the colour information extracted from external images taken at given moments and under specific environmental conditions. On the other hand, we propose an algorithm to directly assign external images onto the complete geometric model, thus avoiding tedious on-line calibration processes. We present the work conducted on two large Roman archaeological sites dating from the first century A.D., namely, the Theatre of Segobriga and the Fori Porticus of Emerita Augusta, both in Spain. The results obtained demonstrate that our approach could be useful in the digitalization and 3D modelling fields.","subset":"pubmed_abstract"} +{"meta":{"pmid":26824961,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Enhanced Bioaccessibility of Curcuminoids in Buttermilk Yogurt in Comparison to Curcuminoids in Aqueous Dispersions.\nCurcuminoids have low bioavailability due to low aqueous solubility. We compared the bioaccessibility of curcuminoids delivered in buttermilk yogurt to that of curcuminoid powder in an aqueous dispersion. Buttermilk containing added curcuminoids (300 mg\/100 g, 0.3% w\/w) was used for yogurt manufacture. We measured percentage of curcuminoids remaining in yogurts after manufacture and after exposure to simulated gastrointestinal fluids, and the in vitro bioaccessibility of the curcuminoids. Curcuminoids were stable during yogurt manufacture. At the end of in vitro digestion, approximately 11% of the curcuminoids delivered in yogurt was degraded compared to <1% for curcuminoids in an aqueous dispersion. However, curcuminoids delivered in yogurt was 15-fold more bioaccessible than curcuminoids in aqueous dispersion. The small change in yogurt properties (decrease in total lactic acid bacteria counts of <1 log and increased viscosity) on addition of curcuminoids has to be balanced against the benefits of increased bioaccessibility of curcuminoids when delivered in yogurts.","subset":"pubmed_abstract"} +{"meta":{"pmid":26854567,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-22":1,"unknown":10}}},"text":"Plasmonic nanofocused four-wave mixing for femtosecond near-field imaging.\nFemtosecond nonlinear optical imaging with nanoscale spatial resolution would provide access to coupled degrees of freedom and ultrafast response functions on the characteristic length scales of electronic and vibrational excitations. Although near-field microscopy provides the desired spatial resolution, the design of a broadband high-contrast nanoprobe for ultrafast temporal resolution is challenging due to the inherently weak nonlinear optical signals generated in subwavelength volumes. Here, we demonstrate broadband four-wave mixing with enhanced nonlinear frequency conversion efficiency at the apex of a nanometre conical tip. Far-field light is coupled through a grating at the shaft of the tip, generating plasmons that propagate to the apex while undergoing asymptotic compression and amplification, resulting in a nonlinear conversion efficiency of up to 1 \u00d7 10(-5). We apply this nonlinear nanoprobe to image the few-femtosecond coherent dynamics of plasmonic hotspots on a nanostructured gold surface with spatial resolution of a few tens of nanometres. The approach can be generalized towards spatiotemporal imaging and control of coherent dynamics on the nanoscale, including the extension to multidimensional spectroscopy and imaging.","subset":"pubmed_abstract"} +{"meta":{"pmid":2982533,"dup_signals":{"dup_doc_count":25,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":2,"2022-33":2,"2022-27":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-40":1,"2018-30":1,"2017-51":1,"2016-44":1,"2023-50":1,"2024-22":2,"2024-26":1}}},"text":"Effects of dietary fish oil supplementation on the fatty acid composition of the human platelet membrane: demonstration of selectivity in the incorporation of eicosapentaenoic acid into membrane phospholipid pools.\nThe fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.","subset":"pubmed_abstract"} +{"meta":{"pmid":23439116,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":9}}},"text":"\"Seq-ing\" insights into the epigenetics of neuronal gene regulation.\nThe epigenetic control of neuronal gene expression patterns has emerged as an underlying regulatory mechanism for neuronal function, identity, and plasticity, in which short- to long-lasting adaptation is required to dynamically respond and process external stimuli. To achieve a comprehensive understanding of the physiology and pathology of the brain, it becomes essential to understand the mechanisms that regulate the epigenome and transcriptome in neurons. Here, we review recent advances in the study of regulated neuronal gene expression, which are dramatically expanding as a result of the development of new and powerful contemporary methodologies, based on next-generation sequencing. This flood of new information has already transformed our understanding of many biological processes and is now driving discoveries elucidating the molecular mechanisms of brain function in cognition, behavior, and disease and may also inform the study of neuronal identity, diversity, and neuronal reprogramming.","subset":"pubmed_abstract"} +{"meta":{"pmid":21855838,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":11}}},"text":"Association of serum uric acid with incident atrial fibrillation (from the Atherosclerosis Risk in Communities [ARIC] study).\nAtrial fibrillation (AF) is one of the most common arrhythmias seen in clinical practice. Current evidence suggests that serum uric acid (SUA) could be a marker of oxidative damage, a factor reported as a part of the mechanisms of AF. The purpose of the present study was to evaluate whether SUA predicted AF in the Atherosclerosis Risk In Communities (ARIC) study. The present analysis included 15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC study, a population-based prospective cohort in the United States. SUA was determined using the uricase-peroxidase method at baseline. The primary outcome was the incidence of AF, defined as the occurrence of AF detected using hospital discharge codes, scheduled study electrocardiograms, and\/or death certificates during the follow-up period (1987 to 2004). We identified 1,085 cases of incident AF. In Cox proportional hazards models adjusted for age, gender, race, center, education, body mass index, serum glucose, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart disease and heart failure, serum creatinine, diuretics, and P-wave duration on the electrocardiogram (as a measure of left atrial size) at baseline, the hazard ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence interval 1.06 to 1.26). The association of SUA with AF risk differed by race and gender (p for interaction <0.01). In conclusion, elevated SUA is associated with a greater risk of AF, particularly among blacks and women. Additional studies should replicate this association and explore potential mechanisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":23297212,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Ingredients of a 2,000-y-old medicine revealed by chemical, mineralogical, and botanical investigations.\nIn archaeology, the discovery of ancient medicines is very rare, as is knowledge of their chemical composition. In this paper we present results combining chemical, mineralogical, and botanical investigations on the well-preserved contents of a tin pyxis discovered onboard the Pozzino shipwreck (second century B.C.). The contents consist of six flat, gray, discoid tablets that represent direct evidence of an ancient medicinal preparation. The data revealed extraordinary information on the composition of the tablets and on their possible therapeutic use. Hydrozincite and smithsonite were by far the most abundant ingredients of the Pozzino tablets, along with starch, animal and plant lipids, and pine resin. The composition and the form of the Pozzino tablets seem to indicate that they were used for ophthalmic purposes: the Latin name collyrium (eyewash) comes from the Greek name \u03bao\u03bb\u03bb\u03c5\u03c1\u03b1, which means \"small round loaves.\" This study provided valuable information on ancient medical and pharmaceutical practices and on the development of pharmacology and medicine over the centuries. In addition, given the current focus on natural compounds, our data could lead to new investigations and research for therapeutic care.","subset":"pubmed_abstract"} +{"meta":{"pmid":16467143,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Directing electron transfer within Photosystem I by breaking H-bonds in the cofactor branches.\nPhotosystem I has two branches of cofactors down which light-driven electron transfer (ET) could potentially proceed, each consisting of a pair of chlorophylls (Chls) and a phylloquinone (PhQ). Forward ET from PhQ to the next ET cofactor (FX) is described by two kinetic components with decay times of approximately 20 and approximately 200 ns, which have been proposed to represent ET from PhQB and PhQA, respectively. Immediately preceding each quinone is a Chl (ec3), which receives a H-bond from a nearby tyrosine. To decrease the reduction potential of each of these Chls, and thus modify the relative yield of ET within the targeted branch, this H-bond was removed by conversion of each Tyr to Phe in the green alga Chlamydomonas reinhardtii. Together, transient optical absorption spectroscopy performed in vivo and transient electron paramagnetic resonance data from thylakoid membranes showed that the mutations affect the relative amplitudes, but not the lifetimes, of the two kinetic components representing ET from PhQ to F(X). The mutation near ec3A increases the fraction of the faster component at the expense of the slower component, with the opposite effect seen in the ec3B mutant. We interpret this result as a decrease in the relative use of the targeted branch. This finding suggests that in Photosystem I, unlike type II reaction centers, the relative efficiency of the two branches is extremely sensitive to the energetics of the embedded redox cofactors.","subset":"pubmed_abstract"} +{"meta":{"pmid":34157093,"dup_signals":{"dup_doc_count":14}},"text":"Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study.\nOmidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299.","subset":"pubmed_abstract"} +{"meta":{"pmid":23274083,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2021-17":1,"2021-04":1,"2018-43":1,"2018-34":1,"2018-22":2,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2023-06":1,"2024-26":1,"2024-30":1}}},"text":"Investigation of the effectiveness of Syzygium aromaticum, Lavandula angustifolia and Geranium robertianum essential oils in the treatment of acute external otitis: a comparative trial with ciprofloxacin.\nAntibiotics and anti-inflammatory agents are the mainstay of acute external otitis (AEO) treatment. The present study investigated the effectiveness of a combination herbal drop (Lamigex) composed of essential oils from Syzygium aromaticum, Lavandula angustifolia, and Geranium robertianum in the alleviation of AEO symptoms and compared its effects to those of ciprofloxacin 0.3% drop. Seventy patients were randomly assigned to receive ciprofloxacin 0.3% (n = 35) or Lamigex (n = 35) drop. Each group was administered with three drops every 12 hours for a week. Patients were examined for AEO symptoms and ear discharge cultures at baseline as well as at the end of trial. Pain severity was also recorded using a visual analogue scale at baseline, the 3(rd) day, and the 7(th) day of the trial. All assessed symptoms (tenderness, itching, erythema, edema and discharge) were equally improved in the ciprofloxacin and Lamigex groups by the end of trial (p > 0.05). There were remarkable reductions in the visual analogue scale score by the end of trial in both groups (p < 0.001). However, the rate of pain improvement was not found to be significantly different between the groups, either at the 3(rd) or 7(th) day of trial (p > 0.05). The numbers of positive cultures for all tested microorganisms were clearly reduced by the end of the trial in both groups but were not significantly different between the groups (p > 0.05). The herbal combination drop that was investigated in the present study exhibited good efficacy in reducing the burden of infection as well as AEO symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":28660064,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-47":1,"2019-43":1,"2018-47":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2020-50":1}}},"text":"Enrichment and fluorogenic labelling of 5-formyluracil in DNA.\nRecently, the detection of natural thymine modified 5-formyluracil has attracted widespread attention. Herein, we introduce a new insight into designing reagents for both the selective biotin enrichment and fluorogenic labelling of 5-formyluracil in DNA. Biotinylated o-phenylenediamine directly tethered to naphthalimide can switch on 5-formyluracil, under physiological conditions, which can then be used in cell imaging after exposure to \u03b3-irradiation. In addition, its labelling property caused the polymerase extension to stop in the 5-formyluracil site, which gave us more information than the fluorescence did itself. The idea of detecting 5-formyluracil might be used in the synthesis of other modified diaminofluoresceins.","subset":"pubmed_abstract"} +{"meta":{"pmid":19702948,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":9}}},"text":"Analysis of Streptococcus mutans biofilm proteins recognized by salivary immunoglobulin A.\nThe purpose of this study was to examine the Streptococcus mutans biofilm cellular proteins recognized by immunoglobulin A (IgA) in saliva from various caries-defined populations. Biofilm and planktonic S. mutans UA159 cells were prepared. The proteins were extracted, separated by two-dimensional gel electrophoresis, transferred to blotting membranes, and probed for IgA using individual saliva samples from three groups of subjects; those who developed 0 caries (no active caries), 5-9 caries (medium), or more than 10 caries (severe) over a 12-month interval. Several proteins were recognized by salivary IgA in all groups of saliva but spot distribution and intensity varied greatly between the groups, and some proteins were recognized more strongly in biofilm cells than in planktonic culture, and vice versa. Furthermore, 15 proteins were only recognized by saliva from the 'no active caries' group, and four proteins were recognized by saliva samples from subjects in all three groups. Specifically, antigen I\/II was recognized less in biofilm cells by caries-free saliva compared with planktonic cells. However, salivary IgA antibody to antigen I\/II was absent in blots using saliva from the 'medium caries' and 'severe caries' groups. The bacterial molecules recognized by caries-free saliva are significant factors for S. mutans caries formation, and their inhibition could be a therapeutic target. In addition, saliva of caries-free subjects includes significant IgA antibody against antigen I\/II of S. mutans, indicating a protective mechanism. However, microorganisms may protect themselves from host immune attack by forming biofilms and decreasing expression of antigen I\/II.","subset":"pubmed_abstract"} +{"meta":{"pmid":22331465,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Loss of cyclin-dependent kinase 2 (CDK2) inhibitory phosphorylation in a CDK2AF knock-in mouse causes misregulation of DNA replication and centrosome duplication.\nCyclin-dependent kinase 1 (CDK1) inhibitory phosphorylation controls the onset of mitosis and is essential for the checkpoint pathways that prevent the G(2)- to M-phase transition in cells with unreplicated or damaged DNA. To address whether CDK2 inhibitory phosphorylation plays a similar role in cell cycle regulation and checkpoint responses at the start of the S phase, we constructed a mouse strain in which the two CDK2 inhibitory phosphorylation sites, threonine 14 and tyrosine 15, were changed to alanine and phenylalanine, respectively (CDK2AF). This approach showed that inhibitory phosphorylation of CDK2 had a major role in controlling cyclin E-associated kinase activity and thus both determined the timing of DNA replication in a normal cell cycle and regulated centrosome duplication. Further, DNA damage in G(1) CDK2AF cells did not downregulate cyclin E-CDK2 activity when the CDK inhibitor p21 was also knocked down. We were surprised to find that this was insufficient to cause cells to bypass the checkpoint and enter the S phase. This led to the discovery of two previously unrecognized pathways that control the activity of cyclin A at the G(1) DNA damage checkpoint and may thereby prevent S-phase entry even when cyclin E-CDK2 activity is deregulated.","subset":"pubmed_abstract"} +{"meta":{"pmid":24751434,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Factors associated with returning to HIV care after a gap in care in New York State.\nRetention in HIV care has important implications. Few studies examining retention include comprehensive and heterogeneous populations, and few examine factors associated with returning to care after gaps in care. We identified reasons for gaps in care and factors associated with returning to care. We extracted medical record and state-wide reporting data from 1865 patients with 1 HIV visit to a New York facility in 2008 and subsequent 6-month gap in care. Using mixed effect logistic regression, we examined sociodemographic, clinical, and facility characteristics associated with returning to care. Most patients were men (63.2%), black (51.4%), had Medicaid (53.9%). Many had CD4 counts >500 cells per cubic millimeter (34.4%) and undetectable viral loads (45.0%). Most (55.9%) had unknown reasons for gaps in care; of those with known reasons, reasons varied considerably. After a gap, 54.6% returned to care. Patients who did (vs. did not) return to care were more likely to have stable housing, longer duration of HIV, high CD4 count, suppressed viral load, antiretroviral medications, and had facilities attempt to contact them. Those who returned to care were less likely to be uninsured and have mental health problems or substance use histories. Over half of our sample of patients in New York with 1 HIV visit and subsequent 6-month gap in care returned to care; no major reasons for gaps emerged. Nevertheless, our findings emphasize that stabilizing patients' psychosocial factors and contacting patients after a gap in care are key strategies to retain HIV-positive patients in care in New York.","subset":"pubmed_abstract"} +{"meta":{"pmid":16741301,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Characterization of the SPECT 5-HT2A receptor ligand 123I-R91150 in healthy volunteers: part 2--ketanserin displacement.\nAs part of the radioiodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2-methoxybenzamide ((123)I-R91150) characterization study, ketanserin challenges were performed on healthy volunteers with the aim of assessing the specificity of (123)I-R91150 binding to subtype 2A of the 5-hydroxytryptamine receptor (5-HT(2A)), the sensitivity of (123)I-R91150 SPECT in measuring ligand displacement, the relationship between ketanserin plasma concentrations and (123)I-R91150 displacement, and the suitability of the cerebellum as a reference region for quantification. Dynamic SPECT was performed on 6 healthy men (mean age +\/- SD, 21 +\/- 0.89 y) from the time of (123)I-R91150 injection until 470 min afterward. Ketanserin was administered intravenously at 210 min after injection at 3 doses: 0.1 mg\/kg (n = 2), 0.05 mg\/kg (n = 2), and 0.015 mg\/kg (n = 2). Blood samples for measurement of ketanserin plasma concentrations were drawn. MRI was performed on all subjects and coregistered to the SPECT data for region-of-interest drawing on cortical regions and cerebellum. The simplified reference tissue model (SRTM) was considered the gold standard for quantification, and results were compared with those obtained with the tissue ratio method (TR). The percentage (123)I-R91150 displacement was calculated with both methods as the percentage difference between baseline and postketanserin scans. Depending on the cerebral regions with the maximum ketanserin dose studied, SRTM and TR mean displacements were 57.1%-95.4% and 71.9%-101.2%, respectively, for the 0.1 mg\/kg dose; 51.7%-91.4% and 56.7%-102.8%, respectively, for the 0.05 mg\/kg dose; and 7.7%-54.5% and 13.8%-47.0%, respectively, for the lowest dose, 0.015 mg\/kg. A good correlation was found between the 2 methods. No ketanserin-induced displacement was observed in the cerebellum time-activity curves, supporting the use of the cerebellum as a reference region. The relationship between displacement and ketanserin plasma concentration fit with a rectangular hyperbola, with a 5.6 ng\/mL concentration associated with 50% of the maximum displacement (EC(50)). EC(50) values calculated using occupancies derived both with SRTM and with TR were in good agreement. (123)I-R91150 SPECT is sensitive enough to measure ketanserin dose-dependent displacement in cerebral regions rich in 5-HT(2A) receptors. These results support the selectivity of (123)I-R91150 for 5-HT(2A) receptors and its use as a SPECT ligand for measurements of drug-induced 5-HT(2A) receptor occupancy in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":25982959,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-10":1,"unknown":13}}},"text":"MMP and TIMP temporal gene expression during osteocytogenesis.\nOsteocytes within bone differentiate from osteoblast precursors which reside in a mineralised extracellular matrix (ECM). Fully differentiated osteocytes are critical for bone development and function but the factors that regulate this differentiation process are unknown. The enzymes primarily responsible for ECM remodelling are matrix metalloproteinases (MMP); however, the expression and role of MMPs during osteocytogenesis is undefined. Here we used MLO-A5 cells to determine the temporal gene expressions of the MMP family and their endogenous inhibitors--tissue inhibitors of metalloproteinases (TIMPs) during osteocytogenesis. RT-qPCR revealed expression of 14 Mmps and 3 Timps in MLO-A5 cells. Mmp2, Mmp23 and Mmp28 were decreased concurrent with mineralisation onset (P < 0.05*). Mmp14 and Mmp19 mRNAs were also significantly increased at day 3 (P < 0.05*) before returning to baseline levels at day 6. Decreased expressions of Timp1, Timp2 and Timp3 mRNA were observed by day 6 compared to day 0 (P < 0.05*). To examine whether these changes are linked to osteocytogenesis, we determined Mmp\/Timp mRNA expressions in mineralisation-limited conditions. RT-qPCR revealed that the previously observed decreases in Mmp2, Mmp23 and Mmp28 were not observed in these mineralisation-limited cultures, therefore closely linking these MMPs with osteocyte differentiation. Similarly, we found differential expression of Timp1, Timp2 and Timp3 mRNA in mineralisation-restricted cultures (P < 0.05*). In conclusion, we have identified several members of the MMP\/TIMP families as regulators of ECM remodelling necessary for the acquisition of the osteocyte phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":23284936,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis.\nNatalizumab is a recombinant monoclonal antibody raised against integrin alpha-4 (CD49d). It is approved for the treatment of patients with multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the CNS. While having shown high therapeutic efficacy, treatment by natalizumab has been linked to progressive multifocal leukoencephalopathy (PML) as a serious adverse effect. Furthermore, drug cessation sometimes induces rebound disease activity of unknown etiology. Here we investigated whether binding of this adhesion-blocking antibody to T lymphocytes could modulate their phenotype by direct induction of intracellular signaling events. Primary CD4(+) T lymphocytes either from healthy donors and treated with natalizumab in vitro or from MS patients receiving their very first dose of natalizumab were analyzed. Natalizumab induced a mild upregulation of IL-2, IFN-\u03b3 and IL-17 expression in activated primary human CD4(+) T cells propagated ex vivo from healthy donors, consistent with a pro-inflammatory costimulatory effect on lymphokine expression. Along with this, natalizumab binding triggered rapid MAPK\/ERK phosphorylation. Furthermore, it decreased CD49d surface expression on effector cells within a few hours. Sustained CD49d downregulation could be attributed to integrin internalization and degradation. Importantly, also CD4(+) T cells from some MS patients receiving their very first dose of natalizumab produced more IL-2, IFN-\u03b3 and IL-17 already 24 h after infusion. Together these data indicate that in addition to its adhesion-blocking mode of action natalizumab possesses mild direct signaling capacities, which can support a pro-inflammatory phenotype of peripheral blood T lymphocytes. This might explain why a rebound of disease activity or IRIS is observed in some MS patients after natalizumab cessation.","subset":"pubmed_abstract"} +{"meta":{"pmid":11911584,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":3,"2024-18":1,"unknown":6}}},"text":"Plasma concentrations of endothelin-like immunoreactivity in healthy horses and horses with naturally acquired gastrointestinal tract disorders.\nTo compare plasma endothelin (ET)- like immunoreactivity between healthy horses and those with naturally acquired gastrointestinal tract disorders. 29 healthy horses and 142 horses with gastrointestinal tract disorders. Blood samples were collected from healthy horses and from horses with gastrointestinal tract disorders prior to treatment. Magnitude and duration of abnormal clinical signs were recorded, and clinical variables were assessed via thorough physical examinations. Plasma concentrations of ET-like immunoreactivity were measured by use of a radioimmunoassay for human endothelin-1, and CBC and plasma biochemical analyses were performed. Plasma ET-like immunoreactivity concentration was significantly increased in horses with gastrointestinal tract disorders, compared with healthy horses. Median plasma concentration of ET-like immunoreactivity was 1.80 pg\/ml (range, 1.09 to 3.2 pg\/ml) in healthy horses. Plasma ET-like immunoreactivity was greatest in horses with strangulating large-intestinal obstruction (median, 10.02 pg\/ml; range, 3.8 to 22.62 pg\/ml), peritonitis (9.19 pg\/ml; 789 to 25.83 pg\/ml), and enterocolitis (8.89 pg\/mI; 6.30 to 18.36 pg\/ml). Concentration of ET-like immunoreactivity was significantly associated with survival, PCV, and duration of signs of pain. However, correlations for associations with PCV and duration of pain were low. Horses with gastrointestinal tract disorders have increased plasma concentrations of ET-like immunoreactivity, compared with healthy horses. The greatest values were detected in horses with large-intestinal strangulating obstructions, peritonitis, and enterocolitis. This suggests a potential involvement of ET in the pathogenesis of certain gastrointestinal tract disorders in horses.","subset":"pubmed_abstract"} +{"meta":{"pmid":18209336,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The spectrum of glomerulonephritis in saudi arabia: the results of the saudi registry.\nOnly few studies regarding glomerulonephritis, with relatively small numbers of patients, have so far been published from different centers in Saudi Arabia, and have reported conflicting results regarding the patterns, even in the same city. The possible reasons for these differences include the small number of patients in the different studies, differences in the indications for renal biopsies, referral bias, geographical differences, and, sometimes, the non-availability of the necessary diagnostic facilities in the reporting centers. In order to overcome these problems, a registry for glomerulonephropathy was attempted in Saudi Arabia. Six large referral hospitals from different regions of Saudi Arabia participated in this registry. Biopsy reports and clinical information of 1294 renal biopsies were obtained. There were 782 renal biopsies due to glomerulonephritis (GN) accounting for 77.2% of the total biopsies. Five hundred eighty seven (72.6%) were primary glomerulonephritidis. Focal and segmental glomerulosclerosis (FSGS) (21.3%) and membrano-proliferative glomerulonephritis (MPGN) (20.7%) were the most common types found in the primary glomerulonephritidis. Membranous glomerulonephritis (MGN) was present in only 10.6% of the cases. IgA nephropathy was found in 6.5% of the cases. Of the secondary glomerulo-nephritides, systemic lupus erythematosus (SLE) was the most common indication for biopsy (57.0%) and amyloidosis was found in only 3.2% of the biopsies. In conclusion, FSGS and MPGN were the most common forms of primary glomerulonephritis in adult patients in Saudi Arabia. MGN was not as common as in the western world. SLE was the commonest cause of secondary GN. Amyloidosis was not as common as in other Arab countries. There is a need for more centers from Saudi Arabia to join this national GN registry. Similar registries can be established in different Arab countries, which all would, hopefully, lead to a Pan-Arab GN registry.","subset":"pubmed_abstract"} +{"meta":{"pmid":18191112,"dup_signals":{"dup_doc_count":17,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1,"unknown":11}}},"text":"The FKBP5-gene in depression and treatment response--an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort.\nIn a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment. There was no association between markers in FKBP5 and disease. The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram. We used clinical data and DNA samples from 1809 outpatients with non-psychotic major depressive disorder (DSM-IV criteria), who received up to 14 weeks of citalopram. A subset of 1523 patients of White non-Hispanic or Black race was matched with 739 control subjects for a case-control analysis. The markers rs1360780 and rs4713916 were genotyped on the Illumina platform. TaqMan-assay was used for marker rs3800373. In the case-control analysis, marker rs1360780 was significantly associated with disease status in the White non-Hispanic sample after correction for multiple testing. A significant association was also found between rs4713916 and remission. Markers rs1360780 and rs4713916 were in strong linkage disequilibrium in the White non-Hispanic but not in the Black population. There was no significant difference in the number of previous episodes of depression between genotypes at any of the three markers. These results indicate that FKBP5 is an important target for further studies of depression and treatment response.","subset":"pubmed_abstract"} +{"meta":{"pmid":4504328,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Ovalbumin messenger RNA of chick oviduct: partial characterization, estrogen dependence, and translation in vitro.\nA rapidly-labeled RNA fraction can be isolated from hen oviduct polysomes that has characteristics of the messenger RNA (mRNA) for the cell-specific protein, ovalbumin. This RNA, which sediments in the 8-17S region of sucrose gradients, possesses properties suggestive of the presence of a polyadenylic acid sequence and can be translated with fidelity in a cell-free protein synthesizing system derived from rabbit reticulocytes. The identity of the protein product as ovalbumin is confirmed by three methods, and translation of ovalbumin mRNA is shown to be dependent both on amount of exogenous mRNA and incubation time. Both rate and extent of ovalbumin synthesis is enhanced by the addition of a protein extract from ribosomes that contains peptide chain initiation factors. Finally, the presence of this specific mRNA is shown to be estrogen-dependent: it is induced by estrogen administration to immature chicks, disappears upon cessation of estrogen treatment, and can be reinduced by a single injection of estrogen to chicks that have been pretreated with estrogen and then withdrawn from the hormone.","subset":"pubmed_abstract"} +{"meta":{"pmid":15158609,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Phagocytosis of M. paratuberculosis fails to activate expression of NADH dehydrogenase and nucleolin-related protein in bovine macrophages.\nMycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is a facultative intracellular bacterium and causal agent of Johne's disease in cattle. Following phagocytosis, M. paratuberculosis resides and replicates in macrophage phagosomes that fail to mature. Differential display reverse transcription polymerase chain reaction (DDRT-PCR) was used as a high throughput initial screen to begin to test the hypothesis that macrophage gene expression patterns would be differentially affected by M. paratuberculosis when compared to readily degraded bacteria or non-degradable latex beads. Gene expression profiles from immortalized bovine macrophage cells (BOMAC) exposed to M. paratuberculosis were compared to gene expression profiles for BOMAC cells exposed to Escherichia coli, latex beads or PBS. Amplicons representing genes specifically activated or repressed during M. paratuberculosis phagocytosis were cloned for further investigation. Northern blot hybridizations preformed using DDRT-PCR-derived amplicons 3-1-4, 5-2-10, 5-4-2 and 4-1-6 confirmed stimuli dependent differential gene expression. Expression pattern observed for amplicon 3-1-4 represents genes that are up-regulated following phagocytosis of E. coli or latex beads, but not M. paratuberculosis. Amplicon 5-2-10 exhibited a pattern of expression representative of genes that are up-regulated strongly following phagocytosis of E. coli or latex beads but only moderately following M. paratuberculosis phagocytosis. Expression pattern of the gene for amplicon 5-4-2 was representative of genes that are specifically suppressed following M. paratuberculosis phagocytosis, while the amplicon 4-1-6 gene expression pattern represented genes that are generally suppressed following phagocytosis of any of the three stimuli. DNA sequencing and Genbank database analysis of these amplicons revealed that amplicon 3-1-4, whose expression failed to activate following M. paratuberculosis phagocytosis, had high levels of similarity to a Rattus norvegicus nucleolin-related protein (NRP). Amplicon 5-2-10, which increased expression moderately following M. paratuberculosis phagocytosis, was a near perfect match to bovine nicotinamide adenine dinucleotide dehydrogenase (FNADH dehydrogenase) subunit 1 (ND1). Failure to activate these two genes at levels observed following phagocytosis of either E. coli or latex beads may uncover new mechanisms for the survival of M. paratuberculosis within bovine macrophage cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":11975328,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Phylogeny of lichen- and non-lichen-forming omphalinoid mushrooms and the utility of testing for combinability among multiple data sets.\nAs an initial step toward developing a model system to study requirements for and consequences of transitions to mutualism, the phylogeny of a group of closely related lichenized and nonlichenized basidiomycetes (Omphalina) was reconstructed. The phylogenetic analyses are based on four data sets representing different regions of the nuclear ribosomal repeat unit (ITS1, 5.8S, ITS2, and 25S) obtained from 30 species of Omphalina and related genera. The resulting phylogenetic trees from each of these four data sets, when analyzed separately, were not identical. Testing for the combinability of these four data sets suggested that they could not be combined in their entirety. The removal of ambiguous alignments and saturated sites was sufficient, after reapplying the combinability test on the pruned data sets, to explain the topological discrepancies. In this process, the first of two complementary tests developed by Rodrigo et al. (1993, N.Z. J. Bot. 31:257-268) to assess whether two data sets are the result of the same phylogenetic history was found to be biased, rejecting the combinability of two data sets even when they are samples of the same phylogenetic history. Combining the four pruned data sets yielded phylogenies that suggest the five lichen-forming species of Omphalina form a monophyletic group. The sister group to this symbiotic clade consists mostly of dark brown Omphalina species intermixed with species from the genera Arrhenia and Phaeothellus. The genera Omphalina and Gerronema are shown to be polyphyletic. The lichen-forming species O. ericetorum and the nonmutualistic species O. velutipes, O. epichysium, and O. sphagnicola are the best candidates for experimental work designed to gain a better understanding of mechanisms involved in symbiotic interactions and the role symbiosis has played in the evolution of fungi.","subset":"pubmed_abstract"} +{"meta":{"pmid":26019246,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Higher Protein Intake Is Associated with Higher Lean Mass and Quadriceps Muscle Strength in Adult Men and Women.\nThe impact of dietary protein intake on lower extremity lean mass and strength in community-dwelling adult Americans is not fully understood. The objective was to determine the associations between total protein (TP), animal protein (AP), and plant protein (PP) intakes and lean mass of the legs and quadriceps muscle strength. We further examined whether the associations with quadriceps strength may be explained by lean mass of the legs. This cross-sectional study included men (n = 1166) and women (n = 1509) from the Framingham Offspring Cohort in Massachusetts. Protein intake in grams per day was measured in either 1995-1998 or 1998-2001. Leg lean mass and isometric quadriceps strength, both in kilograms, were measured in 1996-2001. Multilinear regression models estimated adjusted least squares means of each of the muscle measures by quartile categories of protein intake, adjusting for relevant confounders and covariates. Mean age was 59 \u00b1 9 y (range: 29-86 y) and TP intake was 80 \u00b1 27 g\/d in men and 76 \u00b1 26 g\/d in women. In men and women, leg lean mass was higher in participants in the highest quartiles of TP and AP intake compared with those in the lowest quartiles of intake [least squares means (kg): TP-17.6 vs. 17.1 in men, P-trend: 0.005, and 11.7 vs. 11.4 in women, P-trend: 0.006; AP-17.6 vs. 17.1 in men, P-trend: 0.002, and 11.7 vs. 11.4 in women, P-trend: 0.003]. PP intake was not associated with lean mass in either sex. In men and women, quadriceps strength was higher in participants in the highest quartile of PP intake compared with those in the lowest quartile [least squares means (kg): 22.9 vs. 21.7 in men, P-trend: 0.01, and 19.0 vs. 18.2 in women, P-trend: 0.01]; this association was no longer significant after adjustment for fruit and vegetable intake (P-trend: 0.06 in men and 0.10 in women). Although no significant association was observed for AP intake in either sex, nonsignificant protective trends were observed for TP intake (P-trend: 0.08 in men and 0.10 in women). Our findings suggest that maintaining adequate protein intake with age may help preserve muscle mass and strength in adult men and women. Dietary protein types may differentially affect muscle mass and strength. Whether PP is a marker of dietary quality or has a direct effect on muscle strength (independent of lean mass) needs to be further clarified.","subset":"pubmed_abstract"} +{"meta":{"pmid":27763712,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Conservation implications of a lack of relationship between baseline glucocorticoids and fitness in a wild passerine.\nThe application of physiological measures to conservation monitoring has been gaining momentum and, while a suite of physiological traits are available to ascertain disturbance and condition in wildlife populations, glucocorticoids (i.e., GCs; cortisol and corticosterone) are the most heavily employed. The interpretation of GC levels as sensitive indicators of population change necessitates that GCs and metrics of population persistence are linked. However, the relationship between GCs and fitness may be highly context-dependent, changing direction, or significance, depending on the GC measure, fitness metric, life history stage, or other intrinsic and extrinsic contexts considered. We examined the relationship between baseline plasma corticosterone (CORT) levels measured at two periods of the breeding season and three metrics of fitness (offspring quality, reproductive output, and adult survival) in female Tree Swallows (Tachycineta bicolor). Specifically, we investigated whether (1) a relationship between baseline CORT metrics and fitness exists in our population, (2) whether the inclusion of energetic contexts, such as food availability, reproductive investment, or body mass, could alter or improve the strength of the relationship between CORT and fitness, and (3) whether energetic contexts could better predict fitness compared to CORT metrics. Importantly, we investigated these relationships in both natural conditions and under an experimental manipulation of foraging profitability (feather clipping) to determine the influence of an environmental constraint on GC-fitness relationships. We found a lack of relationship between baseline CORT and both short- and long-term metrics of fitness in control and clipped birds. In contrast, loss in body mass over reproduction positively predicted reproductive output (number of chicks leaving the nest) in control birds; however, the relationship was characterized by a low R2 (5%), limiting the predictive capacity, and therefore the application potential, of such a measure in a conservation setting. Our results stress the importance of ground-truthing GC-fitness relationships and indicate that baseline GCs will likely not be easily employed as conservation biomarkers across some species and life history stages. Given the accumulating evidence of temporally dynamic, inconsistent, and context-dependent GC-fitness relationships, placing effort towards directly measuring fitness traits, rather than plasma GC levels, will likely be more worthwhile for many conservation endeavours.","subset":"pubmed_abstract"} +{"meta":{"pmid":24806327,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Development of an engineered bioluminescent reporter phage for the sensitive detection of viable Salmonella typhimurium.\nBecause foodborne illnesses continuously threaten public health, rapid and sensitive detection of pathogens in food has become an important issue. As an alternative to time-consuming and laborious conventional detection methods, a technique using recombinant reporter phages has been developed. Here, we developed an advanced bioluminescent reporter phage SPC32H-CDABE by inserting a bacterial luxCDABE operon into the Salmonella temperate phage SPC32H genome. Whole SPC32H genome sequencing enabled the selection of nonessential genes, which can be replaced with approximately 6-kb luxCDABE operon, which provides both luciferase (LuxAB) and its substrate, fatty aldehyde, as generated by fatty acid reductase (LuxCDE). Thus, the SPC32H-CDABE detection assay is simpler and more efficient compared to the luxAB-based assay because the substrate addition step is excluded. At least 20 CFU\/mL of pure S. Typhimurium culture was detectable using SPC32H-CDABE within 2 h, and the signals increased proportionally to the number of cells contaminated in lettuce, sliced pork, and milk. These results thereby demonstrate that this phage successfully detects live Salmonella without appreciable interference from food components. Furthermore, the presented data suggest that SPC32H-CDABE represents a promising easy-to-use diagnostic tool for the detection of Salmonella contamination in food.","subset":"pubmed_abstract"} +{"meta":{"pmid":23089160,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The nature and correlates of paid and unpaid work among service users of London Community Mental Health Teams.\nAims. Little is known about how the rates and characteristics of mental health service users in unpaid work, training and study compare with those in paid employment. Methods. From staff report and patient records, 1353 mental health service users of seven Community Mental Health Teams in two London boroughs were categorized as in paid work, unpaid vocational activity or no vocational activity. Types of work were described using Standard Occupational Classifications. The characteristics of each group were reported and associations with vocational status were explored. Results. Of the sample, 5.5% were in paid work and 12.7% were in unpaid vocational activity, (including 5.3% in voluntary work and 8.1% in study or training). People in paid work were engaged in a broader range of occupations than those in voluntary work and most in paid work (58.5%) worked part-time. Younger age and high educational attainment characterized both groups. Having sustained previous employment was most strongly associated with being in paid work. Conclusions. Rates of vocational activity were very low. Results did not suggest a clear clinical distinction between those in paid and unpaid activity. The motivations for and functions of unpaid work need further research.","subset":"pubmed_abstract"} +{"meta":{"pmid":32553191,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":9}}},"text":"Aqueous olanexidine versus aqueous povidone-iodine for surgical skin antisepsis on the incidence of surgical site infections after clean-contaminated surgery: a multicentre, prospective, blinded-endpoint, randomised controlled trial.\nSurgical site infection (SSI) is the most common problem after surgery. Although several guidelines have indicated the efficacy of antiseptics, such as chlorhexidine-alcohol and povidone-iodine, in reducing SSI rate, the optimal recommendation is still not established. Olanexidine might have higher bactericidal activity than other antiseptic agents. However, no randomised study has evaluated the efficacy and safety of olanexidine over conventional antiseptics. We compared the effect of aqueous olanexidine and aqueous povidone-iodine on the incidence of SSI following clean-contaminated surgery. This was a multicentre, prospective, randomised, blinded-endpoint superiority trial for surgical skin antisepsis in clean-contaminated gastrointestinal and hepatobiliary pancreatic surgeries in four Japanese hospitals. Patients aged 20 years or older who underwent elective clean-contaminated wound surgery were randomly assigned in a 1:1 replacement ratio using a computer-generated block randomisation. Patients were randomly assigned to surgical skin antisepsis with an aqueous formulation of 1\u00b75% olanexidine or surgical skin antisepsis with an aqueous formulation of 10% povidone-iodine before surgery. We used olanexidine in a ready-to-use applicator, and povidone-iodine was administered by a brush or by compression using pliers. Both antiseptics were applied from the papilla with a cranial limit and to the upper thigh with a caudal limit. The antiseptics were allowed to dry for 3 min, and then surgery started. Participants, some investigators, and data analysts were masked to treatment allocation. Participant enrolment was done by non-masked investigators. The primary outcome was 30-day SSI assessed in the intention-to-treat population. The surgical wound site of each participant was observed daily. After discharge, participants underwent at least one outpatient visit within 30 days after surgery. This trial is registered with University hospital Medical Information Network, 000031560. Between June 10, 2018, and April 18, 2019, 883 patients were assessed for eligibility. 587 patients were eligible and 294 received olanexidine and 293 received aqueous povidone-iodine before surgery. 30-day SSI occurred in 19 (7%) patients in the olanexidine group and 39 patients (13%) patients in the povidone-iodine group (adjusted risk difference -0\u00b7069; 90% CI -0\u00b7109 to -0\u00b7029; adjusted risk ratio [RR] 0\u00b748, 90% CI 0\u00b730 to 0\u00b774; p=0\u00b7002). Five patients (2%) in the olanexidine group and five (2%) in the povidone-iodine group developed adverse skin reactions (adjusted RR 0\u00b799, 95% CI 0\u00b729 to 3\u00b740; p=1\u00b700). Olanexidine significantly reduced the occurrence of overall SSI and superficial incisional SSI compared with aqueous povidone-iodine in clean-contaminated surgery. Our results indicate that olanexidine might have a role to prevent SSI in patients who undergo clean-contaminated surgeries. Keio University and Ohyama Health Foundation.","subset":"pubmed_abstract"} +{"meta":{"pmid":24463952,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":2,"2024-10":1,"2024-30":1,"unknown":15}}},"text":"Revisiting the classification of curtoviruses based on genome-wide pairwise identity.\nMembers of the genus Curtovirus (family Geminiviridae) are important pathogens of many wild and cultivated plant species. Until recently, relatively few full curtovirus genomes have been characterised. However, with the 19 full genome sequences now available in public databases, we revisit the proposed curtovirus species and strain classification criteria. Using pairwise identities coupled with phylogenetic evidence, revised species and strain demarcation guidelines have been instituted. Specifically, we have established 77 % genome-wide pairwise identity as a species demarcation threshold and 94 % genome-wide pairwise identity as a strain demarcation threshold. Hence, whereas curtovirus sequences with >77 % genome-wide pairwise identity would be classified as belonging to the same species, those sharing >94 % identity would be classified as belonging to the same strain. We provide step-by-step guidelines to facilitate the classification of newly discovered curtovirus full genome sequences and a set of defined criteria for naming new species and strains. The revision yields three curtovirus species: Beet curly top virus (BCTV), Spinach severe surly top virus (SpSCTV) and Horseradish curly top virus (HrCTV).","subset":"pubmed_abstract"} +{"meta":{"pmid":33820526,"dup_signals":{"dup_doc_count":26,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":2,"2024-10":1,"2024-30":1,"unknown":19}}},"text":"To denoise or to cluster, that is not the question: optimizing pipelines for COI metabarcoding and metaphylogeography.\nThe recent blooming of metabarcoding applications to biodiversity studies comes with some relevant methodological debates. One such issue concerns the treatment of reads by denoising or by clustering methods, which have been wrongly presented as alternatives. It has also been suggested that denoised sequence variants should replace clusters as the basic unit of metabarcoding analyses, missing the fact that sequence clusters are a proxy for species-level entities, the basic unit in biodiversity studies. We argue here that methods developed and tested for ribosomal markers have been uncritically applied to highly variable markers such as cytochrome oxidase I (COI) without conceptual or operational (e.g., parameter setting) adjustment. COI has a naturally high intraspecies variability that should be assessed and reported, as it is a source of highly valuable information. We contend that denoising and clustering are not alternatives. Rather, they are complementary and both should be used together in COI metabarcoding pipelines. Using a COI dataset from benthic marine communities, we compared two denoising procedures (based on the UNOISE3 and the DADA2 algorithms), set suitable parameters for denoising and clustering, and applied these steps in different orders. Our results indicated that the UNOISE3 algorithm preserved a higher intra-cluster variability. We introduce the program DnoisE to implement the UNOISE3 algorithm taking into account the natural variability (measured as entropy) of each codon position in protein-coding genes. This correction increased the number of sequences retained by 88%. The order of the steps (denoising and clustering) had little influence on the final outcome. We highlight the need for combining denoising and clustering, with adequate choice of stringency parameters, in COI metabarcoding. We present a program that uses the coding properties of this marker to improve the denoising step. We recommend researchers to report their results in terms of both denoised sequences (a proxy for haplotypes) and clusters formed (a proxy for species), and to avoid collapsing the sequences of the latter into a single representative. This will allow studies at the cluster (ideally equating species-level diversity) and at the intra-cluster level, and will ease additivity and comparability between studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":27248906,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2023-40":1,"2024-18":1}}},"text":"Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome.\nDemonstrating the presence of myelodysplastic syndrome (MDS)-specific molecular abnormalities can aid in diagnosis and patient management. We explored the potential of using peripheral blood (PB) cell-free DNA (cf-DNA) and next-generation sequencing (NGS). We performed NGS on a panel of 14 target genes using total nucleic acid extracted from the plasma of 16 patients, all of whom had confirmed diagnoses for early MDS with blasts <5%. PB cellular DNA from the same patients was sequenced using conventional Sanger sequencing and NGS. Deep sequencing of the cf-DNA identified one or more mutated gene(s), confirming the diagnosis of MDS in all cases. Five samples (31%) showed abnormalities in cf-DNA by NGS that were not detected by Sanger sequencing on cellular PB DNA. NGS of PB cell DNA showed the same findings as those of cf-DNA in four of five patients, but failed to show a mutation in the RUNX1 gene that was detected in one patient's cf-DNA. Mutant allele frequency was significantly higher in cf-DNA compared with cellular DNA (p = 0.008). These data suggest that cf-DNA when analyzed using NGS is a reliable approach for detecting molecular abnormalities in MDS and should be used to determine if bone marrow aspiration and biopsy are necessary.","subset":"pubmed_abstract"} +{"meta":{"pmid":23676497,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":16}}},"text":"Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease.\nA disintegrin and metalloproteinase 10 (ADAM10), a disintegrin and metalloproteinase that resides in the postsynaptic densities (PSDs) of excitatory synapses, has previously been shown to limit \u03b2-amyloid peptide (A\u03b2) formation in Alzheimer's disease (AD). ADAM10 also plays a critical role in regulating functional membrane proteins at the synapse. Using human hippocampal homogenates, we found that ADAM10 removal from the plasma membrane was mediated by clathrin-dependent endocytosis. Additionally, we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. This domain was required for ADAM10 endocytosis and modulation of its plasma membrane levels. We found that the ADAM10\/AP2 association was increased in the hippocampi of AD patients compared with healthy controls. Long-term potentiation (LTP) in hippocampal neuronal cultures induced ADAM10 endocytosis through AP2 association and decreased surface ADAM10 levels and activity. Conversely, long-term depression (LTD) promoted ADAM10 synaptic membrane insertion and stimulated its activity. ADAM10 interaction with the synapse-associated protein-97 (SAP97) was necessary for LTD-induced ADAM10 trafficking and required for LTD maintenance and LTD-induced changes in spine morphogenesis. These data identify and characterize a mechanism controlling ADAM10 localization and activity at excitatory synapses that is relevant to AD pathogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29518593,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Aerobic granular sludge treating high strength citrus wastewater: Analysis of pH and organic loading rate effect on kinetics, performance and stability.\nIn the present paper, the feasibility of citrus wastewater treatment with aerobic granular sludge sequencing batch reactors (AGSBR) was investigated. Two AGSBRs (named R1 and R2, respectively) were operated for 90 days under different organic loading rates (OLR) and pH in two experimental periods. The OLR ranged approximately between 3.0 kg TCOD m-3d-1 and 7 kg TCOD m-3d-1 during Period I, whereas between 7 kg TCOD m-3d-1 and 15 kg TCOD m-3d-1 during Period II. pH was maintained at 7.0 and 5.5 in R1 and R2, respectively. The results revealed that under high OLR and unbalanced feast\/famine regime (Period I), the development of fast-growing microorganisms (fungi and filamentous bacteria) was favoured in both reactors, resulting in granular sludge instability. An extended famine phase and a proper balancing between feast and famine periods (Period II) were favourable for the development of bacteria with low growth rates (0.05 d-1) thus enhancing the granules stability. To the benefit of granular sludge stability and effluent quality, the length of the feast period should not exceed 25% of cycle length. Moreover, under OLR lower than 7 kg TCOD m-3d-1 the removal efficiency of total chemical oxygen demand (TCOD) was approximately 90% in R1 and R2 and no side effects on the organic carbon removal performance related to the pH were observed. In contrast, at higher OLR a significant decrease in the removal efficiency (from 90% to less than 75%) was observed in R2. Results revealed also that under low pH, hydrolysis of proteins occurred and a decrease in the biological kinetic rates proportionally to the applied OLR was observed.","subset":"pubmed_abstract"} +{"meta":{"pmid":27502426,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"A PROCESS OF PRIORITIZING TOPICS FOR HEALTH TECHNOLOGY ASSESSMENT IN KAZAKHSTAN.\nThe aim of this study was to develop criteria for the prioritization of topics for health technology assessment (HTA) in the healthcare system of Kazakhstan. Initial proposals for criteria were suggested through consultation with Ministry of Health (MoH) policy areas. These were refined through a workshop attended by HTA department staff, persons from medical universities and research institutes, and MoH policy makers. The workshop included discussion on methods used in international HTA practice. Opinions of participants on selection of criteria from those specified in a review of prioritization processes were used to define a list for inclusion in an instrument for routine use. A scoring system was established in later discussion. Selected criteria for HTA prioritization were burden of disease, availability of alternative technology, clinical effectiveness, economic efficiency, budget impact, and ethical, legal, and\/or psychosocial aspects. For each criterion, a health technology under consideration is given a score from 3 (High) to 1 (Low). The total score determines whether the technology is of high to medium priority or of low priority. Determination of priorities for assessment, using the instrument, should be carried out by an expert group appointed by the MoH. The process was applied in 2014 to a selection of topics, and three health technologies were chosen for full assessments. Criteria for prioritization have evolved with development of the HTA program in Kazakhstan. A method for HTA prioritization has been developed that is easy to apply, requires comparatively few resources, and is compatible with processes required by the MoH.","subset":"pubmed_abstract"} +{"meta":{"pmid":31507453,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":18}}},"text":"Stronger Is Better: The Impact of Upper Body Strength in Double Poling Performance.\nThe purpose of the present study was to compare time results from a roller-skiing double poling (DP) time trial with different physiological variables, muscular strength variables, and DP characteristics in both male and female young competitive skiers with the same relative training background. In order to do this, 28 (16 women and 12 men) well-trained 16-25-year-old cross-country skiers from three Norwegian high schools for skiers, as well as local high performance competitive skiers from the South-East of Norway were recruited to participate in the study. All participants were tested for; maximal oxygen uptake in running, Peak oxygen uptake in DP, lactate threshold in DP, DP economy, time to voluntary exhaustion in DP, force analyses in DP, one repetition maximum and power output in pulldown, and leg press and a time trial during DP roller skiing. The results expressed strong correlations between roller skiing time trial performance and maximal strength in pull-down, both independent (r xy = -0.83, p < 0.01) and dependent (r xy-z = -0.50, p < 0.02) of sex. Higher maximal upper body strength was related to higher DP peak forces (PF) (r xy = 0.78, p < 0.02), lower DP frequency (r xy = -0.71, p < 0.01), and shorter DP contact time (CT) (r xy = -0.48, p < 0.02). The practical implications of the present study is to acknowledge maximal upper body strength as a performance determining factor in DP. This point at the importance of including maximal strength training in cross-country skiers training programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":24978518,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":2,"unknown":10}}},"text":"Photonic-to-plasmonic mode converter.\nA novel photonic-to-plasmonic mode converter for efficiently converting a silicon strip waveguide mode to a gap surface plasmon polariton (SPP) of a metallic slot structure is proposed. A conversion efficiency of more than 85% is found for metallic slots with a slot size of 30-50 nm. Calculations show that high conversion efficiencies can be achieved for various cladding materials with refractive indices of 1.44, 1.6, and 1.7. The optical 1 dB bandwidth of the converter is around 200 nm. The proposed mode converter shows a good tolerance with respect to fabrication errors, and it requires a simple fabrication procedure only.","subset":"pubmed_abstract"} +{"meta":{"pmid":32407086,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"How the Local Environment of Functional Sites Regulates Protein Function.\nProteins form complex biological machineries whose functions in the cell are highly regulated at both the cellular and molecular levels. Cellular regulation of protein functions involves differential gene expressions, post-translation modifications, and signaling cascades. Molecular regulation, on the other hand, involves tuning an optimal local protein environment for the functional site. Precisely how a protein achieves such an optimal environment around a given functional site is not well understood. Herein, by surveying the literature, we first summarize the various reported strategies used by certain proteins to ensure their correct functioning. We then formulate three key physicochemical factors for regulating a protein's functional site, namely, (i) its immediate interactions, (ii) its solvent accessibility, and (iii) its conformational flexibility. We illustrate how these factors are applied to regulate the functions of free\/metal-bound Cys and Zn sites in proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":26341119,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Impact of Digoxin on Mortality in Patients With Atrial Fibrillation Stratified by Heart Failure: Findings From Gulf Survey of Atrial Fibrillation Events in the Middle East.\nThe use of digoxin in patients having atrial fibrillation (AF) with or without heart failure (HF) is not without controversy. The aim of this study was to examine the impact of digoxin therapy on mortality stratified by HF. Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department of 23 hospitals in 6 countries in the Middle East. Patients were recruited between October 2009 and June 2010 and followed up for 1 year after enrollment. Analyses were performed using univariate and multivariate statistical techniques. The study included a total of 1962 patients with AF, with an overall mean age of 56 \u00b1 16 years, and 52% (n = 1026) were males. At hospital discharge, digoxin was prescribed in 36% (n = 709) of the patients, whereas HF was present in 27% (n = 528) of the cohort. A total of 225 (12.1%) patients died during the 12-month follow-up period after discharge (5.3% [n = 104] were lost to follow-up). Patients with HF were consistently associated with higher mortality at 1 month (5.1% vs 2.1%; P < .001), 6 months (17.2% vs 5.0%; P < 0.001), and 12 months (24.3% vs 7.6%; P < .001) when compared to those without HF. When stratified by HF, digoxin therapy was associated with significantly higher mortality in those without HF at 6 months (8.7% vs 3.7%; adjusted odds ratio (aOR), 5.07; P < .001) and 12 months (12.3% vs 6.0%; aOR, 4.22; P < .001) but not in those with HF (6 months: 18.6% vs 14.7%; aOR, 1.62; P = .177 and 12 months: 25.4% vs 22.4%; aOR, 1.37; P = .317). In patients with AF and HF, digoxin did not offer any survival advantages. However, in those without HF, digoxin therapy was, in fact, associated with significantly higher long-term mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":15777017,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Clinical aspects of reactive oxygen and nitrogen species.\nEndothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and\/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":23048011,"dup_signals":{"dup_doc_count":30,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2020-16":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-39":2,"2018-30":1,"2021-17":1,"2013-48":1,"2013-20":2,"2014-10":1}}},"text":"Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial.\nTo investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women. Open label, randomised controlled trial. Denmark, 1990-93. 1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone. In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years. The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction. At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer. After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke. ClinicalTrials.gov NCT00252408.","subset":"pubmed_abstract"} +{"meta":{"pmid":23407341,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":17}}},"text":"Investigation of Aspergillus fumigatus biofilm formation by various \"omics\" approaches.\nIn the lung, Aspergillus fumigatus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix called biofilm (BF). This extracellular matrix embeds and glues hyphae together and protects the fungus from an outside hostile environment. This extracellular matrix is absent in fungal colonies grown under classical liquid shake conditions (PL), which were historically used to understand A. fumigatus pathobiology. Recent works have shown that the fungus in this aerial grown BF-like state exhibits reduced susceptibility to antifungal drugs and undergoes major metabolic changes that are thought to be associated to virulence. These differences in pathological and physiological characteristics between BF and liquid shake conditions suggest that the PL condition is a poor in vitro disease model. In the laboratory, A. fumigatus mycelium embedded by the extracellular matrix can be produced in vitro in aerial condition using an agar-based medium. To provide a global and accurate understanding of A. fumigatus in vitro BF growth, we utilized microarray, RNA-sequencing, and proteomic analysis to compare the global gene and protein expression profiles of A. fumigatus grown under BF and PL conditions. In this review, we will present the different signatures obtained with these three \"omics\" methods. We will discuss the advantages and limitations of each method and their complementarity.","subset":"pubmed_abstract"} +{"meta":{"pmid":27056346,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Current updates on laboratory techniques for the diagnosis of male reproductive failure.\nThe incidence of male reproductive failure leading to infertility, whether due to delayed parenthood, environmental issues, genetic factors, drugs, etc., is increasing throughout the world. The diagnosis and prognosis of male subfertility have become a challenge. While the basic semen assessment has been performed for many years, a number of studies question the value of the traditional semen characteristics. This is partly due to inadequate methods and standardization, limited knowledge of technical requirements for quality assurance, and an incomplete understanding of what clinical information a semen assessment can provide. Laboratories currently performing semen and endocrine assessment show great variability. The World Health Organization (WHO) manual for the evaluation of semen has been the core of andrology and fertility evaluation that has helped in further development of this field over many years. These include the physical appearance of the ejaculate, assessments of sperm count, motility, vitality, morphology, and functional aspects of the sperm and semen sample. These tests also include male endocrine profile, biochemical evaluation of the semen, detection of antisperm antibodies in serum, the use of computer-aided sperm analysis (CASA), sperm DNA integrity, and its damage due to oxidative stress. Assisted reproductive techniques (e.g., IVF, ICSI) have shown great success but are too expensive. Further development in this field with newer techniques and extensive training\/instructions can improve accuracy and reduce variability, thus maintaining the quality and standards of such an evaluation. There is an urgent need to have standardized training centers and increased awareness in this area of men's health for reproductive success.","subset":"pubmed_abstract"} +{"meta":{"pmid":3612698,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Proper care for the dying: a critical public issue.\nThe ability of the medical profession to sustain life, or more appropriately, to prolong dying, in patients with terminal illness, creates a most complex and controversial situation for all involved: the patient, if mentally alert; the patient's family; and the medical care team including physicians, nurses and attendants. This situation is especially complex in large acute care hospitals where medical and nursing students, residents and house officers receive advanced medical training. A major problem, prolonging the dying of the terminally ill, with its medical, legal, ethical and economic complexities now confronts American society. The problem is particularly acute in teaching hospitals, in which one finds a disproportionate number of terminally ill patients. The ability to work at these questions as a community rather than as adversaries will determine much about the ability of the health care system to respect the dignity and autonomy of those who seek aid and comfort when faced with serious illness and impending death. Better communication between the physicians, health care providers, the lawyers and ethicists must be developed in order to solve these problems. Over the next ten years society and our elected representatives will be making very demanding decisions about the use of the health dollar. One possible way to prevent increasing costs is to reach significant agreement on the proper care of the dying. Proper care for the dying is being considered, discussed, and evaluated by very thoughtful people. It is not governments which should decide who is to live or who is to die. There is the serious problem of the 'slippery slope' to euthanasia by omission if cost containment becomes the major force in formulating policy on the proper care of the dying.","subset":"pubmed_abstract"} +{"meta":{"pmid":21855899,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Mitral regurgitation surgery in patients with ischemic cardiomyopathy and ischemic mitral regurgitation: factors that influence survival.\nThe treatment of patients with ischemic cardiomyopathy and concomitant mitral regurgitation can be challenging and is associated with reduced long-term survival. It is unclear how mitral valve repair versus replacement affects subsequent outcome. Therefore, we conducted this study to understand the predictors of mortality and to delineate the role of mitral valve repair versus replacement in this high-risk population. From 1993 to 2007, 431 patients (mean age, 70 \u00b1 9 years) with ischemic cardiomyopathy (left ventricular ejection fraction \u2264 45%) and significant ischemic mitral regurgitation (>2) were identified. Patients (44) with concomitant mitral stenosis were excluded from the analysis. A homogeneous group of 387 patients underwent combined coronary artery bypass grafting and mitral valve surgery, mitral valve repair in 302 (78%) and mitral valve replacement in 85 (22%). Uni- and multivariate analyses were performed on the entire cohort, and the predictors of mortality were identified in 2 distinct risk phases. Furthermore, we specifically examined the impact of mitral valve repair versus replacement by comparing 2 propensity-matched subgroups. Follow-up was 100% complete (median, 3.6 years; range, 0-15 years). Overall 1-, 5-, and 10-year survivals were 82.7%, 55.2%, and 24.3%, respectively, for the entire group. The risk factors for an increased mortality within the first year of surgery included previous coronary artery bypass grafting (hazard ratio = 3.39; P < .001), emergency\/urgent status (hazard ratio = 2.08; P = .007), age (hazard ratio = 1.5; P = .03), and low left ventricular ejection fraction (hazard ratio = 1.31; P = .026). Thereafter, only age (hazard ratio = 1.58; P < .001), diabetes (hazard ratio = 2.5; P = .001), and preoperative renal insufficiency (hazard ratio = 1.72; P = .025) were predictive. The status of mitral valve repair versus replacement did not influence survival, and this was confirmed by comparable survival in propensity-matched analyses. Survival after combined coronary artery bypass grafting and mitral valve surgery in patients with ischemic cardiomyopathy (left ventricular ejection fraction \u2264 45%) and mitral regurgitation is compromised and mostly influenced by factors related to the patient's condition at the time of surgery. The specifics of mitral valve repair versus replacement did not seem to affect survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":29245011,"dup_signals":{"dup_doc_count":15,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2023-14":3,"2021-17":3,"2020-34":3,"2020-16":2,"2023-40":1,"2024-18":1}}},"text":"Oncogenic Role of THOR, a Conserved Cancer\/Testis Long Non-coding RNA.\nLarge-scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here, we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer\/testis lncRNAs whose structure and function have undergone positive evolutionary selection.","subset":"pubmed_abstract"} +{"meta":{"pmid":29246577,"dup_signals":{"dup_doc_count":22,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-14":2,"2022-33":1,"2022-27":2,"2021-39":2,"2021-31":1,"2020-40":1,"2019-43":1,"2019-22":1,"2023-50":1,"2024-26":2,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes.\nPrevious reports from the Management of Myelomeningocele Study demonstrated that prenatal repair of myelomeningocele reduces hindbrain herniation and the need for cerebrospinal fluid shunting, and improves motor function in children with myelomeningocele. The trial was stopped for efficacy after 183 patients were randomized, but 30-month outcomes were only available at the time of initial publication in 134 mother-child dyads. Data from the complete cohort for the 30-month outcomes are presented here. Maternal and 12-month neurodevelopmental outcomes for the full cohort were reported previously. The purpose of this study is to report the 30-month outcomes for the full cohort of patients randomized to either prenatal or postnatal repair of myelomeningocele in the original Management of Myelomeningocele Study. Eligible women were randomly assigned to undergo standard postnatal repair or prenatal repair <26 weeks gestation. We evaluated a composite of mental development and motor function outcome at 30 months for all enrolled patients as well as independent ambulation and the Bayley Scales of Infant Development, Second Edition. We assessed whether there was a differential effect of prenatal surgery in subgroups defined by: fetal leg movements, ventricle size, presence of hindbrain herniation, gender, and location of the myelomeningocele lesion. Within the prenatal surgery group only, we evaluated these and other baseline parameters as predictors of 30-month motor and cognitive outcomes. We evaluated whether presence or absence of a shunt at 1 year was associated with 30-month motor outcomes. The data for the full cohort of 183 patients corroborate the original findings of Management of Myelomeningocele Study, confirming that prenatal repair improves the primary outcome composite score of mental development and motor function (199.4 \u00b1 80.5 vs 166.7 \u00b1 76.7, P = .004). Prenatal surgery also resulted in improvement in the secondary outcomes of independent ambulation (44.8% vs 23.9%, P = .004), WeeFIM self-care score (20.8 vs 19.0, P = .006), functional level at least 2 better than anatomic level (26.4% vs 11.4%, P = .02), and mean Bayley Scales of Infant Development, Second Edition, psychomotor development index (17.3% vs 15.1%, P = .03), but does not affect cognitive development at 30 months. On subgroup analysis, there was a nominally significant interaction between gender and surgery, with boys demonstrating better improvement in functional level and psychomotor development index. For patients receiving prenatal surgery, the presence of in utero ankle, knee, and hip movement, absence of a sac over the lesion and a myelomeningocele lesion of \u2264L3 were significantly associated with independent ambulation. Postnatal motor function showed no correlation with either prenatal ventricular size or postnatal shunt placement. The full cohort data of 30-month cognitive development and motor function outcomes validate in utero surgical repair as an effective treatment for fetuses with myelomeningocele. Current data suggest that outcomes related to the need for shunting should be counseled separately from the outcomes related to distal neurologic functioning.","subset":"pubmed_abstract"} +{"meta":{"pmid":29758558,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Mild Cognitive Impairment and Dementia Show Contrasting Associations with Risk of Cancer.\nTo investigate and to compare the relation between dementia and cancer with the association between mild cognitive impairment (MCI) and cancer. A total of 13,207 persons from the Rotterdam Study were followed between 1990 and 2013 for the onset of dementia and cancer (sample 1). Between 2002 and 2005, a subset of 5,181 persons underwent extensive cognitive testing for MCI and subsequently were followed up for cancer until 2013 (sample 2). We used Cox proportional hazard models to determine the association between dementia and cancer, and MCI and cancer. In sample 1, 1,404 patients were diagnosed with dementia, and 2,316 developed cancer (63 among dementia cases). Dementia was associated with a decreased risk of cancer (hazard ratio [HR] 0.53; 95% CI 0.41-0.68). In sample 2, 513 persons were diagnosed with MCI and 670 persons developed cancer (81 among MCI cases). In contrast to individuals with dementia, those with MCI tended to have an increased risk of cancer (HR 1.25; 95% CI 0.99-1.58). We found that persons with MCI tended to have an increased risk of cancer, whereas those with dementia have a decreased risk. These findings call into question a biological explanation for the inverse link between dementia and cancer, thereby suggesting the presence of methodological bias.","subset":"pubmed_abstract"} +{"meta":{"pmid":26291665,"dup_signals":{"dup_doc_count":13}},"text":"Current and Future Burden of Chronic Nonmalignant Liver Disease.\nDisease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere.","subset":"pubmed_abstract"} +{"meta":{"pmid":28867292,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Single-Molecule Imaging Reveals How Mre11-Rad50-Nbs1 Initiates DNA Break Repair.\nDNA double-strand break (DSB) repair is essential for maintaining our genomes. Mre11-Rad50-Nbs1 (MRN) and Ku70-Ku80 (Ku) direct distinct DSB repair pathways, but the interplay between these complexes at a DSB remains unclear. Here, we use high-throughput single-molecule microscopy to show that MRN searches for free DNA ends by one-dimensional facilitated diffusion, even on nucleosome-coated DNA. Rad50 binds homoduplex DNA and promotes facilitated diffusion, whereas Mre11 is required for DNA end recognition and nuclease activities. MRN gains access to occluded DNA ends by removing Ku or other DNA adducts via an Mre11-dependent nucleolytic reaction. Next, MRN loads exonuclease 1 (Exo1) onto the free DNA ends to initiate DNA resection. In the presence of replication protein A (RPA), MRN acts as a processivity factor for Exo1, retaining the exonuclease on DNA for long-range resection. Our results provide a mechanism for how MRN promotes homologous recombination on nucleosome-coated DNA.","subset":"pubmed_abstract"} +{"meta":{"pmid":22249835,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Complications of chronic suppurative otitis media: a retrospective review.\nThe purpose of this study was to review our patients with complications of chronic suppurative otitis media (CSOM) and compare with literature. This retrospective study was performed over 10 years in our tertiary referral university hospital. During this period 4,630 patients with CSOM were admitted to the department and 906 patients underwent a surgery. From the records of the 4,630 patients, 121 patients (2.6%) with complications were identified. Of the 906 CSOM patients that underwent a surgery, 511 had cholesteatoma, and 395 had granulation and\/or polyp tissue. Ninety-four of 511 (18.4%) patients with cholesteatoma and 27 of 395 (6.8%) patients with granulation and\/or polyp tissue had a complication. Of the 121 complicated CSOM patients, 57 extracranial (47.1%) and 37 intracranial (30.6%). Multiple combined complications were occurred in 27 (22.3%) patients. The mastoid abscess was the commonest extracranial complication (28.3%); it was followed by labyrinthitis (9%), facial nerve paralysis (8.4%), and Bezold's abscess (1.3%). The most common intracranial complication was lateral sinus thrombophlebitis (19.5%), followed by perisigmoid sinus abscess (13.5%), meningitis (9%), brain abscess (6.5%), and extradural abscess (4.5%). Most frequent intraoperative finding of complicated CSOM patients was cholesteatoma, with the exception of patients with facial nerve paralysis. There was no mortality in any of our patients. The additional morbidities were recorded in 25 patients (20.6%). In this study, we emphasize the importance of an accurate and early diagnosis, followed by adequate surgical therapy and a multidisciplinary approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":15608899,"dup_signals":{"dup_doc_count":11,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":2}}},"text":"[Characterization of assistance among philanthropic hospitals in Brazil].\nTo characterize the Brazilian philanthropic hospital network and its relation to the public and private sectors of the Sistema Unico de Saude (SUS) [Brazilian Unified Health System]. This is a descriptive study that took into consideration the geographic distribution, number of beds, available biomedical equipment, health care complexity as well as the productive and consumer profiles of philanthropic hospitals. It is based on a sample of 175 hospitals, within a universe of 1,917, involving 102 distinct institutions. Among these, there were 66 Brazilian Unified Health System (SUS) inpatient care providers with less than 599 beds randomly included in this study. Twenty-six of the twenty-seven SUS inpatient care providers with at least 599 beds, as well as ten institutions which do not provide their services to SUS, were also included. This is a cross-sectional study and the data was obtained in 2001. Data collection was conducted by trained researchers, who applied a questionnaire in interviews with the hospital's managers. Within the random sample, 81.2% of the hospitals are located in cities outside of metropolitan areas, and 53.6% of these are the only hospitals within their municipalities. Basic clinical hospitals, without ICUs, predominate within the random sample (44.9%). Among the individual hospitals of the large philanthropic institutions and the special hospitals, the majority -- 53% and 60% respectively -- are level II general hospitals, a category of greater complexity. It was verified that complexity of care was associated to hospital size, being that hospitals with the greatest complexity are situated predominantly in the capitals. Given the importance of the philanthropic hospital sector within the SUS [Unified Health System] in Brazil, this paper identifies some ways of formulating appropriate health policies adjusted to the specificities of its different segments.","subset":"pubmed_abstract"} +{"meta":{"pmid":27048302,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"A comparison of cranial fluctuating asymmetry between the two sexes in a Joseon Dynasty population of Korea.\nCranial fluctuating asymmetry (FA) has been used to examine developmental stress levels in various populations. In bioarchaeological studies, developmental stress can be an important factor for inferring standard of living in a population. However, the crania of a Joseon Dynasty population have only been studied in terms of its morphological characteristics. In this regard, the cranial FA of the two sexes from a Joseon Dynasty population of Korea were compared here for examining their aspects of living conditions in relation to developmental stress and socio-cultural factors. In this study, 77 individuals (39 males and 38 females) who belong to the 15th to the early-20th centuries from Seoul and Gyeonggi province in Korea were investigated. Nineteen three-dimensional landmarks on the vault and basicranium were collected using MicroScribe G2X. The coordinate data were aligned into a common coordinate plane by Procrustes least-squares superimposition. Procrustes ANOVA was adopted to evaluate FA at a population level. The FA of males and females were compared with t-test using SPSS 18. There was statistically insignificant difference in FA between the two sexes in the Joseon Dynasty population. The result was interpreted to reflect both relatively high developmental stress and sex-related discrimination in the population. It was postulated that relatively high developmental stress could increase difference in FA between the two sexes in the prenatal term compared to the postnatal term because sex-related discrimination cannot be practiced before birth and males have lower stress resistance than females. Then, the difference between the two sexes in the cranial FA could be decreased during postnatal development related to sex-related discrimination, resulting in insignificant FA difference of the two sexes in spite of high developmental stress of the Joseon Dynasty population. The results will be useful for comparing and reconstructing living conditions of ancient Korean populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":27247687,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Emotional, Cognitive and Self-Enhancement Processes in Aggressive Behavior After Interpersonal Rejection and Exclusion.\nThe relationship between exclusion or rejection and aggression is already well documented, but there is still a debate about the mechanisms that underlie this effect. In two studies we focused on the propensity to react aggressively (readiness for aggression) on the bases of emotional, cognitive or self-enhancement (personality-immanent) processes. In both studies we first measured readiness for aggression and then ego-depleted participants. Next, in Study 1 we excluded participants (n = 96) using an online ball throwing game and measured displaced aggressive behavior - intensity and duration of an unpleasant noise administrated to a stranger. In Study 2 participants (n = 140) were rejected by a peer on the basis of an interview that they gave and then could retaliate by reducing peer's chance for getting a job. The results show that exclusion effect on displaced aggression was moderated by cognitive readiness for aggression, while rejection effect on retaliatory aggression was shaped by emotional and personality-immanent readiness for aggression as well as ego-depletion. The results were discussed in light of the strength model of self-control by Baumeister, Vohs, and Tice (2007).","subset":"pubmed_abstract"} +{"meta":{"pmid":8982832,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-49":1,"2022-05":1,"2021-49":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-29":2,"2023-40":1,"2024-26":1,"2024-30":1}}},"text":"Immunohistochemical study of amoeboid microglial cells in fetal rat brain.\nThe present study examined the expression of different antigens in amoeboid microglial cells (AMC) in fetal rat brain extending from 12 to 20 d postconception (E12-E20) using a panel of monoclonal antibodies which recognised the major histocompatibility complex (MHC) class I (OX-18) and class II (OX-6) antigens, leucocyte common antigen (OX-1), CD4 receptor (OX-35), complement type 3 receptor (OX-42) or macrophage antigens of unknown function (ED1 and ED2). Of the above-mentioned antigens, ED1 and ED2-labelled AMC were observed in the neuroepithelia as early as embryonic day 12 (E12); other antigens were not detected at this stage. At E14, except for MHC class I antigen, all other antigens were expressed by AMC distributed predominantly in the developing white matter. At E16, AMC in the intermediate zone lateral to the striatum were endowed with all the above-mentioned antigens including MHC class I. At E18, the immunoreactivities of AMC stained with OX-6, OX-18, OX-35 and OX-42 antigens were noticeably reduced when compared with those cells at E16. At E20, amoeboid microglial cells exhibited full complement of antigen expression similar to those cells at E16; some of the labelled cells emitted a variable number of cytoplasmic processes. It is suggested that the successive and differential expression of various macrophage related antigens on AMC in fetal brain is related to the specific requirement of local environment in different stages of development.","subset":"pubmed_abstract"} +{"meta":{"pmid":7575977,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"Mechanical property and microstructural variations for recast low-gold alloy.\nUsing polystyrene plastic patterns meeting the dimensional requirements of ANSI\/ADA specification no. 5, tension test specimens were recast multiple times from a popular Type III gold (46%) alloy. The alloy was melted by electrical heating in a graphite crucible and four conditions were compared: new alloy and alloy cast two, three, and four times (n = 4). After casting, age-hardened specimens were loaded at an elongation rate of 0.5 mm\/min until failure, and the stress-strain plots were recorded. Values of yield strength, tensile strength, and percentage elongation for the specimen groups were analyzed by one-way analysis of variance, followed by the Student-Newman-Keuls multiple range test. Significant decreases (P < .01) in yield strength and percentage elongation occurred with recasting, although there were no significant differences (P > .05) in tensile strength. Scanning electron microscope examination revealed that the number of casting defects increased with remelting, and that their presence dominates the tensile fracture process. The variation in mechanical properties of the alloy with remelting was attributed to these casting defects.","subset":"pubmed_abstract"} +{"meta":{"pmid":28576295,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2020-29":1,"2019-35":1,"2019-26":1,"2019-04":1,"2018-43":2,"2018-34":1,"2018-30":1,"2018-22":1,"2018-17":1,"2018-09":1,"2018-05":1,"2021-49":1,"2024-22":1}}},"text":"Alternative payment models lead to strategic care coordination workforce investments.\nCare coordination is generally viewed as a key to success for health systems seeking to adapt to a range of new value-based payment policies. This study explores care coordination staffing in four health systems participating in new payment models, including Medicaid payment reform and Accountable Care Organizations. Comparative case study design is used to describe models of care coordination. Analysis of 43 semi-structured interviews with leadership, clinicians, and care coordination staff at four health systems engaged in value-based contracts. Each of the sites engaged in significant task shifting of low-complexity care coordination activities to licensed practical nurses, medical assistants, and other unlicensed personnel freeing up registered nurses and social workers for more complex patients. Few have care coordination experience, requiring a significant investment in on-the-job training. Payment reform is leading to a greater investment in the care coordination workforce. However, demonstrating the return on investment remains a challenge.","subset":"pubmed_abstract"} +{"meta":{"pmid":29381099,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":12}}},"text":"Quality Evaluation Scores are no more Reliable than Gestalt in Evaluating the Quality of Emergency Medicine Blogs: A METRIQ Study.\nConstruct: We investigated the quality of emergency medicine (EM) blogs as educational resources. Online medical education resources such as blogs are increasingly used by EM trainees and clinicians. However, quality evaluations of these resources using gestalt are unreliable. We investigated the reliability of two previously derived quality evaluation instruments for blogs. Sixty English-language EM websites that published clinically oriented blog posts between January 1 and February 24, 2016, were identified. A random number generator selected 10 websites, and the 2 most recent clinically oriented blog posts from each site were evaluated using gestalt, the Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) score, and the Medical Education Translational Resources: Impact and Quality (METRIQ-8) score, by a sample of medical students, EM residents, and EM attendings. Each rater evaluated all 20 blog posts with gestalt and 15 of the 20 blog posts with the ALiEM AIR and METRIQ-8 scores. Pearson's correlations were calculated between the average scores for each metric. Single-measure intraclass correlation coefficients (ICCs) evaluated the reliability of each instrument. Our study included 121 medical students, 88 EM residents, and 100 EM attendings who completed ratings. The average gestalt rating of each blog post correlated strongly with the average scores for ALiEM AIR (r = .94) and METRIQ-8 (r = .91). Single-measure ICCs were fair for gestalt (0.37, IQR 0.25-0.56), ALiEM AIR (0.41, IQR 0.29-0.60) and METRIQ-8 (0.40, IQR 0.28-0.59). The average scores of each blog post correlated strongly with gestalt ratings. However, neither ALiEM AIR nor METRIQ-8 showed higher reliability than gestalt. Improved reliability may be possible through rater training and instrument refinement.","subset":"pubmed_abstract"} +{"meta":{"pmid":29474526,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-33":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2023-50":1,"2024-26":1}}},"text":"IWTomics: testing high-resolution sequence-based 'Omics' data at multiple locations and scales.\nWith increased generation of high-resolution sequence-based 'Omics' data, detecting statistically significant effects at different genomic locations and scales has become key to addressing several scientific questions. IWTomics is an R\/Bioconductor package (integrated in Galaxy) that, exploiting sophisticated Functional Data Analysis techniques (i.e. statistical techniques that deal with the analysis of curves), allows users to pre-process, visualize and test these data at multiple locations and scales. The package provides a friendly, flexible and complete workflow that can be employed in many genomic and epigenomic applications. IWTomics is freely available at the Bioconductor website (http:\/\/bioconductor.org\/packages\/IWTomics) and on the main Galaxy instance (https:\/\/usegalaxy.org\/). Supplementary data are available at Bioinformatics online.","subset":"pubmed_abstract"} +{"meta":{"pmid":18936702,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients.\nThe role of intensive insulin therapy in medical surgical intensive care patients remains unclear. The objective of this study was to examine the effect of intensive insulin therapy on mortality in medical surgical intensive care unit patients. Randomized controlled trial. Tertiary care intensive care unit. Medical surgical intensive care unit patients with admission blood glucose of > 6.1 mmol\/L or 110 mg\/dL. A total of 523 patients were randomly assigned to receive intensive insulin therapy (target blood glucose 4.4-6.1 mmol\/L or 80-110 mg\/dL) or conventional insulin therapy (target blood glucose 10-11.1 mmol\/L or 180-200 mg\/dL). The primary end point was intensive care unit mortality. Secondary end points included hospital mortality, intensive care unit and hospital length of stay, mechanical ventilation duration, the need for renal replacement therapy and packed red blood cells transfusion, and the rates of intensive care unit acquired infections as well as the rate of hypoglycemia (defined as blood glucose < or = 2.2 mmol\/L or 40 mg\/dL). There was no significant difference in intensive care unit mortality between the intensive insulin therapy and conventional insulin therapy groups (13.5% vs. 17.1%, p = 0.30). After adjustment for baseline characteristics, intensive insulin therapy was not associated with mortality difference (adjusted hazard ratio 1.09, 95% confidence interval 0.70-1.72). Hypoglycemia occurred more frequently with intensive insulin therapy (28.6% vs. 3.1% of patients; p < 0.0001 or 6.8\/100 treatment days vs. 0.4\/100 treatment days; p < 0.0001). There was no difference between the intensive insulin therapy and conventional insulin therapy in any of the other secondary end points. Intensive insulin therapy was not associated with improved survival among medical surgical intensive care unit patients and was associated with increased occurrence of hypoglycemia. Based on these results, we do not advocate universal application of intensive insulin therapy in intensive care unit patients. Current Controlled Trials registry (ISRCTN07413772) http:\/\/www.controlled-trials.com\/ISRCTN07413772\/07413772; 2005.","subset":"pubmed_abstract"} +{"meta":{"pmid":23821694,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":13}}},"text":"Patterns of care and persistence after incident elevated blood pressure.\nScreening for hypertension in children occurs during routine care. When blood pressure (BP) is elevated in the hypertensive range, a repeat measurement within 1 to 2 weeks is recommended. The objective was to assess patterns of care after an incident elevated BP, including timing of repeat BP measurement and likelihood of persistently elevated BP. This retrospective study was conducted in 3 health care organizations. All children aged 3 through 17 years with an incident elevated BP at an outpatient visit during 2007 through 2010 were identified. Within this group, we assessed the proportion who had a repeat BP measured within 1 month of their incident elevated BP and the proportion who subsequently met the definition of hypertension. Multivariate analyses were used to identify factors associated with follow-up BP within 1 month of initial elevated BP. Among 72,625 children and adolescents in the population, 6108 (8.4%) had an incident elevated BP during the study period. Among 6108 with an incident elevated BP, 20.9% had a repeat BP measured within 1 month. In multivariate analyses, having a follow-up BP within 1 month was not significantly more likely among individuals with obesity or stage 2 systolic elevation. Among 6108 individuals with an incident elevated BP, 84 (1.4%) had a second and third consecutive elevated BP within 12 months. Whereas >8% of children and adolescents had an incident elevated BP, the great majority of BPs were not repeated within 1 month. However, relatively few individuals subsequently met the definition of hypertension.","subset":"pubmed_abstract"} +{"meta":{"pmid":12232295,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Inward-Rectifying K+ Channels in Root Hairs of Wheat (A Mechanism for Aluminum-Sensitive Low-Affinity K+ Uptake and Membrane Potential Control).\nK+ is the most abundant cation in cells of higher plants, and it plays vital roles in plant growth and development. Extensive studies on the kinetics of K+ uptake in roots have shown that K+ uptake is mediated by at least two transport mechanisms, one with a high and one with a low affinity for K+. However, the precise molecular mechanisms of K+ uptake from soils into root epidermal cells remain unknown. In the present study we have pursued the biophysical identification and characterization of mechanisms of K+ uptake into single root hairs of wheat (Triticum aestivum L.), since root hairs constitute an important site of nutrient uptake from the soil. These patch-clamp studies showed activation of a large inward current carried by K+ ions into root hairs at membrane potentials more negative than -75 mV. This K+ influx current was mediated by hyperpolarization-activated K+-selective ion channels, with a selectivity sequence for monovalent cations of K+ > Rb+ [almost equal to] NH4+ >> Na+ [almost equal to] Li+ > Cs+. Kinetic analysis of K+ channel currents yielded an apparent K+ equilibrium dissociation constant (Km) of [almost equal to]8.8 mM, which closely correlates to the major component of low-affinity K+ uptake. These channels did not inactivate during prolonged stimulation and would thus enable long-term K+ uptake driven by the plasma membrane proton-extruding pump. Aluminum, which is known to inhibit cation uptake at the root epidermis, blocked these inward-rectifying K+ channels with half-maximal current inhibition at [almost equal to]8 [mu]M free Al3+. Aluminum block of K+ channels at these Al3+ concentrations correlates closely to Al3+ phytotoxicity. It is concluded that inward-rectifying K+ channels in root hairs can function as both a physiologically important mechanism for low-affinity K+ uptake and as regulators of membrane potential. The identification of this mechanism is a major step toward a detailed molecular characterization of the multiple components involved in K+ uptake, transport, and membrane potential control in root epidermal cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":26577697,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-25":1,"2020-29":1,"2019-26":1,"2018-39":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2022-40":1,"2017-13":1}}},"text":"Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2\/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication.\nPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry and causes important economic losses. No effective antiviral drugs against it are commercially available. We recently reported that the culture supernatant of Actinobacillus pleuropneumoniae, the porcine pleuropneumonia causative agent, has an antiviral activity in vitro against PRRSV in SJPL cells. Objectives of this study were (i) to identify the mechanism behind the antiviral activity displayed by A. pleuropneumoniae and (ii) to characterize the active molecules present in the bacterial culture supernatant. Antibody microarray analysis was used in order to point out cellular pathways modulated by the A. pleuropneumoniae supernatant. Subsequent, flow cytometry analysis and cell cycle inhibitors were used to confirm antibody microarray data and to link them to the antiviral activity of the A. pleuropneumoniae supernatant. Finally, A. pleuropneumoniae supernatant characterization was partially achieved using mass spectrometry. Using antibody microarray, we observed modulations in G2\/M-phase cell cycle regulation pathway when SJPL cells were treated with A. pleuropneumoniae culture supernatant. These modulations were confirmed by a cell cycle arrest at the G2\/M-phase when cells were treated with the A. pleuropneumoniae culture supernatant. Furthermore, two G2\/M-phase cell cycle inhibitors demonstrated the ability to inhibit PRRSV infection, indicating a potential key role for PRRSV infection. Finally, mass spectrometry lead to identify two molecules (m\/z 515.2 and m\/z 663.6) present only in the culture supernatant. We demonstrated for the first time that A. pleuropneumoniae is able to disrupt SJPL cell cycle resulting in inhibitory activity against PRRSV. Furthermore, two putative molecules were identified from the culture supernatant. This study highlighted the cell cycle importance for PRRSV and will allow the development of new prophylactic or therapeutic approaches against PRRSV.","subset":"pubmed_abstract"} +{"meta":{"pmid":24948959,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Prescription patterns of general practitioners in peshawar, pakistan.\nTo find out prescription patterns of general practitioners in Peshawar. Cross-sectional survey of drug prescriptions was done at six major hospitals and pharmacies of Peshawar between April and May 2011. A total of 1097 prescriptions that included 3640 drugs, were analyzed to assess completeness, average number of drugs, prescription frequency of various drug classes, and number of brands prescribed. No prescription contained all essential components of a prescription. Legibility was poor in 58.5% prescriptions. Physician's name and registration number were not mentioned in 89% and 98.2% prescriptions respectively. Over 78% prescriptions did not have diagnosis or indication mentioned. Dosage, duration of use, signature of physician and directions for taking drugs were not written in 63.8%, 55.4%, 18.5% and 10.9% of prescriptions respectively. On average each prescription included 3.32 drugs. Most frequently prescribed drug classes included analgesics (61.7%), anti-infective agents (57.2%), multi-vitamins (37.8%) and gastrointestinal drugs (34.4%). We found 206, 130, 105 and 101 different brands of anti-infective agents, gastrointestinal drugs, analgesics and multivitamins being prescribed. We observed a high number of average drugs per prescription mostly using brand names, and over-prescription of analgesics, antimicrobials, multivitamins and anti-ulcer drugs. Quality of written prescriptions was poor in terms of completeness.","subset":"pubmed_abstract"} +{"meta":{"pmid":9017397,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Characterization of functional domains of the su(Hw) protein that mediate the silencing effect of mod(mdg4) mutations.\nThe suppressor of Hairy-wing [su(Hw)] protein represses enhancer function in a unidirectional fashion: enhancers segregated from the promoter by the su(Hw) binding region are rendered inactive. whereas those in the same domain are unaffected. In the case of the gypsy-induced y2 allele, the repressive effect of su(Hw) is rendered bidirectional in mod(mdg4) mutant flies, and all enhancers of the affected gene become inactive. This silencing of enhancer elements might be due to exposure of specific domains of su(Hw) when the mod(mdg4) protein is absent. Two of three regions of su(Hw) that are located adjacent to the leucine zipper motif and are conserved across Drosophila species are necessary for both the unidirectional and bidirectional repression of transcription by su(Hw). In contrast, two acidic domains that are dispensable for the unidirectional repression of enhancer elements are critical for the bidirectional silencing of enhancer activity observed in mutants lacking functional mod(mdg4) protein.","subset":"pubmed_abstract"} +{"meta":{"pmid":30405573,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"ant(6)-I Genes Encoding Aminoglycoside O-Nucleotidyltransferases Are Widely Spread Among Streptomycin Resistant Strains of Campylobacter jejuni and Campylobacter coli.\nThermotolerant Campylobacter species C. jejuni and C. coli are actually recognized as the major bacterial agent responsible for food-transmitted gastroenteritis. The most effective antimicrobials against Campylobacter are macrolides and some, but not all aminoglycosides. Among these, susceptibility to streptomycin is reduced by mutations in the ribosomal RPSL protein or by expression of ANT(6)-I aminoglycoside O-nucleotidyltransferases. The presence of streptomycin resistance genes was evaluated among streptomycin-resistant Campylobacter isolated from humans and animals by using PCR with degenerated primers devised to distinguish ant(6)-Ia, ant(6)-Ib and other ant-like genes. Genes encoding ANT(6)-I enzymes were found in all possible combinations with a major fraction of the isolates carrying a previously described ant-like gene, distantly related and belonging to the new ant(6)-I sub-family ant(6)-Ie. Among Campylobacter isolates, ant(6)-Ie was uniquely found functional in C. coli, as shown by gene transfer and phenotype expression in Escherichia coli, unlike detected coding sequences in C. jejuni that were truncated by an internal frame shift associated to RPSL mutations in streptomycin resistant strains. The genetic relationships of C. coli isolates with ANT(6)-Ie revealed one cluster of strains presented in bovine and humans, suggesting a circulation pathway of Campylobacter strains by consuming contaminated calf meat by bacteria expressing this streptomycin resistance element.","subset":"pubmed_abstract"} +{"meta":{"pmid":28558050,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Citizen science: A new perspective to advance spatial pattern evaluation in hydrology.\nCitizen science opens new pathways that can complement traditional scientific practice. Intuition and reasoning often make humans more effective than computer algorithms in various realms of problem solving. In particular, a simple visual comparison of spatial patterns is a task where humans are often considered to be more reliable than computer algorithms. However, in practice, science still largely depends on computer based solutions, which inevitably gives benefits such as speed and the possibility to automatize processes. However, the human vision can be harnessed to evaluate the reliability of algorithms which are tailored to quantify similarity in spatial patterns. We established a citizen science project to employ the human perception to rate similarity and dissimilarity between simulated spatial patterns of several scenarios of a hydrological catchment model. In total, the turnout counts more than 2500 volunteers that provided over 43000 classifications of 1095 individual subjects. We investigate the capability of a set of advanced statistical performance metrics to mimic the human perception to distinguish between similarity and dissimilarity. Results suggest that more complex metrics are not necessarily better at emulating the human perception, but clearly provide auxiliary information that is valuable for model diagnostics. The metrics clearly differ in their ability to unambiguously distinguish between similar and dissimilar patterns which is regarded a key feature of a reliable metric. The obtained dataset can provide an insightful benchmark to the community to test novel spatial metrics.","subset":"pubmed_abstract"} +{"meta":{"pmid":21528931,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"RS-predictor: a new tool for predicting sites of cytochrome P450-mediated metabolism applied to CYP 3A4.\nThis article describes RegioSelectivity-Predictor (RS-Predictor), a new in silico method for generating predictive models of P450-mediated metabolism for drug-like compounds. Within this method, potential sites of metabolism (SOMs) are represented as \"metabolophores\": A concept that describes the hierarchical combination of topological and quantum chemical descriptors needed to represent the reactivity of potential metabolic reaction sites. RS-Predictor modeling involves the use of metabolophore descriptors together with multiple-instance ranking (MIRank) to generate an optimized descriptor weight vector that encodes regioselectivity trends across all cases in a training set. The resulting pathway-independent (O-dealkylation vs N-oxidation vs Csp(3) hydroxylation, etc.), isozyme-specific regioselectivity model may be used to predict potential metabolic liabilities. In the present work, cross-validated RS-Predictor models were generated for a set of 394 substrates of CYP 3A4 as a proof-of-principle for the method. Rank aggregation was then employed to merge independently generated predictions for each substrate into a single consensus prediction. The resulting consensus RS-Predictor models were shown to reliably identify at least one observed site of metabolism in the top two rank-positions on 78% of the substrates. Comparisons between RS-Predictor and previously described regioselectivity prediction methods reveal new insights into how in silico metabolite prediction methods should be compared.","subset":"pubmed_abstract"} +{"meta":{"pmid":33221672,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Long-rains crops, short-rains crops, permanent crops and fruit crops: The 'hidden' multiple season-cropping system for adaptation to rain variability by smallholder farms.\nTo adapt is to survive. However, sub-Saharan Africa, although highly dependent on agriculture, is vulnerable, most affected, with low-adaptive capacity. Luckily, the region is blessed with inherent adaptation-related strengths that are within reach, to counteract uncertainty in climatic patterns which are expected to continue well into the future. One such strength is a bimodal rainfall pattern that avails the 'hidden' multiple season-cropping systems that have the potential to produce four types of crops in a single plot in a single year: short-rains crops, long-rains crops, permanent crops and fruit crops. Despite burgeoning literature on adaptation, the impact of multiple season-cropping systems has not been adequately investigated. This study applies a novel approach to measure its impact on productivity of more than 10,000 smallholder plots using an endogenous switching regression framework. The study finds that plots that adopt multiple season-cropping systems produce higher quantities, earn more crop revenue, and are less likely to be affected by rainfall variability in comparison to plots that engage in single season-cropping systems. As the fight against climate change continues, there is need to move the needle on adaptation and consider strategies that are within reach. The multiple season-cropping systems provide this opportunity and emphasises the benefit of engaging in agriculture throughout the year and producing long-rains, short rains, permanent and fruits crops.","subset":"pubmed_abstract"} +{"meta":{"pmid":32795466,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A mono-acyl phospholipid (20:1 lyso-PS) activates Toll-Like Receptor 2\/6 hetero-dimer.\nToll-like receptor 2 (TLR2) is an important pattern recognition receptor on the surface of host immune cells that binds a variety of ligands that are released by microorganisms as well as by damaged or dying host cells. According to the current concept, TLR2\/1 and TLR2\/6 heterodimers are activated by tri- or di-acylated ligands, respectively. However, also mono-acyl phospholipid containing lipid fractions derived from parasites, were reported to be able to activate TLR2. In order to provide conclusive evidence for the TLR2 activating capacity of mono-acyl phospholipids derived from pathogens, we developed a biosynthetic method to enzymatically convert commercially available phospholipids into several mono-acyl-phospholipid variants that were examined for their TLR2 activating capacity. These investigations demonstrated that 1-(11Z-eicosenoyl)-glycero-3-phosphoserine 20:1 (20:1 lyso-PS) is a true agonist of the TLR2\/6 heterodimer and that its polar headgroup as well as the length of the acyl chain are crucial for TLR2 activation. In silico modelling further confirmed 20:1 mono-acyl PS as a ligand for TLR2\/6 heterodimer, as this predicted that multiple hydrogen bonds are formed between the polar headgroup of 20:1 mono-acyl PS and amino acid residues of both TLR2 and TLR6. Future studies can now be performed to further assess the functions of 20:1 lyso-PS as an immunological mediator, because this enzymatic method enables its preparation in larger quantities than is possible by isolation from the parasite that naturally produces this compound, Schistosoma mansoni, the source of the original discovery (Van der Kleij et al., 2002).","subset":"pubmed_abstract"} +{"meta":{"pmid":29669102,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Trends in the Prevalence and Disparity in Cognitive Limitations of Americans 55-69 Years Old.\nTo determine whether the prevalence of cognitive limitation (CL) among Americans ages 55 to 69 years changed between 1998 and 2014, and to assess the trends in socioeconomic disparities in CL among groups defined by race\/ethnicity, education, income, and wealth. Logistic regression using 1998-2014 data from the biennial Health and Retirement Study, a nationally representative data set. CL is defined as a score of 0-11 on a 27-point cognitive battery of items focused on memory. Socioeconomic status (SES) measures are classified as quartiles. In models controlling for age, gender, and previous cognitive testing, we find no significant change over time in the overall prevalence of CL, widening disparities in limitation by income and, in some cases, wealth, and improvements among non-Hispanic whites but not other racial\/ethnic groups. Among people 55-69, rates of CL are many times higher for groups with lower SES than those with higher SES, and recent trends show little indication that the gaps are narrowing.","subset":"pubmed_abstract"} +{"meta":{"pmid":21858185,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Testing multiple coordination constraints with a novel bimanual visuomotor task.\nThe acquisition of a new bimanual skill depends on several motor coordination constraints. To date, coordination constraints have often been tested relatively independently of one another, particularly with respect to isofrequency and multifrequency rhythms. Here, we used a new paradigm to test the interaction of multiple coordination constraints. Coordination constraints that were tested included temporal complexity, directionality, muscle grouping, and hand dominance. Twenty-two healthy young adults performed a bimanual dial rotation task that required left and right hand coordination to track a moving target on a computer monitor. Two groups were compared, either with or without four days of practice with augmented visual feedback. Four directional patterns were tested such that both hands moved either rightward (clockwise), leftward (counterclockwise), inward or outward relative to each other. Seven frequency ratios (3\u22361, 2\u22361, 3\u22362, 1\u22361, 2\u22363. 1\u22362, 1\u22363) between the left and right hand were introduced. As expected, isofrequency patterns (1\u22361) were performed more successfully than multifrequency patterns (non 1\u22361). In addition, performance was more accurate when participants were required to move faster with the dominant right hand (1\u22363, 1\u22362 and 2\u22363) than with the non-dominant left hand (3\u22361, 2\u22361, 3\u22362). Interestingly, performance deteriorated as the relative angular velocity between the two hands increased, regardless of whether the required frequency ratio was an integer or non-integer. This contrasted with previous finger tapping research where the integer ratios generally led to less error than the non-integer ratios. We suggest that this is due to the different movement topologies that are required of each paradigm. Overall, we found that this visuomotor task was useful for testing the interaction of multiple coordination constraints as well as the release from these constraints with practice in the presence of augmented visual feedback.","subset":"pubmed_abstract"} +{"meta":{"pmid":7995638,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Systematic difference between blood pressure readings caused by cuff type.\nIn this study we determine whether blood pressure readings using a cuff of fixed size systematically differed from readings made with a triple-bladder cuff (Tricuff) that automatically adjusts bladder width to arm circumference and assessed subsequent clinical and epidemiological effects. Blood pressure was measured with a standard cuff or a Tricuff in 454 patients visiting an outpatient clinic in the Seychelles (Indian Ocean). Overall means of within-individual standard cuff-Tricuff differences in systolic and diastolic blood pressures were examined in relation to arm circumference and sex. The standard cuff-Tricuff difference in systolic and diastolic blood pressures increased monotonically with circumference (from 4.7 +\/- 0.8\/3.2 +\/- 0.7 mm Hg for arm circumference of 30 to 31 cm to 10.0 +\/- 1.1\/8.0 +\/- 0.9 mm Hg for arm circumference > or = 36 cm) and was larger in women than men. Multivariate linear regression indicated independent effects of arm circumference and sex. Forty percent of subjects with a diastolic blood pressure of > or = 95 mm Hg measured with a standard cuff had values less than 95 mm Hg measured with a Tricuff. Extrapolation to the entire population of the Seychelles decreased the prevalence of blood pressure greater than or equal to 160\/95 mm Hg by 11.5% and 24.0% in men and women, respectively, aged 35 to 64 years. The age-adjusted effect of body mass index on systolic and diastolic blood pressures decreased twofold using blood pressure readings made with a Tricuff instead of a standard cuff.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":25906783,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns.\nHuman exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions. Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":24770937,"dup_signals":{"dup_doc_count":17,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2020-50":1,"2020-29":1,"2019-47":1,"2018-22":1,"2017-51":1,"2015-14":1,"2014-42":4,"2014-41":1,"2022-49":1,"2015-11":1,"2015-06":1,"2015-18":1}}},"text":"Coexistence of urinary incontinence and major depressive disorder with health-related quality of life in older Americans with and without cancer.\nThis study evaluates the prevalence and factors associated with major depressive disorder (MDD) in a population of cancer survivors and the impact of co-occurring MDD and urinary incontinence (UI) on health-related quality of life (HRQOL). The prevalence of MDD risk among cancer survivors (breast, prostate, bladder, colorectal, lung, and endometrial\/uterine cancers) and those without cancer was estimated using the Surveillance, Epidemiology and End Results Program-Medicare Health Outcomes Survey (SEER-MHOS) linked database (n = 9,282 with cancer\/n = 289,744 without cancer). Risk for MDD was measured using three items from the Diagnostic Interview Schedule, and HRQOL was measured by the SF-36. UI was defined as self-reported leakage of urine causing a problem in previous 6 months. Factors associated with MDD were investigated using logistic regression, and the impact of co-occurring MDD and UI on HRQOL scores was determined using linear regression. The prevalence of MDD risk ranged from 19.2 % for prostate to 34.1 % for lung. Lung cancer diagnosis was associated with risk of MDD. Being \u22655 years from diagnosis was associated with decreased risk of MDD (prevalence odds ratio (POR) = 0.82, 95 % confidence interval (95 % CI) 0.71, 0.95). The coexistence of both UI and MDD was associated with a decrease across HRQOL subscales; including 40 points on role-emotional (RE) score. Cancer survivors reporting co-occurrence of UI and MDD experienced significant decrements in HRQOL. Understanding the combined effect of UI and MDD may help clinicians to better recognize and alleviate their effects on cancer survivors' HRQOL.","subset":"pubmed_abstract"} +{"meta":{"pmid":33758438,"dup_signals":{"dup_doc_count":60,"dup_dump_count":33,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":1,"2023-14":3,"2023-06":1,"2022-49":1,"2022-33":3,"2022-21":1,"2022-05":2,"2021-49":2,"2021-39":1,"2021-31":3,"2021-25":1,"2021-21":1,"2021-17":2,"2021-10":1,"2020-50":4,"2020-45":1,"2020-40":1,"2020-34":3,"2020-29":2,"2020-10":3,"2019-51":2,"2019-47":1,"2019-43":1,"2019-35":1,"2019-26":1,"2017-39":1,"2016-07":1,"2024-26":2,"2024-22":2,"2024-18":1,"2024-10":3,"2024-30":1}}},"text":"The role of the ocean in the global atmospheric budget of acetone.\nAcetone is one of the most abundant carbonyl compounds in the atmosphere and it plays an important role in atmospheric chemistry. The role of the ocean in the global atmospheric acetone budget is highly uncertain, with past studies reaching opposite conclusions as to whether the ocean is a source or sink. Here we use a global 3-D chemical transport model (GEOS-Chem) simulation of atmospheric acetone to evaluate the role of air-sea exchange in the global budget. Inclusion of updated (slower) photolysis loss in the model means that a large net ocean source is not needed to explain observed acetone in marine air. We find that a simulation with a fixed seawater acetone concentration of 15 nM based on observations can reproduce the observed global patterns of atmospheric concentrations and air-sea fluxes. The Northern Hemisphere oceans are a net sink for acetone while the tropical oceans are a net source. On a global scale the ocean is in near-equilibrium with the atmosphere. Prescribing an ocean concentration of acetone as a boundary condition in the model assumes that ocean concentrations are controlled by internal production and loss, rather than by air-sea exchange. An implication is that the ocean plays a major role in controlling atmospheric acetone. This hypothesis needs to be tested by better quantification of oceanic acetone sources and sinks.","subset":"pubmed_abstract"} +{"meta":{"pmid":19908222,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Apoptosis-inducing effects of Morinda citrifolia L. and doxorubicin on the Ehrlich ascites tumor in Balb-c mice.\nMorinda citrifolia L. (Noni) is a herbal remedy with promising anti-cancer properties. However, its effects on various cancers are to be investigated to make a firm conclusion before implementing it into the clinical practice. Therefore, we investigated the cytotoxic potential of noni on Ehrlich ascites tumor grown in female Balb-c mice and also combined it with a potent anti-cancer agent, doxorubicin. One group received noni only (n = 8), another one doxorubicin (n = 8), and the other one noni + doxorubicin (n = 8) for 14 days after the inoculation of cells. The control group (n = 7) received 0.9% NaCl only. We found that short and long diameters of the tumor tissues were about 40-50% smaller, compared to those in control group. This anti-growth effect resulted from the induction of apoptosis, which was confirmed by the positive results from the Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) analysis and the active caspase-3 cells in tissues. Apoptosis also confirmed by caspase-cleaved cytokeratin 18 elevation in serum of the treated groups. Further, the proliferation was decreased, which was immunohistochemically shown by the PCNA staining. We conclude that noni may be useful in the treatment of breast cancer either on its own or in combination with doxorubicin. Further studies are warranted to assess the dosage and safety of using noni fruit juice in conjuction with anti-cancer drugs against breast cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":15822583,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2024-26":1,"unknown":8}}},"text":"Influence of medetomidine on stress-related neurohormonal and metabolic effects caused by butorphanol, fentanyl, and ketamine administration in dogs.\nTo examine stress-related neurohormonal and metabolic effects of butorphanol, fentanyl, and ketamine administration alone and in combination with medetomidine in dogs. 10 Beagles. 5 dogs received either butorphanol (0.1 mg\/kg), fentanyl (0.01 mg\/kg), or ketamine (10 mg\/kg) IM in a crossover design. Another 5 dogs received either medetomidine (0.02 mg\/kg) and butorphanol (0.1 mg\/kg), medetomidine and fentanyl (0.01 mg\/kg), medetomidine and ketamine (10 mg\/kg), or medetomidine and saline (0.9% NaCI) solution (0.1 mL\/kg) in a similar design. Blood samples were obtained for 6 hours following the treatments. Norepinephrine, epinephrine, cortisol, glucose, insulin, and nonesterified fatty acid concentrations were determined in plasma. Administration of butorphanol, fentanyl, and ketamine caused neurohormonal and metabolic changes similar to stress, including increased plasma epinephrine, cortisol, and glucose concentrations. The hyperglycemic effect of butorphanol was not significant. Ketamine caused increased norepinephrine concentration. Epinephrine concentration was correlated with glucose concentration in the butorphanol and fentanyl groups but not in the ketamine groups, suggesting an important difference between the mechanisms of the hyperglycemic effects of these drugs. Medetomidine prevented most of these effects except for hyperglycemia. Plasma glucose concentrations were lower in the combined sedation groups than in the medetomidine-saline solution group. Opioids or ketamine used alone may cause changes in stress-related biochemical variables in plasma. Medetomidine prevented or blunted these changes. Combined sedation provided better hormonal and metabolic stability than either component alone. We recommend using medetomidine-butorphanol or medetomidine-ketamine combinations for sedation or anesthesia of systemically healthy dogs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26950855,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Lack of VEGFR2 signaling causes maldevelopment of the intestinal microvasculature and facilitates necrotizing enterocolitis in neonatal mice.\nThe pathogenesis of necrotizing enterocolitis (NEC), a common gastrointestinal disease affecting premature infants, remains poorly understood. We previously found that intestinal VEGF-A expression is decreased in human NEC samples and in a neonatal mouse NEC model prior to detectable histological injury. Therefore, we hypothesized that lack of VEGF receptor 2 (VEGFR2) signaling facilitates neonatal intestinal injury by impairing intestinal microvasculature development. Here, we found that intestinal VEGF-A and its receptor, VEGFR2, were highly expressed at the end of fetal life and significantly decreased after birth in mice. Furthermore, selective inhibition of VEGFR2 kinase activity and exposure to a neonatal NEC protocol significantly decreased the density of the intestinal microvascular network, which was further reduced when both interventions were provided together. Furthermore, VEGFR2 inhibition resulted in greater mortality and incidence of severe injury in pups submitted to the NEC model. The percentage of lamina propria endothelial cells was decreased during NEC induction, and further decreased when VEGFR2 signaling was inhibited. This was associated with decreased endothelial cell proliferation rather than apoptosis. In conclusion, we found that VEGF-A and VEGFR2 proteins are highly expressed in the intestine before birth, and are significantly downregulated in the immediate neonatal period. Furthermore, VEGFR2 signaling is necessary to maintain the integrity of the intestinal mucosal microvasculature during the postnatal period and lack of VEGFR2 signaling predisposes to NEC in neonatal mice.","subset":"pubmed_abstract"} +{"meta":{"pmid":20302882,"dup_signals":{"dup_doc_count":14,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2019-26":1,"2019-09":1,"2019-04":2,"2018-43":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2021-17":1,"2013-20":1}}},"text":"Extinction with varenicline and nornicotine, but not ABT-418, weakens conditioned responding evoked by the interoceptive stimulus effects of nicotine.\nThe interoceptive stimulus effects of nicotine acquire control over behavior. This observation, among others, suggests that the stimulus effects of nicotine are important in the development and tenacity of tobacco dependence. Despite this importance, there has been little research examining whether non-reinforced presentations (extinction) of a ligand that share stimulus effects of nicotine will weaken responding controlled by nicotine. Rats were trained to discriminate nicotine (0.4 mg\/kg) from saline using a discriminated goal-tracking task in which nicotine signaled intermittent access to sucrose; sucrose was withheld on saline sessions. Experiment 1 examined substitution for nicotine by ABT-418, nornicotine, epibatidine, varenicline, or cytisine in 4-min extinction tests. Experiments 2-5 [low-dose nicotine (0.05 mg\/kg), ABT-418, nornicotine, or varenicline, respectively] examined whether substitution for nicotine would persist if extinction tests were increased to 20 min and repeated daily for 6 days. Finally, generalization of this extinction back to the nicotine training stimulus was assessed. Full substitution in brief 4-min extinction tests was seen for ABT-418, nornicotine, epibatidine, varenicline, and cytisine. Low-dose nicotine, ABT-418, nornicotine, and varenicline, evoked only a partial 'nicotine-like' response in the first 20-min extinction test. With repeated extinction, only low-dose nicotine, nornicotine, and varenicline continued to substitute. Extinction with nornicotine and varenicline transferred back to nicotine as indicated by a partial conditioned response to the training stimulus. Interpretations regarding 'nicotine-like' effects of a ligand depend on the nature of the test. Understanding the processes mediating transfer of extinction learning with potential pharmacotherapies may reveal new treatment targets.","subset":"pubmed_abstract"} +{"meta":{"pmid":1840923,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Characterization of an immunoglobulin binding protein homolog in the maize floury-2 endosperm mutant.\nThe maize b-70 protein is an endoplasmic reticulum protein overproduced in the floury-2 (fl2) endosperm mutant. The increase in b-70 levels in fl2 plants occurs during seed maturation and is endosperm specific. We have used amino acid sequence homology to identify b-70 as a homolog of mammalian immunoglobulin binding protein (BiP). Purified b-70 fractions contain two 75-kilodalton polypeptides with pl values of 5.3 and 5.4. Both 75-kilodalton polypeptides share several properties with BiP, including the ability to bind ATP and localization within the lumen of the endoplasmic reticulum. In addition, both b-70 polypeptides can be induced in maize cell cultures with tunicamycin treatment. Like BiP, the pl 5.3 form of b-70 is post-translationally modified by phosphorylation and ADP-ribosylation. However, modification of the pl 5.4 species was not detected in vitro or in vivo. Although the b-70 gene is unlinked to fl2, b-70 overproduction is positively correlated with the fl2 gene and is regulated at the mRNA level. In contrast, the fl2 allele negatively affects the accumulation of the major endosperm storage proteins. The physical similarity of b-70 to BiP and its association with abnormal protein accumulation in fl2 endoplasmic reticulum may reflect a biological function to mediate protein folding and assembly in maize endosperm.","subset":"pubmed_abstract"} +{"meta":{"pmid":29651119,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":17}}},"text":"Update on outcome assessment in myositis.\nThe adult and juvenile myositis syndromes, commonly referred to collectively as idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with the hallmarks of muscle weakness and inflammation. Validated, well-standardized measures to assess disease activity, known as core set measures, were developed by international networks of myositis researchers for use in clinical trials. Composite response criteria using weighted changes in the core set measures of disease activity were developed and validated for adult and juvenile patients with dermatomyositis and adult patients with polymyositis, with different thresholds for minimal, moderate and major improvement in adults and juveniles. Additional measures of muscle strength and function are being validated to improve content validity and sensitivity to change. A health-related quality of life measure, which incorporates patient input, is being developed for adult patients with IIM. Disease state criteria, including criteria for inactive disease and remission, are being used as secondary end points in clinical trials. MRI of muscle and immunological biomarkers are promising approaches to discriminate between disease activity and damage and might provide much-needed objective outcome measures. These advances in the assessment of outcomes for myositis treatment, along with collaborations between international networks, should facilitate further development of new therapies for patients with IIM.","subset":"pubmed_abstract"} +{"meta":{"pmid":23399917,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-40":1,"2023-06":1,"2022-40":1,"2022-33":1,"2022-27":1,"2021-49":1,"2021-43":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-34":1,"2023-50":1}}},"text":"An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors.\nMice with a mutation in the Clock gene (Clock\u039419) have been identified as a model of mania; however, the mechanisms that underlie this phenotype, and the changes in the brain that are necessary for lithium's effectiveness on these mice remain unclear. Here, we find that cholecystokinin (Cck) is a direct transcriptional target of CLOCK and levels of Cck are reduced in the ventral tegmental area (VTA) of Clock\u039419 mice. Selective knockdown of Cck expression via RNA interference in the VTA of wild-type mice produces a manic-like phenotype. Moreover, chronic treatment with lithium restores Cck expression to near wild-type and this increase is necessary for the therapeutic actions of lithium. The decrease in Cck expression in the Clock\u039419 mice appears to be due to a lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription, an effect reversed by lithium. Human postmortem tissue from bipolar subjects reveals a similar increase in Cck expression in the VTA with mood stabilizer treatment. These studies identify a key role for Cck in the development and treatment of mania, and describe some of the molecular mechanisms by which lithium may act as an effective antimanic agent.","subset":"pubmed_abstract"} +{"meta":{"pmid":1748557,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Identification of lectin binding proteins in human tears.\nThe identity of glycoproteins in stimulated normal human tears was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of tears onto minigels, blotting, and subsequent incubation with different biotinylated lectins (concanavalin A [Con A], peanut agglutinin [PNA], glycine max agglutinin [SBA], Phaseolus vulgaris agglutinin, wheat germ agglutinin [WGA, native form], Artocarpus integrifolia agglutinin [Jacalin], and Pisum sativum agglutinin). Control proteins included purified secretory immunoglobulin A (sIgA) from human colostrum, human milk lactoferrin, and chicken-egg lysozyme. All samples were prepared in a denaturing (SDS) buffer under nonreducing and reducing conditions. The sIgA in tears and IgA (alpha) heavy chain fragments (reduced sample) were identified with most of the lectins tested. A particular high molecular weight (greater than 200 kD) protein fraction in tears that just entered the separation gel on SDS-PAGE was detected with WGA and Jacalin. This fraction stain poorly with silver. Tear lactoferrin was identified with all lectins used, although binding was low with SBA. Purified milk lactoferrin showed a poor reaction with Jacalin, but a protein in tears of similar mobility bound this lectin (nonreduced samples). Under both nonreducing and reducing conditions, tear-specific prealbumin in tears did not bind any of the lectins tested. Tear lysozyme only reacted with lectin after reduction. The techniques described may provide additional valuable information in addition to commonly used methods for tear protein analysis and further knowledge concerning the role of glycoproteins on the ocular surface.","subset":"pubmed_abstract"} +{"meta":{"pmid":18451306,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-30":1,"unknown":6}}},"text":"MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.\nActivating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F(-) patients and a single V617F(+) patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F(+) ET patients, those with MPL mutations displayed lower hemoglobin and higher platelet levels at diagnosis, higher serum erythropoietin levels, endogenous megakaryocytic but not erythroid colony growth, and reduced bone marrow erythroid and overall cellularity. Compared with V617F(-) patients, those with MPL mutations were older with reduced bone marrow cellularity but could not be identified as a discrete clinicopathologic subgroup. MPL mutations lacked prognostic significance with respect to thrombosis, major hemorrhage, myelofibrotic transformation or survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":33102197,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Assessment of phylogenetic relationship among twenty Curcuma species in Thailand using amplified fragment length polymorphism marker.\nPlants in the genus Curcuma are a rhizomatous perennial herb which is widely distributed in Thailand. It has long been known for their uses as folk medicines, foods, spices, and cosmetics. However, the identification of plants in the genus Curcuma is very difficult due to morphological similarity in the early flowering stage. Recently, the molecular technique is one of the reliable and powerful tools for plant identification. In this study, the genetic relationship among twenty Curcuma species from Thailand was accessed by the amplified fragment length polymorphism (AFLP) method. AFLP fingerprint showed 98.54% highly polymorphisms with the number of bands (617 bands) ranging between 48 and 80 bands. The dendrogram generated from the unweighted pair group method of the arithmetic average could separate these Curcuma species into three major clusters. Cluster I can be subdivided into IA, which composed of Curcuma parviflora, Curcuma sparganiifolia, Curcuma alismatifolia, Curcuma larsenii, Curcuma Gracillima, and Curcuma rhabdota with similarity index (SI) 0.7926-0.9358 and IB composed of Curcuma petiolata and Curcuma rubrobracteata with the SI 0.9240. Cluster II can be subdivided into IIA being composed of Curcuma longa, Curcuma Zedoaria, and Curcuma aromatica with the SI 0.8989-0.9071, whereas Cluster IIB was composed of Curcuma leucorrhiza, Curcuma aeruginosa, Curcuma comosa, Curcuma mangga, Curcuma angustifolia, Curcuma amada, Curcuma sessilis, and Curcuma albicoma with the SI 0.8236-0.9500. Cluster III belongs to Curcuma singularis and Alpinia galanga (outgroup plant), which clearly separated into different clusters from twenty Curcuma species. In summary, the ten successful AFLP primer combinations could be used to determine the genetic relationship among closely related twenty Curcuma species in Thailand.","subset":"pubmed_abstract"} +{"meta":{"pmid":23392352,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera?\nThromboses represent a major cause of morbidity and mortality in polycythemia vera but the contributing mechanisms are not fully described. To evaluate whether environmental conditions such as altitude\/hypoxia could impact thrombosis history, we retrospectively analyzed thrombosis history in 71 polycythemia vera patients living at an elevation of 5000 feet or more in the Salt Lake City (SLC) area and 166 polycythemia vera patients living near sea level in the Baltimore (BLM) area. The SLC cohort was older with a longer disease duration. No significant differences in type of anticoagulation therapy or prothrombotic factors were present between the two cohorts. After adjusting for age, sex and disease duration, SLC patients experienced an estimated 3.9-fold increase in the odds of a history of thrombosis compared with BLM patients (95% confidence interval 1.8-7.6; P=0.0004). A history of a cardiovascular event was present in 58% of the SLC patients compared with 27% of the BLM patients (P<0.0001). Before diagnosis, thrombosis occurred in 18 and 4% of the SLC and BLM groups, respectively (P=0.003). No correlation between the JAK2 allele burden and thrombosis was observed in this study. This retrospective study suggests that even moderate hypoxia associated with 5000 feet elevation should be considered as an independent prothrombotic risk factor. This observation needs to be confirmed by prospective studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":19492833,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Lipid extraction and determination of halogenated phenols and alkylphenols as their pentafluorobenzoyl derivatives in marine organisms.\nA method was developed for the extraction of lipids and analysis of halogenated phenols and alkylphenols in marine organisms. The extraction efficiency was evaluated by comparing the extractable lipid content and the recovery of 13 added phenols from three different marine species (herring, cod, and blue mussel), with the corresponding results from three well-established extraction procedures, the Bligh and Dyer (B&D), the Smedes (S), and the Jensen (J) methods. The J method and the new method, Jensen centrifugation (Jc), gave phenol recoveries of 80-100% for all species, whereas the B&D and S methods gave relatively low recoveries for the most acidic phenols, with recoveries of only 20-50% for pentachlorophenol (PCP) depending on the species. It was concluded that this effect was governed by the dissociation of the phenols and adsorption to the protein tissue during the extraction (due to ionic interactions). To increase the sensitivity of the analysis, the phenols were converted to their pentafluorobenzoyl esters, by using a tetrabutylammonium-catalyzed extractive acylation. The reaction was quantitative within 2 min at room temperature, and the formed derivatives were persistent enough to withstand treatment with concentrated sulfuric acid.","subset":"pubmed_abstract"} +{"meta":{"pmid":8239525,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-30":1,"unknown":10}}},"text":"Similarity of serum-tumor pharmacokinetics of antitumor agents in man and nude mice.\nA pharmacokinetic comparison was made between nude mice and human gastric cancer patients. This comparison is important in order to optimize the human tumor xenograft-nude mouse system as a screening panel for potential antitumor agents. In this report, mitomycin C (MMC), doxorubicin (DXR), 5-fluorouracil (5-FU) and cisplatin (DDP) were administered to nude mice bearing human tumor subcutaneous xenografts in maximum tolerated doses and to patients with gastric cancer at conventional doses. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, by high performance liquid chromatography for DXR, and by atomic absorption method for DDP. Peak drug concentrations in the serum (Cmax) the mice and humans correlated well with statistical significance (R = 0.999, P < 0.0001). When Cmax and drug concentrations in the tumor (T) the mice and human were compared with each other to evaluate the uptake of drugs into the tumor from the serum and calculated as T\/Cmax, similar results were observed for the same agent with statistical significance (r = 0.990, p < 0.02). These results indicate that the human tumor xenograft-nude mouse system and humans are essentially similar pharmacodynamically, which further validates the uses of this system to evaluate potential antitumor agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":26587656,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2021-17":2,"2020-50":1,"2020-34":1,"2020-29":1,"2019-43":1,"2019-35":6}}},"text":"CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease.\nOBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, (*)3, (*)8, (*)17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03-0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08-0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06-1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05-1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.","subset":"pubmed_abstract"} +{"meta":{"pmid":32031399,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Determination of Optimal Electrospray Parameters for Lipidomics in Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging.\nInfrared matrix-assisted laser desorption ionization (IR-MALDESI) is an ambient mass spectrometry imaging (MSI) technique that relies on electrospray ionization (ESI) for ion generation of desorbed neutrals. Although many mechanisms in IR-MALDESI have been studied in depth, there has not yet been a comprehensive study of how the ESI parameters change the profiles of tissue specific lipids. Acetonitrile (ACN)\/water and methanol (MeOH)\/water solvent systems and compositions were varied across a series of applied ESI voltages during IR-MALDESI analysis of rat liver tissue. Gradients of 12 min were run from 5 to 95% organic solvent in both positive and negative polarities across 11 voltages between 2.25 and 4.5 kV. These experiments informed longer gradients (25-30 min) across shorter solvent gradient ranges with fewer voltages. Optimal ESI parameters for lipidomics were determined by the number and abundance of detected lipids and the relative proportion of background ions. In positive polarity, the best solvent composition was 60-75% ACN\/40-25% H2O with 0.2% formic acid at 3.2 kV applied voltage. The best parameters for negative polarity analysis are 45-55% ACN\/55-45% H2O with 1 mM of acetic acid for voltages between 2.25 and 3.2 kV. Using these defined parameters, IR-MALDESI positive polarity lipidomics studies can increase lipid abundances 3-fold, with 15% greater coverage, while an abundance increase of 1.5-fold and 10% more coverage can be achieved relative to commonly used parameters in negative polarity.","subset":"pubmed_abstract"} +{"meta":{"pmid":19073899,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2013-20":4,"unknown":7}}},"text":"Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster.\nDisrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (approximately 50 mM) from a 2 g\/kg injection occurred within 20-40 min with a half-life of approximately 3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.","subset":"pubmed_abstract"} +{"meta":{"pmid":23112416,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Study of antiurolithiatic activity of Asparagus racemosus on albino rats.\nThe aim of this study was to investigate the effect of ethanolic extract of Asparagus racemosus on urolithiasis in rats. Thirty-six male Wistar albino rats were randomly divided into six groups (n = 6). Ethylene glycol (EG) 0.75% and ammonium chloride (AC) 2% in drinking water were fed to all groups (Groups II-VI) except normal control (Group I) rats for 10 days to induce urolithiasis. Group III-VI rats were treated with ethanolic extract of Asparagus racemosus at doses 200, 400, 800, and 1600 mg\/kg, respectively, for 10 days. Positive control (Group II) rats were treated with EG\/AC alone. Group I rats were administered drinking water and distilled water (6 \u03bcl\/g) by gavage. After 10 days, blood samples were collected and analyzed for serum concentrations of calcium, phosphorus, urea, and creatinine. The kidneys were removed and sectioned for histopathological examination. The data were presented as mean \u00b1 standard error of mean and analyzed using one-way analysis of variance and Student's \"t\"-test. P < 0.05 was considered statistically significant. Conventional windows software was used for statistical analysis. The rats treated with ethanolic extract of A. racemosus at doses 800 and 1600 mg\/ kg significantly (P < 0.05) reduced the serum concentrations of calcium, phosphorus, urea, and creatinine. Histopathology of the kidneys in Groups V and VI revealed less tissue damage and were almost similar to Group I rats. The ethanolic extract of A. racemosus has protective effect against urolithiasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":17593148,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2015-18":1,"2014-10":1,"2024-30":1,"unknown":4}}},"text":"Treating adolescents with social anxiety disorder in school: an attention control trial.\nAnxiety disorders are often undetected and untreated in adolescents. This study evaluates the relative efficacy of a school-based, cognitive-behavioral intervention compared to an educational-supportive treatment for adolescents with social anxiety disorder. Thirty-six students (30 females), ages 14 to 16, were randomized to a 12-week specific intervention, Skills for Social and Academic Success (SASS), or a credible attention control matched for structure and contact, conducted in school. Independent evaluations and adolescent self-reports indicated significant reduction in social anxiety for SASS compared to the control group. Parent reports of their children's social anxiety did not discriminate between treatments. In the specific intervention, 59%, compared to 0% in the control, no longer met criteria for social anxiety disorder following treatment. Superiority of the SASS intervention was maintained 6 months after treatment cessation. The study provides evidence that intervention for social anxiety disorder that emphasizes exposure and social skills is efficacious. Results indicate that clinical improvement is sustained for at least 6 months, and that, overall, adolescents with social anxiety disorder do not respond to non-specific treatment. This investigation has public health implications by demonstrating that effective interventions can be transported to nonclinical settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":10209888,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Self-gelatinizable copolymer immobilized glucose biosensor based on prussian blue modified graphite electrode.\nA novel poly(vinyl alcohol) grafting 4-vinylpyridine self-gelatinizable copolymer was adapted to immobilize glucose oxidase. The reduction of hydrogen peroxide (H2O2) was detected at a Prussian Blue (PB) modified graphite electrode. A stable and sensitive glucose amperometric biosensor is described. The copolymer is a good biocompatible polymer in which the glucose oxidase retains high activity. Moreover, the copolymer can adhere firmly to the inorganic PB membrane. The sensor showed an apparent Michaelis-Menten constant of 18 +\/- 0.2 mM and a maximum current density of 1.14 microA cm-2 mM-1. The linear range is from 5 microM to 4.5 mM glucose and the detection limit is 0.5 microM glucose. The catalytic efficiency of PB for the reduction of H2O2 is higher than that for the oxidation of H2O2. Glucose concentrations in serum samples from healthy persons and diabetic patients were determined using the sensor. The results compared well with those provided by the hospital using a spectroscopy method.","subset":"pubmed_abstract"} +{"meta":{"pmid":34255848,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort.\nGreater whole grain (WG) consumption is associated with reduced risk of cardiovascular disease (CVD); however, few prospective studies have examined WG or refined grain (RG) intake and intermediate cardiometabolic risk factors. We examined the longitudinal association between WG and RG intake on changes in waist circumference (WC); fasting HDL cholesterol, triglyceride, and glucose concentrations; and blood pressure. Subjects were participants in the Framingham Offspring cohort study [n = 3121; mean \u00b1 SD baseline age: 54.9 \u00b1 0.2 y; BMI (kg\/m2) 27.2 \u00b1 0.1]. FFQ, health, and lifestyle data were collected approximately every 4 y over a median 18-y follow-up. Repeated measure mixed models were used to estimate adjusted mean changes per 4-y interval in risk factors across increasing categories of WG or RG intake. Greater WG intake was associated with smaller increases in WC (1.4 \u00b1 0.2 compared with 3.0 \u00b1 0.1 cm in the highest compared with the lowest category, respectively; P-trend < 0.001), fasting glucose concentration (0.7 \u00b1 0.4 compared with 2.6 \u00b1 0.2 mg\/dL; P-trend < 0.001), and systolic blood pressure (SBP; 0.2 \u00b1 0.5 compared with 1.4 \u00b1 0.3 mm Hg; P-trend < 0.001) per 4-y interval. When stratified by sex, a stronger association with WC was observed among females than males. Higher intake of WG was associated with greater increases in HDL cholesterol and declines in triglyceride concentrations; however, these differences did not remain significant after adjustment for change in WC. Conversely, greater RG intake was associated with greater increases in WC (2.7 \u00b1 0.2 compared with 1.8 \u00b1 0.1 cm, P-trend < 0.001) and less decline in triglyceride concentration (-0.3 \u00b1 1.3 compared with -7.0 \u00b1 0.7 mg\/dL, P-trend < 0.001). Among middle- to older-age adults, replacing RG with WG may be an effective dietary modification to attenuate abdominal adiposity, dyslipidemia, and hyperglycemia over time, thereby reducing the risk of cardiometabolic diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":32780661,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast-Conserving Surgery in the Modern Treatment Era: A Multicenter, Randomized Controlled Trial From China.\nNo randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019). CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":29207120,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2020-29":1,"2020-24":1,"2019-51":1,"2019-47":1,"2019-26":1,"2019-13":1,"2019-09":2,"2018-47":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2020-50":1}}},"text":"The antibacterial effect of topical ozone on the treatment of MRSA skin infection.\nSkin can be infected by many types of microorganisms, most commonly by gram\u2011positive strains of Staphylococcus and Streptococcus spp. Treatment of Staphylococcus aureus (S. aureus) infections, particularly that of methicillin resistant Staphylococcus aureus (MRSA), is a challenge in clinical practice. Ozone therapy has proven to be one of the strongest antiseptics against the majority of microorganisms involved in skin infections. The purpose of the present study was to evaluate the microbicidal effects of topical ozone therapy on S. aureus and MRSA, and determine the clinical efficacy of ozone therapy on patients with MRSA skin infection. Microbicidal effects of ozonated oil and ozonated water were determined by plating and Kirby Bauer methods. Clinical efficacy and safety of topical ozone were evaluated in two cases with skin MRSA infection. The killing rates of ozonated oil for S. aureus and MRSA were greater when compared with the control oil group. Almost 100% of S. aureus were eliminated by ozonated oil following 5 min. Almost 100% MRSA were eliminated by ozonated oil following 15 min. In addition, 100% S. aureus and 100% MRSA were eliminated by ozonated water in 1 min. The inhibition zone diameters of ozonated oil for S. aureus and MRSA were 17 and 13 mm, respectively, which were significantly larger than the control group. Both cases of skin MRSA infection were completely healed with ozone therapy. In conclusion, ozone therapy is a potential treatment for S. aureus and MRSA skin infection as it has great efficacy, few side effects and low\u2011costs.","subset":"pubmed_abstract"} +{"meta":{"pmid":19005044,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":9}}},"text":"State dependence of network output: modeling and experiments.\nEmerging experimental evidence suggests that both networks and their component neurons respond to similar inputs differently, depending on the state of network activity. The network state is determined by the intrinsic dynamical structure of the network and may change as a function of neuromodulation, the balance or stochasticity of synaptic inputs to the network, and the history of network activity. Much of the knowledge on state-dependent effects comes from comparisons of awake and sleep states of the mammalian brain. Yet, the mechanisms underlying these states are difficult to unravel. Several vertebrate and invertebrate studies have elucidated cellular and synaptic mechanisms of state dependence resulting from neuromodulation, sensory input, and experience. Recent studies have combined modeling and experiments to examine the computational principles that emerge when network state is taken into account; these studies are highlighted in this article. We discuss these principles in a variety of systems (mammalian, crustacean, and mollusk) to demonstrate the unifying theme of state dependence of network output.","subset":"pubmed_abstract"} +{"meta":{"pmid":29023431,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":15}}},"text":"HIV Care Outcomes Among Hispanics or Latinos with Diagnosed HIV Infection - United States, 2015.\nData from CDC's National HIV Surveillance System (NHSS)* are used to monitor progress toward achieving national goals set forth in the Division of HIV\/AIDS Prevention's Strategic Plan (1) and other federal directives\u2020 for human immunodeficiency virus (HIV) testing, care, and treatment outcomes and HIV-related disparities in the United States. Recent data indicate that Hispanics or Latinos\u00a7 are disproportionately affected by HIV infection. Hispanics or Latinos living with diagnosed HIV infection have lower levels of care and viral suppression than do non-Hispanic whites but higher levels than those reported among blacks or African Americans (2). The annual rate of diagnosis of HIV infection among Hispanics or Latinos is three times that of non-Hispanic whites (3), and a recent study found increases in incidence of HIV infection among Hispanic or Latino men who have sex with men (4). Among persons with HIV infection diagnosed through 2013 who were alive at year-end 2014, 70.2% of Hispanics or Latinos received any HIV medical care compared with 76.1% of non-Hispanic whites (2). CDC used NHSS data to describe HIV care outcomes among Hispanics or Latinos. Among male Hispanics or Latinos with HIV infection diagnosed in 2015, fewer males with infection attributed to heterosexual contact (34.6%) had their infection diagnosed at an early stage (stage 1 = 12.0%, stage 2 = 22.6%) than males with infection attributed to male-to-male sexual contact (60.9%: stage 1 = 25.2%, stage 2 = 35.7%). The percentage of Hispanics or Latinos linked to care after diagnosis of HIV infection increased with increasing age; females aged 45-54 years with infection attributed to injection drug use (IDU) accounted for the lowest percentage (61.4%) of persons linked to care. Among Hispanics or Latinos living with HIV infection, care and viral suppression were lower among selected age groups of Hispanic or Latino males with HIV infection attributed to IDU than among males with infection attributed to male-to-male sexual contact and male-to-male sexual contact and IDU. Intensified efforts to develop and implement effective interventions and public health strategies that increase engagement in care and viral suppression among Hispanics or Latinos (3,5), particularly those who inject drugs, are needed to achieve national HIV prevention goals.","subset":"pubmed_abstract"} +{"meta":{"pmid":6848849,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Profile of women practicing breast self-examination.\nThe monthly practice of breast self-examination (BSE) can result in the early diagnosis of breast cancer. To explore factors that influence women's habits in the practice of BSE, we interviewed 616 women using an interactive computer program. We found that these women were more likely to practice BSE on a frequent basis if they were living with their sexual partner, had been shown how to perform BSE, and were confident in their examination technique. Women with a maternal history of breast disease were also more likely to practice monthly BSE. Unlike past reports that women with formal education beyond high school practice BSE more frequently than less-educated women, our study showed no association between monthly BSE practice and formal education. Contrary to our hypothesis that BSE practice was associated with the practice of other preventive health activities, our study did not demonstrate such a relationship. These findings suggest that demonstrating BSE at the periodic health examination may help increase the number of women practicing BSE on a frequent basis.","subset":"pubmed_abstract"} +{"meta":{"pmid":23813667,"dup_signals":{"dup_doc_count":26,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2018-51":1,"2018-43":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":2,"2016-50":1,"2016-44":2,"2019-13":1}}},"text":"Genetics driven interventions for ex situ conservation of red junglefowl (Gallus gallus murghi) populations in India.\nGenetics driven interventions (GDI) are imperative for ex situ conservation to exhort long-term sustenance of small and isolated populations in captivity as they are more prone to an increased extinction risk due to inbreeding and genetic drift. We investigated constitutive genetic attributes of four captive Red Junglefowl (RJF) populations in India, to facilitate the prioritization of the birds to formulate an effective breeding action plan. All the four RJF populations were found to be evident of significant inbreeding but none of them had exhibited any signature of bottleneck footprints in the recent past. Bayesian cluster analysis revealed three distinct groups among the four captive RJF populations. Interestingly, birds of Kufri population were assigned together with Gopalpur as well as with Morni populations, indicating their shared genetic ancestry. Among the four populations, Morni population displayed the richest genetic attributes and was therefore presumed as a key source of genetic variation. Nine birds of Morni population were relatively pure (q-value >0.98) and carried about 50% of the total private alleles of Morni population. Thus, being the foremost reservoir of allelic diversity, these nine birds may be selected for launching alien alleles to other RJF populations to rescue their loss of genetic diversity arising from inbreeding.","subset":"pubmed_abstract"} +{"meta":{"pmid":30028652,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"What is adverse effect of wireless local area network, using 2.45 GHz, on the reproductive system?\nTo investigate the inflammatory effect and testicular damage on rats exposed to low level of electromagnetic fields (EMF) at 2.45 GHz microwave radiation. Twenty two Wistar rats were divided into two groups. Group 1 was the control group and not exposed to EMF. Group 2 was exposed to low level EMF (average E-field 3.68 \u00b1 0.36 V\/m, whole body average SAR, 0.0233 W\/kg, in 10 g tissue) at 2.45 GHz for 1 hour\/day for 30 consecutive days. At the end of the study, interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-32 (IL-32), C-reactive protein (CRP) were measured in rat serum and IL-6, IL-10, IL-32 were measured in rat testis tissue. Furthermore, testicular tissues were evaluated histopathologically in terms of spermatogenesis and coagulation necrosis. Serum IL-6 and CRP levels were found to be significantly different in the study group compared to the control group (p < .05), but no significant difference was found in serum IL-10, IL-32 levels and testis tissue IL-6, IL-10, IL-32 levels compared to the control group (p > .05). On the other hand, histopathological evaluation of testicular tissue revealed a significant difference in necrosis and spermatogenesis when compared with the control group (p < .05). It may be concluded that low level EMF at 2.45 GHz increases inflammation and testicular damage and negative impact on male reproductive system function.","subset":"pubmed_abstract"} +{"meta":{"pmid":23599043,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":18}}},"text":"Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas.\nWe have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4\u207a) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem\/progenitor cell markers. Furthermore, the number of ZSCAN4\u207a cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4\u207a cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas.","subset":"pubmed_abstract"} +{"meta":{"pmid":26477465,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-49":1,"2022-27":1,"2020-29":1,"2020-05":1,"2019-09":1,"2018-51":1,"2018-34":1,"2018-17":1,"2018-09":1,"2023-14":1}}},"text":"Morphological and Functional Characteristic of Senescent Cancer Cells.\nCellular senescence is the state of permanent proliferation cessation. There are two types of cell senescence. One is replicative senescence, which relies on telomere length-dependent limit of cell divisions. The second is stress-induced premature senescence (SIPS) which is telomere- independent. Cell senescence is a barrier to cancer. Paradoxically senescent cells, which are metabolically active secrete factors which can be procancerogenic. The main culprit of cell senescence is DNA damage and DNA damage response. Although cancer cells frequently possess mutations in two main signalling pathways involved in cell senescence, namely p53\/p21 and p16\/Rb, they still preserve the ability to undergo DNA damage-induced senescence. Cancer cell senescence is a new promising target for anticancer therapy. It was shown that many types of cancer cells can undergo SIPS. Senescent cancer cells have generally the same features as normal cells, such as enlarged size, accumulation of DNA damage foci and increased activity of Senescence-Associated \u03b2- galactosidase. Moreover senescent cancer cells are frequently polyploid and it was shown that polyploidy might be connected with abnormal cell division, which leads to the appearance of small descendants. In this review we will focus on morphological hallmarks of senescent cancer cells as well as their functional capabilities, such as secretion, polyploidization, and stemness. We will also discuss links with autophagy, mitotic catastrophe and the propensity of senescent cells to regain proliferative activities. We would like to show the complexity of cancer cell phenotype arising after anticancer treatment and difficulties in interpretation of the experimental data.","subset":"pubmed_abstract"} +{"meta":{"pmid":26975754,"dup_signals":{"dup_doc_count":11}},"text":"Overexpressing enzymes of the Ehrlich pathway and deleting genes of the competing pathway in Saccharomyces cerevisiae for increasing 2-phenylethanol production from glucose.\n2-Phenylethanol (2-PE) is a higher aromatic alcohol that is used in the cosmetics and food industries. The budding yeast Saccharomyces cerevisiae is considered to be a suitable host for the industrial production of higher alcohols, including 2-PE. To produce 2-PE from glucose in S. cerevisiae, we searched for suitable 2-keto acid decarboxylase (KDC) and alcohol dehydrogenase (ADH) enzymes of the Ehrlich pathway for overexpression in strain YPH499, and found that overexpression of the ARO10 and\/or ADH1 genes increased 2-PE production from glucose. Further, we screened ten BY4741 single-deletion mutants of genes involved in the competing pathways for 2-PE production, and found that strains aro8\u0394 and aat2\u0394 displayed increased 2-PE production. Based on these results, we engineered a BY4741 strain that overexpressed ARO10 and contained an aro8\u0394 deletion, and demonstrated that the strain produced 96 mg\/L 2-PE from glucose as the sole carbon source. As this engineered S. cerevisiae strain showed a significant increase in 2-PE production from glucose without the addition of an intermediate carbon substrate, it is a promising candidate for the large-scale production of 2-PE.","subset":"pubmed_abstract"} +{"meta":{"pmid":18273740,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Reducing hazardous material and environmental impact through recycling of scandium nanomaterial waste.\nThe emerging use of scandium and the environmental impact from scandium-containing waste is a rising environmental and health concern. With the development of new materials in the last decade, toxicological studies on those new materials have also been increasing. An example of a process which employs scandium is the generation of metallic nitride fullerene nanomaterials. This process typically generates 99+% scandium waste, as only small amounts of scandium are actually incorporated into the target fullerene molecules. We demonstrate a safe method to recover the scandium content in the waste, reuse the recovered material and successfully demonstrate a comparable product distribution without detectable health and environmental concerns.","subset":"pubmed_abstract"} +{"meta":{"pmid":26324728,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2020-10":1,"2019-47":1,"2019-13":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-43":1,"2017-39":1,"2020-40":1}}},"text":"Spatial Patterns of Plasmodium falciparum Clinical Incidence, Asymptomatic Parasite Carriage and Anopheles Density in Two Villages in Mali.\nHeterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission. In the two study areas that were < 1 km(2) in size, we observed evidence for spatial clustering of Anopheles densities or malaria parasite carriage during the dry season. Anopheles density and malaria prevalence appeared associated in some of our detected hotspots. However, many households with high parasite prevalence or high Anopheles densities were located outside the identified hotspots. Our findings indicate that within small villages exposed to low- or mesoendemic-malaria transmission, spatial patterns in mosquito densities and parasite carriage are best detected in the dry season. Considering the high prevalence of parasite carriage outside detected hotspots, the suitability of the area for targeting control efforts to households or areas of more intense malaria transmission may be limited.","subset":"pubmed_abstract"} +{"meta":{"pmid":7585578,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"p53 point mutation and survival in colorectal cancer patients.\nWe have examined the relationship between point mutation of the p53 tumor suppressor gene and survival in colorectal cancer patients. We found that patients with tumors harboring mutated p53 genes showed a significantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative therapies depended significantly on mutation status in both adjuvant and palliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of the p53 tumor suppressor gene were inherently more aggressive than tumors with point mutations outside of these domains, and mutations of codon 175 were particularly aggressive. These results suggest that knowledge of a patient's p53 status, both with respect to the presence of point mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.","subset":"pubmed_abstract"} +{"meta":{"pmid":24133614,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"In vivo antioxidant, hypoglycemic, and anti-tumor activities of anthocyanin extracts from purple sweet potato.\nAnthocyanin from purple sweet potato (PSP) extracted by microwave baking (MB) and acidified electrolyzed water (AEW) exhibited antioxidant activity. After further purification by macroporous AB-8 resin, the color value of PSP anthocyanin (PSPA) reached 30.15 with a total flavonoid concentration of 932.5 mg\/g. The purified extracts had more potent antioxidant activities than the crude extracts. After continuously administering the PSP extracts to 12-mo-old mice for 1 mo, the anti-aging index of the experimental group was not significantly different from that of 5-mo-old mice. To a certain degree, PSPA was also effective for controlling plasma glucose levels in male Streptozocin (STZ)-treated diabetic mice. In addition, the extracts inhibited Sarcoma S180 cell growth in ICR mice. Mice consuming the PSP extracts formed significantly fewer and smaller sarcomas than mice consuming the control diets. The highest inhibition rate was 69.03%. These results suggest that anthocyanin extracts from PSP not only exert strong antioxidant effects in vitro, but also had anti-aging, anti-hyperglycemic, and anti-tumor activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":30675180,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2022-40":1,"2020-34":2,"2019-51":1,"2019-35":1,"2019-26":2,"2019-22":1,"2019-13":2,"2023-06":1,"2024-22":1}}},"text":"Nucleic acid delivery to mesenchymal stem cells: a review of nonviral methods and applications.\nMesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated and expanded from many tissues, and are being investigated for use in cell therapies. Though MSC therapies have demonstrated some success, none have been FDA approved for clinical use. MSCs lose stemness ex vivo, decreasing therapeutic potential, and face additional barriers in vivo, decreasing therapeutic efficacy. Culture optimization and genetic modification of MSCs can overcome these barriers. Viral transduction is efficient, but limited by safety concerns related to mutagenicity of integrating viral vectors and potential immunogenicity of viral antigens. Nonviral delivery methods are safer, though limited by inefficiency and toxicity, and are flexible and scalable, making them attractive for engineering MSC therapies. Transfection method and nucleic acid determine efficiency and expression profile in transfection of MSCs. Transfection methods include microinjection, electroporation, and nanocarrier delivery. Microinjection and electroporation are efficient, but are limited by throughput and toxicity. In contrast, a variety of nanocarriers have been demonstrated to transfer nucleic acids into cells, however nanocarrier delivery to MSCs has traditionally been inefficient. To improve efficiency, plasmid sequences can be optimized by choice of promoter, inclusion of DNA targeting sequences, and removal of bacterial elements. Instead of DNA, RNA can be delivered for rapid protein expression or regulation of endogenous gene expression. Beyond choice of nanocarrier and nucleic acid, transfection can be optimized by priming cells with media additives and cell culture surface modifications to modulate barriers of transfection. Media additives known to enhance MSC transfection include glucocorticoids and histone deacetylase inhibitors. Culture surface properties known to modulate MSC transfection include substrate stiffness and specific protein coating. If nonviral gene delivery to MSCs can be sufficiently improved, MSC therapies could be enhanced by transfection for guided differentiation and reprogramming, transplantation survival and directed homing, and secretion of therapeutics. We discuss utilized delivery methods and nucleic acids, and resulting efficiency and outcomes, in transfection of MSCs reported for such applications. Recent developments in transfection methods, including nanocarrier and nucleic acid technologies, combined with chemical and physical priming of MSCs, may sufficiently improve transfection efficiency, enabling scalable genetic engineering of MSCs, potentially bringing effective MSC therapies to patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":1763330,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Inhibition of Rap1A binding to cytochrome b558 of NADPH oxidase by phosphorylation of Rap1A.\nRap1A is a low molecular weight guanosine triphosphate (GTP)-binding protein in human neutrophil membranes whose cellular function is unknown. Rap1A was found to form stoichiometric complexes with the cytochrome b558 component of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system. The (guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S)-bound form of Rap1A bound more tightly to cytochrome b558 than did the guanosine diphosphate-bound form. No complex formation was observed between cytochrome b558 and H-Ras-GTP-gamma-S or Rap1A-GTP-gamma-S that had been heat-inactivated, nor between Rap1A-GTP-gamma-S and hydrophobic proteins serving as controls. Complex formation between Rap1A-GTP-gamma-S and cytochrome b558 was inhibited by phosphorylation of Rap1A with cyclic adenosine monophosphate (cAMP)-dependent protein kinase. These observations suggest that Rap1A may participate in the structure or regulation of the NADPH oxidase system and that this function of the Rap1A protein may be altered by phosphorylation.","subset":"pubmed_abstract"} +{"meta":{"pmid":1737651,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"Control of the erythrocyte free Ca2+ concentration in essential hypertension.\nSince Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca2+]i) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca2+]i was measured by using the fluorescent Ca2+ chelator fura-2. Red blood cell [Ca2+]i was increased in hypertensive compared with normotensive subjects in the whole population and further increased when hypertensive were compared with age-matched normotensive subjects. An inverse relation between age and [Ca2+]i was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca2+]i values were associated with a reduced erythrocyte deformability. The initial rate of 45Ca2+ uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca2+ concentration was elevated from 1 to 2 mmol\/l, [Ca2+]i increased by 16 +\/- 4% (p less than 0.03) in red blood cells from both groups, thus maintaining a significant difference between hypertensive and normotensive subjects. Under these conditions, the addition of 10(-7) mol\/l nicardipine, a dihydropyridine Ca2+ antagonist, decreased [Ca2+]i by 15 +\/- 4% (p less than 0.05) and 7 +\/- 5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca2+]i observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca2+]i. In the presence of 5 mumol\/l W7, a calmodulin antagonist, [Ca2+]i increased significantly only in erythrocytes from hypertensive patients (26 +\/- 6%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":12496089,"dup_signals":{"dup_doc_count":12}},"text":"Probing distance and electrical potential within a protein pore with tethered DNA.\nDNA molecules tethered inside a protein pore can be used as a tool to probe distance and electrical potential. The approach and its limitations were tested with alpha-hemolysin, a pore of known structure. A single oligonucleotide was attached to an engineered cysteine to allow the binding of complementary DNA strands inside the wide internal cavity of the extramembranous domain of the pore. The reversible binding of individual oligonucleotides produced transient current blockades in single channel current recordings. To probe the internal structure of the pore, oligonucleotides with 5' overhangs of deoxyadenosines and deoxythymidines up to nine bases in length were used. The characteristics of the blockades produced by the oligonucleotides indicated that single-stranded overhangs of increasing length first approach and then thread into the transmembrane beta-barrel. The distance from the point at which the DNA was attached and the internal entrance to the barrel is 43 A, consistent with the lengths of the DNA probes and the signals produced by them. In addition, the tethered DNAs were used to probe the electrical potential within the protein pore. Binding events of oligonucleotides with an overhang of five bases or more, which threaded into the beta-barrel, exhibited shorter residence times at higher applied potentials. This finding is consistent with the idea that the main potential drop is across the alpha-hemolysin transmembrane beta-barrel, rather than the entire length of the lumen of the pore. It therefore explains why the kinetics and thermodynamics of formation of short duplexes within the extramembranous cavity of the pore are similar to those measured in solution, and bolsters the idea that a \"DNA nanopore\" provides a useful means for examining duplex formation at the single molecule level.","subset":"pubmed_abstract"} +{"meta":{"pmid":9811573,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"XBF-1, a winged helix transcription factor with dual activity, has a role in positioning neurogenesis in Xenopus competent ectoderm.\nNeuronal differentiation in the vertebrate nervous system is temporally and spatially controlled by mechanisms which are largely unknown. Here we investigate the role of XBF-1, an anterior neural plate-specific winged helix transcription factor, in controlling the pattern of neurogenesis in Xenopus ectoderm. We show that, in the anterior neural plate of normal embryos, prospective neurogenesis is positioned at the anterior boundary of the XBF-1 expression domain. By misexpressing XBF-1 in the posterior neural plate we show that a high dose of XBF-1 has a dual effect; it suppresses endogenous neuronal differentiation in high expressing cells and induces ectopic neuronal differentiation in adjacent cells. In contrast, a low dose of XBF-1 does not suppress but instead, expands the domain of neuronal differentiation in the lateral and ventral sides of the embryo. XBF-1 regulates the expression of XSox3, X-ngnr-1, X-Myt-1 and X-&Dgr;-1 suggesting that it acts early in the cascade leading to neuronal differentiation. A fusion of XBF-1 to a strong repressor domain (EnR) mimics most of the XBF-1 effects suggesting that the wild type XBF-1 is a transcriptional repressor. However, fusion of XBF-1 to a strong activation domain (E1A) specifically suppresses neuronal differentiation suggesting that XBF-1 may also work as a transcriptional activator. Based on these findings, we propose that XBF-1 is involved in positioning neuronal differentiation by virtue of its concentration dependent, dual activity, as a suppressor and an activator of neurogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":31641717,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Activate capture and digital counting (AC + DC) assay for protein biomarker detection integrated with a self-powered microfluidic cartridge.\nWe demonstrate a rapid, 2-step, and ultrasensitive assay approach for quantification of target protein molecules from a single droplet test sample. The assay is comprised of antibody-conjugated gold nanoparticles (AuNPs) that are \"activated\" when they are mixed with the test sample and bind their targets. The resulting liquid is passed through a microfluidic channel with a photonic crystal (PC) biosensor that is functionalized with secondary antibodies to the target biomarker, so that only activated AuNPs are captured. Utilizing recently demonstrated hybrid optical coupling between the plasmon resonance of the AuNP and the resonance of the PC, each captured AuNP efficiently quenches the resonant reflection of the PC, thus enabling the captured AuNPs to be digitally counted with high signal-to-noise. To achieve a 2-step assay process that is performed on a single droplet test sample without washing steps or active pump elements, controlled single-pass flow rate is obtained with an absorbing paper pad waste reservoir embedded in a microfluidic cartridge. We use the activate capture and digital counting (AC + DC) approach to demonstrate HIV-1 capsid antigen p24 detection from a 40 \u03bcL spiked-in human serum sample at a one thousand-fold dynamic range (1-103 pg mL-1) with only a 35-minute process that is compatible with point-of-care (POC) analysis. The AC + DC approach allows for ultrasensitive and ultrafast biomolecule detection, with potential applications in infectious disease diagnostics and early stage disease monitoring.","subset":"pubmed_abstract"} +{"meta":{"pmid":12908523,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2021-31":1,"2021-21":1,"2021-10":1,"2020-05":1,"2019-47":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2021-43":1}}},"text":"Magnesium whitlockite, a calcium phosphate crystal of special interest in pathology.\nWhitlockite (in fact magnesium whitlockite) is a calcium orthophosphate crystal in which, in biological conditions, magnesium is partly substituted for calcium. Identified in X-ray or electron diffraction patterns, it occurs in physiological or pathological conditions at extra or intratissular sites, mainly in tissues of non-epithelial origin. In a range of pathological calcifications investigated by X-ray diffraction, we noted that whitlockite appeared to be frequently associated with apatite, particularly in \"dystrophic calcifications\" of tuberculous origin. These personal observations could be correlated with documented data in oral pathology (dental calculus, salivary stones, and dental caries). Whitlockite deposits have also been reported in non-infectious conditions, such as in aortic media, cartilage, and bone tissue. Whereas the formation of both apatite and magnesium whitlockite appears to be caused by the binding of their constituting ions with proteolipids, magnesium inhibits apatite originating from amorphous calcium phosphate to the benefit of whitlockite formation. Possibly, the development of magnesium whitlockite may provide an interesting marker for magnesium metabolism. Further studies linking histology to crystallography might relate the crystal to issues, such as tuberculous calcifications or diseases of bone tissue, and might be useful for potential diagnostic orientation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27500439,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"On-line determination by small angle X-ray scattering of the shape of hen egg white lysozyme immediately following elution from a hydrophobic interaction chromatography column.\nThis study documents the use of an integrated approach, involving on-line hydrophobic interaction chromatography interfaced with Small Angle X-ray Scattering (HIC-SAXS) measurements, to monitor the conformational status of proteins immediately upon elution from a chromatographic column operated at different temperatures. Moreover, this approach provides an additional avenue to interrogate the changes in protein shape that may occur across the eluted chromatographic peak. To this end, radii of gyration were extrapolated from the Guinier approximation with the HIC-SAXS data, whilst pair distribution functions and bead model simulations were generated by using the indirect transform program GNOM and ab initio reconstruction with GASBOR to provide further insight into protein conformational changes that occur during hydrophobic interaction chromatography.","subset":"pubmed_abstract"} +{"meta":{"pmid":22542808,"dup_signals":{"dup_doc_count":35,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":3,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":2,"2021-49":2,"2021-43":2,"2021-39":2,"2021-31":1,"2021-25":1,"2021-17":3,"2021-04":1,"2020-45":2,"2020-40":3,"2023-50":1,"2024-22":2}}},"text":"Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?\nAutophagy is an evolutionarily conserved mechanism for intracellular substance degradation, responsible for the recycling of metabolic substances and the maintenance of intracellular stability. It has early been demonstrated to play a significant role in tumorigenesis, but whether it acts as a promoter or a suppressor during tumorigenesis seems to be context-specific. Moreover, autophagy is also implicated in promoting chemoresistance of cancer cells so as to attenuate therapeutic efficacy of chemotherapy. On the contrary, other reports highlight a tumor-killing role of autophagy during cancer treatment. Herein, this review aims to revisit the key features of autophagy, summarize the seemingly contradictory roles of autophagy during both tumorigenesis and cancer chemotherapy, and evaluate the feasibility of altering the level of cellular autophagy as part of cancer adjuvant treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":30195642,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":12}}},"text":"What happens at the lesion does not stay at the lesion: Transcription-coupled nucleotide excision repair and the effects of DNA damage on transcription in cis and trans.\nUnperturbed transcription of eukaryotic genes by RNA polymerase II (Pol II) is crucial for proper cell function and tissue homeostasis. However, the DNA template of Pol II is continuously challenged by damaging agents that can result in transcription impediment. Stalling of Pol II on transcription-blocking lesions triggers a highly orchestrated cellular response to cope with these cytotoxic lesions. One of the first lines of defense is the transcription-coupled nucleotide excision repair (TC-NER) pathway that specifically removes transcription-blocking lesions thereby safeguarding unperturbed gene expression. In this perspective, we outline recent data on how lesion-stalled Pol II initiates TC-NER and we discuss new mechanistic insights in the TC-NER reaction, which have resulted in a better understanding of the causative-linked Cockayne syndrome and UV-sensitive syndrome. In addition to these direct effects on lesion-stalled Pol II (effects in cis), accumulating evidence shows that transcription, and particularly Pol II, is also affected in a genome-wide manner (effects in trans). We will summarize the diverse consequences of DNA damage on transcription, including transcription inhibition, induction of specific transcriptional programs and regulation of alternative splicing. Finally, we will discuss the function of these diverse cellular responses to transcription-blocking lesions and their consequences on the process of transcription restart. This resumption of transcription, which takes place either directly at the lesion or is reinitiated from the transcription start site, is crucial to maintain proper gene expression following removal of the DNA damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":31799390,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":8}}},"text":"A sperm peptide enhances long-term memory in female Drosophila.\nCan mating influence cognitive functions such as learning and memory in a permanent way? We have addressed this question using a combined behavioral and in vivo imaging approach, finding that aversive long-term memory performance strongly increases in Drosophila females in response to sperm transfer following mating. A peptide in the male sperm, the sex peptide, is known to cause marked changes in female reproductive behavior, as well as other behaviors such as dietary preference. Here, we demonstrate that this sex peptide enhances memory by acting on a single pair of serotonergic brain neurons, in which activation of the sex peptide receptor stimulates the cyclic adenosine monophosphate\/protein kinase A pathway. We thus reveal a strong effect of mating on memory via the neuromodulatory action of a sperm peptide on the female brain.","subset":"pubmed_abstract"} +{"meta":{"pmid":28749884,"dup_signals":{"dup_doc_count":14}},"text":"Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults.\n: Purpose: Red yeast rice (RYR) supplementation has become a popular alternative to statin therapy in treating hypercholesterolemia. This state-of-the-science review seeks to explore the most recent evidence on the effectiveness and safety of RYR supplementation in treating dyslipidemic adults. This review extends the time frame of a meta-analysis performed by Li and colleagues in 2014; specifically, we looked at the literature published between September 2013 and April 2016. We conducted a search of four electronic databases-PsycINFO, CINAHL, PubMed, and Scopus-using the terms red yeast rice and cholesterol. We excluded studies that included berberine or lovastatin. Fifteen articles met the inclusion criteria. Eleven articles reported on randomized controlled trials, one reported on an open-label pilot study, and one reported on an open-label clinical trial. Two articles were meta-analyses. The 13 studies involved a total of 1,246 participants, with an additional 7,467 participants reported in the two meta-analyses. Significant reductions in low-density lipoprotein cholesterol and total cholesterol levels with RYR supplementation were observed in all trials. There were no significant changes in liver and kidney function, and 10 studies noted no significant changes in creatine kinase levels. Although RYR appears to be a safe and effective lipid-lowering agent, there is insufficient evidence to support the recommendation of RYR supplementation to patients. Further research is needed, including long-term studies, studies that include participants with comorbidities and complex medical histories, and studies that take into account the variability of formulation and dosage of RYR in the marketplace.","subset":"pubmed_abstract"} +{"meta":{"pmid":28398875,"dup_signals":{"dup_doc_count":25,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":21}}},"text":"Vulnerability of Barley to African Pathotypes of Puccinia graminis f. sp. tritici and Sources of Resistance.\nThe emergence of widely virulent pathotypes (e.g., TTKSK in the Ug99 race group) of the stem rust pathogen (Puccinia graminis f. sp. tritici) in Africa threatens wheat production on a global scale. Although intensive research efforts have been advanced to address this threat in wheat, few studies have been conducted on barley, even though pathotypes such as TTKSK are known to attack the crop. The main objectives of this study were to assess the vulnerability of barley to pathotype TTKSK and identify possible sources of resistance. From seedling evaluations of more than 1,924 diverse cultivated barley accessions to pathotype TTKSK, more than 95% (1,844) were found susceptible. A similar high frequency (910 of 934 = 97.4%) of susceptibility was found for the wild progenitor (Hordeum vulgare subsp. spontaneum) of cultivated barley. Additionally, 55 barley lines with characterized or putative introgressions from various wild Hordeum spp. were also tested against pathotype TTKSK but none was found resistant. In total, more than 96% of the 2,913 Hordeum accessions tested were susceptible as seedlings, indicating the extreme vulnerability of the crop to the African pathotypes of P. graminis f. sp. tritici. In total, 32 (1.7% of accessions evaluated) and 13 (1.4%) cultivated and wild barley accessions, respectively, exhibited consistently highly resistant to moderately resistant reactions across all experiments. Molecular assays were conducted on these resistant accessions to determine whether they carried rpg4\/Rpg5, the only gene complex known to be highly effective against pathotype TTKSK in barley. Twelve of the 32 (37.5%) resistant cultivated accessions and 11 of the 13 (84.6%) resistant wild barley accessions tested positive for a functional Rpg5 gene, highlighting the narrow genetic base of resistance in Hordeum spp. Other resistant accessions lacking the rpg4\/Rpg5 complex were discovered in the evaluated germplasm and may possess useful resistance genes. Combining rpg4\/Rpg5 with resistance genes from these other sources should provide more durable resistance against the array of different virulence types in the Ug99 race group.","subset":"pubmed_abstract"} +{"meta":{"pmid":2788190,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Alveolar macrophages differ from blood monocytes in human IL-1 beta release. Quantitation by enzyme-linked immunoassay.\nFresh human alveolar macrophages and blood monocytes were stimulated with LPS and assessed for their ability to produce and release antigenic IL-1 beta. Using a sensitive and specific ELISA for IL-1 beta, monocytes released 13.3 +\/- 3.1 ng\/10(6) cells compared to 3.5 +\/- 0.8 ng\/10(6) cells for alveolar macrophages (p less than 0.01). To investigate the reason for this difference in IL-1 beta release, monocytes were compared to alveolar macrophages for total IL-1 beta production (i.e., the amount released plus that detected in the lysates). Monocytes produced a total of 19.0 +\/- 3.2 ng\/10(6) cells whereas alveolar macrophages produced 24.8 +\/- 5.6 ng\/10(6) cells (p = 0.37). The relative increase in alveolar macrophage intracellular IL-1 beta was confirmed by Western blot analysis of cell lysates. Thus, the limitation in IL-1 release from alveolar macrophages appears to be due to a decrease in the processing and release of the IL-1 beta precursor. In addition, TNF production studies demonstrated that the limitation in IL-1 release was not a generalized defect. In contrast to the IL-1 beta data, when TNF was measured from monocytes and macrophages, monocytes released only 14.6 +\/- 3.4 ng\/10(6), whereas macrophages released 101 +\/- 30 ng\/10(6) (p less than 0.02). In this same context, when fresh monocytes were allowed to mature in vitro they took on monokine production characteristics similar to alveolar macrophages. In vitro matured monocytes had a greater than 20-fold decrease in their ability to release IL-1 beta and a 6- to 8-fold increase in their ability to release TNF. Taken together, these studies suggest that IL-1 beta release is limited in mature mononuclear phagocytes as compared to fresh blood monocytes, and furthermore, that IL-1 beta regulation differs significantly from that of TNF-alpha.","subset":"pubmed_abstract"} +{"meta":{"pmid":17668047,"dup_signals":{"dup_doc_count":22,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":13}}},"text":"Genome sequence of Fusobacterium nucleatum subspecies polymorphum - a genetically tractable fusobacterium.\nFusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique to F. nucleatum subsp. polymorphum ATCC 10953 were identified. A large percentage of these mapped within one of 28 regions or islands containing five or more genes. Seventeen percent of the clustered proteins that demonstrated similarity were most similar to proteins from the clostridia, with others being most similar to proteins from other gram-positive organisms such as Bacillus and Streptococcus. A ten kilobase region homologous to the Salmonella typhimurium propanediol utilization locus was identified, as was a prophage and integrated conjugal plasmid. The genome contains five composite ribozyme\/transposons, similar to the CdISt IStrons described in Clostridium difficile. IStrons are not present in the other fusobacterial genomes. These findings indicate that F. nucleatum subsp. polymorphum is proficient at horizontal gene transfer and that exchange with the Firmicutes, particularly the Clostridia, is common.","subset":"pubmed_abstract"} +{"meta":{"pmid":28547643,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-45":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2022-49":1}}},"text":"The nitrogen budget of a pine forest under free air CO2 enrichment.\nElevated concentrations of atmospheric CO2 increase plant biomass, net primary production (NPP) and plant demand for nitrogen (N). The demand for N set by rapid plant growth under elevated CO2 could be met by increasing soil N availability or by greater efficiency of N uptake. Alternatively, plants could increase their nitrogen-use efficiency (NUE), thereby maintaining high rates of growth and NPP in the face of nutrient limitation. We quantified dry matter and N budgets for a young pine forest exposed to 4 years of elevated CO2 using free-air CO2 enrichment technology. We addressed three questions: Does elevated CO2 increase forest NPP and the demand for N by vegetation? Is demand for N met by greater uptake from soils, a shift in the distribution of N between plants, microbes, and soils, or increases in NUE under elevated CO2? Will soil N availability constrain the NPP response of this forest as CO2 fumigation continues? A step-function increase in atmospheric CO2 significantly increased NPP during the first 4 years of this study. Significant increases in NUE under elevated CO2 modulated the average annual requirement for N by vegetation in the first and third growing seasons under elevated CO2; the average stimulation of NPP in these years was 21% whereas the average annual stimulation of the N requirement was only 6%. In the second and fourth growing seasons, increases in NPP increased the annual requirement for N by 27-33%. Increases in the annual requirement for N were largely met by increases in N uptake from soils. Retranslocation of nutrients prior to senescence played only a minor role in supplying the additional N required by trees growing under elevated CO2. NPP was highly correlated with between-plot variation in the annual rate of net N mineralization and CO2 treatment. This demonstrates that NPP is co-limited by C availability, as CO2 from the atmosphere, and N availability from soils. There is no evidence that soil N mineralization rates have increased under elevated CO2. The correlation between NPP and N mineralization rates and the increase in the annual requirement for N in certain years imply that soil N availability may control the long-term productivity response of this ecosystem to elevated CO2. Although we have no evidence suggesting that NPP is declining in response to >4 years of CO2 fumigation, if the annual requirement of N continues to be stimulated by elevated CO2, we predict that the productivity response of this forest ecosystem will decline over time.","subset":"pubmed_abstract"} +{"meta":{"pmid":24348530,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Nutrition care for patients with weight regain after bariatric surgery.\nAchieving optimal weight outcomes for patients with obesity is important to the management of their chronic disease. All interventions present risks for weight regain. Bariatric surgery is the most efficacious treatment, producing greater weight losses that are sustained over more time compared to lifestyle interventions. However, approximately 20-30% of patients do not achieve successful weight outcomes, and patients may experience a regain of 20-25% of their lost weight. This paper reviews several factors that influence weight regain after bariatric surgery, including type of surgery, food tolerance, energy requirements, drivers to eat, errors in estimating intake, adherence, food and beverage choices, and patient knowledge. A comprehensive multidisciplinary approach can provide the best care for patients with weight regain. Nutrition care by a registered dietitian is recommended for all bariatric surgery patients. Nutrition diagnoses and interventions are discussed. Regular monitoring of weight status and early intervention may help prevent significant weight regain.","subset":"pubmed_abstract"} +{"meta":{"pmid":22546987,"dup_signals":{"dup_doc_count":39,"dup_dump_count":20,"dup_details":{"curated_sources":3,"2023-50":3,"2023-40":1,"2023-23":1,"2023-14":1,"2022-49":2,"2022-27":2,"2022-05":2,"2021-39":2,"2021-25":2,"2021-21":2,"2021-17":3,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2024-30":3,"2024-26":1,"2024-18":4,"2024-10":1,"2014-10":1}}},"text":"The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study.\nTo compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells\/\u03bcl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.","subset":"pubmed_abstract"} +{"meta":{"pmid":23671679,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Social and geographical inequalities in suicide in Japan from 1975 through 2005: a census-based longitudinal analysis.\nDespite advances in our understanding of the countercyclical association between economic contraction and suicide, less is known about the levels of and changes in inequalities in suicide. The authors examined social and geographical inequalities in suicide in Japan from 1975 through 2005. Based on quinquennial vital statistics and census data, the authors analyzed the entire population aged 25-64 years. The total number of suicides was 75,840 men and 30,487 women. For each sex, the authors estimated odds ratios (ORs) and 95% credible intervals (CIs) for suicide using multilevel logistic regression models with \"cells\" (cross-tabulated by age and occupation) at level 1, seven different years at level 2, and 47 prefectures at level 3. Prefecture-level variance was used as an estimate of geographical inequalities in suicide. Adjusting for age and time-trends, the lowest odds for suicide was observed among production process and related workers (the reference group) in both sexes. The highest OR for men was 2.52 (95% CI: 2.43, 2.61) among service workers, whereas the highest OR for women was 9.24 (95% CI: 7.03, 12.13) among security workers. The degree of occupational inequalities increased among men with a striking change in the pattern. Among women, we observed a steady decline in suicide risk across all occupations, except for administrative and managerial workers and transport and communication workers. After adjusting for individual age, occupation, and time-trends, prefecture-specific ORs ranged from 0.76 (Nara Prefecture) to 1.36 (Akita Prefecture) for men and from 0.79 (Kanagawa Prefecture) to 1.22 (Akita Prefecture) for women. Geographical inequalities have increased primarily among men since 1995. The present findings demonstrate a striking temporal change in the pattern of social inequalities in suicide among men. Further, geographical inequalities in suicide have considerably increased across 47 prefectures, primarily among men, since 1995.","subset":"pubmed_abstract"} +{"meta":{"pmid":30223499,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Origin of the Low Magnetic Moment in Fe\u2082AlTi: An Ab Initio Study.\nThe intermetallic compound Fe 2 AlTi (alternatively Fe 2 TiAl) is an important phase in the ternary Fe-Al-Ti phase diagram. Previous theoretical studies showed a large discrepancy of approximately an order of magnitude between the ab initio computed magnetic moments and the experimentally measured ones. To unravel the source of this discrepancy, we analyze how various mechanisms present in realistic materials such as residual strain effects or deviations from stoichiometry affect magnetism. Since in spin-unconstrained calculations the system always evolves to the spin configuration which represents a local or global minimum in the total energy surface, finite temperature spin effects are not well described. We therefore turn the investigation around and use constrained spin calculations, fixing the global magnetic moment. This approach provides direct insight into local and global energy minima (reflecting metastable and stable spin phases) as well as the curvature of the energy surface, which correlates with the magnetic entropy and thus the magnetic configuration space accessible at finite temperatures. Based on this approach, we show that deviations from stoichiometry have a huge impact on the local magnetic moment and can explain the experimentally observed low magnetic moments.","subset":"pubmed_abstract"} +{"meta":{"pmid":2509067,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Roles of individual human cytochrome P-450 enzymes in the bioactivation of benzo(a)pyrene, 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and other dihydrodiol derivatives of polycyclic aromatic hydrocarbons.\nHuman liver microsomes oxidized 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene [B(a)P-7,8-diol] to products that yield DNA adduct formation and umu gene expression in the tester system Salmonella typhimurium TA1535\/pSK1002. The umu response is correlated to levels of microsomal cytochrome P-450NF (P-450NF) and nifedipine oxidation in different human liver samples used for activation, and both the (+)- and (-)-enantiomers of B(a)P-7,8-diol gave similar results in these and other assays. The microsomal umu response was inhibited by antibodies raised against P-450NF. 7,8-Benzoflavone stimulated the B(a)P-7,8-diol-dependent umu response observed with purified P-450NF and human liver and lung microsomes. Thus, P-450NF appears to be the major enzyme involved in the activation of B(a)P-7,8-diol in human liver and possibly lung. Similar results were obtained for the activation of trans-9,10-dihydroxy-9,10-dihydrobenzo(b)fluoranthene and trans-3,4-dihydroxy-3,4-dihydro-7,12-dimethylbenz(a)anthracene, compounds that are known to form highly tumorigenic diol-epoxides. The major product of the oxidation of (+)-B(a)P-7,8-diol was the cis-syn isomer of benzo(a)pyrene-7,8,9,10-tetraol[7 beta, 8 alpha, 9 beta, 10 beta-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]. Studies on the nature of the human liver enzymes involved in the formation of B(a)P-7,8-diol [from benzo(a)pyrene] indicate that neither P-450NF, P-450PA, P-450j, P-450DB, nor P-450MP is involved. The correlation of 7,8-diol formation with phenacetin O-deethylation in a set of liver samples and the partial inhibition of the reaction by 7,8-benzoflavone and anti-rat P-450 beta NF-B suggest that the enzyme involved may be P1-450, the human ortholog of rat P-450 beta NF-B, which catalyzes both the formation of B(a)P-7,8-diol and its subsequent oxidation in tissues of polycyclic hydrocarbon-treated rats. The differential effects of inhibitors indicate that benzo(a)pyrene 3-hydroxylation, 4,5-epoxidation, and 9,10-epoxidation are catalyzed by an enzyme(s) distinct from that which forms the 7,8-epoxide. The roles of the human P-450 enzymes differ from the rodent orthologs in the paradigm for bioactivation of polycyclic hydrocarbons; further, flavones appear to have opposing effects on diol formation and further epoxidation in both human liver and lung.","subset":"pubmed_abstract"} +{"meta":{"pmid":27426404,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Paracetamol overdosing in a tertiary care hospital: implementation and outcome analysis of a preventive alert programme.\nParacetamol is a frequently used antipyretic and analgesic drug, but also a dose-dependent hepatotoxin. Unintentional paracetamol overdosing is a common medication error in hospitals. The present study aimed at (i) analysis of unintentional paracetamol overdosing in hospitalized patients; (ii) development, implementation and outcome analysis of an alert algorithm for the prevention of relevant paracetamol overdosing. All patients who received paracetamol in a Swiss tertiary care hospital during 2011 to 2014 were analysed to detect cases of paracetamol overdosing in a local pharmacoepidemiological database. In 2014, an automated algorithm screened the hospital's electronic prescribing system for patients at risk of overdosing, followed by expert validation. When imminent relevant overdosing was confirmed, alerts were issued to prescribers. Relevance was defined as prescriptions that permitted repeated daily paracetamol exposure of \u22655 g. From 2011 to 2013, relevant overdosing occurred in 11 patients (5-8 g\/day for 3 to 5 days), which corresponds to 0\u00b74 % of all patients exposed to any paracetamol overdosing (mean n = 988 per year). In 2014, alerts were issued by experts in 23 cases with subsequent changes to prescriptions in 21 (91\u00b73 %) thereof. Although the occurrence of any paracetamol overdosing declined only marginally in 2014 (n = 914), no relevant overdosing occurred anymore. Unintentional paracetamol overdosing was frequent but only a small fraction thereof was deemed relevant. This proof of concept study analysed local hospital data and developed a preventive system combining sensitive automated detection with subsequent specific expert validation. The resulting alerts achieved high compliance and prevented relevant paracetamol overdosing.","subset":"pubmed_abstract"} +{"meta":{"pmid":17573836,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":16}}},"text":"Hybrid epicardial and endocardial ablation of persistent or permanent atrial fibrillation: a new approach for difficult cases.\nAlthough percutaneous epicardial catheter ablation (PECA) has been used for the management of epicardial ventricular tachycardia, the use of PECA for atrial fibrillation (AF) has not yet been reported. To evaluate the efficacy and feasibility of a hybrid PECA and endocardial ablation for AF. We performed PECA for AF in five patients (48.6 +\/- 8.1 years old, all male, four redo ablation procedures of persistent AF with a risk of pulmonary vein (PV) stenosis, one de novo ablation of permanent [AF]) after an endocardial AF ablation guided by PV potentials and 3D mapping (NavX). Utilizing an open irrigation tip catheter, a left atrial (LA) linear ablation from the roof to the perimitral isthmus or localized ablation at the junction between the LA appendage and left-sided PVs or ligament of Marshall (LOM) was performed. PECA of AF was successful in all patients with an ablation time of <15 minutes. The left-sided PV potentials were eliminated by PECA in all patients. Bidirectional block of the perimitral line was achieved in two of two patients and a left inferior PV tachycardia with conduction block to the LA was observed during the ablation in the area of the LOM in one patient. A hemopericardium developed in one patient, but was controlled successfully. During 8.0 +\/- 6.3 months of follow-up, all patients have remained in sinus rhythm (four patients without antiarrhythmic drugs). A hybrid PECA of AF is feasible and effective in patients with redo-AF ablation procedures and at risk for left-sided PV stenosis or who are resistant to endocardial linear ablation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21850315,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Impaired TGF-\u03b2 signaling and a defect in resolution of inflammation contribute to delayed wound healing in a female rat model of type 2 diabetes.\nWound healing (WH) impairment is a well-documented phenomenon in clinical and experimental diabetes. Sex hormones, in addition to a number of signaling pathways including transforming growth factor-\u03b21 (TGF-\u03b21)\/Smads and TNF-\u03b1\/NF-\u03baB in macrophages and fibroblasts, appear to play a cardinal role in determining the rate and nature of WH. We hypothesized that a defect in resolution of inflammation and an enhancement in TNF-\u03b1\/NF-\u03baB activity induced by estrogen deficiency contribute to the impairment of TGF-\u03b2 signaling and delayed WH in diabetes models. Goto-Kakizaki (GK) rats and full thickness excisional wounds were used as models for type 2 diabetes (T2D) and WH, respectively. Parameters related to the various stages of WH were assessed using histomorphometry, western blotting, real-time PCR, immunofluorescence microscopy and ELISA-based assays. Retarded re-epithelialization, suppressed angiogenesis, delayed wound closure, reduced estrogen level and heightened states of oxidative stress were characteristic features of T2D wounds. These abnormalities were associated with a defect in resolution of inflammation, shifts in macrophage phenotypes, increased \u03b23-integrin expression, impaired wound TGF-\u03b21 signaling (\u2193p-Smad2\/\u2191Smad7) and enhanced TNF-\u03b1\/NF\u03baB activity. Human\/rat dermal fibroblasts of T2D, compared to corresponding control values, displayed resistance to TGF-\u03b2-mediated responses including cell migration, myofibroblast formation and p-Smad2 generation. A pegylated form of soluble TNF receptor-1 (PEG-sTNF-RI) or estrogen replacement therapy significantly improved re-epithelialization and wound contraction, enhanced TGF\u03b2\/Smad signaling, and polarized the differentiation of macrophages toward an M2 or \"alternatively\" activated phenotype, while limiting secondary inflammatory-mediated injury. Our data suggest that reduced estrogen levels and enhanced TNF-\u03b1\/NF-\u03baB activity delayed WH in T2D by attenuating TGF\u03b2\/Smad signaling and impairing the resolution of inflammation; most of these defects were ameliorated with estrogen and\/or PEG-sTNF-RI therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":16505274,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura.\nTo study the expression of claudins in mesothelioma and metastatic pleural adenocarcinoma. Immunohistochemical staining of claudins 1, 2, 3, 4, 5, and 7 was studied in 35 malignant mesotheliomas and the expression compared with 24 cases of pleural metastatic adenocarcinoma. All cases were also immunostained with calretinin. Claudin 1, 2, 3, 4, 5, and 7 expression was seen in 40%, 80%, 18%, 23%, 14%, and 43% of mesotheliomas, respectively, while the corresponding figures for adenocarcinoma were 100%, 88%, 90%, 100%, 50%, and 92%. Claudins 1, 3, 4, 5, and 7 were significantly less positive in mesothelioma than in metastatic adenocarcinoma, while no difference was observed for claudin 2. Claudins 1, 3, 4, 5, and 7 were also inversely associated with calretinin positivity. Sarcomatoid and biphasic mesothelioma subtypes appeared more negative for these claudins than pure epithelioid subtypes. Claudin expression was not associated with survival of patients with malignant mesotheliomas. The results show that malignant mesotheliomas have a lower expression of claudins 1, 3, 4, 5, and 7 than adenocarcinomas, and their expression could thus be used as an adjunct in differential diagnosis between the two. The difference was most evident for claudins 3 and 4, which were nearly as good as calretinin in mesothelioma detection. Sarcomatoid and biphasic mesotheliomas showed expression of these claudins only occasionally, which could be due to or contribute to their less epithelial appearance.","subset":"pubmed_abstract"} +{"meta":{"pmid":23093878,"dup_signals":{"dup_doc_count":68,"dup_dump_count":62,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-27":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":2,"2019-43":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":2,"2014-41":1,"2014-35":1,"2014-23":1,"2023-40":1,"2024-22":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1}}},"text":"Medicines information in medical journal advertising in Australia, Malaysia and the United States: A comparative cross-sectional study.\nThe aim of this study was to compare the provision of medicines information in medical journal advertising in Australia, Malaysia and the United States. A consecutive sample of 85 unique advertisements from each country was selected from the advertisements published between January 2004 to December 2006 in three widely circulated medical journals and one prescribing reference manual. The availability of brand name and generic name, indication, contraindications, dosage, side-effects, warnings, interactions and precautions was compared between the three countries. We examined 255 distinct advertisements for 136 pharmaceutical products. Journal advertising in Australia, Malaysia and the US usually provided brand names and generic names (range 96 -100%). Information on dosage was significantly less likely to be mentioned (32%) in the US than in Australia (92%) and Malaysia (48%) (P < 0.001). Warning information was significantly less likely to be provided in Australia (5%) than in the US (81%) and Malaysia (9%) (P < 0.001). Apart from information on brand name, generic name, warnings and dosage, other product information significantly less likely to be provided in journal advertising in Malaysia than in Australia and the US (P < 0.001). Similar trends in the provision of product information for the same medicines published in these countries were noted. Brand name and generic name were always provided in the three countries (100%). However, information on the negative effects of medicines was less frequently provided in Malaysia than in Australia and the US. Journal advertising in Australia, Malaysia and the US failed to provide complete product information. Low quality of information provided in Malaysia indicates the need for effective regulation of provision of medicines information in journal advertising. Different standards of medicines information provided in these three countries suggest that pharmaceutical promotion needs to be better controlled at the international level.","subset":"pubmed_abstract"} +{"meta":{"pmid":29156234,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Candida albicans-epithelial interactions and induction of mucosal innate immunity.\nCandida albicans is a human fungal pathogen that causes millions of mucosal and life-threatening infections annually. C. albicans initially interacts with epithelial cells, resulting in fungal recognition and the formation of hyphae. Hypha formation is critical for host cell damage and immune activation, which are both driven by the secretion of Candidalysin, a recently discovered peptide toxin. Epithelial activation leads to the production of inflammatory mediators that recruit innate immune cells including neutrophils, macrophages and innate Type 17 cells, which together work with epithelial cells to clear the fungal infection. This review will focus on the recent discoveries that have advanced our understanding of C. albicans-epithelial interactions and the induction of mucosal innate immunity.","subset":"pubmed_abstract"} +{"meta":{"pmid":6182148,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Cytoplasmic structure in rapid-frozen axons.\nTurtle optic nerves were rapid-frozen from the living state, fractured, etched, and rotary shadowed. Stereo views of fractured axons show that axoplasm consists of three types of longitudinally oriented domains. One type consists of neurofilament bundles in which individual filaments are interconnected by a cross-bridging network. Contiguous to neurofilament domains are domains containing microtubules suspended in a loose, granular matrix. A third domain is confined to a zone, 80-100 nm wide, next to the axonal membrane and consists of a dense filamentous network connecting the longitudinal elements of the axonal cytoskeleton to particles on the inner surface of the axolemma. Three classes of membrane-limited organelles are distinguished: axoplasmic reticulum, mitochondria, and discrete vesicular organelles. The vesicular organelles must include lysosomes, multivesicular bodies, and vesicles which are retrogradely transported in axons, though some vesicular organelles may be components of the axoplasmic reticulum. Organelles in each class have a characteristic relationship to the axonal cytoskeleton. The axoplasmic reticulum enters all three domains of axoplasm, but mitochondria and vesicular organelles are excluded from the neurofilament bundles, a distribution confirmed in thin sections of cryoembedded axons. Vesicular organelles differ from mitochondria in at least three ways with respect to their relationships to adjacent axoplasm: (a) one, or sometimes both, of their ends are associated with a gap in the surrounding granular axoplasm; (b) an appendage is typically associated with one of their ends; and (c) they are not attached or closely apposed to microtubules. Mitochondria, on the other hand, are only rarely associated with gaps in the axoplasm, do not have an appendage, and are virtually always attached to one or more microtubules by an irregular array of side-arms. We propose that the longitudinally oriented microtubule domains are channels within which organelles are transported. We also propose that the granular material in these channels may constitute the myriad enzymes and other nonfibrous components that slowly move down the axon.","subset":"pubmed_abstract"} +{"meta":{"pmid":28895560,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia.\nThe fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest in this setting as they are associated with unfavorable prognosis. Because of sequence-dependent protein conformational changes FLT3-ITD tends to autophosphorylate and displays a constitutive intracellular localization. Here, we analyzed the effect of tyrosine kinase inhibitors (TKIs) on the localization of the FLT3 receptor and its mutants. TKI treatment increased the surface expression through upregulation of FLT3 and glycosylation of FLT3-ITD and FLT3-D835Y mutants. In T cell-mediated cytotoxicity (TCMC) assays, using a bispecific FLT3 \u00d7 CD3 antibody construct, the combination with TKI treatment increased TCMC in the FLT3-ITD-positive AML cell lines MOLM-13 and MV4-11, patient-derived xenograft cells and primary patient samples. Our findings provide the basis for rational combination of TKI and FLT3-directed immunotherapy with potential benefit for FLT3-ITD-positive AML patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":22388839,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"[Chronic hepatitis C virus infection: clinical picture and treatment possibilities].\nIt has been estimated that between 1.5 and 2 million people in Italy have anti-HCV antibodies. The vast majority are chronically infected with HCV and are unaware of the infection. Chronic hepatitis C is asymptomatic during most of its course, which lasts decades. The diagnosis is based on anti-HCV antibodies and, subsequently, an HCV-RNA test, to be performed in all subjects with persistently elevated ALT and in those who are at risk of HCV infection. The identification of infected subjects allows prophylaxis of advanced liver disease, cirrhosis and hepatocellular carcinoma by antiviral treatment, which is effective in about 50% of patients. The current standard of care for chronic HCV infection is the combination of pegylated interferon and ribavirin. Their dosage and the duration of therapy are tailored to the HCV genotype and the time to viral response. The frequent occurrence of adverse events, mainly hematological, requires careful monitoring, dose reduction in some cases, and, rarely, the use of erythrocyte or leukocyte growth factors. A new class of drugs for HCV treatment, the direct acting antivirals, is currently under development. Two of these drugs, the viral protease inhibitors boceprevir and telaprevir, are awaiting registration in Europe for use in association with pegylated interferon and ribavirin. These drugs are expected to ameliorate the virus eradication rates in patients who have not received previous antiviral treatment and, more importantly, to accomplish effective treatment in those patients who are partial responders to the current standard of care.","subset":"pubmed_abstract"} +{"meta":{"pmid":12215076,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":6}}},"text":"Fusiform gyrus volume reduction in first-episode schizophrenia: a magnetic resonance imaging study.\nThe fusiform gyrus (occipitotemporal gyrus) is thought to be critical for face recognition and may possibly be associated with impaired facial recognition and interpretation of facial expression in schizophrenia. of postmortem studies have suggested that fusiform gyrus volume is reduced in schizophrenia, but there have been no in vivo structural studies of the fusiform gyrus in schizophrenia using magnetic resonance imaging. High-spatial resolution magnetic resonance images were used to measure the gray matter volume of the fusiform gyrus in 22 patients with first-episode schizophrenia (first hospitalization), 20 with first-episode affective psychosis (mainly manic), and 24 control subjects. Patients with first-episode schizophrenia had overall smaller relative volumes (absolute volume\/intracranial contents) of fusiform gyrus gray matter compared with controls (9%) and patients with affective psychosis (7%). For the left fusiform gyrus, patients with schizophrenia showed an 11% reduction compared with controls and patients with affective psychosis. Right fusiform gyrus volume differed in patients with schizophrenia only compared with controls (8%). Schizophrenia is associated with a bilateral reduction in fusiform gyrus gray matter volume that is evident at the time of first hospitalization and is different from the presentation of affective psychosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":22708709,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":1,"2024-10":1,"unknown":9}}},"text":"Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.\nThis pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery. Women (N = 30) with early-stage breast cancer received either PBRT, Mammosite brachytherapy at dose of 34 Gy 10 fractions\/5 days, (N = 15) or WBRT, 3-D conformal techniques at dose of 50 Gy +10 Gy Boost\/30 fractions, (N = 15). Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need. Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy. At each assessment, blood was obtained for determination of NKCA and the following instruments were administered: Perceived Stress Scale (PSS), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Functional Assessment of Cancer Therapy-General (FACT-G). Hierarchical linear modeling (HLM) was used to evaluate group differences in initial outcomes and change in outcomes over time. Fatigue (FACT-F) levels, which were similar prior to radiation therapy, demonstrated a significant difference in trajectory. Women who received PBRT reported progressively lower fatigue; conversely fatigue worsened over time for women who received WBRT. No difference in perceived stress was observed between women who received PBRT or WBRT. Both groups of women reported similar levels of quality of life (FACT-G) prior to initiation of radiation therapy. However, HLM analysis revealed significant group differences in the trajectory of quality of life, such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy; whereas women receiving WBRT showed a decreasing trajectory. NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy. Compared to WBRT, PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy. Additionally, better quality of life predicts higher NKCA against tumor targets, emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28571156,"dup_signals":{"dup_doc_count":22,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2018-30":1,"2018-22":1,"2018-17":2,"2018-13":1,"2018-05":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":2,"2017-17":2,"2018-43":1}}},"text":"Blastoid Variant of Mantle Cell Lymphoma with Leukemic Presentation - A Rare Case Report.\nMantle Cell Lymphoma (MCL) is a type of Non-Hodgkin's lymphoma and has a wide spectrum of histopathological subtypes of which the blastoid or the blastic variant constitutes 10-15% of all cases. It is difficult to diagnose blastoid variant of MCL on the basis of morphology alone as it mimics lymphoblastic lymphoma and centroblastic large cell lymphoma, hence additional analysis like immunophenotyping and molecular studies aid in its diagnosis. We present a case of 45-year-old male who presented to medicine OPD with chief complaints of fever, fatigability and inguinal swelling. Complete blood count, peripheral smear and bone marrow examination was performed. Peripheral smear showed thrombocytopenia along with 53% abnormal cells. On bone marrow examination 43% abnormal lymphoid cells were seen. This case was diagnosed as blastoid variant of MCL on the basis of routine morphology and immunohistochemistry on bone marrow biopsy and flow cytometric immunophenotyping on peripheral blood.","subset":"pubmed_abstract"} +{"meta":{"pmid":30986173,"dup_signals":{"dup_doc_count":22,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2020-34":1,"2020-16":1,"2020-10":1,"2019-43":2,"2019-39":1,"2019-30":3,"2019-26":1,"2019-22":1,"2019-18":1,"2019-13":2,"2019-04":1,"2018-47":2,"2023-14":1,"2024-10":1}}},"text":"Long-Term Survival of Patients with Tracheostomy Having Different Diseases Followed up in the Respiratory Intensive Care Unit Outpatient Clinic: Which Patients are Lucky?\nTracheostomy is a method of separating a patient from the mechanical ventilator in the intensive care unit (ICU). The long-term survivors among patients followed up with tracheostomy and ventilator in the respiratory ICU (RICU) outpatient clinic due to different diseases were investigated. This was a retrospectively designed cohort study between January 2004 and July 2018. Patients with chronic respiratory failure followed up with tracheostomy and\/or ventilator at the RICU outpatient clinic were included in the study. Age, gender, indications and date of tracheostomy, use of domestic mechanical ventilation, and mortality were recorded. The groups were compared according to age, gender, and tracheostomy indication diseases, and the 1-3-year long-term mortality rates were analyzed by the Kaplan-Meier survival analysis, and the Cox regression test was performed. A total of 134 (64% male) patients with a median age of 66 (54-73) years were included in the study. The indications for tracheostomy were heart failure (HF) and cerebrovascular diseases (38.1%), chronic obstructive pulmonary disease (COPD) (23.1%), neuromuscular diseases (22.4%), obesity hypoventilation (9.7%), and kyphoscoliosis (6.7%). Mortality was higher in patients >75 years old in the 3-year follow-up (p=0.022). The 3-year mortality hazard ratio (HR) factors and 95% confidence interval (CI) were as follows: age >75 years HR=1.71 (95% CI, 1.03-2.82; p<0.036) and HF and cerebrovascular disease diseases sequela HR=1.84 (95% CI, 1.03-3.29; p<0.041) significantly increased the 3-year mortality, and having COPD decreased mortality in 46% (p<0.041). Patients with neuromuscular disorders, kyphoscoliosis, and COPD who have undergone tracheostomy were the luckiest group according to the 3-year survival rates, whereas patients with HF and cerebrovascular diseases were the unluckiest ones. The most important decision triangle is the patient's acceptance (A), family support (B), and tracheostomy indication (C), and this may vary from country to country depending on the beliefs of subjects.","subset":"pubmed_abstract"} +{"meta":{"pmid":20738139,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Confinement effects on monosaccharide transport in nanochannels.\nTransport theories based on the continuum hypothesis may not be appropriate at the nanoscale in view of surface effects. We employed molecular dynamics simulations to study the effects of confinement and concentration on diffusive transport of glucose in silica nanochannels (10 nm or smaller). We found that glucose modifies the electrical properties of nanochannels and that, below 5 nm in channel height, glucose adsorption and diffusivity are significantly reduced. With increasing concentration, the diffusivity is reduced linearly in the bulk, while it is reduced nonlinearly at the interface. The effective diffusivity reduction is related to the interface thickness, which can be 2-4 nm depending on concentration, and has an unexpected reduction at low concentrations. Results suggest that nanochannels present a one-dimensional cage environment that affects diffusivity in a fashion similar to cage-breaking diffusion. Our simulation results, consistent with the experimental observations presented here, suggest that nanoconfinement is the essential cause of the observed altered fluid diffusive transport, not accounted for by classical theories, because of coupling of confinement and concentration effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":33233802,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"Associations between Urinary, Dietary, and Water Fluoride Concentrations among Children in Mexico and Canada.\nFluoride, which may be toxic to the developing brain, is added to salt in Mexico and drinking water in Canada to prevent dental caries. We compared childhood urinary fluoride (CUF) concentrations in Mexico City and Canada to characterize patterns of fluoride exposure in these two populations. We also examined associations of CUF with dietary and water fluoride levels in Mexico City and Canada respectively. We included 561 children (ages 4\u20136; mean age 4.8 years) from the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) cohort in Mexico City, and 645 children (ages 2\u20136; mean age 3.7 years) from the Maternal\u2013Infant Research on Environmental Chemicals (MIREC) cohort in Canada. We applied Spearman correlations, T-tests, ANOVA or covariate-adjusted linear regression to examine associations of CUF (mg\/L; adjusted for specific gravity) with demographics and dietary or water fluoride concentrations. We used Welch equivalence testing to compare means across cohorts. Mean (SD) CUF was equivalent (t = 4.26, p < 0.001) in PROGRESS: 0.74 (0.42) and fluoridated Canadian communities: 0.66 (0.47), but lower in non-fluoridated Canadian communities: 0.42 (0.31) (t = \u22126.37, p < 0.001). Water fluoride concentrations were significantly associated with CUF after covariate adjustment for age and sex in MIREC (B = 0.44, 95% CI: 0.30, 0.59, p < 0.001). In contrast, daily food and beverage fluoride intake was not associated with CUF in PROGRESS (p = 0.82). We found that CUF levels are comparable among children in Mexico City and fluoridated Canadian communities, despite distinct sources of exposure. Community water fluoridation is a major source of fluoride exposure for Canadian children.","subset":"pubmed_abstract"} +{"meta":{"pmid":24196086,"dup_signals":{"dup_doc_count":87,"dup_dump_count":41,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-23":2,"2023-14":3,"2023-06":3,"2022-49":1,"2022-40":1,"2022-27":2,"2022-21":3,"2022-05":1,"2021-43":4,"2021-31":4,"2021-21":3,"2021-17":4,"2021-10":2,"2021-04":2,"2020-50":2,"2020-45":2,"2020-40":3,"2020-24":1,"2019-30":1,"2019-22":2,"2019-18":1,"2019-09":1,"2019-04":2,"2018-51":1,"2018-47":1,"2018-43":2,"2018-39":2,"2018-34":1,"2018-30":2,"2018-22":1,"2018-17":3,"2018-13":1,"2018-09":2,"2017-51":4,"2017-43":4,"2017-34":2,"2024-22":2,"2024-18":2,"2024-30":1}}},"text":"Toxicology study assessing efficacy and safety of repeated administration of lipid\/DNA complexes to mouse lung.\nFor gene therapy to improve lung function in cystic fibrosis (CF) subjects, repeated administration of the gene transfer agent over the lifetime of patients is likely to be necessary. This requirement limits the utility of adenoviral and adeno-associated viral vectors (both previously evaluated in CF gene therapy trials) because of induced adaptive immune responses that render repeated dosing ineffective. For CF gene therapy trials, non-viral vectors are currently the only viable option. We previously showed that the cationic lipid formulation GL67A is the most efficient of several non-viral vectors analysed for airway gene transfer. Here, we assessed the efficacy and safety of administering 12 inhaled doses of GL67A complexed with pGM169, a CpG-free plasmid encoding human CFTR complementary DNA, into mice. We show that repeated administration of pGM169\/GL67A to murine lungs is feasible, safe and achieves reproducible, dose-related and persistent gene expression (>140 days after each dose) using an aerosol generated by a clinically relevant nebuliser. This study supports progression into the first non-viral multidose lung trial in CF patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":31486355,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Linking agroecosystems producing farmed seafood with food security and health status to better address the nutritional challenges in Bangladesh.\nAquaculture is one of the fastest-growing food production sectors in many low-income and food-deficit countries with aquatic ecozones. Yet its specific impact on nutrition and livelihood in local communities, where commercial and\/or export-orientated aquaculture activities are developed, is largely unknown. The present narrative and argumentative review aims to provide an overview of our current understanding of the connections between aquaculture agroecosystems, local and national fish production, fish consumption patterns and nutrition and health outcomes. The agroecological dynamic in a coastal-estuarine zone, where the aquatic environment ranges from fully saline to freshwater, is complex, with seasonal and annual fluctuations in freshwater supply creating a variable salinity gradient which impacts on aquatic food production and on food production more generally. The local communities living in these dynamic aquatic ecozones are vulnerable to poverty, poor diet and health, while these ecosystems produce highly valuable and nutritious aquatic foods. Policies addressing the specific challenges of risk management of these communities are limited by the sectoral separation of aquatic food production - the fisheries and aquaculture sector, the broader food sector - and public health institutions. Here we provide an argument for the integration of these factors to improve aquaculture value chains to better address the nutritional challenges in Bangladesh.","subset":"pubmed_abstract"} +{"meta":{"pmid":27245670,"dup_signals":{"dup_doc_count":39,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-14":2,"2022-33":2,"2022-21":1,"2021-43":1,"2021-25":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-16":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-22":1,"2019-13":1,"2019-04":2,"2018-47":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-43":1,"2017-39":2,"2017-30":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":2,"2016-50":1,"2016-44":1,"2023-23":1,"2017-13":1}}},"text":"Perinatal maternal depression and cortisol function in pregnancy and the postpartum period: a systematic literature review.\nPerinatal depression has a significant impact on both mother and child. However, the influence of hormonal changes during pregnancy and the postpartum period remains unclear. This article provides a systematic review of studies examining the effects of maternal cortisol function on perinatal depression. A systematic search was conducted of six electronic databases for published research on the relationship between cortisol and perinatal depression. The databases included; MEDLINE complete, PsychINFO, SCOPUS, Psychology and Behavioural Sciences, Science Direct and EBSCO, for the years 1960 to May 2015. Risk of bias was assessed and data extraction verified by two investigators. In total, 47 studies met criteria and studies showed considerable variation in terms of methodology including sample size, cortisol assays, cortisol substrates, sampling processes and outcome measures. Those studies identified as higher quality found that the cortisol awakening response is positively associated with momentary mood states but is blunted in cases of major maternal depression. Furthermore, results indicate that hypercortisolemia is linked to transient depressive states while hypocortisolemia is related to chronic postpartum depression. Future research should aim to improve the accuracy of cortisol measurement over time, obtain multiple cortisol samples in a day and utilise diagnostic measures of depression. Future studies should also consider both antenatal and postnatal depression and the differential impact of atypical versus melancholic depression on cortisol levels, as this can help to further clarify the relationship between perinatal depression and maternal cortisol function across pregnancy and the postpartum period.","subset":"pubmed_abstract"} +{"meta":{"pmid":19939251,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":1,"unknown":9}}},"text":"Emergent management of postpartum hemorrhage for the general and acute care surgeon.\nPostpartum hemorrhage is one of the rare occasions when a general or acute care surgeon may be emergently called to labor and delivery, a situation in which time is limited and the stakes high. Unfortunately, there is generally a paucity of exposure and information available to surgeons regarding this topic: obstetric training is rarely found in contemporary surgical residency curricula and is omitted nearly completely from general and acute care surgery literature and continuing medical education. The purpose of this manuscript is to serve as a topic specific review for surgeons and to present a surgeon oriented management algorithm. Medline and Ovid databases were utilized in a comprehensive literature review regarding the management of postpartum hemorrhage and a management algorithm for surgeons developed based upon a collaborative panel of general, acute care, trauma and obstetrical surgeons' review of the literature and expert opinion. A stepwise approach for surgeons of the medical and surgical interventions utilized to manage and treat postpartum hemorrhage is presented and organized into a basic algorithm. The manuscript should promote and facilitate a more educated, systematic and effective surgeon response and participation in the management of postpartum hemorrhage.","subset":"pubmed_abstract"} +{"meta":{"pmid":3524504,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Microcirculation of the pancreas in the rat and rabbit with special reference to the insulo-acinar portal system and emissary vein of the islet.\nMicrocirculation of the pancreas in the rat and rabbit with special reference to the islets was studied by scanning electron microscopy (SEM) of vascular corrosion casts, light microscopy (LM) of India ink-injected\/cleared tissues, and intravital microscopy of in situ organs. The following observations were made: Approximately 10-20% of the total terminal arterioles supplied the islets, while the remainder directly supplied the exocrine pancreas. The vas afferens of the islets divided into sinusoidal capillaries with frequent U-shaped turns in the cortical A and D cell area of the islets, and their secondary branches supplied the core B cell area. Intravital microscopy confirmed that blood irrigated the cortex of the islets first and the core portion second. All islets observed possessed insulo-acinar portal vessels. About 60% of the islets in the rat possessed emissary veins leading directly into the systemic circulation, while in the rabbit, less than 5% of islets possessed emissary venules of small diameter. Thus, the well-developed emissary veins of the islets seemed characteristic of the rat, as compared with the rabbit and several other mammals examined previously. The insulo-acinar portal system seems to represent a short vascular route through which islet secretions are transported in high concentrations to the exocrine pancreas, there to exert their actions. The emissary veins of the islet seem to serve for the quick conveyance of insular secretions into general circulation. It is suggested that the pancreatic lobule is made up of subdivisions or microcirculatory units, each of which is supplied centrally by the insulo-acinar portal system, while peripherally the unit also receives direct branches of intralobular arterioles. The veins run the periphery of the unit. The occurrence of sphincters in the vas afferens and the emissary veins of the islets is suggested as being involved in the regulation of the islet blood flow.","subset":"pubmed_abstract"} +{"meta":{"pmid":18005435,"dup_signals":{"dup_doc_count":26,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2018-30":1,"2015-18":1,"2013-48":1,"2017-13":1}}},"text":"Reliability of journal impact factor rankings.\nJournal impact factors and their ranks are used widely by journals, researchers, and research assessment exercises. Based on citations to journals in research and experimental medicine in 2005, Bayesian Markov chain Monte Carlo methods were used to estimate the uncertainty associated with these journal performance indicators. Intervals representing plausible ranges of values for journal impact factor ranks indicated that most journals cannot be ranked with great precision. Only the top and bottom few journals could place any confidence in their rank position. Intervals were wider and overlapping for most journals. Decisions placed on journal impact factors are potentially misleading where the uncertainty associated with the measure is ignored. This article proposes that caution should be exercised in the interpretation of journal impact factors and their ranks, and specifically that a measure of uncertainty should be routinely presented alongside the point estimate.","subset":"pubmed_abstract"} +{"meta":{"pmid":22246625,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2018-39":1,"2018-17":1,"2017-47":2,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-31":1,"2017-13":1}}},"text":"Characterization of the promoter and the transcriptional regulation of the lipoxin A4 receptor (FPR2\/ALX) gene in human monocytes and macrophages.\nThe lipoxin A4 receptor FPR2\/ALX plays an important part in host defense and inflammation. The receptor binds structurally diverse agonistic ligands, which mainly regulate chemotaxis and activation of leukocytes. However, little is known about the promoter region of the FPR2\/ALX gene and its transcriptional regulation in leukocytes. We identified two TATA-less promoter regions, separated by 224 bp, that drive the expression of FPR2\/ALX in macrophages. Both promoter regions increased transcription in a reporter assay, and the basal transcription factors OCT1 and SP1 were shown to bind the first and the second promoter, respectively, and to transactivate transcription. Although monocytes expressed high levels of FPR2\/ALX mRNA from the second promoter region, differentiation into macrophages abrogated FPR2\/ALX expression. Stimulation of macrophages with a set of cytokines revealed that only IFN-\u03b3 and LPS increased FPR2\/ALX expression from the first promoter to levels similar to those detected in monocytes. The upregulation by IFN-\u03b3 is in part mediated by the interaction of IFN regulatory factor 1 with an IFN-responsive sequence element transcription factor binding site located in the first promoter region of the FPR2\/ALX gene. However, this upregulation on the mRNA level did not translate into FPR2\/ALX protein expression in macrophages owing to reduced translation of the longer mRNA from the first promoter. In contrast, FPR2\/ALX mRNA transcribed from the second promoter was translated into surface expression of FPR2\/ALX in monocytes. These data support a model in which FPR2\/ALX plays a role in chemotaxis and activation of monocytes; however, they also suggest that its function in resident tissue macrophages is limited.","subset":"pubmed_abstract"} +{"meta":{"pmid":19073578,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[Cloning and expression analysis of two salt and Fusarium graminearum stress associated UDP-glucosyltransferases genes in wheat].\nGlycosyltransferases (GTs) play important roles in stress responses of plants by glycosylating hormones and secondary metabolites. UDP-glucosyltransferases (UGTs), which use UDP-glucuronic acid in animals, UDP-glucose, UDP-galactose, and UDP- rhamnose in plant as sugar donors, belong to family 1 of GTs. As a secondary metabolite produced by Fusarium graminearum during infection of grains, deoxynivalenol (DON) is not only harmful to human and animal's health by inhibiting protein synthesis, but also acts as a virulence factor during fungal pathogenesis. In order to study expression profile of UGT genes in wheat, two UGTs, designated TaUGT1 and TaUGT2, were isolated from bread wheat (Triticum aestivum L.) by reverse transcriptase-polymerase chain reaction. The genomic sequences of both genes had one intron. Their coding sequences shared 91% and 90% similarities at nucleic acid level and the deduced protein sequence level. The analysis of conserved domain revealed that these two cDNAs encoded UDP-glucoronosyl and UDP-glucosyl transferase with PSPG (Putative secondary plant glycosyltransferase) domain. Real-time PCR was carried out to detect the expression profiles of the two UGTs in wheat under various stress conditions. In young spikes infected by Fusarium graminearum, TaUGT2 was induced but TaUGT1 was repressed. These two genes were upregulated under higher NaCl concentration. In conclusion, TaUGT2 may participate in wheat resistance to Fusarium head blight in which mycotoxin DON plays a role, and these two genes might be involved in responses of wheat to salt stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":22699837,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Improved outcomes with quality improvement interventions in pediatric inflammatory bowel disease.\nVariations in chronic illness care are common in our health care system and may lead to suboptimal outcomes. Specifically, inconsistent use and suboptimal medication dosing have been demonstrated in the care of patients with inflammatory bowel disease (IBD). Quality improvement (QI) efforts have improved outcomes in conditions such as asthma and diabetes mellitus, but have not been well studied in IBD. We hypothesized that QI efforts would lead to improved outcomes in our pediatric IBD population. A QI team was formed within our IBD center in 2005. By 2007, we began prospectively capturing physician global assessment (PGA) and patient-reported global assessment. Significant QI interventions included creating evidence-based medication guidelines, joining a national QI collaborative, initiation of preclinic planning, and monitoring serum 25-hydroxyvitamin D. From 2007 to 2010, 505 patients have been followed at our IBD center. During this time, the frequency of patients in clinical remission increased from 59% to 76% (P < 0.05), the frequency of patients who report that their global assessment is >7 increased from 69% to 80% (P < 0.05), and the frequency of patients with a Short Pediatric Crohn's Disease Activity Index (sPCDAI) <15 increased from 60% to 77% (P < 0.05). The frequency of repeat steroid use decreased from 17% to 10% (P < 0.05). We observed an association between the use of a vitamin D supplement (P = 0.02), serum 25-hydroxyvitamin D (P < 0.05), and quiescent disease activity. Our results show that significant improvements in patient outcomes are associated with QI efforts that do not rely on new medication or therapies.","subset":"pubmed_abstract"} +{"meta":{"pmid":32784608,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Mesenchymal Stem\/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications.\nRheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem\/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.","subset":"pubmed_abstract"} +{"meta":{"pmid":30862765,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"The changing pattern of fever of unknown origin in the Republic of North Macedonia.\nThe study aimed to compare the etiologic spectrum of diseases causing fever of unknown origin (FUO) and methods for definitive diagnosis in a tertiary care hospital in the Republic of North Macedonia during two different time periods. There were analysed retrospectively the causes for FUO and final diagnostic approaches in 185 patients with classic FUO that were treated at the University Hospital for Infectious Diseases in Skopje during two time periods. Seventy nine patients were treated during 1991 to 1995 and 106 patients during 2011 to 2015. When comparing these two periods, infections were present in 46.8% and 29.2% (p = 0.014), non-infective inflammatory disorders in 22.8% and 25.5% (p = 0.674), neoplasms in 10.1% and 13.2% (p = 0.522), miscellaneous in 8.9% and 12.3% (p = 0.461) and undiagnosed cases in 11.4% and 19.8% (p = 0.124), respectively. The most common causes for FUO during the first period were abscesses (8.9%), tuberculosis and systemic lupus erythematosus (7.6% each), whereas in the second period the commonest causes were adult onset Still disease and solid organ neoplasm (7.6% each), polymyalgia rheumatica, abscesses and visceral leishmaniasis (5.7% each). The newer imaging techniques and clinical course evaluation had superior diagnostic significance during the second period. A changing pattern of diseases causing FUO during the examined periods was evident. Infections continue to be the most common cause but with decreasing incidence when compared to 20 years ago. Even nowadays clinical evaluation and follow-up still remain the vital diagnostic tools in determining the etiology of FUO.","subset":"pubmed_abstract"} +{"meta":{"pmid":29075335,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The Virtual Multifrequency Spectrometer: a new paradigm for spectroscopy.\nOn going developments of hardware and software are changing computational spectroscopy from a strongly specialized research area to a general tool in the inventory of most researchers. Increased interactions between experimentally-oriented users and theoretically-oriented developers of new methods and models would result in more robust, flexible and reliable tools and studies for the systems of increasing complexity, which are of current scientific and technological interest. This is the philosophy behind this review, which presents the development of a so-called virtual multi-frequency spectrometer (VMS) including state-of-the-art approaches in a user-friendly frame. The current status of the VMS tool will be illustrated by a number of case studies with special reference to infrared and UV-vis regions of the electro-magnetic spectrum including also chiral spectroscopies. Only the basic theoretical background will be provided avoiding explicit equations as far as possible, and pointing out the most recent advancements beyond the standard rigid-rotor harmonic-oscillator model coupled to vertical electronic excitation energies.","subset":"pubmed_abstract"} +{"meta":{"pmid":17319964,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-21":1,"2021-21":1,"2020-05":1,"2019-30":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-39":2,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-50":1,"2017-13":1}}},"text":"Mapping the contribution of beta3-containing GABAA receptors to volatile and intravenous general anesthetic actions.\nAgents belonging to diverse chemical classes are used clinically as general anesthetics. The molecular targets mediating their actions are however still only poorly defined. Both chemical diversity and substantial differences in the clinical actions of general anesthetics suggest that general anesthetic agents may have distinct pharmacological targets. It was demonstrated previously that the immobilizing action of etomidate and propofol is completely, and the immobilizing action of isoflurane partly mediated, by beta3-containing GABAA receptors. This was determined by using the beta3(N265M) mice, which carry a point mutation known to decrease the actions of general anesthetics at recombinant GABAA receptors. In this communication, we analyzed the contribution of beta3-containing GABAA receptors to the pharmacological actions of isoflurane, etomidate and propofol by means of beta3(N265M) mice. Isoflurane decreased core body temperature and heart rate to a smaller degree in beta3(N265M) mice than in wild type mice, indicating a minor but significant role of beta3-containing GABAA receptors in these actions. Prolonged time intervals in the ECG and increased heart rate variability were indistinguishable between genotypes, suggesting no involvement of beta3-containing GABAA receptors. The anterograde amnesic action of propofol was indistinguishable in beta3(N265M) and wild type mice, suggesting that it is independent of beta3-containing GABAA receptors. The increase of heart rate variability and prolongation of ECG intervals by etomidate and propofol were also less pronounced in beta3(N265M) mice than in wild type mice, pointing to a limited involvement of beta3-containing GABAA receptors in these actions. The lack of etomidate- and propofol-induced immobilization in beta3(N265M) mice was also observed in congenic 129X1\/SvJ and C57BL\/6J backgrounds, indicating that this phenotype is stable across different backgrounds. Our results provide evidence for a defined role of beta3-containing GABAA receptors in mediating some, but not all, of the actions of general anesthetics, and confirm the multisite model of general anesthetic action. This pharmacological separation of anesthetic endpoints also suggests that subtype-selective substances with an improved side-effect profile may be developed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26111965,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Economic benefits of the Mediterranean-style diet consumption in Canada and the United States.\nThe Mediterranean-style diet (MedDiet) is an established healthy-eating behavior that has consistently been shown to favorably impact cardiovascular health, thus likely improving quality of life and reducing costs associated with cardiovascular disease (CVD). Data on the economic benefits of MedDiet intakes are, however, scarce. The objective of this study was to estimate the annual healthcare and societal cost savings that would accrue to the Canadian and American public, independently, as a result of a reduction in the incidence of CVD following adherence to a MedDiet. A variation in cost-of-illness analysis entailing three stages of estimations was developed to 1) identify the proportion of individuals who are likely to adopt a MedDiet in North America, 2) assess the impact of the MedDiet intake on CVD incidence reduction, and 3) impute the potential savings in costs associated with healthcare and productivity following the estimated CVD reduction. To account for the uncertainty factor, a sensitivity analysis of four scenarios, including ideal, optimistic, pessimistic, and very-pessimistic assumptions, was implemented within each of these stages. Significant improvements in CVD-related costs were evident with varying MedDiet adoption and CVD reduction rates. Specifically, CAD $41.9 million to 2.5 billion in Canada and US $1.0-62.8 billion in the United States were estimated to accrue as total annual savings in economic costs, given the 'very-pessimistic' through 'ideal' scenarios. Closer adherence to dietary behaviors that are consistent with the principles of the MedDiet is expected to contribute to a reduction in the monetary burdens of CVD in Canada, the United States, and possibly other parts of the world.","subset":"pubmed_abstract"} +{"meta":{"pmid":15589793,"dup_signals":{"dup_doc_count":51,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":3,"2023-14":2,"2022-49":2,"2022-40":1,"2022-27":2,"2022-21":3,"2021-43":3,"2021-31":2,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":3,"2020-50":1,"2020-45":1,"2020-40":3,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2023-50":1,"2024-26":2,"2024-22":2,"2024-10":1}}},"text":"The influence of urbanisation on measures of Plasmodium falciparum infection prevalence in East Africa.\nThere is a growing interest in the effects of urbanisation in Africa on Plasmodium falciparum risks and disease outcomes. We undertook a review of published and unpublished literature to identify parasite survey data from communities in East Africa. Data were selected to represent the most reliable and contemporary estimates of infection prevalence and were categorised by urban or rural status using a number of approaches. We identified 329 spatially distinct surveys undertaken since 1980 in the sub-region of which 37 were undertaken in urban settlements and 292 in rural settlements. Overall rural settlements reported significantly higher parasite prevalence among children aged 0-14 than urban settlements (on average 10% higher infection rates; p<0.05). No urban settlements recorded parasite prevalence in excess of 75%. In areas of East Africa where climatic conditions are likely to support higher parasite transmission, the rural-urban difference was most marked. There was a significant trend towards documenting higher classes of parasite prevalence in rural compared to urban settlements (p<0.05) and the mean difference between rural and urban samples was 18% (p<0.001). These results further highlight the need to better define urban extents in Africa in order to capture the non-climatic determinants of infection and disease risk and provide a more informed approach to describing the burden of disease across the continent.","subset":"pubmed_abstract"} +{"meta":{"pmid":22268559,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":2,"2022-21":1,"2021-43":1,"2020-45":1,"2018-47":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-23":1,"2024-10":2}}},"text":"Heavy maternal alcohol consumption and cerebral palsy in the offspring.\nThe aim of this study was to investigate the association between heavy maternal alcohol consumption and pre- peri- and postneonatally acquired cerebral palsy (CP). The records of all mothers with an International Classification of Diseases, revision 9 or 10 (ICD-9\/-10) alcohol-related diagnostic code, indicating heavy alcohol consumption, recorded on population-based health, mental health, and drug and alcohol data sets from 1983 to 2007, and their children were identified through the Western Australian Data-linkage System. This 'exposed' cohort was frequency matched with mothers without an alcohol-related diagnosis and their offspring (comparison group). Cases of CP were identified through linkage with the Western Australia CP Register. Analyses were undertaken using multivariate logistic regression. There were 23 573 live births in the exposed group (58.6% non-Aboriginal; 41.4% Aboriginal) and 292 cases of CP. The odds of pre\/perinatally acquired CP were elevated for children of non-Aboriginal mothers with an alcohol-related diagnosis recorded during pregnancy (adjusted odds ratio 3.32; 95% confidence interval [CI] 1.30-8.48) and for Aboriginal children when an alcohol-related diagnosis was recorded up to 12 months before the mother's pregnancy (adjusted odds ratio 2.49; 95% CI 0.99-6.25). Increased odds of postneonatally acquired CP following any alcohol-related diagnosis were found for non-Aboriginal children (adjusted odds ratio 7.92; 95% CI 2.23-28.14). These results suggest that heavy maternal alcohol consumption is a direct cause of pre\/perinatally acquired CP, and an indirect cause of postneonatally acquired CP, in non-Aboriginal children. The lack of an association for Aboriginal children requires further investigation but may be due to under ascertainment of alcohol use disorders during pregnancy and other aetiological pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":23027273,"dup_signals":{"dup_doc_count":28,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":3,"2016-36":4,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-35":2,"2015-32":3,"2015-27":2,"2015-22":2,"2015-18":1}}},"text":"Terahertz single-shot quadrature phase-shifting interferometry.\nA single-shot quadrature phase-shifting interferometry architecture is presented that is applicable to antenna coupled detector technologies. The method is based on orthogonally polarized object and reference beams and on linear and circular polarization sensitive antennas in space-division multiplexing. The technique can be adapted to two-, three-, and four-step and Gabor holography recordings. It is also demonstrated that the space-division multiplexing does not necessarily cause sparse sampling. A sub-THz detector array is presented containing multiple on-chip antennas and FET plasma wave detectors implemented in a 90 nm complementary metal-oxide semiconductor technology. As an example, two-step phase-shifting reconstruction results are given at 360 GHz.","subset":"pubmed_abstract"} +{"meta":{"pmid":30671007,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":12}}},"text":"Eating Disorder Symptoms and Proneness in Gay Men, Lesbian Women, and Transgender and Non-conforming Adults: Comparative Levels and a Proposed Mediational Model.\nIn this study we sought to compare eating disorder attitudes and behaviors, and proneness to an eating disorder (\"ED proneness\"), between gay men, lesbian women, and transgender and non-conforming (TGNC) adults. A further aim was to identify and compare risk and protective factors, and examine a mediational model based on the interpersonal theory of eating disorders (IPT-ED), whereby the association between interpersonal factors and ED proneness would be mediated by psychological constructs pertaining to the self and negative affect. Data was obtained from a larger national study of health risk and protective factors among sexual minority and gender diverse populations. The sample included 97 gay men, 82 lesbian women, and 138 TGNC adults. Participants completed the National College Health Assessment, Eating Disorders Screen for Primary Care, Patient Health Questionnaire Depression scale, Generalized Anxiety Disorder 7 scale, Self-Compassion Scale-Short Form, Negative Social Exchange subscale of the Multidimensional Health Profile, Interpersonal Needs Questionnaire, and Perceived Stigma Scale. There was a significant difference between groups in ED proneness, with lesbian women (66.7%) having a significantly higher percentage than gay men (47.6%). There was also a significant difference between groups in weight-based self-worth, with the lowest percentage in gay men (63%) and the highest percentage in lesbian women (82%), as well as dissatisfaction with eating patterns, with the highest percentage in TGNC adults (69.8%) and the lowest percentage in gay men (47.7%). There was a low percentage of inappropriate compensatory behaviors, with no significant difference between groups. Logistic regression analyses showed that the predictor variables of ED proneness were depression, perceived stigma, and self-compassion in gay men; depression in lesbian women; and self-compassion in the TGNC adults. Mediation analyses showed that thwarted belongingness (i.e., an unmet to belong) and perceived stigma had an indirect association with ED proneness that was mediated by self-compassion and depression (for perceived stigma alone) in gay men, depression in lesbian women, and self-compassion in TGNC adults. The interpersonal theory of eating disorders therefore extends to sexual minority and gender diverse populations; however, the results suggest a broadening of theoretical models and intervention programs to include the role of stigma and self-compassion.","subset":"pubmed_abstract"} +{"meta":{"pmid":28963831,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-14":1,"2023-06":2,"2022-27":1,"2021-43":1,"2021-21":1,"2021-04":1,"2020-45":1,"2020-16":1,"2020-10":1,"2019-39":1,"2018-34":1,"2023-40":1,"2024-22":2,"2024-26":1}}},"text":"[Neprilysin inhibition and chronic kidney disease].\nPatients with chronic kidney disease (CKD) have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to end-stage renal disease (ESRD) Inhibition of neprilysin, in addition to offering a new therapeutic target in patients with heart failure, could represent a potential improvement strategy in cardiovascular and renal outcome of patients with CKD. Inhibition of neprilysin by inhibiting the breakdown of natriuretic peptides, increases their bioavailability resulting in an increase in diuresis and sodium excretion and, in addition to exerting an inhibition of the renin-angiotensin-aldosterone (RAAS) system. Inhibition of RAAS, in turn, generates a series of counter-regulations that can balance the adverse effects present in CKD and heart failure (HF). The idea of blocking neprilysin is not very recent, but the first drugs used as inhibitors had an inadmissible incidence of angioedema. Among the latest generation molecules that can perform a specific inhibitory action on the neprilysin receptor and, at the same time, on the angiotensin II receptor thanks to the association with valsartan there is the LCZ696 (sacubitril \/ valsartan). This drug has shown promising benefits both in the treatment arterial hypertension and heart failure. It is hoped that equally positive effects may occur in CKD patients, particularly those with macroproteinuria.","subset":"pubmed_abstract"} +{"meta":{"pmid":8039837,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Adaptation, allometry, and hypertension.\nEssential hypertension is a \"disease of civilization\" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the \"slavery\" and \"thrifty gene\" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.","subset":"pubmed_abstract"} +{"meta":{"pmid":8976333,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Physicians' attitudes toward patients' use of alternative cancer therapies.\nTo determine physicians' attitudes and reactions to their patients' use of alternative cancer therapies, factors that affect these reactions and physicians' views of how the use of such therapies affects the physician-patient relationship. Qualitative study involving in-depth semistructured interviews. Toronto. Nineteen oncologists and 35 general practitioners (GPs) were selected by means of purposive sampling; 18 oncologists and 12 GPs agreed to participate. Attitudes and reactions to patients' use of alternative cancer therapies; factors affecting physicians' reactions to such use; and physicians' views of how the use of such therapies affects the physician-patient relationship. Many physicians perceived themselves to be unfamiliar with available alternative cancer therapies and indicated that their main sources of information were their patients and the lay press. Although most of the physicians viewed the efficacy of such therapies as scientifically unproven, they would respect their patients' decision to use them and encourage them to continue with standard treatment. Factors found to influence the physicians' reactions included the prognosis with standard treatments, the exclusivity of the use of alternative therapies and whether the alternative therapies were harmful. Although many of the participants felt that a patient's use of alternative cancer therapies did not affect the physician-patient relationship, a few indicated that it did cause some tension. Because many physicians lack information on alternative cancer therapies and most of these therapies have not been scientifically proven, physicians' attitudes and reactions to their use by patients are influenced to a greater degree by the efficacy or inefficacy of standard treatment and the invasiveness of the alternative therapy than by the efficacy of the alternative therapy used.","subset":"pubmed_abstract"} +{"meta":{"pmid":22455582,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2019-39":1}}},"text":"Antimicrobial action of chelating agents: repercussions on the microorganism development, virulence and pathogenesis.\nInfections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and\/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.","subset":"pubmed_abstract"} +{"meta":{"pmid":6166713,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Antigen-specific T lymphocyte clones. I. Characterization of a T lymphocyte clone expressing antigen-specific suppressive activity.\nWe have generated continuously propagatable T lymphocyte clones to study antigen-specific T cell functions. All Ly-2+ clones mediate suppressive activity and secrete a characteristic pattern of polypeptides that differs from Ly-2- T cell clones. Cells of one clone, Cl.Ly23\/4, specifically bind glycophorin from sheep erythrocytes (SRBC). After incubation with [35S]methionine, supernate material from this clone also contains biosynthetically labeled 70,000-mol wt proteins that specifically bind to SRBC and this binding is inhibited by glycophorin from sheep but not other erythrocytes. These antigen-binding 70,000-mol wt peptides specifically and completely suppress primary anti-SRBC responses generated by mixtures of primed Ly-1+2- cells and B cells. Suppression by these antigen-binding peptides reflects direct inhibition of T-helper activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28299116,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-39":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2019-47":1}}},"text":"Challenges to Implementing a National Health Information System in Cameroon: Perspectives of Stakeholders.\nIn the early 90s, the Cameroon Ministry of Health implemented a National Health Information System (NHIS) based on a bottom-up approach of manually collecting and reporting health data. Little is known about the implementation and functioning of the NHIS. The purpose of this study was to assess the implementation of the NHIS by documenting experiences of individual stakeholders, and to suggest recommendations for improvement. We reviewed relevant documents and conducted face-to-face interviews (N=4) with individuals directly involved with data gathering, reporting and storage. Content analysis was used to analyze textual data. We found a stalled and inefficient NHIS characterized by general lack of personnel, a labor-intensive process, delay in reporting data, much reliance on field staff, and lack of incentives. A move to an electronic health information system without involving all stakeholders and adequately addressing the issues plaguing the current system is premature.","subset":"pubmed_abstract"} +{"meta":{"pmid":16987312,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Implementing the Institute of Medicine definition of disparities: an application to mental health care.\nIn a recent report, the Institute of Medicine (IOM) defines a health service disparity between population groups to be the difference in treatment or access not justified by the differences in health status or preferences of the groups. This paper proposes an implementation of this definition, and applies it to disparities in outpatient mental health care. Health Care for Communities (HCC) reinterviewed 9,585 respondents from the Community Tracking Study in 1997-1998, oversampling individuals with psychological distress, alcohol abuse, drug abuse, or mental health treatment. The HCC is designed to make national estimates of service use. Expenditures are modeled using generalized linear models with a log link for quantity and a probit model for any utilization. We adjust for group differences in health status by transforming the entire distribution of health status for minority populations to approximate the white distribution. We compare disparities according to the IOM definition to other methods commonly used to assess health services disparities. Our method finds significant service disparities between whites and both blacks and Latinos. Estimated disparities from this method exceed those for competing approaches, because of the inclusion of effects of mediating factors (such as income) in the IOM approach. A rigorous definition of disparities is needed to monitor progress against disparities and to compare their magnitude across studies. With such a definition, disparities can be estimated by adjusting for group differences in models for expenditures and access to mental health services.","subset":"pubmed_abstract"} +{"meta":{"pmid":22390460,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":1,"unknown":12}}},"text":"Psychosocial factors associated with mouth and throat cancer examinations in rural Florida.\nWe examined the knowledge and prevalence of mouth and throat cancer examinations in a sample drawn from rural populations in north Florida. Telephone interviews were conducted across rural census tracts throughout north Florida in 2009 and 2010, in a survey that had been adapted for cultural appropriateness using cognitive interviews. The sample consisted of 2526 respondents (1132 men and 1394 women; 1797 Whites and 729 African Americans). Awareness of mouth and throat cancer examination (46%) and lifetime receipt (46%) were higher than reported in statewide studies performed over the past 15 years. Only 19% of the respondents were aware of their examination, whereas an additional 27% reported having the examination when a description was provided, suggesting a lack of communication between many caregivers and rural patients. Surprisingly, anticipated racial\/ethnic differences were diminished when adjustments were made for health literacy and several measures of socioeconomic status. These findings support the notion that health disparities are multifactorial and include characteristics such as low health literacy, lack of access to care, and poor communication between patient and provider.","subset":"pubmed_abstract"} +{"meta":{"pmid":23968407,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":5,"2024-18":2,"2024-10":1,"unknown":7}}},"text":"Behavioral Indices of Multisensory Integration: Orientation to Visual Cues is Affected by Auditory Stimuli.\nPhysiological studies have demonstrated that inputs from different sensory modalities converge on, and are integrated by, individual superior colliculus neurons and that this integration is governed by specific spatial rules. The present experiments were an attempt to relate these neural processes to overt behavior by determining if behaviors believed to involve the circuitry of the superior colliculus would show similar multisensory dependencies and be subject to the same rules of integration. The neurophysiological-behavioral parallels proved to be striking. The effectiveness of a stimulus of one modality in eliciting attentive and orientation behaviors was dramatically affected by the presence of a stimulus from another modality in each of the three behavioral paradigms used here. Animals trained to approach a low intensity visual cue had their performance significantly enhanced when a brief, low intensity auditory stimulus was presented at the same location as the visual cue, but their performance was significantly depressed when the auditory stimulus was disparate to it. These effects were independent of the animals' experience with the modifying (i.e. auditory) stimulus and exceeded what might have been predicted statistically based on the animals' performance with each single-modality cue. The multiplicative nature of these multisensory interactions and their dependence on the relative positions and intensities of the two stimuli were all very similar to those observed physiologically for single cells. The few differences that were observed appeared to reflect the fact that understanding integration at the level of the single cell requires reference to the individual cell's multisensory receptive field properties, while at the behavioral level populations of receptive fields must be evaluated. These data illustrate that the rules governing multisensory integration at the level of the single cell also predict responses to these stimuli in the intact behaving organism.","subset":"pubmed_abstract"} +{"meta":{"pmid":18215114,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":16}}},"text":"A two-phase innate host response to alphavirus infection identified by mRNP-tagging in vivo.\nA concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during infection. However, elucidation of this cascade in vivo has been limited by a general inability to distinguish changes occurring in the minority of infected cells from those in surrounding uninfected cells. To circumvent this inherent limitation of traditional gene expression profiling methods, an innovative mRNP-tagging technique was implemented to isolate host mRNA specifically from infected cells in vitro as well as in vivo following Venezuelan equine encephalitis virus (VEE) infection. This technique facilitated a direct characterization of the host defense response specifically within the first cells infected with VEE, while simultaneous total RNA analysis assessed the collective response of both the infected and uninfected cells. The result was a unique, multifaceted profile of the early response to VEE infection in primary dendritic cells, as well as in the draining lymph node, the initially targeted tissue in the mouse model. A dynamic environment of complex interactions was revealed, and suggested a two-step innate response in which activation of a subset of host genes in infected cells subsequently leads to activation of the surrounding uninfected cells. Our findings suggest that the application of viral mRNP-tagging systems, as introduced here, will facilitate a much more detailed understanding of the highly coordinated host response to infectious agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":22040244,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Pillbox: a solid dosage medication identification tool.\nPillbox is a tool that can be used to rapidly identify solid dosage medications. The database, created and maintained by the National Library of Medicine with the support of the Food and Drug Administration, seeks to enhance patient safety through the identification of solid dosage medication. Users enter physical characteristics of a medication, possible matches are provided, and links to additional resources are offered. A comparison with comparable resources was conducted, and future enhancements to Pillbox are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":18056805,"dup_signals":{"dup_doc_count":18,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":2,"2015-11":3,"2015-06":1,"2014-10":3,"2013-48":1,"2013-20":2,"2024-26":1,"unknown":2}}},"text":"MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia.\nAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genome-wide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias.","subset":"pubmed_abstract"} +{"meta":{"pmid":33017922,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Information Dynamics Analysis: A new approach based on Sparse Identification of Linear Parametric Models.\nThe framework of information dynamics allows to quantify different aspects of the statistical structure of multivariate processes reflecting the temporal dynamics of a complex network. The information transfer from one process to another can be quantified through Transfer Entropy, and under the assumption of joint Gaussian variables it is strictly related to the concept of Granger Causality (GC). According to the most recent developments in the field, the computation of GC entails representing the processes through a Vector Autoregressive (VAR) model and a state space (SS) model typically identified by means of the Ordinary Least Squares (OLS). In this work, we propose a new identification approach for the VAR and SS models, based on Least Absolute Shrinkage and Selection Operator (LASSO), that has the advantages of maintaining good accuracy even when few data samples are available and yielding as output a sparse matrix of estimated information transfer. The performances of LASSO identification were first tested and compared to those of OLS by a simulation study and then validated on real electroencephalographic (EEG) signals recorded during a motor imagery task. Both studies indicated that LASSO, under conditions of data paucity, provides better performances in terms of network structure. Given the general nature of the model, this work opens the way to the use of LASSO regression for the computation of several measures of information dynamics currently in use in computational neuroscience.","subset":"pubmed_abstract"} +{"meta":{"pmid":30634185,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Separating memoranda in depth increases visual working memory performance.\nVisual working memory is the mechanism supporting the continued maintenance of information after sensory inputs are removed. Although the capacity of visual working memory is limited, memoranda that are spaced farther apart on a 2-D display are easier to remember, potentially because neural representations are more distinct within retinotopically organized areas of visual cortex during memory encoding, maintenance, or retrieval. The impact on memory of spatial separability in depth is less clear, even though depth information is essential to guiding interactions with objects in the environment. On one account, separating memoranda in depth may facilitate performance if interference between items is reduced. However, depth information must be inferred indirectly from the 2-D retinal image, and less is known about how visual cortex represents depth. Thus, an alternative possibility is that separation in depth does not attenuate between-items interference; it may even impair performance, as attention must be distributed across a larger volume of 3-D space. We tested these alternatives using a stereo display while participants remembered the colors of stimuli presented either near or far in the 2-D plane or in depth. Increasing separation in-plane and in depth both enhanced performance. Furthermore, participants who were better able to utilize stereo depth cues showed larger benefits when memoranda were separated in depth, particularly for large memory arrays. The observation that spatial separation in the inferred 3-D structure of the environment improves memory performance, as is the case in 2-D environments, suggests that separating memoranda in depth might reduce neural competition by utilizing cortically separable resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":27227080,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"The experienced temperature sensitivity and regulation survey.\nIndividuals differ in thermosensitivity, thermoregulation, and zones of thermoneutrality and thermal comfort. Whereas temperature sensing and -effectuating processes occur in part unconsciously and autonomic, awareness of temperature and thermal preferences can affect thermoregulatory behavior as well. Quantification of trait-like individual differences of thermal preferences and experienced temperature sensitivity and regulation is therefore relevant to obtain a complete understanding of human thermophysiology. Whereas several scales have been developed to assess instantaneous appreciation of heat and cold exposure, a comprehensive scale dedicated to assess subjectively experienced autonomic or behavioral thermoregulatory activity has been lacking so far. We constructed a survey that specifically approaches these domains from a trait-like perspective, sampled 240 volunteers across a wide age range, and analyzed the emergent component structure. Participants were asked to report their thermal experiences, captured in 102 questions, on a 7-point bi-directional Likert scale. In a second set of 32 questions, participants were asked to indicate the relative strength of experiences across different body locations. Principal component analyses extracted 21 meaningful dimensions, which were sensitive to sex-differences and age-related changes. The questions were also assessed in a matched sample of 240 people with probable insomnia to evaluate the sensitivity of these dimensions to detect group differences in a case-control design. The dimensions showed marked mean differences between cases and controls. The survey thus has discriminatory value. It can freely be used by anyone interested in studying individual or group differences in thermosensitivity and thermoregulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":37170569,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Non-perfusion severity correlates with central macular thickness and microvascular impairment in branch retinal vein occlusions.\nTo study peripheral capillary non-perfusion (PCN-P) in branch retinal vein occlusion (BRVO) by means of ultra wide-field fluorescein angiography (UWFFA), and to correlate its extent and severity with optical coherence tomography (OCT) and OCT-angiography (OCTA) parameters and best corrected visual acuity (BCVA). Prospective case series with 2 years of planned follow-up. We recruited patients from June 2019 to December 2019. Ophthalmologic examination included BCVA, UWFFA, OCT and OCTA. Partial (p) and complete (c) ischemic index (ISI) were evaluated on UWFFA images. Vessel density (VD) in both the macular region and the optic nerve head (ONH) was calculated. Twelve BRVO subjects and 12 healthy controls were recruited. Mean age was 63.8 \u00b1 8.74 years. Mean BCVA improved from 0.43 \u00b1 0.25 logMAR to 0.15 \u00b1 0.18 after two years (p < 0.01), while mean central macular thickness (CMT) decreased from 463.83 \u00b1 200.85 \u00b5m to 353.17 \u00b1 108.85 \u00b5m (p > 0.05). Mean cISI, pISI and total ISI were 25.2 \u00b1 13.0%, 6.3 \u00b1 5.0% and 31.5 \u00b1 12.0%, respectively. Except for VDs of the superficial capillary plexus and choriocapillaris in the macular region, all VDs were lower in the BRVO group (p < 0.01). cISI and tISI negatively correlated with mDCP (p < 0.01), whereas only pISI correlated with CMT at baseline (p < 0.05). Additionally, cISI also negatively correlated with VD at the ONH (p < 0.05). The amount of complete and partial ischemia may have different implications in BRVO, with the former being more associated with microvascular impairment and the latter with macular edema.","subset":"pubmed_abstract"} +{"meta":{"pmid":23438411,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effects of a forgiveness intervention for older adults.\nThe authors' aim in the present study was to examine the effects of a brief forgiveness intervention for older adults. The psychoeducational group intervention consists of (a) established core components of previous forgiveness interventions and (b) additional components considering specific needs of older adults. Seventy-eight older adults (mean age 70.1 years) were randomized to a treatment condition or a waiting-list control condition. The intervention reduced the levels of perceived actual transgression painfulness, transgression-related emotions and cognitions, and negative affect. These findings suggest the promise of forgiveness interventions for older adults that help participants clarify and deal with past, present, and future interpersonal transgressions.","subset":"pubmed_abstract"} +{"meta":{"pmid":21780914,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2014-10":1,"2013-20":1,"unknown":9}}},"text":"Utilization of screening mammography among middle-aged and older women.\nThis study examines patterns of screening mammogram use, investigating the relationship of screening with demographic, health status, and healthcare factors. Data from 1242 women aged ?41 were obtained from a random sample of mailed surveys to community households in an eight-county region in Central Texas in 2010. The dependent variable was the timing of the participants' most recent screening mammography (in the past 12 months, between 1 and 2 years, or >2 years). Predictor variables included demographic, health status, and healthcare access factors. Multinomial logistic regression identified variables associated with screening mammography practices. The majority of women reported having at least one mammogram during their lifetime (93.0%) and having a mammography within the past 2 years (76.2%). Participants who reported not having a routine checkup in the past 12 months (odds ratio [OR] 0.12, p<0.001), having a lapse of insurance in the past 3 years (OR 2.95, p<0.05), and living in a health provider shortage area (OR 1.42, p<0.05) were less likely to be screened within the past 2 years. Routine healthcare plays a major role in preventive screening, which indicates screening mammography practices can be enhanced by improving participation in routine checkups with medical providers, continuity of insurance coverage, and women's access to healthcare. Interventions to encourage screening mammography may be particularly needed for women who have experienced a lapse in insurance or have not had a checkup in the past year.","subset":"pubmed_abstract"} +{"meta":{"pmid":26966638,"dup_signals":{"dup_doc_count":29,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2022-21":2,"2021-43":1,"2021-17":1,"2021-10":1,"2020-10":1,"2019-43":1,"2019-26":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2024-10":2,"2017-13":1,"2024-26":1}}},"text":"Oral Mineralocorticoid-Receptor Antagonists: Real-Life Experience in Clinical Subtypes of Nonresolving Central Serous Chorioretinopathy With Chronic Epitheliopathy.\nTo evaluate the efficacy and safety of oral mineralocorticoid-receptor antagonist (MRa) therapy in three clinical presentations of nonresolving central serous chorioretinopathy (CSCR) with chronic epitheliopathy. Retrospective case series of consecutive patients with nonresolving CSCR treated with oral eplerenone or spironolactone. Treatment criteria were: persistent CSCR with subretinal fluid (SRF) lasting longer than 4 months; recurrent CSCR with SRF lasting longer than 2 months; persistent CSCR (SRF \u2265 4 months) with fundus autofluorescence gravitational tracks. Outcomes at 1, 3, and 6 months were: foveal SRF height, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), best-corrected visual acuity (BCVA), and occurrence of side effects. Among 54 eyes from 42 patients (mean age: 53 years), mean foveal SRF, CMT, and SFCT decreased significantly at 1, 3, and 6 months after treatment initiation. Mean BCVA improved significantly at 6 months. In the subgroup analysis, mean foveal SRF, CMT, and SFCT decreased significantly at 3 and 6 months in the persistent and recurrent groups. In persistent cases with tracks, a significant diminution of mean CMT and SFCT was achieved at 6 months. Treatment-related side effects were observed in 6 patients, prompting treatment discontinuation in one case. Response to treatment was observed in the three subgroups. In persistent CSCR with tracks the response was delayed compared with persistent and recurrent cases, suggesting that longer treatment durations would be beneficial in patients with gravitational tracks of RPE alteration. The clinical response to oral MRa is consistent with the involvement of the mineralocorticoid pathway in CSCR pathogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":1735567,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose-finding pilot study.\nThe antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache).","subset":"pubmed_abstract"} +{"meta":{"pmid":23574705,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-27":1,"2021-10":1,"2019-51":1,"2019-18":1,"2019-09":1,"2018-34":1,"2018-09":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2023-23":1,"2017-13":1}}},"text":"Laboratory tests of antifungal agents to treat tadpoles against the pathogen Batrachochytrium dendrobatidis .\nThe fungus Batrachochytrium dendrobatidis (Bd), which is the etiological agent of the disease chytridiomycosis, is threatening both wild and captive amphibians. While there are some methods of treating amphibians in captivity, no method has yet been shown to be a promising treatment for amphibian populations in natural habitats. Here we present the results of a laboratory experiment in which we tested 2 antifungal agents that might be used to treat amphibians in the field. As a first step towards the goal of developing mitigation methods, we tested the efficiency of these agents in reducing Bd prevalence and loads (zoospore counts) in the laboratory. We exposed naturally infected tadpoles of the midwife toad Alytes obstetricans to different concentrations of the antifungal agents for 7 d. We found that Virkon Aquatic\u00ae affected neither Bd prevalence nor loads. At 0.625 ml l-1 of General Tonic\u00ae, prevalence was reduced to 60%, and infected animals had greatly reduced burdens. However, tadpole length was reduced by 19% and mass by 32% on average compared to the control group, suggesting a negative effect on fitness. Tadpole survival was not affected at 0.625 ml l-1 or 1.25 ml l-1, but was reduced to 60% at 2.5 ml l-1. Keeping animals in a dilution of General Tonic\u00ae for 7 d at a concentration of 0.625 ml l-1 might be an easy way to reduce zoospore counts in large numbers of animals at relatively low cost.","subset":"pubmed_abstract"} +{"meta":{"pmid":10319820,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":18}}},"text":"Breaking colinearity in the mouse HoxD complex.\nVertebrate Hox genes are activated in a spatiotemporal sequence that reflects their clustered organization. While this colinear relationship is a property of most metazoans with an anterior to posterior polarity, the underlying molecular mechanisms are unknown. Previous work suggested that Hox genes were made progressively available for transcription in the course of gastrulation, implying the existence of an element capable of initiating a repressive conformation, subsequently relieved from the clusters sequentially. We searched for this element by combining a genomic walk with successive transgene insertions upstream of the HoxD complex followed by a series of deletions. The largest deficiency induced posterior homeotic transformations coincidentally with an earlier activation of Hoxd genes. These data suggest that a regulatory element located upstream of the complex is necessary for setting up the early pattern of Hox gene colinear activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":33441175,"dup_signals":{"dup_doc_count":11}},"text":"Subconjunctival injection of mesenchymal stem cells for corneal failure due to limbal stem cell deficiency: state of the art.\nMesenchymal stem cells (MSCs) have unique and beneficial properties and are currently used to treat a broad variety of diseases. These properties include the potential for differentiation into other cell types, secretion of different trophic factors that promote a regenerative microenvironment, anti-inflammatory actions, selective migration to damaged tissues, and non-immunogenicity. MSCs are effective for the treatment of ocular surface diseases such as dry eye, corneal burns, and limbal stem cell deficiency (LSCD), both in experimental models and in humans. LSCD is a pathological condition in which damage occurs to the limbal epithelial stem cells, or their niche, that are responsible for the continuous regeneration of the corneal epithelium. If LSCD is extensive and\/or severe, it usually causes corneal epithelial defects, ulceration, and conjunctival overgrowth of the cornea. These changes can result in neovascularization and corneal opacity, severe inflammation, pain, and visual loss. The effectiveness of MSCs to reduce corneal opacity, neovascularization, and inflammation has been widely studied in different experimental models of LSCD and in some clinical trials; however, the methodological disparity used in the different studies makes it hard to compare outcomes among them. In this regard, the MSC route of administration used to treat LSCD and other ocular surface diseases is an important factor. It should be efficient, minimally invasive, and safe. So far, intravenous and intraperitoneal injections, topical administration, and MSC transplantation using carrier substrata like amniotic membrane (AM), fibrin, or synthetic biopolymers have been the most commonly used administration routes in experimental models. However, systemic administration carries the risk of potential side effects and transplantation requires surgical procedures that could complicate the process. Alternatively, subconjunctival injection is a minimally invasive and straightforward technique frequently used in ophthalmology. It enables performance of local treatments using high cell doses. In this review, we provide an overview of the current status of MSC administration by subconjunctival injection, analyzing the convenience, safety, and efficacy for treatment of corneal failure due to LSCD in different experimental models. We also provide a summary of the clinical trials that have been completed, are in progress, or being planned.","subset":"pubmed_abstract"} +{"meta":{"pmid":29523857,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-10":3,"2024-26":1,"unknown":5}}},"text":"Physical Exercise and Spatial Training: A Longitudinal Study of Effects on Cognition, Growth Factors, and Hippocampal Plasticity.\nPhysical exercise has been suggested to improve cognitive performance through various neurobiological mechanisms, mediated by growth factors such as BDNF, IGF-I, and VEGF. Moreover, animal research has demonstrated that combined physical and cognitive stimulation leads to increased adult neurogenesis as compared to either experimental condition alone. In the present study, we therefore investigated whether a sequential combination of physical and spatial training in young, healthy adults elicits an additive effect on training and transfer gains. To this end, we compared the effects of (i) eight 20-minute sessions of cycling, (ii) sixteen 30-minute sessions of spatial training, (iii) a combination of both, and included (iv) a passive control cohort. We assessed longitudinal changes in cognitive performance, growth factor levels, and T1 relaxation of hippocampal subfields (acquired with 7 T MRI). While substantial physical and spatial training gains were elicited in all trained groups, longitudinal transfer changes did not differ between these groups. Notably, we found no evidence for an additive effect of sequential physical and spatial training. These results challenge the extrapolation from the findings reported in animals to young, healthy adults.","subset":"pubmed_abstract"} +{"meta":{"pmid":30978166,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":12}}},"text":"Influence of preoperative hydronephrosis and ureteral orifice involvement in the survival of patients undergoing radical cystectomy: A retrospective comparative study.\nThe aim of the present study was to evaluate the influence of preoperative hydronephrosis and ureteral orifice involvement (UOI) on survival of patients undergoing radical cystectomy (RC) for bladder cancer (BC). A total of 162 patients with BC underwent RC between January 2006 and March 2017. Patients were divided into two groups for both presences of preoperative hydronephrosis and orifice involvement at final pathology. Additionally, tumors with orifice involvement were subgrouped histopathologically after RC as those with only UOI and those with invasive to the ureter with an additional concurrent site at final pathology. Preoperative hydronephrosis was detected in 57 patients. Preoperative and postoperative creatinine on month 3 were higher in the preoperative hydronephrosis (+) group (p<0.001). In addition, postoperative T stage, surgical margin positivity, invasion of urethra, and pathological upstaging were higher in this group. Cancer-specific survival (CSS) and overall survival (OS) were better in the hydronephrosis (-) group than in the hydronephrosis (+) group (p=0.001 and p=0.001, respectively). Preoperative hydronephrosis was found to be an independent factor in pathological upstaging. Patients were divided into two groups according to the presence of UOI. Group 1 consisted of patients without UOI, and group 2 with UOI. Preoperative hydronephrosis, hydronephrosis grade, and T stage were statistically higher in tumors with UOI. Moreover, CSS and OS were lower in group 2 than in group 1. Preoperative hydronephrosis and UOI are predicting factors on survival of patients undergoing RC for BC. Preoperative hydronephrosis was found to be an independent factor in pathological upstaging.","subset":"pubmed_abstract"} +{"meta":{"pmid":30932296,"dup_signals":{"dup_doc_count":12}},"text":"Trastuzumab-related cardiotoxicity in patients with nonlimiting cardiac comorbidity.\nSignificant and symptomatic cardiac comorbidity is a contraindication to adjuvant trastuzumab in breast cancer patients. However, some patients with asymptomatic, nonlimiting cardiac comorbidity and normal baseline left ventricular ejection fraction (LVEF) receive adjuvant trastuzumab in the clinical practice. We sought to describe the tolerability of trastuzumab in these patients. Retrospective analysis of patients with baseline asymptomatic, nonlimiting cardiac comorbidity receiving adjuvant trastuzumab at six Institutions between July 2007 and January 2016. Thirty-seven patients with HER2-positive, surgery treated breast cancer at high risk of relapse were studied. Median age was 64 years (range 36-82), median baseline LVEF 61% (range 50%-85%). Thirteen patients (35%) received trastuzumab with adjuvant anthracycline and taxane-based regimens, 19 (51%) with taxane-based, three (8%) with off-label vinorelbine and two (5%) with off-label endocrine therapy. Most frequent cardiac comorbidities were ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), and conduction disorders (14%). Nine patients (24.3%) experienced a cardiac event: congestive heart failure (one patient, 3%), asymptomatic LVEF reduction (six patients, 16%), and rhythm disturbances (two patients, 5%). Trastuzumab had to be discontinued either permanently (five patients, 14%) or temporarily (two patients, 5%). At the time of last follow-up visit, all patients showed LVEF within normal limits, except one who had experienced a symptomatic cardiac event (LVEF value at last follow-up 46%). Caution is needed in patients with significant ongoing cardiovascular risk factors, but when adjuvant trastuzumab is deemed beneficial on breast cancer outcomes, nonlimiting cardiac comorbidity should not preclude treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":26834199,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2020-34":1,"2020-16":1,"2019-47":1,"2019-18":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2021-04":1}}},"text":"Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.\nInterferon-gamma (IFN-\u03b3) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-\u03b3-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-\u03b3. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD\u00ae In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem\u00ae). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-\u03b3 and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-\u03b3 and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":9822302,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Analysis of neomycin, kanamycin, tobramycin and amikacin resistance mechanisms in gentamicin-resistant isolates of Enterobacteriaceae.\nTwenty-four gentamicin-resistant isolates of Enterobacteriaceae, obtained from the clinical laboratories of three health centres in Nablus, Palestine, were tested for susceptibility to neomycin, kanamycin, tobramycin and amikacin. Resistance rates were 29.2% for neomycin, 58.3% for kanamycin, 45.8% for tobramycin and 8.3% for amikacin. Fourteen (58.3%) isolates were noted to be multiresistant, i.e., resistant to gentamicin and two or more other aminoglycosides; resistance to gentamicin, kanamycin and tobramycin was the most common pattern of multiple resistance. This pattern implies the involvement of adenyltransferase ANT(\")-I activity. Plasmid profiles and curing experiments suggested a plasmid localisation of gentamicin, neomycin, kanamycin and tobramycin resistance genes. However, a chromosomal location is proposed for plasmid-deficient strains. Cross-resistance in two isolates to all aminoglycosides tested suggested membrane impermeability to aminoglycosides as the mechanism of resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":33303551,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Functional respiratory imaging provides novel insights into the long-term respiratory sequelae of bronchopulmonary dysplasia.\nBronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Lung function and imaging are classically used to assess BPD. Functional respiratory imaging (FRI) combines a structural and functional assessment of the airways and their vasculature. We aimed to assess BPD using FRI and to correlate these findings with the clinical presentation. We included 37 adolescents with a history of preterm birth (22 BPD cases and 15 preterm controls). The study protocol included a detailed history, lung function testing and computed tomography (CT) (at total lung capacity (TLC) and functional residual capacity (FRC)) with FRI. CT images were also assessed using the Aukland scoring system. BPD patients had lower forced expiratory volume in 1 s to forced vital capacity ratio (p=0.02) and impaired diffusion capacity (p=0.02). Aukland CT scores were not different between the two groups. FRI analysis showed higher lobar volumes in BPD patients at FRC (p<0.01), but not at TLC. Airway resistance was significantly higher in the BPD group, especially in the distal airways. Additionally, FRI showed more air trapping in BPD patients, in contrast to findings on conventional CT images. This study is the first to use FRI in research for BPD. FRI analysis showed higher lobar volumes in BPD patients, indicating air trapping and reduced inspiratory capacity. In contrast to Aukland CT scores, FRI showed more air trapping in the BPD group, suggesting that FRI might be a more sensitive detection method. Importantly, we also showed increased distal airway resistance in BPD patients. By combining structural and functional assessment, FRI may help to better understand the long-term sequelae of BPD.","subset":"pubmed_abstract"} +{"meta":{"pmid":25997160,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-40":1,"2021-25":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-47":2,"2019-39":1,"2019-30":1,"2019-18":1,"2019-09":1,"2023-50":1}}},"text":"Metal extent in blood of livestock from Dandora dumping site, Kenya: Source identification of Pb exposure by stable isotope analysis.\nNairobi city in Kenya produces 2000 tons\/day of garbage, and most of it is dumped onto the Dandora dumping site, home to a quarter-million residents. This study was conducted (1) to assess the contamination levels of nine metals and a metalloid (arsenic) in the blood of pigs, goats, sheep and cattle from Dandora, and (2) to identify a possible source of lead (Pb) pollution. Cadmium (Cd, 0.17-4.35 \u03bcg\/kg, dry-wt) and Pb (90-2710 \u03bcg\/kg) levels in blood were generally high, suggesting human exposure to Cd through livestock consumption and Pb poisoning among pigs (2600 \u03bcg\/kg) and cattle (354 \u03bcg\/kg). Results of Pb isotope ratios indicated that the major exposure route might differ among species. Our results also suggested a possibility that the residents in Dandora have been exposed to the metals through livestock consumption.","subset":"pubmed_abstract"} +{"meta":{"pmid":19597486,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":9}}},"text":"A two-step model for senescence triggered by a single critically short telomere.\nTelomeres protect chromosome ends from fusion and degradation. In the absence of a specific telomere elongation mechanism, their DNA shortens progressively with every round of replication, leading to replicative senescence. Here, we show that telomerase-deficient cells bearing a single, very short telomere senesce earlier, demonstrating that the length of the shortest telomere is a major determinant of the onset of senescence. We further show that Mec1p-ATR specifically recognizes the single, very short telomere causing the accelerated senescence. Strikingly, before entering senescence, cells divide for several generations despite complete erosion of their shortened telomeres. This pre-senescence growth requires RAD52 (radiation sensitive) and MMS1 (methyl methane sulfonate sensitive), and there is no evidence for major inter-telomeric recombination. We propose that, in the absence of telomerase, a very short telomere is first maintained in a pre-signalling state by a RAD52-MMS1-dependent pathway and then switches to a signalling state leading to senescence through a Mec1p-dependent checkpoint.","subset":"pubmed_abstract"} +{"meta":{"pmid":29800358,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Does Implicit Voice Learning Improve Spoken Language Processing? Implications for Clinical Practice.\nIn typical interactions with other speakers, including a clinical environment, listeners become familiar with voices through implicit learning. Previous studies have found evidence for a Familiar Talker Advantage (better speech perception and spoken language processing for familiar voices) following explicit voice learning. The current study examined whether a Familiar Talker Advantage would result from implicit voice learning. Thirty-three adults and 16 second graders were familiarized with 1 of 2 talkers' voices over 2 days through live interactions as 1 of 2 experimenters administered standardized tests and interacted with the listeners. To assess whether this implicit voice learning would generate a Familiar Talker Advantage, listeners completed a baseline sentence recognition task and a post-learning sentence recognition task with both the familiar talker and the unfamiliar talker. No significant effect of voice familiarity was found for either the children or the adults following implicit voice learning. Effect size estimates suggest that familiarity with the voice may benefit some listeners, despite the lack of an overall effect of familiarity. We discuss possible clinical implications of this finding and directions for future research.","subset":"pubmed_abstract"} +{"meta":{"pmid":36284858,"dup_signals":{"dup_doc_count":15,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2022-27":1,"2022-21":3,"2022-05":2,"2021-49":2,"2021-43":1,"2021-04":1,"2022-33":1}}},"text":"Microsurgical resection of medullary cavernoma via the olivary zone by the retrosigmoid supracondylar approach.\nMicrosurgical resection of the medullary cavernoma is rare, comprising less than 15% of more than 250 surgeries of brainstem cavernoma performed by the senior author (H.B.).1 This video demonstrates a case of a cavernous malformation inside the lateral part of the medulla, which was surgically treated via the olivary zone by the retrosigmoid supracondylar approach in a half-sitting position. Osseous drilling of the lateral foramen magnum provided wide exposure of the cerebellomedullary cistern around the olive.2,3 The lesion was completely dissected at the appropriate cleavage plane from the normal parenchyma. The patient developed no new neurological deficits and had no recurrence during 3 years of follow-up after the operation. The video can be found here: https:\/\/youtu.be\/7i7SccS5HmU.","subset":"pubmed_abstract"} +{"meta":{"pmid":9125003,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"The polyuria of solute diuresis.\nPolyuria is an important symptom or sign because of its potential severity, diverse causes, and interesting pathophysiology. Whereas polyuria induced by water diuresis is reasonably well understood and easily recognized by clinicians, that produced by solute diuresis is more likely to cause confusion. In this article, we focus on solute diuresis as a cause of polyuria, review the classification and pathophysiology of polyuria, and describe the clinical and laboratory studies useful for the evaluation of the polyuric patient. A stepwise, logical approach is provided (1) to determine whether a patient has a water diuresis, a solute diuresis, or both (concurrently), and (2) if a solute diuresis is present, to determine if it is caused by electrolytes (eg, sodium chloride sodium bicarbonate), by nonelectrolytes (eg, glucose, urea), or by both. How to assess these possibilities and to determine the specific cause of the diuresis is discussed in detail. Three representative case examples are provided. Selected causes of a solute diuresis also are reviewed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8312032,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effectiveness and cost of different strategies for information feedback in general practice.\nThe aim of this study was to determine the effectiveness and relative cost of three forms of information feedback to general practices--graphical, graphical plus a visit by a medical facilitator and tabular. Routinely collected, centrally-held data were used where possible, analysed at practice level. Some non-routine practice data in the form of risk factor recording in medical notes, for example weight, smoking status, alcohol consumption and blood pressure, were also provided to those who requested it. The 52 participating practices were stratified and randomly allocated to one of the three feedback groups. The cost of providing each type of feedback was determined. The immediate response of practitioners to the form of feedback (acceptability), ease of understanding (intelligibility), and usefulness of regular feedback was recorded. Changes introduced as a result of feedback were assessed by questionnaire shortly after feedback, and 12 months later. Changes at the practice level in selected indicators were also assessed 12 and 24 months after initial feedback. The resulting cost per effect was calculated to be 46.10 pounds for both graphical and tabular feedback, 132.50 pounds for graphical feedback plus facilitator visit and 773.00 pounds for the manual audit of risk factors recorded in the practice notes. The three forms of feedback did not differ in intelligibility or usefulness, but feedback plus a medical facilitator visit was significantly less acceptable. There was a high level of self-reported organizational change following feedback, with 69% of practices reporting changes as a direct result; this was not significantly different for the three types of feedback. There were no significant changes in the selected indicators at 12 or 24 months following feedback. The practice characteristic most closely related to better indicators of preventive practice was practice size, smaller practices performing significantly better. Separate clinics were not associated with better preventive practice. It is concluded that feedback strategies using graphical and tabular comparative data are equally cost-effective in general practice with about two thirds of practices reporting organizational change as a consequence; feedback involving unsolicited medical facilitator visits is less cost-effective. The cost-effectiveness of manual risk factor audit is also called into question.","subset":"pubmed_abstract"} +{"meta":{"pmid":24359423,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Vector-borne agents detected in fleas of the northern white-breasted hedgehog.\nThis is the first large-scale molecular investigation of fleas from a geographically widespread and highly urbanized species, the northern white-breasted hedgehog. In this study, 759 fleas (the majority were Archaeopsylla erinacei) collected from 134 hedgehogs were molecularly analyzed individually or in pools for the presence of three groups of vector-borne pathogens. All flea samples were positive for rickettsiae: In two samples (1.5%) Rickettsia helvetica and in 10% of the others a novel rickettsia genotype were identified. Additionally, Bartonella henselae (the causative agent of cat scratch disease in humans) was demonstrated in one flea (0.7%), and hemoplasmas of the hemofelis group were identified in seven other samples (5.2%). The findings of vector-borne agents not detected before in A. erinacei fleas broaden the range of those diseases of veterinary-medical importance, of which hedgehogs may play a role in the epidemiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":7046917,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Thymic origin of the prolactin-dependent Nb2 lymphoma cell line.\nBlast cells in acute leukemia and lymphoma appear to be \"frozen\" at various stages of lymphoid cell differentiation. The enzymatic and antigenic phenotypes expressed by these cells often correspond to the gene products of their normal precursors. We have used various immunocytochemical and enzymatic techniques to identify membrane, nuclear, and cytoplasmic markers associated with the prolactin-dependent Nb2 lymphoma cell line. The Nb2 cells, whether stationary or in log-phase growth, did not express any surface immunoglobulin. However, 100% of the Nb2 cells bound both a monoclonal antibody raised to rat thymocyte W3\/25-HLK, which specifically binds an antigenic determinant on rat T-helper cells, and second monoclonal antibody OX8-HL, which identifies rat nonhelper T-cells. Transmission electron microscopy showed no evidence of phagocytic vacuoles, and activity of the lysosomal enzyme muramidase was also absent. There was no evidence of the DNA polymerase enzyme terminal deoxynucleotidyl transferase. alpha-Naphthyl acetate esterase activity was indicated in about 50% of the Nb2 cells by a faint particulate cytoplasmic staining similar to that found in thymocytes. Rosette formation with guinea pig erythrocytes, a property of mature rat thymocytes, was not observed with Nb2 cells. The data suggest that the Nb2 tumor may have arisen from a thymocyte at an intermediate stage of differentiation. The presence of Thy-like alpha-naphthyl acetate esterase pattern and the binding of both W3\/25-HLK and OX8-HL support the thymic origin and relative immaturity of these lymphoid cells. It is becoming increasingly apparent that a significant proportion of lymphomas and leukemias also originate in undifferentiated thymic cels.","subset":"pubmed_abstract"} +{"meta":{"pmid":32121431,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Isoprene Oxidation by the Gram-Negative Model bacterium Variovorax sp. WS11.\nPlant-produced isoprene (2-methyl-1,3-butadiene) represents a significant portion of global volatile organic compound production, equaled only by methane. A metabolic pathway for the degradation of isoprene was first described for the Gram-positive bacterium Rhodococcus sp. AD45, and an alternative model organism has yet to be characterised. Here, we report the characterisation of a novel Gram-negative isoprene-degrading bacterium, Variovorax sp. WS11. Isoprene metabolism in this bacterium involves a plasmid-encoded iso metabolic gene cluster which differs from that found in Rhodococcus sp. AD45 in terms of organisation and regulation. Expression of iso metabolic genes is significantly upregulated by both isoprene and epoxyisoprene. The enzyme responsible for the initial oxidation of isoprene, isoprene monooxygenase, oxidises a wide range of alkene substrates in a manner which is strongly influenced by the presence of alkyl side-chains and differs from other well-characterised soluble diiron monooxygenases according to its response to alkyne inhibitors. This study presents Variovorax sp. WS11 as both a comparative and contrasting model organism for the study of isoprene metabolism in bacteria, aiding our understanding of the conservation of this biochemical pathway across diverse ecological niches.","subset":"pubmed_abstract"} +{"meta":{"pmid":32029712,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":4,"2024-18":2,"unknown":6}}},"text":"Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis.\nRheumatoid arthritis affects individuals commonly during the most productive years of adulthood. Poor response rates and high costs associated with treatment mandate the search for new therapies. Here we show that targeting a specific G-protein coupled receptor promotes senescence in synovial fibroblasts, enabling amelioration of joint inflammation. Following activation of the melanocortin type 1 receptor (MC1), synovial fibroblasts acquire a senescence phenotype characterized by arrested proliferation, metabolic re-programming and marked gene alteration resembling the remodeling phase of wound healing, with increased matrix metalloproteinase expression and reduced collagen production. This biological response is attained by selective agonism of MC1, not shared by non-selective ligands, and dependent on downstream ERK1\/2 phosphorylation. In vivo, activation of MC1 leads to anti-arthritic effects associated with induction of senescence in the synovial tissue and cartilage protection. Altogether, selective activation of MC1 is a viable strategy to induce cellular senescence, affording a distinct way to control joint inflammation and arthritis.","subset":"pubmed_abstract"} +{"meta":{"pmid":22254857,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Multivariate synchrony modules identified through multiple subject community detection in functional brain networks.\nThe functional connectivity of the human brain may be described by modeling interactions among its neural assemblies as a graph composed of vertices and edges. It has recently been shown that functional brain networks belong to a class of scale-free complex networks for which graphs have helped define an association between function and topology. These networks have been shown to possess a heterogenous structure composed of clusters, dense regions of strongly associated nodes, which represent multivariate relationships among nodes. Network clustering algorithms classify the nodes based on a similarity measure representing the bivariate relationships and similar to unsupervised learning is performed without a priori information. In this paper, we propose a method for partitioning a set of networks representing different subjects and reveal a community structure common to multiple subjects. We apply this community identifying algorithm to functional brain networks during a cognitive control task, in particular the error-related negativity (ERN), to evaluate how the brain organizes itself during error-monitoring.","subset":"pubmed_abstract"} +{"meta":{"pmid":11085224,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The infection of human skin by schistosome cercariae: studies using Franz cells.\nFranz cells (2-chambered, air\/fluid phase static diffusion devices, previously used for the study of drugs across viable human skin) are utilized for the first time to investigate the process of infection of human skin by Schistosoma mansoni cercariae. Skin obtained from cosmetic surgery sources was used in the Franz cells to describe the temporal dynamics of the early interaction of cercariae with skin. At 38 degrees C, about 50% of cercariae applied in water to the epidermal surface of the skin were irreversibly attached within 1 min and after 5 min about 85%, were similarly irrecoverable. The technique also provides the means of following the early penetration path of cercariae by histological methods. Franz cell results on the dynamics of attachment\/early penetration have been compared with those obtained using artificial skin equivalents and non-human mammalian skin models in the context of the physical and chemical differences between these systems and viable human skin. It is concluded that Franz cells provide a convenient system for directly investigating the early phases of S. mansoni cercariae interaction with human skin.","subset":"pubmed_abstract"} +{"meta":{"pmid":7904281,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Depression in late life: the use of clinical characteristics to focus screening efforts.\nThe objective of the study was to identify clinical characteristics associated with depressive symptoms in late life so that screening could focus on elderly patients most likely to benefit from further evaluation. We used cross-sectional screening for significant symptoms of depression using the Center for Epidemiologic Studies Depression scale and identification of patients' clinical characteristics from patient interviews and a computerized medical record. The setting was an academic primary care group practice at an urban ambulatory care center. Participants were 1,633 consecutively consenting patients aged 60 and older who visited the center between January and August 1991. Mean age was 70 years; 72% were women, 32% were White, 47% had less than 8 years of education, and 7% had no health insurance. There were 251 (15%) patients with significant symptoms of depression. Antidepressants were prescribed to 1 in 7 patients with such symptoms, with amitriptyline being the most commonly prescribed. Bivariate analyses indicated that patients with significant symptoms of depression were more likely to be White, female, without health insurance, and were more likely to have probable alcoholism, mild cognitive loss, and to receive narcotics, histamine H2 antagonists, and\/or benzodiazepines. Depressive symptoms were not significantly correlated with age, education, income, or chronic medical conditions. Significant symptoms of depression were common and correlated with several readily available clinical variables. However, these variables lack sufficient discriminatory power to allow for the selective screening of elderly patients most likely to suffer from symptoms of depression. Thus, formal screening for depression among all elderly patients in primary care may be necessary to improve the recognition of this morbid illness.","subset":"pubmed_abstract"} +{"meta":{"pmid":18613788,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Nomenclature of robotic procedures in urology.\nTo standardize nomenclature and acronyms applied to robotic procedures in urology. A review of the literature for robotic procedures in urology was performed. In addition, various acronyms were queried and frequency of use was noted. Additional literature reviewed included articles on standardization of scientific nomenclature used in other disciplines of health care. This topic was discussed within the newly formed working group of urologic robotic surgeons (WURS). There is wide variation in the terminology and use of acronyms for robotic prostate and kidney procedures. The application of robotic, robot, robotic laparoscopic, robot laparoscopic, robotic-assisted, robot-assisted, robotic assisted, robot assisted, robotic-assisted laparoscopic, robot-assisted laparoscopic, robotic assisted laparoscopic, robot assisted laparoscopic, and robotic computer-assisted to procedures such as pyeloplasty and radical prostatectomy is far from uniform or standardized. Queries and searches using acronyms such as RALP, RARP, RRP, and RP yielded publications discussing both prostate and renal procedures applying the same acronyms. There are established databases of abbreviations and acronyms, including ARGH, SaRad, Acromed, and the Stanford Biomedical Abbreviation Server. Standardization of the nomenclature applied to urologic robotic surgery is needed as the robotic literature continues to grow. The recommendation from the Scientific Committee of the Working Group of Urologic Robotic Surgeons is to apply \"robot assisted\" to the already established nomenclature currently used to describe equivalent open procedures. The use of standardized and uniform terminology for procedures performed with robots will facilitate literature search and research efforts in the future. The role of standardized nomenclature for billing purposes remains to be seen.","subset":"pubmed_abstract"} +{"meta":{"pmid":21322565,"dup_signals":{"dup_doc_count":24,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":19}}},"text":"Photosynthetic light-harvesting is tuned by the heterogeneous polarizable environment of the protein.\nIn photosynthesis, special antenna proteins that contain multiple light-absorbing molecules (chromophores) are able to capture sunlight and transfer the excitation energy to reaction centers with almost 100% quantum efficiencies. The critical role of the protein scaffold in holding the appropriate arrangement of the chromophores is well established and can be intuitively understood given the need to keep optimal dipole-dipole interactions between the energy-transferring chromophores, as described by F\u00f6rster theory more than 60 years ago. However, the question whether the protein structure can also play an active role by tuning such dipole-dipole interactions has not been answered so far, its effect being rather crudely described by simple screening factors related to the refractive index properties of the system. Here, we present a combined quantum chemical\/molecular mechanical approach to compute electronic couplings that accounts for the heterogeneous dielectric nature of the protein-solvent environment in atomic detail. We apply the method to study the effect of dielectric heterogeneity in the energy migration properties of the PE545 principal light-harvesting antenna of the cryptomonad Rhodomonas CS24. We find that dielectric heterogeneity can profoundly tune by a factor up to \u223c4 the energy migration rates between chromophore sites compared to the average continuum dielectric view that has historically been assumed. Our results indicate that engineering of the local dielectric environment can potentially be used to optimize artificial light-harvesting antenna systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":30323769,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Associations Between Types of Balance Performance in Healthy Individuals Across the Lifespan: A Systematic Review and Meta-Analysis.\nBackground: The objective of this systematic review and meta-analysis was to quantify and statistically compare correlations between types of balance performance in healthy individuals across the lifespan. Methods: Literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus. Studies were included if they investigated healthy individuals aged \u22656 years and reported measures of static\/dynamic steady-state, proactive, and\/or reactive balance. The included studies were coded as follows: age group, gender, and balance type, test, parameter. Pearson's correlation coefficients were extracted, transformed (i.e., Fisher's z-transformed r z -value), aggregated (i.e., weighted mean r z -value), back-transformed to r-values, classified according to their magnitude, and statistically compared. The methodological quality of each study was assessed using the Appraisal tool for Cross-Sectional Studies. Results: We detected twenty-six studies that examined associations between types of balance and exclusively found small-sized correlations, irrespective of the age group considered. More specifically, the weighted mean r z-values amounted to 0.61 (back-transformed r-value: 0.54) in old adults for the correlation of dynamic steady-state with proactive balance. For correlations between dynamic and static steady-state balance, the weighted mean r z-values amounted to 0.09 in children (r-value: 0.09) and to 0.32 in old adults (r-value: 0.31). Further, correlations of proactive with static steady-state balance revealed weighted mean r z-values of 0.24 (r-value: 0.24) in young adults and of 0.31 (r-value: 0.30) in old adults. Additionally, correlations between reactive and static steady-state balance yielded weighted mean r z-values of 0.21 (r-value: 0.21) in young adults and of 0.19 (r-value: 0.19) in old adults. Moreover, significantly different correlation coefficients (z = 8.28, p < 0.001) were only found for the association between dynamic and static steady-state balance in children (r = 0.09) compared to old adults (r = 0.31). Lastly, we detected trivial to considerable heterogeneity (i.e., 0% \u2264 I2 \u2264 83%) between studies. Conclusions: Our systematic review and meta-analysis showed exclusively small-sized correlations between types of balance performance across the lifespan. This indicates that balance performance seems to be task-specific rather than a \"general ability.\" Further, our results suggest that for assessment\/training purposes a test battery\/multiple exercises should be used that include static\/dynamic steady-state, proactive, and reactive types of balance. Concerning the observed significant age differences, further research is needed to investigate whether they are truly existent or if they are caused by methodological inconsistencies.","subset":"pubmed_abstract"} +{"meta":{"pmid":23749989,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2017-13":1,"unknown":12}}},"text":"A de novo X;8 translocation creates a PTK2-THOC2 gene fusion with THOC2 expression knockdown in a patient with psychomotor retardation and congenital cerebellar hypoplasia.\nWe identified a balanced de novo translocation involving chromosomes Xq25 and 8q24 in an eight year-old girl with a non-progressive form of congenital ataxia, cognitive impairment and cerebellar hypoplasia. Breakpoint definition showed that the promoter of the Protein Tyrosine Kinase 2 (PTK2, also known as Focal Adhesion Kinase, FAK) gene on chromosome 8q24.3 is translocated 2 kb upstream of the THO complex subunit 2 (THOC2) gene on chromosome Xq25. PTK2 is a well-known non-receptor tyrosine kinase whereas THOC2 encodes a component of the evolutionarily conserved multiprotein THO complex, involved in mRNA export from nucleus. The translocation generated a sterile fusion transcript under the control of the PTK2 promoter, affecting expression of both PTK2 and THOC2 genes. PTK2 is involved in cell adhesion and, in neurons, plays a role in axonal guidance, and neurite growth and attraction. However, PTK2 haploinsufficiency alone is unlikely to be associated with human disease. Therefore, we studied the role of THOC2 in the CNS using three models: 1) THOC2 ortholog knockout in C.elegans which produced functional defects in specific sensory neurons; 2) Thoc2 knockdown in primary rat hippocampal neurons which increased neurite extension; 3) Thoc2 knockdown in neuronal stem cells (LC1) which increased their in vitro growth rate without modifying apoptosis levels. We suggest that THOC2 can play specific roles in neuronal cells and, possibly in combination with PTK2 reduction, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28718325,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Collaborative Care for Psychiatric Disorders in Older Adults: A Systematic Review.\nTo evaluate the mode of implementation, clinical outcomes, cost-effectiveness, and the factors influencing uptake and sustainability of collaborative care for psychiatric disorders in older adults. Systematic review. Primary care, home health care, seniors' residence, medical inpatient and outpatient. Studies with a mean sample age of 60 years and older. Collaborative care for psychiatric disorders. PubMed, MEDLINE, Embase, and Cochrane databases were searched up until October 2016. Individual randomized controlled trials and cohort, case-control, and health service evaluation studies were selected, and relevant data were extracted for qualitative synthesis. Of the 552 records identified, 53 records (from 29 studies) were included. Very few studies evaluated psychiatric disorders other than depression. The mode of implementation differed based on the setting, with beneficial use of telemedicine. Clinical outcomes for depression were significantly better compared with usual care across settings. In depression, there is some evidence for cost-effectiveness. There is limited evidence for improved dementia care and outcomes using collaborative care. There is a lack of evidence for benefit in disorders other than depression or in settings such as home health care and general acute inpatients. Attitudes and skill of primary care staff, availability of resources, and organizational support are some of the factors influencing uptake and implementation. Collaborative care for depressive disorders is feasible and beneficial among older adults in diverse settings. There is a paucity of studies on collaborative care in conditions other than depression or in settings other than primary care, indicating the need for further evaluation.","subset":"pubmed_abstract"} +{"meta":{"pmid":7416951,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Gastric volvulus in the newborn.\nA review of the world literature has revealed only 11 cases of gastric volvulus symptomatic in the first month of life. To those 11, this report adds two cases of intrathoracic organoaxial gastric volvulus that were observed in the first week of life and were managed operatively. Gastric volvulus should be considered in the differential diagnosis of newborn infants initially observed to have persisting regurgitation, vomiting, and respiratory distress. The diagnosis can be made with plain thoracoabdominal roentgenograms and confirmed by upper gastrointestinal contrast studies. Prompt surgical management is indicated and should include reduction and fixation of the stomach and repair of associated anomalies. The results of early surgery are excellent.","subset":"pubmed_abstract"} +{"meta":{"pmid":28088864,"dup_signals":{"dup_doc_count":16,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2021-21":2,"2021-04":1,"2020-34":1,"2019-43":1,"2019-35":3,"2019-26":1,"2019-13":1,"2019-04":1,"2021-25":1}}},"text":"Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action.\nAn understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action. Platform validation using cisplatin as a test compound demonstrates quantification of over 10 000 unique, significant molecular changes in less than 30 days. These data provide excellent coverage of known cisplatin-induced molecular changes and previously unrecognized insights into cisplatin resistance. This proof-of-principle study demonstrates the value of this platform as a resource to understand complex cellular responses in a high-throughput manner.","subset":"pubmed_abstract"} +{"meta":{"pmid":26081477,"dup_signals":{"dup_doc_count":79,"dup_dump_count":54,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-14":1,"2023-06":1,"2022-49":3,"2022-40":1,"2022-33":2,"2022-27":2,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2020-10":2,"2020-05":1,"2019-51":1,"2019-47":1,"2019-39":2,"2019-09":2,"2018-47":2,"2018-43":1,"2018-39":2,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":2,"2017-39":2,"2017-34":1,"2017-30":2,"2017-26":1,"2017-22":2,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":2,"2024-30":2,"2024-22":1,"2024-18":1,"2024-10":1,"2017-13":2}}},"text":"Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort.\nThe role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV\/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g\/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g\/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g\/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated\/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV\/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":29361188,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study.\nObesity is often associated with impaired sleep, whereas the impact of body mass index (BMI) at younger age and previous weight gain on sleep problems remains unknown. The present study utilized data from the Swedish EpiHealth cohort study. A total of 15845 participants (45-75 years) filled out an internet-based questionnaire. BMI was calculated from both measured data at study time and self-reported data at age 20 from the questionnaire. Sleep-related symptoms were most common among obese individuals (BMI > 30 kg\/m2). An association between weight gain and sleep problems was found and those with a low BMI at age 20 were most vulnerable to weight gain when it came to risk of sleep problems. Among those who were underweight (BMI < 18.5 kg\/m2) at age 20, weight gain (kg\/year) was associated with difficulties initiating sleep with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex, smoking, alcohol consumption, physical activity, education, and civil status. The corresponding adjusted OR's among those who had been normal weight (BMI 18.5-24.99) and overweight (BMI 25-29.99 kg\/m2) at age 20 were 1.89 (1.47-2.45) and 1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring were most strongly related to weight gain among those who were underweight at age 20 with decreasing odds with increasing BMI at that age. Sleep problems are related to weight gain and obesity. The impact of weight is most pronounced among those who had a low BMI when young.","subset":"pubmed_abstract"} +{"meta":{"pmid":29524948,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"BRIC Health Systems and Big Pharma: A Challenge for Health Policy and Management.\nBRIC nations - Brazil, Russia, India, and China - represent 40% of the world's population, including a growing aging population and middle class with an increasing prevalence of chronic disease. Their healthcare systems increasingly rely on prescription drugs, but they differ from most other healthcare systems because healthcare expenditures in BRIC nations have exhibited the highest revenue growth rates for pharmaceutical multinational corporations (MNCs), Big Pharma. The response of BRIC nations to Big Pharma presents contrasting cases of how governments manage the tensions posed by rising public expectations and limited resources to satisfy them. Understanding these tensions represents an emerging area of research and an important challenge for all those who work in the field of health policy and management (HPAM).","subset":"pubmed_abstract"} +{"meta":{"pmid":19487266,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2022-33":1,"2021-43":1,"2021-31":1,"2021-21":1,"2020-50":1,"2020-45":1,"2020-24":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2023-23":1}}},"text":"Health-related quality of life and its relationship to patient disease course in childhood-onset systemic lupus erythematosus.\nTo (1) estimate the health-related quality of life (HRQOL) of children with childhood-onset systemic lupus erythematosus (cSLE) and compare it to that of normative cohorts; (2) assess the relationship of HRQOL with cSLE disease activity and damage; and (3) determine the effects of changes of disease activity on HRQOL. Patients with cSLE (n = 98) followed every 3 months completed HRQOL measures, the Pediatric Quality of Life Inventory Generic Core scale (PedsQL-GC), the Rheumatology Module (PedsQL-RM), and the Child Health Questionnaire (CHQ). The British Isles Lupus Activity Group Index (BILAG) was used to measure organ-system-specific disease activity. Physicians rated the course of cSLE between visits. At baseline, mean (standard deviation, SD) score [parent report] of the PedsQL-GC and the PedsQL-RM was 75 (17) and 79 (14), respectively; the mean (SD) of the CHQ physical summary score (CHQ-PHS) was 49 (7) and that of the CHQ psychological summary score was 42 (12). Higher BILAG scores, especially in the general, musculoskeletal, neurological, and vascular, but not the mucocutaneous, renal, cardiovascular, or hematological BILAG domains, were associated with a significantly lower HRQOL. Patients with damage had lower HRQOL than those without damage. All HRQOL measures included were at most modestly responsive to clinically important changes with cSLE. HRQOL with cSLE is significantly lower than that reported in healthy populations. Organ-specific involvement with cSLE has a differential effect on HRQOL. Higher disease activity and damage are associated with significantly lower HRQOL as measured by the PedsQL-RM and the CHQ-PHS, and worsening of cSLE leads to a further decline.","subset":"pubmed_abstract"} +{"meta":{"pmid":19886503,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":13}}},"text":"Do modified habitats have direct or indirect effects on epifauna?\nReplacing natural habitats with artificial structures such as pier-pilings, jetties, and seawalls has important consequences to abundances of biota. It is, however, not often known whether these are direct (the novel habitat alters abundances of some species) or indirect (the novel habitat directly alters some aspect of the behavior or ecology of some species, which, in turn, alter abundances of other species). Marine animals in some modified habitats in Sydney Harbour provide experimental opportunities to test hypotheses to distinguish between direct and indirect processes. Covers of bryozoans and hydroids were greater on kelp growing on pilings than on kelp growing on natural reefs. The epifauna may be affected directly by the pilings or indirectly, i.e., the structure affects characteristics of the kelp which, in turn, influence covers of epifauna. Thus, differences in covers of epifauna on kelp can be due to: (1) factors associated with the primary habitats (pilings vs. reefs), (2) differences between characteristics of the kelp found in each habitat, or (3) an interaction between these factors (habitat and\/or type of kelp). Kelp were experimentally transplanted between pilings and reefs, demonstrating that properties of the habitat directly affected covers of epifauna, which were not influenced by the type of kelp that grows on pilings or rocky reefs. Manipulative experiments to unconfound multiple components of habitats influencing disturbances to biota are needed to understand human impacts on natural systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":26861793,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2021-31":1,"2021-25":1,"2020-50":1,"2020-34":1,"2020-29":1,"2020-24":1,"2020-10":1,"2019-47":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":2,"2019-09":1,"2018-51":2,"2018-17":2,"2018-05":1,"2017-43":1,"2021-49":1}}},"text":"Identification of Evidence for Key Parameters in Decision-Analytic Models of Cost Effectiveness: A Description of Sources and a Recommended Minimum Search Requirement.\nThis paper proposes recommendations for a minimum level of searching for data for key parameters in decision-analytic models of cost effectiveness and describes sources of evidence relevant to each parameter type. Key parameters are defined as treatment effects, adverse effects, costs, resource use, health state utility values (HSUVs) and baseline risk of events. The recommended minimum requirement for treatment effects is comprehensive searching according to available methodological guidance. For other parameter types, the minimum is the searching of one bibliographic database plus, where appropriate, specialist sources and non-research-based and non-standard format sources. The recommendations draw on the search methods literature and on existing analyses of how evidence is used to support decision-analytic models. They take account of the range of research and non-research-based sources of evidence used in cost-effectiveness models and of the need for efficient searching. Consideration is given to what constitutes best evidence for the different parameter types in terms of design and scientific quality and to making transparent the judgments that underpin the selection of evidence from the options available. Methodological issues are discussed, including the differences between decision-analytic models of cost effectiveness and systematic reviews when searching and selecting evidence and comprehensive versus sufficient searching. Areas are highlighted where further methodological research is required.","subset":"pubmed_abstract"} +{"meta":{"pmid":21975894,"dup_signals":{"dup_doc_count":22,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2018-26":2,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":2,"2017-17":1}}},"text":"Contextualizing SEGUE: Evaluating Residents' Communication Skills Within the Framework of a Structured Medical Interview.\nThe SEGUE (Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter) Framework is a checklist-style rating scale to facilitate the teaching and assessment of communication skills in medical learners. It has been used for over 15 years, and it is recommended in the Accreditation Council for Graduate Medical Education toolbox of assessment methods for resident training. When it was developed, its ability to provide objective scoring was a substantial improvement over global ratings. In this article we describe the strengths and weaknesses of the SEGUE Framework. We highlight one residency program's experience with using the SEGUE Framework to evaluate residents' communication skills. Specifically, we cite previous studies and describe our own analysis of resident interviewing performance that demonstrates how the SEGUE Framework did not distinguish between different levels of interviewing skill level in our sample. Two case examples illustrate how the SEGUE Framework is not an ideal instrument to measure either the quality or the process of medical interviews. Therefore, we propose a new method of contextualized assessment that builds on the SEGUE Framework. Our system evaluates discrete interviewing behaviors within the context of an ambulatory medical interview. We describe our interview structure, as well as a new instrument (the Wy-Mii, pronounced \"why me\"), to assess both communication and interpersonal skills. We expect that our new method of contextualized assessment will better differentiate between beginning and advanced levels of medical interviewing skills for residents.","subset":"pubmed_abstract"} +{"meta":{"pmid":28007463,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Electroretinographic anomalies in medicated and drug free patients with major depression: Tagging the developmental roots of major psychiatric disorders.\nThe retina is tagged as an approachable part of the brain due to its common embryonic origin and appears as a promising site of investigation for psychiatric disorders. Retinal function is assessed best with the electroretinogram (ERG), which was obtained in a large sample of patients with major depressive disorder and matched controls. ERG cone and rod luminance response functions were recorded in non-dilated eyes in 100 major depressive disorder patients (MDD) and 100 controls, (mean age of 42.8 and 40.9y. o. respectively). Amongst MDD patients, 17 were drug free (mean age 41.2y. o). In medicated patients, at the cone level, a prolonged b-wave was observed (p\u22640.01). In drug free patients a prolonged b-wave was discovered only when averaging the implicit time of the 3 highest b-wave amplitudes of the photopic hill. For the medicated patients, the mixed rods\/cones a-wave was reduced (p=0.01) whereas a trend (p=0.06) was observed for the pure rod b-wave (reduced) and the mixed rods\/cones (reduced and prolonged; p=0.05). In drug free patients, a similar pattern could be observed in terms of effect sizes. Overall, medicated and drug free MDD patients shared some deficits suggesting that some anomalies are present above and beyond the effect of medication. Of interest, the prolonged cone and reduced rod amplitude were reported by our group in schizophrenia patients, suggesting a common neurodevelopmental root of major psychiatric disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":8823261,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis.\nRadiation-induced emesis is one of the most disturbing side effects of total body irradiation (TBI). To evaluate the efficacy and to determine the best schedule of granisetron (a selective 5-hydroxytryptamine3 serotonin receptor antagonist) administration in the prevention of radiation-induced nausea and vomiting, we conducted a trial involving patients receiving single-dose TBI before bone marrow transplantation (BMT). Thirty-six patients with non-Hodgkin's lymphoma (n = 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chronic myeloid leukemia (n = 3) referred to our department between March 1992 and February 1994 were enrolled in this study to assess the efficacy of granisetron during single-dose TBI before autologous BMT (n = 26), allogeneic BMT (n = 8), or syngeneic BMT (n = 2). The male-to-female ratio was 22:14 (1.57), and the mean age was 41 +\/- 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg\/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6. All patients received single-dose TBI (10 Gy administered to the midplane at L4, and 8 Gy to the lungs). The mean instantaneous and average dose rates were 0.039 +\/- 0.012 Gy\/min (range 0.031-0.058), and 0.025-0.006 Gy\/min (range 2.08-3.96), respectively. Granisetron was administered 30-45 min before TBI according to two different modalities: a total dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%). Depending on the BMT teams, hyperdiuresis was continued (n = 19, 53%) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were assessed during the TBI session and the following 12 h, and were scored as follows: S1 = no nausea or vomiting; S2 = moderate nausea; S3 = severe nausea and\/or single episode of vomiting; and S4 = multiple episodes of vomiting. During TBI, 18 (50%) patients were scored as complete responders (S1), 1 (3%) as a major responder (S2), 9 (25%) as minor responders (S3), and 8 (22%) as nonresponders (S4). During the following 12 h, 28 (78%) patients were free of severe nausea and vomiting (S1 or S2), whereas 8 (22%) vomited (S3 or S4). In univariate analyses, the 12-h probability of emesis was significantly higher in patients undergoing hyperdiuresis (63% vs. 30%; p = 0.05), and in patients older than 45 years (65% for age > 45 vs. 33% for age < or = 45; p = 0.05). The probability of S3 or S4 emesis was 50% with Treatment A and 47% with Treatment B (p = 0.86). Sex, body weight, and type of conditioning chemotherapy did not influence the 12-h probability of emesis. Multivariate analysis revealed that hyperdiuresis (p = 0.02) and Treatment A (p = 0.04) were independently associated with radiation-induced emesis, whereas sex (p = 0.85), body weight (p = 0.13), age (p = 0.12), and type of conditioning chemotherapy (p = 0.92) were not. No early toxicity related to granisetron was observed. Granisetron is a well-tolerated and effective antiemetic agent that can be used as monotherapy during single-dose TBI. Good control of nausea and vomiting is obtained with this antiemetic drug, and its effect is increased when hyperdiuresis is suspended during TBI.","subset":"pubmed_abstract"} +{"meta":{"pmid":27996298,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Genetic Interactions in Nonsyndromic Orofacial Clefts in Europe-EUROCRAN Study.\nNonsyndromic cleft lip with or without cleft palate (nsCL\u00b1P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated gene-environment and gene-gene joint effects in a large multicenter study of case-parent triads. The nsCL\u00b1P or nsCP triads were recruited in 11 European countries between 2001 and 2005. We collected DNA samples from infants and from their mothers and fathers, and mothers completed a questionnaire on exposures, including smoking and folic acid supplement use during pregnancy. We used log-linear regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between nsCL\u00b1P or nsCP and variants in MTHFR, MTHFD1, TGFA, SATB2, and MSX1, stratifying by environmental or genetic factors. We obtained genotype and exposure data for 728 nsCL\u00b1P triads and 292 nsCP triads. In male infants, there was no association between the mother's homozygous MSX1 p(CA) *4\/*4 genotype and nsCL\u00b1P (RR, 0.98; 95% CI, 0.63-1.54), but this maternal genotype resulted in a doubling of risk for female infants (RR, 2.21; 95% CI, 1.13-4.34). There was evidence suggestive of gene-gene joint-effects between MTHFR-TGFA for nsCP but not for nsCL\u00b1P. Although we chose the genes and their variants and putative joint effects based on associations previously reported in the literature, we replicated few associations. These results do not provide evidence supporting associations between these genes and oral clefts in European populations, although gene-environment and gene-gene interactions could play a role in oral cleft etiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":19583207,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Crystallographic snapshots of cyanide- and water-bound C-clusters from bifunctional carbon monoxide dehydrogenase\/acetyl-CoA synthase.\nNickel-containing carbon monoxide dehydrogenases (CODHs) reversibly catalyze the oxidation of carbon monoxide to carbon dioxide and are of vital importance in the global carbon cycle. The unusual catalytic CODH C-cluster has been crystallographically characterized as either a NiFe(4)S(4) or a NiFe(4)S(5) metal center, the latter containing a fifth, additional sulfide that bridges Ni and a unique Fe site. To determine whether this bridging sulfide is catalytically relevant and to further explore the mechanism of the C-cluster, we obtained crystal structures of the 310 kDa bifunctional CODH\/acetyl-CoA synthase complex from Moorella thermoacetica bound both with a substrate H(2)O\/OH(-) molecule and with a cyanide inhibitor. X-ray diffraction data were collected from native crystals and from identical crystals soaked in a solution containing potassium cyanide. In both structures, the substrate H(2)O\/OH(-) molecule exhibits binding to the unique Fe site of the C-cluster. We also observe cyanide binding in a bent conformation to Ni of the C-cluster, adjacent the substrate H(2)O\/OH(-) molecule. Importantly, the bridging sulfide is not present in either structure. As these forms of the C-cluster represent the coordination environment immediately before the reaction takes place, our findings do not support a fifth, bridging sulfide playing a catalytic role in the enzyme mechanism. The crystal structures presented here, along with recent structures of CODHs from other organisms, have led us toward a unified mechanism for CO oxidation by the C-cluster, the catalytic center of an environmentally important enzyme.","subset":"pubmed_abstract"} +{"meta":{"pmid":10975368,"dup_signals":{"dup_doc_count":18,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2017-39":1,"2016-50":2,"2016-44":3,"2016-36":2,"2016-30":1,"2015-40":2,"2015-35":1,"2015-22":1,"2017-43":1}}},"text":"Cantor set fiber Bragg grating\nThe theory of fractals has already been applied to many fields in science, such as physics, biology, and chemistry. One of the most commonly used fractals in these applications is the Cantor set. Novel fiber Bragg gratings are proposed that combine the present technology of fiber Bragg gratings with the theory of Cantor sets. The principal goal of this work is to analyze how Cantor sets, applied to gratings, can alter their reflectivity spectra. Specifically, it is observed that, as the order of the Cantor set increases, the bandpass reflectivity spectra of these gratings broaden and evolve into more-complex patterns. Also, self-similarity properties can be observed in the spectra of these gratings. Numerical examples demonstrate variations in the spectra of these structures as the fractal order increases.","subset":"pubmed_abstract"} +{"meta":{"pmid":12396639,"dup_signals":{"dup_doc_count":13,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"[End-stage renal disease among patients in a referral hospital in El Salvador].\nEl Salvador is a country with high mortality from end-stage renal disease (ESRD). The objective of this study was to determine the epidemiological characteristics of a series of new cases of ESRD seen in a referral hospital in the country. A cross-sectional study was conducted of all the new cases that initiated chronic dialysis between November 1999 and March 2000. Using a personal interview, data were obtained on the patients' clinical, demographic, and occupational characteristics, among others. During the five months that the study lasted, 205 new cases of ESRD were observed. Among the 202 interviewees, two groups were clearly distinguished. One group, of 67 patients (33%), had known risk factors for ESRD, similar to those for developed countries (basically, diabetes mellitus, hypertension, and chronic consumption of non-steroidal anti-inflammatories). Another group of 135 patients (67%) had unusual characteristics that were not associated with the known risk factors. The majority of the patients in this second group were male, farmers, residents of coastal areas or areas next to rivers, and some years before had been exposed, without adequate protection, to agricultural insecticides or pesticides through their work. We have identified an important group of patients with ESRD who seem to lack a cause for their disease. Their special characteristics make it possible to suspect a relationship with the occupational exposure to insecticides or pesticides. New studies are needed in order to confirm this hypothesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29380412,"dup_signals":{"dup_doc_count":25,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"From Drug Safety to Drug Security: A Contemporary Shift in the Policing of Health.\nThe counterfeiting of medication is increasingly seen as a major threat to health, especially in the light of both the everyday reliance on and a broadening of world-wide access to pharmaceuticals. Exaggerated or real, this threat has inaugurated, this article argues, a shift from a drug safety regime to a drug security regime that governs the flow of pharmaceuticals and brings together markets, police, and health actors in new ways. This entails a shift from soft disciplinary means aimed at incremental and continued inclusion of defaulters, to one of drastically sovereign measures of exclusion and banishment aimed at fake goods and the people associated with them, in the name of health. Through a multi-sited ethnographic study, this article shows how such new drug security efforts play themselves out especially in (South) Africa, highlighting a modus operandi of spectacular performativity and of working through suspicion and association rather than factuality, producing value less so for those in need of health than for a petty security industry itself.","subset":"pubmed_abstract"} +{"meta":{"pmid":15528785,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Colorectal carcinogenesis: MSI-H versus MSI-L.\nMicrosatellite instability (MSI) is a well-recognized phenomenon that is classically a feature of tumors in the hereditary non-polyposis colorectal syndrome. Ten to 15% of sporadic colorectal cancers, however, will have MSI. Microsatellite unstable tumors can be divided into two distinct MSI phenotypes: MSI-high (MSI-H) and MSI-low (MSI-L). MSI sporadic colorectal cancers with a high level of MSI (MSI-H) form a well defined group with distinct clinicopathologic features characterized by an overall better long-term prognosis. These sporadic MSI-H colorectal tumors most often arise from the epigenetic silencing of the mismatch repair gene MLH1. In contrast, MSI-L colorectal tumors have not been shown to differ in their clinicopathologic features or in most molecular features from microsatellite stable (MSS) tumors. Unlike MSI-H tumors, MSI-L tumors appear to arise through the chromosomal instability carcinogenesis pathway, similar to MSS tumors. Some groups have reported more frequent mutations in K-ras and in the methylation of methylguanine transferase in MSI-L tumors, but others have questioned these findings. Therefore, although the use of the MSI-L category is widespread, there continues to be some debate as to whether a discrete MSI-L group truly exists. Rather, it has been suggested that MSI-L tumors differ quantitatively from MSS tumors but do not differ qualitatively. Future studies will need to evaluate the specific mutations in non-MSI-H tumors in an attempt to sub-classify MSI-L tumors with regard to MSS tumors so that subtle differences between these two sub-groups can be identified.","subset":"pubmed_abstract"} +{"meta":{"pmid":28747371,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa.\nOur objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of \u226599% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of \u226599% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.","subset":"pubmed_abstract"} +{"meta":{"pmid":31075749,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-06":1,"2022-49":1,"2021-25":1,"2020-34":1,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-26":1,"2023-50":1,"2024-10":1}}},"text":"Complex relationships between greenness, air pollution, and mortality in a population-based Canadian cohort.\nEpidemiological studies have consistently demonstrated that exposure to fine particulate matter (PM2.5) is associated with increased risks of mortality. To a lesser extent, a series of studies suggest that living in greener areas is associated with reduced risks of mortality. Only a handful of studies have examined the interplay between PM2.5, greenness, and mortality. We investigated the role of residential greenness in modifying associations between long-term exposures to PM2.5 and non-accidental and cardiovascular mortality in a national cohort of non-immigrant Canadian adults (i.e., the 2001 Canadian Census Health and Environment Cohort). Specifically, we examined associations between satellite-derived estimates of PM2.5 exposure and mortality across quintiles of greenness measured within 500 m of individual's place of residence during 11 years of follow-up. We adjusted our survival models for many personal and contextual measures of socioeconomic position, and residential mobility data allowed us to characterize annual changes in exposures. Our cohort included approximately 2.4 million individuals at baseline, 194,270 of whom died from non-accidental causes during follow-up. Adjustment for greenness attenuated the association between PM2.5 and mortality (e.g., hazard ratios (HRs) and 95% confidence intervals (CIs) per interquartile range increase in PM2.5 in models for non-accidental mortality decreased from 1.065 (95% CI: 1.056-1.075) to 1.041 (95% CI: 1.031-1.050)). The strength of observed associations between PM2.5 and mortality decreased as greenness increased. This pattern persisted in models restricted to urban residents, in models that considered the combined oxidant capacity of ozone and nitrogen dioxide, and within neighbourhoods characterised by high or low deprivation. We found no increased risk of mortality associated with PM2.5 among those living in the greenest areas. For example, the HR for cardiovascular mortality among individuals in the least green areas was 1.17 (95% CI: 1.12-1.23) compared to 1.01 (95% CI: 0.97-1.06) among those in the greenest areas. Studies that do not account for greenness may overstate the air pollution impacts on mortality. Residents in deprived neighbourhoods with high greenness benefitted by having more attenuated associations between PM2.5 and mortality than those living in deprived areas with less greenness. The findings from this study extend our understanding of how living in greener areas may lead to improved health outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":7807017,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes.\nWe and others have previously reported that melanoma-specific, cytotoxic T lymphocytes (CTL) define a minimum of six class I-presented peptide epitopes common to most HLA-A2+ melanomas. Here we show that three of these peptide epitopes are coordinately recognized by a CTL clone obtained by limiting dilution from the peripheral blood of an HLA-A2+ melanoma patient. Tandem mass spectrometry was used to characterize and sequence one of these three naturally processed melanoma peptides. One of the potential forms of the deduced peptide sequence (XXTVXXGVX, X = I or L) matches positions 32-40 of the recently identified melanoma gene MART-1\/Melan-A. This peptide (p939; ILTVILGVL) binds to HLA-A2 with an intermediate-to-low affinity and is capable of sensitizing the HLA-A2+ T2 cell line to lysis by CTL lines and clones derived from five different melanoma patients. A relative high frequency of anti-p939-specific effector cells appear to be present in situ in HLA-A2+ melanoma patients, since p939 is also recognized by freshly isolated tumor infiltrating lymphocytes. p939 represents a good candidate for the development of peptide-based immunotherapies for the treatment of patients with melanoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":28640306,"dup_signals":{"dup_doc_count":30,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2022-40":1,"2022-33":1,"2021-31":1,"2021-21":1,"2020-50":1,"2020-45":3,"2020-40":1,"2020-34":1,"2020-24":1,"2019-35":1,"2018-51":1,"2018-26":2,"2018-22":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":2,"2017-39":3,"2022-49":1,"2024-10":1}}},"text":"Tip-enhanced Raman spectroscopy - from early developments to recent advances.\nAn analytical technique operating at the nanoscale must be flexible regarding variable experimental conditions while ideally also being highly specific, extremely sensitive, and spatially confined. In this respect, tip-enhanced Raman scattering (TERS) has been demonstrated to be ideally suited to, e.g., elucidating chemical reaction mechanisms, determining the distribution of components and identifying and localizing specific molecular structures at the nanometre scale. TERS combines the specificity of Raman spectroscopy with the high spatial resolution of scanning probe microscopies by utilizing plasmonic nanostructures to confine the incident electromagnetic field and increase it by many orders of magnitude. Consequently, molecular structure information in the optical near field that is inaccessible to other optical microscopy methods can be obtained. In this general review, the development of this still-young technique, from early experiments to recent achievements concerning inorganic, organic, and biological materials, is addressed. Accordingly, the technical developments necessary for stable and reliable AFM- and STM-based TERS experiments, together with the specific properties of the instruments under different conditions, are reviewed. The review also highlights selected experiments illustrating the capabilities of this emerging technique, the number of users of which has steadily increased since its inception in 2000. Finally, an assessment of the frontiers and new concepts of TERS, which aim towards rendering it a general and widely applicable technique that combines the highest possible lateral resolution and extreme sensitivity, is provided.","subset":"pubmed_abstract"} +{"meta":{"pmid":21533024,"dup_signals":{"dup_doc_count":17,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-18":1,"unknown":8}}},"text":"Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci.\nSoluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 \u00d7 10(-9)), PNPLA3 (rs738409, P = 5.8 \u00d7 10(-9)), RELA (rs1049728, P = 2.7 \u00d7 10(-16)), and SH2B3 (rs3184504, P = 2.9 \u00d7 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.","subset":"pubmed_abstract"} +{"meta":{"pmid":22675580,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Complete genome sequence of Hirschia baltica type strain (IFAM 1418(T)).\nThe family Hyphomonadaceae within the Alphaproteobacteria is largely comprised of bacteria isolated from marine environments with striking morphologies and an unusual mode of cell growth. Here, we report the complete genome sequence Hirschia baltica, which is only the second a member of the Hyphomonadaceae with a published genome sequence. H. baltica is of special interest because it has a dimorphic life cycle and is a stalked, budding bacterium. The 3,455,622 bp long chromosome and 84,492 bp plasmid with a total of 3,222 protein-coding and 44 RNA genes were sequenced as part of the DOE Joint Genome Institute Program CSP 2008.","subset":"pubmed_abstract"} +{"meta":{"pmid":24748279,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Decreased resting functional connectivity after traumatic brain injury in the rat.\nTraumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.","subset":"pubmed_abstract"} +{"meta":{"pmid":28844614,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":14}}},"text":"Responsiveness of gait analysis parameters in a cohort of 71 CMT subjects.\nDetection of worsening in the slowly progressive Charcot-Marie-Tooth disease (CMT) is difficult. As previous clinical scales showed low responsiveness, novel outcome measures are under study, including innovative approaches such as quantitative muscle MRI and instrumented movement analysis. Since gait analysis proved able to reliably quantify CMT locomotor deficits, we aimed to explore whether it can be a sensitive-to-change outcome measure in CMT studies. Clinical and biomechanical evaluations were performed in 71 CMT subjects at baseline and after a mean (\u00b1sd) of 28.9 \u00b1 9.5 months. Locomotor tasks included natural walking, ascending and descending steps. Instrumented analysis of such tasks provided indexes related to muscle strength (kinetic parameters) and joint movement (kinematic parameters). Parameter responsiveness was expressed as Standardized Response Mean (SRM). Considering the whole CMT group, several parameters showed moderate responsiveness; subgrouping subjects according to disease severity allowed reaching high responsiveness (SRM >0.80). CMT Examination Score showed moderate responsiveness (SRM 0.53) in the minimally affected group; kinematic parameters were more responsive in this group, whereas kinetic parameters in the most severely affected one. Biomechanical parameters can represent suitable outcome measures for CMT by showing moderate-to-high responsiveness. These data suggest that appropriate selection of patient population and outcome measures is crucial for clinical trials' design.","subset":"pubmed_abstract"} +{"meta":{"pmid":19000003,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A novel homeobox-like gene associated with reaction to stripe rust and powdery mildew in common wheat.\nStripe rust and powdery mildew, caused by Puccinia striiformis f. sp. tritici and Blumeria graminis f. sp. tritici, respectively, are severe diseases in wheat (Triticum aestivum) worldwide. In our study, differential amplification of a 201-bp cDNA fragment was obtained in a cDNA-amplified fragment length polymorphism (AFLP) analysis between near-isogenic lines Yr10NIL and Avocet S, inoculated with P. striiformis f. sp. tritici race CYR29. A full-length cDNA (1,357 bp) of a homeobox-like gene, TaHLRG (GenBank accession no. EU385606), was obtained in common wheat based on the sequence of GenBank accession AW448633 with high similarity to the above fragment. The genomic DNA sequence (2,396 bp) of TaHLRG contains three exons and two introns. TaHLRG appeared to be a novel homeobox-like gene, encoding a protein with a predicted 66-amino-acid homeobox domain. It was involved in race-specific responses to stripe rust in real-time quantitative polymerase chain reaction (PCR) analyses with Yr9NIL, Yr10NIL, and Avocet S. It was also associated with adult-plant resistance to stripe rust and powdery mildew based on the field trials of doubled haploid lines derived from the cross Bainong 64\/Jingshuang 16 and two F(2:3) populations from the crosses Lumai 21\/Jingshuang 16 and Strampelli\/Huixianhong. A functional marker, THR1 was developed based on the sequence of TaHLRG and located on chromosome 6A using a set of Chinese Spring nulli-tetrasomic lines.","subset":"pubmed_abstract"} +{"meta":{"pmid":1842361,"dup_signals":{"dup_doc_count":36,"dup_dump_count":30,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":2,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-24":1,"2018-51":1,"2018-39":1,"2018-26":2,"2018-13":1,"2018-05":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2023-40":1,"2024-10":1,"2017-13":1,"2024-26":1}}},"text":"The early development of the frog retinotectal projection.\nThe guidance of retinal ganglion cell axons has been investigated in embryos of the frog Xenopus. During the initial development of the brain a series of axon tracts are laid down forming a basic 'scaffold' or framework. Retinal axons grow through one of these tracts, the tract of the post-optic commissure (tPOC). This is the only tract that extends through the rostral part of the brain at these early stages of development. The origin and development of the tPOC has been studied using antibodies which label neurons at their earliest stages of differentiation. The first sign of the tPOC is a chain of neurons which differentiate simultaneously in the caudolateral part of the diencephalon. Axons from these neurons grow the short distance between adjacent cells interlinking the chain to form a descending tract. A series of other axon projections are then added to the tPOC, each of which is segregated into a particular subregion of the tract. Retinal axons are added to the tract approximately 18 h after its formation. They grow in the sub-pial part of the tract and always occupy the rostral-most edge. Retinal axons follow the tract to the region of the developing tectum where they leave, turn dorsally, and terminate. The reliance of retinal axons on this pre-existing pathway has been demonstrated by experimentally altering the course of the tPOC during its early development. The caudo-lateral wall of the diencephalon has been rotated through 90 degrees at a stage just before the tPOC neurons differentiate. Confirmation of the predicted alteration in the course of the tPOC has been made using immunocytochemistry. In such manipulated brains, retinal axons maintain their strong affinity for the rostral edge of the tPOC, following its altered course through the diencephalon.","subset":"pubmed_abstract"} +{"meta":{"pmid":12883962,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-22":1,"unknown":9}}},"text":"The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus.\nIt has long been known that very acidic conditions can be found in degenerate discs. The effect of these acid conditions on matrix turnover are, however, unknown. This study aimed to examine the effect of acidity on production of matrix components and on agents which break down the matrix in order to gain insight into the effect of pathological values of pH on matrix turnover. Cells were isolated from the nucleus of bovine discs and from bovine articular cartilage, embedded in alginate beads and cultured at pH levels maintained within the ranges seen in normal and pathological discs: pH 7.4-pH 6.3 for 48 h. Rates of sulphated glycosaminoglycan (GAG) and protein synthesis were measured, as well as rates of production of some agents involved in matrix breakdown, i.e. total and activated matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). The results showed that acid conditions had a profound effect on cell matrix turnover; at pH 6.4, total production of most species measured was inhibited by more than 50% compared to production at pH 7.2; production of sulphated GAGs and of TIMP-1 fell by >90%. However production of active metalloproteinases by disc cells was relatively insensitive to pH, with activity at pH 6.3 not statistically different from that at pH 7.2. These findings indicate that exposure to acid conditions appears particularly deleterious for the disc matrix, as it inhibits the disc cells from synthesising functionally important molecules such as the sulphated GAGs but does not prevent the production of agents able to degrade matrix components. The low values of pH seen in some degenerate discs are thus likely to be involved in breakdown of the disc matrix.","subset":"pubmed_abstract"} +{"meta":{"pmid":33804216,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":11}}},"text":"Isolation and Characterisation of Bacteriophages with Activity against Invasive Non-Typhoidal Salmonella Causing Bloodstream Infection in Malawi.\nIn recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in Sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting S. Typhimurium and S. Enteritidis, from water sources in Malawi and the UK. The phages were classified in three major phylogenetic clusters that were geographically distributed. In terms of host range, Cluster 1 phages were able to infect all bacterial hosts tested, whereas Clusters 2 and 3 had a more restricted profile. Cluster 3 contained two sub-clusters, and 3.b contained the most novel isolates. This study represents the first exploration of the potential for phages to target the lineages of Salmonella that are responsible for bloodstream infections in Sub-Saharan Africa.","subset":"pubmed_abstract"} +{"meta":{"pmid":30246526,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Fe-N-C Artificial Enzyme: Activation of Oxygen for Dehydrogenation and Monoxygenation of Organic Substrates under Mild Condition and Cancer Therapeutic Application.\nDeveloping highly efficient biomimetic catalysts that directly use O2 as the terminal oxidant to dehydrogenate and monoxygenate substrates with high selectivity under mild conditions has long been pursued but rarely achieved yet. Herein, we report that heterogeneous Fe-N-C, which is commonly used as an electrocatalyst for oxygen reduction reaction, had unusual biomimetic catalytic activity in both dehydrogenation and monoxygenation of a series of organic molecules (\u223c100% selectivity) by directly using O2. The Fe-N x center was verified to be the active site that reductively activated O2 by spontaneously generating specific reactive oxygen species (ROS) (1O2, O2\u2022-, and H2O2). Aided by these ROS, under physiological conditions, the Fe-N-C was further successfully exampled to kill proliferative lung cancer cells. Fe-N-C had several striking superior features with respect to natural enzymes, classical heterogeneous nanozymes, and homogeneous artificial enzymes incapable of working under harsh conditions (extreme pH and high temperature), ease of separation and recycling, and direct use of O2. It would open up a new vista of Fe-N-C as an artificial enzyme in biomimetic catalysis, ranging from fundamental simulation of oxidase\/oxygenase metabolism to industrial oxidation processes and to disease treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":22174203,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"Osteochondral destruction in pigmented villonodular synovitis during the clinical course.\nIn pigmented villonodular synovitis (PVNS), some cases recur and progress to osteochondral destruction. The aim of our study was to clarify the occurrence of osteochondral destruction according to the location of PVNS during the clinical course. Seventy-two patients with PVNS (43 female, 29 male) with a mean age of 40 years (range 3-87 yrs) had been referred to our institutions. Factors influencing the occurrence of osteochondral destruction were investigated. Mean followup was 60 months (range 12-190 mo). Adjacent bone change occurred in 24 (42%) of 57 patients, who were evaluated at the time of the first consultation. Eight (89%) of 9 patients with hip lesions initially had bone lesions, significantly more frequently than those with other lesions (p = 0.038). Duration of symptoms was significantly correlated with the occurrence of bone lesions in diffuse knee lesions (p = 0.005). During followup, patients with location in the knee had a significantly higher incidence of osteoarthritic change (73%) compared to those with foot and ankle involvement (p = 0.027). Re-operation was more frequently required for knee lesions due to the high recurrence rate (32%). Patients who required re-operation had significantly more marked osteoarthritic change in knees (p = 0.001) during followup than those who did not. For PVNS arising in knees, repeated recurrences followed by re-operation resulted in the progression of osteoarthritic change. PVNS arising in hips, feet, and ankles developed bone lesions initially, probably due to the limited volume of these joints. The indications for re-operation for recurrent knee lesions require careful consideration regarding progression of osteoarthritic change.","subset":"pubmed_abstract"} +{"meta":{"pmid":2398007,"dup_signals":{"dup_doc_count":14}},"text":"Adsorption and desorption of noble gases on activated charcoal: I. 133Xe studies in a monolayer and packed bed.\nDetailed desorption studies using petroleum-based activated charcoals were conducted in monolayers and packed beds. Less extensive studies were conducted on several other types of charcoal. Kinetic studies, using 133Xe, demonstrated the existence of a micropore volume with entrance capillaries that together determined the response characteristics of charcoal to external concentration gradients of tracer gases. This new two-phase model, composed of micropores and entrance capillaries, describes the desorption dynamics of an adsorbed gas in the presence of water vapor. Condensed water vapor in the entrance capillaries of the charcoal reduced the effective pore radius and increased the diffusion half-time. Water could also adversely affect the integrating capability of the charcoal dramatically if the adsorbed water completely blocked the entrance capillaries. The amount of adsorbed water required to block the capillaries varied with the charcoal type and was termed here as the \"break-point.\" The desorption parameters measured in this work can be used to design an improved passive Rn monitor to effectively integrate during a 3-7 d exposure period by eliminating the adverse effects of water vapor. The improved canister design would provide more accurate and reproducible measurements of indoor Rn concentrations than are currently available.","subset":"pubmed_abstract"} +{"meta":{"pmid":20181084,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2024-26":1,"unknown":7}}},"text":"Dietary behaviours during pregnancy: findings from first-time mothers in southwest Sydney, Australia.\nLimited prevalence data are available for nutrition related health behaviours during pregnancy. This study aimed to assess dietary behaviours during pregnancy among first-time mothers, and to investigate the relationships between these behaviours and demographic characteristics, so that appropriate dietary intervention strategies for pregnant women can be developed. An analysis of cross-sectional survey was conducted using data from 409 first-time mothers at 26-36 weeks of pregnancy, who participated in the Healthy Beginnings Trial conducted in southwestern Sydney, Australia. Dietary behaviours, including consumption of vegetables, fruit, water, milk, soft drinks, processed meat products, fast foods\/take away and chips, were assessed using the New South Wales Health Survey questionnaire through face-to-face interviews. Factors associated with dietary behaviours were determined by logistic regression modeling. Log-binomial regression was used to calculate adjusted risk ratios (ARR). Only 7% of mothers reported meeting the recommended vegetable consumption and 13% reported meeting the recommended fruit consumption. Mean and median intakes per day were 2.3 (SD 1.3) and 2 serves of vegetables, and 2.1 (SD 1.4) and 2 serves of fruit respectively. About one fifth of mothers (21%) reported drinking 2 cups (500 ml) or more of soft drink per day and 12% reported consuming more than 2 meals or snacks from fast-food or takeaway outlets per week. A small percentage of mothers (5%) had experienced food insecurity over the past 12 months. There were significant inverse associations between water and soft drink consumption (Spearman's rho -0.20, P < 0.001), and between fruit and fast food\/takeaway consumption (Spearman's rho -0.16, P = 0.001). The dietary behaviours were associated with a variety of socio-demographic characteristics, but no single factor was associated with all the dietary behaviours. There were low reported levels of vegetable and fruit consumption and high reported levels of soft drink and takeaway\/fast food consumption among pregnant women. Dietary interventions to prevent adverse health consequences need to be tailored to meet the needs of pregnant women of low socio-economic status in order to improve their own healthy eating behaviors. Increasing water and fruit consumption could lead to reduced consumption of soft drink and takeaway\/fast food among pregnant women. HBT is registered with the Australian Clinical Trial Registry (ACTRNO12607000168459).","subset":"pubmed_abstract"} +{"meta":{"pmid":28719257,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":11}}},"text":"No Serologic Evidence of Middle East Respiratory Syndrome Coronavirus Infection Among Camel Farmers Exposed to Highly Seropositive Camel Herds: A Household Linked Study, Kenya, 2013.\nAbstractHigh seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) among camels has been reported in Kenya and other countries in Africa. To date, the only report of MERS-CoV seropositivity among humans in Kenya is of two livestock keepers with no known contact with camels. We assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. In 2013, 760 human and 879 camel sera were collected from 275 and 85 households respectively in Marsabit County. Data on human and animal demographics and type of contact with camels were collected. Human and camel sera were tested for anti-MERS-CoV IgG using a commercial enzyme-linked immunosorbent assay (ELISA) test. Human samples were confirmed by plaque reduction neutralization test (PRNT). Logistic regression was used to identify factors associated with seropositivity. The median age of persons sampled was 30 years (range: 5-90) and 50% were males. A quarter (197\/760) of the participants reported having had contact with camels defined as milking, feeding, watering, slaughtering, or herding. Of the human sera, 18 (2.4%) were positive on ELISA but negative by PRNT. Of the camel sera, 791 (90%) were positive on ELISA. On univariate analysis, higher prevalence was observed in female and older camels over 4 years of age (P < 0.05). On multivariate analysis, only age remained significantly associated with increased odds of seropositivity. Despite high seroprevalence among camels, there was no serological confirmation of MERS-CoV infection among camel pastoralists in Marsabit County. The high seropositivity suggests that MERS-CoV or other closely related virus continues to circulate in camels and highlights ongoing potential for animal-to-human transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":18991625,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Correlates of unprotected anal intercourse in HIV positive men attending an HIV\/AIDS clinic in Sydney.\nWe examined the impact of cognitive and biomedical variables on unprotected anal intercourse between HIV-1 infected men and casual sexual partners in a Sydney-based cohort. Participants answered questionnaires examining insertive and receptive intercourse with and without ejaculation. They completed a modified optimism-scepticism scale, a sexual beliefs scale and a clinical\/demographics questionnaire. CD4 count, blood and semen VL were assessed. 43 of 109 reported anal intercourse with HIV+ partners, 33 with HIV- partners and 38 with partners of unknown status. With HIV+ partners past sexually transmittable infections were associated with receptive intercourse without ejaculation (p = 0.03) and insertive intercourse without ejaculation (p = 0.06) while sexual beliefs were associated with insertive intercourse without ejaculation (p = 0.038), receptive intercourse with ejaculation (p = 0.016) and insertive intercourse with ejaculation (p = 0.077). Sexual beliefs were found to have some association with unprotected receptive intercourse without ejaculation with HIV- partners (p = 0.071). With unknown serostatus partners, treatment-optimism (p = 0.026) had association with insertive intercourse with ejaculation while optimism (p = 0.002), sexual beliefs (p = 0.039) and recent VL (p = 0.059) had associations with insertive intercourse without ejaculation. Current STI had association with receptive intercourse with ejaculation with unknown status partners (p = 0.014). We found between-group differences in variables associated with different types of unprotected anal intercourse that may guide the development of prevention strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":7931561,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2022-27":1,"2021-25":1,"2021-21":2,"2020-34":1,"2020-16":1,"2018-13":1,"2017-43":1,"2017-22":1,"2022-33":1}}},"text":"EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar \"mossy\" cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices.\nWhen hippocampal slices are exposed to GABAA antagonists, area CA3 pyramidal cells and dentate hilar \"mossy\" cells discharge in synchronized epileptiform bursts (M\u00fcller and Misgeld, 1991; Scharfman, 1994b). Dentate interneurons are excited simultaneously, but the degree of discharge varies (Scharfman, 1994b). This study primarily examined the activity of dentate granule cells simultaneous to the epileptiform bursts of pyramidal cells and mossy cells. EPSPs followed by large GABAB receptor-mediated IPSPs were generated in granule cells during all epileptiform bursts of pyramidal cells and mossy cells, regardless of whether they were evoked or spontaneous. By simultaneous recording it was determined that granule cell EPSPs began several milliseconds after the start of pyramidal cell bursts (n = 48 simultaneous recordings) and immediately after the first action potential of a mossy cell burst (n = 77). Interneurons were similar to granule cells in the timing of their depolarizations relative to the onset of pyramidal cell (n = 24; Scharfman, 1994b) and mossy cell (n = 9) bursts. All excitatory activity was blocked by bath application of the glutamatergic AMPA\/kainate receptor antagonist CNQX (5 microM, n = 5), but not the NMDA receptor antagonist D-APV (25-50 microM, n = 9). Granule cell EPSPs were decreased after focal application of CNQX to the molecular layer at a site close to the impaled granule cell (n = 5), whereas D-APV had no effect (n = 3). EPSPs also decreased after focal application of CNQX to the hilus, in two of four slices tested. The extracellularly recorded EPSP of granule cells was maximal in the inner molecular layer (n = 33), the site of the mossy cell axonal plexus. Severing the junction of the dentate gyrus and area CA3 blocked all spontaneous and evoked activity of dentate neurons without affecting burst discharges in area CA3a and CA3b (n = 6). None of the excitatory activity of any cell type was affected by cholinergic antagonists (atropine and mecamylamine, 25 microM each, n = 5; pirenzipine and dihydro-beta-erythroidine, 25 microM each, n = 5). The results suggest that there is a glutamatergic, AMPA\/kainate receptor-mediated, excitatory pathway from area CA3 to the dentate gyrus in disinhibited slices. The pharmacological results, analyses of latency, as well as the known axonal projections of the sampled cells, suggest that the excitatory pathway begins within area CA3 and leads to granule cells via mossy cells. The data also suggest that dentate interneurons are excited by mossy cells, and possibly by pyramidal cells as well.(ABSTRACT TRUNCATED AT 400 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":23370328,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":3,"unknown":14}}},"text":"Sirtuin-1 regulates acinar-to-ductal metaplasia and supports cancer cell viability in pancreatic cancer.\nThe exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD(+)-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1 activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and \u03b2-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1\/2 inhibitor Tenovin-6. In PDAC, acetylation of \u03b2-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":21204865,"dup_signals":{"dup_doc_count":22,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":4,"2024-26":1,"2024-22":3,"2024-18":6,"2024-10":4,"unknown":2}}},"text":"Opa proteins and CEACAMs: pathways of immune engagement for pathogenic Neisseria.\nNeisseria meningitidis and Neisseria gonorrhoeae are globally important pathogens, which in part owe their success to their ability to successfully evade human immune responses over long periods. The phase-variable opacity-associated (Opa) adhesin proteins are a major surface component of these organisms, and are responsible for bacterial adherence and entry into host cells and interactions with the immune system. Most immune interactions are mediated via binding to members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family. These Opa variants are able to bind to different receptors of the CEACAM family on epithelial cells, neutrophils, and T and B lymphocytes, influencing the innate and adaptive immune responses. Increased epithelial cell adhesion creates the potential for prolonged infection, invasion and dissemination. Furthermore, Opa proteins may inhibit T-lymphocyte activation and proliferation, B-cell antibody production, and innate inflammatory responses by infected epithelia, in addition to conferring increased resistance to antibody-dependent, complement-mediated killing. While vaccines containing Opa proteins could induce adhesion-blocking and bactericidal antibodies, the consequence of CEACAM binding by a candidate Opa-containing vaccine requires further investigation. This review summarizes current knowledge of the immunological consequences of the interaction between meningococcal and gonococcal Opa proteins and human CEACAMs, considering the implications for pathogenesis and vaccine development.","subset":"pubmed_abstract"} +{"meta":{"pmid":29365036,"dup_signals":{"dup_doc_count":19,"dup_dump_count":8,"dup_details":{"curated_sources":3,"2019-35":1,"2019-22":2,"2019-13":2,"2019-04":3,"2018-43":2,"2018-34":2,"2018-26":3,"2019-39":1}}},"text":"Real World Home Blood Pressure Variability in Over 56,000 Individuals With Nearly 17 Million Measurements.\nUsing the data from 56,365 individuals, from 185 countries, and a Nokia Health Wireless blood pressure (BP) monitor, we investigated real-world characteristics of BP variability (BPV). All included individuals self-measured and uploaded their BP using Bluetooth at least 20 times over a period of \u22651 month at a frequency and duration of their choosing. In total, 16,904,844 BP measurements were analyzed, with a median of 146 measurements per person (interquartile range [IQR] 73-321) over a median of 14 months (IQR 7-31). SD, coefficient of variation, maximum BP, and maximum minus minimum BP difference were all calculated as measures of BPV. BPV showed a distinct pattern, influenced by season of year, day of week, and time of day. BPV index was higher in females compared with males (P < 0.001) and increased with age (P < 0.001). Compared to the weekend, the weekday BPV index was significantly higher, and this finding was more prominent in females (P = 0.001). In multivariate analysis, BPV index were significantly associated with age, gender, geographic location, and mean BP values. Using the largest BP data set we are aware of, with the benefits and limitations of real-world measurement, we could show the pattern of BPV and provide reference values that may be helpful in understanding the nature of BPV as self-measurement at home becomes more common, and help guide individualized management.","subset":"pubmed_abstract"} +{"meta":{"pmid":23569512,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Permanent neonatal diabetes mellitus.\nNeonatal diabetes is a rare cause of hyperglycemia, affecting 1: 500,000 births, with persistent hyperglycemia occurring in the first months of life lasting more than 2 weeks and requiring insulin. This condition in infants less than 6 months of age is considered as permanent neonatal diabetes mellitus. A rare case of permanent neonatal diabetes mellitus presented with intrauterine growth retardation (IUGR; birth weight: 1460 grams; female), hyperglycemia, glycosuria, and mild dehydration, a normal Apgar score of 8 and 9 at 1 and 5 minutes, respectively. The parents, of consanguineous union, had no prior history of diabetes mellitus. Of their 4 children, the first child had a diagnosis similar to the patient (their last child). The patient was initially started on continuous infusion of insulin, and then switched to regular insulin subcutaneously, but response was sub-optimal. She was started on neutral protamine Hagedorn, following which her condition improved. She was discharged on neutral protamine Hagedorn with regular follow-up. In view of widespread consanguinity in Saudi Arabia it appears prudent and pertinent to suspect permanent neonatal diabetes mellitus following diagnosis of hyperglycemia in small-for-age infants, especially those with positive family history of diabetes. Close blood glucose monitoring is essential as long as hyperglycemia persists. Prolong follow-up is imperative.","subset":"pubmed_abstract"} +{"meta":{"pmid":24750353,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-10":1,"unknown":15}}},"text":"Genome-wide single-generation signatures of local selection in the panmictic European eel.\nNext-generation sequencing and the collection of genome-wide data allow identifying adaptive variation and footprints of directional selection. Using a large SNP data set from 259 RAD-sequenced European eel individuals (glass eels) from eight locations between 34 and 64(o) N, we examined the patterns of genome-wide genetic diversity across locations. We tested for local selection by searching for increased population differentiation using F(ST) -based outlier tests and by testing for significant associations between allele frequencies and environmental variables. The overall low genetic differentiation found (F(ST) = 0.0007) indicates that most of the genome is homogenized by gene flow, providing further evidence for genomic panmixia in the European eel. The lack of genetic substructuring was consistent at both nuclear and mitochondrial SNPs. Using an extensive number of diagnostic SNPs, results showed a low occurrence of hybrids between European and American eel, mainly limited to Iceland (5.9%), although individuals with signatures of introgression several generations back in time were found in mainland Europe. Despite panmixia, a small set of SNPs showed high genetic differentiation consistent with single-generation signatures of spatially varying selection acting on glass eels. After screening 50 354 SNPs, a total of 754 potentially locally selected SNPs were identified. Candidate genes for local selection constituted a wide array of functions, including calcium signalling, neuroactive ligand-receptor interaction and circadian rhythm. Remarkably, one of the candidate genes identified is PERIOD, possibly related to differences in local photoperiod associated with the >30\u00b0 difference in latitude between locations. Genes under selection were spread across the genome, and there were no large regions of increased differentiation as expected when selection occurs within just a single generation due to panmixia. This supports the conclusion that most of the genome is homogenized by gene flow that removes any effects of diversifying selection from each new generation.","subset":"pubmed_abstract"} +{"meta":{"pmid":32395541,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm.\nThe \"novel\" coronavirus disease 2019 (abbreviated \"COVID-19\") is the third coronavirus outbreak emerging during the past two decades. This infectious disease, sustained by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been recently declared a global pandemic by the World Health Organization. Despite the concerning epidemiological burden, many people, including some policymakers, are underestimating this pandemic and are remaining enigmatically inactive against a human pathology which, for a combination of reasons, can be reasonably defined as a perfect storm (i.e., the \"wrong virus\" at the \"wrong time\"). These many paradigmatic aspects include SARS-CoV-2 structure and peculiar biology of infection, high risk of inter-human transmission, long incubation time combined with early and sustained viral load, existence of asymptomatic or mildly-symptomatic carriers, viral shedding for days after symptom relief, unfavorable progression towards respiratory distress and death in up to 5-10% of patients thus causing dramatic healthcare challenges, as well as environmental contamination. Last but not least, the combination of the current case fatality rate with the extraordinary number of people that could be potentially infected by SARS-CoV-2 would permit to estimate that the worldwide deaths for COVID-19 may even approximate those recorded during World War II if appropriate restrictive measures for preventing human-to-human transmission are not readily undertaken. Everybody should be inexcusably aware that this is not a drill, and that the consequences of inadequate action will be tragedy.","subset":"pubmed_abstract"} +{"meta":{"pmid":10894994,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":13}}},"text":"Transient ischemic attack in heavy cannabis smokers--how 'safe' is it?\nDrugs are lately considered high-risk factors for cerebrovascular disease. Three male patients (mean age 24.6 years) who were heavy cannabis smokers presented with transient ischemic attacks (TIA) shortly after cannabis abuse. The complete examination of all 3 consisted of: EEG, brain CT scan, brain MRI, cerebral vessel angiography (digital subtraction and magnetic resonance angiography); also a full cerebrospinal fluid, urine and blood analysis (immunological, biochemical and hormonal tests were included). Urine was further examined for drug metabolites. An extensive cardiological investigation was carried out. Small vessel leukoencephalopathy was revealed by the brain CT and MRI. EEG recordings of the first patient showed paroxysmal sharp waves with left hemispheric dominance. The other 2 patients had diffuse delta and theta activity in their EEG tracings. The urine analysis was positive for cannabis metabolites. There were no other abnormal findings in the rest of the meticulous and thorough study of all 3 patients, which leads to the conclusion that cannabis was the only risk factor responsible for the observed TIA, contradictory to other studies, which support that cannabis is a 'safe' drug. More research is required in order for this issue to be completely elucidated.","subset":"pubmed_abstract"} +{"meta":{"pmid":16221325,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Socioeconomic status does not moderate the familiality of cognitive abilities in the Hawaii family study of cognition.\nData from 949 families of Caucasian and 400 families of Japanese ancestry who took part in the Hawaii Family Study of Cognition were used to ascertain the associations of parental cognitive ability, parental education and paternal occupation with offspring cognitive ability. In particular, analyses were focused on testing the possible moderating effects of parental socioeconomic status on the familial transmission of cognitive abilities. Parental cognitive ability was substantially associated and parental education and paternal occupation only trivially associated with offspring performance. In contrast to the findings of Turkheimer et al. (2003), there was no evidence in these data that familiality for cognitive abilities was lower in the lower as opposed to upper levels of socioeconomic status. These results were consistent across measures, ethnicity and sex of offspring.","subset":"pubmed_abstract"} +{"meta":{"pmid":23048008,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"An optimized web-based approach for collaborative stereoscopic medical visualization.\nMedical visualization tools have traditionally been constrained to tethered imaging workstations or proprietary client viewers, typically part of hospital radiology systems. To improve accessibility to real-time, remote, interactive, stereoscopic visualization and to enable collaboration among multiple viewing locations, we developed an open source approach requiring only a standard web browser with no added client-side software. Our collaborative, web-based, stereoscopic, visualization system, CoWebViz, has been used successfully for the past 2 years at the University of Chicago to teach immersive virtual anatomy classes. It is a server application that streams server-side visualization applications to client front-ends, comprised solely of a standard web browser with no added software. We describe optimization considerations, usability, and performance results, which make CoWebViz practical for broad clinical use. We clarify technical advances including: enhanced threaded architecture, optimized visualization distribution algorithms, a wide range of supported stereoscopic presentation technologies, and the salient theoretical and empirical network parameters that affect our web-based visualization approach. The implementations demonstrate usability and performance benefits of a simple web-based approach for complex clinical visualization scenarios. Using this approach overcomes technical challenges that require third-party web browser plug-ins, resulting in the most lightweight client. Compared to special software and hardware deployments, unmodified web browsers enhance remote user accessibility to interactive medical visualization. Whereas local hardware and software deployments may provide better interactivity than remote applications, our implementation demonstrates that a simplified, stable, client approach using standard web browsers is sufficient for high quality three-dimensional, stereoscopic, collaborative and interactive visualization.","subset":"pubmed_abstract"} +{"meta":{"pmid":23862598,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Treating patients as persons: a capabilities approach to support delivery of person-centered care.\nHealth services internationally struggle to ensure health care is \"person-centered\" (or similar). In part, this is because there are many interpretations of \"person-centered care\" (and near synonyms), some of which seem unrealistic for some patients or situations and obscure the intrinsic value of patients' experiences of health care delivery. The general concern behind calls for person-centered care is an ethical one: Patients should be \"treated as persons.\" We made novel use of insights from the capabilities approach to characterize person-centered care as care that recognizes and cultivates the capabilities associated with the concept of persons. This characterization unifies key features from previous characterisations and can render person-centered care applicable to diverse patients and situations. By tying person-centered care to intrinsically valuable capability outcomes, it incorporates a requirement for responsiveness to individuals and explains why person-centered care is required independently of any contribution it may make to health gain.","subset":"pubmed_abstract"} +{"meta":{"pmid":24610919,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Aromatase transgenic upregulation modulates basal cardiac performance and the response to ischemic stress in male mice.\nEstrogen in females is conventionally considered a cardioprotective influence, but a role for estrogen in male cardioprotection has yet to be defined. Estrogen biosynthesis from testosterone is regulated by aromatase. Aromatase has recently been shown to be expressed in the adult heart, although little is known about its involvement in the regulation of myocardial function and stress responses. The goal of this study was to determine whether upregulation of tissue aromatase expression could improve ischemic resilience in male hearts. Isolated hearts from male transgenic aromatase-overexpressing (AROM(+); high estrogen, low testosterone) mice and wild-type (WT) mice (12 wk) were Langendorff perfused and subjected to ischemia-reperfusion (25 min ischemia and 60 min of reperfusion). Basal systolic function was lower in AROM(+) hearts (dP\/dtmax: 4,121 \u00b1 255 vs. 4,992 \u00b1 283 mmHg\/s, P < 0.05) and associated with augmented Akt phosphorylation, consistent with a suppressor action of estrogen on contractility. Ischemic contracture was attenuated in AROM(+) hearts (43 \u00b1 3 vs. 55 \u00b1 4 mmHg, P < 0.05), yet AROM(+) hearts were more arrhythmic in early reperfusion. At the end of 60 min of reperfusion, AROM(+) systolic functional recovery was lower (left ventricular developed pressure: 39 \u00b1 6 vs. 56 \u00b1 5 %basal, P < 0.05) and diastolic dysfunction was accentuated (36 \u00b1 4 vs. 24 \u00b1 2 mmHg, P < 0.05). This is the first study to show that in vivo aromatase upregulation modulates basal cardiac performance and the response to ischemic stress. These data suggest that while chronic exposure to enhanced estrogenic influence may have benefits in limiting ischemic contracture severity, acute functional recovery in reperfusion is compromised. A temporally targeted, tissue-specific intervention combining aromatase treatment with inotropic support may offer therapeutic potential for men and women.","subset":"pubmed_abstract"} +{"meta":{"pmid":26859746,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells.\nCancer stem cells (CSCs) typically have the capacity to evade chemotherapy and may be the principal source of metastases. CSCs for human pancreatic ductal carcinoma (PDAC) have been identified, but neither the metastatic potential nor the chemoresistance of these cells has been adequately evaluated. We have addressed these issues by examining side-population (SP) cells isolated from the Panc-1 and BxPC3 lines of human PDAC cells, the oncogenotypes of which differ. SP cells could be isolated from monolayers of Panc-1, but only from spheroids of BxPC3. Using orthotopic xenografts into the severely immunocompromised NSG mouse, we found that SP cells isolated from both cell lines produced tumors that were highly metastatic, in contrast to previous experience with PDAC cell lines. SP cells derived from both cell lines expressed the ABCG2 transporter, which was demonstrably responsible for the SP phenotype. SP cells gave rise to non-SP (NSP) cells in vitro and in vivo, a transition that was apparently due to posttranslational inhibition of the ABCG2 transporter. Twenty-two other lines of PDAC cells also expressed ABCG2. The sensitivity of PDAC SP cells to the vinca alkaloid vincristine could be greatly increased by verapamil, a general inhibitor of transporters. In contrast, verapamil had no effect on the killing of PDAC cells by gemcitabine, the current first-line therapeutic for PDAC. We conclude that the isolation of SP cells can be a convenient and effective tool for the study of PDAC CSCs; that CSCs may be the principal progenitors of metastasis by human PDAC; that the ABCG2 transporter is responsible for the SP phenotype in human PDAC cells, and may be a ubiquitous source of drug-resistance in PDAC, but does not confer resistance to gemcitabine; and that inhibition of ABCG2 might offer a useful adjunct in a therapeutic attack on the CSCs of PDAC.","subset":"pubmed_abstract"} +{"meta":{"pmid":22731764,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Racial and ethnic differences in adjuvant hormonal therapy use.\nIn the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial\/ethnic differences in adjuvant hormonal therapy use among women aged 18-64 years, diagnosed with hormone receptor-positive breast cancer, using data collected by the Northern California Breast Cancer Family Registry (NC-BCFR), and explored changes in use over time. Odds ratios (OR) comparing self-reported ever-use by race\/ethnicity (African American, Hispanic, non-Hispanic white vs. Asian American) were estimated using multivariable adjusted logistic regression. Analyses were stratified by recruitment phase (phase I, diagnosed January 1995-September 1998, phase II, diagnosed October 1998-April 2003) and genetic susceptibility, as cases with increased genetic susceptibility were oversampled. Among 1385 women (731 phase I, 654 phase II), no significant racial\/ethnic differences in use were observed among phase I or phase II cases. However, among phase I cases with no susceptibility indicators, African American and non-Hispanic white women were less likely than Asian American women to use hormonal therapy (OR 0.20, 95% confidence interval [CI]0.06-0.60; OR 0.40, CI 0.17-0.94, respectively). No racial\/ethnic differences in use were observed among women with 1+ susceptibility indicators from either recruitment phase. Racial\/ethnic differences in adjuvant hormonal therapy use were limited to earlier diagnosis years (phase I) and were attenuated over time. Findings should be confirmed in other populations but indicate that in this population, treatment disparities between African American and Asian American women narrowed over time as adjuvant hormonal treatments became more commonly prescribed.","subset":"pubmed_abstract"} +{"meta":{"pmid":17072489,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Using short-term concentration measures and intelligence in rehabilitation settings.\nPsychological assessment of cognitive functioning among clinical groups that include psychiatric and geriatric patients is a difficult task. This study examines the interrelationship between intelligence and concentrative ability for a group of psychiatric patients. Intellectual and concentrative ability were assessed among a group of 85, predominantly schizophrenic, patients (mean age 32 years) from a Sheltered Workshop (GWN) and neurological-psychiatric institutionalized care units within the Neuss region of North-Rhine Westphalia, Germany. Moderate bivariate relationships were found between all IQ subtests and the concentration performance variables (d2). A substantial overlap in variance was found between \"nonverbal\" intelligence and the concentration variables (using multiple regression and discrimination analysis). Error rate on the concentration task was significantly negatively correlated with the IQ variables, the magnitude of the correlation coefficient increasing as a function of the time on the task. Future studies would benefit from comparisons in factor structure similarity between abnormal and normal groups as well as between-clinical groups. At a practical level, the relatively easy use (less complex administration) and less obtrusive (hence, low level of personal threat) and inexpensive procedures of the letter cancellation task makes it a useful, albeit \"approximate\", measure of cognitive functioning.","subset":"pubmed_abstract"} +{"meta":{"pmid":23407836,"dup_signals":{"dup_doc_count":37,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2021-49":1,"2021-10":2,"2021-04":3,"2019-51":2,"2019-47":3,"2016-50":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2022-49":1,"2015-18":1,"2015-11":1,"2015-06":1,"2024-18":1}}},"text":"Artificial light at night advances avian reproductive physiology.\nArtificial light at night is a rapidly increasing phenomenon and it is presumed to have global implications. Light at night has been associated with health problems in humans as a consequence of altered biological rhythms. Effects on wild animals have been less investigated, but light at night has often been assumed to affect seasonal cycles of urban dwellers. Using light loggers attached to free-living European blackbirds (Turdus merula), we first measured light intensity at night which forest and city birds are subjected to in the wild. Then we used these measurements to test for the effect of light at night on timing of reproductive physiology. Captive city and forest blackbirds were exposed to either dark nights or very low light intensities at night (0.3 lux). Birds exposed to light at night developed their reproductive system up to one month earlier, and also moulted earlier, than birds kept under dark nights. Furthermore, city birds responded differently than forest individuals to the light at night treatment, suggesting that urbanization can alter the physiological phenotype of songbirds. Our results emphasize the impact of human-induced lighting on the ecology of millions of animals living in cities and call for an understanding of the fitness consequences of light pollution.","subset":"pubmed_abstract"} +{"meta":{"pmid":29156151,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Limited evidence of fungicide-driven triazole-resistant Aspergillus fumigatus in Hamilton, Canada.\nAspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that can cause aspergillosis in humans. Over the last decade there have been increasing global reports of treatment failure due to triazole resistance. An emerging hypothesis states that agricultural triazole fungicide use causes clinical triazole resistance. Here we test this hypothesis in Hamilton, Ontario, Canada, by examining a total of 195 agricultural, urban, and clinical isolates using 9 highly polymorphic microsatellite markers. For each isolate, the in vitro susceptibilities to itraconazole and voriconazole, 2 triazole drugs commonly used in the management of patients, were also determined. Our analyses suggested frequent gene flow among the agricultural, urban environmental, and clinical populations of A. fumigatus and found evidence for widespread sexual recombination within and among the different populations. Interestingly, all 195 isolates analyzed in this study were susceptible to both triazoles tested. However, compared with the urban population, agricultural and clinical populations showed significantly reduced susceptibility to itraconazole and voriconazole, consistent with ecological niche-specific selective pressures on A. fumigatus populations in Hamilton. Frequent gene flow and genetic recombination among these populations suggest greater attention should be paid to monitor A. fumigatus populations in Hamilton and other similar jurisdictions.","subset":"pubmed_abstract"} +{"meta":{"pmid":23671040,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":13}}},"text":"Regulation of cardiac autophagy by insulin-like growth factor 1.\nInsulin-like growth factor-1 (IGF-1) signaling is a key pathway in the control of cell growth and survival. Three critical nodes in the IGF-1 signaling pathway have been described in cardiomyocytes: protein kinase Akt\/mammalian target of rapamycin (mTOR), Ras\/Raf\/extracellular signal-regulated kinase (ERK), and phospholipase C (PLC)\/inositol 1,4,5-triphosphate (InsP3 )\/Ca(2+) . The Akt\/mTOR and Ras\/Raf\/ERK signaling arms govern survival in the settings of cardiac stress and hypertrophic growth. By contrast, PLC\/InsP3 \/Ca(2+) functions to regulate metabolic adaptability and gene transcription. Autophagy is a catabolic process involved in protein degradation, organelle turnover, and nonselective breakdown of cytoplasmic components during nutrient starvation or stress. In the heart, autophagy is observed in a variety of human pathologies, where it can be either adaptive or maladaptive, depending on the context. We proposed the hypothesis that IGF-1 protects the heart by rescuing the mitochondrial metabolism and the energetics state, reducing cell death and controls the potentially exacerbate autophagic response to nutritional stress. In light of the importance of IGF-1 and autophagy in the heart, we review here IGF-1 signaling and autophagy regulation in the context of cardiomyocyte nutritional stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":11100972,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":9}}},"text":"Tubulin and neurofilament proteins are transported differently in axons of chicken motoneurons.\n1. We previously showed that actin is transported in an unassembled form with its associated proteins actin depolymerizing factor, cofilin, and profilin. Here we examine the specific activities of radioactively labeled tubulin and neurofilament proteins in subcellular fractions of the chicken sciatic nerve following injection of L-[35S]methionine into the lumbar spinal cord. 2. At intervals of 12 and 20 days after injection, nerves were cut into 1-cm segments and separated into Triton X-100-soluble and particulate fractions. Analysis of the fractions by high-resolution two-dimensional gel electrophoresis, immunoblotting, fluorography, and computer densitometry showed that tubulin was transported as a unimodal wave at a slower average rate (2-2.5 mm\/day) than actin (4-5 mm\/day). Moreover, the specific activity of soluble tubulin was five times that of its particulate form, indicating that tubulin is transported in a dimeric or small oligomeric form and is assembled into stationary microtubules. 3. Neurofilament triplet proteins were detected only in the particulate fractions and transported at a slower average rate (1 mm\/day) than either actin or tubulin. 4. Our results indicate that the tubulin was transported in an unpolymerized form and that the neurofilament proteins were transported in an insoluble, presumably polymerized form.","subset":"pubmed_abstract"} +{"meta":{"pmid":24732921,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.\nP2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients \u226575 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit\/risk ratio.","subset":"pubmed_abstract"} +{"meta":{"pmid":33096869,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Non-Invasive Luciferase Imaging of Type I Interferon Induction in a Transgenic Mouse Model of Biomaterial Associated Bacterial Infections: Microbial Specificity and Inter-Bacterial Species Interactions.\nThe performance of biomaterials is often compromised by bacterial infections and subsequent inflammation. So far, the conventional analysis of inflammatory processes in vivo involves time-consuming histology and biochemical assays. The present study employed a mouse model where interferon beta (IFN-\u03b2) is monitored as a marker for non-invasive rapid detection of inflammation in implant-related infections. The mouse model comprises subcutaneous implantation of morphologically modified titanium, followed by experimental infections with four taxonomically diverse oral bacteria: Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola (as mono culture or selected mixed-culture). IFN-\u03b2 expression increased upon infections depending on the type of pathogen and was prolonged by the presence of the implant. IFN-\u03b2 expression kinetics reduced with two mixed species infections when compared with the single species. Histological and confocal microscopy confirmed pathogen-specific infiltration of inflammatory cells at the implant-tissue interface. This was observed mainly in the vicinity of infected implants and was, in contrast to interferon expression, higher in infections with dual species. In summary, this non-invasive mouse model can be used to quantify longitudinally host inflammation in real time and suggests that the polymicrobial character of infection, highly relevant to clinical situations, has complex effects on host immunity.","subset":"pubmed_abstract"} +{"meta":{"pmid":12675829,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":9}}},"text":"Lizards in 'nuclear families': a novel reptilian social system in Egernia saxatilis (Scincidae).\nRecent research has revealed unsuspected complexity in social organization among squamate reptiles. In particular, large Australian scincid lizards of the genus Egernia have been reported to occur in large aggregations of closely related individuals. However, the 'nuclear family' structure found in many other 'social' organisms (especially birds) has not been reported from reptiles. Our field studies on black rock skinks (Egernia saxatilis) in southeastern Australia document exactly this pattern. We quantified group composition using behavioural observations at regular intervals over three field seasons, and took tissue samples for parentage analysis. On the focal rock outcrop 72% of lizards were typically found as part of a stable social grouping, with individuals physically associated with other group members in a third of observations. Eighty-five per cent of juveniles lived in social groups, 65% in family groups with at least one of their parents (including 39% with both parents as revealed by parentage analysis of five microsatellite loci). Broader sampling in surrounding areas revealed similar patterns of group size, composition and relatedness. Overall, of the groups that contained more than one adult, 83% contained a single adult pair. Long-term monogamy and group stability were evident from our genetic data, with up to three annual cohorts of full-sib offspring living with their biological parents. Our data expand the range of social systems known for reptiles, and reveal strong convergence towards 'nuclear family' systems in distantly related vertebrates.","subset":"pubmed_abstract"} +{"meta":{"pmid":24602405,"dup_signals":{"dup_doc_count":21,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2017-13":1,"2024-30":1,"unknown":17}}},"text":"Polyamines are essential for virulence in Salmonella enterica serovar Gallinarum despite evolutionary decay of polyamine biosynthesis genes.\nSerovars of Salmonella enterica exhibit different host-specificities where some have broad host-ranges and others, like S. Gallinarum and S. Typhi, are host-specific for poultry and humans, respectively. With the recent availability of whole genome sequences it has been reported that host-specificity coincides with accumulation of pseudogenes, indicating adaptation of host-restricted serovars to their narrow niches. Polyamines are small cationic amines and in Salmonella they can be synthesized through two alternative pathways directly from l-ornithine to putrescine and from l-arginine via agmatine to putrescine. The first pathway is not active in S. Gallinarum and S. Typhi, and this prompted us to investigate the importance of polyamines for virulence in S. Gallinarum. Bioinformatic analysis of all sequenced genomes of Salmonella revealed that pseudogene formation of the speC gene was exclusive for S. Typhi and S. Gallinarum and happened through independent events. The remaining polyamine biosynthesis pathway was found to be essential for oral infection with S. Gallinarum since single and double mutants in speB and speE, encoding the pathways from agmatine to putrescine and from putrescine to spermidine, were attenuated. In contrast, speB was dispensable after intraperitoneal challenge, suggesting that putrescine was less important for the systemic phase of the disease. In support of this hypothesis, a \u0394speE;\u0394potCD mutant, unable to synthesize and import spermidine, but with retained ability to import and synthesize putrescine, was attenuated after intraperitoneal infection. We therefore conclude that polyamines are essential for virulence of S. Gallinarum. Furthermore, our results point to distinct roles for putrescine and spermidine during systemic infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":25883858,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-40":1,"2023-06":1,"2022-40":1,"2022-21":1,"2020-50":1,"2020-45":1,"2019-09":1,"2018-26":1,"2017-51":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2023-50":1,"2024-26":2,"2024-22":1}}},"text":"Uterine fibroid embolization for symptomatic fibroids: study at a teaching hospital in kenya.\nCharacterization of magnetic (MRI) features in women undergoing uterine fibroid embolization (UFE) and identification of clinical correlates in an African population. Patients with symptomatic fibroids who are selected to undergo UFE at the hospital formed the study population. The baseline MRI features, baseline symptom score, short-term imaging outcome, and mid-term symptom scores were analyzed for interval changes. Assessment of potential associations between short-term imaging features and mid-term symptom scores was also done. UFE resulted in statistically significant reduction (P < 0.001) of dominant fibroid, uterine volumes, and reduction of symptom severity scores, which were 43.7%, 40.1%, and 37.8%, respectively. Also, 59% of respondents had more than 10 fibroids. The predominant location of the dominant fibroid was intramural. No statistically significant association was found between clinical and radiological outcome. The response of uterine fibroids to embolization in the African population is not different from the findings reported in other studies from the west. The presence of multiple and large fibroids in this study is consistent with the case mix described in other studies of African-American populations. Patient counseling should emphasize the independence of volume reduction and symptom improvement. Though volume changes are of relevance for the radiologist in understanding the evolution of the condition and identifying potential technical treatment failures, it should not be the main basis of evaluation of treatment success.","subset":"pubmed_abstract"} +{"meta":{"pmid":30631315,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Electron and Proton Flux for Carbon Dioxide Reduction in Methanosarcina barkeri During Direct Interspecies Electron Transfer.\nDirect interspecies electron transfer (DIET) is important in diverse methanogenic environments, but how methanogens participate in DIET is poorly understood. Therefore, the transcriptome of Methanosarcina barkeri grown via DIET in co-culture with Geobacter metallireducens was compared with its transcriptome when grown via H2 interspecies transfer (HIT) with Pelobacter carbinolicus. Notably, transcripts for the F420H2 dehydrogenase, Fpo, and the heterodisulfide reductase, HdrABC, were more abundant during growth on DIET. A model for CO2 reduction was developed from these results in which electrons delivered to methanophenazine in the cell membrane are transferred to Fpo. The external proton gradient necessary to drive the otherwise thermodynamically unfavorable reverse electron transport for Fpo-catalyzed F420 reduction is derived from protons released from G. metallireducens metabolism. Reduced F420 is a direct electron donor in the carbon dioxide reduction pathway and also serves as the electron donor for the proposed HdrABC-catalyzed electron bifurcation reaction in which reduced ferredoxin (also required for carbon dioxide reduction) is generated with simultaneous reduction of CoM-S-S-CoB. Expression of genes for putative redox-active proteins predicted to be localized on the outer cell surface was higher during growth on DIET, but further analysis will be required to identify the electron transfer route to methanophenazine. The results indicate that the pathways for electron and proton flux for CO2 reduction during DIET are substantially different than for HIT and suggest that gene expression patterns may also be useful for determining whether Methanosarcina are directly accepting electrons from other extracellular electron donors, such as corroding metals or electrodes.","subset":"pubmed_abstract"} +{"meta":{"pmid":25769343,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":14}}},"text":"Completely transparent conducting oxide-free and flexible dye-sensitized solar cells fabricated on plastic substrates.\nTo achieve commercialization and widespread application of next-generation photovoltaics, it is important to develop flexible and cost-effective devices. Given this, the elimination of expensive transparent conducting oxides (TCO) and replacement of conventional glass substrates with flexible plastic substrates presents a viable strategy to realize extremely low-cost photovoltaics with a potentially wide applicability. To this end, we report a completely TCO-free and flexible dye-sensitized solar cell (DSSC) fabricated on a plastic substrate using a unique transfer method and back-contact architecture. By adopting unique transfer techniques, the working and counter electrodes were fabricated by transferring high-temperature-annealed TiO2 and Pt\/carbon films, respectively, onto flexible plastic substrates without any exfoliation. The fabricated working electrode with the conventional counter electrode exhibited a record efficiency for flexible DSSCs of 8.10%, despite its TCO-free structure. In addition, the completely TCO-free and flexible DSSC exhibited a remarkable efficiency of 7.27%. Furthermore, by using an organic hole-transporting material (spiro-MeOTAD) with the same transfer method, solid-state flexible TCO-free DSSCs were also successfully fabricated, yielding a promising efficiency of 3.36%.","subset":"pubmed_abstract"} +{"meta":{"pmid":23860515,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Differential effects of professional leaders on health care teams in chronic disease management groups.\nLeadership by health care professionals is likely to vary because of differences in the social contexts within which they are situated, socialization processes and societal expectations, education and training, and the way their professions define and operationalize key concepts such as teamwork, collaboration, and partnership. This research examines the effect of the nurse and physician leaders on interdependence and encounter preparedness in chronic disease management practice groups. The aim of this study was to examine the effect of complementary leadership by nurses and physicians involved in jointly producing a health care service on care team functioning. The design is a retrospective observational study based on survey data. The unit of analysis is heart failure care groups in U.S. Veterans Health Administration medical centers. Survey and administrative data were collected in 2009 from 68 Veterans Health Administration medical centers. Key variables include nurse and physician leadership, interdependence, psychological safety, coordination, and encounter preparedness. Reliability and validity of survey measures were assessed with exploratory factor analysis and Cronbach alphas. Multivariate analyses tested hypotheses. Professional leadership by nurses and physicians is related to encounter preparedness by different paths. Nurse leadership is associated with greater team interdependence, and interdependence is positively associated with respect. Physician leadership is positively associated with greater psychological safety, respect, and shared goals but is not associated with interdependence. Respect is associated with involvement in learning activities, and shared goals are associated with coordination. Coordination and involvement in learning activities are positively associated with encounter preparedness. By focusing on increasing interdependence and a constructive climate, nurse and physician leaders have the opportunity to increase care coordination and involvement in learning activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":4062651,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Brain-stem auditory-evoked potentials during lidocaine infusion in humans.\nAuditory brain-stem responses (ABR) were recorded in six healthy male volunteers during intravenous infusion of lidocaine that achieved systemic blood levels similar to those seen with conduction anesthesia and antiarrhythmic therapy. Following an initial loading dose of lidocaine (1 mg\/kg), subjects noted prominent tinnitus, perioral numbness, and drowsiness. All of these symptoms except drowsiness abated during continued infusion as blood concentrations reached equilibrium. All subjects noted that the click stimuli used to elicit ABR varied markedly in intensity and character throughout the lidocaine infusion. Although waves I and III were unaffected by lidocaine, wave V exhibited significant decreases in amplitude and increases in latency. Therefore, the more central components of the auditory system seem to be the prominent site of lidocaine's central nervous system effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":16687585,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Escherichia coli interactions with Acanthamoeba: a symbiosis with environmental and clinical implications.\nThe ability of Acanthamoeba to feed on Gram-negative bacteria, as well as to harbour potential pathogens, such as Legionella pneumophila, Coxiella burnetii, Pseudomonas aeruginosa, Vibrio cholerae, Helicobacter pylori, Listeria monocytogenes and Mycobacterium avium, suggest that both amoebae and bacteria are involved in complex interactions, which may play important roles in the environment and in human health. In this study, Acanthamoeba castellanii (a keratitis isolate belonging to the T4 genotype) was used and its interactions with Escherichia coli (strain K1, a cerebrospinal fluid isolate from a meningitis patient, O18 : K1 : H7, and a K-12 laboratory strain, HB101) were studied. The invasive K1 isolate exhibited a significantly higher association with A. castellanii than the non-invasive K-12 isolate. Similarly, K1 showed significantly increased invasion and\/or uptake by A. castellanii in gentamicin protection assays than the non-invasive K-12. Using several mutants derived from K1, it was observed that outer-membrane protein A (OmpA) and LPS were crucial bacterial determinants responsible for E. coli K1 interactions with A. castellanii. Once inside the cell, E. coli K1 remained viable and multiplied within A. castellanii, while E. coli K-12 was killed. Again, OmpA and LPS were crucial for E. coli K1 intracellular survival in A. castellanii. In conclusion, these findings suggest that E. coli K1 interactions with A. castellanii are carefully regulated by the virulence of E. coli.","subset":"pubmed_abstract"} +{"meta":{"pmid":8166698,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Accumulation of human apolipoprotein-E in rat plasma after in vivo intramuscular injection of naked DNA.\nNaked DNA was found to be incorporated and consistently expressed after in vivo direct injection into striated muscle. In addition to the local expression of muscle-related or exogenous proteins, intramuscular direct gene transfer may be a useful tool to deliver recombinant proteins into the blood stream. However, no direct demonstration of recombinant protein secretion from muscle to the circulation has been reported thus far. We have injected a naked plasmid DNA containing the human receptor-binding defective apo-E2 cDNA, under the control of CMV promoter, into the quadriceps of Yoshida rats, affected by hereditary hypercholesterolemia and altered LDL-receptor activity. Plasma accumulation of human apo-E2 was demonstrated for at least 45 days after injection. On the contrary, the expression of the normal human apo-E3, injected into the muscle of normal Wistar rats, was demonstrated only in the area of muscular injection and not in the blood plasma. Endogenous rat apo-E expression was not affected by the exogenous human apo-E2 production. Our results demonstrate the availability of intramuscular direct gene transfer as a safe and simple method for the chronic systemic delivery of recombinant proteins to the circulation, although further improvements are needed in order to enhance the efficiency and stability of expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":31812914,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Biorefinery of Dunaliella salina: Sustainable recovery of carotenoids, polar lipids and glycerol.\nDunaliella salina is well-known for its high content in carotenoids and glycerol. Nevertheless, Dunaliella salina has also a high content in lipids, including polar lipids, which are suitable for nutraceutical\/cosmeceutical applications. This work proposes a sustainable process to maximise the potential of Dunaliella salina for the production of distinct fractions of carotenoids, glycerol, polar lipids and proteins, which may contribute to improve the revenues of the microalgae industry. In this work, extraction with non-hazardous solvents and organic solvent nanofiltration are integrated, in order to obtain added-value products and glycerol. Also, aiming to separate carotenoids from glycerides, a saponification process is proposed. High overall recoveries were obtained for carotenoids (85%), glycerol (86%), polar lipids (94%) and proteins (95%). In order to evaluate the profitability of the proposed biorefinery, an economic assessment was accomplished. Both CAPEX and OPEX (Capital and Operating expenditure) were calculated, likewise the Return of Investment (ROI).","subset":"pubmed_abstract"} +{"meta":{"pmid":32284396,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":18}}},"text":"PET Imaging of Phosphodiesterase-4 Identifies Affected Dysplastic Bone in McCune-Albright Syndrome, a Genetic Mosaic Disorder.\nMcCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3',5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gs\u03b1. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gs\u03b1 in the affected tissues. The Gs\u03b1 mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS but not in humans with fibrous dysplasia. PET imaging of PDE4 with 11C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods:11C-(R)-rolipram whole-body and brain PET scans were performed on 6 individuals with MAS (3 for brain scans and 6 for whole-body scans) and 9 healthy controls (7 for brain scans and 6 for whole-body scans). Results:11C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in 11C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected-a finding that could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with 11C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":30229751,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Efficacy and Safety of High-Dose Controlled-Release Oxycodone in the Treatment of Moderate to Severe Pain in Patients with Advanced Cancer: A Retrospective Study.\nBACKGROUND Opioid analgesics are used to relieve pain in patients with cancer and can improve their quality of life. This study aimed to investigate the efficacy and tolerability of high-dose (>150 mg\/day) controlled-release oxycodone for the control of pain in patients with advanced solid malignant tumors. MATERIAL AND METHODS A retrospective clinical study was undertaken to include patients with advanced cancer treated at the Zhejiang Cancer Hospital who had treatment that included high-dose controlled-release oxycodone. The subjective numeric rating scale (NRS) for assessment of pain intensity (scores between 0-10) was used in all cases. RESULTS The study included 131 patients with advanced solid tumors with moderate to severe cancer pain. The mean NRS score before commencing high-dose controlled-release oxycodone was 7.10. The effective rate of relief pain was achieved in 90.1% (118\/131) of patients, with an average effective dose of controlled-release oxycodone of 177.18\u00b111.71 mg\/day, resulting in a mean NRS of 2.15. There were 51 patients who achieved pain relief with mean treatment duration of 49.98\u00b111.71 days. Combination therapy was required in 79 patients. Additional drugs included gabapentin (43 patients), pregabalin (10 patients) and non-steroidal anti-inflammatory drugs (NSAIDS) (26 patients). The main side effects of high-dose controlled-release oxycodone included constipation, nausea, vomiting, dysuria, dizziness, and drowsiness, but no patients discontinued treatment because of these. CONCLUSIONS This study showed that high-dose controlled-release oxycodone could effectively relieve moderate to severe cancer pain, without side effects that were severe enough to result in discontinuation of treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":24819876,"dup_signals":{"dup_doc_count":17,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2021-25":2,"2021-04":2,"2020-45":1,"2019-43":2,"2019-35":2,"2019-26":1,"2019-13":1,"2019-04":1,"2024-22":1}}},"text":"Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer.\nWe identified acyl-coenzyme A-binding protein (ACBP) as part of a proteomic signature predicting the risk of having lung cancer. Because ACBP is known to regulate \u03b2-oxidation, which in turn controls cellular proliferation, we hypothesized that ACBP contributes to regulation of cellular proliferation and survival of non-small cell lung cancer (NSCLC) by modulating \u03b2-oxidation. We used matrix-assisted laser desorption\/ionization-imaging mass spectrometry (MALDI-IMS) and immunohistochemistry (IHC) to confirm the tissue localization of ABCP in pre-invasive and invasive NSCLCs. We correlated ACBP gene expression levels in NSCLCs with clinical outcomes. In loss-of-function studies, we tested the effect of the downregulation of ACBP on cellular proliferation and apoptosis in normal bronchial and NSCLC cell lines. Using tritiated-palmitate ((3)H-palmitate), we measured \u03b2-oxidation levels and tested the effect of etomoxir, a \u03b2-oxidation inhibitor, on proliferation and apoptosis. MALDI-IMS and IHC analysis confirmed that ACBP is overexpressed in pre-invasive and invasive lung cancers. High ACBP gene expression levels in NSCLCs correlated with worse survival (HR = 1.73). We observed a 40% decrease in \u03b2-oxidation and concordant decreases in proliferation and increases in apoptosis in ACBP-depleted NSCLC cells as compared with bronchial airway epithelial cells. Inhibition of \u03b2-oxidation by etomoxir in ACBP-overexpressing cells produced dose-dependent decrease in proliferation and increase in apoptosis (P = 0.01 and P < 0.001, respectively). These data suggest a role for ACBP in controlling lung cancer progression by regulating \u03b2-oxidation.","subset":"pubmed_abstract"} +{"meta":{"pmid":16771892,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":3,"2022-05":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-05":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2023-14":1}}},"text":"The dynamics of injection drug users' personal networks and HIV risk behaviors.\nWhile studies of the social networks of injection drug users (IDUs) have provided insight into how the structures of interpersonal relationships among IDUs affect HIV risk behaviors, the majority of these studies have been cross-sectional. The present study examined the dynamics of IDUs' social networks and HIV risk behaviors over time. Using data from a longitudinal HIV-intervention study conducted in Baltimore, MD, this study assessed changes in the composition of the personal networks of 409 IDUs. We used a multi-nomial logistic regression analysis to assess the association between changes in network composition and simultaneous changes in levels of injection HIV risk behaviors. Using the regression parameters generated by the multi-nomial model, we estimated the predicted probability of being in each of four HIV risk behavior change groups. Compared to the base case, individuals who reported an entirely new set of drug-using network contacts at follow-up were more than three times as likely to be in the increasing risk group. In contrast, reporting all new non-drug-using contacts at follow-up increased the likelihood of being in the stable low-risk group by almost 50% and decreased the probability of being in the consistently high-risk group by more than 70%. The findings from this study show that, over and above IDUs' baseline characteristics, changes in their personal networks are associated with changes in individuals' risky injection behaviors. They also suggest that interventions aimed at reducing HIV risk among IDUs might benefit from increasing IDUs' social contacts with individuals who are not drug users.","subset":"pubmed_abstract"} +{"meta":{"pmid":26290240,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":11}}},"text":"Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum.\nAddiction is thought to be a maladaptive form of learning and memory caused by drug-evoked aberrant synaptic plasticity. We previously showed that alcohol facilitates synaptic plasticity in the dorsomedial striatum (DMS), a brain region that drives goal-directed behaviors. The majority of DMS cells are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1Rs) or D2 receptors (D2Rs), which drive \"Go\" or \"No-Go\" behaviors, respectively. Here, we report that alcohol induces cell type-specific synaptic and structural plasticity in the DMS. Using mice that express a fluorescence marker to visualize D1R or D2R MSNs, we show that repeated cycles of systemic administration of alcohol or alcohol consumption induces a long-lasting increase in AMPAR activity specifically in DMS D1R but not in D2R MSNs. Importantly, we report that alcohol consumption increases the complexity of dendritic branching and the density of mature mushroom-shaped spines selectively in DMS D1R MSNs. Finally, we found that blockade of D1R but not D2R activity in the DMS attenuates alcohol consumption. Together, these data suggest that alcohol intake produces profound functional and structural plasticity events in a subpopulation of neurons in the DMS that control reinforcement-related learning. Alcohol addiction is considered maladaptive learning and memory processes. Here we unraveled a long-lasting cellular mechanism that may contribute to the memory of alcohol-seeking behaviors. Specifically, we found that alcohol consumption produces a long-lasting enhancement of channel activity and persistent alterations of neuronal morphology in a part of the brain (DMS) that controls alcohol-drinking behaviors. Furthermore, we show that these alterations occur only in a subpopulation of neurons that positively control reward and reinforcement of drugs of abuse. Finally, we report that blocking the activity of this neuronal population reduces alcohol intake. As such synaptic and structural changes are the cellular hallmarks of learning and memory, and these neuroadaptations may drive the development of pathological heavy alcohol consumption.","subset":"pubmed_abstract"} +{"meta":{"pmid":21542916,"dup_signals":{"dup_doc_count":24,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":1,"2024-18":3,"2024-10":4,"2024-30":1,"unknown":14}}},"text":"Challenges of maintaining research protocol fidelity in a clinical care setting: a qualitative study of the experiences and views of patients and staff participating in a randomized controlled trial.\nTrial research has predominantly focused on patient and staff understandings of trial concepts and\/or motivations for taking part, rather than why treatment recommendations may or may not be followed during trial delivery. This study sought to understand why there was limited attainment of the glycaemic target (HbA(1c) \u22646.5%) among patients who participated in the Treating to Target in Type 2 Diabetes Trial (4-T). The objective was to inform interpretation of trial outcomes and provide recommendations for future trial delivery. In-depth interviews were conducted with 45 patients and 21 health professionals recruited from 11 of 58 trial centres in the UK. Patients were broadly representative of those in the main trial in terms of treatment allocation, demographics and glycaemic control. Both physicians and research nurses were interviewed. Most patients were committed to taking insulin as recommended by 4-T staff. To avoid hypoglycaemia, patients occasionally altered or skipped insulin doses, normally in consultation with staff. Patients were usually unaware of the trial's glycaemic target. Positive staff feedback could lead patients to believe they had been 'successful' trial participants even when their HbA(1c) exceeded 6.5%. While some staff felt that the 4-T automated insulin dose adjustment algorithm had increased their confidence to prescribe larger insulin doses than in routine clinical practice, all described situations where they had not followed its recommendations. Staff regarded the application of a 'one size fits all' glycaemic target during the trial as contradicting routine clinical practice where they would tailor treatments to individuals. Staff also expressed concerns that 'tight' glycaemic control might impose an unacceptably high risk of hypoglycaemia, thus compromising trust and safety, especially amongst older patients. To address these concerns, staff tended to adapt the trial protocol to align it with their clinical practices and experiences. To understand trial findings, foster attainment of endpoints, and promote protocol fidelity, it may be necessary to look beyond individual patient characteristics and experiences. Specifically, the context of trial delivery, the impact of staff involvement, and the difficulties staff may encounter in balancing competing 'clinical' and 'research' roles and responsibilities may need to be considered and addressed.","subset":"pubmed_abstract"} +{"meta":{"pmid":24349421,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Gathering and exploring scientific knowledge in pharmacovigilance.\nPharmacovigilance plays a key role in the healthcare domain through the assessment, monitoring and discovery of interactions amongst drugs and their effects in the human organism. However, technological advances in this field have been slowing down over the last decade due to miscellaneous legal, ethical and methodological constraints. Pharmaceutical companies started to realize that collaborative and integrative approaches boost current drug research and development processes. Hence, new strategies are required to connect researchers, datasets, biomedical knowledge and analysis algorithms, allowing them to fully exploit the true value behind state-of-the-art pharmacovigilance efforts. This manuscript introduces a new platform directed towards pharmacovigilance knowledge providers. This system, based on a service-oriented architecture, adopts a plugin-based approach to solve fundamental pharmacovigilance software challenges. With the wealth of collected clinical and pharmaceutical data, it is now possible to connect knowledge providers' analysis and exploration algorithms with real data. As a result, new strategies allow a faster identification of high-risk interactions between marketed drugs and adverse events, and enable the automated uncovering of scientific evidence behind them. With this architecture, the pharmacovigilance field has a new platform to coordinate large-scale drug evaluation efforts in a unique ecosystem, publicly available at http:\/\/bioinformatics.ua.pt\/euadr\/.","subset":"pubmed_abstract"} +{"meta":{"pmid":18215727,"dup_signals":{"dup_doc_count":11}},"text":"Differences in sensitivity to cold in Japanese men and postmenopausal women aged > or =50 years.\nSensitivity to cold is associated with several factors, such as aging, sex, and body composition. However, no previous studies have examined the differences in sensitivity to cold in men and women or the association of hormonal levels with sensitivity to cold. The aim of the present study was to clarify both the change in sensitivity to cold with aging and the difference in sensitivity to cold between men and women. Associations were also examined between circulating hormonal concentrations and the changes with aging and differences in sensitivity. This population-based cohort study enrolled healthy Japanese men and women aged > or = 50 years. A standardized 210-item health questionnaire was used to obtain information on symptoms of sensitivity to cold. Serum concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG) were measured. Of the 154 men and 180 women enrolled in this study, more women than men had sensitivity to cold. Whereas the percentage of men who had sensitivity to cold significantly increased with aging (P < 0.05), the percentage of women who had sensitivity to cold was already high (23.7%) at 50 to 60 years of age and did not change with aging. In men, advancing age and low body mass index (BMI) were significantly associated with sensitivity to cold (P < 0.05); however, age and BMI in women were not similarly associated. In addition, the effect of sex after adjustment for age was significant (P < 0.05), and there was also a numeric but nonsignificant effect of sex after adjustment for BMI. In men, low serum levels of the gonadal hormone FSH were significantly associated with sensitivity to cold in logistic analysis, but this association was nonsignificant after multivariate analysis. Serum concentrations of gonadal hormones and SHBG in women were not associated with sensitivity to col. The association of age with sensitivity to cold was different in men and women; the association of BMI with sensitivity to cold might be different in men and women. In addition, these changes in sensitivity to cold were not associated with circulating hormonal concentrations.","subset":"pubmed_abstract"} +{"meta":{"pmid":30301740,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Genome Instability Is Promoted by the Chromatin-Binding Protein Spn1 in Saccharomyces cerevisiae.\nCells expend a large amount of energy to maintain their DNA sequence. DNA repair pathways, cell cycle checkpoint activation, proofreading polymerases, and chromatin structure are ways in which the cell minimizes changes to the genome. During replication, the DNA-damage tolerance pathway allows the replication forks to bypass damage on the template strand. This avoids prolonged replication fork stalling, which can contribute to genome instability. The DNA-damage tolerance pathway includes two subpathways: translesion synthesis and template switch. Post-translational modification of PCNA and the histone tails, cell cycle phase, and local DNA structure have all been shown to influence subpathway choice. Chromatin architecture contributes to maintaining genome stability by providing physical protection of the DNA and by regulating DNA-processing pathways. As such, chromatin-binding factors have been implicated in maintaining genome stability. Using Saccharomyces cerevisiae, we examined the role of Spn1 (Suppresses postrecruitment gene number 1), a chromatin-binding and transcription elongation factor, in DNA-damage tolerance. Expression of a mutant allele of SPN1 results in increased resistance to the DNA-damaging agent methyl methanesulfonate, lower spontaneous and damage-induced mutation rates, along with increased chronological life span. We attribute these effects to an increased usage of the template switch branch of the DNA-damage tolerance pathway in the spn1 strain. This provides evidence for a role of wild-type Spn1 in promoting genome instability, as well as having ties to overcoming replication stress and contributing to chronological aging.","subset":"pubmed_abstract"} +{"meta":{"pmid":10785857,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Mx mRNA expression and RFLP analysis of rainbow trout Oncorhynchus mykiss genetic crosses selected for susceptibility or resistance to IHNV.\nThree interferon-inducible Mx genes have been identified in rainbow trout Oncorhynchus mykiss and their roles in virus resistance have yet to be determined. In mice, expression of the Mx1 protein is associated with resistance to influenza virus. We report a study to determine whether there was a correlation between the expression of Mx in rainbow trout and resistance to a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV). A comparison of Mx mRNA expression was made between different families of cultured rainbow trout selected for resistance or for susceptibility to IHNV. A trout-specific Mx cDNA gene probe was used to determine whether there was a correlation between Mx mRNA expression and resistance to the lethal effects of IHNV infection. Approximately 99% of trout injected with a highly virulent strain of the fish rhabdovirus, IHNV, were able to express full length Mx mRNA at 48 h post infection. This is markedly different from the expression of truncated, non-functional Mx mRNA found in most laboratory strains of mice, and the ability of only 25% of wild mice to express functional Mx protein. A restriction fragment length polymorphism (RFLP) assay was developed to compare the Mx locus between individual fish and between rainbow trout genetic crosses bred for IHNV resistance or susceptibility. The assay was able to discriminate 7 distinct RFLP patterns in the rainbow trout crosses. One cross was identified that showed a correlation between homozygosity at the Mx locus and greater susceptibility to IHN-caused mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":24030706,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-26":1,"unknown":11}}},"text":"Patient perspectives of dabigatran: analysis of online discussion forums.\nIn 2010 the US FDA approved dabigatran, the first new anticoagulant for stroke prevention in non-valvular atrial fibrillation (AF) since 1954. To date there is little data that reflects the experiences and perceptions of real-world patients with dabigatran. The abundance of Internet-based discussion forums and support groups related to AF or anticoagulation may provide a low-cost resource for assessing patient experiences. The aim of this study was to determine patient experiences and perceptions regarding dabigatran through qualitative thematic content analysis of comments posted on publicly accessible virtual discussion forums and Internet support groups. Comments posted between January 2011 and September 2012 were downloaded from websites focusing on support of patients with AF or on anticoagulation therapy. Comments were analyzed for thematic content. Five broad thematic categories emerged from the posted comments: general concerns about safety and efficacy, questions about indications and contraindications, questions about proper use and storage, questions about diet and drug restrictions, and experiences with perceived side effects. Our data revealed that a primary concern for patients taking dabigatran is the lack of antidote to reverse the effects of dabigatran if bleeding occurs. Several questions pertaining to the use of dabigatran with other medications or medical conditions were noted, and multiple patients expressed confusion about instructions for using dabigatran before and after medical procedures. An unexpected finding included several criticisms of the medication packaging, which many patients found inconvenient or difficult to open. Finally, several perceived side effects were noted, including some not reported in clinical trials. Online communities may provide information about topics that are a concern to patients and that may not be discernible in clinical trials, such as medication side effects, proper use, and safety. Our data also highlighted potential topics that may not be a priority to researchers but are nevertheless important to patients (e.g. medication convenience or packaging). Despite the growing use of online health-related communities, very little research makes use of this low-cost resource for identifying patient interests regarding therapeutic treatments to guide patient-oriented research.","subset":"pubmed_abstract"} +{"meta":{"pmid":11178117,"dup_signals":{"dup_doc_count":12,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":1,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2}}},"text":"The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma.\nThe anti-PM\/Scl autoantibodies are known to characterize a subset of autoimmune patients with myositis, scleroderma (Scl), and the PM\/Scl overlap syndrome. The major autoantigens that are recognized by anti-PM\/Scl autoantibodies are designated PM\/Scl-100 and PM\/Scl-75. These autoantigens have been reported to associate into a large complex consisting of 11 to 16 proteins and to play a role in ribosome synthesis. Recently, it was discovered that the PM\/Scl complex is the human counterpart of the yeast (Saccharomyces cerevisiae) exosome, which is an RNA-processing complex consisting of 11 3' --> 5' exoribonucleases. To date, 10 human exosome components have been identified, although only some of these were studied in more detail. In this review, we discuss some recent advances in the characterization of the PM\/Scl complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":20042626,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"The nonserotypeable pneumococcus: phenotypic dynamics in the era of anticapsular vaccines.\nNonserotypeable pneumococci (NSP) are commonly carried by Australian Indigenous children in remote communities. The purpose of this study was to characterize carriage isolates of NSP from Indigenous children vaccinated with the seven-valent pneumococcal conjugate vaccine (PCV7) and to use these data to guide decisions on reporting of NSP. A total of 182 NSP were characterized by BOX typing, antibiogram analysis, and multilocus sequence typing (MLST) of common BOX types. NSP positive for the wzg capsule gene were analyzed by a multiplex PCR-based reverse line blot hybridization assay (mPCR\/RLB-H) targeting capsule genes to determine the serotype. Among 182 NSP, 49 BOX types were identified. MLST of 10 representative isolates found 7 STs, including ST448 (which accounted for 11% of NSP). Non-penicillin susceptibility was evident in 51% of the isolates. Pneumococcal wzg sequences were detected in only 23 (13%) NSP, including 10 that contained an approximately 1.2-kb insert in the region. mPCR\/RLB-H identified serotype 14 wzy sequences in all 10 NSP, and 1 also contained a serotype 3-specific wze sequence. Among the remaining 13 wzg-positive NSP, few belonged to the serotypes represented in PCV7. It appears that most NSP identified in Australian Indigenous children are from a true nonencapsulated lineage. Few NSP represented serotypes in PCV7 that suppress capsular expression. High rates of carriage and penicillin resistance and the occasional presence of capsule genes suggest a role for NSP in the maintenance and survival of capsulated pneumococci. To avoid the inflation of pneumococcal carriage and antibiotic resistance rates, in clinical trials, we recommend separate reporting of rates of capsular strains and NSP and the exclusion of data for NSP from primary analyses.","subset":"pubmed_abstract"} +{"meta":{"pmid":26049483,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Assessment of TD-DFT and LF-DFT for study of d - d transitions in first row transition metal hexaaqua complexes.\nHerein, we present the systematic, comparative computational study of the d - d transitions in a series of first row transition metal hexaaqua complexes, [M(H2O)6](n+) (M(2+\/3+) = V (2+\/3+), Cr(2+\/3+), Mn(2+\/3+), Fe(2+\/3+), Co(2+\/3+), Ni(2+)) by the means of Time-dependent Density Functional Theory (TD-DFT) and Ligand Field Density Functional Theory (LF-DFT). Influence of various exchange-correlation (XC) approximations have been studied, and results have been compared to the experimental transition energies, as well as, to the previous high-level ab initio calculations. TD-DFT gives satisfactory results in the cases of d(2), d(4), and low-spin d(6) complexes, but fails in the cases when transitions depend only on the ligand field splitting, and for states with strong character of double excitation. LF-DFT, as a non-empirical approach to the ligand field theory, takes into account in a balanced way both dynamic and non-dynamic correlation effects and hence accurately describes the multiplets of transition metal complexes, even in difficult cases such as sextet-quartet splitting in d(5) complexes. Use of the XC functionals designed for the accurate description of the spin-state splitting, e.g., OPBE, OPBE0, or SSB-D, is found to be crucial for proper prediction of the spin-forbidden excitations by LF-DFT. It is shown that LF-DFT is a valuable alternative to both TD-DFT and ab initio methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":17641561,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":3,"unknown":13}}},"text":"Acupuncture for anxiety and anxiety disorders--a systematic literature review.\nThe aim of this study was to evaluate the evidence for the efficacy of acupuncture in the treatment of anxiety and anxiety disorders by systematic review of the relevant research. Searches of the major biomedical databases (MEDLINE, EMBASE, ClNAHL, PsycINFO, Cochrane Library) were conducted between February and July 2004. Specialist complementary medicine databases were also searched and efforts made to identify unpublished research. No language restrictions were imposed and translations were obtained where necessary. Study methodology was appraised and clinical commentaries obtained for studies reporting clinical outcomes. Twelve controlled trials were located, of which 10 were randomised controlled trials (RCTs). Four RCTs focused on acupuncture in generalised anxiety disorder or anxiety neurosis, while six focused on anxiety in the perioperative period. No studies were located on the use of acupuncture specifically for panic disorder, phobias or obsessive-compulsive disorder. In generalised anxiety disorder or anxiety neurosis, it is difficult to interpret the findings of the studies of acupuncture because of the range of interventions against which acupuncture was compared. All trials reported positive findings but the reports lacked many basic methodological details. Reporting of the studies of perioperative anxiety was generally better and the initial indications are that acupuncture, specifically auricular acupuncture, is more effective than acupuncture at sham points and may be as effective as drug therapy in this situation. The results were, however, based on subjective measures and blinding could not be guaranteed. Positive findings are reported for acupuncture in the treatment of generalised anxiety disorder or anxiety neurosis but there is currently insufficient research evidence for firm conclusions to be drawn. No trials of acupuncture for other anxiety disorders were located. There is some limited evidence in favour of auricular acupuncture in perioperative anxiety. Overall, the promising findings indicate that further research is warranted in the form of well designed, adequately powered studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":32563242,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-22":1,"unknown":10}}},"text":"Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis.\nRecently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous\/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous\/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous\/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28-1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55-0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference - 1.27, 95% Confidence Interval - 2.45-0.08, P = 0.04) in critically ill patients. Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous\/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C\/PI as a dosing strategy.","subset":"pubmed_abstract"} +{"meta":{"pmid":24131864,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":8}}},"text":"The demonstration of a theory-based approach to the design of localized patient safety interventions.\nThere is evidence of unsafe care in healthcare systems globally. Interventions to implement recommended practice often have modest and variable effects. Ideally, selecting and adapting interventions according to local contexts should enhance effects. However, the means by which this can happen is seldom systematic, based on theory, or made transparent. This work aimed to demonstrate the applicability, feasibility, and acceptability of a theoretical domains framework implementation (TDFI) approach for co-designing patient safety interventions. We worked with three hospitals to support the implementation of evidence-based guidance to reduce the risk of feeding into misplaced nasogastric feeding tubes. Our stepped process, informed by the TDF and key principles from implementation literature, entailed: involving stakeholders; identifying target behaviors; identifying local factors (barriers and levers) affecting behavior change using a TDF-based questionnaire; working with stakeholders to generate specific local strategies to address key barriers; and supporting stakeholders to implement strategies. Exit interviews and audit data collection were undertaken to assess the feasibility and acceptability of this approach. Following audit and discussion, implementation teams for each Trust identified the process of checking the positioning of nasogastric tubes prior to feeding as the key behavior to target. Questionnaire results indicated differences in key barriers between organizations. Focus groups generated innovative, generalizable, and adaptable strategies for overcoming barriers, such as awareness events, screensavers, equipment modifications, and interactive learning resources. Exit interviews identified themes relating to the benefits, challenges, and sustainability of this approach. Time trend audit data were collected for 301 patients over an 18-month period for one Trust, suggesting clinically significant improved use of pH and documentation of practice following the intervention. The TDF is a feasible and acceptable framework to guide the implementation of patient safety interventions. The stepped TDFI approach engages healthcare professionals and facilitates contextualization in identifying the target behavior, eliciting local barriers, and selecting strategies to address those barriers. This approach may be of use to implementation teams and policy makers, although our promising findings confirm the need for a more rigorous evaluation; a balanced block evaluation is currently underway.","subset":"pubmed_abstract"} +{"meta":{"pmid":24920827,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":12}}},"text":"G-quadruplex conformation and dynamics are determined by loop length and sequence.\nThe quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity.","subset":"pubmed_abstract"} +{"meta":{"pmid":30010122,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":14}}},"text":"Distinct Neuroanatomical Correlates of Neuropsychiatric Symptoms in the Three Main Forms of Genetic Frontotemporal Dementia in the GENFI Cohort.\nThe overlap between frontotemporal dementia (FTD) and primary psychiatric disorders has been brought to light by reports of prominent neuropsychiatric symptoms (NPS) in FTD-related genetic mutations, particularly among C9orf72 and GRN carriers. It has been recently demonstrated that early neuroanatomical changes in genetic FTD may be different across the major disease-causing mutations. We aimed to identify whether NPS could be driven by distinct structural correlates. One hundred and sixty-seven mutation carriers (75 GRN, 60 C9orf72, and 32 MAPT) were included from the Genetic FTD Initiative (GENFI) study, a large international cohort of genetic FTD. Neuropsychiatric symptoms including delusions, hallucinations (visual, auditory, and tactile), depression, and anxiety were investigated using a structured interview. Voxel-based morphometry was performed to identify neuroanatomical correlates of NPS. Psychotic symptoms correlated mainly with grey matter (GM) atrophy in the anterior insula, left thalamus, cerebellum, and cortical regions including frontal, parietal, and occipital lobes in GRN mutations carriers. GM atrophy in posterior structures of the default-mode network was associated with anxiety in the GRN group. Delusions in C9orf72 expansion carriers were mainly associated with left frontal cortical atrophy. Cerebellar atrophy was found to be correlated only with anxiety in C9orf72 carriers. NPS in the MAPT group were mainly associated with volume loss in the temporal lobe. Neuroanatomical correlates of NPS appear to be distinct across the main forms of genetic FTD. Overall, our findings support overlapping brain structural changes between FTD and primary psychiatric disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":25653078,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Enhancing the usefulness of the Mini-BESTest for measuring dynamic balance: a Rasch validation study.\nRecently, a new balance scale, the Mini-BESTest, was introduced. This scale can be administered in about 15 min, and focuses on \"dynamic balance\". In spite of the recently increased use of this scale, further psychometric studies seem called for to enhance confidence in its use in different fields of clinical practice and research. To re-examine through Rasch analysis the metric properties of the Mini-BESTest and provide a nomogram that allow to quickly transform raw scores of the scale into linear estimates of dynamic balance. Observational cross-sectional study. Rehabilitation hospital. A total of 234 patients were consecutively admitted with a variety of neurological diseases causing balance impairment. Internal construct validity was assessed by determining how well data fit the Rasch model. Reliability was estimated for both persons and items. Scale unidimensionality and local independence of items were analysed performing a principal component analysis (PCA) on the standardized residuals. Also, a differential item functioning (DIF) analysis was run to assess the stability of item calibration across subsamples of patients. All 14 items of Mini-BESTest fitted the \"dynamic balance\" construct, i.e., the mean of the squared residuals for both the infit and outfit was between 0.8 and 1.2. The person abilities-item difficulty matching was very good. The reliability indices of the Mini-BESTest were as follows: person separation index=3.24 and person reliability=0.91; item separation index=12.00 and item reliability=0.99. The PCA of standardized residuals showed that the variance attributable to the Rasch factor was good (68%) and the eigenvalue of the unexplained variance in the first contrast was just 1.9, thus confirming the unidimensionality of the scale. No DIF was found across gender and age groups. The reliability indexes confirmed their high values, giving a high degree of confidence in the consistency of both person-ability and item-difficulty estimates. Results allowed to transform the ordinal summed raw scores of the Mini-BESTest into interval-level measurements using a nomogram. Since no significant local dependence between items was found, this means that each Mini-BESTest item is appropriate for measuring the variable of interest (dynamic balance) and not redundant. DIF analysis showed the stability of item hierarchy and difficulty among subsamples of patients of different gender and age. This study further increases confidence in use of the Mini-BESTest for clinical assessment of dynamic balance in patients undergoing rehabilitation.","subset":"pubmed_abstract"} +{"meta":{"pmid":32362245,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study.\nA new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions.Communicated by Ramaswamy H. Sarma.","subset":"pubmed_abstract"} +{"meta":{"pmid":32362965,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":9}}},"text":"The Relationship Between Number of Comorbidities and Age of Colorectal Cancer Diagnosis in US Male Veteran Population: A Single-Center Experience.\nComorbidities of tobacco and alcohol abuse and obesity are major risk factors for colon carcinogenesis. These risk factors are considered the most prevalent modifiable risk factors linked to malignancies including colorectal cancer (CRC) in both high- and low-income countries. The aim of this study was to investigate the relationship between number of comorbidities and age of CRC diagnosis in US male veteran population. A retrospective single-center study using chart review and the International Classification of Diseases, Ninth Revision (ICD-9) codes to identify patients with a diagnosis of CRC and comorbidities of tobacco abuse, alcohol abuse, hypertension (HTN), diabetes mellitus (DM) and chronic kidney disease (CKD). The primary aim was to study effect of these comorbidities on age of CRC diagnosis. Univariable and then multivariable logistic regression models were fit to age at diagnosis for each patient variable. A total of 362 patients were included in the study. The mean age of CRC diagnosis was 66.8. Eighty percent were Caucasians, and 20% were African Americans. African Americans were diagnosed with CRC 3.8 years younger compared to Caucasians (P = 0.01). Controlling for other variables in the multivariable model, age at CRC diagnosis was significantly lower for African Americans and for patients with higher total counts for tobacco and alcohol abuse and obesity. HTN, DM and CKD were not associated with a lower age of CRC diagnosis. Tobacco and alcohol abuse and obesity have negative cumulative effect on age of CRC diagnosis in US male veteran population. Patients with increasing number of these comorbidities are associated with significantly lower age of CRC diagnosis. It is important to identify veterans with these comorbidities and encourage CRC screening.","subset":"pubmed_abstract"} +{"meta":{"pmid":18279971,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":20}}},"text":"Genetically encoded chloride indicator with improved sensitivity.\nChloride (Cl) is the most abundant physiological anion. Abnormalities in Cl regulation are instrumental in the development of several important diseases including motor disorders and epilepsy. Because of difficulties in the spectroscopic measurement of Cl in live tissues there is little knowledge available regarding the mechanisms of regulation of intracellular Cl concentration. Several years ago, a CFP-YFP based ratiometric Cl indicator (Clomeleon) was introduced [Kuner, T., Augustine, G.J. A genetically encoded ratiometric indicator for chloride: capturing chloride transients in cultured hippocampal neurons. Neuron 2000; 27: 447-59]. This construct with relatively low sensitivity to Cl (K(app) approximately 160 mM) allows ratiometric monitoring of Cl using fluorescence emission ratio. Here, we propose a new CFP-YFP-based construct (Cl-sensor) with relatively high sensitivity to Cl (K(app) approximately 30 mM) due to triple YFP mutant. The construct also exhibits good pH sensitivity with pK(alpha) ranging from 7.1 to 8.0 pH units at different Cl concentrations. Using Cl-sensor we determined non-invasively the distribution of [Cl](i) in cultured CHO cells, in neurons of primary hippocampal cultures and in photoreceptors of rat retina. This genetically encoded indicator offers a means for monitoring Cl and pH under different physiological conditions and high-throughput screening of pharmacological agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":28655639,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-40":2,"2023-23":1,"2023-14":1,"2021-39":2,"2021-21":1,"2021-17":1,"2020-40":1,"2020-05":1,"2019-47":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1}}},"text":"Inflammatory cell infiltrates in advanced metastatic uveal melanoma.\nCurrent treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few and to date have demonstrated only marginal success. High densities of tumor-associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole-tissue sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal antibodies against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial distribution of TILs were highlighted using antibodies against CD3 (pan-lymphocyte marker), CD4 (T-helper cells), and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumor in all 35 specimens; their density was \"moderate\" in 50% of cases and \"few\" in 43%, and the majority showed an \"indeterminate\" phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumor. Of these, CD8+ TILs were \"few\" in number within mUM but were predominantly seen peritumorally at the tumor\/normal liver interface, whereas CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of \"indeterminate\" morphology were observed in mUM, suggesting a tendency toward the protumorigenic M2 phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peritumoral. The biological and functional roles of inflammatory cells in mUM require further investigation to determine if they represent potential targets for future therapies in mUM.","subset":"pubmed_abstract"} +{"meta":{"pmid":21502540,"dup_signals":{"dup_doc_count":40,"dup_dump_count":32,"dup_details":{"curated_sources":3,"2017-30":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":1,"2023-40":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1}}},"text":"Conducting cancer control and survivorship research via cooperative groups: a report from the American Society of Preventive Oncology.\nAs the number of cancer survivors expands, the need for cancer control and survivorship research becomes increasingly important. The National Cancer Institute (NCI) Cooperative Groups may offer a viable platform to perform such research. Observational, preventive, and behavioral research can often be performed within the cooperative group setting, especially if resources needed for evaluation are fairly simple, if protocols are easily implemented within the typical clinical setting, and if interventions are well standardized. Some protocols are better suited to cooperative groups than are others, and there are advantages and disadvantages to conducting survivorship research within the cooperative group setting. Behavioral researchers currently involved in cooperative groups, as well as program staff within the NCI, can serve as sources of information for those wishing to pursue symptom management and survivorship studies within the clinical trial setting. The structure of the cooperative groups is currently changing, but going forward, survivorship is bound to be a topic of interest and one that perhaps may be more easily addressed using the proposed more centralized structure.","subset":"pubmed_abstract"} +{"meta":{"pmid":23519848,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Importance of anorectal manometry after definitive surgery for Hirschsprung's disease in children.\nThe purpose of this investigation is to evaluate anorectal function after definitive surgery for Hirschsprung's disease (HD) by anorectal manometry. We evaluated the anorectal manometric assessment of 18 children who were operated for HD. Functional outcomes were determined by a questionnaire. Rectoanal inhibitory reflex (RAIR) and maximum anal resting pressure (MARP) were monitored. The results were compared between obstructive patients and asymptomatic patients. The median age at definitive operation was 19 months (range 12-72 months). Anorectal manometry was performed in 14 male and 4 female patients. All the cases underwent three staged procedure for HD and modified Duhamel procedure was performed as definitive procedure for all the patients. Mean age was 4.3 months (range 25 days to 5 years) at time of diagnosis. Post-operative enterocolitis or severe constipation was observed in seven patients (38.8%). There were no patients with incontinence. Eighteen patients underwent anorectal manometry meanly 2 years after definitive operation. RAIR was absent in 14 (77.7%) patients and abnormal in 4 (22.2%). There were no significant differences in the MARP values between symptomatic and asymptomatic patients. The results of our study showed that the majority of the patients have impaired anorectal motility. There were no significant differences in the results of the functional studies for the seven patients with symptoms of obstruction or constipation when compared with asymptomatic patients after surgery for HD.","subset":"pubmed_abstract"} +{"meta":{"pmid":21643395,"dup_signals":{"dup_doc_count":31,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2016-44":2,"2016-40":1,"2016-36":3,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":3,"2015-40":3,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":4,"2017-39":1,"2015-18":1}}},"text":"Mie scattering in the time domain. Part II. The role of diffraction.\nThe p=0 term of the Mie-Debye scattering amplitude contains the effects of external reflection and diffraction. We computed the reflected intensity in the time domain as a function of the scattering angle and delay time for a short electromagnetic pulse incident on a spherical particle and compared it to the predicted behavior in the forward-focusing region, the specular reflection region, and the glory region. We examined the physical consequences of three different approaches to the exact diffraction amplitude, and determined the signature of diffraction in the time domain. The external reflection surface wave amplitude gradually replaces the diffraction amplitude in the angular transition region between forward-focusing and the region of specular reflection. The details of this replacement were studied in the time domain.","subset":"pubmed_abstract"} +{"meta":{"pmid":2560022,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Medical screening of 1500 patients in a dental surgery: a prospective study.\nCommunication between medical and dental practitioners about patients they have in common enhances total patient care, but such communication rarely occurs. This may be due to lack of appreciation by doctors of the medical risks to certain patients undergoing dental treatment. To ascertain a relevant medical history, prospective medical screening was performed on 1500 new patients attending a general dental practice using a standard health questionnaire followed by an interview between the patient and dentist. There were 382 (25.5%) patients with a current or past medical history of relevance to dentistry, 90 (6.0%) were taking medication of potential importance and 105 (7.0%) considered they had an intolerance to certain drugs. The screening provided a patient data base for medical and medico-legal purposes. A total of 376 (25.1%) questionnaires were filled out incorrectly and 63 of these (16.8%) had major misinformation about medical history. A small but important group deliberately misled the dentist either from fear of refusal of treatment or embarrassment about their medical history. Therefore interviews are an essential adjunct to written health questionnaires in eliciting accurate information. Formal screening of new patients is essential in general dental practice. Furthermore, general medical practitioners need to become aware of the common risks to patients undergoing dentistry. Better formal and informal communication between general medical and dental practitioners is recommended for the benefit of their mutual patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":27032686,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"On a New Species of Parasitic Barnacle (Crustacea: Rhizocephala), Sacculina shiinoi sp. nov., Parasitizing Japanese Mud Shrimps Upogebia spp. (Decapoda: Thalassinidea: Upogebiidae), Including a Description of a Novel Morphological Structure in the Rhizocephala.\nThe rhizocephalan Sacculina shiinoi sp. nov. parasitizes three species of Upogebia in Japan. It is described morphologically and compared with another Upogebia parasite, Sacculina upogebiae Shiino, 1943 from Japan and Korea. These two species are the only sacculinids that parasitize mud shrimps. DNA analyses clearly show the two species to be separate and not closely related. The cuticle differs in being provided with close-set, branched, and spiny excrescences in S. shiinoi, while it lacks excrescences, but forms small scales in S. upogebiae. In S. upogebiae, the bulbous sperm-producing part and the narrow receptacle duct are separated by a compartmentalized mid portion, which is missing in S. shiinoi. A ridge, having a thickened, fluffy cuticle with a U-shaped course, passes across the visceral mass between the two receptacle openings in S. shiinoi. Such a structure has never been described in other rhizocephalans, and its function is uncertain.","subset":"pubmed_abstract"} +{"meta":{"pmid":18202836,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-20":1,"2017-13":1,"unknown":11}}},"text":"Animal models for genetic neuromuscular diseases.\nThe neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL\/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy\/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)\/dy(2J) mouse, both presenting significant reduction of alpha2-laminin in the muscle and a severe phenotype. The myodystrophy mouse (Large(myd)) harbors a mutation in the glycosyltransferase Large, which leads to altered glycosylation of alpha-DG, and also a severe phenotype. Other informative models for muscle proteins include the knockout mouse for myostatin, which demonstrated that this protein is a negative regulator of muscle growth. Additionally, the stress syndrome in pigs, caused by mutations in the porcine RYR1 gene, helped to localize the gene causing malignant hypertermia and Central Core myopathy in humans. The study of animal models for genetic diseases, in spite of the existence of differences in some phenotypes, can provide important clues to the understanding of the pathogenesis of these disorders and are also very valuable for testing strategies for therapeutic approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":16953881,"dup_signals":{"dup_doc_count":52,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2019-43":1,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":1,"2014-52":2,"2014-49":1,"2014-42":8,"2014-41":3,"2014-35":3,"2014-23":4,"2014-15":2,"2023-06":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":3,"2013-48":2,"2013-20":1}}},"text":"Acute effect of meal glycemic index and glycemic load on blood glucose and insulin responses in humans.\nFoods with contrasting glycemic index when incorporated into a meal, are able to differentially modify glycemia and insulinemia. However, little is known about whether this is dependent on the size of the meal. The purposes of this study were: i) to determine if the differential impact on blood glucose and insulin responses induced by contrasting GI foods is similar when provided in meals of different sizes, and; ii) to determine the relationship between the total meal glycemic load and the observed serum glucose and insulin responses. Twelve obese women (BMI 33.7 +\/- 2.4 kg\/m2) were recruited. Subjects received 4 different meals in random order. Two meals had a low glycemic index (40-43%) and two had a high-glycemic index (86-91%). Both meal types were given as two meal sizes with energy supply corresponding to 23% and 49% of predicted basal metabolic rate. Thus, meals with three different glycemic loads (95, 45-48 and 22 g) were administered. Blood samples were taken before and after each meal to determine glucose, free-fatty acids, insulin and glucagon concentrations over a 5-h period. An almost 2-fold higher serum glucose and insulin incremental area under the curve (AUC) over 2 h for the high- versus low-glycemic index same sized meals was observed (p < 0.05), however, for the serum glucose response in small meals this was not significant (p = 0.38). Calculated meal glycemic load was associated with 2 and 5 h serum glucose (r = 0.58, p < 0.01) and insulin (r = 0.54, p < 0.01) incremental and total AUC. In fact, when comparing the two meals with similar glycemic load but differing carbohydrate amount and type, very similar serum glucose and insulin responses were found. No differences were observed for serum free-fatty acids and glucagon profile in response to meal glycemic index. This study showed that foods of contrasting glycemic index induced a proportionally comparable difference in serum insulin response when provided in both small and large meals. The same was true for the serum glucose response but only in large meals. Glycemic load was useful in predicting the acute impact on blood glucose and insulin responses within the context of mixed meals.","subset":"pubmed_abstract"} +{"meta":{"pmid":24784106,"dup_signals":{"dup_doc_count":17,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2016-44":1,"2016-36":2,"2016-30":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":2,"2015-22":2,"2017-39":1,"2015-18":1}}},"text":"Mode-coupling polarization rotator based on plasmonic waveguide.\nA novel polarization rotator (PR) based on mode coupling in plasmonic waveguides is demonstrated by simulation. A silicon waveguide with asymmetric claddings of silicon oxide and metal is applied to induce a hybridization of the polarization modes. Operating at the telecommunication wavelength of 1.55 \u03bcm, polarization conversion efficiency of 99.7% can be achieved in a device at a length of 9.7 \u03bcm with an insertion loss of 2.2 dB. This PR can be easily fabricated by oblique deposition of the claddings after etching the silicon waveguide without precise alignment for two-step lithography as required in a previous design.","subset":"pubmed_abstract"} +{"meta":{"pmid":22639894,"dup_signals":{"dup_doc_count":55,"dup_dump_count":30,"dup_details":{"curated_sources":3,"2023-40":2,"2023-14":1,"2023-06":1,"2022-40":2,"2022-21":2,"2021-49":2,"2021-43":2,"2021-31":2,"2021-21":2,"2021-10":2,"2020-50":1,"2020-40":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-34":1,"2018-30":1,"2018-26":3,"2018-22":1,"2018-17":1,"2018-13":2,"2018-09":1,"2017-51":3,"2017-43":3,"2017-34":3,"2017-26":2,"2024-18":3,"2024-10":2,"2024-22":1}}},"text":"The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials.\nPremature neonates commonly receive red blood cell (RBC) transfusions. This study systematically identified and appraised randomized controlled trials (RCTs) where the intervention was 'transfusion of red blood cells' from searches of multiple databases. Primary review outcomes were mortality, neurodevelopmental and respiratory endpoints. Two reviewers extracted data and assigned overall quality. Twenty-seven RCTs were identified and grouped into four predefined categories: trials comparing RBC transfusion versus no transfusion\/placebo (n = 3); different thresholds for transfusion (n = 6); differing doses or administration schedule (n = 4), or different types or products of RBC (n = 14). In the threshold group of trials, enrolling 679 neonates, no significant differences in mortality (relative risk 1\u00b722, 95% confidence interval 0\u00b784-1\u00b775) or chronic lung disease were found. Only two trials assessed neurodevelopment outcomes, both within the threshold group, but with differing results. The largest subgroup of RCTs by number evaluated different media for storage of red cells (n = 7), enrolling 221 neonates. The methodological quality of many RCTs was poor. The design of future RCTs can be informed by the lessons from this review. Many trials failed to report on outcomes that would be considered of primary importance to clinicians. Consistent reporting of adverse events is required, and endpoints need to include neurodevelopmental outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":9021173,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-47":1,"2017-13":1}}},"text":"Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract.\nTo be therapeutically active, oral hyperimmune bovine immunoglobulin concentrate (BIC) must survive its passage through the intestinal tract. This led us to study the gastrointestinal stability of orally administered BIC directed against Clostridium difficile toxins (BIC-C. difficile). BIC-C. difficile was stable at neutral pH in vitro but was degraded at low pH, particularly in the presence of pepsin. Healthy volunteers (n = 6) took BIC-C. difficile (45 or 8 g) as a single oral dose. Total bovine immunoglobulin G (IgG) and specific anti-C. difficile IgG were measured in the stool. BIC was given under the following conditions: in the fasting state, in the fed state, with antacid, during omeprazole therapy, or in enteric capsules (released at pH > 6). The mean fecal bovine IgG content of 3-day stool collections was similar in the fasting (536 mg; 3.8% of the ingested dose of BIC), fed (221 mg; 1.6%), and antacid (381 mg; 2.7%) groups. Omeprazole therapy was associated with increased fecal bovine IgG levels (1253 mg; 8.8%), but this difference did not reach statistical significance (P = 0.07). Administration of 8 g of BIC-C. difficile in enteric capsules resulted in substantially higher fecal bovine IgG levels (1,124 mg; 32.7% of the oral dose) than those obtained after administration of nonencapsulated BIC (22 MG; 0.6%; P = 0.004). An inverse relationship was noted between intestinal transit time and fecal bovine IgG content (R = 0.83; P = 0.04 [data from omeprazole group]). Filtrates of stool samples collected after oral administration of BIC-C. difficile neutralized the cytotoxicity of C. difficile toxins A and B, whereas control stool filtrates did not. Bovine colostral IgG undergoes partial degradation in the intestinal tract. Exposure to acidic gastric secretions and prolonged colonic transit may both contribute to IgG degradation. Nonetheless, humans taking BIC-C. difficile orally have neutralizing antitoxin activity in their stool.","subset":"pubmed_abstract"} +{"meta":{"pmid":6129277,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":14}}},"text":"Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure.\nLong-term functional capacities of marrow cell lines were defined by competitive repopulation, a technique capable of detecting a small decline in repopulating abilities. There was little or no difference between cells from old and young donors, but a single serial transplantation caused a large decline in repopulating ability. Varying the numbers of marrow cells transplanted into the initial carrier from 10(5) to 10(7) did not alter the ability of the carrier's marrow cells to repopulate in competition with previously untransplanted cells. This ability was improved only in carriers that had received 10(8) marrow cells, although deleterious effects of transplantation were still present. These effects were not solely caused by cell damage from the transplantation procedure, because transplantation by parabiosis, or recovery from sublethal irradiation without transplantation, reduced repopulating abilities as much as transplanting 10(5) to 10(7) marrow cells. The transplantation effect also was not caused solely by irradiation, because the same effect appeared in unirradiated W\/Wv carriers. The transplantation effect was more pronounced when donors were identified by hemoglobin type than by chromosome markers, implying that nonerythroid cell lines may be less affected by transplantation than erythroid precursor cells. When the effects of a lifetime of normal function and a single transplantation were compared, the latter caused 3-7 times more decline in repopulating abilities of phytohemagglutinin-responsive cell precursors, and at least 10-20 times more decline in erythroid cell precursors. Stem cell lines can be serially transplanted at least five times before losing their ability to repopulate and save lethally irradiated recipients or to cure genetically anemic mice. Therefore, if transplantation causes an acceleration of the normal aging process, these figures suggest that stem cells should be able to function normally through at least 15-50 life spans.","subset":"pubmed_abstract"} +{"meta":{"pmid":16129404,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2023-40":1,"2015-18":1}}},"text":"The neural basis of financial risk taking.\nInvestors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.","subset":"pubmed_abstract"} +{"meta":{"pmid":2967682,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2018-47":1,"2018-39":1,"2018-26":1,"2018-05":1,"2017-47":1,"2017-30":1,"2017-17":1,"2023-40":1,"2017-13":1}}},"text":"Self-management for medication reduction in chronic low back pain.\nIt has been demonstrated that pain relief is seldom produced by medication or surgical methods where there is evidence of emotional disturbance, as indicated by the MMPI. A program that attempts to engender a high level of patient responsibility in a population of chronic low back pain patients is described. Self-managed reduction of drug dependence is a major component of this program. The data indicate that the program produces a significant reduction in dependence on opiates, derivatives, synthetic opiates, hypnotics, sedatives, tranquilizers, and analgesics. Follow-up data (with attrition controlled) at six months and 12 months postdischarge do not provide any evidence for deterioration (ie, return to pretreatment levels of drug dependence). Thus, it appears that the programmatic impact is stable over at least a 12-month period postdischarge. Implications of these findings for the low back pain population, as well as other chronic pain populations, are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":12660312,"dup_signals":{"dup_doc_count":19,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":6,"2024-26":3,"2024-22":1,"2024-18":1,"2024-10":1,"unknown":5}}},"text":"Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.\nThe effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT\/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng\/ml and 17.44 ng\/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.","subset":"pubmed_abstract"} +{"meta":{"pmid":26209413,"dup_signals":{"dup_doc_count":36,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":2,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-10":1,"2019-30":1,"2019-18":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-51":2,"2017-43":1,"2017-34":2,"2017-30":1,"2016-44":2,"2023-23":1}}},"text":"PoMo: An Allele Frequency-Based Approach for Species Tree Estimation.\nIncomplete lineage sorting can cause incongruencies of the overall species-level phylogenetic tree with the phylogenetic trees for individual genes or genomic segments. If these incongruencies are not accounted for, it is possible to incur several biases in species tree estimation. Here, we present a simple maximum likelihood approach that accounts for ancestral variation and incomplete lineage sorting. We use a POlymorphisms-aware phylogenetic MOdel (PoMo) that we have recently shown to efficiently estimate mutation rates and fixation biases from within and between-species variation data. We extend this model to perform efficient estimation of species trees. We test the performance of PoMo in several different scenarios of incomplete lineage sorting using simulations and compare it with existing methods both in accuracy and computational speed. In contrast to other approaches, our model does not use coalescent theory but is allele frequency based. We show that PoMo is well suited for genome-wide species tree estimation and that on such data it is more accurate than previous approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":11292519,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":9}}},"text":"Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments.\nReactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and\/or in red blood cells. Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. CLINICAL IMPLICATION AND LIMITATION: AEAs might be used for monitoring SSRIs effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":15554560,"dup_signals":{"dup_doc_count":26,"dup_details":{"curated_sources":2,"unknown":24}}},"text":"Olives and olive oil in cancer prevention.\nEpidemiologic studies conducted in the latter part of the twentieth century demonstrate fairly conclusively that the people of the Mediterranean basin enjoy a healthy lifestyle with decreased incidence of degenerative diseases. The data show that populations within Europe that consume the so-called 'Mediterranean diet' have lower incidences of major illnesses such as cancer and cardiovascular disease. Studies have suggested that the health-conferring benefits of the Mediterranean diet are due mainly to a high consumption of fibre, fish, fruits and vegetables. More recent research has focused on other important factors such as olives and olive oil. Obviously fibre (especially wholegrain-derived products), fruits and vegetables supply an important source of dietary antioxidants. What is the contribution from olives and olive oil? Apparently the potential is extremely high but epidemiologic studies rarely investigate consumption of these very important products in-depth, perhaps due to a lack of exact information on the types and amounts of antioxidants present. Recent studies have shown that olives and olive oil contain antioxidants in abundance. Olives (especially those that have not been subjected to the Spanish brining process) contain up to 16 g\/kg typified by acteosides, hydroxytyrosol, tyrosol and phenyl propionic acids. Olive oil, especially extra virgin, contains smaller amounts of hydroxytyrosol and tyrosol, but also contains secoiridoids and lignans in abundance. Both olives and olive oil contain substantial amounts of other compounds deemed to be anticancer agents (e.g. squalene and terpenoids) as well as the peroxidation-resistant lipid oleic acid. It seems probable that olive and olive oil consumption in southern Europe represents an important contribution to the beneficial effects on health of the Mediterranean diet.","subset":"pubmed_abstract"} +{"meta":{"pmid":16463896,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-21":1,"2020-05":1,"2019-26":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-21":1,"2017-13":1}}},"text":"The antioxidant effect of N-acethylcysteine on experimental contusion in rats.\nN-acethylcysteine (NAC) is known to have direct and indirect antioxidant abilities. We investigated the potential protective effect of NAC on ICP, brain edema and contusion volume after Controlled Cortical Impact (CCI) injury. A moderate CCI injury was induced on the left hemisphere in 48 Sprague Dawley rats. The animals were treated with intraperitoneal injection of NAC (163 mg\/kg\/KG) or physiological saline. Measurements of intracranial pressure (ICP) were performed and brains were removed at 24 hours. Gravimetric analysis of post-traumatic edema and morphometric measurements (TTC staining) of contusion volume were carried out in 24 animals, respectively. ICP measurements increased significantly over time with no significant differences between both groups. The relative difference in water content in NAC treated animals (1.45 +\/- 0.1%) did not differ significantly versus placebo (1.47 +\/- 0.2%). The contusion volume was diminished by 19% in the NAC group (53.52 +\/- 5.3 mm3) versus placebo (66.28 +\/- 4.7 mm3) without showing statistical significance. The antioxidant properties of NAC did not affect intracranial pressure or posttraumatic brain edema formation, although the moderate reduction of contusion volume might reveal beneficial effects on focal contusion.","subset":"pubmed_abstract"} +{"meta":{"pmid":14654674,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":16}}},"text":"The role of race and ethnicity in the State Children's Health Insurance Program (SCHIP) in four states: are there baseline disparities, and what do they mean for SCHIP?\nElimination of racial and ethnic disparities in health has become a major national goal. The State Children's Health Insurance Program (SCHIP) has the potential to reduce disparities among the children who enroll if they exhibit the same disparities that have been documented in previous studies of low-income children. To determine the potential impact of SCHIP on racial and ethnic disparities, it is critical to assess baseline levels of health disparities among children enrolling in SCHIP. To use data from the Child Health Insurance Research Initiative (CHIRI) to 1) describe the sociodemographic profile of new enrollees in SCHIP in Alabama, Florida, Kansas, and New York; 2) determine if there were differences in health insurance and health care experiences among white, black, and Hispanic SCHIP enrollees before enrollment in SCHIP; and 3) explore whether race or ethnicity, controlled for other factors, affected pre-SCHIP access to health coverage and health care. SCHIP programs in Alabama, Florida, Kansas, and New York, which together include 26% of SCHIP enrollees nationwide. Telephone interview (mailed survey in Alabama) about the child's health, health insurance, and health care experiences conducted shortly after SCHIP enrollment to assess experience during the time period before SCHIP. New SCHIP enrollees (0-17.9 years old in Alabama, Kansas, and New York and 11.5-17.9 years old in Florida). Stratified sampling was performed in Kansas and New York, with results weighted to reflect statewide populations of new SCHIP enrollees. Sociodemographic characteristics including income, education, employment, and other characteristics of the child and the family, race and ethnicity (white non-Hispanic, black non-Hispanic, and Hispanic [any race]), prior health insurance, health care access and utilization, and health status. Bivariate analyses were used to compare baseline measures upon enrollment for white, black, and Hispanic SCHIP enrollees. Multivariate analyses were performed to assess health status and health care access measures (prior insurance, presence of a usual source of care (USC), and use of preventive care), controlling for demographic factors described above. Weighted analyses (where appropriate) were performed by using SPSS, STATA, or SUDAAN. Racial and ethnic composition varied across the SCHIP cohorts studied, with black and Hispanic children comprising the following proportion of enrollees, respectively: Alabama, 33% and <1%; Florida, 16% and 26%; Kansas, 12% and 15%; and New York, 24% and 36%. Black and Hispanic children were more likely to reside in single-parent and lower-income families. With some variation by state, children from minority groups were more likely to report poorer health status than were white children. Relative to white children, children from minority groups in Florida and New York were more likely to have been uninsured for the entire year before SCHIP enrollment. In all states, children from minority groups who had prior coverage were more likely to have previously been enrolled in Medicaid than in private health insurance and were less likely to have had employer-sponsored coverage compared with white children. Except in Alabama, there was a difference in having a USC, with children from minority groups less likely to have had a USC before SCHIP enrollment compared with white children. No consistent pattern of health care utilization before SCHIP was noted across states with respect to race or ethnicity. Findings from multivariate analyses, controlling for sociodemographic factors, generally confirmed that black and Hispanic children were more likely to have lacked insurance or a USC before enrollment in SCHIP and to have poorer health status compared with white children. SCHIP is enrolling substantial numbers of racial and ethnic minority children. There are baseline racial and ethnic disparities among new enrollees in SCHIP, with black and Hispanic children faring worse than white children on many sociodemographic and health system measures, and there are differences among states in the prevalence and magnitude of these disparities. After controlling for sociodemographic factors, these disparities persisted. IMPLICATIONS FOR MONITORING AND IMPROVING SCHIP: SCHIP has the potential to play a critical role in efforts to eliminate racial and ethnic disparities in health among the children it serves. However, study findings indicate that programmatic efforts are necessary to ensure that disparities are not perpetuated. Program effectiveness and outcomes should be monitored by race and ethnicity to ensure equity in access, use, and outcomes across all racial and ethnic groups. Assessing the health characteristics and needs of new SCHIP enrollees can provide a benchmark for evaluating the program's impact on eliminating racial and ethnic disparities in health and inform service delivery enhancements.","subset":"pubmed_abstract"} +{"meta":{"pmid":29077092,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-50":2,"2023-14":2,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-21":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":1,"2024-22":1,"2024-26":1}}},"text":"PAXX and Xlf interplay revealed by impaired CNS development and immunodeficiency of double KO mice.\nThe repair of DNA double-stranded breaks (DNAdsb) through non-homologous end joining (NHEJ) is a prerequisite for the proper development of the central nervous system and the adaptive immune system. Yet, mice with Xlf or PAXX loss of function are viable and present with very mild immune phenotypes, although their lymphoid cells are sensitive to ionizing radiation attesting for the role of these factors in NHEJ. In contrast, we show here that mice defective for both Xlf and PAXX are embryonically lethal owing to a massive apoptosis of post-mitotic neurons, a situation reminiscent to XRCC4 or DNA Ligase IV KO conditions. The development of the adaptive immune system in Xlf-\/-PAXX-\/- E18.5 embryos is severely affected with the block of B- and T-cell maturation at the stage of IgH and TCR\u03b2 gene rearrangements, respectively. This damaging phenotype highlights the functional nexus between Xlf and PAXX, which is critical for the completion of NHEJ-dependent mechanisms during mouse development.","subset":"pubmed_abstract"} +{"meta":{"pmid":27027705,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":3,"2024-22":1,"unknown":6}}},"text":"Radiographic evaluation of the width of the femorotibial joint space in horses.\nTo measure the minimal joint space width (mJSW) in caudocranial radiographic views of orthopedically normal femorotibial joints of horses, to compare the accuracy of measurements with those of a software program designed for humans, and to identify the ideal caudocranial radiographic projection angle for mJSW measurement. ANIMALS 12 healthy mares (22 femorotibial joints) and 3 equine cadavers (6 stifle joints). Caudocranial views of femorotibial joints were acquired in the proximodistal plane at 5\u00b0, 10\u00b0, and 15\u00b0 (caudo-5\u00b0-proximal-craniodistal oblique, 10\u00b0, and 15\u00b0) and lateromedial plane (caudo-10\u00b0-proximo-5\u00b0-lateral-craniodistomedial oblique and caudo-10\u00b0-proximo-5\u00b0-medial-craniodistolateral oblique). The mJSWs of medial and lateral femorotibial joint compartments were measured manually by 2 evaluators and automatically by a digital analysis software program. Interevaluator reproducibility was assessed. Post hoc tests were used to identify the projection angle that provided the largest measurements. Validation of mJSW measurements was performed by evaluation of 6 stifle joints ex vivo. Excellent agreement was achieved between the 2 evaluators and between the veterinary radiologist and the analysis software for the medial and lateral compartments of femorotibial joints. Angle of caudocranial view in the proximodistal but not lateromedial plane had a significant effect on the medial compartment mJSW measurements. Mean mJSW for the medial compartment was significantly higher for the caudoproximal-craniodistal oblique projection made at 10\u00b0 from the horizontal than for other angles. Angle had no significant effect on mean mJSW for the lateral compartment. Agreement between automated measurements of mJSW in the medial compartment and thickness of nonmineralized cartilage in histologic preparations of associated tissues was excellent. Measurements of mJSW in the medial compartment of femorotibial joints, the most common site of osteoarthritis in horses, were reproducible and optimal with a caudoproximal-craniodistal oblique radiographic projection made at 10\u00b0 from the horizontal.","subset":"pubmed_abstract"} +{"meta":{"pmid":9134487,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":12}}},"text":"Ethics and the GMC core curriculum: a survey of resources in UK medical schools.\nTo study the resources available and resources needed for ethics teaching to medical students in UK medical schools as required by the new GMC core curriculum. A structured questionnaire was piloted and then circulated to deans of medical schools. All UK medical schools. Eighteen out of 28 schools completed the questionnaire, the remainder either indicating that their arrangements were \"under review\" (4) or not responding (6). Among those responding: 1) library resources, including video and information technology were found to be fairly well developed; 2) many schools had a good supply of handouts and sample cases for teaching; 3) most had a written syllabus, and 4) two-thirds examined in the subject. However, many schools indicated that there was an urgent need for: 1) full-time teachers (most ethics teaching is still by part-time and voluntary staff); funding for books and journals, and 3) additional teaching materials (including further case vignettes, handouts and sample exam questions). There has been a considerable overall improvement in resources for medical ethics teaching since the time of the last national survey (The Pond Report). However, provision varies widely from medical school to medical school. The particular needs identified were for full-time teachers, library resources and teaching materials. Wider use of existing organisations concerned with medical ethics could help to meet these needs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26101135,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Ginger extract prevents high-fat diet-induced obesity in mice via activation of the peroxisome proliferator-activated receptor \u03b4 pathway.\nThe initiation of obesity entails an imbalance wherein energy intake exceeds expenditure. Obesity is increasing in prevalence and is now a worldwide health problem. Food-derived peroxisome proliferator-activated receptor \u03b4 (PPAR\u03b4) stimulators represent potential treatment options for obesity. Ginger (Zingiber officinale Roscoe) was previously shown to regulate the PPAR\u03b3 signaling pathway in adipocytes. In this study, we investigated the antiobesity effects of ginger in vivo and the mechanism of action in vitro. Energy expenditure was increased, and diet-induced obesity was attenuated in C57BL\/6J mice treated with dietary ginger extract (GE). GE also increased the number of Type I muscle fibers, improved running endurance capacity and upregulated PPAR\u03b4-targeted gene expression in skeletal muscle and the liver. 6-Shogaol and 6-gingerol acted as specific PPAR\u03b4 ligands and stimulated PPAR\u03b4-dependent gene expression in cultured human skeletal muscle myotubes. An analysis of cellular respiration revealed that pretreating cultured skeletal muscle myotubes with GE increased palmitate-induced oxygen consumption rate, which suggested an increase in cellular fatty acid catabolism. These results demonstrated that sustained activation of the PPAR\u03b4 pathway with GE attenuated diet-induced obesity and improved exercise endurance capacity by increasing skeletal muscle fat catabolism. 6-Shogaol and 6-gingerol may be responsible for the regulatory effects of dietary ginger on PPAR\u03b4 signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":19302981,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2020-10":1,"2019-13":1,"2018-47":1,"2018-30":1,"2018-09":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2020-16":1,"2017-13":1}}},"text":"Neuroplasticity and neuroprotection in enteric neurons: role of epithelial cells.\nNeurons of enteric nervous system (ENS) regulate intestinal epithelial cells (IEC) functions but whether IEC can impact upon the neurochemical coding and survival of enteric neurons remain unknown. Neuro-epithelial interactions were studied using a coculture model composed of IEC lines and primary culture of rat ENS or human neuroblastoma cells (SH-SY5Y). Neurochemical coding of enteric neurons was analysed by immunohistochemistry and quantitative PCR. Neuroprotective effects of IEC were tested by measuring neuron specific enolase (NSE) release or cell permeability to 7-amino-actinomycin D (7-AAD). Following coculture with IEC, the percentage of VIP-immunoreactive (IR) neurons but not NOS-IR and VIP mRNA expression were significantly increased. IEC significantly reduced dopamine-induced NSE release and 7-AAD permeability in culture of ENS and SH-SY5Y, respectively. Finally, we showed that NGF had neuroprotective effects but reduced VIP expression in enteric neurons. In conclusion, our study identified a novel role for IEC in the regulation of enteric neuronal properties.","subset":"pubmed_abstract"} +{"meta":{"pmid":18620618,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":17}}},"text":"Molecular methods for identification of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus using methionine biosynthesis and 16S rRNA genes.\nYoghurt and starter culture producers are still searching strains of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus to produce healthier yogurt with longer shelf life, better texture, taste and quality. However, selective identification of Lb. delbrueckii subsp. bulgaricus and Strep. thermophilus from a mixed population using microbiological and biochemical methods is difficult, time consuming and may not be accurate. In this study, a quick, sensitive and accurate method is proposed to identify both Lb. delbrueckii subsp. bulgaricus and Strep. thermophilus using PCR. The method is comprised of two parts. In the first part, methionine biosynthesis genes, known to be present in both species were partially amplified by designed primers (cysmet2F and cysmet2R). Partial amplification of the methionine biosynthesis gene which gives 700 bp fragment resulted in selective identification of Lb. bulgaricus and Strep. thermophilus. All 16 Lb. bulgaricus and 6 Strep. thermophilus isolates assessed by this method gave the expected amplification. On the other hand, further analysis of other closely related species with the same primers have indicated that the same product was also amplified in two more lactobacilli namely, Lb. delbrueckii subsp. lactis and Lb. helveticus species. Thus, in the second part of the method, further differentiation of Lb. delbrueckii subsp. bulgaricus and Strep. thermophilus from each other and these species was achieved using restriction analysis of 16S rRNA gene with EcoRI.","subset":"pubmed_abstract"} +{"meta":{"pmid":1893371,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A case-control study of serum folate levels and invasive cervical cancer.\nAlthough small intervention trials have suggested that folate supplementation reduces cervical dysplasia, the association of blood folate concentrations with invasive cervical cancer risk has not been investigated in well-controlled epidemiological studies. A study was conducted with newly diagnosed Stage I and II invasive cervical cancer cases and controls in 4 Latin American countries. Ninety-five% of subjects donated blood samples, resulting in 330 case and 565 control serum samples analyzed for folate concentrations by radioassay. Cases did not differ significantly from controls in mean levels of folate (5.00 and 4.90 ng\/ml, respectively). No associations were observed between quartiles of serum folate and risk of cervical cancer after adjustment for other risk factors, and no interactions with established risk factors were observed. Folate levels were also unrelated to risk among women who might have compromised folate status because of recent or extended oral contraceptive usage or multiple pregnancies. Further, mean levels of folate were similar by stage of disease, arguing against an effect of disease progression on serum values. These results do not support a role for serum folate in the etiology of invasive cervical cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":19288138,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Production and characterization of lipopeptide biosurfactant by a sponge-associated marine actinomycetes Nocardiopsis alba MSA10.\nA sponge-associated marine actinomycetes Nocardiopsis alba MSA10 was screened and evaluated for the production of biosurfactant. Biosurfactant production was confirmed by conventional screening methods including hemolytic activity, drop collapsing test, oil displacement method, lipase production and emulsification index. The active compound was extracted with three solvents including ethyl acetate, diethyl ether and dichloromethane. The diethyl ether extract was fractionated by TLC and semi-preparative HPLC to isolate the pure compound. In TLC, a single discrete spot was obtained with the R (f) 0.60 and it was extrapolated as valine. Based on the chemical characterization, the active compound was partially confirmed as lipopeptide. The optimum production was attained at pH 7, temperature 30 degrees C, and 1% salinity with glucose and peptone supplementation as carbon and nitrogen sources, respectively. Considering the biosurfactant production potential of N. alba, the strain could be developed for large-scale production of lipopeptide biosurfactant.","subset":"pubmed_abstract"} +{"meta":{"pmid":8845304,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A recessive mutant of the U937 cell line acquired resistance to anti-Fas and anti-p55 tumor necrosis factor receptor antibody-induced apoptosis.\nHuman monocytic leukemia U937 cells readily undergo apoptosis when cells are treated with various stimuli including antitumor agents, tumor necrosis factor (TNF)-alpha and anti-Fas antibody. However, the signal transduction mechanism resulting in apoptosis is unclear. To study the mechanism of apoptosis, we isolated and characterized a mutant, UK110, from U937 cells, which was resistant to TNF-alpha and anti-Fas antibody-induced apoptosis but was less resistant to etoposide-induced apoptosis. TNF-alpha induced signals are mediated by two types of TNF receptors (TNFR), p55- and p75-TNFR, and p55-TNFR is homologous to the Fas antigen. Interestingly, UK110 cells showed resistance to apoptosis by agonistic anti-p55-TNFR antibody, indicating that UK110 cells were resistant to Fas- and p55-TNFR-mediated apoptosis. Because expression of apoptosis-associated molecules, such as c-Myc, Bcl-2, and Bax, was similar between U937 and UK110 cells an undetermined pathway for apoptosis through Fas and p55-TNFR could be mutated in UK110 cells. To clarify the genetic phenotype of UK110 cells, we performed somatic cell hybridization with parental U937 and the UK110 cells. All of the hybrid clones were as sensitive as the parental U937 cells to apoptosis by both anti-Fas and anti-p55-TNFR antibodies, indicating that the apoptosis resistance in UK110 cells resulted from recessive genotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":29422661,"dup_signals":{"dup_doc_count":34,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-40":3,"2023-23":3,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-21":2,"2021-17":1,"2021-10":2,"2021-04":2,"2020-45":1,"2020-40":1,"2023-50":1,"2024-22":2,"2024-18":1,"2024-30":1}}},"text":"Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.\nChronic obstructive pulmonary disease (COPD) is a major health burden in adults and cigarette smoking is considered the most important environmental risk factor of COPD. Chromosome 15q25.1 locus is associated with both COPD and smoking. Our study aims at understanding the mechanism underlying the association of chromosome 15q25.1 with COPD through epigenetic and transcriptional variation in a population-based setting. To assess if COPD-associated variants in 15q25.1 are methylation quantitative trait loci, epigenome-wide association analysis of four genetic variants, previously associated with COPD (P < 5 \u00d7 10-8) in the 15q25.1 locus (rs12914385:C>T-CHRNA3, rs8034191:T>C-HYKK, rs13180:C>T-IREB2 and rs8042238:C>T-IREB2), was performed in the Rotterdam study (n = 1489). All four variants were significantly associated (P < 1.4 \u00d7 10-6) with blood DNA methylation of IREB2, CHRNA3 and PSMA4, of which two, including IREB2 and PSMA4, were also differentially methylated in COPD cases and controls (P < 0.04). Further additive and multiplicative effects of smoking were evaluated and no significant effect was observed. To evaluate if these four genetic variants are expression quantitative trait loci, transcriptome-wide association analysis was performed in 1087 lung samples. All four variants were also significantly associated with differential expression of the IREB2 3'UTR in lung tissues (P < 5.4 \u00d7 10-95). We conclude that regulatory mechanisms affecting the expression of IREB2 gene, such as DNA methylation, may explain the association between genetic variants in chromosome 15q25.1 and COPD, largely independent of smoking.","subset":"pubmed_abstract"} +{"meta":{"pmid":28722171,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study.\nFew studies have investigated the link between individual antibiotics and major congenital malformations (MCMs) including specific malformations owing to small sample size. We aimed to quantify the association between exposure to gestational antibiotic and the risk of MCMs. Using the Quebec pregnancy cohort (1998-2008), we included a total of 139 938 liveborn singleton alive whose mothers were covered by the \"R\u00e9gie de l'assurance maladie du Qu\u00e9bec\" drug plan for at least 12 months before and during pregnancy. Antibiotic exposure was assessed in the first trimester and MCMs were identified within the first year of life. After adjusting for potential confounders, clindamycin exposure was associated with an increased risk of MCMs (aOR 1.34, 95% CI 1.02-1.77, 60 exposed cases), musculoskeletal system malformations (aOR 1.67, 95% CI 1.12-2.48, 29 exposed cases) and ventricular\/atrial septal defect (aOR 1.81, 95% CI 1.04-3.16, 13 exposed cases). Doxycycline exposure increased the risk of circulatory system malformation, cardiac malformations and ventricular\/atrial septal defect (aOR 2.38, 95% CI 1.21-4.67, 9 exposed cases; aOR 2.46, 95% CI 1.21-4.99, 8 exposed cases; aOR 3.19, 95% CI 1.57-6.48, 8 exposed cases, respectively). Additional associations were seen with quinolone (1 defect), moxifloxacin (1 defect), ofloxacin (1 defect), macrolide (1 defect), erythromycin (1 defect) and phenoxymethylpenicillin (1 defect). No link was observed with amoxicillin, cephalosporins and nitrofurantoin. Similar results were found when penicillins were used as the comparator group. Clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin in utero exposure were linked to organ-specific malformations. Amoxicillin, cephalosporins and nitrofurantoin were not associated with MCMs.","subset":"pubmed_abstract"} +{"meta":{"pmid":16217601,"dup_signals":{"dup_doc_count":13}},"text":"The oryza map alignment project: the golden path to unlocking the genetic potential of wild rice species.\nThe wild species of the genus Oryza offer enormous potential to make a significant impact on agricultural productivity of the cultivated rice species Oryza sativa and Oryza glaberrima. To unlock the genetic potential of wild rice we have initiated a project entitled the 'Oryza Map Alignment Project' (OMAP) with the ultimate goal of constructing and aligning BAC\/STC based physical maps of 11 wild and one cultivated rice species to the International Rice Genome Sequencing Project's finished reference genome--O. sativa ssp. japonica c. v. Nipponbare. The 11 wild rice species comprise nine different genome types and include six diploid genomes (AA, BB, CC, EE, FF and GG) and four tetrapliod genomes (BBCC, CCDD, HHKK and HHJJ) with broad geographical distribution and ecological adaptation. In this paper we describe our strategy to construct robust physical maps of all 12 rice species with an emphasis on the AA diploid O. nivara--thought to be the progenitor of modern cultivated rice.","subset":"pubmed_abstract"} +{"meta":{"pmid":38013837,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Deep homography estimation in dynamic surgical scenes for laparoscopic camera motion extraction.\nCurrent laparoscopic camera motion automation relies on rule-based approaches or only focuses on surgical tools. Imitation Learning (IL) methods could alleviate these shortcomings, but have so far been applied to oversimplified setups. Instead of extracting actions from oversimplified setups, in this work we introduce a method that allows to extract a laparoscope holder's actions from videos of laparoscopic interventions. We synthetically add camera motion to a newly acquired dataset of camera motion free da Vinci surgery image sequences through a novel homography generation algorithm. The synthetic camera motion serves as a supervisory signal for camera motion estimation that is invariant to object and tool motion. We perform an extensive evaluation of state-of-the-art (SOTA) Deep Neural Networks (DNNs) across multiple compute regimes, finding our method transfers from our camera motion free da Vinci surgery dataset to videos of laparoscopic interventions, outperforming classical homography estimation approaches in both, precision by 41%, and runtime on a CPU by 43%.","subset":"pubmed_abstract"} +{"meta":{"pmid":17682040,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Ehrlichia canis gp200 contains dominant species-specific antibody epitopes in terminal acidic domains.\nSpecies-specific antibody epitopes within several major immunoreactive protein orthologs of Ehrlichia species have recently been identified and molecularly characterized. In this study, dominant B-cell epitopes within the acidic (pI 5.35) ankyrin repeat-containing 200-kDa major immunoreactive protein (gp200) of Ehrlichia canis were defined. The E. canis gp200 gene (4,263 bp; 1,421 amino acids) was cloned and expressed as four (N-terminal, 1,107 bp; N-internal, 910 bp; C-internal, 1,000 bp; and C-terminal, 1,280 bp) overlapping recombinant proteins. The N-terminal, C-internal, and C-terminal polypeptides (369, 332, and 426 amino acids, respectively) were strongly recognized by antibody, and the major epitope(s) in these polypeptides was mapped to four polypeptide regions (40 to 70 amino acids). Smaller overlapping recombinant polypeptides (14 to 15 amino acids) spanning these regions identified five strongly immunoreactive species-specific epitopes that exhibited conformational dependence. The majority of the epitopes (four) were located in two strongly acidic (pI 4 to 4.9) domains in the distal N- and C-terminal regions of the protein flanking the centralized ankyrin domain-containing region. The amino acid content of the epitope-containing domains included a high proportion of strongly acidic amino acids (glutamate and aspartate), and these domains appear to have important biophysical properties that influence the antibody response to gp200.","subset":"pubmed_abstract"} +{"meta":{"pmid":32264224,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Temporal and spatial programming in soft composite hydrogel objects.\nSoft composite hydrogel objects formed from the biopolymer sodium alginate, the enzyme urease, and oil droplets are formed by a simple gelation procedure to produce autonomous bodies with both time and spatial programming. These continuous objects of non-uniform dimensional composition selectively respond to an environmental stimulus of urea and change colour or disintegrate at pre-defined locations within the hydrogel structure after pre-set time intervals. The spatial and temporal responses of these hydrogels to an environmental stimulus are valuable tools in areas such as soft robotics.","subset":"pubmed_abstract"} +{"meta":{"pmid":18292195,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell.\nAndrogen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized. In this study AR expression was detected in HPEC in vivo in clinical specimens of benign prostate and prostate cancer, and AR function as a transcription factor was demonstrated in HPEC in primary xenografts of human benign prostate tissue transplanted into severe combined immunodeficient mice by iv administration of adenoviral mouse mammary tumor virus-driven luciferase expression vector. AR expression and functionality were maintained in vitro in primary cultures of HPEC that coexpressed CD31, CD34, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2 but did not express prostate-specific antigen. AR expression in primary cultures of HPEC isolated from surgical specimens of benign prostate was validated using RT-PCR, cDNA sequencing, immunocytochemistry, and Western blot analyses. Scatchard analyses demonstrated a single ligand-binding site for R1881 in primary cultures of HPEC, with dissociation constant of 0.25 nm, and AR-mediated transcriptional activity was demonstrated using adenoviral mouse mammary tumor virus-driven luciferase reporters. Dihydrotestosterone increased proliferation in primary cultures of HPEC in a dose-dependent manner without modulating endothelial tube formation in Matrigel (BD Biosciences, Bedford, MA). Therefore, HPECs express functional AR, and androgen plays a direct role in modulating HPEC biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":28402551,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A risk prediction score for acute kidney injury in the intensive care unit.\nAcute kidney injury (AKI) is common in critically ill patients and is associated with high morbidity and mortality. Early identification of high-risk patients provides an opportunity to develop strategies for prevention, early diagnosis and treatment of AKI. We undertook this multicenter prospective cohort study to develop and validate a risk score for predicting AKI in patients admitted to an intensive care unit (ICU). Patients were screened for predictor variables within 48 h of ICU admission. Baseline and acute risk factors were recorded at the time of screening and serum creatinine was measured daily for up to 7 days. A risk score model for AKI was developed with multivariate regression analysis combining baseline and acute risk factors in the development cohort (573 patients) and the model was further evaluated on a test cohort (144 patients). Validation was performed on an independent prospective cohort of 1300 patients. The discriminative ability of the risk model was assessed by the area under the receiver operating characteristic curve (AUROC) and model calibration was evaluated by Hosmer-Lemeshow statistic. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria (absolute change of 0.3 mg\/dL or relative change of 50% from baseline serum creatinine in 48 h to 7 days, respectively). AKI developed in 754 (37.2%) patients. In the multivariate model, chronic kidney disease, chronic liver disease, congestive heart failure, hypertension, atherosclerotic coronary vascular disease, pH \u2264 7.30, nephrotoxin exposure, sepsis, mechanical ventilation and anemia were identified as independent predictors of AKI and the AUROC for the model in the test cohort was 0.79 [95% confidence interval (CI) 0.70-0.89]. On the external validation cohort, the AUROC value was 0.81 (95% CI 0.78-0.83). The risk model demonstrated good calibration in both cohorts. Positive and negative predictive values for the optimal cutoff value of \u2265 5 points in test and validation cohorts were 22.7 and 96.1% and 31.8 and 95.4%, respectively. A risk score model integrating chronic comorbidities and acute events at ICU admission can identify patients at high risk to develop AKI. This risk assessment tool could help clinicians to stratify patients for primary prevention, surveillance and early therapeutic intervention to improve care and outcomes of ICU patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":25274533,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Telomere shortening: a new prognostic factor for cardiovascular disease post-radiation exposure.\nTelomere length has been proposed as a marker of mitotic cell age and as a general index of human organism aging. Telomere shortening in peripheral blood lymphocytes has been linked to cardiovascular-related morbidity and mortality. The authors investigated the potential correlation of conventional risk factors, radiation dose and telomere shortening with the development of coronary artery disease (CAD) following radiation therapy in a large cohort of Hodgkin lymphoma (HL) patients. Multivariate analysis demonstrated that hypertension and telomere length were the only independent risk factors. This is the first study in a large cohort of patients that demonstrates significant telomere shortening in patients treated by radiation therapy who developed cardiovascular disease. Telomere length appears to be an independent prognostic factor that could help determine patients at high risk of developing CAD after exposure in order to implement early detection and prevention.","subset":"pubmed_abstract"} +{"meta":{"pmid":28663364,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Platelet count and mean platelet volume predict outcome in adults with Eisenmenger syndrome.\nAlthough a significant proportion of patients with cyanotic congenital heart disease are thrombocytopaenic, its prevalence and clinical significance in adults with Eisenmenger syndrome (ES) is not well studied. Accordingly, we examined the relationship of thrombocytopaenia and mean platelet volume (MPV) to bleeding or thrombotic complications and survival in a contemporary cohort of patients with ES, including patients with Down syndrome. Demographics, laboratory and clinical data were analysed from 226 patients with ES under active follow-up over 11 years. Age at baseline was 34.6\u00b111.4 years and 34.1% were men. Mean platelet count and MPV were 152.6\u00b173.3\u00d7109\/L and 9.6\u00b11.2 fL, respectively. A strong inverse correlation was found between platelet count and haemoglobin concentration and MPV. During the study, there were 39 deaths, and 21 thrombotic and 43 bleeding events. On univariate Cox regression analysis, patients with a platelet count <100\u00d7109\/L had a twofold increased mortality (HR 2.10, 95% CI 1.10 to 4.01, p=0.024). Platelet count was not associated with an increased risk of thrombosis. However, there was a threefold increased thrombotic risk with MPV >9.5 fL (HR 3.50, 95% CI 1.28 to 9.54, p=0.015). Patients with either severe secondary erythrocytosis (>220g\/L) or anaemia (<130g\/L) were at higher risk of thrombotic events (HR 3.93, 95% CI 1.60 to 9.67, p=0.003; and HR 4.75, 95% CI 1.03 to 21.84, p=0.045, respectively). Thrombocytopaenia significantly increased the risk of mortality in ES. Furthermore, raised MPV, severe secondary erythrocytosis and anaemia, but not platelet count, were associated with an increased risk of thrombotic events in our adult cohort.","subset":"pubmed_abstract"} +{"meta":{"pmid":29737522,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.\nRegularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands; which can be prevented and treated with iron chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and well-being, which may affect adherence. To identify and assess the effectiveness of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) to improve adherence to iron chelation therapy in people with SCD or thalassaemia. We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (01 February 2017). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (12 December 2017). For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion.For studies including psychological and psychosocial interventions, educational Interventions, or multi-component interventions, non-RCTs, controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion. Three authors independently assessed trial eligibility, risk of bias and extracted data. The quality of the evidence was assessed using GRADE. We included 16 RCTs (1525 participants) published between 1997 and 2017. Most participants had \u03b2-thalassaemia major; 195 had SCD and 88 had \u03b2-thalassaemia intermedia. Mean age ranged from 11 to 41 years. One trial was of medication management and 15 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral-chelating agents, deferiprone and deferasirox.We rated the quality of evidence as low to very low across all outcomes identified in this review.Three trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL.Deferiprone versus deferoxamineWe are uncertain whether deferiprone increases adherence to iron chelation therapy (four trials, very low-quality evidence). Results could not be combined due to considerable heterogeneity (participants' age and different medication regimens). Medication adherence was high (deferiprone (85% to 94.9%); deferoxamine (71.6% to 93%)).We are uncertain whether deferiprone increases the risk of agranulocytosis, risk ratio (RR) 7.88 (99% confidence interval (CI) 0.18 to 352.39); or has any effect on all-cause mortality, RR 0.44 (95% CI 0.12 to 1.63) (one trial; 88 participants; very low-quality evidence).Deferasirox versus deferoxamineWe are uncertain whether deferasirox increases adherence to iron chelation therapy, mean difference (MD) -1.40 (95% CI -3.66 to 0.86) (one trial; 197 participants; very-low quality evidence). Medication adherence was high (deferasirox (99%); deferoxamine (100%)). We are uncertain whether deferasirox decreases the risk of thalassaemia-related serious adverse events (SAEs), RR 0.95 (95% CI 0.41 to 2.17); or all-cause mortality, RR 0.96 (95% CI 0.06 to 15.06) (two trials; 240 participants; very low-quality evidence).We are uncertain whether deferasirox decreases the risk of SCD-related pain crises, RR 1.05 (95% CI 0.68 to 1.62); or other SCD-related SAEs, RR 1.08 (95% CI 0.77 to 1.51) (one trial; 195 participants; very low-quality evidence).Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT)Deferasirox FCT may make little or no difference to adherence, RR 1.10 (95% CI 0.99 to 1.22) (one trial; 173 participants; low-quality evidence). Medication adherence was high (FCT (92.9%); DT (85.3%)).We are uncertain if deferasirox FCT increases the incidence of SAEs, RR 1.22 (95% CI 0.62 to 2.37); or all-cause mortality, RR 2.97 (95% CI 0.12 to 71.81) (one trial; 173 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if deferiprone and deferoxamine combined increases adherence to iron chelation therapy (very low-quality evidence). Medication adherence was high (deferiprone 92.7% (range 37% to 100%) to 93.6% (range 56% to 100%); deferoxamine 70.6% (range 25% to 100%).Combination therapy may make little or no difference to the risk of SAEs, RR 0.15 (95% CI 0.01 to 2.81) (one trial; 213 participants; low-quality evidence).We are uncertain if combination therapy decreases all-cause mortality, RR 0.77 (95% CI 0.18 to 3.35) (two trials; 237 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferoxamine aloneDeferiprone and deferoxamine combined may have little or no effect on adherence to iron chelation therapy (four trials; 216 participants; low-quality evidence). Medication adherence was high (deferoxamine 91.4% to 96.1%; deferiprone: 82.4%)Deferiprone and deferoxamine combined, may have little or no difference in SAEs or mortality (low-quality evidence). No SAEs occurred in three trials and were not reported in one trial. No deaths occurred in two trials and were not reported in two trials.Deferiprone and deferoxamine combined versus deferiprone and deferasirox combinedDeferiprone and deferasirox combined may improve adherence to iron chelation therapy, RR 0.84 (95% CI 0.72 to 0.99) (one trial; 96 participants; low-quality evidence). Medication adherence was high (deferiprone and deferoxamine: 80%; deferiprone and deferasirox: 95%).We are uncertain if deferiprone and deferasirox decreases the incidence of SAEs, RR 1.00 (95% CI 0.06 to 15.53) (one trial; 96 participants; very low-quality evidence).There were no deaths in the trial (low-quality evidence).Medication management versus standard careWe are uncertain if medication management improves health-related QoL (one trial; 48 participants; very low-quality evidence). Adherence was only measured in one arm of the trial. The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects.Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation.Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy.Due to lack of evidence this review cannot comment on intervention strategies for different age groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":26062629,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":11}}},"text":"Clinical effect of white matter network disruption related to amyloid and small vessel disease.\nWe tested our hypothesis that the white matter network might mediate the effect of amyloid and small vessel disease (SVD) on cortical thickness and\/or cognition. We prospectively recruited 232 patients with cognitive impairment. Amyloid was assessed using Pittsburgh compound B-PET. SVD was quantified as white matter hyperintensity volume and lacune number. The regional white matter network connectivity was measured as regional nodal efficiency by applying graph theoretical analysis to diffusion tensor imaging data. We measured cortical thickness and performed neuropsychological tests. SVD burden was associated with decreased nodal efficiency in the bilateral frontal, lateral temporal, lateral parietal, and occipital regions. Path analyses showed that the frontal nodal efficiency mediated the effect of SVD on the frontal atrophy and frontal-executive dysfunction. The temporoparietal nodal efficiency mediated the effect of SVD on the temporoparietal atrophy and memory dysfunction. However, Pittsburgh compound B retention ratio affected cortical atrophy and cognitive impairment without being mediated by nodal efficiency. We suggest that a disrupted white matter network mediates the effect of SVD, but not amyloid, on specific patterns of cortical atrophy and\/or cognitive impairment. Therefore, our findings provide insight to better understand how amyloid and SVD burden can give rise to brain atrophy or cognitive impairment in specific patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":28005795,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Orbitocranial Fibrous Dysplasia: Outcome of Radical Resection and Immediate Reconstruction With Titanium Mesh and Pericranial Flap.\nFibrous dysplasia (FD) is a non-neoplastic developmental fibro-osseous disease. It represents 2.5% of all bone tumors and 5% to 7% of the benign bone tumors. Orbitocranial region is involved in about 20% of the patients. The main presentations are craniofacial deformity and headache. Loss of vision is the most devastating result of this disease. There is no medical treatment to cure or prevent FD. Radiation therapy is contraindicated. Surgery for the orbitocranial FD is often challenging because of the proximity of neurovascular and ocular structures. Conservative surgical shaving and recontouring is always associated with suboptimal results. Radical excision is potentially curative with no extra morbidity. Orbital hypertelorism, dystopia, or proptosis can be corrected only by radical excision and reconstruction. The aim of the study was to evaluate the outcome of radical excision of the orbitocranial FD and immediate reconstruction using titanium mesh and pericranial flap. This prospective study had been conducted on 22 patients with orbitocranial FD with age range from 17 to 52 years (mean 29.5). Radical excision of the lesions was done for all patients through transcranial approach. Immediate reconstruction was achieved using titanium mesh and pericranial flap. Intraoperative dural tears and cerebrospinal fluid leak were reported in 2 patients and repaired with galeal graft. Supraorbital anesthesia occurred in 6 patients. Of these, 2 patients were transient, while the remaining 4 patients were permanent. Wound infection was noticed in 1 patient who improved by medical treatment. Temporary postoperative diplopia occurred in 1 patient and temporary postoperative impaired vision in 1 other patient. In all patients, acceptable or good aesthetic results were observed. No recurrence was detected in our series during the follow-up period that ranged from 24 to 58 months (mean 37.5 months). Radical excision of orbitocranial FD is potentially curative with no extra morbidity. It can achieve good aesthetic and functional results with no recurrence.","subset":"pubmed_abstract"} +{"meta":{"pmid":17332371,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":9}}},"text":"Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma.\nInfectious mononucleosis (IM) has been associated with an increased risk of Hodgkin lymphoma (HL), implicating a role for Epstein-Barr virus (EBV) in HL development. Although essential to the understanding of the association, it has remained uncertain if the relationship is restricted to the EBV-positive subset of HL. We collected information on mononucleosis history and childhood socioenvironmental characteristics in a population-based study of 586 patients with classic HL and 3,187 controls in Denmark and Sweden. Tumor EBV status was established for 499 cases by immunohistochemistry and in situ hybridization techniques. Odds ratios (OR) for the relationship between HL risk and mononucleosis and other risk factors were estimated by logistic regression for HL in younger (18-44 years) and older (45-74 years) adults, overall and by tumor EBV status. All analyses were adjusted for country-specific measures of maternal education and mononucleosis history. IM was associated with an increased risk of EBV-positive [OR, 3.23; 95% confidence interval (95% CI) 1.89-5.55] but not EBV-negative HL (OR, 1.35; 95% CI, 0.86-2.14). Risk of EBV-positive HL varied with time since IM and was particularly pronounced in younger adults (OR, 3.96; 95% CI, 2.19-7.18). IM-associated lymphomas occurred with a median of 2.9 years (1.8-4.9 years) after infection. The EBV specificity of the IM association was corroborated by a case-case comparison of IM history between younger adult EBV-positive and EBV-negative HL patients (OR(IM EBV+ HL versus EBV- HL), 2.68; 95% CI, 1.40-5.12). We found further evidence that IM is associated only with EBV-positive HL. This finding is compatible with the notion that EBV-positive and EBV-negative HL may have different etiologies.","subset":"pubmed_abstract"} +{"meta":{"pmid":9464396,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":5,"2021-31":1,"2021-04":1,"2020-16":3,"2019-26":1,"2019-04":1,"2018-39":1,"2018-26":1,"2018-17":1,"2017-43":1,"2023-06":1,"2013-20":1}}},"text":"Prevalence of broad-host-range lytic bacteriophages of Sphaerotilus natans, Escherichia coli, and Pseudomonas aeruginosa.\nTwo bacteriophage collections were examined with regard to their ability to form plaques on multiple bacterial host species. Nine of 10 phages studied were found to be broad-host-range bacteriophages. These phages fell into two groups. Group 1, the SN series, was isolated from sewage treatment plant samples with Sphaerotilus natans ATCC 13338 as a host. The DNAs of these bacteriophages contained modified bases and were insensitive to cleavage by type I and II restriction endonucleases. The efficiency of plating of these bacteriophages was changed only slightly on the alternate host. Group 2, the BHR series, was isolated by a two-host enrichment protocol. These bacteriophages were sensitive to restriction, and their efficiency of plating was dramatically reduced on the alternate host. Our results suggest that a multiple-host enrichment protocol may be more effective for the isolation of broad-host-range bacteriophages by avoiding the selection bias inherent in single-host methods. At least two of the broad-host-range bacteriophages mediated generalized transduction. We suggest that broad-host-range bacteriophages play a key role in phage ecology and gene transfer in nature.","subset":"pubmed_abstract"} +{"meta":{"pmid":30384572,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"The effect of neutrophil-lymphocyte ratio on the postoperative course of coronary artery bypass graft surgery\nBackground\/aim: Recovery after coronary artery bypass graft surgery (CABG) can be complicated, leading to postoperative morbidity. The roles of hematologic and surgery-related parameters are important. The main purpose of this study is to determine the role of preoperative and postcardiopulmonary bypass neutrophil\/lymphocyte ratio (NLR) on postoperative recovery. Materials and methods: Sixty-two patients aged between 41 and 80 years, scheduled for elective CABG surgery with ASA I-II risk and without a history of preoperative blood transfusion, were included in the study. Three patients were excluded due to their need for additional surgical procedures other than CABG. The patients were divided into two groups that were formed depending on preoperative NLR cut-off values below (Group 1, n = 37) and above 4 (Group 2, n = 22). Postoperative data such as length of stay in the hospital and in the intensive care unit (ICU), chest tube drainage, and incidence of atrial fibrillation were recorded for all patients. Results: Preoperative NLR was significantly lower in Group 1 (P < 0.0001), and there was no significant difference between the groups in terms of postoperative NLR (P = 0.217) when the two groups were compared. The patients in Group 2 had a longer length of stay in the ICU (P = 0.035) and in the hospital (P = 0.034). There was a positive correlation between preoperative NLR and length of stay in the ICU (P = 0.017) and the hospital (P = 0.014). No statistically significant differences in postoperative drainage or incidence of postoperative atrial fibrillation were detected between the two groups. Conclusion: The results of our study demonstrate that the postoperative NLR may be useful to predict the length of hospital and ICU stays and help the management of follow-up and treatment processes in patients undergoing CABG surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":31921188,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Immune Checkpoints in Circulating and Tumor-Infiltrating CD4+ T Cell Subsets in Colorectal Cancer Patients.\nBlockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3-\/+Helios-\/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":18252013,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":3,"unknown":14}}},"text":"Intralesional triamcinolone acetonide injection in hypertrophic skin surrounding the percutaneous titanium implant of a bone-anchored hearing aid.\nWe present a patient with persistent hypertrophic skin surrounding the percutaneous implant of a bone-anchored hearing aid system, successfully treated with intralesional applied corticosteroids. Case report and review of the world literature concerning bone-anchored hearing aid implantation and intralesional applied corticosteroids for the treatment of hypertrophic scars and keloids. Eight weeks after revision surgery to reduce surplus skin and subcutaneous scar tissue overgrowing the abutment, skin and subcutaneous scar tissue overgrowth reoccurred. As an alternative to yet another surgical procedure, the hypertrophic skin was treated with intralesional injections of triamcinolone acetonide. Three weeks after the treatment, a satisfying result was seen, and no subsequent relapse was observed. To our knowledge, this is the first, photographically well documented case report of a patient with persistent hypertrophic skin surrounding a percutaneous bone-anchored hearing aid implant, successfully treated with intralesional applied corticosteroids.","subset":"pubmed_abstract"} +{"meta":{"pmid":17087541,"dup_signals":{"dup_doc_count":96,"dup_dump_count":43,"dup_details":{"curated_sources":4,"2022-33":1,"2022-27":1,"2021-49":1,"2021-21":1,"2021-17":1,"2021-04":2,"2020-45":1,"2020-16":1,"2020-10":1,"2019-51":1,"2018-47":1,"2018-34":1,"2018-22":2,"2018-17":1,"2018-09":3,"2017-47":1,"2017-39":3,"2017-30":3,"2017-22":3,"2017-04":2,"2016-44":3,"2016-40":3,"2016-36":3,"2016-30":3,"2016-26":3,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2014-52":3,"2014-49":2,"2014-42":7,"2014-41":3,"2014-35":5,"2014-23":6,"2023-50":1,"2017-13":3,"2015-18":1,"2015-06":2,"2014-10":3,"2013-48":3,"2013-20":2,"2024-30":1}}},"text":"Links between social network closure and child well-being: the organizing role of friendship context.\nThird grade children (N = 404) and their mothers completed questionnaires and participated in interviews designed to identify children's friendships across multiple contexts, determine levels of social network closure for these friendships, and assess child well-being. Cluster analyses revealed distinct patterns in the contexts in which children's friendships were maintained. Closure was highest for children whose friendship clusters heavily represented relatives as friends and lowest when friends were from schools and the broader community. Intermediate levels of closure were observed for the clusters of neighborhood friends and friends from church and school. Both friendship cluster and, to some extent, ethnicity moderated associations between closure and indicators of well-being.","subset":"pubmed_abstract"} +{"meta":{"pmid":21876859,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Should albumin be used in all patients with spontaneous bacterial peritonitis?\nPatients with cirrhosis who develop spontaneous bacterial peritonitis (SBP) have been reported to experience a high incidence of renal impairment and mortality. Renal dysfunction is possibly related to altered systemic hemodynamics that leads to decreased effective arterial blood volume. Albumin, a plasma volume expander, has been investigated to determine whether it plays a role in patients with SBP. The current literature suggests that albumin can reduce renal impairment and mortality in high-risk SBP patients, defined as patients with a serum bilirubin level of greater than 68.4 \u03bcmol\u2044L, a blood urea nitrogen level of greater than 10.7 mmol\u2044L or a serum creatinine level greater than 88.4 \u03bcmol\u2044L. The rationale for albumin and other volume expanders in SBP is discussed, accompanied by a review of the current literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":19594789,"dup_signals":{"dup_doc_count":19,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":2,"2013-20":2,"2024-22":1,"unknown":6}}},"text":"Large drinks are no mistake: glass size, not shape, affects alcoholic beverage drink pours.\nAlcohol content in drinks has been shown to be variable. This study evaluates claims regarding the effects of glass size and glass shape on the amount of alcohol served in on-premise drinks. Wine and spirits drinks were purchased and measured in 80 on-premise establishments in 10 Northern California Counties. Alcohol content was measured as the liquid volume of the drink multiplied by the percentage alcohol by volume of given brands or from analysis of mixed drink and wine samples. Spirits drinks were classified as either straight shots or mixed drinks. Mixed drinks poured in short wide glasses were not found to contain more alcohol than those poured in tall thin glasses. Straight shots and mixed drinks served in the relatively large pint glass and variable 'other' glass type were found to contain more alcohol than drinks served in a short wide glass. No other significant differences were found between glass types. Analyses of establishment characteristics found that bars with mostly black patrons serve spirits drinks with more alcohol than bars with other patron types. Glass shape does not affect actual drink pours in the USA but glass size does in some cases. Consumer education programs should foster awareness of the relatively high alcohol content of on-premise wine and mixed spirits drinks. More research is needed to evaluate potential differences in drink pours by patron race and ethnicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":17729045,"dup_signals":{"dup_doc_count":11,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":2}}},"text":"Being restricted in participation after a traumatic brain injury is negatively associated by passive coping style of the caregiver.\nTo examine whether the caregivers' coping style is associated with the functional outcome of the traumatic brain injury (TBI) patient 1 year post-injury. A cross-sectional study among patients with a TBI, including their primary caregivers. The study included 51 patients aged 17-64 years with a moderate-to-severe TBI and 51 caregivers (23 parents and 28 partners) aged 23-67 years. The coping preferences of the caregivers were assessed at minimum 6 and maximum 12 months post-injury, by filling out the Utrecht Coping List (UCL) and were related to limitations in activity, as measured with the Frenchay Activities Index and with restrictions in participation as measured with the Sickness Impact Profile-68 of TBI patients 1 year post-injury. The patients were interviewed at their homes; the caregivers received and returned the UCL by mail. The patients' age and the caregivers' coping style are independently associated with restrictions in participation 1 year post-injury. A passive coping style of the primary caregiver is negatively associated with the patient's functional outcome in terms of participation in society.","subset":"pubmed_abstract"} +{"meta":{"pmid":10984153,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"The locomotion of dairy cows on concrete floors that are dry, wet, or covered with a slurry of excreta.\nSix dairy cows were trained to individually walk down a concrete aisle for a food reward. Their locomotion was then examined in a switchback experiment as the floor surface of the aisle was changed from dry to wetted concrete or concrete covered by shallow (5 cm) or deep (12.5 cm) slurry from cattle excreta. The static and dynamic frictional coefficients were measured by a tribometer, but did not give a clear indication of the risk of slipping. Cow locomotion was measured over the second half of the aisle, and limb angles recorded as the cow passed a video camera. Wetting the floor did not affect the walking or stepping rate, but it reduced the arc made by the joints of the hindlimb during the supporting phase. Slurry caused the cows to keep their legs more vertical at the end of the support phase, probably to aid lifting the limb out of the slurry. It also caused the cows to place their forelimbs down less vertically at the start of the support phase, probably because of the reduced risk of slip in the slurry. When the floor was covered with either the deep or, to a lesser extent, the shallow slurry, the cows' walking and stepping rates were reduced, and on the floor covered with deep slurry their step length was increased. Therefore slurry reduces the cow's walking speed and alters limb angles during the support phase, producing a different walking pattern from cows on dry or wetted concrete.","subset":"pubmed_abstract"} +{"meta":{"pmid":24349821,"dup_signals":{"dup_doc_count":25,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":21}}},"text":"Vitamin d predicts all-cause and cardiac mortality in females with suspected acute coronary syndrome: a comparison with brain natriuretic Peptide and high-sensitivity C-reactive protein.\nVitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 \u00b1 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33-0.93), 0.29 (95% CI 0.15-0.55), and 0.13 (95% CI 0.06-0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS.","subset":"pubmed_abstract"} +{"meta":{"pmid":19944157,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":6}}},"text":"Self-control with spiking and non-spiking neural networks playing games.\nSelf-control can be defined as choosing a large delayed reward over a small immediate reward, while precommitment is the making of a choice with the specific aim of denying oneself future choices. Humans recognise that they have self-control problems and attempt to overcome them by applying precommitment. Problems in exercising self-control, suggest a conflict between cognition and motivation, which has been linked to competition between higher and lower brain functions (representing the frontal lobes and the limbic system respectively). This premise of an internal process conflict, lead to a behavioural model being proposed, based on which, we implemented a computational model for studying and explaining self-control through precommitment behaviour. Our model consists of two neural networks, initially non-spiking and then spiking ones, representing the higher and lower brain systems viewed as cooperating for the benefit of the organism. The non-spiking neural networks are of simple feed forward multilayer type with reinforcement learning, one with selective bootstrap weight update rule, which is seen as myopic, representing the lower brain and the other with the temporal difference weight update rule, which is seen as far-sighted, representing the higher brain. The spiking neural networks are implemented with leaky integrate-and-fire neurons with learning based on stochastic synaptic transmission. The differentiating element between the two brain centres in this implementation is based on the memory of past actions determined by an eligibility trace time constant. As the structure of the self-control problem can be likened to the Iterated Prisoner's Dilemma (IPD) game in that cooperation is to defection what self-control is to impulsiveness or what compromising is to insisting, we implemented the neural networks as two players, learning simultaneously but independently, competing in the IPD game. With a technique resembling the precommitment effect, whereby the payoffs for the dilemma cases in the IPD payoff matrix are differentially biased (increased or decreased), it is shown that increasing the precommitment effect (through increasing the differential bias) increases the probability of cooperating with oneself in the future, irrespective of whether the implementation is with spiking or non-spiking neural networks.","subset":"pubmed_abstract"} +{"meta":{"pmid":28678697,"dup_signals":{"dup_doc_count":24,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":20}}},"text":"In-Ear Audio Wearable: Measurement of Heart and Breathing Rates for Health and Safety Monitoring.\nThis paper examines the integration of a noninvasive vital sign monitoring feature into the workers' hearing protection devices (HPDs) by using a microphone positioned within the earcanal under the HPD. 25 test-subjects were asked to breathe at various rhythms and intensities and these realistic sound events were recorded in the earcanal. Digital signal processing algorithms were then developed to assess heart and breathing rates. Finally, to test the robustness of theses algorithms in noisy work environments, industrial noise was added to the in-ear recorded signals and an adaptive denoising filter was used. The developed algorithms show an absolute mean error of 4.3 beats per minute (BPM) and 2.7 cycles per minute (CPM). The mean difference estimate is -0.44 BPM with a limit of agreement (LoA) interval of -14.3 to 13.4 BPM and 2.40 CPM with a LoA interval of -2.62 to 7.48 CPM. Excellent denoising is achieved with the adaptive filter, able to cope with ambient sound pressure levels of up to 110 dB SPL, resulting in a small error for heart rate detection, but a much larger error for breathing rate detection. Extraction of the heart and breathing rates from an acoustical measurement in the occluded earcanal under an HPD is possible and can even be conducted in the presence of a high level of ambient noise. This proof of concept enables the development of a wide range of noninvasive health and safety monitoring audio wearables for industrial workplaces and life-critical applications where HPDs are used.","subset":"pubmed_abstract"} +{"meta":{"pmid":27462087,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"The NK1R-\/- mouse phenotype suggests that small body size, with a sex- and diet-dependent excess in body mass and fat, are physical biomarkers for a human endophenotype with vulnerability to attention deficit hyperactivity disorder.\nThe abnormal behaviour of NK1R-\/- mice (locomotor hyperactivity, inattentiveness and impulsivity in the 5-Choice Serial Reaction-Time Test) is arguably analogous to that of patients with attention deficit hyperactivity disorder (ADHD). Evidence suggests that small body size and increased body weight are risk factors for ADHD. Here, we compared the body size, body mass and body composition of male and female NK1R-\/- mice and their wildtypes that had been fed either standard laboratory chow or a high-fat (45%: 'Western') diet. Male NK1R-\/- mice from both cohorts were approximately 7% shorter than wildtypes. A similar trend was evident in females. Male NK1R-\/- mice fed the normal diet weighed less than wildtypes but the 'body mass index' ('mBMI': weight (mg)\/length (cm)(2)) of female NK1R-\/- mice was higher than wildtypes. When given the high-fat diet, the mBMI of both male and female NK1R-\/- mice was higher than wildtypes. There were no consistent genotype or sex differences in protein, ash or water content of mice from the two cohorts. However, the fat content of male NK1R-\/- mice on the Western diet was considerably (35%) higher than wildtypes and resembled that of females from both genotypes. We conclude that a lack of functional NK1R is associated with small body size but increases vulnerability to an increase in mBMI and fat content, especially in males. This phenotype could also be evident in ADHD patients with polymorphism(s) of the TACR1 gene (the human equivalent of Nk1r).","subset":"pubmed_abstract"} +{"meta":{"pmid":19038599,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Positron emission tomography as a diagnostic tool in infection: present role and future possibilities.\nThe past decade has witnessed the emergence of yet another promising application of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in the detection and management of patients with infection and inflammatory disorders. This phenomenon is quite evident when the peer-reviewed scientific literature is searched for on this topic. Among these scientific communications, the 6 conditions in which FDG-PET has demonstrated its greatest utility include (1) chronic osteomyelitis, (2) complicated lower-limb prostheses, (3) complicated diabetic foot, (4) fever of unknown origin, (5) acquired immunodeficiency syndrome (ie, AIDS), and (6) vascular graft infection and fistula. On the basis of published literature, orthopedic infections, particularly those related to implanted prostheses and osteomyelitis (including that occurring in the setting of a complicated diabetic foot), can be detected successfully by the use of FDG-PET and, therefore, this modality has great promise for becoming the study of choice in these complex settings. Increasingly, this technique is being used to detect infection in soft tissues, including those representing the sources of fever of unknown origin. The ability of FDG-PET to diagnose vascular graft infection and fistula, even when the anatomical imaging modalities are inconclusive, is of considerable interest to practitioners of vascular surgery. Combined PET\/computed tomography (CT) imaging has the potential to determine the sites of infection or inflammation with high precision. The data on the role of PET\/CT imaging in the assessment of infection and inflammation is sparse, but this combined modality approach may prove to be the study of choice in foreseeable future for precise localization of involved sites. However, the role of PET\/CT may be limited in the presence of metallic artifacts (such as those caused by prostheses) adjacent to the sites of infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":7981449,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Relationship of serum and tumor levels of iron and iron-binding proteins to lymphocyte immunity against tumor antigen in breast cancer patients.\nFifty-two breast cancer patients were evaluated for levels of several molecules related to iron metabolism including determining their tumor tissue and serum ferritin levels, serum transferrin levels, and serum iron levels. In addition the patients' lymphocyte immunity against autologous tumor antigen was investigated. Forty percent (21 of 52) of the patients had lymphocyte immunity against tumor antigen. Iron metabolism molecules were expressed in abnormal quantities in some breast cancer patients: 27% (13 of 49) had elevated tumor tissue ferritin levels, 4% (2 of 49) had abnormally high serum ferritin, 10% (5 of 49) had abnormally low serum transferrin levels, and 43% (21 of 49) had depressed serum iron levels. None of these abnormalities in iron metabolism are associated with tumor immunity. These iron metabolism molecules may be indicative of rates of cell proliferation or may influence growth of breast cancer cells, but do not appear to influence host lymphocyte immunity against tumor associated antigens.","subset":"pubmed_abstract"} +{"meta":{"pmid":20163697,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":7}}},"text":"Dystroglycan versatility in cell adhesion: a tale of multiple motifs.\nDystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular alpha-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane beta-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin\/radixin\/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatio-temporal regulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27393422,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":1,"2024-22":2,"2024-18":1,"2024-30":1,"unknown":5}}},"text":"The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors.\nMelanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN-melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region.","subset":"pubmed_abstract"} +{"meta":{"pmid":8846783,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2016-40":1,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2016-44":1,"2013-48":1,"2015-18":1}}},"text":"Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating.\nA STE20\/p65pak homolog was isolated from fission yeast by PCR. The pak1+ gene encodes a 72 kDa protein containing a putative p21-binding domain near its amino-terminus and a serine\/threonine kinase domain near its carboxyl-terminus. The Pak1 protein autophosphorylates on serine residues and preferentially binds to activated Cdc42p both in vitro and in vivo. This binding is mediated through the p21 binding domain on Pak1p and the effector domain on Cdc42p. Overexpression of an inactive mutant form of pak1 gives rise to cells with markedly abnormal shape with mislocalized actin staining. Pak1 overexpression does not, however, suppress lethality associated with cdc42-null cells or the morphologic defeat caused by overexpression of mutant cdc42 alleles. Gene disruption of pak1+ establishes that, like cdc42+, pak1+ function is required for cell viability. In budding yeast, pak1+ expression restores mating function to STE20-null cells and, in fission yeast, overexpression of an inactive form of Pak inhibits mating. These results indicate that the Pak1 protein is likely to be an effector for Cdc42p or a related GTPase, and suggest that Pak1p is involved in the maintenance of cell polarity and in mating.","subset":"pubmed_abstract"} +{"meta":{"pmid":19907552,"dup_signals":{"dup_doc_count":35,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2017-39":1,"2016-44":2,"2016-40":1,"2016-36":5,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":2,"2015-40":3,"2015-35":4,"2015-32":4,"2015-22":3,"2018-17":1,"2015-18":1}}},"text":"Demonstration of 12 nm resolution Fresnel zone plate lens based soft x-ray microscopy.\nTo extend soft x-ray microscopy to a resolution of order 10 nm or better, we developed a new nanofabrication process for Fresnel zone plate lenses. The new process, based on the double patterning technique, has enabled us to fabricate high quality gold zone plates with 12 nm outer zones. Testing of the zone plate with the full-field transmission x-ray microscope, XM-1, in Berkeley, showed that the lens clearly resolved 12 nm lines and spaces. This result represents a significant step towards 10 nm resolution and beyond.","subset":"pubmed_abstract"} +{"meta":{"pmid":12711947,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"An outcome analysis comparing the thoracodorsal and internal mammary vessels as recipient sites for microvascular breast reconstruction: a prospective study of 100 patients.\nThe thoracodorsal vessels have been the standard recipient vessels for the majority of surgeons performing free transverse rectus abdominis musculocutaneous (TRAM) flap reconstructions. Recently, the internal mammary vessels have been recommended as the first-choice recipient vessels for microvascular breast reconstruction. This approach requires a shorter pedicle length, allows for central placement of flap tissue, and avoids axillary scarring. The use of the internal mammary vessels may provide for a shorter operative time and a higher-quality aesthetic reconstruction. The authors performed a prospective trial examining the differences in operative and aesthetic outcomes between each recipient site. A prospective trial of 108 consecutive free-tissue transfers was conducted in 100 patients. The first 60 TRAM flap patients were randomized so that 30 flaps were anastomosed to the internal mammary vessels and 30 were anastomosed to the thoracodorsal vessels, whereas the recipient vessels for the remaining 40 patients were left to the discretion of the surgeon. Of the 40 nonrandomized patients, 10 patients underwent reconstruction using the internal mammary vessels and 30 patients underwent reconstruction using the thoracodorsal vessels. The patients' medical history and hospital course were noted. To evaluate aesthetic outcome, a group of five blinded nonmedical observers and three blinded plastic surgeons graded the reconstructions in the 60 TRAM flap patients for symmetry and overall aesthetic result on a scale of 1 to 5. Blinded practitioners administered postoperative questionnaires to patients regarding recovery time and satisfaction with the aesthetic result. Forty-three flaps were transferred to the internal mammary vessels and 65 were transferred to the thoracodorsal vessels. No significant differences existed between groups with regard to age of preoperative risk factors. Average operative time was 6 hours in each group. Average hospital stay was 5.8 days in each group. Conversion from initial recipient vessel to a secondary recipient site occurred in 12.5 percent of internal mammary reconstructions and 7 percent of thoracodorsal reconstructions. All converted internal mammary cases occurred in left-sided reconstructions and were attributable to problems with the veins. Overall, 20 percent of left-sided internal mammary reconstructions were found to have an inadequate recipient vein. Unusable thoracodorsal vessels were found only in delayed reconstructions, at a rate of 15 percent in the delayed setting. All flaps from converted procedures survived without complications. Average follow-up was 20 months, during which time there was one flap loss in the thoracodorsal group. There were no significant differences in complication rates between groups. Average aesthetic grade was 3.6 in each group. Postoperative recovery time and overall patient satisfaction were not significantly different between groups. Either recipient site can provide for a safe and acceptable result; however, surgeons should be aware of conversion rates and plan appropriately if recipient vessels appear unusable for free-tissue transfer.","subset":"pubmed_abstract"} +{"meta":{"pmid":31881460,"dup_signals":{"dup_doc_count":11}},"text":"Stressors and coping of nursing students in clinical placement: A qualitative study contextualizing their resilience and burnout.\nThe aim of this study was to explore the stressors and coping of nursing students with differing levels of resilience and burnout during clinical placement. A qualitative descriptive study was conducted with twenty-four final-year baccalaureate nursing students, who were identified in the quantitative phase of the study as having scores indicating either: a) low resilience and high burnout; or b) high resilience and low burnout. Ten focus group interviews were conducted using a semi-structured interview guide. A thematic analysis of the data identified two main themes: a) stressors arising from the students aligning their expectations with the demands of the clinical placement (i.e., practice demands in busy wards, striving for learning opportunities, and discovering the social rules), and b) coping as a process of fitting into the ward culture. Those students with high resilience and low burnout scores had self-directed goals and coped by using self-regulation strategies. Those with low resilience and high burnout adopted external orientation and self-blame strategies. As suggested by the findings, the following approaches are recommended: offering interventions to enable students to fit actively into the clinical environment; encouraging engagement in reflection to facilitate self-awareness; and encouraging flexible use of personal and external resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":6292164,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Mapping of Streptococcus faecalis plasmids pAD1 and pAD2 and studies relating to transposition of Tn917.\nPlasmids pAD1 (37.8 megadaltons) and pAD2 (17.1 megadaltons) of Streptococcus faecalis strain DS16 have been mapped with restriction enzymes. The location of a hemolysin-bacteriocin determinant on the conjugative pAD1 plasmid was derived from analyses of transposon insertions. Electron microscope and hybridization analyses located Tn917(Em) and the streptomycin (Sm) and kanamycin (Km) resistance determinants on the nonconjugative pAD2 plasmid. It was shown previously that the erythromycin (Em) resistance associated with Tn917 is inducible and that transposition from pAD2 to pAD1 is also stimulated by exposure of cells to low concentrations of Em. Here we show that inducing concentrations of Em also increase the conjugative transfer potential of pAD1; this is possibly related to a mild and short-lived inhibitory stress placed on the cells before full induction of resistance. Selection of Em-resistant transconjugants arising from matings between DS16 and a plasmid-free recipient gave rise to transconjugants which primarily harbor stable pAD1::pAD2 cointegrates. A 30-min exposure of donors to Em (0.5 microgram\/ml) before mating resulted in a severalfold increase in the number of such transconjugants. However, a small fraction (e.g., 3 of 40) of these Emr Smr Kmr transconjugants harbored pAD1::Tn917 and pAD2 molecules. Since we believe pAD2 is incapable of being mobilized by pAD1 without being covalently linked, it is likely that transfer in these cases involved cointegrates representing structural intermediates in the transposition of Tn917 from pAD2 to pAD1. It follows that such intermediates probably had two copies of Tn917 and readily resolved after transfer. (These cointegrates are different from the stable cointegrates which were shown to have only a single copy of Tn917; the latter are assumed not to be related to transposition.) Two variants with altered Tn917 transposition properties were derived. One of them transposed at an elevated frequency, whereas the other showed no detectabel transposition. In neither case was transposition influenced by Em exposure; however, both remained inducible for Em resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":25861077,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Current status of residency training in laparoscopic surgery in Brazil: a critical review.\nThe surgeon's formation process has changed in recent decades. The increase in medical schools, new specialties and modern technologies induce an overhaul of medical education. Medical residency in surgery has established itself as a key step in the formation of the surgeon, and represents the ideal and natural way for teaching laparoscopy. However, the introduction of laparoscopic surgery in the medical residency programs in surgical specialties is insufficient, creating the need for additional training after its termination. To review the surgical teaching ways used in services that published their results. Survey of relevant publications in books, internet and databases in PubMed, Lilacs and Scielo through july 2014 using the headings: laparoscopy; simulation; education, medical; learning; internship and residency. The training method for medical residency in surgery focused on surgical procedures in patients under supervision, has proven successful in the era of open surgery. However, conceptually turns as a process of experimentation in humans. Psychomotor learning must not be developed directly to the patient. Training in laparoscopic surgery requires the acquisition of psychomotor skills through training conducted initially with surgical simulation. Platforms based teaching problem solving as the Fundamentals of Laparoscopic Surgery, developed by the American Society of Gastrointestinal Endoscopic Surgery and the Laparoscopic Surgical Skills proposed by the European Society of Endoscopic Surgery has been widely used both for education and for the accreditation of surgeons worldwide. The establishment of a more appropriate pedagogical process for teaching laparoscopic surgery in the medical residency programs is mandatory in order to give a solid surgical education and to determine a structured and safe professional activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":18295927,"dup_signals":{"dup_doc_count":47,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":2,"2021-04":1,"2015-18":1,"2015-06":2,"2014-10":1,"2013-48":2,"2013-20":3,"2017-13":1}}},"text":"Balancing health and industrial policy objectives in the pharmaceutical sector: lessons from Australia.\nPolicy-makers worldwide struggle to balance health with industrial policy objectives in the pharmaceutical sector. Tensions arise over pricing and reimbursement in particular. What health plans view as necessary to maintain equitable access to medicines, industry views as inimical to R&D and innovation. Australia has grappled with this issue for years, even incorporating the goal of \"maintaining a responsible and viable medicines industry\" into its National Medicines Policy. This case study was conducted via a narrative review that examined Australia's experiences balancing health and industrial policy objectives in the pharmaceutical sector. The review included electronic databases, grey literature and government publications for reports on relevant Australian policy published over the period 1985-2007. While pharmaceutical companies claim that Australia's pricing and reimbursement policies suppress drug prices and reduce profits, national policy audits indicate these claims are misguided. Australia appears to have secured relatively low prices for generics and \"me-too drugs\" while paying internationally competitive prices for \"breakthrough\" medicines. Simultaneously, Australia has focused efforts on local pharmaceutical investment through a variety of industry-targeted R&D incentive policies. Despite the fact that policy reviews suggest that Australia has achieved balance between health and industrial policy objectives, the country continues to face criticism from industry that its health goals harm innovation and R&D. Recent reforms raise the question whether Australia can sustain the apparent balance.","subset":"pubmed_abstract"} +{"meta":{"pmid":27428784,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience.\nThe role of stereotactic radiosurgery (SRS) for recurrent glioblastoma and the radionecrosis risk in this setting remain unclear. To perform a large retrospective study to help inform proper indications, efficacy, and anticipated complications of SRS for recurrent glioblastoma. We retrospectively analyzed patients who underwent Gamma Knife SRS between 1991 and 2013. We used the partitioning deletion\/substitution\/addition algorithm to identify potential predictor covariate cut points and Kaplan-Meier and proportional hazards modeling to identify factors associated with post-SRS and postdiagnosis survival. One hundred seventy-four glioblastoma patients (median age, 54.1 years) underwent SRS a median of 8.7 months after initial diagnosis. Seventy-five percent had 1 treatment target (range, 1-6), and median target volume and prescriptions were 7.0 cm 3 (range, 0.3-39.0 cm 3 ) and 16.0 Gy (range, 10-22 Gy), respectively. Median overall survival was 10.6 months after SRS and 19.1 months after diagnosis. Kaplan-Meier and multivariable modeling revealed that younger age at SRS, higher prescription dose, and longer interval between original surgery and SRS are significantly associated with improved post-SRS survival. Forty-six patients (26%) underwent salvage craniotomy after SRS, with 63% showing radionecrosis or mixed tumor\/necrosis vs 35% showing purely recurrent tumor. The necrosis\/mixed group had lower mean isodose prescription compared with the tumor group (16.2 vs 17.8 Gy; P = .003) and larger mean treatment volume (10.0 vs 5.4 cm 3 ; P = .009). Gamma Knife may benefit a subset of focally recurrent patients, particularly those who are younger with smaller recurrences. Higher prescriptions are associated with improved post-SRS survival and do not seem to have greater risk of symptomatic treatment effect.","subset":"pubmed_abstract"} +{"meta":{"pmid":9535996,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Intravenous and oral l-alpha-acetylmethadol: pharmacodynamics and pharmacokinetics in humans.\nLevo-alpha-acetylmethadol (LAAM) is a long-acting opioid agonist approved for use as a maintenance treatment for opioid dependence. Previous clinical studies report that the onset of the effects of LAAM is slower after parenteral administration than oral administration; however, preclinical studies suggest otherwise. This study examined the pharmacodynamic and pharmacokinetic profile of LAAM when given orally and intravenously to humans. Opioid-experienced volunteers (n = 6), who were not physically dependent on opioids, received LAAM (20 and 40 mg\/70 kg i.v. and p.o.) and placebo under double-blind, double-dummy conditions during five weekly experimental sessions. Behavioral, physiological, subjective and pharmacokinetic measures were collected before and for 96 hr after drug administration. Intravenous LAAM produced significant subjective and physiological effects that appeared within 5 min, whereas the effects of oral LAAM appeared more slowly within 1 to 2 hr after drug administration. Pharmacokinetic data indicate that the immediate effects of intravenous LAAM are largely attributable to the parent drug rather than the active metabolites, nor-LAAM and dinor-LAAM. LAAM produced prototypic opioid agonist effects (i.e., miosis, subjective ratings of high, nodding) that were of equal magnitude across routes, dose-related and of long duration (up to 60 hr). These data are in contrast to previous clinical reports and indicate that LAAM produces effects of immediate onset when administered parenterally, which suggests that intravenous LAAM possesses greater abuse potential than previously believed.","subset":"pubmed_abstract"} +{"meta":{"pmid":17846989,"dup_signals":{"dup_doc_count":59,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2022-05":2,"2021-43":1,"2021-31":1,"2021-25":2,"2021-17":1,"2019-18":1,"2019-04":2,"2018-51":1,"2018-47":1,"2018-43":3,"2018-39":1,"2018-34":2,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":2,"2018-13":3,"2018-09":3,"2018-05":2,"2017-51":3,"2017-47":5,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":2,"2022-33":1,"2017-13":4}}},"text":"CT measurement of trunk muscle areas in patients with chronic low back pain.\nThe objective of this study was to determine the cross-sectional area changes of the paraspinal, isolated multifidus, quadratus lumborum, psoas, and the gluteus maximus muscles with CT in patients with chronic low back pain. In this study, we evaluated 36 patients with chronic low back pain and 34 healthy volunteers. The mean age of the patients was 43.2 +\/- 6.9 years (range, 30- 58 years) and the mean age of control group was 44.4 +\/- 6.9 years (range, 31-61 years). We defined pain that lasts more then one year as chronic pain. Female patients were selected for standardization. All patients were housewives. None of the patients or controls engaged in physical activity other than routine housework. We used a visual analog scale and the Oswestry Pain Questionnaire for clinical evaluation. We made CT cross-sections of the paraspinal muscles at the upper and lower endplates of L4, and of the gluteus maximus at the head of the interfoveal level. In the patient group the multifidus, psoas, and quadratus lumborum cross-sectional areas were smaller than in the control group, and the P values were P = 0.002, P = 0.042, and P = 0.047, respectively, at the L4 endplate. At the L4 endplate level, cross-sectional areas of the multifidus and paravertebral muscles in the patient group were smaller than in the control group, and the difference was statistically significant (P = 0.001, P = 0.010, respectively). We did not find any significant difference between the patient and the control groups in gluteus maximus cross-sectional area. Chronic low back pain caused atrophy of the paraspinal, isolated multifidus, quadratus lumborum, psoas, and the gluteus maximus muscles to varying degrees, which was most prominent in the multifidus. Atrophy was noted in all of the studied muscles, except the gluteus maximus. The reliability of CT in measuring the cross-sectional areas of the back muscles was acceptable.","subset":"pubmed_abstract"} +{"meta":{"pmid":28425439,"dup_signals":{"dup_doc_count":12}},"text":"Activation of the hypothalamic feeding centre upon visual prey detection.\nThe visual system plays a major role in food\/prey recognition in diurnal animals, and food intake is regulated by the hypothalamus. However, whether and how visual information about prey is conveyed to the hypothalamic feeding centre is largely unknown. Here we perform real-time imaging of neuronal activity in freely behaving or constrained zebrafish larvae and demonstrate that prey or prey-like visual stimuli activate the hypothalamic feeding centre. Furthermore, we identify prey detector neurons in the pretectal area that project to the hypothalamic feeding centre. Ablation of the pretectum completely abolishes prey capture behaviour and neurotoxin expression in the hypothalamic area also reduces feeding. Taken together, these results suggest that the pretecto-hypothalamic pathway plays a crucial role in conveying visual information to the feeding centre. Thus, this pathway possibly converts visual food detection into feeding motivation in zebrafish.","subset":"pubmed_abstract"} +{"meta":{"pmid":31415079,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2022-27":2,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-34":1,"2019-39":3,"2022-49":1,"2024-10":1}}},"text":"Quantification of Retinal and Choriocapillaris Perfusion in Different Stages of Macular Telangiectasia Type 2.\nTo quantify the retinal and choriocapillaris perfusion in different disease stages of macular telangiectasia type 2 (MacTel) using optical coherence tomography-angiography (OCT-A). We examined 76 eyes of 76 patients and 24 eyes of 24 age-related controls. Participants underwent multimodal imaging, including OCT and OCT-A. Patients' eyes were divided into three groups considering predefined criteria from funduscopy, OCT, and fluorescein angiography, thus reflecting the disease severity (\"early,\" \"advanced,\" and \"neovascular\"). Quantitative analyses of vessel density (VD), skeleton density (SD), and fractal dimension (FD) were conducted in the superficial and deep retinal plexus and in the avascular layer. The choriocapillaris was analyzed for mean signal intensity and percentage of nondetectable perfused choriocapillaris-area (PNPA). The deep retinal plexus showed a progressive decrease of mean VD, SD, and FD in the temporal parafovea in all disease stages. In the superficial layer, VD, SD, and FD were significantly decreased in the temporal parafovea of advanced and neovascular stages, while these parameters did not differ from controls in early stages. In MacTel, signals of blood flow were also detectable at the level of the avascular layer and showed a significant increase with disease progression. The choriocapillaris in MacTel showed a significant increase of mean PNPA and a decrease of mean signal intensity in comparison to controls. These findings were consistent in all disease stages. Quantitative OCT-A data show a progressive rarefication of the retinal microvasculature in MacTel. We propose an altered choriocapillaris perfusion as a possibly early alteration of the disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":21427450,"dup_signals":{"dup_doc_count":13,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2017-13":1,"unknown":3}}},"text":"Parenting and feeding behaviors associated with school-aged African American and White children.\nPediatric obesity is multifactorial and difficult to treat. Parenting and feeding behaviors have been shown to influence a child's weight status. Most prior studies have focused on preschool-aged White children. Additional complicating factors include parents' inability to accurately identify their child's abnormal weight status. Parenting and feeding behaviors used by 176 African American and White parents of school-age children were examined. Assessment included (a) identifying what behaviors were reported when parent expressed concern with child's weight and (b) the relationship of these behaviors on child's body mass index percentile (BMI%), considering ethnicity, socioeconomic status (SES), and parent's body mass index (BMI). Findings included African American parents and parents concerned about their child's weight exhibited increased controlling\/authoritarian parenting and feeding behaviors. Parents were able to accurately identify their child's weight status. Parenting and feeding behaviors played a significant role in the children's BMI% even when controlling for ethnicity, SES, and parent's BMI.","subset":"pubmed_abstract"} +{"meta":{"pmid":7086338,"dup_signals":{"dup_doc_count":27,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2022-21":2,"2020-16":2,"2020-10":2,"2019-22":1,"2018-39":1,"2018-30":1,"2017-51":1,"2017-39":1,"2017-22":1,"2017-09":1,"2016-44":2,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2022-27":1}}},"text":"Energetic advantages of burst-and-coast swimming of fish at high speeds.\nA theoretical model describes how an intermittent swimming style can be energetically advantageous over continuous swimming at high average velocities. Kinematic data are collected from high-speed cin\u00e9 pictures of free swimming cod and saithe at high velocities in a burst-and-coast style. These data suggest that fish make use of the advantages shown by choosing initial and final burst velocities close to predicted optimal values. The limiting role of rapid glycogen depletion in fast white anaerobic muscle fibres is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":28079709,"dup_signals":{"dup_doc_count":11}},"text":"Meaningful Use of Electronic Health Records by Outpatient Physicians and Readmissions of Medicare Fee-for-Service Beneficiaries.\nNearly one-fifth of hospitalized Medicare fee-for-service beneficiaries are readmitted within 30 days. Participation in the Meaningful Use initiative among outpatient physicians may reduce readmissions. To evaluate the impact of outpatient physicians' participation in Meaningful Use on readmissions. The study population included 90,774 Medicare fee-for-service beneficiaries from New York State (2010-2012). We compared changes in the adjusted odds of readmission for patients of physicians who participated in Meaningful Use-stage 1, before and after attestation as meaningful users, with concurrent patients of matched control physicians who used paper records or electronic health records without Meaningful Use participation. Three secondary analyses were conducted: (1) limited to patients with 3+ Elixhauser comorbidities; (2) limited to patients with conditions used by Medicare to penalize hospitals with high readmission rates (acute myocardial infarction, congestive heart failure, and pneumonia); and (3) using only patients of physicians with electronic health records who were not meaningful users as the controls. Thirty-day readmission. Patients of Meaningful Use physicians had 6% lower odds of readmission compared with patients of physicians who were not meaningful users, but the estimate was not statistically significant (odds ratio: 0.94, 95% confidence interval, 0.88-1.01). Estimated odds ratios from secondary analyses were broadly consistent with our primary analysis. Physician participation in Meaningful Use was not associated with reduced readmissions. Additional studies are warranted to see if readmissions decline in future stages of Meaningful Use where more emphasis is placed on health information exchange and outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":11450179,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"The Stanley Foundation Bipolar Network. I. Rationale and methods.\nThe Stanley Foundation Bipolar Network (SFBN) was created to address the paucity of help studies in bipolar illness. To describe the rationale and methods of the SFBN. The SFBN includes five core sites and a number of affiliated sites that have adopted consistent methodology for continuous longitudinal monitoring of patients. Open and controlled studies are performed as patients' symptomatology dictates. The reliability of SFBN raters and the validity of the rating instruments have been established. More than 500 patients are in continuous daily longitudinal follow-up. More than 125 have been randomised to one of three of the newer antidepressants (bupropion, sertraline and venlafaxine) as adjuncts in a study of mood stabilizers and 93 to omega-3 fatty acids. A number of open clinical case series have been published. Well-characterised patients are followed in a detailed continuous longitudinal fashion in both opportunistic case series and double-blind, randomised controlled trials with reliable and validated measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":29170787,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Synthesis, computational, and spectroscopic analysis of tunable highly fluorescent BN-1,2-azaborine derivatives containing the N-BOH moiety.\nNine new polycyclic aromatic BN-1,2-azaborine analogues containing the N-BOH moiety were synthesized using a convenient two-step, one-pot procedure. Characterization of the prepared compounds show the luminescence wavelength and the quantum yields of the azaborines were tunable by controlling the power and location of the donor and acceptor substituents on the chromophore. UV-visible spectroscopy and density functional theory (DFT) computations revealed that the addition of electron-donating moieties to the isoindolinone hemisphere raised the energy of the HOMO, resulting in the reduction of the HOMO-LUMO gap. The addition of an electron-accepting moiety to the isoindolinone hemisphere and an electron-donating group to the boronic acid hemisphere decreased the HOMO-LUMO gap considerably, leading to emission properties from partial intramolecular charge transfer (ICT) states. The combined effect of an acceptor on the isoindolinone side and a donor on the boronic acid side (strong acceptor-\u03c0-donor) gave the most red-shifted absorption. The polycyclic aromatic BN-1,2-azaborines emitted strong fluorescence in solution and in the solid-state with the largest red-shifted emission at 640 nm and a Stokes shift of \u0394\u03bb = 218 nm, or \u0394\u03bd = 8070 cm-1.","subset":"pubmed_abstract"} +{"meta":{"pmid":32383636,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Nurses' self-efficacy, rather than their knowledge, is associated with their engagement in advance care planning in nursing homes: A survey study.\nConsidering social cognitive theory and current literature about successful advance care planning in nursing homes, sufficient knowledge and self-efficacy are important preconditions for staff to be able to carry out advance care planning in practice. Exploring to what extent nurses' knowledge about and self-efficacy is associated with their engagement in advance care planning in nursing homes. Survey study as part of a baseline measurement of a randomised controlled cluster trial (NCT03521206). Nurses in a purposive sample of 14 nursing homes in Belgium. A survey was distributed among nurses, evaluating knowledge (11 true\/false items), self-efficacy (12 roles and tasks on 10-point Likert-type scale) and six advance care planning practices (yes\/no), ranging from performing advance care planning conversations to completing advance directives. A total of 196 nurses participated (66% response rate). While knowledge was not significantly associated with advance care planning practices, self-efficacy was. One unit's increase in self-efficacy was statistically associated with an estimated 32% increase in the number of practices having carried out. Nurses' engagement in advance care planning practices is mainly associated with their self-efficacy rather than their knowledge. Further research is necessary to improve the evidence regarding the causal relationship between constructs. However, these results suggest that educational programmes that focus solely on knowledge might not lead to increasing uptake of advance care planning in nurses.","subset":"pubmed_abstract"} +{"meta":{"pmid":24186566,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-21":1,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":1,"2019-35":1,"2019-22":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-22":1,"2022-27":1,"2024-10":2,"2024-18":1}}},"text":"Pulmonary hypertension leads to a loss of gravity dependent redistribution of regional lung perfusion: a SPECT\/CT study.\nPre-capillary pulmonary hypertension (PHT) is characterised by progressive pulmonary vascular obliteration and loss of vascular reserves. In health, regional lung perfusion redistributes under the influence of gravity due to the presence of recruitable vessels. We investigated a combined single photon emission computed tomography\/CT (SPECT\/CT) method for assessing the pulmonary circulation by quantifying the gravity dependent redistribution of lung perfusion. Characterisation of patients versus healthy controls. 15 patients with pre-capillary PHT and 11 healthy controls. University hospital clinic. Regional lung perfusion was measured using SPECT\/CT in two different postures (supine vs upright). A perfusion redistribution index (PRI) was used to quantify the cranial-caudal shift in regional lung perfusion resulting from gravitational (postural) change. PRI was compared between cases and controls, and correlated with markers of disease severity in cases. Patients with pre-capillary PHT had notably reduced PRI compared to controls (0.02\u00b10.06 vs. 0.28\u00b10.15 normalised perfusion\/cm, p<0.0001). PRI was significantly associated with prognostic parameters such as 6 min walk distance (r=0.60, p=0.018), functional class (p=0.008), and tricuspid annular plane systolic excursion (r=0.58, p=0.022). The receiver operating characteristic curve showed that PRI differentiated patients with pre-capillary PHT from controls with AUC=0.94 (p<0.001). With SPECT\/CT, gravity dependent redistribution of lung perfusion can be quantified using the PRI derived from supine and upright perfusion analysis. The potential utility of PRI for the non-invasive detection of PHT and assessment of disease severity warrants further study.","subset":"pubmed_abstract"} +{"meta":{"pmid":27497431,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":14}}},"text":"Genetic rescue in a severely inbred wolf population.\nNatural populations are becoming increasingly fragmented which is expected to affect their viability due to inbreeding depression, reduced genetic diversity and increased sensitivity to demographic and environmental stochasticity. In small and highly inbred populations, the introduction of only a few immigrants may increase vital rates significantly. However, very few studies have quantified the long-term success of immigrants and inbred individuals in natural populations. Following an episode of natural immigration to the isolated, severely inbred Scandinavian wolf (Canis lupus) population, we demonstrate significantly higher pairing and breeding success for offspring to immigrants compared to offspring from native, inbred pairs. We argue that inbreeding depression is the underlying mechanism for the profound difference in breeding success. Highly inbred wolves may have lower survival during natal dispersal as well as competitive disadvantage to find a partner. Our study is one of the first to quantify and compare the reproductive success of first-generation offspring from migrants vs. native, inbred individuals in a natural population. Indeed, our data demonstrate the profound impact single immigrants can have in small, inbred populations, and represent one of very few documented cases of genetic rescue in a population of large carnivores.","subset":"pubmed_abstract"} +{"meta":{"pmid":20215561,"dup_signals":{"dup_doc_count":29,"dup_dump_count":23,"dup_details":{"curated_sources":3,"2023-40":3,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-24":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-47":1,"2017-39":1,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Binding of inositol 1,4,5-trisphosphate (IP3) and adenophostin A to the N-terminal region of the IP3 receptor: thermodynamic analysis using fluorescence polarization with a novel IP3 receptor ligand.\nInositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)R) are intracellular Ca(2+) channels. Their opening is initiated by binding of IP(3) to the IP(3)-binding core (IBC; residues 224-604 of IP(3)R1) and transmitted to the pore via the suppressor domain (SD; residues 1-223). The major conformational changes leading to IP(3)R activation occur within the N terminus (NT; residues 1-604). We therefore developed a high-throughput fluorescence polarization (FP) assay using a newly synthesized analog of IP(3), fluorescein isothiocyanate (FITC)-IP(3), to examine the thermodynamics of IP(3) and adenophostin A binding to the NT and IBC. Using both single-channel recording and the FP assay, we demonstrate that FITC-IP(3) is a high-affinity partial agonist of the IP(3)R. Conventional [(3)H]IP(3) and FP assays provide similar estimates of the K(D) for both IP(3) and adenophostin A in cytosol-like medium at 4 degrees C. They further establish that the isolated IBC retains the ability of full-length IP(3)R to bind adenophostin A with approximately 10-fold greater affinity than IP(3). By examining the reversible effects of temperature on ligand binding, we established that favorable entropy changes (T Delta S) account for the greater affinities of both ligands for the IBC relative to the NT and for the greater affinity of adenophostin A relative to IP(3). The two agonists differ more substantially in the relative contribution of Delta H and T Delta S to binding to the IBC relative to the NT. This suggests that different initial binding events drive the IP(3)R on convergent pathways toward a similar open state.","subset":"pubmed_abstract"} +{"meta":{"pmid":30949808,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"Genome mining and metabolic profiling illuminate the chemistry driving diverse biological activities of Bacillus siamensis SCSIO 05746.\nBacillus spp. are important producers of bioactive natural products with potential applications in medicine and agriculture. Bacillus sp. SCSIO 05476 from a deep-sea sediment exhibits broad-spectrum antimicrobial activities and strong cytotoxic activity. Here, an integrative approach combining genome mining and metabolic profiling has been applied to decipher the chemical origins of this strain's varied and significant biological activities. First, genome mining revealed 19 candidate gene clusters encoding the biosynthesis of diverse secondary metabolites. Then, a series of bacillibactins, fengycins, bacillomycins, surfactins, bacillaenes, macrolactins, and related species were found by LC-DAD-MS. Finally, three new linear bacillibactins, linbacillibactins A-C (1-3), along with 11 known secondary metabolites, bacillibactin (4), normal-C13 Val7 surfactin (5), anteiso-C13 Leu7 surfactin (6), iso-C14 Leu7 surfactin (7), normal-C14 Leu7 surfactin (8), anteiso-C14 Leu7 surfactin (9), macrolactin D (10), normal-C14 bacillomycin D (11), iso-C16 bacillomycin D (12), normal-C17 bacillomycin D (13), and iso-C17 bacillomycin D (14), were obtained and elucidated by bioactivity and structure-guided isolation from the fermentation of strain SCSIO 05746. Among them, new compounds 1-3 show significant siderophore activities comparable to that of bacillibactin (4), compounds 13 and 14 exhibit strong cytotoxic activity. At the same time, the strain classification status was confirmed by genomic analyses, and the complete genome sequence of Bacillus siamensis was presented firstly. This study provides a foundation for understanding the mechanisms driving SCSIO 05746's multiple bioactivities and demonstrates a successful way of discovering bioactive metabolites using a combination of genome mining and metabolic profiling methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":35608038,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Liberal-secular power and the traps of muslim integration in Western Europe.\nThroughout the last decades, integration programmes in Western Europe have centrally revolved around debates on Muslim populations and the institutionalization of Islam. The concept of integration has become a master paradigm with which to structure plurality of immigration societies across Western Europe. Critically reflecting this inflation, this article argues that the integration of Muslims is animated by a contingent liberal-secular matrix through which the sovereign state, in close connection with civil society, is enabled to decide what counts as proper and improper religion. Integration directed toward Muslims as a \"religious minority\" is therefore indicative of the very problems that it purports to resolve. In a genealogical vein, the article begins by suggesting that integration is a liberal \"recursion\" of earlier projects of minority management such as assimilation and conditional recognition within emerging nation-states. It argues that the epistemological ground which animated the assimilatory forces of the modern nation-state has been intimately bound by an imperial knowledge order which classifies and hierarchizes people along a race-religion nexus. The analysis continues by dwelling on contemporary examples of state organized dialog with Muslims, and more specifically the establishment of Islamic Theology Chairs at state universities. Through these examples the article shows that the institutionalization of Islam in Europe reconfigures a pattern which conditionally embraces religious difference, while at the same time continuing hierarchical rankings and by transforming it to make it fit for religion's legitimate place in public life. Finally, the article suggests that the somatic aspirations prevalent in assimilation projects and imperial race-religion constellations are both inscribed and concealed in the frequent invocation of Muslims to reveal their loyalty to the liberal-secular contract by bracketing their religious sensibilities for the sake of secular reason.","subset":"pubmed_abstract"} +{"meta":{"pmid":28268306,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"In-silico pre-clinical trials for implantable cardioverter defibrillators.\nRegulatory authorities require that the safety and efficacy of a new high-risk medical device be proven in a Clinical Trial (CT), in which the effects of the device on a group of patients are compared to the effects of the current standard of care. Phase III trials can run for several years, cost millions of dollars, and expose patients to an unproven device. In this paper, we demonstrate how to use a large group of synthetic patients based on computer modeling to improve the planning of a CT so as to increase the chances of a successful trial for implantable cardioverter defibrillators (ICDs). We developed a computer model of the electrical generation and propagation in the heart. This model was used to generate a large group of heart instances capable of producing episodes of 19 different arrhythmias. We also implemented two arrhythmia detection algorithms from the literature: Rhythm ID from Boston Scientific and PR Logic + Wavelet from Medtronic. Using this setup, we conducted multiple in-silico trials to compare the ability of the two algorithms to appropriately discriminate between potentially fatal Ventricular Tachy-arrhythmias (VT) and nonfatal Supra-Ventricular Tachy-arrhythmias (SVTs). The results of our in-silico trial indicate that Rhythm ID was less able to discriminate between SVT and VT and so may lead to more cases of inappropriate therapy. This corroborates the findings of the Rhythm ID Going Head to Head Trial (RIGHT), a clinical trial that compared the two algorithms in patients. We further demonstrated that the result continues to hold if we vary the distribution of arrhythmias in the synthetic population. We also used the same in-silico cohort to explore the sensitivity of the outcome to different parameter settings of the device algorithms, which is not feasible in a real clinical trial. In-silico trials can provide early insight into the factors which affect the outcome of a CT at a fraction of the cost and duration and without the ethical issues.","subset":"pubmed_abstract"} +{"meta":{"pmid":17322371,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":8}}},"text":"Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kappaB component RelB.\nThe transcription factor aryl hydrocarbon receptor (AhR) plays an important role in the response to environmental pollutants. However, its role in normal physiology is unclear. To investigate the role of AhR in acute lung inflammation, control and AhR knockout (KO) mice were exposed to inhaled cigarette smoke or bacterial endotoxin. Smoke-induced lung inflammation was twofold to threefold more severe in AhR KO mice than controls. Intriguingly, levels of tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage of air-exposed KO mice were equal to the levels seen in smoke-exposed controls, suggesting that AhR-deficient mice are inflammation prone. AhR KO mice challenged with inhaled endotoxin, which does not contain AhR ligands, also developed greater lung neutrophilia than controls, and bronchoalveolar lavage cells from AhR KO mice produced elevated levels of tumor necrosis factor-alpha and interleukin-6 when treated with endotoxin in vitro. Nuclear factor-kappaB DNA-binding activity was elevated in smoke-exposed AhR KO mice compared with controls and was associated with a rapid loss of RelB only in the KO mice. We propose that AhR is a previously unrecognized regulator of inflammation that interacts with nuclear factor-kappaB so that in the absence of AhR RelB is prematurely degraded, resulting in heightened inflammatory responses to multiple proinflam-matory stimuli.","subset":"pubmed_abstract"} +{"meta":{"pmid":27801778,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":11}}},"text":"Antiviral Screening of Multiple Compounds against Ebola Virus.\nIn light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":29222463,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"The genome sequence of Bipolaris cookei reveals mechanisms of pathogenesis underlying target leaf spot of sorghum.\nBipolaris cookei (=Bipolaris sorghicola) causes target leaf spot, one of the most prevalent foliar diseases of sorghum. Little is known about the molecular basis of pathogenesis in B. cookei, in large part due to a paucity of resources for molecular genetics, such as a reference genome. Here, a draft genome sequence of B. cookei was obtained and analyzed. A hybrid assembly strategy utilizing Illumina and Pacific Biosciences sequencing technologies produced a draft nuclear genome of 36.1 Mb, organized into 321 scaffolds with L50 of 31 and N50 of 378 kb, from which 11,189 genes were predicted. Additionally, a finished mitochondrial genome sequence of 135,790 bp was obtained, which contained 75 predicted genes. Comparative genomics revealed that B. cookei possessed substantially fewer carbohydrate-active enzymes and secreted proteins than closely related Bipolaris species. Novel genes involved in secondary metabolism, including genes implicated in ophiobolin biosynthesis, were identified. Among 37 B. cookei genes induced during sorghum infection, one encodes a putative effector with a limited taxonomic distribution among plant pathogenic fungi. The draft genome sequence of B. cookei provided novel insights into target leaf spot of sorghum and is an important resource for future investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":36758014,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":3,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Physicians' attitudes towards ethical issues and end-of-life decision-making for pediatric patients with unresponsive wakefulness syndrome: An international survey.\nWe examined physicians' perspectives on the mental capabilities of pediatric patients with unresponsive wakefulness syndrome (UWS) and their attitudes towards limiting life-sustaining treatment (LST) in an international context. A questionnaire survey was conducted among 267 neuropediatricians, practicing in 65 countries. Comparisons were made according to the Human Development Index (HDI) of the countries. The Idler Index of Religiosity was applied to determine religiosity. Participants from countries with a very high HDI were generally more favorable to limiting LST (p < 0.001), specifically cardiopulmonary resuscitation (p = 0.021), intubation\/ventilation (p = 0.014), hemodialysis\/hemofiltration (p < 0.001), and antibiotic therapy (p < 0.001). Treatment costs that were too high had a weaker influence on their decisions (p < 0.001). Participants who found it never ethically justifiable to limit LST had a higher mean Idler Index of private (p = 0.001) and general (p = 0.020) religiosity and were less satisfied with treatment decisions (p < 0.001) and the communication during the process (p = 0.016). The perspectives towards limiting LST for pediatric patients with UWS are markedly different between physicians from countries with very high and lower HDIs.","subset":"pubmed_abstract"} +{"meta":{"pmid":29780503,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":13}}},"text":"A high throughput screening method for the nano-crystallization of salts of organic cations.\nThe generation of solid salts of organic molecules is important to the chemical and pharmaceutical industry. Commonly used salt screening methods consume a lot of resources. We employed a combination of ion exchange screening and vapour diffusion for crystallization. This technique is semi-automatic and requires just nanoliters of the solution of the analyte to be crystallized. This high throughput screening yielded single crystals of sufficient size and quality for single-crystal X-ray structure determination using an in-house X-ray diffractometer. The broad scope of our method has been shown by challenging it with 7 very different organic cations, whose aqueous solubilities vary by a factor of almost 1000. At least one crystal structure for 6 out of 7 tested cations was determined; 4 out of the successful 6 ones had never been crystallized before. Our method is extremely attractive for high throughput salt screening, especially for active pharmaceutical ingredients (APIs), as about 40% of all APIs are cationic salts. Additionally, our screening is a new and very promising procedure for the crystallization of salts of organic cations.","subset":"pubmed_abstract"} +{"meta":{"pmid":15795964,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"A preliminary report on a skills-based telephone-administered peer support programme for patients with multiple sclerosis.\nPeer-support interventions have shown no statistically significant or clinically meaningful effect on quality of life (QOL) or depressive symptoms for multiple sclerosis (MS) patients. Peer-support interventions for MS generally provide support but no skills training. The aim of this study was to evaluate a brief telephone-administered skills-training model of peer-support for patients with MS. Sixteen patients with MS showing signs of moderate distress received eight sessions of telephone-administered peer support (TAPS). TAPS is a manualized programme administered by peer-support counsellors diagnosed with MS. Using a workbook, peer-support counsellors teach skills to manage distress and MS symptoms. Subjective depression was assessed using the Center for Epidemiological Studies Depression Scale while objective depression was rated using the Hamilton Rating Scale for Depression. QOL was measured pre- and post-treatment using the SF-36. The participants showed significant improvements on both the CESD (p = 0.04) and the HRSD (p = 0.01). Overall QOL improved significantly (p = 0.045), however this was not reflected in either the Physical Health composite score or the Mental Health Composite Scale (p > 0.17). These findings suggest that TAPS may prove to be an efficacious peer-support model for patients with MS.","subset":"pubmed_abstract"} +{"meta":{"pmid":7852358,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Differential recognition of alpha 1-antitrypsin-elastase and alpha 1-antichymotrypsin-cathepsin G complexes by the low density lipoprotein receptor-related protein.\nTwo multifunctional receptors, low density lipoprotein receptor-related protein (LRP) and gp330, have been implicated in the cellular uptake and degradation of a wide spectrum of functionally diverse ligands including plasma lipoproteins, proteases, and proteinase-inhibitor complexes. The two receptors show distinct tissue-specific expression patterns, suggesting different physiological functions. We have examined the cellular degradation of two serine proteinase inhibitor (serpin)-protease complexes, alpha 1-antitrypsin-neutrophil elastase (alpha 1AT.NEL) and alpha 1-antichymotrypsin-cathepsin G (alpha 1ACT.CathG) by normal murine fibroblasts (MEF) expressing LRP, and by a mutant fibroblast cell line (PEA13) which is genetically deficient for LRP. alpha 1AT.NEL complexes bound to LRP on ligand blots and were degraded efficiently by the MEF cells, but not by PEA13 cells. Degradation of the complexes was also significantly reduced by antibodies directed against LRP, further suggesting that fibroblasts require LRP for the cellular uptake and degradation of alpha 1AT.NEL complexes. In contrast to alpha 1AT.NEL, MEF cells did not degrade alpha 1ACT.CathG complexes. However, these complexes were rapidly degraded by the rat embryonal carcinoma cell line L2p58 which abundantly expresses gp330, raising the possibility that the alpha 1ACT.CathG complex might be recognized by gp330. Both complexes were efficiently metabolized by the hepatoma cell line HepG2, presumably involving the serpin-enzyme complex receptor. The differential recognition of serpin-protease complexes by fibroblasts and hepatoma cells, however, indicates that LRP, gp330, and the serpin-enzyme complex receptor are distinct proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":30443308,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Comparative study of the usability of two software programs for visualization and analysis of digital orthodontic models.\nBackground. Software programs for visualization and analysis of digital orthodontic models, apart from presenting the necessary features for diagnosis and treatment planning, also need to be user-friendly. This characteristic refers to software' usability, a measure that evaluates how easy it is to use it is by a specific group of professionals. The aim of this study was to compare the usability of free available versions of two software programs for visualization and analysis of digital orthodontic models. Methods. Digimodel\u00ae and OrthoCAD\u00ae usability were evaluated through their interface analysis and executing the following procedures: malocclusion classification and models analysis (arch-length and tooth-size discrepancies). Results. Digimodel\u00ae and OrthoCAD\u00ae software programs had an installer only for Windows platform, occupied less than 110 megabytes of virtual space and only read files from their respective manufacturers. None possessed Portuguese as a language option. Both allowed visualization of the models in different axes through options present in initial screen, at a click. For model analysis, both software programs required to measure tooth to tooth and performed necessary calculations automatically. However, OrthoCAD\u00ae software program was less intuitive because the option for these actions was among several others, within menus, which could cause confusion during navigation. In addition, the marking of points did not always obey the clicked site. Conclusion. The free access version of the evaluated software programs exhibited usability limitations related to language, supported file format and even the model analysis execution for orthodontic diagnosis. Although OrthoCAD\u00ae was inferior, both did not meet orthodontists' clinical demand against these factors in the evaluated versions.","subset":"pubmed_abstract"} +{"meta":{"pmid":28659736,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Folate intake in a Swedish adult population: Food sources and predictive factors.\nIntroduction: Folate plays an important role in cell metabolism, but international studies show that intake is currently below recommendations, especially among women. The study objective was to identify folate food sources by food group, gender, and age group, and to identify factors influencing folate intake, based on food consumption data for Swedish adults in the 2010-11 Riksmaten study. Methods: The sample included a representative Swedish population aged 18-80 years (n = 1657; 56.3% female). Food and nutrient intakes were estimated from self-reported food records during 4 consecutive days. Food consumption was categorized into 26 food groups. Stepwise regression was used to analyze food groups as folate sources for participants. Factors predicting the highest folate intake (third tertile) were determined by logistic regression analysis. Results: Vegetables and pulses represented the most important folate source for all age groups and both genders, especially in women aged 45-64 years (49.7% of total folate intake). The next folate source in importance was dairy products for the youngest group (18-30 years), bread for men, and fruit and berries for women. The likelihood of being in the highest tertile of folate intake (odds ratio = 1.69, 95% confidence interval 1.354-2.104) was higher for men. Influencing factors for folate intake in the highest tertile were low body mass index and high educational level in the men, and high educational level, vegetarian diet, organic product consumption, non-smoking, and alcohol consumption within recommendations in the women. Conclusion: This study describes the folate intake per food group of Swedish adults according to the 2010-11 Riksmaten survey, identifying vegetables and pulses as the most important source. Data obtained on factors related to folate consumption may be useful for the development of specific nutrition education programs to increase the intake of this vitamin in high-risk groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":31373467,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2021-49":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-04":1,"2020-45":1,"2020-34":2,"2020-16":1,"2020-10":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2023-14":1,"2024-30":2,"2024-10":2}}},"text":"[Peritoneal dialysis catheter infection with abscess of the abdominal wall in a ADPKD patient].\nInfections to the peritoneal catheter are common in Peritoneal Dialysis (PD). We report the clinical case of a 49-year-old male patient in PD, who showed an atypical manifestation of tunnel infection caused by Staphylococcus aureus. The infection was characterized by a little abscess, on the left pararectal abdominal line, 6 cm far from exit-site of the peritoneal catheter. The diagnosis was made using ultrasonography (US), which showed a fistulous communication from subcutaneous cuff to the skin. We treated the infection conservatively by performing cuff-shaving and drainage of the abscess, associated to antibiotic therapy (teicoplanin). Due to the persistence of the infection, we added oral and topical rifampicin, and advanced medication with freez-dried collagen plant impregnated with extended-release gentamicin. The complete resolution of the infection allowed us to avoid removing the catheter.","subset":"pubmed_abstract"} +{"meta":{"pmid":15870514,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A prospective evaluation of \"see and treat\" in women with HSIL Pap smear results: is this an appropriate strategy?\nThe evaluation of abnormal cervical cytologic results is time consuming and costly. Most patients with high-grade squamous intraepithelial lesion (HSIL)-cervical intraepithelial neoplasia 3 (CIN 3) Pap smear results require an excisional procedure for diagnostic or therapeutic reasons. \"See and treat\" is a surgical procedure that involves a loop electrosurgical excisional procedure (LEEP) simultaneously to diagnose and to treat premalignant cervical disease in one visit. This procedure eliminates a second visit that typically is required for treatment. Data is lacking on the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear result. The objective of this study was to determine the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear using a see-and-treat protocol. Women referred from local health departments to our university-based colposcopy clinic for evaluation of an HSIL (CIN 2) Pap smear result were evaluated for inclusion in a see and treat protocol. All eligible patients underwent colposcopy to rule out an obvious cervical carcinoma followed by an immediate LEEP to remove the transformation zone. A colposcopic impression was made using the Reid colposcopic index. Pathologic specimens were analyzed for the presence of CIN and the incidence of CIN 2 and CIN 3 was determined. To date, 51 patients have been enrolled in the study. Exclusion criteria included age less than 19 years, pregnancy, or medical contraindications. The mean age of the patients was 26 years (range, 19-45 years). Forty-seven percent were white, 47% were black, and 6% were Hispanic. Of the 51 patients who underwent LEEP, 43 of 51 (85%) had satisfactory colposcopy and no patient had a lesion suspicious for cervical carcinoma. The average Reid colposcopic index was 3.5. Of the 51 LEEP specimens, 4 of 51 had no evidence of CIN (8%), 4 of 51 (8%) had CIN 1, 18 of 51 (35%) had CIN 2, and 25 of 51 (49%) had CIN 3. Eighty-four percent of patients had either CIN 2 or CIN 3, resulting in an overtreatment rate (CIN 1 or less) of 16%. The use of a see and treat protocol for patients with HSIL (CIN 2) Pap smear results may be an acceptable treatment option because of a high incidence of CIN 2 and CIN 3.","subset":"pubmed_abstract"} +{"meta":{"pmid":10888691,"dup_signals":{"dup_doc_count":43,"dup_dump_count":36,"dup_details":{"curated_sources":3,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":1,"2014-15":1,"2019-09":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1}}},"text":"Child development services in Medicaid managed care organizations: what does it take?\nWe sought to understand why certain Medicaid managed care organizations (MMCOs) implemented child development services or programs and how they had done so. We also sought to identify barriers and facilitators to successful initiation and implementation of child development programs. We conducted 9 key informant interviews and 4 site visits, and performed qualitative analyses to identify major themes across responses. We identified a small number of MMCOs with child development services. High-level support was crucial for program initiation; physician buy-in, staff support, and strong working relationships with outside health professionals or agencies were principal factors in successful program implementation. MMCOs that were committed to implementing child development services were successful in doing so, without external funding or regulatory mandate. The results provide valuable strategies for MMCOs interested in developing programs and for researchers and advocates interested in promoting child development services for low-income children.","subset":"pubmed_abstract"} +{"meta":{"pmid":10323348,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":4,"unknown":9}}},"text":"A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.\nThe World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution\/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution\/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.","subset":"pubmed_abstract"} +{"meta":{"pmid":11356983,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Hepatic and renal toxicities associated with perchloroethylene.\nMetabolism of perchloroethylene (Perc) occurs by cytochrome P450-dependent oxidation and glutathione (GSH) conjugation. The cytochrome P450 pathway generates tri- and dichloroacetate as metabolites of Perc, and these are associated with hepatic toxicity and carcinogenicity. The GSH conjugation pathway is associated with generation of reactive metabolites selectively in the kidneys and with Perc-induced renal toxicity and carcinogenicity. Physiologically based pharmacokinetic models have been developed for Perc in rodents and in humans. We propose the addition of a submodel that incorporates the GSH conjugation pathway and the kidneys as a target organ. Long-term bioassays of Perc exposure in laboratory animals have identified liver tumors in male and female mice, kidney tumors in male rats, and mononuclear cell leukemia in male and female rats. Increases in incidence of non-Hodgkin's lymphoma and of cervical, esophageal, and urinary bladder cancer have been observed for workers exposed to Perc. Limited, and not always consistent, evidence is available concerning the kidneys as a target organ for Perc in humans. Three potential modes of action for Perc-induced liver tumorigenesis are: 1) modification of signaling pathways; 2) cytotoxicity, cell death, and reparative hyperplasia; and 3) direct DNA damage. Four potential modes of action for Perc-induced renal tumorigenesis are: 1) peroxisome proliferation, 2) alpha-2u-globulin nephropathy, 3) genotoxicity leading to somatic mutation, and 4) acute cytotoxicity and necrosis leading to cell proliferation. Finally, the epidemiological and experimental data are assessed and use of toxicity information in the development of a reference dose and a reference concentration for human Perc exposure are presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":17873992,"dup_signals":{"dup_doc_count":27,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":20}}},"text":"Patterns of influenza infections among different risk groups in Brazil.\nInfluenza virus infections are associated with high morbidity and mortality. Influenza activity varies worldwide, and regional detection is influenced by geographic conditions, demographic and patient-risk factors. We assessed influenza activity and patterns of seasonality during three consecutive years (2001-2003) in three risk groups in S\u00e3o Paulo city. Four-hundred-twelve outpatients with acute respiratory infection were subjected to epidemiological, clinical and laboratory investigations; these included community population (N=140), health-care workers (N=203), and renal-transplanted patients (N=69). Nasal wash samples were tested by direct fluorescent assay for influenza, parainfluenza, adenovirus, and respiratory syncytial virus. Overall Influenza positivity was 21%, and a progressive decline was observed in all groups over time. Influenza A and B co-circulated at the same time in 2001 and 2002, but not in 2003. Low influenza-vaccination rates (19%) were reported by health-care workers. Unexpected low levels of etiological agents were detected in renal-transplanted patients, and infected cases were less symptomatic than immunocompetent patients. Based on this study, we conclude that health-care worker-immunization programs should be implemented and the clinical patterns of infected influenza patients should be used as a guide for better case-definition criteria for adequate influenza surveillance, particularly for renal-transplant patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":24488746,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Risk and prevalence of developmental delay in young children with congenital heart disease.\nChildren with congenital heart disease (CHD) are at risk for developmental delay (DD). Changes in cognitive, language, and motor skills in early childhood have not been described. We report the results of a structured approach using longitudinal testing to identify problems and ensure early intervention in accordance with published guidelines. Bayley Scales of Infant Development, Third Edition, were used to assess cognitive, language, and motor skills in 99 children with CHD. Subjects were evaluated 3 to 6 times in the first 3 years of life. DD was defined as scores >1 SD below the population mean. Cardiac anatomy was single ventricle (1V) in 34 subjects and 2 ventricles (2V) in 65. Medical comorbidities were present in 21% and genetic syndromes in 19%. Most subjects (75%) had DD in \u22651 area at \u22651 assessments. Subjects with 1V anatomy had equivalent outcomes to those with 2V. Cognitive and language scores declined in subjects with genetic syndromes but were stable and within the average range for subjects with 1V and 2V. Motor scores improved for subjects with 1V and 2V but remained low for those with genetic syndromes. In addition to age, need for supplemental tube feeding, longer cardiopulmonary bypass time, and shorter time since last hospitalization were significant predictors of developmental outcomes. DDs in young children with CHD are both common and dynamic. Providers should encourage longitudinal surveillance for children with CHD because exposure to risk and prevalence of DD change over time.","subset":"pubmed_abstract"} +{"meta":{"pmid":18447482,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":12}}},"text":"A molecular simulation study of an organosilane self-assembled monolayer\/SiO2 substrate interface.\nThe bonding network of an alkylsilane self-assembled monolayer (SAM)SiO(2) substrate interface is investigated by means of canonical Monte Carlo (MC) simulations. SAMSiO(2) systems with different interfacial bonding topologies are sampled by the Metropolis MC method, and the AMBER potential with a newly developed organosilicon parameters are used to obtain an optimized structure with a given bonding topology. The underlying substrates are modeled as hydroxy-terminated (100) or (111) cristobalites. The SAMSiO(2) interface is characterized by a polysiloxane bonding network which comprises anchoring bonds and cross-linking bonds, namely, molecule-substrate and molecule-molecule Si-O-Si bonds, respectively. We show that at thermal equilibrium, the ratio of the number of anchoring bonds to cross-linking bonds decreases as a total Si-O-Si bond density increases, and that nevertheless, number of anchoring bonds always dominate over that of cross-linking bonds. Moreover we show that the total Si-O-Si bond density strongly affects the lateral ordering of the alkylsilane molecules, and that increase in the Si-O-Si bond density disorders the molecular packing. Our results imply that a lab-to-lab variation in the experimentally prepared SAMs can be attributed to different Si-O-Si bond densities at the SAMSiO(2) interface.","subset":"pubmed_abstract"} +{"meta":{"pmid":12791511,"dup_signals":{"dup_doc_count":17,"dup_dump_count":10,"dup_details":{"curated_sources":6,"2021-31":1,"2021-10":1,"2020-50":2,"2020-40":1,"2019-51":1,"2018-39":1,"2018-26":1,"2018-09":1,"2017-47":1,"2022-33":1}}},"text":"Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL downregulation, and Cdc2 kinase activity.\nGenistein, biochanin-A, and daidzein, the predominant soy isoflavones, have been reported to lower the risk of cancer, but it is not known whether they protect against human hepatoma cancer. This study was designed to investigate their effects on cell growth, the cell cycle, and apoptosis induction in the human hepatoma cell lines, HepG2, Hep3B, Huh7, PLC, and HA22T. Genistein, biochanin-A, and daidzein inhibited growth of all five lines in a dose-dependent manner. DNA fragmentation studies and the TUNEL assay demonstrated that isoflavones caused tumor cell death by induction of apoptosis. Activation of caspase-3 and cleavage of the caspase-3 substrate, poly(ADP-ribose)polymerase, was seen in hepatoma cells after 24 hours' exposure to isoflavones. In addition, isoflavone cytotoxicity correlated with downregulation of Bcl-2 and Bcl-XL expression. Synergistic effects of the three isoflavones were observed on cell growth inhibition, apoptosis induction, and anti-apoptotic protein expression. Flow cytometry showed that genistein, but not biochanin-A or daidzein, induced progressive and sustained accumulation of hepatoma cancer cells in the G2\/M phase as a result of inhibition of Cdc2 kinase activity. Coapplication of caffeine prevented this cell cycle arrest, but not apoptosis, showing that cell cycle arrest was not necessary for apoptosis. Furthermore, the isoflavones combination also had a significant tumor-suppressive effect in nude mice. These results suggest that isoflavones might be promising agents for the treatment of human hepatoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":22303469,"dup_signals":{"dup_doc_count":18,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2,"2017-13":1,"unknown":3}}},"text":"Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity.\nThe inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV) vaccine, that can target conserved internal antigens such as the nucleoprotein (NP) and\/or matrix protein (M1) need to be explored. In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs), protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA) severely compromises fusion activity of the virus, while inactivation with \u03b2-propiolactone (BPL) preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane fusion activity and full immunogenicity of the vaccine.","subset":"pubmed_abstract"} +{"meta":{"pmid":29204259,"dup_signals":{"dup_doc_count":21}},"text":"Early development of infants with neurofibromatosis type 1: a case series.\nProspective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder.","subset":"pubmed_abstract"} +{"meta":{"pmid":10605445,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Intracellular divalent cation release in pancreatic acinar cells during stimulus-secretion coupling. II. Subcellular localization of the fluorescent probe chlorotetracycline.\nSubcellular distribution of the divalent cation-sensitive probe chlorotetracycline (CTC) was observed by fluorescence microscopy in isolated pancreatic acinar cells, dissociated hepatocytes, rod photoreceptors, and erythrocytes. In each cell type, areas containing membranes fluoresced intensely while areas containing no membranes (nuclei and zymogen granules) were not fluorescent. Cell compartments packed with rough endoplasmic reticulum or Golgi vesicles (acinar cells) or plasma membrane-derived membranes (rod outer segments) exhibited a uniform fluorescence. In contrast, cell compartments having large numbers of mitochondria (hepatocytes and the rod inner segment) exhibited a punctate fluorescence. Punctate fluorescence was prominent in the perinuclear and peri-granular areas of isolated acinar cells during CTC efflux, suggesting that under these conditions mitochondrial fluorescence may account for a large portion of acinar cell fluorescence. Fluorometry of dissociated pancreatic acini, preloaded with CTC, showed that application of the mitochondrial inhibitors antimycin A, NaCN, rotenone, or C1CCP, or of the divalent cation ionophore A23187 (all agents known to release mitochondrial calcium) rapidly decreased the fluorescence of acini. In the case of mitochondrial inhibitors, this response could be elicited before but not following the loss of CTC fluorescence induced by bethanechol stimulation. Removal of extracellular Ca2+ and Mg2+ or addition of EDTA also decreased fluorescence but did not prevent secretagogues or mitochondrial inhibitors from eliciting a further response. These data suggest that bethanechol acts to decrease CTC fluorescence at the same intracellular site as do mitochondrial inhibitors. This could be due to release of calcium from either mitochondria or another organelle that requires ATP to sequester calcium.","subset":"pubmed_abstract"} +{"meta":{"pmid":21792377,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":1,"2013-48":1,"2013-20":1,"unknown":8}}},"text":"Post-traumatic Stress Disorder and Cardiovascular Disease.\nThis review provides an up-to-date summary of the evidence from clinical and epidemiologic studies indicating that persons with post-traumatic stress disorder (PTSD) may have an increased risk of coronary heart disease and possibly thromboembolic stroke. Persons with PTSD, a common anxiety disorder in both veteran and nonveteran populations, have been reported to have an increased risk of hypertension, hyperlipidemia, obesity, and cardiovascular disease. Increased activity of the sympathoadrenal axis may contribute to cardiovascular disease through the effects of catecholamines on the heart, vasculature, and platelet function. Reported links between PTSD and hypertension and other cardiovascular risk factors may partly account for reported associations between PTSD and heart disease. The associations observed between PTSD and cardiovascular diseases have implications for cardiology practice and research.","subset":"pubmed_abstract"} +{"meta":{"pmid":26076054,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2022-40":1,"2022-21":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-10":1,"2019-43":1,"2019-26":1,"2019-13":1,"2018-51":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2023-06":1}}},"text":"Circumcising Circumcision: Renegotiating Beliefs and Practices among Somali Women in Johannesburg and Nairobi.\nFemale circumcision among Somalis is a deeply personal and subjective practice, framed within traditional norms and cultural practices, but negotiated within contemporary realities to produce a set of processes and practices that are nuanced, differentiated, and undergoing change. Based on ethnographic research among Somali women in Johannesburg and Nairobi, we argue that the context of forced migration provides women with opportunities to renegotiate and reinvent what female circumcision means to them. The complex, subjective, and diverse perceptions and experiences of circumcision as embedded processes, within the context of migration, we argue has been overlooked in the literature, which has tended to be framed within a normative discourse concerned with the medical effects of the practice, or in anthropological studies, counter to the normative discourse based on personal narratives.","subset":"pubmed_abstract"} +{"meta":{"pmid":18445487,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2021-31":1,"2020-29":1,"2019-39":1,"2019-18":1,"2018-51":1,"2018-30":1,"2018-09":1,"2017-43":1,"2017-39":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-49":1,"2017-13":1}}},"text":"RecJ nuclease is required for SOS induction after introduction of a double-strand break in a RecA loading deficient recB mutant of Escherichia coli.\nThe SOS response is an important mechanism which allows Escherichia coli cells to maintain genome integrity. Two key proteins in SOS regulation are LexA (repressor) and RecA (coprotease). The signal for SOS induction is generated at the level of a RecA filament. Depending on the type of DNA damage, a RecA filament is produced by specific activities (helicase, nuclease and RecA loading) of either RecBCD, RecF or a hybrid recombination pathway. It was recently demonstrated that RecA loading activity is essential for the induction of the SOS response after UV-irradiation. In this paper we studied the genetic requirements for SOS induction after introduction of a double-strand break (DSB) by the I-SceI endonuclease in a RecA loading deficient recB mutant (recB1080). We monitored SOS induction by assaying beta-galactosidase activity and compared induction of the response between strains having one or more inactivated mechanisms of RecA loading and their derivatives. We found that simultaneous inactivation of both RecA loading functions (in recB1080 recO double mutant) partially impairs SOS induction after introduction of a DSB. However, we found that the RecJ nuclease is essential for SOS induction after the introduction of a DSB in the recB1080 mutant. This result indicates that RecJ is needed to prepare ssDNA for subsequent loading of RecA protein. It implies that an additional type of RecA loading could exist in the cell.","subset":"pubmed_abstract"} +{"meta":{"pmid":16513201,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Ex vivo expansion of hematopoietic stem cells derived from umbilical cord blood in rotating wall vessel.\nExpansion of umbilical cord blood mononuclear cells (UCB MNCs) was carried out in a rotating wall vessel (RWV) bioreactor and tissue culture flasks (T-flasks) in serum-containing medium supplemented with relatively low doses of purified recombinant human cytokines (5.33 ng\/ml IL-3, 16 ng\/ml SCF, 3.33 ng\/ml G-CSF, 2.13 ng\/ml GM-CSF, 7.47 ng\/ml FL and 7.47 ng\/ml TPO) for 8 days. The cell density, pH and osmolality of the culture medium in the two culture systems were measured every 24h. Flow cytometric assay for CD34+ cells was carried out at 0, 144 and 197 h and methylcellulose colony assays were performed at 0, 72, 144 and 197 h. The pH and osmolality of the medium in the two culture systems were maintained in the proper ranges for hematopoietic stem cells (HSCs) and progenitors culture. The RWV bioreactor, combined with a cell-dilution feeding protocol, was efficient to expand UCB MNCs. At the end of 200 h culture, the total cell number was multiplied by 435.5+\/-87.6 times, and CD34+ cells 32.7+\/-15.6 times, and colony-forming units of granulocyte-macrophage (CFU-GM) 21.7+\/-4.9 times. While in T-flasks, however, total cells density changed mildly, CD34+ cells and CFU-GM decreased in number. It is demonstrated that the RWV bioreactor can provide a better environment for UCB MNCs expansion, enhance the contact between HSCs and accessory cells and make the utilization of cytokines more effective than T-flask.","subset":"pubmed_abstract"} +{"meta":{"pmid":2465388,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":7}}},"text":"Progressive language impairment without dementia: a case with isolated category specific semantic defect.\nA patient is described with a 5 year progressive defect of naming and auditory verbal comprehension, the pathological nature of which was presumably degenerative. The auditory comprehension defect unevenly affected different semantic categories, and was particularly severe for the names of animals, fruits and vegetables. The patients showed loss of the verbal knowledge of the physical attributes of the concepts corresponding to the words he was unable to understand, and sparing of the verbal knowledge of the functional attributes. His performance was defective also on the colour-figure and sound-picture matching test.","subset":"pubmed_abstract"} +{"meta":{"pmid":22978579,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Bidirectional associations between insomnia symptoms and unhealthy behaviours.\nIt has been suggested that there are associations among insomnia symptoms and unhealthy behaviours. However, previous studies are sparse and mainly cross-sectional, and have not been focused on several key unhealthy behaviours. The aim of this study was to examine whether the associations are bidirectional, i.e. whether insomnia symptoms are associated with subsequent unhealthy behaviours, and whether unhealthy behaviours are associated with subsequent insomnia symptoms. The data were derived from the Helsinki Health Study prospective cohort study. The baseline data were collected in 2000-02 (n = 8960, response rate 67%) among 40-60-year-old employees of the City Helsinki, Finland. The follow-up data were collected in 2007 (n = 7332, response rate 83%). Logistic regression analysis was used to examine the associations among insomnia symptoms and unhealthy behaviours, including smoking, heavy and binge drinking, physical inactivity and unhealthy food habits. Frequent insomnia symptoms at baseline were associated with subsequent heavy drinking [odds ratio (OR): 1.34; 95% confidence interval (CI): 1.07-1.68] and physical inactivity (OR: 1.27; 95% CI: 1.08-1.48) after full adjustment for gender, age, corresponding unhealthy behaviour at baseline, marital status, occupational class, sleep duration and common mental disorders. Additionally, heavy drinking (OR: 1.48; 95% CI: 1.22-1.80) and binge drinking (OR: 1.26; 95% CI: 1.08-1.46) at baseline were associated with subsequent insomnia symptoms at follow-up after full adjustment. In conclusion, insomnia symptoms were associated with subsequent heavy drinking and physical inactivity, and heavy and binge drinking were also associated with subsequent insomnia symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":26045304,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Analysis of the genetic architecture of susceptibility to cervical cancer indicates that common SNPs explain a large proportion of the heritability.\nThe genetic architecture of susceptibility to cervical cancer is not well-understood. By using a genome-wide association study (GWAS) of 1034 cervical cancer patients and 3948 controls with 632668 single-nucleotide polymorphisms (SNPs), we estimated that 24.0% [standard error (SE) = 5.9%, P = 3.19\u00d710(-6)] of variation in liability to cervical cancer is captured by autosomal SNPs, a bit lower than the heritability estimated from family study (27.0%), suggesting that a substantial proportion of the heritability is tagged by common SNPs. The remaining missing heritability most probably reflects incomplete linkage disequilibrium between causal variants and the genotyped SNPs. The variance explained by each chromosome is not related to its length (R (2) = 0.020, P = 0.516). Published genome-wide significant variants only explain 2.1% (SE = 1.5%, P = 0) of phenotypic variance, which reveals that most of the heritability has not been detected, presumably due to small individual effects. Another 2.1% (SE = 1.1%, P = 0.013) of variation is attributable to biological pathways associated with risk of cervical cancer, supporting that pathway analysis can identify part of the hidden heritability. Except for human leukocyte antigen genes and MHC class I polypeptide-related sequence A (MICA), none of the 82 candidate genes\/regions reported in other association studies contributes to the heritability of cervical cancer in our dataset. This study shows that risk of cervical cancer is influenced by many common germline genetic variants of small effects. The findings are important for further study design to identify the hiding heritability that has not yet been revealed. More susceptibility loci are yet to be found in GWASs with higher power.","subset":"pubmed_abstract"} +{"meta":{"pmid":30659156,"dup_signals":{"dup_doc_count":14}},"text":"Nonequilibrium correlations in minimal dynamical models of polymer copying.\nLiving systems produce \"persistent\" copies of information-carrying polymers, in which template and copy sequences remain correlated after physically decoupling. We identify a general measure of the thermodynamic efficiency with which these nonequilibrium states are created and analyze the accuracy and efficiency of a family of dynamical models that produce persistent copies. For the weakest chemical driving, when polymer growth occurs in equilibrium, both the copy accuracy and, more surprisingly, the efficiency vanish. At higher driving strengths, accuracy and efficiency both increase, with efficiency showing one or more peaks at moderate driving. Correlations generated within the copy sequence, as well as between template and copy, store additional free energy in the copied polymer and limit the single-site accuracy for a given chemical work input. Our results provide insight into the design of natural self-replicating systems and can aid the design of synthetic replicators.","subset":"pubmed_abstract"} +{"meta":{"pmid":32111371,"dup_signals":{"dup_doc_count":41,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":4,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-21":4,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":2,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":2,"2020-40":1,"2024-18":1,"2024-10":3,"2024-22":1}}},"text":"The case for statin use to reduce perioperative adverse cardiovascular and cerebrovascular events.\nIschaemic heart disease and stroke are the leading causes of death worldwide at 119 per 100,000 and 85 per 100,000 population. For the USA, heart disease is leading cause of death at 165 per 100,000 population. In developed countries, strokes and acute myocardial infarction in the general population have fallen from smoking reduction, lifestyle modifications and therapeutic interventions including statins. In a population-based stroke study in the UK involving primary care practices, of in-hospital strokes 90% were ischaemic, and 37% occurred within 1 week of an operation. Approximately 50% of the patients were not on a statin. In the UK, there is a national screening initiative for the prevention of atherosclerotic cardiovascular disease (ASCVD) offered to people aged 40-74 yr old. The QRISK3 tool calculates the risk of developing heart disease or stroke over 10 yr, from which recommendations are made on interventions for the prevention of ASCVD up to age 84 yr, with similar screening and assessment tools in Europe and the US. If the QRISK3 score tool for calculating cardiovascular risk is considered sufficiently robust for population screening in primary care, should anaesthetists not use the same screening for secondary care? We present a case for statin use over the perioperative period, to reduce early vascular adverse events based on statins' early pleiotropic actions, using the primary care QRISK tool for screening of ASCVD risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":20964857,"dup_signals":{"dup_doc_count":12}},"text":"High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.\nThe Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.","subset":"pubmed_abstract"} +{"meta":{"pmid":8286687,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Congenital anomalies of the female reproductive tract.\nExternal and internal anomalies can result from enzyme or chromosome defects, and prenatal drug exposure. Major new developments in this field include better understanding of the genetics of enzymatic defects, laparoscopic and hysteroscopic modifications of older procedures, the advent of magnetic resonance imaging for diagnosis, and better understanding of the psychosocial impact and timing of therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23037435,"dup_signals":{"dup_doc_count":28,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":2,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":2,"2015-40":1,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-18":2}}},"text":"Imaging velocities of a vibrating object by stroboscopic sideband holography.\nWe propose here to combine sideband holography with stroboscopic illumination synchronized with the vibration of an object. By sweeping the optical frequency of the reference beam such a way the holographic detection is tuned on the successive sideband harmonic ranks, we are able to image the instantaneous velocities of the object. Since the stroboscopic illumination is made with an electronic device, the method is compatible with fast (up to several MHz) vibration motions. The method is demonstrated with a vibrating clarinet reed excited sinusoidally at 2 kHz, and a stroboscopic illumination with cyclic ratio 0.15. Harmonic rank up to n = \u00b1 100 are detected, and a movie of the instantaneous velocities is reported.","subset":"pubmed_abstract"} +{"meta":{"pmid":28842566,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":3,"unknown":7}}},"text":"Improved Self-cleaning Properties of an Efficient and Easy to Scale up TiO2 Thin Films Prepared by Adsorptive Self-Assembly.\nTransparent titania coatings have self-cleaning and anti-reflection properties (AR) that are of great importance to minimize soiling effect on photovoltaic modules. In this work, TiO2 nanocolloids prepared by polyol reduction method were successfully used as coating thin films onto borosilicate glass substrates via adsorptive self-assembly process. The nanocolloids were characterized by transmission electron microscopy and x-ray diffraction. The average particle size was around 2.6 nm. The films which have an average thickness of 76.2 nm and refractive index of 1.51 showed distinctive anti soiling properties under desert environment. The film surface topography, uniformity, wettability, thickness and refractive index were characterized using x-ray diffraction, atomic force microscopy, scanning electron microscopy, water contact angle measurements and ellipsometry. The self-cleaning properties were investigated by optical microscopy and UV-Vis spectroscopy. The optical images show 56% reduction of dust deposition rate over the coated surfaces compared with bare glass substrates after 7 days of soiling. The transmission optical spectra of these films collected at normal incidence angle show high anti-reflection properties with the coated substrates having transmission loss of less than 6% compared to bare clean glass.","subset":"pubmed_abstract"} +{"meta":{"pmid":24015955,"dup_signals":{"dup_doc_count":24,"dup_dump_count":18,"dup_details":{"curated_sources":6,"2020-45":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2021-04":1}}},"text":"How do PDP models learn quasiregularity?\nParallel distributed processing (PDP) models have had a profound impact on the study of cognition. One domain in which they have been particularly influential is learning quasiregularity, in which mastery requires both learning regularities that capture the majority of the structure in the input plus learning exceptions that violate the regularities. How PDP models learn quasiregularity is still not well understood. Small- and large-scale analyses of a feedforward, 3-layer network were carried out to address 2 fundamental issues about network functioning: how the model can learn both regularities and exceptions without sacrificing generalizability and the nature of the hidden representation that makes this learning possible. Results show that capacity-limited learning pressures the network to form componential representations, which ensures good generalizability. Small and highly local perturbations of this representational system allow exceptions to be learned while minimally disrupting generalizability. Theoretical and methodological implications of the findings are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":24865947,"dup_signals":{"dup_doc_count":31,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":3,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":2,"2020-45":2,"2024-18":1,"2024-10":1,"2024-26":1}}},"text":"The structure, function and properties of sirohaem decarboxylase--an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway.\nSome bacteria and archaea synthesize haem by an alternative pathway, which involves the sequestration of sirohaem as a metabolic intermediate rather than as a prosthetic group. Along this pathway the two acetic acid side-chains attached to C12 and C18 are decarboxylated by sirohaem decarboxylase, a heterodimeric enzyme composed of AhbA and AhbB, to give didecarboxysirohaem. Further modifications catalysed by two related radical SAM enzymes, AhbC and AhbD, transform didecarboxysirohaem into Fe-coproporphyrin III and haem respectively. The characterization of sirohaem decarboxylase is reported in molecular detail. Recombinant versions of Desulfovibrio desulfuricans, Desulfovibrio vulgaris and Methanosarcina barkeri AhbA\/B have been produced and their physical properties compared. The D. vulgaris and M. barkeri enzyme complexes both copurify with haem, whose redox state influences the activity of the latter. The kinetic parameters of the D. desulfuricans enzyme have been determined, the enzyme crystallized and its structure has been elucidated. The topology of the enzyme reveals that it shares a structural similarity to the AsnC\/Lrp family of transcription factors. The active site is formed in the cavity between the two subunits and a AhbA\/B-product complex with didecarboxysirohaem has been obtained. A mechanism for the decarboxylation of the kinetically stable carboxyl groups is proposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":3119871,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-20":2,"unknown":2}}},"text":"Pathogenesis of infection with Sarcocystis rauschorum (Apicomplexa) in experimentally infected varying lemmings (Dicrostonyx richardsoni).\nThis study describes the sequential formation of lesions associated with the endogenous development of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in varying lemmings, Dicrostonyx richardsoni. Lethal doses of sporocysts (greater than 500) were orally administered to lemmings examined 1-6 days postinoculation (DPI) whereas sublethal doses were administered to lemmings examined subsequently. Transient necrosis and purulent inflammation, in association with precystic merogony, occurred in the liver by 4.5 DPI, peaked at 6 DPI and subsided beginning at 11 DPI with the liver returning to normal by 15 DPI. Cyst formation in skeletal and cardiac muscle was associated with purulent inflammation and sarcolemmal proliferation beginning at 9 DPI. These lesions persisted to 42 DPI. In addition, multifocal nonsuppurative meningoencephalitis was present in six of 11 infected lemmings examined between 11 and 15 DPI.","subset":"pubmed_abstract"} +{"meta":{"pmid":30325880,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2020-10":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2023-40":1}}},"text":"Statistical Fragility and the Role of P Values in the Sports Medicine Literature.\nComparative trials evaluating categorical outcomes have important implications on surgical decision making. The purpose of this study was to examine the statistical stability of sports medicine research. Comparative clinical sports medicine research studies involving anterior cruciate ligament, meniscus, and knee instability were reviewed in two journals between 2006 and 2016. The statistical stability for each study outcome was determined by the number of event reversals required to change the P value to either greater or less than 0.05. The number of patients lost to follow-up was also determined. Of the 1,505 studies screened, 102 studies were included for analysis, 40 of which were randomized controlled trials. There were 339 total outcome events, with 98 significant and 241 not significant. The Fragility Index, or the median number of events required to change the statistical significance of the overall study, was five (interquartile range, 3 to 8) or 5.4% of the total study population. In addition, the average number of patients lost to follow-up was 7.9, which is greater than the number needed to change the significance of each study arm and the entire study population. Results in the comparative sports medicine literature may not be as stable as previously thought, with only a small percentage of outcome events needed to change study significance. Outcomes research based on a single discreet P value cutoff may be misleading.","subset":"pubmed_abstract"} +{"meta":{"pmid":7291241,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2023-40":1,"2024-18":3,"2024-10":1,"2024-30":1}}},"text":"Aversive stimulus properties of scopolamine.\nThe drug state produced in rats by intraperitoneal injections of scopolamine hydrobromide (1.2 mg\/kg) was treated as a putative aversive US. This US was paired with a distinctive spatial location in a shuttle box for 6 of 12 daily sessions by confining the subject to one side following scopolamine and to the other side following saline (6 sessions). Two groups of 8 subjects each received zero and 20 min post-injection delays respectively. Following zero delay, but not 20 min delay, subjects avoided the side associated with scopolamine in drug-free, free choice tests. This is evidence that the immediate post-injection drug state induced by scopolamine is aversive.","subset":"pubmed_abstract"} +{"meta":{"pmid":11914316,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Validity and repeatability of the EPIC-Norfolk Physical Activity Questionnaire.\nPhysical activity is an important lifestyle which is often poorly assessed in epidemiological studies. The European Prospective Investigation into Cancer Study-Norfolk cohort (EPIC-Norfolk), a large population-based cohort study, has developed a comprehensive questionnaire to assess activity in different domains of life aimed at assessing total energy expenditure. We report the repeatability of this instrument and its validity against repeated objective measures of fitness and energy expenditure undertaken throughout the time frame of reference of the questionnaire. The validity of the instrument was measured in 173 individuals randomly selected from a continuing population-based cohort study. Energy expenditure was assessed by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole body calorimetry and doubly-labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed the physical activity questionnaire that assesses past-year activity at home, work and in recreation. Repeatability was assessed in a separate group of 399 randomly selected participants in EPIC who completed the physical activity questionnaire twice with a 3-month interval. The age- and sex-adjusted correlation between the objective measure of daytime energy expenditure and the sum of recreational and occupational reported physical activity (in MET h per week) was 0.28 (P < 0.001). The reported time spent in vigorous activity was correlated with cardio-respiratory fitness (0.16, P < 0.05) and with the proportion of time when energy expenditure was more than five times basal (0.17, P < 0.05). The repeatability of the sum of recreational and occupational reported activity was high, r = 0.73. The indices of physical activity derived from this questionnaire have levels of validity and repeatability comparable to other physical activity instruments that are used in large epidemiological studies and which have undergone such intense development and testing.","subset":"pubmed_abstract"} +{"meta":{"pmid":11007238,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Oral budesonide in the treatment of primary sclerosing cholangitis.\nThis study was designed to evaluate the safety and estimate the efficacy of oral budesonide in patients with primary sclerosing cholangitis (PSC). Twenty-one patients with PSC were treated with 9 mg daily of oral budesonide for 1 yr. Significant, but marginally important, improvement in serum alkaline phosphatase (1,235 +\/- 190 vs 951 +\/-206 U\/L, p = 0.003) and AST levels (119 +\/- 14 vs 103 +\/- 19 U\/L, p = 0.02) was noted at the end of the treatment period. Serum bilirubin levels increased significantly in the 18 patients who completed 1 yr of treatment (1.1 +\/- 0.1 vs 1.4 +\/- 0.3, p = 0.01) and no significant changes in liver tests were noted 3 months after budesonide was discontinued. The Mayo risk score did not change significantly, and although a significant improvement in the degree of portal inflammation was noted at the end of the treatment period, the degree of fibrosis and stage of disease were not significantly affected. There was a marked loss of bone mass of the femoral neck (0.851 +\/- 0.02 vs 0.826 +\/- 0.02 g\/cm2, p = 0.002) and lumbar spine (1.042 +\/- 0.02 vs 1.029 +\/- 0.02 g\/cm2, p = 0.09) at 1 yr of treatment with budesonide. Two patients required evaluation for liver transplantation during treatment, and two patients developed cosmetic side effects. Oral budesonide appears to be of minimal, if any, benefit and it is associated with a significant worsening of osteoporosis in patients with PSC.","subset":"pubmed_abstract"} +{"meta":{"pmid":30318534,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"High magnetoresistance in ultra-thin two-dimensional Cr-based MXenes.\nDeveloping effective magnetoresistance devices has become beneficial due to their extensive applications in electronics such as data storage. One challenge is to reduce the scale of devices while maintaining a high magnetoresistance. Another challenge for the applications of magnetoresistance devices involves synthesizing them with stable interfaces. Antiferromagnetic Cr-based MXenes are similar to tunneling magnetoresistance junctions, and can be synthesized in a straightforward manner. Density functional theory calculations show that the medium adhesion strength between Au electrodes and Cr-based MXene can ensure the formation of stable interfaces. Exchange coupling between Cr atoms in different atomic layers is found to decrease to 0.4 meV with increasing thickness. Magnetoresistance values are higher than 400% with 1.0 V. The results show that Cr-based MXenes are promising magnetoresistance devices with high magnetoresistance values and ultra-thin layers (about 1 nm) and exhibit tunable exchange coupling between Cr atoms through thickness control.","subset":"pubmed_abstract"} +{"meta":{"pmid":10479070,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Fluoride-induced depletion of polyphosphoinositides in rat brain cortical slices: a rationale for the inhibitory effects on phospholipase C.\nFluoride, which is used commonly as a pharmacological tool to activate phosphoinositide-phospholipase C coupled to the heterotrymeric Gq\/11 proteins, inhibited the phosphorylation of phosphatidylinositol (PtdIns) to polyphosphoinositides (PtdIns4P and PtdIns4,5P2) in membranes from rat brain cortex. Fluoride enhanced basal production of 3H-inositol phosphates in membranes prepared from brain cortical slices that had been prelabeled with [3H]inositol, but inhibited the stimulation elicited by carbachol in the presence of GTPgammaS. However in both cases fluoride depleted [3H]PtdIns4P content by 95%. The inhibitory effects of fluoride on the release of 3H-inositol phosphates in slices were not apparent in a pulse [3H]inositol-labeling strategy, but became dramatic in a continuous labeling protocol, particularly at long incubation times. Prelabeling slices with [3H]inositol in the presence of fluoride precluded polyphosphoinositide labeling, and eliminated phospholipase C responsiveness to carbachol under normal or depolarizing conditions, and to the calcium ionophore ionomycin. The lack of response of 3H-polyphosphoinositide-depleted slices to phospholipase C stimuli was not due to fluoride poisoning, unaccessibility of the [3H]inositol label to phospholipase C or desensitization of Gq\/11, as the effect of carbachol and GTPgammaS was restored, in the presence of ATP, in membranes prepared from slices that had been labeled in the presence of fluoride. In conclusion, our data show that fluoride, at a concentration similar to that used to stimulate directly Gq\/11-coupled phospholipase C, effectively blocks the synthesis of phospholipase C substrates from PtdIns.","subset":"pubmed_abstract"} +{"meta":{"pmid":21906302,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2015-18":1,"unknown":9}}},"text":"Portion control for the treatment of obesity in the primary care setting.\nThe increasing prevalence of obesity is a significant health threat and a major public health challenge. A critical need exists to develop and evaluate practical methods for the treatment of obesity in the clinical setting. One of the factors contributing to the obesity epidemic is food portion sizes. Limited data are available on the efficacy of visual or tactile devices designed to enhance patient understanding and control of portion sizes. A portion control plate is a commercially-available product that can provide visual cues of portion size and potentially contribute to weight loss by enhancing portion size control among obese patients. This tool holds promise as a useful adjunct to dietary counseling. Our objective was to evaluate a portion control intervention including dietary counseling and a portion control plate to facilitate weight loss among obese patients in a primary care practice. We randomized 65 obese patients [body mass index (BMI) \u2265 30 and < 40] to an intervention including counseling by a dietitian incorporating a portion control plate or to usual care. Following initial consultation, patients in the intervention arm were contacted at 1, 3, and 5 months by the dietician for brief follow-up counseling. Usual care subjects received instructional handouts on diet and exercise. Forty-two (65%) subjects returned to have weight assessed at 6 months. Subjects in the portion control intervention had a greater percentage change (\u00b1 SD) in weight from baseline at 3 months (-2.4% \u00b1 3.7% vs. -0.5% \u00b1 2.2%; p = 0.041) and a non significant trend in weight change from baseline at 6 months (-2.1% \u00b1 3.8% vs. -0.7% \u00b1 3.7%; p = 0.232) compared with usual care. Nearly one-half of patients assigned to the portion control intervention who completed the study reported the overall intervention was helpful and the majority would recommend it to others. Our findings suggest that a portion control intervention incorporating dietary counseling and a portion control plate may be effective for enhancing weight loss among obese subjects. A portion control intervention deserves further evaluation as a weight control strategy in the primary care setting. Current controlled trials NCT01451554.","subset":"pubmed_abstract"} +{"meta":{"pmid":22180196,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-30":1,"unknown":9}}},"text":"Medical center characteristics associated with PSA screening in elderly veterans with limited life expectancy.\nAlthough guidelines recommend against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, screening is common. We sought to identify medical center characteristics associated with screening in this population. We conducted a prospective study of 622,262 screen-eligible men aged 70+ seen at 104 VA medical centers in 2003. Primary outcome was the percentage of men at each center who received PSA screening in 2003, based on VA data and Medicare claims. Men were stratified into life expectancy groups ranging from favorable (age 70-79 with Charlson score = 0) to limited (age 85+ with Charlson score \u22651 or age 70+ with Charlson score \u22654). Medical center characteristics were obtained from the 1999-2000 VA Survey of Primary Care Practices and publicly available VA data sources. Among 123,223 (20%) men with limited life expectancy, 45% received PSA screening in 2003. Across 104 VAs, the PSA screening rate among men with limited life expectancy ranged from 25-79% (median 43%). Higher screening was associated with the following center characteristics: no academic affiliation (50% vs. 43%, adjusted RR = 1.14, 95% CI 1.04-1.25), a ratio of midlevel providers to physicians \u22653:4 (55% vs. 45%, adjusted RR = 1.20, 95% CI 1.09-1.32) and location in the South (49% vs. 39% in the West, adjusted RR = 1.25, 95% CI 1.12-1.40). Use of incentives and high scores on performance measures were not independently associated with screening. Within centers, the percentages of men screened with limited and favorable life expectancies were highly correlated (r = 0.90). Substantial practice variation exists for PSA screening in older men with limited life expectancy across VAs. The high center-specific correlation of screening among men with limited and favorable life expectancies indicates that PSA screening is poorly targeted according to life expectancy.","subset":"pubmed_abstract"} +{"meta":{"pmid":29297374,"dup_signals":{"dup_doc_count":30,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":3,"2024-30":1,"unknown":24}}},"text":"Using Theories of Change to inform implementation of health systems research and innovation: experiences of Future Health Systems consortium partners in Bangladesh, India and Uganda.\nThe Theory of Change (ToC) is a management and evaluation tool supporting critical thinking in the design, implementation and evaluation of development programmes. We document the experience of Future Health Systems (FHS) Consortium research teams in Bangladesh, India and Uganda with using ToC. We seek to understand how and why ToCs were applied and to clarify how they facilitate the implementation of iterative intervention designs and stakeholder engagement in health systems research and strengthening. This paper combines literature on ToC, with a summary of reflections by FHS research members on the motivation, development, revision and use of the ToC, as well as on the benefits and challenges of the process. We describe three FHS teams' experiences along four potential uses of ToCs, namely planning, communication, learning and accountability. The three teams developed ToCs for planning and evaluation purposes as required for their initial plans for FHS in 2011 and revised them half-way through the project, based on assumptions informed by and adjusted through the teams' experiences during the previous 2 years of implementation. All teams found that the revised ToCs and their accompanying narratives recognised greater feedback among intervention components and among key stakeholders. The ToC development and revision fostered channels for both internal and external communication, among research team members and with key stakeholders, respectively. The process of revising the ToCs challenged the teams' initial assumptions based on new evidence and experience. In contrast, the ToCs were only minimally used for accountability purposes. The ToC development and revision process helped FHS research teams, and occasionally key local stakeholders, to reflect on and make their assumptions and mental models about their respective interventions explicit. Other projects using the ToC should allow time for revising and reflecting upon the ToCs, to recognise and document the adaptive nature of health systems, and to foster the time, space and flexibility that health systems strengthening programmes must have to learn from implementation and stakeholder engagement.","subset":"pubmed_abstract"} +{"meta":{"pmid":32802956,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Integrated sequencing and array comparative genomic hybridization in familial Parkinson disease.\nTo determine how single nucleotide variants (SNVs) and copy number variants (CNVs) contribute to molecular diagnosis in familial Parkinson disease (PD), we integrated exome sequencing (ES) and genome-wide array-based comparative genomic hybridization (aCGH) and further probed CNV structure to reveal mutational mechanisms. We performed ES on 110 subjects with PD and a positive family history; 99 subjects were also evaluated using genome-wide aCGH. We interrogated ES and aCGH data for pathogenic SNVs and CNVs at Mendelian PD gene loci. We confirmed SNVs via Sanger sequencing and further characterized CNVs with custom-designed high-density aCGH, droplet digital PCR, and breakpoint sequencing. Using ES, we discovered individuals with known pathogenic SNVs in GBA (p.Glu365Lys, p.Thr408Met, p.Asn409Ser, and p.Leu483Pro) and LRRK2 (p.Arg1441Gly and p.Gly2019Ser). Two subjects were each double heterozygotes for variants in GBA and LRRK2. Based on aCGH, we additionally discovered cases with an SNCA duplication and heterozygous intragenic GBA deletion. Five additional subjects harbored both SNVs (p.Asn52Metfs*29, p.Thr240Met, p.Pro437Leu, and p.Trp453*) and likely disrupting CNVs at the PRKN locus, consistent with compound heterozygosity. In nearly all cases, breakpoint sequencing revealed microhomology, a mutational signature consistent with CNV formation due to DNA replication errors. Integrated ES and aCGH yielded a genetic diagnosis in 19.3% of our familial PD cohort. Our analyses highlight potential mechanisms for SNCA and PRKN CNV formation, uncover multilocus pathogenic variation, and identify novel SNVs and CNVs for further investigation as potential PD risk alleles.","subset":"pubmed_abstract"} +{"meta":{"pmid":24842082,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Filament perforation model for mouse subarachnoid hemorrhage: surgical-technical considerations.\nMouse subarachnoid hemorrhage (SAH) models are becoming increasingly important. We aimed to report and discuss the detailed technical-surgical approach and difficulties associated with the circle of Willis perforation (cWp) model, with reference to the existing literature. First, the cWp model was reproduced using ddY mice following scarification at 0 h, Days 1, 2, and 3 after SAH. Second, C57BL\/6 mice were subjected to SAH with histological examination on Days 1, 2, and 3. Sham-operated mice were sacrificed on Day 2. Neurological performance, amount of subarachnoid blood, cerebral vasospasm (CVS), and neuronal injury were assessed. Relevant articles found in the MEDLINE database were reviewed. Induction of SAH was successfully reproduced. The volume of subarachnoid blood decreased with time due to resorption. Neurological performance was worse in SAH compared with sham. Signs of CVS could be confirmed on Days 2 and 3, but not Day 1. The cumulative number of microthrombi was significantly higher on Days 2 and 3, but not Day 1. Apoptotic and degenerative neurons were found in the cortex and hippocampal area. Our review of the literature revealed the cWp model to be the most frequently used. The present findings largely confirmed previously published results. However, detailed technical-surgical description and its discussion were sparse, which we provide here. The current study provides additional useful information characterizing the cWp model. This model may be of first choice at present, as important pathologies can be reproduced and most findings in the literature are based on it.","subset":"pubmed_abstract"} +{"meta":{"pmid":8853216,"dup_signals":{"dup_doc_count":37,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2024-18":1}}},"text":"The effects of paroxetine and nefazodone on sleep: a placebo controlled trial.\nWe studied the effect of acute (1 day) and subacute (16 days) administration of the new antidepressant, nefazodone (400 mg daily), and the selective serotonin re-uptake inhibitor (SSRI), paroxetine (30 mg daily), on the sleep polysomnogram of 37 healthy volunteers using a random allocation, double-blind, placebo-controlled design. Compared to placebo, paroxetine lowered rapid eye movement (REM) sleep and increased REM latency. In addition, paroxetine increased awakenings and reduced Actual Sleep Time and Sleep Efficiency. In contrast, nefazodone did not alter REM sleep and had little effect on measures of sleep continuity. We conclude that in contrast to typical SSRIs, nefazodone administration has little effect on sleep architecture in healthy volunteers.","subset":"pubmed_abstract"} +{"meta":{"pmid":8610639,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Single institution experience with recombinant gamma-interferon in the treatment of patients with metastatic renal cell carcinoma.\nWe report the clinical course of eight patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant gamma-interferon (Immuneron) as part of a phase II-III study comparing the safety and efficacy of gamma-interferon with that of medroxyprogesterone acetate (Depo-Provera). There were no objective responders among the eight patients treated with recombinant gamma-interferon at an i.v. dose of 1 mg\/m(2) daily for five days every other week for four weeks then 1 mg\/m(2) three times a week given every other week until there was documented disease progression or complete response (CR). Overall median survival was 17.3 months (range 1.4 to 184). The major side effects of treatment included fever\/chills (75%), mild anorexia and fatigue (75%), nausea\/vomiting (80%), leukopenia (38%), and abnormal liver function tests (25%). There were no life-threatening side effects observed. At our institution, in a random cohort of eight patients with metastatic RCC, recombinant gamma-interferon when given at a dose of 1 mg\/m(2) per day given three times per week on an every other week schedule yields no clinical antitumor activity. A review of the literature on the use of gamma-interferon for metastatic RCC suggests that low-dose combination therapy with other cytokines may yield the best response-to-side effect ratio. Higher doses yield more responses but an added cost of more toxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":11013303,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats.\nThe Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.","subset":"pubmed_abstract"} +{"meta":{"pmid":1824781,"dup_signals":{"dup_doc_count":14,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-21":1,"2021-10":1,"2020-50":2,"2020-40":1,"2023-40":1,"2024-18":1}}},"text":"The inhibitory effect of trifluoromethylphenylpiperazine on [3H]acetylcholine release in guinea pig hippocampal synaptosomes is mediated by a 5-hydroxytryptamine1 receptor distinct from 1A, 1B, and 1C subtypes.\nThe effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K(+)-evoked [3H]acetylcholine [( 3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5-1,000 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)\/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C\/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K(+)-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29370821,"dup_signals":{"dup_doc_count":11}},"text":"PhenoDis: a comprehensive database for phenotypic characterization of rare cardiac diseases.\nThoroughly annotated data resources are a key requirement in phenotype dependent analysis and diagnosis of diseases in the area of precision medicine. Recent work has shown that curation and systematic annotation of human phenome data can significantly improve the quality and selectivity for the interpretation of inherited diseases. We have therefore developed PhenoDis, a comprehensive, manually annotated database providing symptomatic, genetic and imprinting information about rare cardiac diseases. PhenoDis includes 214 rare cardiac diseases from Orphanet and 94 more from OMIM. For phenotypic characterization of the diseases, we performed manual annotation of diseases with articles from the biomedical literature. Detailed description of disease symptoms required the use of 2247 different terms from the Human Phenotype Ontology (HPO). Diseases listed in PhenoDis frequently cover a broad spectrum of symptoms with 28% from the branch of 'cardiovascular abnormality' and others from areas such as neurological (11.5%) and metabolism (6%). We collected extensive information on the frequency of symptoms in respective diseases as well as on disease-associated genes and imprinting data. The analysis of the abundance of symptoms in patient studies revealed that most of the annotated symptoms (71%) are found in less than half of the patients of a particular disease. Comprehensive and systematic characterization of symptoms including their frequency is a pivotal prerequisite for computer based prediction of diseases and disease causing genetic variants. To this end, PhenoDis provides in-depth annotation for a complete group of rare diseases, including information on pathogenic and likely pathogenic genetic variants for 206 diseases as listed in ClinVar. We integrated all results in an online database ( http:\/\/mips.helmholtz-muenchen.de\/phenodis\/ ) with multiple search options and provide the complete dataset for download. PhenoDis provides a comprehensive set of manually annotated rare cardiac diseases that enables computational approaches for disease prediction via decision support systems and phenotype-driven strategies for the identification of disease causing genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":28832883,"dup_signals":{"dup_doc_count":24,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":19}}},"text":"Association Between Mitochondrial DNA Haplogroup Variation and Autism Spectrum Disorders.\nAutism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and repetitive or restrictive behavior. Although multiple physiologic and biochemical studies have reported defects in mitochondrial oxidative phosphorylation in patients with ASD, the role of mitochondrial DNA (mtDNA) variation has remained relatively unexplored. To assess what impact mitochondrial lineages encompassing ancient mtDNA functional polymorphisms, termed haplogroups, have on ASD risk. In this cohort study, individuals with autism and their families were studied using the Autism Genetic Resource Exchange cohort genome-wide association studies data previously generated at the Children's Hospital of Philadelphia. From October 2010 to January 2017, we analyzed the data and used the mtDNA single-nucleotide polymorphisms interrogated by the Illumina HumanHap 550 chip to determine the mtDNA haplogroups of the individuals. Taking into account the familial structure of the Autism Genetic Resource Exchange data, we then determined whether the mtDNA haplogroups correlate with ASD risk. Odds ratios of mitochondrial haplogroup as predictors of ASD risk. Of 1624 patients with autism included in this study, 1299 were boys (80%) and 325 were girls (20%). Families in the Autism Genetic Resource Exchange collection (933 families, encompassing 4041 individuals: 1624 patients with ASD and 2417 healthy parents and siblings) had been previously recruited in the United States with no restrictions on age, sex, race\/ethnicity, or socioeconomic status. Relative to the most common European haplogroup HHV, European haplogroups I, J, K, O-X, T, and U were associated with increased risk of ASD, as were Asian and Native American haplogroups A and M, with odds ratios ranging from 1.55 (95% CI, 1.16-2.06) to 2.18 (95% CI, 1.59-3) (adjusted P < .04). Hence, mtDNA haplogroup variation is an important risk factor for ASD. Because haplogroups I, J, K, O-X, T, and U encompass 55% of the European population, mtDNA lineages must make a significant contribution to overall ASD risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":19595705,"dup_signals":{"dup_doc_count":46,"dup_dump_count":31,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":5,"2023-06":3,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-40":2,"2020-34":1,"2020-29":2,"2020-24":1,"2020-05":3,"2019-51":1,"2019-35":1,"2019-09":1,"2018-47":1,"2018-26":1,"2018-17":1,"2017-30":1,"2024-22":1}}},"text":"Reference noise method of removing powerline noise from recorded signals.\nPowerline contamination of recorded signals represents a major source of noise in electrophysiology and impairs the use of recordings for research. In this article we present simple and effective method for cancelling 50 Hz (or 60 Hz) noise using a reference noise signal and average noise cycle subtraction. This method is capable of reliably removing not only the fundamental powerline frequency but also its harmonic frequencies. The efficiency of this method appears to be superior to other commonly used methods such as notch filtering or adaptive filtering. Our experience and results show that this method can be efficiently used with very low signal-to-noise ratios, while preserving original signal waveform.","subset":"pubmed_abstract"} +{"meta":{"pmid":33585414,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Multi-Omics Driven Metabolic Network Reconstruction and Analysis of Lignocellulosic Carbon Utilization in Rhodosporidium toruloides.\nAn oleaginous yeast Rhodosporidium toruloides is a promising host for converting lignocellulosic biomass to bioproducts and biofuels. In this work, we performed multi-omics analysis of lignocellulosic carbon utilization in R. toruloides and reconstructed the genome-scale metabolic network of R. toruloides. High-quality metabolic network models for model organisms and orthologous protein mapping were used to build a draft metabolic network reconstruction. The reconstruction was manually curated to build a metabolic model using functional annotation and multi-omics data including transcriptomics, proteomics, metabolomics, and RB-TDNA sequencing. The multi-omics data and metabolic model were used to investigate R. toruloides metabolism including lipid accumulation and lignocellulosic carbon utilization. The developed metabolic model was validated against high-throughput growth phenotyping and gene fitness data, and further refined to resolve the inconsistencies between prediction and data. We believe that this is the most complete and accurate metabolic network model available for R. toruloides to date.","subset":"pubmed_abstract"} +{"meta":{"pmid":33101523,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-10":1,"unknown":13}}},"text":"Safety of Schizochytrium sp. oil as a novel food pursuant to Regulation (EU) 2015\/2283.\nFollowing a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015\/2283. Schizochytrium sp. is a single-cell microalga. The strain WZU477, used by the applicant (Progress Biotech bv), was found to belong to the species Schizochytrium limacinum and was obtained in a marine environment from rotted mangrove forest leaves. The NF, an oil rich in docosahexaenoic acid (DHA), is isolated from the microalgae by mechanical extraction. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016\/127, which states the mandatory addition of DHA to IF and FOF at the level of 20-50 mg\/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. The composition of the NF indicates the absence of marine biotoxins in the NF. Furthermore, Schizochytrium limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Based on the information provided, the microalga is not expected to survive the manufacturing process. Toxicological tests conducted with the NF were not performed. However, based on the available toxicological data on various forms of oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process and the composition of the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.","subset":"pubmed_abstract"} +{"meta":{"pmid":27498567,"dup_signals":{"dup_doc_count":28,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-33":1,"2021-39":1,"2018-26":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-43":2,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":2,"2016-50":1,"2023-50":1,"2024-26":2,"2024-22":1,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"The Demographic Development of the First Farmers in Anatolia.\nThe archaeological documentation of the development of sedentary farming societies in Anatolia is not yet mirrored by a genetic understanding of the human populations involved, in contrast to the spread of farming in Europe [1-3]. Sedentary farming communities emerged in parts of the Fertile Crescent during the tenth millennium and early ninth millennium calibrated (cal) BC and had appeared in central Anatolia by 8300 cal BC [4]. Farming spread into west Anatolia by the early seventh millennium cal BC and quasi-synchronously into Europe, although the timing and process of this movement remain unclear. Using genome sequence data that we generated from nine central Anatolian Neolithic individuals, we studied the transition period from early Aceramic (Pre-Pottery) to the later Pottery Neolithic, when farming expanded west of the Fertile Crescent. We find that genetic diversity in the earliest farmers was conspicuously low, on a par with European foraging groups. With the advent of the Pottery Neolithic, genetic variation within societies reached levels later found in early European farmers. Our results confirm that the earliest Neolithic central Anatolians belonged to the same gene pool as the first Neolithic migrants spreading into Europe. Further, genetic affinities between later Anatolian farmers and fourth to third millennium BC Chalcolithic south Europeans suggest an additional wave of Anatolian migrants, after the initial Neolithic spread but before the Yamnaya-related migrations. We propose that the earliest farming societies demographically resembled foragers and that only after regional gene flow and rising heterogeneity did the farming population expansions into Europe occur.","subset":"pubmed_abstract"} +{"meta":{"pmid":34412116,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":14}}},"text":"Emergence of Content-Agnostic Information Processing by a Robot Using Active Inference, Visual Attention, Working Memory, and Planning.\nGeneralization by learning is an essential cognitive competency for humans. For example, we can manipulate even unfamiliar objects and can generate mental images before enacting a preplan. How is this possible? Our study investigated this problem by revisiting our previous study (Jung, Matsumoto, & Tani, 2019), which examined the problem of vision-based, goal-directed planning by robots performing a task of block stacking. By extending the previous study, our work introduces a large network comprising dynamically interacting submodules, including visual working memory (VWMs), a visual attention module, and an executive network. The executive network predicts motor signals, visual images, and various controls for attention, as well as masking of visual information. The most significant difference from the previous study is that our current model contains an additional VWM. The entire network is trained by using predictive coding and an optimal visuomotor plan to achieve a given goal state is inferred using active inference. Results indicate that our current model performs significantly better than that used in Jung et al. (2019), especially when manipulating blocks with unlearned colors and textures. Simulation results revealed that the observed generalization was achieved because content-agnostic information processing developed through synergistic interaction between the second VWM and other modules during the course of learning, in which memorizing image contents and transforming them are dissociated. This letter verifies this claim by conducting both qualitative and quantitative analysis of simulation results.","subset":"pubmed_abstract"} +{"meta":{"pmid":23680819,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2018-34":1,"2017-13":1}}},"text":"Topographical and chemical effects of electrochemically assisted deposited hydroxyapatite coatings on osteoblast-like cells.\nA recently commercialised hydroxyapatite electrochemically assisted chemical deposition technique (BoneMaster) has been shown to induce increased bone apposition; whether this response is caused by the surface topography or chemistry is unknown. An in-vitro examination using human osteoblast-like cells was performed on a series of BoneMaster-coated surfaces. The chemistry was separated from the topography using a thin gold coating; Thermanox coverslips were used as a control. BoneMaster surfaces showed significantly greater alkaline phosphatase activity and osteocalcin production compared with controls; however, no difference was found between the gold-coated and uncoated BoneMaster samples, indicating topography is the main contributing factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":29318038,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":13}}},"text":"Vision Improvement with Refractive Correction Does Not Completely Exclude Major Eye Diseases: Analyses of Visually Impaired South Korean Population in the Korea National Health and Nutrition Examination Survey 2009-2011.\nTo investigate the association between vision improvement with refractive correction in the visually impaired eyes and the prevalence of ocular comorbidities in the South Korean population. The data of 24,620 individuals in the Korea National Health and Nutrition Examination Survey (KNHANES 2009-2011) were reviewed. Visual impairment was defined as a presenting visual acuity < 20\/60. The participants with visual impairment in at least one eye were divided into 3 groups according to the best-corrected visual acuity (group 1: <20\/30, group 2: \u226520\/30 but <20\/25, and group 3: \u226520\/25). The prevalence of ocular comorbidities was estimated and compared between the three groups. Visual impairment in at least one eye was found in 3031 individuals. Groups 1, 2, and 3 comprised 23.5%, 22.2%, and 54.3% of these visually impaired eyes, respectively. The prevalence of cataract, diabetic retinopathy, age-related macular degeneration, corneal opacity, blepharoptosis, and pterygium was similar to or even higher in group 2 compared to group 1. The prevalence of glaucoma and age-related macular degeneration was 5.40% and 11.39%, respectively, in group 2 and 3.31% and 3.76%, respectively, in group 3. Appropriate ophthalmologic examination is necessary even if people exhibit vision improvement after optical correction.","subset":"pubmed_abstract"} +{"meta":{"pmid":29157514,"dup_signals":{"dup_doc_count":17}},"text":"A psycho-legal perspective on sexual offending in individuals with autism Spectrum disorder.\nIt is important to consider whether there are innate vulnerabilities that increase the risk of an individual with an autistic spectrum disorder (ASD), predominantly those defendants with a diagnosis of Asperger's Syndrome, being charged and convicted of a sexual offence. The significance of such can be readily seen in recent English case law, with judgments on appeal finding convictions unsafe where there have been a number of failings in the Judge's summing up. In this article, we will consider the gravity of Judges omitting to highlight a defendant's diagnosis of autism spectrum disorder and the necessity of detailed explanations to jury members regarding the condition and its effect upon thoughts and behaviour. Consideration will be specifically given to the necessity to prove sexual motivation in such offences and the judicial direction required in relation to whether the appellant's actions had been sexually motivated. Recognition of the social impairments inherent in ASDs are vital to this work and we shall consider whether the difficulty with the capacity to develop appropriate, consenting sexual relationships as a result of impaired social cognition may be one of the factors which increases the risk of sexual offending in individuals with ASD (Higgs & Carter, 2015).","subset":"pubmed_abstract"} +{"meta":{"pmid":24920274,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-04":1,"2018-47":2,"2018-34":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-30":1,"2017-22":1,"2017-04":1,"2019-18":1,"2017-13":1}}},"text":"Meiotic long non-coding meiRNA accumulates as a dot at its genetic locus facilitated by Mmi1 and plays as a decoy to lure Mmi1.\nLong non-coding RNAs (lncRNAs) play key roles in the formation of nuclear bodies. In the fission yeast Schizosaccharomyces pombe, a lncRNA species termed meiRNA forms a nuclear dot structure at its own genetic locus, the sme2 locus, with its protein-binding partner Mei2. This dot structure, called Mei2 dot, promotes the progression of meiosis by suppressing Mmi1, a crucial factor involved in the selective elimination of meiosis-specific transcripts. The meiRNA itself is a target of Mmi1-mediated elimination and is supposed to function as a decoy to lure Mmi1. However, detailed mechanisms underlying the formation of Mei2 dot and inactivation of Mmi1 remain ambiguous. Here, we show that the localization of meiRNA, at its genetic locus sme2, depends on its association with Mmi1. We also demonstrate that one of the multiple Mmi1 foci in mitotic cells localizes to the sme2 locus. Furthermore, the overexpression of meiRNA promotes the accumulation of Mmi1 to the sme2 locus even in the absence of Mei2 and reduces the activity of Mmi1. These findings indicate that the retention of meiRNA at its genetic locus is facilitated by Mmi1, which then attracts scattered Mmi1 to inhibit its function.","subset":"pubmed_abstract"} +{"meta":{"pmid":32353463,"dup_signals":{"dup_doc_count":32,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":2,"2023-06":2,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-31":2,"2021-21":1,"2021-17":3,"2021-10":2,"2020-50":3,"2020-45":2,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Benchmarking pluripotent stem cell-derived organoid models.\nCerebral organoids are stem cell-derived, self-organizing three-dimensional cultures. Owing to the remarkable degree to which they recreate the cellular diversity observed in the human brain, they have attracted significant interest as a novel model system for research and drug development, as well as capturing the public imagination. However, many questions remain about the extent to which these cultures recapitulate neurodevelopment and the defining features of the human brain. To clarify the fidelity of human organoid models, Bhaduri and colleagues compared the molecular profile of brain organoid cells with that of primary cells from fetal brain. They observed that, whilst brain organoids broadly recapitulate the cellular profile of human brain, they lack the subtypes of cell classes seen in human brain. In addition, they showed marked expression of cellular stress markers, which could be reversed by transplanting organoid cells into neonatal mouse brain. The authors hypothesise that in vitro culture induces a cellular stress response and that it is this that impairs maturation. Thus, whilst their findings strike a note of caution in the use of organoids as a model for early human brain development, they lay a foundation for improving the accuracy of organoid models in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":16080957,"dup_signals":{"dup_doc_count":41,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2022-49":2,"2022-40":1,"2022-21":1,"2022-05":1,"2021-43":2,"2021-31":2,"2021-21":2,"2021-17":2,"2021-04":2,"2020-45":2,"2019-22":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-34":2,"2018-26":1,"2018-22":1,"2018-13":2,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2023-23":1,"2024-10":1,"2017-13":1,"2024-26":1}}},"text":"Cytogenetic characterization of a BCR-ABL transduced mouse cell line.\nMost patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) show evidence of secondary chromosome aberrations that may influence the course of disease and response to treatment. To better understand how these secondary chromosomal aberrations occur and to investigate whether the p185\/p190 BCR-ABL fusion protein may directly induce an increased chromosomal instability and subsequently the appearance of clonal chromosome aberrations, three BRC-ABL (p185\/ p190)-transduced mouse pre-B cell lines were analyzed by spectral karyotyping and fluorescence in situ hybridization. The human wild-type BCR-ABL gene was expressed at a level comparable with that in human Ph-positive leukemias at diagnosis. All BCR-ABL-transduced cell lines acquired similar clonal chromosomal aberrations. Trisomy 5 was always present, followed by loss of the Y chromosome, trisomy of chromosomes 12 and 18, and an unbalanced translocation between chromosomes X and 12. Thus, ectopic p185\/p190 BCR-ABL expression, such as p210 BCR-ABL, PML-RARA, or C-MYC transduction, may induce an increased chromosomal instability leading to clonal karyotypic evolution, which may mimic secondary chromosome aberrations in human Ph-positive ALL.","subset":"pubmed_abstract"} +{"meta":{"pmid":28583113,"dup_signals":{"dup_doc_count":19}},"text":"Patterns, control and complications of diabetes from a hospital based registry established in a low income country.\nDiabetes registry enables practitioners to measure the characteristics and patterns of diabetes across their patient population. They also provide insight into practice patterns which can be very effective in improving care and preventing complications. The aim of this study was to assess the patterns, control levels and complications at the baseline of the patients attending clinic at the large tertiary care hospital in Karachi, Pakistan with the help of the registry. This can be used as a reference to monitor the control and also for a comparison between peer groups. This was a cross sectional study with the data obtained from diabetes registry collected with the help of pre-designed questionnaire. HbA1c was used as a central diabetes measure and other related factors and complications were assessed with it. Only 16.6% of the participants had optimal HbA1c \u2264 7.0%. 52.9% of the patients were classified as having poor control defined by HbA1c of >8%. Three fourth of the study population were obese according to Asian specific BMI cutoffs and majority had type 2 diabetes with duration of diabetes ranging from less than one to about 35 years, mean(SD) duration being 7.6 years (7.1). Overall only 4% of the patients were on combine target of HbA1c, LDL and BP. Results of multivariable logistic regression showed that the odds of having optimal glycemic control increased by 3% with every one year increase in age. In addition, having longer duration of diabetes was associated with 56% lower odds of having good glycemic control. Moreover, having higher triglyceride levels was associated with 1% lower odds of having good glycemic control. This highlights the large burden of sub optimally controlled people with diabetes in Pakistani population, a low income country with huge diabetes prevalence and ineffective primary health care system creating enormous health and economic burden.","subset":"pubmed_abstract"} +{"meta":{"pmid":33196305,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Changes in attentional processing following neurofeedback in patients with persistent post-concussive symptoms: a pilot study.\nPersistent post-concussive symptoms (PPCS) often include attention deficits, particularly orienting and executive attention. Research in other clinical populations has demonstrated that neurofeedback therapy (NFT) is effective at improving orienting and executive attention, although its effects on attentional networks in patients with PPCS are unknown. In this single-group pilot study, we examined attention-related event-related potentials (ERPs) - N1 and P3 - and cognitive outcomes following Live Z-score training (LZT), a variant of NFT. No changes in early selective attention, as indexed by N1 amplitude, were observed; however, P3 amplitude, which indexes neural resource allocation, increased following LZT and returned to baseline by 3 months. Cognitive performance improved following treatment, which was sustained at 3 months. The magnitude of change in P3 and ANT performance did not differ between orienting or executive attention, suggesting LZT improved general attentional processing efficiency. Our results suggest that LZT may positively affect attention globally, but does not target specific attention networks. These pilot data warrant the initiation of a clinical trial evaluating the effectiveness of LZT for treating attention deficits in patients with PPCS.","subset":"pubmed_abstract"} +{"meta":{"pmid":32841224,"dup_signals":{"dup_doc_count":21,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2023-06":2,"2022-33":11,"2020-45":1,"2020-40":1,"2023-23":1,"2024-30":1}}},"text":"Germline biallelic Mcm8 variants are associated with early-onset Lynch-like syndrome.\nLynch syndrome is the most common cause of hereditary colorectal cancer (CRC), and it is characterized by DNA mismatch repair (MMR) deficiency. The term Lynch-like syndrome (LLS) is used for patients with MMR-deficient tumors and neither germline mutation in MLH1, MSH2, MSH6, PMS2, or EPCAM nor MLH1 somatic methylation. Biallelic somatic inactivation or cryptic germline MMR variants undetected during genetic testing have been proposed to be involved. Sixteen patients with early-onset LLS CRC were selected for germline and tumor whole-exome sequencing. Two potentially pathogenic germline MCM8 variants were detected in a male patient with LLS with fertility problems. A knockout cellular model for MCM8 was generated by CRISPR\/Cas9 and detected genetic variants were produced by mutagenesis. DNA damage, microsatellite instability, and mutational signatures were monitored. DNA damage was evident for MCM8KO cells and the analyzed genetic variants. Microsatellite instability and mutational signatures in MCM8KO cells were compatible with the involvement of MCM8 in MMR. Replication in an independent familial cancer cohort detected additional carriers. Unexplained MMR-deficient CRC cases, even showing somatic biallelic MMR inactivation, may be caused by underlying germline defects in genes different than MMR genes. We suggest MCM8 as a gene involved in CRC germline predisposition with a recessive pattern of inheritance.","subset":"pubmed_abstract"} +{"meta":{"pmid":18197778,"dup_signals":{"dup_doc_count":26,"dup_dump_count":23,"dup_details":{"curated_sources":3,"2021-43":1,"2020-45":1,"2020-05":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2022-49":1,"2024-10":1,"2017-13":1,"2024-18":1}}},"text":"A novel terrestrial fish habitat inside emergent logs.\nReports of new habitats for a major group of organisms are rare. Fishes display diverse adaptations for temporary (amphibious) existence on land, but to our knowledge, none have ever been reported regularly living inside emergent logs. Here, we show that the mangrove killifish, Kryptolebias marmoratus, a species previously known to emerse (leave the water) regularly, is now known to emerse and aggregate in large numbers inside decaying mangrove logs that have been \"galleried\" by terrestrial insects. This behavior has now been documented in both Belize, Central America, and Florida, U.S.A., populations and represents the first known case of fishes entering terrestrial woody material. The dense packing of fish in the narrow log galleries may imply a novel social context in which intraspecific aggressive behaviors are reduced, possibly mediated by the physiological limitations imposed within this restrictive habitat.","subset":"pubmed_abstract"} +{"meta":{"pmid":19478348,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Perceptions and practices of adapted physical educators on the teaching of social skills.\nThe purpose of this study was to determine adapted physical educators' perceptions and practices about teaching social skills to students with disabilities. A questionnaire based on Bandura's social learning theory concept of modeling was developed and mailed to an entire frame of 426 adapted physical education teachers in the state of Ohio. Face and content validity as well as test\/retest reliability (0.89) were established. Of those that were surveyed, 53% (225 teachers; 148 females and 77 males) responded. Results indicate that 93% (209) believe it is important to explicitly teach social skills in PE; however, 60% (135) expressed not feeling properly prepared to teach them. Teachers with more than 20 years of teaching experience were more likely to actually teach social skills. When compared with other teachers with less years teaching, however, they identified a greater need for training in the teaching of social skills. Results are discussed relative to teacher preparation and practices as well as social skills taught for general education and community integration.","subset":"pubmed_abstract"} +{"meta":{"pmid":7449258,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Erythrocyte 22Na efflux and urinary sodium excretion in essential hypertension.\n1. The rate constant for total 22Na efflux from erythrocytes was examined in patients with mild to moderate hypertension and in normotensive controls. No difference in 22Na efflux rate constant was found when the cells from both groups were incubated in artificial medium. When the cells from both groups were incubated in their own plasma, the rate constant for Na efflux was significantly elevated for hypertensive patients compared with controls (0.40 +\/- 0.02, 0.36 +\/- 0.01 respectively; P < 0.05). 2. In hypertensive patients sodium efflux rate constant varied inversely with 24 h urinary sodium excretion when erythrocytes were incubated in artificial medium (r = -0.34, P < 0.05) or in plasma (r = -0.42, P < 0.05). No association between sodium efflux rate constant and urinary sodium excretion occurred in normotensive subjects. 3. These findings provide further evidence that sodium is an important aetiological factor in hypertension. In 'salt-sensitive' individuals dietary sodium may interact with the regulation of cellular sodium transport via both humoral and cellular mechanisms to elevate blood pressure.","subset":"pubmed_abstract"} +{"meta":{"pmid":16390204,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Inhibition of angiotensin converting enzyme activity by flavanol-rich foods.\nAngiotensin converting enzyme (ACE) activity was evaluated in the presence of flavanol-rich foods, i.e., wines, chocolates, and teas, and of purified flavonoids. All foods assayed inhibited ACE activity, red wines being more effective than white wine, and green tea more effective than black tea. The inhibition of ACE activity was associated with both phenolic and flavanol content in the foods. When isolated polyphenols were assayed, procyanidins (dimer and hexamer) and epigallocatechin significantly inhibited enzyme activity; similar concentrations of (+)-catechin, (-)-epicatechin, gallic acid, chlorogenic acid, caffeic acid, quercetin, kaempferol, and resveratrol were ineffective. When ACE activity was assayed in rat kidney membranes in the presence of chocolate extracts or purified procyanidins, it was observed that the inhibition depended on the chocolate content of flavanols and the number of flavanol units constituting the procyanidin. These experiments demonstrate that flavanols either isolated or present in foods could inhibit ACE activity. The occurrence of such inhibition in vivo needs to be determined, although is supported by the association between the consumption of flavanol-rich foods and reductions in blood pressure observed in several experimental models.","subset":"pubmed_abstract"} +{"meta":{"pmid":23381240,"dup_signals":{"dup_doc_count":39,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":4,"2016-36":5,"2016-30":3,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":3,"2015-40":1,"2015-35":3,"2015-32":3,"2015-27":2,"2015-22":2,"2017-51":1}}},"text":"Asynchronous spiking photonic neuron for lightwave neuromorphic signal processing.\nWe developed an asynchronous spiking photonic neuron that forms the basic building block for hybrid analog\/digital lightwave neuromorphic processing. Our approach enables completely asynchronous spiking in response to input signals while maximizing the throughput relative to synchronous approaches. Asynchronous operation is achieved by generating the spike source for the photonic neuron through four-wave mixing. This hybrid analog\/digital photonic neuron has an electro-absorption modulator as the temporal integration unit for analog processing, while the digital processing portion employs optical thresholding in a highly Ge-doped nonlinear loop mirror.","subset":"pubmed_abstract"} +{"meta":{"pmid":19494071,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Genes related to long polar fimbriae of pathogenic Escherichia coli strains as reliable markers to identify virulent isolates.\nLpf (stands for long polar fimbriae) is one of the few adhesive factors of enterohemorrhagic Escherichia coli O157:H7 associated with colonization of the intestine. E. coli O157:H7 strains possess two lpf loci encoding highly regulated fimbrial structures. Database analysis of the genes encoding the major fimbrial subunits demonstrated that they are present in commensal as well as pathogenic (both intestinal and extraintestinal) E. coli strains and in Salmonella strains and that the lpfA1 and lpfA2 genes are highly prevalent among LEE (locus of enterocyte effacement)-positive E. coli strains associated with severe and\/or epidemic disease. Further DNA sequence analysis of the lpfA1 and lpfA2 genes from different attaching-and-effacing E. coli strains has led us to the identification of several polymorphisms and the classification of the major fimbrial subunits into distinct variants. Using collections of pathogenic E. coli isolates from Europe and Latin America, we demonstrated that the different lpfA types are associated with the presence of specific intimin (eae) adhesin variants and, most importantly, that they are found in specific E. coli pathotypes. Our results showed that the use of these fimbrial genes as markers, in combination with the different intimin types, resulted in a specific test for the identification of E. coli O157:H7, distinguishing it from other pathogenic E. coli strains.","subset":"pubmed_abstract"} +{"meta":{"pmid":37336483,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":5,"unknown":6}}},"text":"Role of CBCT in Prediction of Oro-antral Communication Post Third Molar Extraction: A Retrospective Study.\nOro-antral communication (OAC) is one of the most frequently encountered complications during third molar extraction. Various radiographic factors, like excessive maxillary sinus pneumatization, long periods of edentulism, periapical lesions, etc., have been considered high-risk factors for OAC. However, a panoramic radiograph has not proven to be accurate in predicting the chances of OAC. Through this retrospective study, we evaluated the efficacy of a CBCT in predicting the incidence of OAC after maxillary third molar extraction. We conducted a retrospective study in our department, which included the patients who had undergone extraction of a maxillary third molar over five years with the presence of panoramic X-rays and\/or CBCT scans prior to extraction. Primary outcomes assessed from the case files were intra-operative complications like OAC, root fracture, tuberosity fracture, pterygoid plate fracture, etc. The incidence of these complications was correlated with the presence or absence of CBCT before extraction. Out of 920 extracted maxillary third molar, only 148 teeth (16.1%) had a CBCT record before extraction. The most commonly encountered complication was broken inaccessible root piece\/s (4.9%), followed by OAC (3.5%). An inter-group comparison showed that a significantly higher percentage of patients (p < 0.001) with CBCT records had an incidence of OAC (11.5%) as against the group of patients with no CBCT record (1.9%). A CBCT scan prior to cases with high-risk factors for OAC can be a valuable tool in accurately predicting the chances of OAC after maxillary third molar extraction.","subset":"pubmed_abstract"} +{"meta":{"pmid":15534893,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"A Welch-type test for homogeneity of contrasts under heteroscedasticity with application to meta-analysis.\nA common problem that arises in the meta-analysis of several studies, each with independent treatment and control groups, is to test for the homogeneity of effect sizes without the assumptions of equal variances of the treatment and the control groups and of equal variances among the separate studies. A commonly used test statistic, frequently denoted as Q, is the weighted sum of squares of the differences of the individual effect sizes from the mean effect size, with weights inversely proportional to the variances of the effect sizes. The primary contributions of this article are the presentation of improved and very accurate approximations to the distributions of the Q statistic when the effect size is a linear contrast such as the difference between the treatment and control means. Our improved approximation to the distribution of Q under the null hypothesis is based on a multiple of an F-distribution; its use yields a substantial reduction in the type I error rate of the homogeneity test. Our improved approximation to the distribution of Q under an alternative hypothesis is based on a shift of a chi-square distribution; its use allows for much greater accuracy in the computation of the power of the homogeneity test. These two improved approximate distributions are developed using the Welch methodology of approximating the moments of Q by the use of multivariate Taylor expansions. The quality of these approximations is studied by simulation. A secondary contribution of this article is a study of how best to combine the variances of the treatment and control groups (needed for the calculation of weights in the Q statistic). Our conclusion, based on simulations, is that use of pooled variances can result in substantially erroneous conclusions.","subset":"pubmed_abstract"} +{"meta":{"pmid":18173630,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":12}}},"text":"In vivo gastrocnemius muscle fascicle length in children with and without diplegic cerebral palsy.\nThe effect of spastic cerebral palsy on in vivo gastrocnemius muscle fascicle length is not clear. Similarity of fascicle lengths in children with diplegia and typically developing children, but shortening of fascicle lengths in the paretic legs of children with hemiplegia compared with the non-paretic legs, are both reported. In the former case, comparisons were made between fascicle lengths normalized to leg length, whereas in the latter case, absolute fascicle lengths were compared. The inherent assumptions when normalizing fascicle length (measured via ultrasonography) were not validated, raising the possibility that inappropriate normalization contributed to the controversy. We used statistical methods to control the potential confounding effect of leg length on fascicle length, and tested the feasibility of the normalization method for a group of 18 children with diplegia (nine males, nine females; mean age 8y 7mo [SD 3y 11mo], range 2-15y; Gross Motor Function Classification System levels II and III) and 50 typically developing children (20 males, 30 females; mean age 9y 1mo [SD 2y 4mo], range 4-14y). Children with diplegia, as a group, had shorter absolute and normalized fascicle lengths (p<0.05) but we could not refute the appropriateness of the normalization method. Other methodological issues (such as sample characteristics) might have contributed to the apparent controversy between the studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":29756963,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Cardiorespiratory fitness and fat oxidation during exercise as protective factors for insulin resistance in sedentary women with overweight or obesity.\nobesity is a global pandemic and it is the biggest risk factor for death worldwide nowadays. Studies suggest that both cardiorespiratory fitness and fat oxidation in exercise are related to insulin resistance and type 2 diabetes mellitus, and they could be used as metabolic fitness markers. the aim of this study is to determine if cardiorespiratory fitness (VO2) and fat oxidation during exercise are protective factors of insulin resistance (IR) in sedentary women with obesity or overweight. sixty women were selected for fat oxidation analysis and 55 for cardiorespiratory fitness analysis that fitted the inclusion and exclusion criteria. VO2, maximal fat oxidation (MFO) and the intensity where MFO is reached (FATmax) were determined through an incremental test on a cycle ergometer with gas analysis. The subjects with a Homeostatic model assessment of IR index greater or equal to 2.5 were considered as insulin-resistant. Participants were divided into 2 groups, IR group (n = 38) and Non-IR group (n = 22). VO2(%) and MFO were lower in the IR group (76.1% vs.83.2%; p = 0.015 and 1.08 mg \u00d7 kg-1 \u00d7 min-1 vs. 1.62 mg \u00d7 kg-1 \u00d7 min-1; p= 0.044, respectively) compared to the Non-IR group. There was an association between VO2(%) and IR (OR = 0.92, p = 0.017) and between MFO and IR (OR = 0.52, p = 0.035), both models adjusted for age and body mass index. VO2(%) and MFO are independent protective factors for IR. No association was found between FATmax and IR.","subset":"pubmed_abstract"} +{"meta":{"pmid":24957527,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism.\nThe oocyte-to-embryo transition (OET) is thought to be mainly driven by post-transcriptional gene regulation. However, expression of both RNAs and proteins during the OET has not been comprehensively assayed. Furthermore, specific molecular mechanisms that regulate gene expression during OET are largely unknown. Here, we quantify and analyze transcriptome-wide, expression of mRNAs and thousands of proteins in Caenorhabditis elegans oocytes, 1-cell, and 2-cell embryos. This represents a first comprehensive gene expression atlas during the OET in animals. We discovered a first wave of degradation in which thousands of mRNAs are cleared shortly after fertilization. Sequence analysis revealed a statistically highly significant presence of a polyC motif in the 3' untranslated regions of most of these degraded mRNAs. Transgenic reporter assays demonstrated that this polyC motif is required and sufficient for mRNA degradation after fertilization. We show that orthologs of human polyC-binding protein specifically bind this motif. Our data suggest a mechanism in which the polyC motif and binding partners direct degradation of maternal mRNAs. Our data also indicate that endogenous siRNAs but not miRNAs promote mRNA clearance during the OET.","subset":"pubmed_abstract"} +{"meta":{"pmid":32278821,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":10}}},"text":"Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies.\nNext-generation sequencing (NGS) has revolutionized the scale and depth of biomedical sciences. Because of its unique ability for the detection of sub-clonal variants within genetically diverse populations, NGS has been successfully applied to analyze and quantify the exceptionally-high diversity within viral quasispecies, and many low-frequency drug- or vaccine-resistant mutations of therapeutic importance have been discovered. Although many works have intensively discussed the latest NGS approaches and applications in general, none of them has focused on applying NGS in viral quasispecies studies, mostly due to the limited ability of current NGS technologies to accurately detect and quantify rare viral variants. Here, we summarize several error-correction strategies that have been developed to enhance the detection accuracy of minority variants. We also discuss critical considerations for preparing a sequencing library from viral RNAs and for analyzing NGS data to unravel the mutational landscape.","subset":"pubmed_abstract"} +{"meta":{"pmid":22943488,"dup_signals":{"dup_doc_count":22,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":2,"2013-20":1,"2014-10":1,"unknown":17}}},"text":"Sex and vision II: color appearance of monochromatic lights.\nBecause cerebral cortex has a very large number of testosterone receptors, we examined the possible sex differences in color appearance of monochromatic lights across the visible spectrum. There is a history of men and women perceiving color differently. However, all of these studies deal with higher cognitive functions which may be culture-biased. We study basic visual functions, such as color appearance, without reference to any objects. We present here a detailed analysis of sex differences in primary chromatic sensations. We tested large groups of young adults with normal vision, including spatial and temporal resolution, and stereopsis. Based on standard color-screening and anomaloscope data, we excluded all color-deficient observers. Stimuli were equi-luminant monochromatic lights across the spectrum. They were foveally-viewed flashes presented against a dark background. The elicited sensations were measured using magnitude estimation of hue and saturation. When the only permitted hue terms are red (R) yellow (Y), green (G), blue (B), alone or in combination, such hue descriptions are language-independent and the hue and saturation values can be used to derive a wide range of color-discrimination functions. There were relatively small but clear and significant, differences between males and females in the hue sensations elicited by almost the entire spectrum. Generally, males required a slightly longer wavelength to experience the same hue as did females. The spectral loci of the unique hues are not correlated with anomaloscope matches; these matches are directly determined by the spectral sensitivities of L- and M-cones (genes for these cones are on the X-chromosomes). Nor are there correlations between loci of pairs of unique hues (R, Y, G, B). Wavelength-discrimination functions derived from the scaling data show that males have a broader range of poorer discrimination in the middle of the spectrum. The precise values for all the data depend on whether Newtonian or Maxwellian optics were used, but the sex differences were the same for both optical systems. As with our associated paper on spatio-temporal vision, there are marked sex differences in color vision. The color-appearances we measured are determined by inputs from thalamic neurons (LGN) to individual neurons in primary visual cortex. This convergence from LGN to cortex is guided by the cortex during embryogenesis. We hypothesize that testosterone plays a major role, somehow leading to different connectivities for males and females: color appearance requires a re-combination and re-weighting of neuronal inputs from the LGN to the cortex, which, as we show, depends on the sex of the participant.","subset":"pubmed_abstract"} +{"meta":{"pmid":19391165,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2022-27":1,"2021-17":1,"2021-10":1,"2019-47":1,"2019-43":1,"2019-35":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-22":1,"2017-51":1,"2016-44":1,"2023-40":1}}},"text":"Oxidized proteins: mechanisms of removal and consequences of accumulation.\nElevated levels of oxidized proteins are reported in diseased tissue from age-related pathologies such as atherosclerosis, neurodegenerative disorders, and cataract. Unlike the precise mechanisms that exist for the repair of nucleic acids, lipids, and carbohydrates, the primary pathway for the repair of oxidized proteins is complete catabolism to their constitutive amino acids. This process can be inefficient as is evidenced by their accumulation. It is generally considered that damaged proteins are degraded by the proteasome; however, this is only true for mildly oxidized proteins, because substrates must be unfolded to enter the narrow catalytic core. Rather, evidence suggests that moderately or heavily oxidized proteins are endocytosed and enter the endosomal\/lysosomal system, indicating co-operation between the proteasomes and the lysosomes. Heavily modified substrates are incompletely degraded and accumulate within the lysosomal compartments resulting in the formation of lipofuscin-like, autofluorescent aggregates. Accumulation eventually results in impaired turnover of large organelles such as proteasomes and mitochondria, lysosomal destablization, leakage of proteases into the cytosol and apoptosis. In this review, we summarize reports published since our last assessments of the field of oxidized protein degradation including a role for modified proteins in the induction of apoptosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":19392994,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma 'epidemic'.\nAllergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA(2)LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan-European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA(2)LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project-related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA(2)LEN are reported in this paper.","subset":"pubmed_abstract"} +{"meta":{"pmid":8104130,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":1,"2022-40":1,"2021-49":2,"2021-43":1,"2021-17":1,"2021-10":1,"2020-05":1,"2019-43":1,"2019-26":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-05":1,"2017-34":1,"2024-26":1}}},"text":"Development of a simple incubation system for metabolism studies with precision-cut liver slices.\nThe use of precision-cut liver slices for toxicity and drug metabolism studies becomes more and more popular. So far, most of these studies are conducted using the dynamic organ culture system as incubation system. However, this system has some disadvantages, especially for the study of drug metabolism. Therefore, the aim of this study was to develop a simple incubation system for precision-cut liver slices. Rat liver slices were incubated individually in 12-well culture plates filled with 1.5 ml Krebs-Henseleit buffer, pH 7.4. Instead of glucose, fructose was used as carbohydrate source. The plates were put on a gyratory shaker (90 rpm) in a temperature controlled incubator (37 degrees C) under an atmosphere of 95% air\/5% CO2. Under these conditions slices could be kept viable for at least 11 hr, which seems to be long enough for metabolism studies. Slice thickness was a critical factor in both studies on optimal incubation conditions and metabolism studies. A correlation was found between slice thickness (i.e. slice weight) and metabolite production (amount formed\/mg slice) as demonstrated with tolbutamide and diazepam as test substances. It is demonstrated that a variation in slice thickness does not alter the number of cells involved in drug metabolism (i.e. the absolute amount of metabolite formed per slice does not alter). In conclusion, the way liver slices are incubated as well as the thickness of slices highly determines the results of studies on incubation conditions and metabolism studies with precision-cut liver slices.","subset":"pubmed_abstract"} +{"meta":{"pmid":30940660,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":11}}},"text":"Molecular Imaging of Deoxycytidine Kinase Activity Using Deoxycytidine-Enhanced CEST MRI.\nDeoxycytidine kinase (DCK) is a key enzyme for the activation of a broad spectrum of nucleoside-based chemotherapy drugs (e.g., gemcitabine); low DCK activity is one of the most important causes of cancer drug-resistance. Noninvasive imaging methods that can quantify DCK activity are invaluable for assessing tumor resistance and predicting treatment efficacy. Here we developed a \"natural\" MRI approach to detect DCK activity using its natural substrate deoxycytidine (dC) as the imaging probe, which can be detected directly by chemical exchange saturation transfer (CEST) MRI without any synthetic labeling. CEST MRI contrast of dC and its phosphorylated form, dCTP, successfully discriminated DCK activity in two mouse leukemia cell lines with different DCK expression. This dC-enhanced CEST MRI in xenograft leukemic cancer mouse models demonstrated that DCK(+) tumors have a distinctive dynamic CEST contrast enhancement and a significantly higher CEST contrast than DCK(-) tumors (AUC0-60 min = 0.47 \u00b1 0.25 and 0.20 \u00b1 0.13, respectively; P = 0.026, paired Student t test, n = 4) at 1 hour after the injection of dC. dC-enhanced CEST contrast also correlated well with tumor responses to gemcitabine treatment. This study demonstrates a novel MR molecular imaging approach for predicting cancer resistance using natural, nonradioactive, nonmetallic, and clinically available agents. This method has great potential for pursuing personalized chemotherapy by stratifying patients with different DCK activity. SIGNIFICANCE: A new molecular MRI method that detects deoxycytidine kinase activity using its natural substrate deoxycytidine has great translational potential for clinical assessment of tumor resistance and prediction of treatment efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":19073723,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":16}}},"text":"High-resolution functional profiling of a gammaherpesvirus RTA locus in the context of the viral genome.\nGammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus are associated with multiple human cancers. Our goal was to develop a quantitative, high-throughput functional profiling system to identify viral cis-elements and protein subdomains critical for virus replication in the context of the herpesvirus genome. In gamma-2 herpesviruses, the transactivating factor RTA is essential for initiation of lytic gene expression and viral reactivation. We used the RTA locus as a model to develop the functional profiling approach. The mutant murine gammaherpesvirus 68 viral library, containing 15-bp random insertions in the RTA locus, was passaged in murine fibroblast cells for multiple rounds of selection. The effect of each 15-bp insertion was characterized using fluorescent-PCR profiling. We identified 1,229 insertions in the 3,845-bp RTA locus, of which 393, 282, and 554 were critically impaired, attenuated, and tolerated, respectively, for viral growth. The functional profiling phenotypes were verified by examining several individual RTA mutant clones for transactivating function of the RTA promoter and transcomplementing function of the RTA-null virus. Thus, the profiling approach enabled us to identify several novel functional domains in the RTA locus in the context of the herpesvirus genome. Importantly, our study has demonstrated a novel system to conduct high-density functional genetic mapping. The genome-scale expansion of the genetic profiling approach will expedite the functional genomics research on herpesvirus.","subset":"pubmed_abstract"} +{"meta":{"pmid":10977030,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.\nTo study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol\/l were determined over an 8-h period after administration. After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+\/-47 vs. 182+\/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+\/-2.6 vs. 8.8+\/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+\/-0.25 vs. 0.59+\/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+\/-0.76 vs. 2.56+\/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+\/-3.5% (absolute bioefficacy 10.1+\/-3.1%) but was highest in the first 2 h after application (18.5+\/-3.7%; absolute bioefficacy 8.2+\/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+\/-9% for the maximal glucose infusion rate, 15+\/-10% for the time-to-maximal effect, and 16+\/-12% for the total amount of glucose infused. This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.","subset":"pubmed_abstract"} +{"meta":{"pmid":19875616,"dup_signals":{"dup_doc_count":11}},"text":"Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies.\nThe aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I(2) = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.","subset":"pubmed_abstract"} +{"meta":{"pmid":23966294,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction.\nBone metastasis greatly deteriorates the quality of life in patients with cancer. Although mechanisms have been widely investigated, the relationship between cancer bone metastasis and antitumor immunity in the host has been much less studied. Here, we report a novel mechanism of bone metastasis mediated by FSTL1, a follistatin-like glycoprotein secreted by Snail(+) tumor cells, which metastasize frequently to bone. We found that FSTL1 plays a dual role in bone metastasis-in one way by mediating tumor cell invasion and bone tropism but also in a second way by expanding a population of pluripotent mesenchymal stem-like CD45(-)ALCAM(+) cells derived from bone marrow. CD45(-)ALCAM(+) cells induced bone metastasis de novo, but they also generated CD8(low) T cells with weak CTL activity in the periphery, which also promoted bone metastasis in an indirect manner. RNA interference-mediated attenuation of FSTL1 in tumor cells prevented bone metastasis along with the parallel increase in ALCAM(+) cells and CD8(low) T cells. These effects were accompanied by heightened antitumor immune responses in vitro and in vivo. In clinical specimens of advanced breast cancer, ALCAM(+) cells increased with FSTL1 positivity in tumor tissues, but not in adjacent normal tissues, consistent with a causal connection between these molecules. Our findings define FSTL1 as an attractive candidate therapeutic target to prevent or treat bone metastasis, which remains a major challenge in patients with cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":8163654,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Intact human ceruloplasmin oxidatively modifies low density lipoprotein.\nCeruloplasmin is a plasma protein that carries most of the copper found in the blood. Although its elevation after inflammation and trauma has led to its classification as an acute phase protein, its physiological role is uncertain. A frequently reported activity of ceruloplasmin is its ability to suppress oxidation of lipids. In light of the intense recent interest in the oxidation of plasma LDL, we investigated the effects of ceruloplasmin on the oxidation of this lipoprotein. In contrast to our expectations, highly purified, undegraded human ceruloplasmin enhanced rather than suppressed copper ion-mediated oxidation of LDL. Ceruloplasmin increased the oxidative modification of LDL as measured by thiobarbituric acid-reacting substances by at least 25-fold in 20 h, and increased electrophoretic mobility, conjugated dienes, and total lipid peroxides. In contrast, ceruloplasmin that was degraded to a complex containing 115- and 19-kD fragments inhibited cupric ion oxidation of LDL, as did commercial preparations, which were also degraded. However, the antioxidant capability of degraded ceruloplasmin in this system was similar to that of other proteins, including albumin. The copper in ceruloplasmin responsible for oxidant activity was not removed by ultrafiltration, indicating a tight association. Treatment of ceruloplasmin with Chelex-100 removed one of seven copper atoms per molecule and completely blocked oxidant activity. Restoration of the copper to ceruloplasmin also restored oxidant activity. These data indicate that ceruloplasmin, depending on the integrity of its structure and its bound copper, can exert a potent oxidant rather than antioxidant action on LDL. Our results invite speculation that ceruloplasmin may be in part responsible for oxidation of LDL in blood or in the arterial wall and may thus have a physiological role that is quite distinct from what is commonly believed.","subset":"pubmed_abstract"} +{"meta":{"pmid":15774680,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Exiguobacterium aestuarii sp. nov. and Exiguobacterium marinum sp. nov., isolated from a tidal flat of the Yellow Sea in Korea.\nThree Gram-variable, rod-shaped bacterial strains, TF-16(T), TF-19 and TF-80(T), were isolated from a tidal flat of Daepo Beach (Yellow Sea) near Mokpo City, Korea, and their taxonomic positions were investigated by a polyphasic approach. These isolates grew optimally in the presence of 2 % NaCl and at 30 degrees C. Their peptidoglycan types were based on l-Lys-Gly. The predominant menaquinone detected in the three strains was MK-7. The three strains contained large amounts of the branched fatty acids iso-C(17 : 0), anteiso-C(13 : 0), iso-C(13 : 0) and iso-C(15 : 0). The DNA G+C contents of strains TF-16(T), TF-19 and TF-80(T) were 48.6, 48.4 and 48.0 mol%, respectively. The three strains formed a coherent cluster with Exiguobacterium species in a phylogenetic tree based on 16S rRNA gene sequences. They showed closest phylogenetic affiliation to Exiguobacterium aurantiacum, with 16S rRNA gene sequence similarity values of 98.1-98.3 %. The three strains exhibited 16S rRNA gene sequence similarity values of 94.0-94.6 % to the type strains of other Exiguobacterium species. Levels of DNA-DNA relatedness indicated that strains TF-16(T) and TF-19 and strain TF-80(T) are members of two species that are separate from E. aurantiacum. On the basis of phenotypic, phylogenetic and genetic data, strains TF-16(T) and TF-19 and strain TF-80(T) represent two novel species in the genus Exiguobacterium; the names Exiguobacterium aestuarii sp. nov. (type strain TF-16(T)=KCTC 19035(T)=DSM 16306(T); reference strain TF-19) and Exiguobacterium marinum sp. nov. (type strain TF-80(T)=KCTC 19036(T)=DSM 16307(T)) are proposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":30155100,"dup_signals":{"dup_doc_count":19,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2021-25":1,"2021-10":1,"2021-04":1,"2020-16":1,"2019-18":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2023-14":1}}},"text":"The role of dynamic ligand exchange in the oxidation chemistry of cerium(iii).\nThe CeIII\/IV couple is useful for many applications in organic, inorganic, and materials chemistry. However, attaining a general method to access both oxidations states through reversible solution redox chemistry remains challenging. Herein we report the synthesis, characterization, and oxidation chemistry of the novel Ce\/Li REMB heterochiral diastereomer, 1-Ce(het). The solution exchange processes of 1-RE(het) (RE = Ce and Yb) were investigated to estimate rates of ligand and cation exchange relevant in homochiral and heterochiral frameworks. A detailed mechanistic investigation following the solution dynamics of 1-Ce(het) revealed reactivity controlled both by ligand reorganization and redistribution processes. Ligand reorganization was responsible for the kinetics associated with the chemical oxidation reaction, whereas ligand redistribution and exchange dictated the isolated products.","subset":"pubmed_abstract"} +{"meta":{"pmid":25547122,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Harnessing tunable scanning probe techniques to measure shear enhanced adhesion of gecko-inspired fibrillar arrays.\nThe hierarchical arrays of mesoscale to nanoscale fibrillar structures on a gecko's foot enable the animal to climb surfaces of varying roughness. Adhesion force between the fibrillar structures and various surfaces is maximized after the gecko drags its foot in one direction, which has also been demonstrated to improve the adhesion forces of artificial fibrillar arrays. Essential conditions that influence the magnitude of these interactions include the lateral distance traveled and velocity between the contacting surfaces, as well as the velocity at which the two surfaces are subsequently separated. These parameters have, however, not been systematically investigated to assess the adhesion properties of artificial adhesives. We introduce a systematic study that investigates these conditions using a scanning probe microscope to measure the adhesion forces of artificial adhesives through a process that mimics the mechanism by which a gecko climbs. The measured adhesion response was different for arrays of shorter and longer fibrils. These results from 9000 independent measurements also provide further insight into the dynamics of the interactions between fibrillar arrays and contacting surfaces. These studies establish scanning probe microscopy techniques as a versatile approach for measuring a variety of adhesion properties of artificial fibrillar adhesives.","subset":"pubmed_abstract"} +{"meta":{"pmid":16235311,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":13}}},"text":"Traction for low-back pain with or without sciatica.\nVarious types of traction are used in the treatment of low-back pain (LBP), often in conjunction with other treatments. To determine the effectiveness of traction in the management of LBP. We searched The Cochrane Library 2004, Issue 4, MEDLINE, EMBASE, and CINAHL to November 2004, references in relevant reviews, and our personal files. Randomized controlled trials (RCTs) examining any type of traction for the treatment of acute (less than four weeks duration), sub-acute (four to 12 weeks) or chronic (more than 12 weeks) non-specific LBP with or without sciatica. Study selection, methodological quality assessment and data extraction were done independently by sets of two reviewers. As available studies did not provide sufficient data for statistical pooling, a qualitative analysis was performed. Twenty-four RCTs, involving 2177 patients (1016 receiving traction) were included in the review. Five trials were considered high quality. There is strong evidence that there is no significant difference in short or long-term outcomes between either continuous or intermittent traction and placebo, sham, or other treatments for patients with a mixed duration of LBP, with or without sciatica. There is moderate evidence that: autotraction is more effective other forms of traction are no more effective than placebo, sham or no treatment for patients with a mixed duration of LBP with sciatica. There is limited evidence that: there is no significant difference in outcomes between a standard physical therapy program with continuous traction and the same program without traction, for patients with a mixed duration of LBP, with or without sciatica autotraction on its own is more effective than a physical therapy program that includes Tru-Trac traction for patients with a mixed duration of LBP with sciatica. There is conflicting evidence regarding the short-term effectiveness of either continuous or intermittent traction compared to placebo, sham or other treatments, in the management of patients who have either chronic LBP or a mixed duration of LBP with sciatica. The evidence suggests that traction is probably not effective. Neither continuous nor intermittent traction by itself was more effective in improving pain, disability or work absence than placebo, sham or other treatments for patients with a mixed duration of LBP, with or without sciatica. Although trials studying patients with sciatica had methodological limitations and inconsistent results, there was moderate evidence that autotraction was more effective than mechanical traction for global improvement in this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":30622239,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2022-05":1,"2020-24":1,"2019-43":3,"2019-35":1,"2019-30":3,"2019-26":1,"2022-49":1}}},"text":"The cirrhotic liver is depleted of docosahexaenoic acid (DHA), a key modulator of NF-\u03baB and TGF\u03b2 pathways in hepatic stellate cells.\nLiver cirrhosis results from chronic hepatic damage and is characterized by derangement of the organ architecture with increased liver fibrogenesis and defective hepatocellular function. It frequently evolves into progressive hepatic insufficiency associated with high mortality unless liver transplantation is performed. We have hypothesized that the deficiency of critical nutrients such as essential omega-3 fatty acids might play a role in the progression of liver cirrhosis. Here we evaluated by LC-MS\/MS the liver content of omega-3 docosahexaenoic fatty acid (DHA) in cirrhotic patients and investigated the effect of DHA in a murine model of liver injury and in the response of hepatic stellate cells (HSCs) (the main producers of collagen in the liver) to pro-fibrogenic stimuli. We found that cirrhotic livers exhibit a marked depletion of DHA and that this alteration correlates with the progression of the disease. Administration of DHA exerts potent anti-fibrogenic effects in an acute model of liver damage. Studies with HSCs show that DHA inhibits fibrogenesis more intensely than other omega-3 fatty acids. Data from expression arrays revealed that DHA blocks TGF\u03b2 and NF-\u03baB pathways. Mechanistically, DHA decreases late, but not early, SMAD3 nuclear accumulation and inhibits p65\/RelA-S536 phosphorylation, which is required for HSC survival. Notably, DHA increases ADRP expression, leading to the formation of typical quiescence-associated perinuclear lipid droplets. In conclusion, a marked depletion of DHA is present in the liver of patients with advanced cirrhosis. DHA displays anti-fibrogenic activities on HSCs targeting NF-\u03baB and TGF\u03b2 pathways and inducing ADPR expression and quiescence in these cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":29226966,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"Using trial-level data and multilevel modeling to investigate within-task change in event-related potentials.\nEEG data, and specifically the ERP, provide psychologists with the power to examine quickly occurring cognitive processes at the native temporal resolution at which they occur. Despite the advantages conferred by ERPs to examine processes at different points in time, ERP researchers commonly ignore the trial-to-trial temporal dimension by collapsing across trials of similar types (i.e., the signal averaging approach) because of constraints imposed by repeated measures ANOVA. Here, we present the advantages of using multilevel modeling (MLM) to examine trial-level data to investigate change in neurocognitive processes across the course of an experiment. Two examples are presented to illustrate the usefulness of this technique. The first demonstrates decreasing differentiation in N170 amplitude to faces of different races across the course of a race categorization task. The second demonstrates attenuation of the ERN as participants commit more errors within a task designed to measure implicit racial bias. Although the examples presented here are within the realm of social psychology, the use of MLM to analyze trial-level EEG data has the potential to contribute to a number of different theoretical domains within psychology.","subset":"pubmed_abstract"} +{"meta":{"pmid":9824196,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Severe hemorrhage complicating the Klippel-Tr\u00e9naunay-Weber syndrome.\nThe Klippel-Tr\u00e9naunay-Weber (KTW) syndrome is a congenital disorder of angiogenesis characterized by macular nevus, skeletal and soft tissue hypertrophy, venous varicosities, and arteriovenous fistulas. Disseminated intravascular coagulation (DIC) and the Kasabach-Merritt syndrome, a consumptive coagulopathy with thrombocytopenia, are both associated with the KTW syndrome. We describe a 30-year-old woman with KTW syndrome and Kasabach-Merritt syndrome who had DIC with severe hemorrhage after a routine gynecologic procedure. The bleeding was controlled with the use of intravenous low-dose heparin and antithrombin III.","subset":"pubmed_abstract"} +{"meta":{"pmid":19102584,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":3,"2023-06":1,"2022-33":1,"2021-39":1,"2020-10":1,"2020-05":1,"2019-43":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":2,"2017-51":1,"2017-43":1,"2017-34":1,"2023-14":1,"2013-20":1,"2024-30":1}}},"text":"Reproductive health of bass in the Potomac, U.S.A., drainage: part 1. Exploring the effects of proximity to wastewater treatment plant discharge.\nIntersex (specifically, testicular oocytes) has been observed in male smallmouth bass (SMB; Micropterus dolomieu) and other centrarchids in the South Branch of the Potomac River, U.S.A., and forks of the Shenandoah River, U.S.A., during the past five years. This condition often is associated with exposure to estrogenic endocrine-disrupting chemicals in some fish species, but such chemicals and their sources have yet to be identified in the Potomac. In an attempt to better understand the plausible causes of this condition, we investigated the reproductive health of bass sampled up- and downstream of wastewater treatment plant (WWTP) effluent point sources on the Potomac River in Maryland, U.S.A. Smallmouth bass were sampled from the Conococheague Creek and the Monocacy River, and largemouth bass (LMB; Micropterus salmoides) were collected near the Blue Plains WWTP on the mainstem of the Potomac River. Chemical analyses of compounds captured in passive samplers at these locations also were conducted. A high prevalence of intersex (82-100%) was identified in male SMB at all sites regardless of collection area. A lower prevalence of intersex (23%) was identified in male LMB collected at the Blue Plains site. When up- and downstream fish were compared, significant differences were noted only in fish from the Conococheague. Differences included condition factor, gonadosomatic index, plasma vitellogenin concentration, and estrogen to testosterone ratio. In general, chemicals associated with wastewater effluent, storm-water runoff, and agriculture were more prevalent at the downstream sampling sites. An exception was atrazine and its associated metabolites, which were present in greater concentrations at the upstream sites. It appears that proximity to effluent from WWTPs may influence the reproductive health of bass in the Potomac watershed, but inputs from other sources likely contribute to the widespread, high incidence of testicular oocytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29519924,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-04":1,"2020-40":1,"2019-35":1,"2019-22":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2023-40":1,"2024-18":1}}},"text":"Aminopeptidase N\/CD13 as a potential therapeutic target in malignant pleural mesothelioma.\nAngiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM) and antiangiogenic strategies might be effective against MPM. Aminopeptidase N (APN)\/CD13 promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN\/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanised anti-APN\/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN\/CD13) and MSTO-211H (scarcely expressing APN\/CD13) MPM cells.High tumour APN\/CD13 expression was associated with poor prognosis in MPM patients (p=0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10 but not MSTO-211H cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together, these results suggest that APN\/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN\/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN\/CD13 expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":1295493,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis.\nThe infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.","subset":"pubmed_abstract"} +{"meta":{"pmid":18282049,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Atomic partition of the optical rotatory power of methylhydroperoxide.\nWe applied a methodology capable of resolving the optical rotatory power into atomic contributions. The individual atomic contributions to the optical rotatory power and molecular chirality of the methylhydroperoxide are obtained via a canonical transformation of the Hamiltonian by which the electric dipolar moment operator is transformed to the acceleration gauge formalism and the magnetic dipolar moment operator to the torque formalism. The gross atomic isotropic contributions have been evaluated for the carbon, the nonequivalent oxygen, and the nonequivalent hydrogen atoms of methylhydroperoxide, employing a very large Gaussian basis set which is close to the Hartree-Fock limit.","subset":"pubmed_abstract"} +{"meta":{"pmid":18177195,"dup_signals":{"dup_doc_count":28,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2024-18":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":17}}},"text":"Functional outcomes of cleft lip surgery. Part III: Measurement of lip forces.\nTo investigate lip force dynamics among participants with a repaired cleft of the lip and noncleft control participants. A parallel, three-group, nonrandomized clinical trial. Forty-eight participants with cleft lip and 36 noncleft participants. Participants attended two separate visits. At each visit, they were instructed to produce fine motor control and maximum compression forces with each upper and lower lip in response to visual force targets. Measures of force were extracted, and the data were fit using regression techniques. The upper and lower lips of the participants with a cleft lip demonstrated less time on target, while the lower lips had shorter rise time but higher peak forces, a higher rate of force recruitment, and increased maxima of the first derivative of force compared with the noncleft participants. For all participants, there was a learning effect for certain force variables between the two visits and with increasing age. For participants with a cleft lip, force regulation of the circumoral region within the operating range presumed important for facial and speech animation is compromised because of impairments in force recruitment, gradation, fractionation, and stability. In the presence of a change in upper lip tissue mechanics due to scarring or neuromotor impairment, such as a cleft, the lower lip typically exhibits compensatory motor actions.","subset":"pubmed_abstract"} +{"meta":{"pmid":28754131,"dup_signals":{"dup_doc_count":11}},"text":"A translocator protein 18 kDa agonist protects against cerebral ischemia\/reperfusion injury.\nCerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia\/reperfusion. We used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine. TSPO was upregulated in Iba1+ or CD11b+CD45int cells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1\u03b2, interleukin-6, tumor necrosis factor-\u03b1, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor. These findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia\/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":22481238,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":13}}},"text":"Surgical outcome of stage IIIA- cN2\/pN2 non-small-cell lung cancer patients in Japanese lung cancer registry study in 2004.\nThe role of surgery in the treatment of non-small-cell lung cancer (NSCLC) with clinically manifested mediastinal node metastasis is controversial even in resectable cases because it is often accompanied by systemic micrometastasis. However, surgery is occasionally indicated for cases with single-station N2 disease or within multimodal treatment regimens, and in clinical trials. The aim of this study is to evaluate surgical outcomes in a modern cohort of patients with clinical (c-) stage IIIA-N2 NSCLC whose nodal metastasis was confirmed by pathology (cN2\/pN2). From the central database of lung cancer patients undergoing surgery in 2004, which was founded by the Japanese Joint Committee for Lung Cancer Registration, data of patients having all conditions of NSCLC, c-stage IIIA, cN2, and pN2 were extracted, and the clinicopathologic profile of patients and surgical outcomes were evaluated. Among 11,663 registered NSCLC cases, 436 patients (3.8%) (332 men and 104 women) had been extracted. Their mean age was 65 years, and histologic types included adenocarcinoma (n = 246), squamous cell carcinoma (n = 132), and others (n = 58). The proportion of R0 resection was 82.5% and the proportion of the hospital deaths among the cause of death was 2.3%. The 5-year survival rate was 30.1% for the selected group of patients. The postoperative prognosis was significantly better than those of corresponding populations extracted from the 1994 (p = 0.0001) and 1999 databases (p = 0.0411). Men and women experienced a significantly different survival outcome (p = 0.025) with 5-year survivals of 27.5% and 37.8%, respectively. Single-station N2 cases occupied 60.9 % of the cohort and showed a significantly better prognosis than multistation N2 (p = 0.0053, 35.8 % versus 22.0 % survival rate at 5 years). The surgical outcomes of c-stage IIIA-cN2\/pN2 NSCLC patients in 2004 were favorable in comparison with those ever reported.","subset":"pubmed_abstract"} +{"meta":{"pmid":12216697,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-43":1,"2021-31":1,"2021-25":1,"2021-04":1,"2019-43":1,"2019-26":1,"2019-13":1,"2018-43":2,"2018-34":1,"2018-30":1,"2018-17":1,"2017-51":1,"2021-49":1}}},"text":"Unsubscribe, pleeezz!!!: management and training of media competence in computer-mediated communication.\nComputer-mediated communication (CMC) has created a new communication divide. Mostly, this division is due to technical and access problems. Overlooked is yet another divide in terms of user communication competence. This contribution focuses on media competence based on theories about communication competence and theories about CMC. Two field studies are presented: an analysis of a virtual seminar chat communication (22 participants, 3 weeks' duration) and an analysis of unsubscribe-failures within 2 years of a German mailing list (average of 1,000 subscriptions). Data from both studies reveal that help-seeking CMC users with low media-specific competence experience setbacks in terms of interpersonal relations and information gathering. There is a spiral of neutral to negative reactions and an increase in stress and aggression-related language in the reaction of the addressed peers. From the perspective of external raters, we found a contraintuitive result: The style, content, and wording of the message of the respondent is considered as an indicator for a less competent and socially attractive person behind the follow-up message than those of the initial message. On the one hand, media experts are needed and appreciated as technical problem-solvers; on the other hand, they might be perceived as socially narrow-minded freaks who are less interested in the task itself than in CMC-based task completion. This leads to the question of how sensibility for the social context, task orientation, and media competence can be combined (and trained for) in one person. Two competence trainings for text-based synchronous and asynchronous communication are introduced as interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30398487,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Mechanisms of action of Ru(ii) polypyridyl complexes in living cells upon light irradiation.\nThe unique photophysical properties of Ru(ii) polypyridyl complexes make them very attractive candidates as photosensitisers in Photodynamic Therapy (PDT). However, to date, there are not many studies exploring in detail the mechanism(s) of action of such compounds in living systems upon light irradiation. This feature article provides an overview of the most in-depth biological studies on such compounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":30846737,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Inhibition of parasite invasion by monoclonal antibody against epidermal growth factor-like domain of Plasmodium vivax merozoite surface protein 1 paralog.\nThe Plasmodium vivax merozoite surface protein 1 paralog (PvMSP1P), which has epidermal growth factor (EGF)-like domains, was identified as a novel erythrocyte adhesive molecule. This EGF-like domain (PvMSP1P-19) elicited high level of acquired immune response in patients. Antibodies against PvMSP1P significantly reduced erythrocyte adhesion activity to its unknown receptor. To determine PvMSP1P-19-specific antibody function and B-cell epitopes in vivax patients, five monoclonal antibodies (mAbs) and 18-mer peptides were generated. The mAb functions were determined by erythrocyte-binding inhibition assay and invasion inhibition assay with P. knowlesi. B-cell epitopes of PvMSP1P-19 domains were evaluated by peptide microarray. The pvmsp1p-19 sequences showed limited polymorphism in P. vivax worldwide isolates. The 1BH9-A10 showed erythrocyte binding inhibitory by interaction with the N-terminus of PvMSP1P-19, while this mAb failed to recognize PkMSP1P-19 suggesting the species-specific for P. vivax. Other mAbs showed cross-reactivity with PkMSP1P-19. Among them, the 2AF4-A2 and 2AF4-A6 mAb significantly reduced parasite invasion through C-terminal recognition. The linear B-cell epitope in naturally exposed P. vivax patient was identified at three linear epitopes. In this study, PvMSP1P-19 N-terminal-specific 1BH9-A10 and C-terminal-specific 2AF4 mAbs showed functional activity for epitope recognition suggesting that PvMSP1P may be useful for vaccine development strategy for specific single epitope to prevent P. vivax invasion.","subset":"pubmed_abstract"} +{"meta":{"pmid":21450451,"dup_signals":{"dup_doc_count":16,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":8}}},"text":"CO\u2082 emission factors for waste incineration: Influence from source separation of recyclable materials.\nCO(2)-loads from combustible waste are important inputs for national CO(2) inventories and life-cycle assessments (LCA). CO(2) emissions from waste incinerators are often expressed by emission factors in kg fossil CO(2) emitted per GJ energy content of the waste. Various studies have shown considerable variations between emission factors for different incinerators, but the background for these variations has not been thoroughly examined. One important reason may be variations in collection of recyclable materials as source separation alters the composition of the residual waste incinerated. The objective of this study was to quantify the importance of source separation for determination of emission factors for incineration of residual household waste. This was done by mimicking various source separation scenarios and based on waste composition data calculating resulting emission factors for residual waste routed to incineration. Emission factors ranged from 27 to 40 kg CO(2)\/GJ. The results appeared most sensitive towards variations in waste composition and water content. Recycling rates and lower heating values could not be used as simple indicators of the resulting emission factors for residual household waste; however the fossil carbon ratio of the waste after source separation was found to be appropriately correlated with the emission factor. Based on the results, it is recommended to carefully evaluate the source separation and collection systems behind reported literature values when comparing different studies and when using the values for environmental assessment purposes.","subset":"pubmed_abstract"} +{"meta":{"pmid":32719334,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs.\nGlycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structures have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unanswered. Here, we present Cryo-EM structures of the full-length GlyR protein complex reconstituted into lipid nanodiscs that are captured in the unliganded (closed), glycine-bound (open and desensitized), and allosteric modulator-bound conformations. A comparison of these states reveals global conformational changes underlying GlyR channel gating and modulation. The functional state assignments were validated by molecular dynamics simulations, and the observed permeation events are in agreement with the anion selectivity and conductance of GlyR. These studies provide the structural basis for gating, ion selectivity, and single-channel conductance properties of GlyR in a lipid environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":8299456,"dup_signals":{"dup_doc_count":25,"dup_details":{"curated_sources":2,"unknown":23}}},"text":"Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus.\nTo identify phenotypic, genotypic, and metabolic parameters measured at the time of antepartum diagnosis of gestational diabetes mellitus that can indicate the risk of diabetes mellitus at early postpartum (< or = 6 mo after delivery) and at a 5-yr follow-up. The recommendations from the National Diabetes Data Group and International Workshop Conferences on Gestational Diabetes Mellitus were used for screening, diagnosing, and subclassifying gestational diabetes mellitus. National Diabetes Data Group criteria were also used for classification of glucose tolerance postpartum. Plasma glucose, insulin, and free fatty acids were measured after an overnight fast. Plasma glucose and insulin were measured 15, 30, 60, 120, and 180 min after the 100-g oral glucose load. Postpartum glucose tolerance was evaluated at 3-6 mo (early), 1 yr, and annually thereafter. The 5-yr cumulative incidence of diabetes during follow-up after gestational diabetes mellitus was nearly 50%. Among those who had diabetes within 5 yr, a history of diabetes in only the mother was nearly threefold more common than a history of diabetes in only the father (30 vs. 11%, P < 0.01). Those who displayed diabetes at early postpartum (< or = 6 mo) testing had significantly higher antepartum glucose levels at 60, 120, and 180 min compared with those whose early postpartum results were normal. They were also relatively insulinopenic at antepartum testing. Their fasting, acutely stimulated (15 and 30 min), and integrated 3-h response to oral glucose were all significantly lower relative to women who remained normal or had impaired glucose tolerance at early postpartum testing. Women who developed diabetes between 6 mo and 5 yr postpartum were more obese before the index pregnancy, and they had lower fasting, acutely stimulated (15 and 30 min), and integrated (1-3 h) insulin levels compared with women who remained normal or displayed impaired glucose tolerance at 5 yr postpartum. A multiple logistic regression model showed that diabetes present at early postpartum testing was independently associated with higher 2-h glucose and lower basal and total integrated insulin level. Later (> or = 6 mo-5 yr postpartum) development of diabetes was independently associated with prepregnancy weight and impaired insulin secretion at diagnosis of gestational diabetes mellitus. Impaired beta-cell function and obesity at diagnosis of GDM were associated with the development of diabetes during a 5-yr, follow-up period. Studies designed to prevent diabetes in this high-risk group should examine strategies to maintain both optimal beta-cell function and maximum insulin sensitivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":23383029,"dup_signals":{"dup_doc_count":39,"dup_dump_count":36,"dup_details":{"curated_sources":3,"2023-14":1,"2023-06":1,"2022-40":1,"2022-21":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-23":1,"2017-13":1,"2024-26":1}}},"text":"Virtual superheroes: using superpowers in virtual reality to encourage prosocial behavior.\nRecent studies have shown that playing prosocial video games leads to greater subsequent prosocial behavior in the real world. However, immersive virtual reality allows people to occupy avatars that are different from them in a perceptually realistic manner. We examine how occupying an avatar with the superhero ability to fly increases helping behavior. Using a two-by-two design, participants were either given the power of flight (their arm movements were tracked to control their flight akin to Superman's flying ability) or rode as a passenger in a helicopter, and were assigned one of two tasks, either to help find a missing diabetic child in need of insulin or to tour a virtual city. Participants in the \"super-flight\" conditions helped the experimenter pick up spilled pens after their virtual experience significantly more than those who were virtual passengers in a helicopter. The results indicate that having the \"superpower\" of flight leads to greater helping behavior in the real world, regardless of how participants used that power. A possible mechanism for this result is that having the power of flight primed concepts and prototypes associated with superheroes (e.g., Superman). This research illustrates the potential of using experiences in virtual reality technology to increase prosocial behavior in the physical world.","subset":"pubmed_abstract"} +{"meta":{"pmid":33728215,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":2,"2024-26":1,"unknown":9}}},"text":"Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study.\nIntroduction Annually, 500,000 episodes of alcohol withdrawal syndrome (AWS) are severe enough to require clinical attention. A symptom-triggered lorazepam regimen remains the standard of care for the management of hospitalized AWS patients. However, phenobarbital has also been shown to be an effective adjunctive therapy for severe AWS, reducing benzodiazepine use in the emergency department (ED) and the intensive care unit (ICU). The purpose of this study is to compare hospital length of stay (LOS) for AWS patients using phenobarbital-based versus lorazepam-based treatment protocols as monotherapy for management of AWS on general medical units. Methods This is a retrospective cohort study over a two-year period (March, 2016 to March, 2018), conducted at three hospitals within the St. Joseph Mercy Health System. We included 606 patients with a primary diagnosis of AWS or alcohol intoxication who met our inclusion criteria (543 in the lorazepam cohort and 63 in the phenobarbital cohort). Adjusted comparisons were done using propensity scoring methods. Hospital LOS was set as the primary outcome. Secondary outcomes included all-cause 30-day readmission, alcohol-related 30-day readmission, 30-day ED visits after discharge, and need for ICU transfer during hospital stay. Results Patients who received phenobarbital had a statistically significant shorter hospital LOS as compared to patients who received lorazepam (2.8 versus 3.6 days, P < 0.001). Furthermore, the phenobarbital treatment group had statistically significant lower rates of all-cause 30-day readmission (11.11% versus 14.18%, P = 0.020) and 30-day ED visits after discharge (11.11% versus 18.6%, P = 0.015). No statistical significance was detected for alcohol-related 30-day readmission and the need for ICU transfer between the treatment groups. Conclusion This study suggests that phenobarbital may be a reasonable alternative to lorazepam in the management of AWS patients admitted to general medical units. Larger scale, well-executed, and adequately powered prospective studies and randomized controlled trials are needed to corroborate these findings.","subset":"pubmed_abstract"} +{"meta":{"pmid":24758871,"dup_signals":{"dup_doc_count":55,"dup_dump_count":35,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":3,"2023-23":2,"2023-14":1,"2023-06":3,"2022-49":2,"2022-40":2,"2022-27":1,"2022-21":2,"2021-49":1,"2021-43":2,"2021-31":2,"2021-21":2,"2021-17":2,"2021-04":2,"2020-45":1,"2020-40":1,"2020-24":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":2,"2024-30":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":2}}},"text":"Structure-activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1.\nA naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pKa, inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors.","subset":"pubmed_abstract"} +{"meta":{"pmid":22959874,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-30":1,"unknown":15}}},"text":"Improvement of image quality using BLADE sequences in brain MR imaging.\nThe purpose of this study is to compare two types of sequences in brain magnetic resonance (MR) examinations of uncooperative and cooperative patients. For each group of patients, the pairs of sequences that were compared were two T2-weighted (T2-W) fluid attenuated inversion recovery sequences with different k-space trajectories (conventional Cartesian and BLADE) and two T2-TSE weighted with different k-space trajectories (conventional Cartesian and BLADE). Twenty-three consecutive uncooperative patients and 44 cooperative patients, who routinely underwent brain MR imaging examination, participated in the study. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio, contrast-to-noise ratio (CNR), and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of motion, other (e.g., Gibbs, susceptibility artifacts, phase encoding from vessels) artifacts and pulsatile flow artifacts was evaluated. In the uncooperative group of patients, BLADE sequences were superior to the corresponding conventional sequences in all the cases. Furthermore, the differences were found to be statistically significant in almost all the cases. In the cooperative group of patients, BLADE sequences were superior to the conventional sequences with the differences of the CNR and ReCon values in nine cases being statistically significant. Furthermore, BLADE sequences eliminated motion and other artifacts and T2 FLAIR BLADE sequences eliminated pulsatile flow artifacts. BLADE sequences (T2-TSE and T2 FLAIR) should be used in brain MR examinations of uncooperative patients. In cooperative patients, T2-TSE BLADE sequences may be used as part of the routine protocol and orbital examinations. T2 FLAIR BLADE sequences may be used optionally in examinations of AVM, orbits, haemorrhages, ventricular lesions, lesions in the frontal lobe, periventricular lesions, lesions in regions close to artifacts and lesions in posterior fossa.","subset":"pubmed_abstract"} +{"meta":{"pmid":29174650,"dup_signals":{"dup_doc_count":11}},"text":"Orphan neuropeptides and receptors: Novel therapeutic targets.\nNeuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with known functions, many peptides have been identified in mammalian brain for which the cognate receptors have not been identified. Similarly, dozens of \"orphan\" G protein-coupled receptors have been identified in the mammalian genome. While it would seem straightforward to match the orphan peptides and receptors, this is not always easily accomplished. In this review we focus on peptides named PEN and big LEN, which are among the most abundant neuropeptides in mouse brain, and their recently identified receptors: GPR83 and GPR171. These receptors are co-expressed in some brain regions and are able to interact. Because PEN and big LEN are produced from the same precursor protein and co-secreted, the interaction of GPR83 and GPR171 is physiologically relevant. In addition to interactions of these two peptides\/receptors, PEN and LEN are co-localized with neuropeptide Y and Agouti-related peptide in neurons that regulate feeding. In this review, using these peptide receptors as an example, we highlight the multiple modes of regulation of receptors and present the emerging view that neuropeptides function combinatorially to generate a network of signaling messages. The complexity of neuropeptides, receptors, and their signaling pathways is important to consider both in the initial deorphanization of peptides and receptors, and in the subsequent development of therapeutic applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":28550377,"dup_signals":{"dup_doc_count":25}},"text":"Acceptability of and Adherence to an Antiretroviral-Based Vaginal Microbicide among Pregnant Women in the United States.\nThe MTN-008 trial was the first multi-dose study conducted to evaluate the safety of a microbicide gel (2:1 randomized to tenofovir 1% or hydroxycellulose (HEC) placebo gel) during pregnancy. The study aim was to evaluate safety, tolerability and pharmacokinetics of the study products. Procedures included daily gel administration, with Day 0 and Day 6 in clinic, and Days 1-5 at home. Because pregnancy may pose unique challenges to consistent gel use and acceptability, evaluation of adherence and acceptability was a secondary objective of the trial. The study enrolled healthy, HIV-negative, pregnant women aged 18-40 in Pittsburgh, PA and Birmingham, AL, USA in 2 consecutive groups: cohort 1 was 37-39 weeks gestation, cohort 2 was 34-36 weeks. Ninety-one women completed the study (45 and 46 in each cohort, respectively) and were evaluable per protocol. Adherence was evaluated using self-reports: participants completed a web-based computer-assisted self-interview (CASI) at Days 0 and 6 about gel attitudes and behaviors. At Day 6 trained research staff conducted a short interviewer-administered questionnaire with both structured and open-ended questions. Frequencies of quantitative data were tabulated in SAS and descriptive statistics are presented; open-ended textual data were summarized by a behavioral scientist experienced in qualitative analysis. Participants reported generally neutral perceptions of gel characteristics. A small number of women (7-8%) reported pain (6\/90), other physical discomfort (7\/90), or mental discomfort (7\/90) associated with the process of applicator insertion. About 5% reported the same for the gel itself. Two-thirds (61\/90) thought the gel was runny, many complained of bothersome gel leakage and several cited this reason for not inserting a full dose. The majority were not worried the gel would cause problems for their pregnancy or babies. Ninety-seven percent (83\/86) said they would use the gel in the future if they were pregnant, and 90% (81\/90) when nonpregnant. Self-reported adherence was high with 88% (79\/90) reporting daily gel use on both the computerized and interviewer-administered questionnaires. The majority (67\/90) reported no difficulty with daily use. However, drug was undetectable (<0.31 ng\/mL) among 45% (27\/60; 95% CI 32-58%) of the women on active product prior to observed dosing at Day 6. The most common reason for reported nonuse (N = 6) was forgetting. Study gel was generally acceptable, but many complained of a runny consistency (61\/90) and leakage (83\/90). No frequent or strong concerns about the effects of the study gel on the pregnancy\/fetus were reported. Self-reported adherence to study gel self-administered at home for 5 days was high, however plasma drug levels suggest actual use may have been considerably lower. Findings from this study can provide insights relevant to use of other antiretroviral-based, vaginally-inserted HIV prevention methods during pregnancy.","subset":"pubmed_abstract"} +{"meta":{"pmid":32262213,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-06":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2018-05":1,"2023-23":1}}},"text":"Evaluation of borate bioactive glass scaffolds as a controlled delivery system for copper ions in stimulating osteogenesis and angiogenesis in bone healing.\nBiocompatible synthetic scaffolds with enhanced osteogenic and angiogenic capacity are of great interest for the repair of large (critical size) bone defects. In this study, we investigated an approach based on the controlled delivery of copper (Cu) ions from borate bioactive glass scaffolds for stimulating angiogenesis and osteogenesis in a rodent calvarial defect model. Borate glass scaffolds (pore size = 200-400 \u03bcm) doped with varying amounts of Cu (0-3.0 wt% CuO) were created using a polymer foam replication technique. When immersed in simulated body fluid (SBF) in vitro, the scaffolds released Cu ions into the medium at a rate that was dependent on the amount of Cu in the glass and simultaneously converted to hydroxyapatite (HA). At the concentrations used, the Cu in the glass was not cytotoxic to human bone marrow derived stem cells (hBMSCs) cultured on the scaffolds and the alkaline phosphatase activity of the hBMSCs increased with increasing Cu in the glass. When implanted in rat calvarial defects for 8 weeks, the scaffolds doped with 3 wt% CuO showed a significantly better capacity to stimulate angiogenesis and regenerate bone when compared to the undoped glass scaffolds. Together, these results indicate that the controlled delivery of Cu ions from borate bioactive glass implants is a promising approach in healing bone defects.","subset":"pubmed_abstract"} +{"meta":{"pmid":23988511,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-48":1,"unknown":9}}},"text":"Nutrient profiles of vegetarian and nonvegetarian dietary patterns.\nDifferences in nutrient profiles between vegetarian and nonvegetarian dietary patterns reflect nutritional differences that can contribute to the development of disease. Our aim was to compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. We conducted a cross-sectional study of 71,751 subjects (mean age=59 years) from the Adventist Health Study 2. Data were collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were nonvegetarian, semi-vegetarian, pesco vegetarian, lacto-ovo vegetarian, and strict vegetarian. Analysis of covariance was used to analyze differences in nutrient intakes by dietary patterns and was adjusted for age, sex, and race. Body mass index and other relevant demographic data were reported and compared by dietary pattern using \u03c7(2) tests and analysis of variance. Many nutrient intakes varied significantly between dietary patterns. Nonvegetarians had the lowest intakes of plant proteins, fiber, beta carotene, and magnesium compared with those following vegetarian dietary patterns, and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2,000 kcal\/day, with the exception of semi-vegetarians, who had an intake of 1,707 kcal\/day. Mean body mass index was highest in nonvegetarians (mean=28.7 [standard deviation=6.4]) and lowest in strict vegetarians (mean=24.0 [standard deviation=4.8]). Nutrient profiles varied markedly among dietary patterns that were defined by meat and dairy intakes. These differences are of interest in the etiology of obesity and chronic diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":28863411,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":8}}},"text":"Sirtuin 1 Levels in Recurrent Implantation Failure.\nSirtuin 1 has an important role in cellular processes, including apoptosis and cellular stress. The purpose of this study was to assess serum sirtuin 1 levels in women with recurrent implantation failure (RIF). In this cross-sectional study, we included 28 women with RIF, 29 healthy women who had conceived by in vitro fertilization (IVF), and 30 women with a 1-cycle failure of IVF as controls. Human serum nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1\/SIRT2L1) levels were detected using a commercial colorimetric kit. Recurrent implantation failure patients have higher sirtuin 1 levels than non-pregnant women and healthy pregnant women, but this difference did not reach statistical significance due to the low number of patients in our study. These higher sirtuin 1 levels may result from the inflammation imbalance of RIF patients. The only statistically significant correlation found was between age and sirtuin (r = 0.277, p = 0.009).","subset":"pubmed_abstract"} +{"meta":{"pmid":17329332,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Progression of fibrosis during chronic hepatitis C is associated with rapid virus evolution.\nHepatic fibrosis is the primary mediator of disease due to chronic infection with hepatitis C virus (HCV). HCV exists as a quasispecies in each infected individual, and longitudinal viral sequence changes may reveal viral dynamics and the selection pressures applied by the host immune system. Thus, we hypothesized that patterns of sequence change might reveal the immunopathogenesis of fibrosis progression. We tested this hypothesis by studying individuals enrolled in a prospective study of chronic HCV-related hepatic fibrosis with little or no fibrosis at first biopsy (stage 0 or 1) and a second planned liver biopsy sample obtained 4 years later. Serum was obtained from five individuals with fast progression (FP; defined as a >2-stage change between visits) and 10 carefully matched individuals with slow progression (SP; defined as a <2-stage change between visits). We sequenced multiple cloned hemigenomic cDNAs from each person spanning six genes (core through NS3). Phylogenetic analysis revealed temporal shifts in phylogenetic clustering over time, suggesting frequent quasispecies replacement rather than simple diversification. In addition, mixed infections were detected in three subjects, with coexistence in two subjects (one FP, one SP) of subtypes 1a and 1b throughout the 4-year biopsy interval. Subjects with FP had a higher rate of evolution than subjects with SP, with a preponderance of synonymous changes, suggesting purifying selection, except in hypervariable region 1, where positive selection pressure is frequently detected. Thus, in a small but carefully matched cohort we found evidence for rapid neutral evolution of HCV in persons with rapid progression of hepatic fibrosis, suggesting higher turnover of infected cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":29678198,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-21":1,"2022-05":1,"2021-21":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-30":1,"2019-22":1,"2023-14":1}}},"text":"Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota.\nThe dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes. A feeding study using deuterated TMAO in C57BL6\/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal\/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.","subset":"pubmed_abstract"} +{"meta":{"pmid":24009054,"dup_signals":{"dup_doc_count":12,"dup_dump_count":6,"dup_details":{"curated_sources":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":3}}},"text":"Rectal prolapse in young women.\nRectal prolapse belongs to the group of rare diseases of the rectum and anus. It is mostly observed in elderly multiparous women in the seventh and eighth decade. The precise cause of this pathology is not thoroughly understood that is why there are no optimal standards of treatment. The aim of the study was to present pathophysiology, diagnostics and optimal surgical procedures employed in young patients with rectal prolapse. Out of a 56-patient group treated in Department of General and Colorectal Surgery in the years 2006-2011 a smaller one consisting of 11 young women between the ages 20-40 was selected. According to the literature this is a very rare time of the mentioned pathology occurrence. In the studied females grade of rectal prolapse as well as faecal incontinence based on Jorge-Wexner's (Cleveland) scale were assessed before and after the operative treatment. All of them underwent transabdominal Wells and Frikman-Goldberg prolapse procedures. Transabdominal approaches repair pathologies of the pelvic floor and have promising longstanding results improving quality of life. No rectal prolapse recurrences were observed. The mean score of the Wexner's grading system was 7.81 diminishing to 1.9 points postoperatively. Rectal prolapse if untreated, is a pathology that substantially changes patients' quality of life for the worse. Individual, standardized surgical approach to each patient is necessary. Transabdominal methods carry a low risk of complications and improve quality of life of young patients enabling a relatively quick return to normal life.","subset":"pubmed_abstract"} +{"meta":{"pmid":24622829,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-23":1,"2024-22":1}}},"text":"Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia.\nThe effect of dehydroepiandrosterone (DHEA) on memory and cognition in experimental animals is well known, but its efficacy in clinical dementia is unproven. So, the aim of the present study was to investigate the effect of DHEA on learning and memory activities in a rat model of vascular dementia (VD). Forty-eight male rats that positively passed the holeboard memory test were chosen for the study before bilateral permanent occlusion of the common carotid artery. They were divided into four groups (n=12, each) as follows (i) untreated control, (ii) rats exposed to surgical permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (iii) rats exposed to BCCAO then received DHEA (BCCAO + DHEA) and (i.v.) rats exposed to BCCAO then received donepezil (BCCAO + DON). Holeboard memory test was used to assess the time, latency, working memory and reference memory. Central level of acetylcholine, norepinephrine and dopamine in the hippocampus were measured. Furthermore, the expression of brain derived neurotrophic factor (BDNF) in the hippocampus was determined. Histopathological studies of the cerebral cortex and transmission electron microscope of the hippocampus were performed. BCCAO decreased the learning and memory activities in the holeboard memory. Also, it decreased the expression of BDNF as well as the central level of acetylcholine, noradrenaline and dopamine as compared to control rats. Treatment with DHEA and donepezil increased the working and reference memories, BDNF expression as well as the central acetylcholine in the hippocampus as compared to BCCAO rats. DHEA produced neuroprotective effects through increasing the expression of BDNF as well as increasing the central level of acetylcholine and catecholamines which are non-comparable to donepezil effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":22973830,"dup_signals":{"dup_doc_count":32,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2017-13":1,"2013-48":1,"2013-20":1,"2024-22":1,"unknown":27}}},"text":"Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue.\nAs Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-\u03b3, TNF-\u03b1 and TNF-\u03b2 in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-\u03b3 also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.","subset":"pubmed_abstract"} +{"meta":{"pmid":37330123,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"The effect of digital health interventions on postpartum depression or anxiety: a systematic review and meta-analysis of randomized controlled trials.\nThis study aimed to examine the effect of digital health interventions compared with treatment as usual on preventing and treating postpartum depression and postpartum anxiety. Searches were conducted in Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. The systematic review included full-text randomized controlled trials comparing digital health interventions with treatment as usual for preventing or treating postpartum depression and postpartum anxiety. Two authors independently screened all abstracts for eligibility and independently reviewed all potentially eligible full-text articles for inclusion. A third author screened abstracts and full-text articles as needed to determine eligibility in cases of discrepancy. The primary outcome was the score on the first ascertainment of postpartum depression or postpartum anxiety symptoms after the intervention. Secondary outcomes included screening positive for postpartum depression or postpartum anxiety --as defined in the primary study --and loss to follow-up, defined as the proportion of participants who completed the final study assessment compared with the number of initially randomized participants. For continuous outcomes, the Hedges method was used to obtain standardized mean differences when the studies used different psychometric scales, and weighted mean differences were calculated when studies used the same psychometric scales. For categorical outcomes, pooled relative risks were estimated. Of 921 studies originally identified, 31 randomized controlled trials-corresponding to 5532 participants randomized to digital health intervention and 5492 participants randomized to treatment as usual-were included. Compared with treatment as usual, digital health interventions significantly reduced mean scores ascertaining postpartum depression symptoms (29 studies: standardized mean difference, -0.64 [95% confidence interval, -0.88 to -0.40]; I2=94.4%) and postpartum anxiety symptoms (17 studies: standardized mean difference, -0.49 [95% confidence interval, -0.72 to -0.25]; I2=84.6%). In the few studies that assessed screen-positive rates for postpartum depression (n=4) or postpartum anxiety (n=1), there were no significant differences between those randomized to digital health intervention and treatment as usual. Overall, those randomized to digital health intervention had 38% increased risk of not completing the final study assessment compared with those randomized to treatment as usual (pooled relative risk, 1.38 [95% confidence interval, 1.18-1.62]), but those randomized to app-based digital health intervention had similar loss-to-follow-up rates as those randomized to treatment as usual (relative risk, 1.04 [95% confidence interval, 0.91-1.19]). Digital health interventions modestly, but significantly, reduced scores assessing postpartum depression and postpartum anxiety symptoms. More research is needed to identify digital health interventions that effectively prevent or treat postpartum depression and postpartum anxiety but encourage ongoing engagement throughout the study period.","subset":"pubmed_abstract"} +{"meta":{"pmid":20671737,"dup_signals":{"dup_doc_count":23,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2021-49":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-34":1,"2020-16":1,"2019-47":1,"2019-30":1,"2023-23":1,"2024-18":2}}},"text":"Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions.\nIn eukaryotes, only a fraction of replication origins fire at each S phase. Local histone acetylation was proposed to control firing efficiency of origins, but conflicting results were obtained. We report that local histone acetylation does not reflect origin efficiencies along the adenosine monophosphate deaminase 2 locus in mammalian fibroblasts. Reciprocally, modulation of origin efficiency does not affect acetylation. However, treatment with a deacetylase inhibitor changes the initiation pattern. We demonstrate that this treatment alters pyrimidine biosynthesis and decreases fork speed, which recruits latent origins. Our findings reconcile results that seemed inconsistent and reveal an unsuspected effect of deacetylase inhibitors on replication dynamics.","subset":"pubmed_abstract"} +{"meta":{"pmid":16384451,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Search for coherent charged pion production in neutrino-carbon interactions.\nWe report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.","subset":"pubmed_abstract"} +{"meta":{"pmid":26348783,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2024-30":1,"unknown":7}}},"text":"Managing Multiple Mandates: A System of Systems Model to Analyze Strategies for Producing Cellulosic Ethanol and Reducing Riverine Nitrate Loads in the Upper Mississippi River Basin.\nImplementing public policies often involves navigating an array of choices that have economic and environmental consequences that are difficult to quantify due to the complexity of multiple system interactions. Implementing the mandate for cellulosic biofuel production in the Renewable Fuel Standard (RFS) and reducing hypoxia in the northern Gulf of Mexico by reducing riverine nitrate-N loads represent two such cases that overlap in the Mississippi River Basin. To quantify the consequences of these interactions, a system of systems (SoS) model was developed that incorporates interdependencies among the various subsystems, including biofuel refineries, transportation, agriculture, water resources and crop\/ethanol markets. The model allows examination of the impact of imposing riverine nitrate-N load limits on the biofuel production system as a whole, including land use change and infrastructure needs. The synergies of crop choice (first versus second generation biofuel crops), infrastructure development, and environmental impacts (streamflow and nitrate-N load) were analyzed to determine the complementarities and trade-offs between environmental protection and biofuel development objectives. For example, the results show that meeting the cellulosic biofuel target in the RFS using Miscanthus x giganteus reduces system profits by 8% and reduces nitrate-N loads by 12% compared to the scenario without a mandate. However, greater water consumption by Miscanthus is likely to reduce streamflow with potentially adverse environmental consequences that need to be considered in future decision making.","subset":"pubmed_abstract"} +{"meta":{"pmid":12913453,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Anthelmintic effect of oxantel pamoate and pyrantel pamoate suspension against intestinal nematode infestations.\nA total of 56 subjects with multiple nematode infections with T. trichiura, Ascaris, hookworms and Enterobius were treated with oxantel and pyrantel pamoate mixture in a paratable suspension(50 mg of each per ml). A single dose of 10 mg per kg body weight in each cured 100 per cent of 54 subjects with Ascaris, 97.1 per cent of 35 subjects with hookworms, 77.8 per cent of 36 with Enterobius and 73.2 per cent of 56 subjects with T. trichiura infestation. The mean egg per gram stool reduction rate in T. trichiura infection was 91.9%. Of the 31 subjects infected with Ancylostoma doudenale 96.8% were cured with a single dose and 4 infected with Necator americanus showed a 100% cure rate with a similar daily dose on 3 consecutive days. Side effects were few and mild. There was no clinical or laboratory evidence of drug toxicity. These findings show a single dose of oxantel and pyrantel pamoate mixture to be a highly effective and acceptable treatment for multiple infections with these nematodes.","subset":"pubmed_abstract"} +{"meta":{"pmid":32302967,"dup_signals":{"dup_doc_count":15,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2023-06":2,"2022-49":1,"2022-27":1,"2020-29":4,"2020-24":2,"2024-10":1}}},"text":"Mechanisms of epigenetic inheritance of variable traits through the germline.\nDuring the past half century, evidence for inheritance of variable traits has accumulated from experiments in plants and animals and epidemiological studies in humans. Here, we summarize some of the reported cases of epigenetic inheritance and the proposed mechanisms involved in the transmission of non-genetic information between generations in plants, nematodes, flies and mammals. It has long been accepted that information is epigenetically inherited in plants. Although many questions regarding the underlying mechanisms remain to be answered, it is now evident that epigenetic mechanisms are also responsible for the transmission of phenotypes in animals. We highlight similarities and differences between models and species.","subset":"pubmed_abstract"} +{"meta":{"pmid":29659651,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"STAT3 is required for proliferation and exhibits a cell type-specific binding preference in mouse female germline stem cells.\nLIF-mediated STAT3 signaling is critically involved in stem cells and development. However, its function in mouse female germline cells (FGSCs) remains elusive. In this study, we demonstrated that LIF-induced STAT3 activation contributes to the proliferation and undifferentiation maintenance of mouse FGSCs. Characterization of the STAT3-mediated transcriptional network by intersecting ChIP-seq and RNA-seq datasets revealed 405 direct target genes of STAT3, which are primarily involved in proliferation and germline development. In particular, we observed that STAT3 exhibits a FGSC-specific binding pattern when compared with mouse embryonic stem cells. Taken together, our study reported that the LIF-mediated STAT3 activation is actively involved in FGSCs and functions through a distinctive binding pattern across the FGSC genome. This cell-type specific binding preference provides an insight into understanding the genetic base for STAT3-driven cellular functions in germline stem cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":18945470,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2023-40":2,"2022-33":1,"2021-49":1,"2021-39":1,"2021-21":2,"2021-17":2,"2021-10":1,"2023-50":1,"2024-18":1}}},"text":"Influence of pH on bioactivity of cinnamon oil against Legionella pneumophila and its disinfection efficacy in hot springs.\nCinnamon oil extracted from leaves of Cinnamomum osmophloeum has recently been proved as a promising antibacterial agent against Legionella pneumophila, an etiological agent of human pneumonia known as Legionnaires' disease. However, the pH effects on the efficacy of cinnamon oil against L. pneumophila and its applicability to recreational spring water remain unknown. We therefore determined the bactericidal activity of cinnamon oil at pH 3-10 in phosphate-buffered saline (PBS) and in four kinds of springs with various conductivity (259-5595 micros cm(-1)) and pH (2.1-7.7) levels. Results show L. pneumophila cells were more susceptible to cinnamon oil at pH 8-10 than at pH 4-6 in PBS, which became more evident as increasing contact time from 10 to 60 min. An increase in concentration of cinnamon oil and contact time significantly increased the anti-L. pneumophila activity (P< or =0.001), indicating a consistent biocidal effect regardless of pH. Interestingly, this dose-response biocidal effect was also observed in spring waters. Moreover, L. pneumophila of 4 log CFU ml(-1) in spring waters was completely inactivated within 60 min by cinnamon oil at 300-750 microg ml(-1), with the highest inactivation in alkaline hydrogen carbonate spring. The great bioactivity of cinnamon oil demonstrates its potential to be used to control Legionella growth in recreational spring water and possibly other niches generally at basic pH, e.g., cooling towers.","subset":"pubmed_abstract"} +{"meta":{"pmid":8376779,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes.\nWe recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1\/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex. LPS caused a rise to peak within 2 to 3 h in serum concentrations of free NAP-1 and MCP-1, followed by an almost equally rapid fall toward base-line levels by about 5 h postinjection. MCP-1 concentration in sera from the 11 subjects rose to a peak of 330 +\/- 52 pM. The peak value for NAP-1 was 80 +\/- 11 pM. In 10 of the 11 subjects, free IgG autoantibody to MCP-1 decreased from a mean pre-LPS value of 1820 +\/- 660 pM to a mean low of 53% of the respective initial values. Corresponding data for IgG anti-NAP-1 were a pre-LPS concentration of 216 +\/- 7 pM, which decreased to a mean low of 44% of the respective initial values. The finding in some subjects of a rapid rise in free antibody after the nadir suggests the possibility of acute regulation of autoantibody secretion rates. Although the results suggested that LPS-induced chemoattractant combined with free antibody, serum concentrations of MCP-1-IgG or NAP-1-IgG did not increase, which points to an as yet unknown mechanism for trapping and elimination of the immune complexes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22137762,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-40":2,"2022-40":1,"2022-21":1,"2021-39":1,"2020-50":1,"2020-45":1,"2020-34":1,"2020-29":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2017-34":1,"2024-22":1,"2024-30":1}}},"text":"Prepatterning of developmental gene expression by modified histones before zygotic genome activation.\nA hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.","subset":"pubmed_abstract"} +{"meta":{"pmid":26208378,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Effect of Prior Aspirin Treatment on Patients With Acute Coronary Syndromes: Insights From the PROSPECT Study.\nPrior aspirin treatment is considered a risk factor for adverse outcomes in acute coronary syndrome (ACS) patients. The relationships between aspirin pretreatment and findings on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), as well as clinical outcomes, are not well understood. In the PROSPECT trial, QCA and triple-vessel IVUS imaging were performed after successful percutaneous coronary intervention (PCI) of the culprit lesion(s) in ACS patients. We compared patients receiving aspirin within 7 days of enrollment to those naive to aspirin. Propensity score matching was performed to adjust for differences in baseline characteristics. Aspirin-pretreated patients (n = 236; 35%) were older and more likely to have known coronary disease than those without pretreatment (P\u2264.01 for all). Pretreated patients had more untreated non-culprit lesions with angiographic and IVUS characteristics predictive of future events (53.1% vs 38.6%; P<.001). There were no significant differences in overall major adverse cardiac event (MACE) rates at 3 years between the aspirin and no-aspirin groups (23.6% vs 18.8%, respectively; P=.17) in unadjusted or propensity-adjusted analyses. Prior aspirin use was not an independent predictor of MACE at 3 years (hazard ratio, 1.21; 95% confidence interval, 0.73-2.01; P=.45). In the PROSPECT trial, aspirin pretreatment identifies an older population with more advanced coronary disease. Aspirin pretreatment was not an independent predictor of MACE in ACS patients treated with an early invasive strategy. The extent to which aspirin pretreatment is a risk factor for adverse events after PCI in ACS should be revisited.","subset":"pubmed_abstract"} +{"meta":{"pmid":20040134,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Synthesis of trans- and cis-4'-hydroxylomustine and development of validated analytical method for lomustine and trans- and cis-4'-hydroxylomustine in canine plasma.\nIn veterinary medicine, lomustine has been successfull used primarily for the treatment of resistant lymphoma and also for the treatment of mast cell tumors, intracranial meningioma, epitheliotropic lymphoma, and histiocytic sarcoma in dogs either alone or in combination with other chemotherapeutic agents. Even though lomustine is commonly used in dogs primarily for the treatment of resistant lymphoma, there is no pharmacokinetics information available regarding this compound in dogs. In the present study, we developed and validated a simple high-performance liquid chromatography (HPLC) method with a one-step liquid-liquid extraction procedure to detect and quantify lomustine and its two monohydroxylated metabolites (trans- and cis-4'-hydroxylomustine) in canine plasma for future pharmacokinetic studies. The HPLC-diode-array detection method reported here readily detects lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in canine plasma with a limit of detection of lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in plasma of about 10 ng\/120 microL, 5 ng\/120 microL, and 5 ng\/120 microL, respectively. The mean extraction efficiency values for lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine were 73%, 90%, and 89%, respectively, from canine plasma samples on HPLC. The present study also provides stability information about lomustine and its two monohydroxylated metabolites in canine plasma and methanol solution stored at various conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":20577365,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":8}}},"text":"Temperature dependent nonlinearity effects of a QED-200 detector in the visible.\nThe spectral response of the United Detector Technologies model QED-200 quantum efficiency detector, along with that of other photodiodes, has been measured for two different wavelengths in the visible. The QED shows a strong temperature dependent response at certain power levels. It is shown that the effect comes from an increase in internal quantum efficiency due to a supralinearity effect at power levels of ~1 mW.","subset":"pubmed_abstract"} +{"meta":{"pmid":25890302,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2022-40":1,"2022-21":2,"2021-43":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-34":1,"2020-29":1,"2020-16":1,"2020-10":1,"2019-51":1,"2019-39":1,"2023-23":1,"2024-18":1,"2024-22":1}}},"text":"Phylogenetic and syntenic data support a single horizontal transference to a Trypanosoma ancestor of a prokaryotic proline racemase implicated in parasite evasion from host defences.\nProline racemase (PRAC) enzymes of Trypanosoma cruzi (TcPRAC), the agent of Chagas disease, and Trypanosoma vivax (TvPRAC), the agent of livestock trypanosomosis, have been implicated in the B-cells polyclonal activation contributing to immunosuppression and the evasion of host defences. The similarity to prokaryotic PRAC and the absence in Trypanosoma brucei and Trypanosoma congolense have raised many questions about the origin, evolution, and functions of trypanosome PRAC (TryPRAC) enzymes. We identified TryPRAC homologs as single copy genes per haploid genome in 12 of 15 Trypanosoma species, including T. cruzi and T. cruzi marinkellei, T. dionisii, T. erneyi, T. rangeli, T. conorhini and T. lewisi, all parasites of mammals. Polymorphisms in TcPRAC genes matched T. cruzi genotypes: TcI-TcIV and Tcbat have unique genes, while the hybrids TcV and TcVI contain TcPRACA and TcPRACB from parental TcII and TcIII, respectively. PRAC homologs were identified in trypanosomes from anurans, snakes, crocodiles, lizards, and birds. Most trypanosomes have intact PRAC genes. T. rangeli possesses only pseudogenes, maybe in the process of being lost. T. brucei, T. congolense and their allied species, except the more distantly related T. vivax, have completely lost PRAC genes. The genealogy of TryPRAC homologs supports an evolutionary history congruent with the Trypanosoma phylogeny. This finding, together with the synteny of PRAC loci, the relationships with prokaryotic PRAC inferred by taxon-rich phylogenetic analysis, and the absence in trypanosomatids of any other genera or in bodonids or euglenids suggest that a common ancestor of Trypanosoma gained PRAC gene by a single and ancient horizontal gene transfer (HGT) from a Firmicutes bacterium more closely related to Gemella and other species of Bacilli than to Clostridium as previously suggested. Our broad phylogenetic study allowed investigation of TryPRAC evolution over long and short timescales. TryPRAC genes diverged to become species-specific and genotype-specific for T. cruzi and T. rangeli, with resulting genealogies congruent with those obtained using vertically inherited genes. The inventory of TryPRAC genes described here is the first step toward the understanding of the roles of PRAC enzymes in trypanosomes differing in life cycles, virulence, and infection and immune evasion strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":27189278,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.\nOur previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":12717384,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells.\nThe liver is generally considered negative for the vitamin D nuclear receptor (VDR(n)), even though several studies have shown significant effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on liver cell physiology. The low abundance of VDR(n) in the liver led us to propose that hepatocytes (the largest hepatic cell population) were most likely negative for the receptor, whereas the small hepatic sinusoidal and ductular cell populations that contain cell types known to express VDR(n) in other tissues should express the receptor. Using freshly isolated cells from normal livers as well as biliary and epithelial hepatic cell lines, our data show that the human, rat, and mouse hepatocytes express very low VDR(n) messenger RNA (mRNA) and protein levels. In contrast, sinusoidal endothelial, Kupffer, and stellate cells of normal rat livers as well as the mouse biliary cell line BDC and rat hepatic neonatal epithelial SD6 cells clearly expressed both VDR(n) mRNA and protein. In addition, specimens of human hepatocarcinoma as well as intrahepatic colon adenocarcinoma metastases were also found to express the VDR(n) gene transcript. Kupffer, stellate, and endothelial cells responded to 1,25(OH)(2)D(3) by a significant increase in the CYP24, indicating that the VDR(n) is fully functional in these cells. In conclusion, selective hepatic cell populations are targets for the vitamin D endocrine\/paracrine\/intracrine system.","subset":"pubmed_abstract"} +{"meta":{"pmid":28725309,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Cronkhite-Canada Syndrome: A Rare Cause of Chronic Diarrhea.\nCronkhite-Canada syndrome (CCS) is a rare non-hereditary disease characterized by chronic diarrhea, diffuse intestinal polyposis and onychodystrophy. We present here a case of a middle-aged female who presented with chronic intermittent bloody diarrhea associated alopecia and loss of finger and toe nails. Labs were remarkable for microcytic anemia and severe hypoalbuminemia. Endoscopy showed numerous polyps scattered throughout the colon. She was treated with nutritional support and corticosteroid with complete resolution of her symptoms and endoscopic findings. CCS is associated with high mortality and gastrointestinal malignancies. Clinicians should consider CCS in a patient with unexplained chronic diarrhea and ectodermal abnormalities.","subset":"pubmed_abstract"} +{"meta":{"pmid":23324306,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Gefitinib, but not erlotinib, is a possible inducer of Fra-1-mediated interstitial lung disease.\nGefitinib is an anticancer drug developed to inhibit the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Two structurally-related EGFR tyrosine kinase inhibitors, gefitinib (Iressa) and erlotinib (Tarceva), are used as oral chemotherapy by patients with non-small-cell lung cancer. Immediately after introduction of gefitinib to clinical practice, interstitial lung disease was identified as a life-threatening adverse effect, although this condition can be well managed. It is still unclear whether gefitinib and other EGFR inhibitors induce similar adverse effects in lung. We previously established mouse models of interstitial lung disease in which gefitinib induces expression of Fosl1 (which encodes the AP-1 transcription factor Fra-1) in the presence of exogenous or endogenous Toll-like receptor ligands, leading to abnormal cytokine and chemokine expression. Here, we compared and monitored the effects of EGFR inhibitors gefitinib, erlotinib and AG1517 (PD153035) on the mRNA expression levels of Fosl1, Tnf and Ccl2. Unexpectedly, gefitinib, but not the other tyrosine kinase inhibitors, elicited the Fosl1 expression profile proposed to be predictive of interstitial lung disease, suggesting that gefitinib-induced interstitial lung disease is an off-target effect not elicited by erlotinib.","subset":"pubmed_abstract"} +{"meta":{"pmid":24850093,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Combined effect of tissue stabilization and protein extraction methods on phosphoprotein analysis.\nPreanalytical conditions applied during sample collection and processing can affect the detection or quantification of unstable phosphoprotein biomarkers. We evaluated the consequences of tissue stabilization and protein extraction methods on phosphoprotein analysis. The effects of stabilization techniques (heat stabilization, snap-freezing) and time on the levels of phosphoproteins, including phospho-Akt, p-ERK 1\/2, p-IkB\u03b1, p-JNK, and p38 MAPK, were evaluated using a BioPlex phosphoprotein assay. Additionally, two different protein extraction protocols, using different extraction buffers (8 M urea buffer, or Bio-Rad buffer without urea) were tested. For snap-frozen samples, protein extraction yields were comparable with the two buffer systems. For heat-stabilized samples, total protein yields were significantly lower following extraction in non-urea buffer. However, the concentrations of specific phosphoproteins were significantly higher in heat-stabilized samples than in the corresponding snap-frozen samples, indicating that this tissue processing method better preserved phosphoproteins. Significant differences were found between the measured phosphoprotein levels in heat-stabilized and snap-frozen tissue, suggesting that alterations occur very rapidly after tissue excision. Our results suggest that heat stabilization can be used as a tissue processing method for subsequent phosphoprotein analyses, but also suggest that the BioPlex phosphoprotein assay could be used as a possible quality control method to assess tissue sample integrity.","subset":"pubmed_abstract"} +{"meta":{"pmid":21629784,"dup_signals":{"dup_doc_count":22,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":4,"2013-20":5,"unknown":9}}},"text":"A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer.\nProstate cancer exhibits tremendous variability in clinical behavior, ranging from indolent to lethal disease. Better prognostic markers are needed to stratify patients for appropriately aggressive therapy. By expression profiling, we can identify a proliferation signature variably expressed in prostate cancers. Here, we asked whether one or more tissue biomarkers might capture that information, and provide prognostic utility. We assayed three proliferation signature genes: MKI67 (Ki-67; also a classic proliferation biomarker), TOP2A (DNA topoisomerase II, alpha), and E2F1 (E2F transcription factor 1). Immunohistochemical staining was evaluable on 139 radical prostatectomy cases (in tissue microarray format), with a median clinical follow-up of eight years. Each of the three proliferation markers was by itself prognostic. Notably, combining the three markers together as a \"proliferation index\" (0 or 1, vs. 2 or 3 positive markers) provided superior prognostic performance (hazard ratio = 2.6 (95% CI: 1.4-4.9); P = 0.001). In a multivariate analysis that included preoperative serum prostate specific antigen (PSA) levels, Gleason grade and pathologic tumor stage, the composite proliferation index remained a significant predictor (P = 0.005). Analysis of receiver-operating characteristic (ROC) curves confirmed the improved prognostication afforded by incorporating the proliferation index (compared to the clinicopathologic data alone). Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":28989547,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-10":2,"2024-26":1,"unknown":12}}},"text":"Teaching Mindfulness to Teachers: a Systematic Review and Narrative Synthesis.\nSchool teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher. Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress. This article reviews research on one such approach: mindfulness-based interventions (MBIs) for school teachers. A systematic review and narrative synthesis were conducted for quantitative and qualitative studies that report the effects of MBIs for teachers of children aged 5-18 years on symptoms of stress and emotion regulation and self-efficacy. Twelve independent publications were identified meeting the inclusion criteria and these gave a total of 13 samples. Quality appraisal of the identified articles was carried out. The effect sizes and proportion of significant findings are reported for relevant outcomes. The quality of the literature varied, with main strengths in reporting study details, and weaknesses including sample size considerations. A range of MBIs were employed across the literature, ranging in contact hours and aims. MBIs showed strongest promise for intermediary effects on teacher emotion regulation. The results of the review are discussed in the context of a model of teacher stress. Teacher social and emotional competence has implications for pupil wellbeing through teacher-pupil relationships and effective management of the classroom. The implications for practice and research are considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":26578793,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":5,"2024-10":2,"unknown":15}}},"text":"Fat, weather, and date affect migratory songbirds' departure decisions, routes, and time it takes to cross the Gulf of Mexico.\nApproximately two thirds of migratory songbirds in eastern North America negotiate the Gulf of Mexico (GOM), where inclement weather coupled with no refueling or resting opportunities can be lethal. However, decisions made when navigating such features and their consequences remain largely unknown due to technological limitations of tracking small animals over large areas. We used automated radio telemetry to track three songbird species (Red-eyed Vireo, Swainson's Thrush, Wood Thrush) from coastal Alabama to the northern Yucatan Peninsula (YP) during fall migration. Detecting songbirds after crossing \u223c1,000 km of open water allowed us to examine intrinsic (age, wing length, fat) and extrinsic (weather, date) variables shaping departure decisions, arrival at the YP, and crossing times. Large fat reserves and low humidity, indicative of beneficial synoptic weather patterns, favored southward departure across the Gulf. Individuals detected in the YP departed with large fat reserves and later in the fall with profitable winds, and flight durations (mean = 22.4 h) were positively related to wind profit. Age was not related to departure behavior, arrival, or travel time. However, vireos negotiated the GOM differently than thrushes, including different departure decisions, lower probability of detection in the YP, and longer crossing times. Defense of winter territories by thrushes but not vireos and species-specific foraging habits may explain the divergent migratory behaviors. Fat reserves appear extremely important to departure decisions and arrival in the YP. As habitat along the GOM is degraded, birds may be limited in their ability to acquire fat to cross the Gulf.","subset":"pubmed_abstract"} +{"meta":{"pmid":15588040,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":13}}},"text":"Measurement of agreement on health-related quality of life changes in response to respiratory rehabilitation by patients and physicians--a prospective study.\nTo provide optimal care for patients with chronic obstructive pulmonary disease physicians need to understand if their patients benefit from an intervention. The objective of this study was to assess agreement between patients and physicians on health-related quality of life (HRQL) changes in response to respiratory rehabilitation and to explore sources for disagreement. Sixty-one patients rated their health states on a validated preference-based instrument, the feeling thermometer (FT). In an analogous manner, the eight treating physicians rated the patients' health states on the FT. Patients and physicians were blinded to each other's ratings. We calculated intraclass correlation coefficients (ICC) to assess agreement between patients and physicians and used HRQL instruments and the 6-min walking test to assess the evaluative properties of the FT. We found moderate agreement at baseline (ICC 0.40, P = 0.018) and follow-up (ICC 0.49, P = 0.008) but large disagreement about change scores (ICC 0.02, P = 0.46). Patients' FTchange scores correlated well with change scores of the Chronic Respiratory Questionnaire, SF-36 and the Borg scale for dyspnoea whereas physicians' FT change scores correlated significantly with the change score of the 6- min walking test (r = 0.33). Physicians' ratings showed an inconsistent pattern for correlations with HRQL measures. There is large disagreement between patients and physicians on HRQL changes in response to respiratory rehabilitation. Investigators should assess whether the introduction of HRQL instruments into clinical practice raises the awareness of physicians towards HRQL and improves agreement with their patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":36451712,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":7,"unknown":7}}},"text":"Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.\nThe Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":9354475,"dup_signals":{"dup_doc_count":11}},"text":"Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation.\nEfficient T cell activation requires the engagement of a variety of ligand\/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)\/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activation. The present study dissects the roles of LFA-1 and CD28 in the activation of naive virus-specific CD8+ T cells. We demonstrate that LFA-1 facilitates T cell activation by lowering the amounts of antigen necessary for T cell activation. In the absence of LFA-1, 100-fold more antigen was required for T cell-antigen-presenting cell (APC) conjugation and all subsequent events of T cell activation, including TCR down-regulation, Ca2+-flux, T cell proliferation, and lytic effector cell induction. Thus, LFA-1 facilitates the functional triggering of TCRs by promoting adhesion of T cells to APCs but does not affect T cell activation otherwise. In contrast, CD28 played an entirely different role during T cell activation. CD28 reduced the number of TCRs that had to be triggered for T cell activation and allowed activation of T cells by low affinity ligands. CD28 but not LFA-1 prevented induction of T cell unresponsiveness after stimulation of TCRs. These results demonstrate that LFA-1 and CD28 exhibit distinct, nonoverlapping ways to influence T cell activation and suggest that the terms costimulation and signal 2 should be revisited.","subset":"pubmed_abstract"} +{"meta":{"pmid":11993182,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":8}}},"text":"Enteric lipopolysaccharide raises plasma IL-6 levels in the hepatoportal vein during non-inflammatory stress in the rat.\nIt has long been known that plasma interleukin (IL)-6 levels elevate during non-inflammatory, physico\/psychological stresses such as immobilization (IMB) and electric foot shock (FS). We previously demonstrated that an IMB-induced rise in plasma IL-6 in the rat was caused, at least partly, by an increased production of IL-6 in hepatic reticulo-endothelial cells which were induced by enteric flora-derived lipopolysccharide (LPS). This study investigated whether such enteric flora-derived LPS may produce IL-6 also in the mesentery and the mesenteric lymphoid nodes (MLN) before it reaches the liver. We found a rise in the IL-6 levels in the hepatoportal vein (PV) within 30 min during FS, while the IL-6 levels in the jugular vein showed a smaller and delayed rise with slower recovery. Plasma IL-6 levels near the exit of the hepatic vein in the inferior vena cava was highest at both control and stressed conditions, compared with those in the PV and any other extra-hepatic circulation. The stress-induced IL-6 elevation in the PV was abolished by an in vivo neutralization of LPS with continuous infusion of polymyxin B. Furthermore, the amount of LPS as assessed by its bioactivity increased rapidly in the mesentery, the MLN and the liver within 15 min after the initiation of FS. Finally, fluorescent dye-labeled LPS infused into the lumen of the ileum was found in the extra-intestinal tissues and systemic vein, and FS increased the optical density in them. The findings suggest that lymphoid tissues in the gut associated lymphoid organs are continuously exposed to LPS at the basal condition, and that FS facilitates the LPS\/bacterial translocation across the intestinal wall and thereby increases the production of IL-6 before LPS reaches the liver.","subset":"pubmed_abstract"} +{"meta":{"pmid":10368805,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support.\nHistorically, large doses of proteolytic enzymes, along with diet, nutritional supplements, and \"detoxification\" procedures, have been used in alternative therapies to treat all forms of cancer, without formal clinical studies to support their use. A 2-year, unblinded, 1-treatment arm, 10-patient, pilot prospective case study was used to assess survival in patients suffering inoperable stage II-IV pancreatic adenocarcinoma treated with large doses of orally ingested pancreatic enzymes, nutritional supplements, \"detoxification\" procedures, and an organic diet. From January 1993 to April 1996 in the authors' private practice, 10 patients with inoperable, biopsy-proven pancreatic adenocarcinoma were entered into the trial. After one patient dropped out, an 11th patient was added to the study (however, all 11 are considered in the data tabulation). Patients followed the treatment at home, under the supervision of the authors. As of 12 January 1999, of 11 patients entered into the study, 9 (81%) survived one year, 5 (45%) survived two years, and at this time, 4 have survived three years. Two patients are alive and doing well: one at three years and the other at four years. These results are far above the 25% survival at one year and 10% survival at two years for all stages of pancreatic adenocarcinoma reported in the National Cancer Data Base from 1995. This pilot study suggests that an aggressive nutritional therapy with large doses of pancreatic enzymes led to significantly increased survival over what would normally be expected for patients with inoperable pancreatic adenocarcinoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":11442229,"dup_signals":{"dup_doc_count":25,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2020-10":1,"2019-43":1,"2019-39":1,"2019-35":2,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-04":1,"2020-34":1,"2017-13":1}}},"text":"Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.\nThis report updates and consolidates all previous U.S. Public Health Service recommendations for the management of health-care personnel (HCP) who have occupational exposure to blood and other body fluids that might contain hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Recommendations for HBV postexposure management include initiation of the hepatitis B vaccine series to any susceptible, unvaccinated person who sustains an occupational blood or body fluid exposure. Postexposure prophylaxis (PEP) with hepatitis B immune globulin (HBIG) and\/or hepatitis B vaccine series should be considered for occupational exposures after evaluation of the hepatitis B surface antigen status of the source and the vaccination and vaccine-response status of the exposed person. Guidance is provided to clinicians and exposed HCP for selecting the appropriate HBV PEP. Immune globulin and antiviral agents (e.g., interferon with or without ribavirin) are not recommended for PEP of hepatitis C. For HCV postexposure management, the HCV status of the source and the exposed person should be determined, and for HCP exposed to an HCV positive source, follow-up HCV testing should be performed to determine if infection develops. Recommendations for HIV PEP include a basic 4-week regimen of two drugs (zidovudine [ZDV] and lamivudine [3TC]; 3TC and stavudine [d4T]; or didanosine [ddI] and d4T) for most HIV exposures and an expanded regimen that includes the addition of a third drug for HIV exposures that pose an increased risk for transmission. When the source person's virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source person's virus is unlikely to be resistant is recommended. In addition, this report outlines several special circumstances (e.g., delayed exposure report, unknown source person, pregnancy in the exposed person, resistance of the source virus to antiretroviral agents, or toxicity of the PEP regimen) when consultation with local experts and\/or the National Clinicians' Post-Exposure Prophylaxis Hotline ([PEPline] 1-888-448-4911) is advised. Occupational exposures should be considered urgent medical concerns to ensure timely postexposure management and administration of HBIG, hepatitis B vaccine, and\/or HIV PEP.","subset":"pubmed_abstract"} +{"meta":{"pmid":23434567,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A phase 1b clinical trial evaluating sifalimumab, an anti-IFN-\u03b1 monoclonal antibody, shows target neutralisation of a type I IFN signature in blood of dermatomyositis and polymyositis patients.\nTo assess the pharmacodynamic effects of sifalimumab, an investigational anti-IFN-\u03b1 monoclonal antibody, in the blood and muscle of adult dermatomyositis and polymyositis patients by measuring neutralisation of a type I IFN gene signature (IFNGS) following drug exposure. A phase 1b randomised, double-blinded, placebo controlled, dose-escalation, multicentre clinical trial was conducted to evaluate sifalimumab in dermatomyositis or polymyositis patients. Blood and muscle biopsies were procured before and after sifalimumab administration. Selected proteins were measured in patient serum with a multiplex assay, in the muscle using immunohistochemistry, and transcripts were profiled with microarray and quantitative reverse transcriptase PCR assays. A 13-gene IFNGS was used to measure the pharmacological effect of sifalimumab. The IFNGS was suppressed by a median of 53-66% across three time points (days 28, 56 and 98) in blood (p=0.019) and 47% at day 98 in muscle specimens post-sifalimumab administration. Both IFN-inducible transcripts and proteins were prevalently suppressed following sifalimumab administration. Patients with 15% or greater improvement from baseline manual muscle testing scores showed greater neutralisation of the IFNGS than patients with less than 15% improvement in both blood and muscle. Pathway\/functional analysis of transcripts suppressed by sifalimumab showed that leucocyte infiltration, antigen presentation and immunoglobulin categories were most suppressed by sifalimumab and highly correlated with IFNGS neutralisation in muscle. Sifalimumab suppressed the IFNGS in blood and muscle tissue in myositis patients, consistent with this molecule's mechanism of action with a positive correlative trend between target neutralisation and clinical improvement. These observations will require confirmation in a larger trial powered to evaluate efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":24841937,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":10}}},"text":"Quantum mechanical fragment methods based on partitioning atoms or partitioning coordinates.\nConspectus The development of more efficient and more accurate ways to represent reactive potential energy surfaces is a requirement for extending the simulation of large systems to more complex systems, longer-time dynamical processes, and more complete statistical mechanical sampling. One way to treat large systems is by direct dynamics fragment methods. Another way is by fitting system-specific analytic potential energy functions with methods adapted to large systems. Here we consider both approaches. First we consider three fragment methods that allow a given monomer to appear in more than one fragment. The first two approaches are the electrostatically embedded many-body (EE-MB) expansion and the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), which we have shown to yield quite accurate results even when one restricts the calculations to include only electrostatically embedded dimers. The third fragment method is the electrostatically embedded molecular tailoring approach (EE-MTA), which is more flexible than EE-MB and EE-MB-CE. We show that electrostatic embedding greatly improves the accuracy of these approaches compared with the original unembedded approaches. Quantum mechanical fragment methods share with combined quantum mechanical\/molecular mechanical (QM\/MM) methods the need to treat a quantum mechanical fragment in the presence of the rest of the system, which is especially challenging for those parts of the rest of the system that are close to the boundary of the quantum mechanical fragment. This is a delicate matter even for fragments that are not covalently bonded to the rest of the system, but it becomes even more difficult when the boundary of the quantum mechanical fragment cuts a bond. We have developed a suite of methods for more realistically treating interactions across such boundaries. These methods include redistributing and balancing the external partial atomic charges and the use of tuned fluorine atoms for capping dangling bonds, and we have shown that they can greatly improve the accuracy. Finally we present a new approach that goes beyond QM\/MM by combining the convenience of molecular mechanics with the accuracy of fitting a potential function to electronic structure calculations on a specific system. To make the latter practical for systems with a large number of degrees of freedom, we developed a method to interpolate between local internal-coordinate fits to the potential energy. A key issue for the application to large systems is that rather than assigning the atoms or monomers to fragments, we assign the internal coordinates to reaction, secondary, and tertiary sets. Thus, we make a partition in coordinate space rather than atom space. Fits to the local dependence of the potential energy on tertiary coordinates are arrayed along a preselected reaction coordinate at a sequence of geometries called anchor points; the potential energy function is called an anchor points reactive potential. Electrostatically embedded fragment methods and the anchor points reactive potential, because they are based on treating an entire system by quantum mechanical electronic structure methods but are affordable for large and complex systems, have the potential to open new areas for accurate simulations where combined QM\/MM methods are inadequate.","subset":"pubmed_abstract"} +{"meta":{"pmid":8531072,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Relative vulnerability of dopamine and GABA neurons in mesencephalic culture to inhibition of succinate dehydrogenase by malonate and 3-nitropropionic acid and protection by NMDA receptor blockade.\nThe effects of different severities of metabolic stress on dopamine (DA) and gamma-aminobutyric acid (GABA) cell loss were examined in rat mesencephalic culture. Partial metabolic inhibition was induced in 12-day-old cultures by a 24-hr treatment with various concentrations of 3-nitropropionic acid(3-NPA, 0.1-0.5 mM) or malonate (10-50 mM), irreversible and reversible inhibitors of the Krebs cycle enzyme, succinate dehydrogenase. Cell damage to the DA and GABA populations was assessed after a 48-hr recovery period by simultaneous measurement of high affinity uptake for 3H-DA and 14C-GABA. 3-NPA or malonate caused a dose-dependent loss of DA uptake (EC50 0.21 or 42 mM, respectively). 3-NPA treatment was equally detrimental to the GABA population, whereas malonate exposure did not cause any significant loss of GABA uptake. The presence of the NMDA antagonist, MK-801 (1 microM), during 24 hr of 3-NPA or malonate treatment fully protected against DA and GABA loss with 50 mM malonate or 0.25 mM 3-NPA and partially protected versus 0.5 mM 3-NPA. To determine the degree of metabolic stress imposed by 3-NPA and malonate, 12-day-old cultures were treated with 0.5 mM 3-NPA or 50 mM malonate for 3 hr and the rate of lactate formation was measured. lactate was increased nearly 2-fold at 3 hr of treatment with 3-NPA, but was not significantly elevated above basal with malonate treatment. SDH activity was decreased by 48 or 58% after 3 hr of treatment with 0.25 and 0.5 mM 3-NPA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":22353955,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Hemoglobin A1c and postpartum abnormal glucose tolerance among women with gestational diabetes mellitus.\nTo analyze the association of hemoglobin A1c (HbA1c) at gestational diabetes mellitus (GDM) diagnosis with postpartum abnormal glucose in a cohort of women with GDM. Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy program located in Charlotte, North Carolina, who completed a postpartum 2-hour oral glucose tolerance test were eligible for inclusion in this retrospective cohort study. Clinical information, including maternal HbA1c at diagnosis, was abstracted from medical records. A parametric survival model was used to assess the association of HbA1c at GDM diagnosis with postpartum maternal abnormal glucose including impaired fasting glucose, impaired glucose tolerance, and any postpartum abnormal glucose. Of the 277 postpartum women with GDM, 75 (32%) had impaired fasting glucose, 61 (28%) had impaired glucose tolerance, and 15 (9%) were diagnosed with type 2 diabetes mellitus after delivery. After adjustment for clinic, maternal age, parity, prepregnancy body mass index 25 or higher, nonwhite race or ethnicity, and gestational week at first HbA1c, we detected a trend of increased risk for impaired fasting glucose (P=.01), impaired glucose tolerance (P=.002), and any glucose abnormality (P<.001) associated with increased quartile of HbA1c at GDM diagnosis. Hemoglobin A1c measured at GDM diagnosis may be a useful tool for identifying patients with GDM at highest risk of developing postpartum abnormal glucose.","subset":"pubmed_abstract"} +{"meta":{"pmid":6857250,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Nuclear transplantation in the mouse embryo by microsurgery and cell fusion.\nNuclear transplantation in the mouse embryo was achieved by using a method that combines microsurgical removal of the zygote pronuclei with the introduction of a donor nucleus by a virus-mediated cell fusion technique. Survival of embryos was greater than 90 per cent in tests of this procedure. The embryos developed to term at a frequency not significantly different from that of nonmanipulated control embryos. Because nuclei and cytoplasm from genetically distinct inbred mouse strains can be efficiently interchanged, this procedure may be useful in characterizing possible cytoplasmic contributions to the embryonic and adult phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":21357237,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":1,"2013-20":1,"2017-13":1,"unknown":14}}},"text":"Natural pedagogy as evolutionary adaptation.\nWe propose that the cognitive mechanisms that enable the transmission of cultural knowledge by communication between individuals constitute a system of 'natural pedagogy' in humans, and represent an evolutionary adaptation along the hominin lineage. We discuss three kinds of arguments that support this hypothesis. First, natural pedagogy is likely to be human-specific: while social learning and communication are both widespread in non-human animals, we know of no example of social learning by communication in any other species apart from humans. Second, natural pedagogy is universal: despite the huge variability in child-rearing practices, all human cultures rely on communication to transmit to novices a variety of different types of cultural knowledge, including information about artefact kinds, conventional behaviours, arbitrary referential symbols, cognitively opaque skills and know-how embedded in means-end actions. Third, the data available on early hominin technological culture are more compatible with the assumption that natural pedagogy was an independently selected adaptive cognitive system than considering it as a by-product of some other human-specific adaptation, such as language. By providing a qualitatively new type of social learning mechanism, natural pedagogy is not only the product but also one of the sources of the rich cultural heritage of our species.","subset":"pubmed_abstract"} +{"meta":{"pmid":34981785,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Moving toward genome-editing therapies for cardiovascular diseases.\nThe rapid invention of genome-editing technologies over the past decade, which has already been transformative for biomedical research, has raised the tantalizing prospect of an entirely new therapeutic modality. Whereas the treatment of chronic cardiovascular diseases has heretofore entailed the use of chronic therapies that typically must be taken repeatedly and frequently for the remainder of the lifetime, genome editing will enable the development of \"one-and-done\" therapies with durable effects. This Review summarizes the variety of available genome-editing approaches, including nuclease editing, base editing, epigenome editing, and prime editing; illustrates how these various approaches could be implemented as novel therapies for cardiovascular diseases; and outlines a path from technology development to preclinical studies to clinical trials. Although this Review focuses on PCSK9 as an instructive example of the various genome-editing approaches under active investigation, the lessons learned will be broadly applicable to the treatment of a variety of diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":8314837,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy.\nThe nuclear pore complex spans the nuclear envelope and functions as a macromolecular transporter in the ATP-dependent process of nucleocytoplasmic transport. In this report, we present three dimensional (3D) structures for both membrane-associated and detergent-extracted Xenopus NPCs, imaged in frozen buffers by cryo-electron microscopy. A comparison of the differing configurations present in the 3D maps suggests that the spokes may possess an intrinsic conformational flexibility. When combined with recent data from a 3D map of negatively stained NPCs (Hinshaw, J. E., B. O. Carragher, and R. A. Milligan. 1992. Cell. 69:1133-1141), these observations suggest a minimal domain model for the spoke-ring complex which may account for the observed plasticity of this assembly. Moreover, lumenal domains in adjacent spokes are interconnected by radial arm dimers, forming a lumenal ring that may be responsible for anchoring the NPC within the nuclear envelope pore. Importantly, the NPC transporter is visualized as a centrally tapered cylinder that spans the entire width of the NPC, in a direction normal to the nuclear envelope. The central positioning, tripartite structure, and hollow nature of the transporter suggests that it may form a macromolecular transport channel, with a globular gating domain at each end. Finally, the packing of the transporter within the spokes creates a set of eight internal channels that may be responsible, in part, for the diffusion of ions and small molecules across the nuclear envelope.","subset":"pubmed_abstract"} +{"meta":{"pmid":32099910,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Partial silencing of fucosyltransferase 8 gene expression inhibits proliferation of Ishikawa cells, a cell line of endometrial cancer.\nEndometrial cancer is the most common gynecologic malignancy and is associated with increased morbidity each year, including young people. However, its mechanisms of proliferation and progression are not fully elucidated. It is well known that abnormal glycosylation is involved in oncogenesis, and fucosylation is one of the most important types of glycosylation. In particular, fucosyltransferase 8 (FUT8) is the only FUT responsible for \u03b11, 6-linked fucosylation (core fucosylation), and it is involved in various physiological as well as pathophysiological processes, including cancer biology. Therefore, we aimed to identify the expression of FUT8 in endometrial endometrioid carcinoma and investigate the effect of the partial silencing of the FUT8 gene on the cell proliferation of Ishikawa cells, an epithelial-like endometrial cancer cell line. Quantitative real-time PCR analysis showed that FUT8 gene expression was significantly elevated in the endometrial endometrioid carcinoma, compared to the normal endometrium. The immunostaining of FUT8 and Ulex europaeus Agglutinin 1 (UEA-1), a kind of lectin family specifically binding to fucose, was detected endometrial endometrioid carcinoma. The proliferation assay showed FUT8 partial knockdown by transfection of siRNA significantly suppressed the proliferation of Ishikawa cells, concomitant with the upregulation in the gene expressions associated with the interesting pathways associated with de-ubiquitination, aspirin trigger, mesenchymal-epithelial transition (MET) et al. It was suggested that the core fucosylation brought about by FUT8 might be involved in the proliferation of endometrial endometrioid carcinoma cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":8585095,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"(Evaluation of neutralizing ability of four commercially available antivenoms against the venom of Bothrops asper from Costa Rica)\nWe studied the ability of four commercially available antivenoms to neutralize several toxic and enzymatic activities of Bothrops asper (terciopelo) venom from Costa Rica. Experiments with preincubation of venom and antivenom were carried out to test the neutralization of lethal, hemorrhagic, coagulant and indirect hemolytic activities. In addition, antibody titers against crude venom and myotoxin II purified from this venom were determined by enzyme immunoassay (ELISA). Results indicate that polyvalent antivenom from Instituto Clodomiro Picado (Costa Rica) has the highest neutralizing ability against lethal, coagulant and indirect hemolytic activities, whereas MYN polyvalent antivenom (M\u00e9xico) has the highest neutralization against hemorrhagic activity. Antivenom from Instituto Clodomiro Picado also has the highest antibody titers against crude B. asper venom and against myotoxin II. Antivenoms from Universidad Central de Venezuela (Venezuela), Vencofarma (Brazil) and MYN (M\u00e9xico) failed to neutralize the lethal effect of this venom. These results stress the need for rigorous quality control systems to evaluate the neutralizing ability of antivenoms in Central America.","subset":"pubmed_abstract"} +{"meta":{"pmid":31071591,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"Rare earth elements (REY) sorption on soils of contrasting mineralogy and texture.\nRare earth elements (REY) are the lanthanide elements (Z = 57-71), which have an ever-growing occurrence in present-day industries, agriculture, and modern life. Consequently, environmental concentrations are expected to increase accordingly as a result of intensified utilization. Soils are an important sink for REY, yet little research has been conducted concerning activity, inputs, and lability in soil systems. This study evaluated the REY (lanthanides + yttrium) sorption and partition coefficients (Kd) in two broadly representative natural soils (A horizon), with contrasting mineralogy and organic character, formed under distinct environmental conditions: an Oxisol from Brazil and a Mollisol from the USA. Batch reactions of soils suspended in a background electrolyte solution of 5 \u03bcmoles kg-1 of Ca(NO3)2 at 1:100 solid to solution were reacted with 80 \u03bcmoles kg-1 REY added individually and in multi-REY competitive systems to evaluated adsorption after 3 h and 72 h over a wide pH range (from ca. 2 to 8). Results showed sorption was similar for all REY within each soil type when examined at the natural measured soil pH; Mollisol pH 6.85, Oxisol pH 4.35. However, REY sorption (by Kd) was nearly two-fold greater in the Mollisol compared to the Oxisol for the single REY experiments. Multi-REY competitive sorption reactions showed a decrease in Kd for both soils at 3 and 72 h, and to a greater extent for the Mollisol, indicating soil type had a strong effect on the sorption affinity of each REY. It was also observed that REY sorption increased from low to high pH (pH 2-8) in the Oxisol, and increased with pH from 2 up to the point zero charge (PZC) in the Mollisol, then stabilized. The varying REY Kd values from these two distinct and abundant soils, with and without REY competition, and over a range of pH are explained in terms of soil mineralogy (i.e., 2:1 clays in the Mollisol; oxides in the Oxisol) and organic matter content. Our findings show that soil characteristic controls sorption, precipitation, and cation exchange capacity, which are the key mechanisms for predicting REY fate and transport in the environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":18273371,"dup_signals":{"dup_doc_count":31,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":4,"2016-30":3,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":2,"2015-40":2,"2015-35":1,"2015-32":4,"2015-27":1,"2015-22":3,"2015-18":2}}},"text":"Design of efficient lens ducts.\nLens ducts have the potential to couple the output from a laser diode array efficiently into the gain medium of a solid-state laser in an end-pumped configuration. Using a ray-tracing method we investigate different design approaches of lens ducts and demonstrate the possibility to obtain an output beam with a symmetric profile that is insensitive to the small displacement from the output surface of a lens duct.","subset":"pubmed_abstract"} +{"meta":{"pmid":19690906,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2021-31":1,"2019-09":1,"2018-34":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-39":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-49":1,"2017-13":1}}},"text":"Adaptive metabolic changes in CADASIL white matter.\nCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using (1)H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. (1)H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T (E) = 288 ms) and non-accelerated medium-resolution MRSI (T (E) = 35 ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre\/Cho, Glx\/Cho and Glx\/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx\/Cre and mI\/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx\/Cre and mI\/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":12187767,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"[Fundamental and applied studies on transport and metabolism of electrolytes and glucose--aim to contact with molecular biology].\nThe authors' research focuses on polyuria, natriuresis, glucosuria, glycemia, and renal calcification in occupational lead poisoning and endemic fluorosis. Changes in electrolyte mobilization and in glucose metabolism and transport following the administration of lead compounds or fluoride were examined to elucidate these mechanisms. The results suggest fundamental approaches to the mechanism of aging and life style diseases. Our results show that: 1) Natriuresis and polyuria in lead poisoning and fluorosis are due to a decrease in renal Na\/K-ATPase activity; 2) Renal calcification in fluorosis is due to stimulation of parathyroid function and activation of the renal phosphatidylinositol cascade; 3) Glycemia in fluorosis is due to elevation of renal and hepatic glucose-6-phosphatase activities; 4) Glusosuria in fluorosis is due to decreased renal Na\/K-ATPase activity (but fluoride administered directly did not damage the renal Na\/glucose cotransporter (SGLT); 5) Renal calcification in fluorosis is due to stimulation of parathyroid function; and 6) The decrease in renal Na\/K-ATPase and SGLT activities with aging and hypertension is due to a decrease in phosphorylation activity by protein kinase C (PKC) etc. (decrease in PKC productivity with aging and hypertension).","subset":"pubmed_abstract"} +{"meta":{"pmid":10480643,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2015-18":1,"unknown":14}}},"text":"Antibody responses after Sendai virus infection and their role in upper and lower respiratory tract disease in rats.\nSendai virus infection in rats is an excellent model for studying development and role of host defenses throughout the respiratory tract after this infection. Therefore, development of serum antibody responses and disease were studied. Forty-two anesthetized pathogen-free 3- to 4- week-old LEW\/NCr rats were inoculated intranasally with Sendai virus. At postinoculation days 0, 2, 3, 5, 8, 10, and 14, rats were euthanized by administration of a pentobarbital sodium overdose followed by exsanguination. Serum was obtained from all animals, and nasal wash and bronchoalveolar lavage specimens were collected during selected experiments. An ELISPOT assay was used to measure numbers of Sendai virus-specific antibody-forming cells in respiratory tract lymphoid tissue. Recovery from disease and clearance of virus from respiratory tract tissues coincided with development of serum antibody responses. Upper respiratory tract lymph nodes were the initial and major sites of appearance of antibody-forming cells. Immunoglobulin G was the predominant subtype of these cells during recovery from the infection and in rats resistant to infection. Passive transfer of antisera or specific IgG protected the lower but not the upper respiratory tract. Circulating components of immunity have a major role in resistance and recovery from disease in the lower respiratory tract, whereas local responses are likely involved in protection of the upper respiratory tract. Local lymphoid tissues are the major production sites of IgG, which contributes to resistance to and recovery from respiratory tract diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":26975031,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2019-39":1,"2019-26":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2021-17":1}}},"text":"Prevalence of Age-Related Cataract and Cataract Surgery in a Chinese Adult Population: The Taizhou Eye Study.\nTo study the prevalence of age-related cataract (ARC), cataract surgery, and visual outcomes in a Chinese adult population in Taizhou, China. A population-based, cross-sectional study was conducted using a random cluster sampling method. We evaluated 10,234 eligible subjects 45 years or older (response rate 78.1%) in the Taizhou Eye Study. We conducted a detailed eye examination in all participants, including presenting visual acuity (PVA), best-corrected visual acuity (BCVA), slit-lamp assessment of lens opacities using the Lens Opacities Classification System III (LOCS III), and fundus examination. The standardized prevalences of cortical, nuclear, and posterior subcapsular cataract (PSC) were 28.6%, 24.3%, and 4.4%, respectively, and combined nuclear and cortical cataract was the most common cataract type (40.0%). According to the US visual impairment (VI) criteria and World Health Organization VI criteria, 40.6% and 21.8% of PSC participants had binocular VI, respectively; these values were higher than the VI rates in cortical and nuclear cataract (all P < 0.001). Of 148 patients (3.5%) who had cataract surgeries, 41.2% had PVA <20\/63, and 19.6% had PVA <20\/200. The main causes of poor visual outcome after cataract surgery were ocular comorbidities (41.3%), uncorrected refractive error (30.0%), surgical complications (15.0%), and posterior capsular opacification (PCO; 13.7%). The high prevalence of cataract and high rate of VI from ARC in the adult Chinese population remains a severe public health problem. Cataract surgery remains insufficient in mainland China and poor visual outcomes were frequent. Surgical complications and PCO were important avoidable causes that attributed to poor visual outcomes after cataract surgeries.","subset":"pubmed_abstract"} +{"meta":{"pmid":886698,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"[Effect of hyperbaric oxygenation on the circulatory function in rheumatic mitral valve disease].\nThe effect of a hyperbaric oxygenation course (10-14 exposures, one exposure daily at 0.7-1.0 ATA) upon the circulation function was studied in 61 patients with rheumatic mitral valve disease combined with systemic circulation insufficiency. The obtained results (reduction of the heart volume, acceleration of the blood stream within the heart and the body, increase of the stroke index, of the blood flow in the muscles of the extremities, reduction of the arterial and central venous pressure) demonstrate that the contractility of the myocardium and redistribution of the cardiac output between separate vascular regions is improved under the effect of hyperbaric oxygenation. The authors suggest that the increase of contractility in the right or left heart predominantly depends on the prevalence of mitral stenosis or circulatory insufficiency.","subset":"pubmed_abstract"} +{"meta":{"pmid":29213939,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Cost-of-illness study in a retrospective cohort of patients with dementia in Lima, Peru.\nDementia is a major cause of dependency and disability among older persons, and imposes huge economic burdens. Only a few cost-of-illness studies for dementia have been carried out in middle and low-income countries. The aim of this study was to analyze costs of dementia in demented patients of a private clinic in Lima, Peru. We performed a retrospective, cohort, 3-month study by extracting information from medical records of demented patients to assess the use of both healthcare and non-healthcare resources. The total costs of the disease were broken down into direct (medical and social care costs) and indirect costs (informal care costs). In 136 outpatients, we observed that while half of non-demented patients had total care costs of less than US$ 23 over three months, demented patients had costs of US$ 1500 or over (and more than US$ 1860 for frontotemporal dementia). In our study, the monthly cost of a demented patient (US$ 570) was 2.5 times higher than the minimum wage (legal minimum monthly wage in Peru for 2011: US$ 222.22). Dementia constitutes a socioeconomic problem even in developing countries, since patients involve high healthcare and non-healthcare costs, with the costs being especially high for the patient's family.","subset":"pubmed_abstract"} +{"meta":{"pmid":23429198,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State.\nCadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to different respiratory diseases and toxic effects, among which alterations of the physiological redox state in individuals exposed to the metal have been described. Host-cell redox changes characteristic of oxidative stress facilitate the progression of viral infection through different mechanisms. In this paper, we have demonstrated that pre-treatment with CdCl(2) of MDCK cells increased influenza virus replication in a dose-dependent manner. This phenomenon was related to increased viral protein expression (about 40% compared with untreated cells). The concentration of CdCl(2), able to raise the virus titer, also induced oxidative stress. The addition of two antioxidants, a glutathione (GSH) derivative or the GSH precursor, N-acetyl-L-cysteine, to Cd pre-treated and infected cells restored the intracellular redox state and significantly inhibited viral replication. In conclusion, our data demonstrate that Cd-induced oxidative stress directly increases the ability of influenza virus to replicate in the host-cell, thus suggesting that exposure to heavy metals, such as this, could be a risk factor for individuals exposed to a greater extent to the contaminant, resulting in increased severity of virus-induced respiratory diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":16776899,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":3,"2021-31":1,"2021-21":2,"2021-17":1,"2020-50":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2021-49":1,"2017-13":1}}},"text":"Healthy Weigh (El camino saludable) phase 1: a retrospective critical examination of program evaluation.\nHealthy Weigh (El camino saludable) is an obesity prevention program for low-income, predominantly Hispanic and African American families in an urban community in Tarrant County, Texas. Healthy Weigh Phase 1 was a successful community-campus partnership that took place in summer (June-August) and fall (September-November) 2003. The program met stated objectives and extensively engaged students from several health disciplines in service learning. This article describes what we learned about the evaluation of the program by examining the phase 1 evaluation process. Family environments are important intervention settings for establishing life-long dietary practices. Available in English and Spanish, Healthy Weigh Phase 1 helped families that were at risk for overweight and obesity to adopt healthy eating, physical activity, and weight management patterns. Analysis of a program logic model and formative evaluation data identified evaluation questions that could have improved the phase 1 evaluation process. Questions were categorized according to Donabedian's structure-process-outcome framework, and potential benefits of each question were identified. The Centers for Disease Control and Prevention's Framework for Program Evaluation in Public Health standards were used to judge the overall quality of the phase 1 evaluation process. The phase 1 evaluation process successfully assessed the program's effects and generally met evaluation standards. Our critical examination also highlighted structure and process evaluation issues with potential for strengthening future interventions, community partnerships, and program outcomes. Lessons learned influenced the phase 2 grant activities. Most importantly, we learned that involvement of program participants as full partners in program design, evaluation, and implementation is essential. Our understanding and practice of program evaluation evolved as Healthy Weigh became a true community-based participatory research endeavor.","subset":"pubmed_abstract"} +{"meta":{"pmid":31500596,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2023-06":2,"2021-25":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-05":1,"2019-47":1,"2023-50":1,"2024-10":2,"2024-30":1}}},"text":"Assessing the micro-scale environment using Google Street View: the Virtual Systematic Tool for Evaluating Pedestrian Streetscapes (Virtual-STEPS).\nAltering micro-scale features of neighborhood walkability (e.g., benches, sidewalks, and cues of social disorganization or crime) could be a relatively cost-effective method of creating environments that are conducive to active living. Traditionally, measuring the micro-scale environment has required researchers to perform observational audits. Technological advances have led to the development of virtual audits as alternatives to observational field audits with the enviable properties of cost-efficiency from elimination of travel time and increased safety for auditors. This study examined the reliability of the Virtual Systematic Tool for Evaluating Pedestrian Streetscapes (Virtual-STEPS), a Google Street View-based auditing tool specifically designed to remotely assess micro-scale characteristics of the built environment. We created Virtual-STEPS, a tool with 40 items categorized into 6 domains (pedestrian infrastructure, traffic calming and streets, building characteristics, bicycling infrastructure, transit, and aesthetics). Items were selected based on their past abilities to predict active living and on their feasibility for a virtual auditing tool. Two raters performed virtual and field audits of street segments in Montreal neighborhoods stratified by the Walkscore that was used to determine the 'walking-friendliness' of a neighborhood. The reliability between virtual and field audits (n = 40), as well as inter-rater reliability (n = 60) were assessed using percent agreement, Cohen's Kappa statistic, and the Intra-class Correlation Coefficient. Virtual audits and field audits (excluding travel time) took similar amounts of time to perform (9.8 versus 8.2 min). Percentage agreement between virtual and field audits, and for inter-rater agreement was 80% or more for the majority of items included in the Virtual-STEPS tool. There was high reliability between virtual and field audits with Kappa and ICC statistics indicating that 20 out of 40 (50.0%) items had almost perfect agreement and 13 (32.5%) items had substantial agreement. Inter-rater reliability was also high with 17 items (42.5%) with almost perfect agreement and 11 (27.5%) items with substantial agreement. Virtual-STEPS is a reliable tool. Tools that measure the micro-scale environment are important because changing this environment could be a relatively cost-effective method of creating environments that are conducive to active living.","subset":"pubmed_abstract"} +{"meta":{"pmid":30686771,"dup_signals":{"dup_doc_count":60,"dup_dump_count":21,"dup_details":{"curated_sources":1,"2023-06":1,"2022-33":3,"2022-27":2,"2022-21":2,"2022-05":1,"2021-49":3,"2021-43":2,"2021-39":8,"2021-04":2,"2020-50":2,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":1,"2020-05":7,"2019-47":7,"2019-43":6,"2019-39":1,"2019-30":5,"2019-22":2,"2023-14":1}}},"text":"The translational regulator FMRP controls lipid and glucose metabolism in mice and humans.\nThe Fragile X Mental Retardation Protein (FMRP) is a widely expressed RNA-binding protein involved in translation regulation. Since the absence of FMRP leads to Fragile X Syndrome (FXS) and autism, FMRP has been extensively studied in brain. The functions of FMRP in peripheral organs and on metabolic homeostasis remain elusive; therefore, we sought to investigate the systemic consequences of its absence. Using metabolomics, in vivo metabolic phenotyping of the Fmr1-KO FXS mouse model and in vitro approaches, we show that the absence of FMRP induced a metabolic shift towards enhanced glucose tolerance and insulin sensitivity, reduced adiposity, and increased \u03b2-adrenergic-driven lipolysis and lipid utilization. Combining proteomics and cellular assays, we highlight that FMRP loss increased hepatic protein synthesis and impacted pathways notably linked to lipid metabolism. Mapping metabolomic and proteomic phenotypes onto a signaling and metabolic network, we predicted that the coordinated metabolic response to FMRP loss was mediated by dysregulation in the abundances of specific hepatic proteins. We experimentally validated these predictions, demonstrating that the translational regulator FMRP associates with a subset of mRNAs involved in lipid metabolism. Finally, we highlight that FXS patients mirror metabolic variations observed in Fmr1-KO mice with reduced circulating glucose and insulin and increased free fatty acids. Loss of FMRP results in a widespread coordinated systemic response that notably involves upregulation of protein translation in the liver, increased utilization of lipids, and significant changes in metabolic homeostasis. Our study unravels metabolic phenotypes in FXS and further supports the importance of translational regulation in the homeostatic control of systemic metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":28176627,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"A Review of Ruthenium Complexes Activities on Breast Cancer Cells.\nCancer is one of the main causes of death worldwide. Breast cancer is the most prevalent type of cancer in women and the leading cause of cancer deaths due to its high metastasis to the lymph nodes, lungs bones and brain. Interactions with the stromal microenvironment surrounding tumor cells facilitate tumor cell migration and invasion of tissues and dissemination to other organs, to form metastasis. The development of antitumor metal-based drugs was originated with the discovery of cisplatin, however, its severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as promising antitumor drugs. In this review, we focused on the effects of Ru complexes on breast cancer cells and their impact on different steps of the metastatic process.","subset":"pubmed_abstract"} +{"meta":{"pmid":18355999,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Regional migratory osteoporosis.\nRegional migratory osteoporosis (RMO) is an uncommon disease characterised by a migrating arthralgia involving the weight bearing joints of the lower limb. The typical imaging findings on radiographs, magnetic resonance imaging, computed tomography and bone scintigraphy are described and illustrated. Men in their fifth and sixth decades of life are most commonly affected. The most common presentation is with proximal to distal spread in the lower limb. The world literature has been reviewed which has revealed 63 documented cases of regional osteoporosis or bone marrow oedema with migratory symptoms. Most of these cases have not been labelled as RMO and therefore the condition is probably under-diagnosed. The radiology of RMO is indistinguishable from transient osteoporosis of the hip (TOH) except for the migratory symptoms and the two conditions are likely to be part of the same spectrum of disease. Systemic osteoporosis is a more recently recognised accompanying feature that hints at an underlying aetiology and an approach to the management of this condition.","subset":"pubmed_abstract"} +{"meta":{"pmid":14735949,"dup_signals":{"dup_doc_count":23,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2018-09":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-44":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-27":1,"2015-22":1,"2018-26":1}}},"text":"Building a cascade detector and its applications in automatic target detection.\nA hierarchical classifier (cascade) is proposed for target detection. In building an optimal cascade we considered three heuristics: (1) use of a frontier-following approximation, (2) controlling error rates, and (3) weighting. Simulations of synthetic data with various underlying distributions were carried out. We found that a weighting heuristic is optimal in terms of both computational complexity and error rates. We initiate a systematic comparison of several potential heuristics that can be utilized in building a hierarchical model. A range of discussions regarding the implications and the promises of cascade architecture as well as of techniques that can be integrated into this framework is provided. The optimum heuristic--weighting algorithms--was applied to an IR data set. It was found that these algorithms outperform some state-of-the-art approaches that utilize the same type of simple classifier.","subset":"pubmed_abstract"} +{"meta":{"pmid":23327239,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Unintended consequences: abortion training in the years after Roe v Wade.\nThe US Supreme Court's 1973 Roe v Wade decision had clear implications for American women's reproductive rights and physician ability to carry out patient choices. Its effect on physician abortion training was less apparent. In an effort to increase patient access to abortions after Roe, provision shifted from hospitals to nonhospital clinics. However, these procedures and patients were taken out of the medical education realm, and physicians became vulnerable to intimidation. The consequent provider shortage created an unexpected barrier to abortion access. Medical Students for Choice was founded in 1993 to increase abortion-training opportunities for medical students and residents. Its mission ensures that motivated medical students will learn and a growing number of physicians will commit to comprehensive abortion provision.","subset":"pubmed_abstract"} +{"meta":{"pmid":20303601,"dup_signals":{"dup_doc_count":11,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"Influence of age on the efficacy of electroconvulsive therapy in major depression: a retrospective study.\nSeveral variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant. At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1-3 days prior to ECT and 1-3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features. Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p=0.84). The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study. This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":26831629,"dup_signals":{"dup_doc_count":88,"dup_dump_count":44,"dup_details":{"curated_sources":4,"2023-40":4,"2023-23":2,"2023-14":2,"2023-06":2,"2022-49":2,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":1,"2021-43":2,"2021-39":1,"2021-31":3,"2021-25":1,"2021-21":2,"2021-17":4,"2021-04":6,"2020-45":3,"2020-40":2,"2020-34":2,"2020-29":1,"2020-16":5,"2020-10":1,"2019-47":2,"2019-43":1,"2019-35":2,"2019-30":1,"2019-26":2,"2019-22":1,"2019-18":1,"2019-13":3,"2019-09":1,"2019-04":2,"2018-51":1,"2018-43":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":2,"2023-50":1,"2024-26":4,"2024-22":1,"2024-18":1,"2024-10":3,"2024-30":1}}},"text":"Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial.\nPlatelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA). Randomized controlled trial; Level of evidence, 1. In accordance with FDA protocol, patient selection was based on strict inclusion\/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year. No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group. ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":26013103,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-49":1,"2022-33":1,"2020-10":1,"2019-43":1,"2019-35":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-17":1,"2018-09":1,"2023-14":1}}},"text":"Oxidative stress, telomere shortening, and DNA methylation in relation to low-to-moderate occupational exposure to welding fumes.\nEvidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined relationships between low-to-moderate occupational exposure to particles from welding fumes and cancer-related biomarkers for oxidative stress, changes in telomere length, and alterations in DNA methylation. We enrolled 101 welders and 127 controls (all currently nonsmoking men) from southern Sweden. We performed personal sampling of respirable dust and measured 8-oxodG concentrations in urine using a simplified liquid chromatography tandem mass spectrometry method. Telomere length in peripheral blood was measured by quantitative polymerase chain reaction. Methylation status of 10 tumor suppressor genes was determined by methylation-sensitive high-resolution melting analysis. All analyses were adjusted for age, body mass index, previous smoking, passive smoking, current residence, and wood burning stove\/boiler at home. Welders were exposed to respirable dust at 1.2 mg\/m(3) (standard deviation, 3.3 mg\/m(3); range, 0.1-19.3), whereas control exposures did not exceed 0.1 mg\/m(3) (P < 0.001). Welders and controls did not differ in 8-oxodG levels (\u03b2 = 1.2, P = 0.17) or relative telomere length (\u03b2 = -0.053, P = 0.083) in adjusted models. Welders showed higher probability of adenomatous polyposis coli (APC) methylation in the unadjusted model (odds ratio = 14, P = 0.014), but this was not significant in the fully adjusted model (P = 0.052). Every working year as a welder was associated with 0.0066 units shorter telomeres (95% confidence interval -0.013 to -0.00053, P = 0.033). Although there were no clear associations between concentrations of respirable dust and the biomarkers, there were modest signs of associations between oxidative stress, telomere alterations, DNA methylation, and occupational exposure to low-to-moderate levels of particles.","subset":"pubmed_abstract"} +{"meta":{"pmid":28670879,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Molecular Subtypes of Breast Cancers from Myanmar Women: A Study of 91 Cases at Two Pathology Centers\nBackground: Breast cancer is the most common cancer in Myanmar women. Revealing the hormonal receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression is useful for estimating patient prognosis as well as determination of treatment strategy. However, immunohistochemical features and classification of molecular subtypes in breast cancers from Myanmar remain unknown. Methods: The clinicopathological features of 91 breast cancers from Myanmar women were examined. Immunohistochemistry was performed on tissue specimens with antibodies to estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki-67, cytokeratin (CK)5\/6 and CK14. Immunohistochemistry-based molecular subtyping was conducted. Results: Breast cancers in Myanmar women were relatively large, high grade with frequent metastatic lymph nodes. Of the 91 patients, tumors with ER positive, PgR positive, and HER2 positive were 57.1%, 37.4%, and 28.6%, respectively. The most prevalent subtype was luminal B (HER2-) (39.6%), followed by HER2 (22.0%), triple negative (TN)-basal-like (12.1%), luminal A (11.0%), TN-null (8.8%) and luminal B (HER2+) (6.6%). The mean Ki-67 expression of 91 cases was 33.9% (33.9% \u00b1 19.2%) and the median was 28% (range; 4%-90%). The mean Ki-67 expression of luminal A, luminal B, HER2 and TN-basal-like\/ null was 7%, 30%, 40%, and 57%\/43%, respectively. A higher Ki-67 expression significantly correlated with a higher grade, larger size and higher stage of malignancy. Conclusions: We, for the first time, investigated the histopathological features of breast cancers from Myanmar women. Myanmar breast cancers appeared to be aggressive in nature, as evidenced by high frequency of poor-prognosis subtypes with high level of Ki-67 expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":22247485,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Bmp signaling exerts opposite effects on cardiac differentiation.\nThe importance for Bmp signaling during embryonic stem cell differentiation into myocardial cells has been recognized. The question when and where Bmp signaling in vivo regulates myocardial differentiation has remained largely unanswered. To identify when and where Bmp signaling regulates cardiogenic differentiation. Here we have observed that in zebrafish embryos, Bmp signaling is active in cardiac progenitor cells prior to their differentiation into cardiomyocytes. Bmp signaling is continuously required during somitogenesis within the anterior lateral plate mesoderm to induce myocardial differentiation. Surprisingly, Bmp signaling is actively repressed in differentiating myocardial cells. We identified the inhibitory Smad6a, which is expressed in the cardiac tissue, to be required to inhibit Bmp signaling and thereby promote expansion of the ventricular myocardium. Bmp signaling exerts opposing effects on myocardial differentiation in the embryo by promoting as well as inhibiting cardiac growth.","subset":"pubmed_abstract"} +{"meta":{"pmid":18367785,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Variability analysis of SAR from 20 MHz to 2.4 GHz for different adult and child models using finite-difference time-domain.\nThis paper deals with the variability of body models used in numerical dosimetry studies. Six adult anthropomorphic voxel models have been collected and used to build 5-, 8- and 12-year-old children using a morphing method respecting anatomical parameters. Finite-difference time-domain calculations of a specific absorption rate (SAR) have been performed for a range of frequencies from 20 MHz to 2.4 GHz for isolated models illuminated by plane waves. A whole-body-averaged SAR is presented as well as the average on specific tissues such as skin, muscles, fat or bones and the average on specific parts of the body such as head, legs, arms or torso. Results point out the variability of adult models. The standard deviation of whole-body-averaged SAR of adult models can reach 40%. All phantoms are exposed to the ICNIRP reference levels. Results show that for adults, compliance with reference levels ensures compliance with basic restrictions, but concerning children models involved in this study, the whole-body-averaged SAR goes over the fundamental safety limits up to 40%.","subset":"pubmed_abstract"} +{"meta":{"pmid":26020317,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":8}}},"text":"Energy concentration and amino acid digestibility in high-protein canola meal, conventional canola meal, and soybean meal fed to growing pigs.\nTwo experiments were conducted to determine DE and ME and the standardized ileal digestibility (SID) of CP and AA in 2 sources of high-protein canola meal (CM-HP1 and CM-HP2), conventional canola meal (CM-CV), and soybean meal (SBM) fed to growing pigs. In Exp. 1, 40 barrows (51.5 \u00b1 4.0 kg initial BW) were housed in metabolism cages and randomly allotted to 1 of 5 diets with 8 replicate pigs per diet. A corn-based diet (97.4% corn) and 4 diets that contained both corn and each of the 3 sources of canola meal or SBM were formulated. Feces and urine were collected for 5 d after a 5-d adaptation period. The DE and ME were 3,347 and 3,268 kcal\/kg in corn, 3,312 and 2,893 kcal\/kg in CM-HP1, 3,627 and 3,346 kcal\/kg in CM-HP2, 2,798 and 2,492 kcal\/kg in CM-CV, and 4,000 and 3,796 kcal\/kg in SBM, respectively. Values for DE and ME were greater (P< 0.05) in SBM than in all other ingredients, but DE and ME were greater (P < 0.05) in corn and the 2 high-protein canola meals than in CM-CV. The DE and ME were also greater (P< 0.05) in CM-HP2 than in CM-HP1. In Exp. 2, 10 barrows (65.3 \u00b1 10.4 kg initial BW) were equipped with a T-cannula in the distal ileum and randomly allotted to a replicated 5 \u00d7 5 Latin square design with 5 diets and 5 periods in each square. A N-free diet and 4 corn starch-based diets that contained CM-HP1, CM-HP2, CM-CV, or SBM as the sole source of AA were formulated. Each period lasted 7 d and ileal digesta were collected on d 6 and 7 of each period. The SID of CP and all AA except Pro were greater (P < 0.05) in SBM than in the 3 sources of canola meal. With the exception of His and Lys, no differences in SID of indispensable AA were observed among the 3 sources of canola meal. The SID of His and Lys were greater (P < 0.05) in CM-HP1 and CM-HP2 than in CM-CV and the SID of CP was greater (P < 0.05) in CM-HP2 than in CM-CV, but no differences in the SID of indispensable AA were observed between CM-HP1 and CM-HP2. In conclusion, the 2 high-protein canola meals used in this experiment have ME values that are not different from corn but greater than in CM-CV. The SID of most AA is greater in SBM than in canola meals, but SID of His and Lys are greater in high-protein canola meals than in CM-CV. As a consequence, high-protein canola meals supply more ME and SID of AA for growing pigs than CM-CV.","subset":"pubmed_abstract"} +{"meta":{"pmid":7491555,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels. Group Health Medical Associates.\nThe role of lower respiratory tract illnesses (LRIs) in the development of allergies is not well understood. The relation of wheezing and non-wheezing LRIs to serum IgE levels and atopy was studied in 888 children. Total serum IgE levels were measured at birth, nine months and six years of age; and interferon gamma production by blood mononuclear cells was measured at birth and nine months. Atopy was determined by skin prick tests at age six. Wheezing and non-wheezing LRIs up to age three were diagnosed by a physician. Cord serum IgE levels were similar between all LRI groups and the no LRI group. Children who had wheezing LRIs until the age of three had IgE levels at nine months and at six years within normal ranges for age. In contrast, children who had a non-wheezing LRI before the nine month IgE sample had lower IgE levels at nine months and six years (geometric mean 1.8 IU\/ml and 9.9 IU\/ml, respectively) compared with children who had no LRIs (3.9 IU\/ml and 38.3 IU\/ml, respectively). Children who had non-wheezing LRIs after the nine month IgE sample had normal nine month IgE levels (3.2 IU\/ml) but decreased IgE levels at six years of age (15.7 IU\/ml). Children with more than one non-wheezing LRI before the age of three were less likely to be atopic than those with no LRI (odds radio 0.2). Interferon gamma production was higher in the non-wheezing LRI group at nine months than in the no LRI or wheezing LRI groups. Non-wheezing LRIs are associated with subsequent depression of IgE levels and reduced skin test reactivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":17299588,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2017-13":1,"2024-26":1,"unknown":9}}},"text":"Mortality, recruitment and change of desert tree populations in a hyper-arid environment.\nLong-term vegetation changes in hyper-arid areas have long been neglected. Mortality, recruitment and change in populations of the ecologically and culturally important and drought persistent Acacia tortilis and Balanites aegyptiaca are therefore estimated in the Eastern Desert of Egypt, and are related to the primary agents of change, water conditions and human intervention. A change analysis using high-resolution Corona images (1965) in combination with field data (2003) is the basis for recruitment, mortality and change estimates. For assessing the influence of water conditions on patterns in recruitment and survival, different types of generalized linear models are tested. The overall trend in population size in that part of the Eastern Desert studied here is negative. At some sites this negative trend is alarming, because the reduction in mature trees is substantial (>50%) at the same time as recruitment is nearly absent. At a few sites there is a positive trend and better recruitment. Frequent observations of sprouting in saplings indicate that this is an important mechanism to increase their persistence. It is the establishment itself that seems to be the main challenge in the recruitment process. There are indications that hydrological variables and surface water in particular can explain some of the observed pattern in mortality, but our results indicate that direct human intervention, i.e., charcoal production, is the main cause of tree mortality in the Eastern Desert.","subset":"pubmed_abstract"} +{"meta":{"pmid":21339499,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-10":1,"unknown":5}}},"text":"Language skills of school-aged children prenatally exposed to antiepileptic drugs.\nFetal exposure to some antiepileptic drugs (AEDs) carries increased risk of major birth defects, and may be associated with reduced intellectual abilities. The impact on language remains unclear. This study aimed to investigate the impact of fetal AED exposure on language skills. Women with epilepsy and their children were recruited to this observational study through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. Language skills of 102 AED-exposed children were assessed using the Clinical Evaluation of Language Fundamentals, fourth edition (CELF-4). Assessments were conducted blind to drug. Maternal epilepsy, pregnancy, and medical histories were obtained from prospectively collected records. Mean CELF-4 Core Language scores of children exposed to sodium valproate in monotherapy (mean 91.5, SD 17.5) or polytherapy (mean 73.4, SD = 22.3) were significantly below the standardized test mean of 100 (p < 0.05). Mean language scores of children exposed to carbamazepine or lamotrigine monotherapy, or polytherapy without sodium valproate, were not significantly different from normal. First-trimester sodium valproate dose was negatively correlated with language scores, and significantly predicted language scores after controlling for other group differences. Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age.","subset":"pubmed_abstract"} +{"meta":{"pmid":21537536,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Evaluation of liquid ingestion after bariatric surgery.\nBariatric surgery is an effective treatment for obesity; however, after surgery the patient may have difficulty in swallowing liquid and solid foods. To evaluate liquid ingestion in patients who had undergone bariatric surgery. We studied 43 volunteers with normal body mass index (BMI) (BMI: 18.5-24.9 kg\/m\u00b2), 55 subjects with class III obesity (BMI: >40.0 kg\/m\u00b2), and 48 subjects with bariatric surgery for treatment of class III obesity. The method chosen for evaluation was the water swallowing test. The subjects drank in triplicate 50 mL of water while being precisely timed and the number of swallows were counted. There was no difference between subjects with normal BMI and subjects with class III obesity. During the first 2 months after bariatric surgery the patients showed an increase in the time needed to drink the entire volume, in the number of swallows, and in the inter-swallow interval, and a decrease in the volume swallowing capacity (volume\/swallowing) and swallowing flow rate (volume swallowed\/second). After 2 months, the results of the swallowing measurements moved in the direction of normal values. Bariatric surgery may cause more intense alterations of liquid bolus swallowing within 2 months after the procedure, which moved to normal values after this time.","subset":"pubmed_abstract"} +{"meta":{"pmid":7059323,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Triglyceride and cholesterol metabolism in primary hypertriglyceridemia.\nTo determine mechanisms of elevated plasma triglycerides (TG) in patients with primary hypertriglyceridemias, simultaneous studies were carried out on kinetics of very low density lipoprotein-triglycerides (VLDL-TG) and synthesis of cholesterol and bile acids. Sixteen hypertriglyceridemic patients with familial combined hyperlipidemia (FCHL) and 12 patients with poorly classified, primary hypertriglyceridemia were studied, and their results were compared to a series of normal and obese subjects previously studied in our laboratory. The mean value for transport (synthesis) of VLDL-TG in patients with FCHL was about twice normal. Although the upper normal synthesis rates overlapped with transport rates of some patients with FCHL, it appeared that the major cause of hypertriglyceridemia in FCHL was an elevated production of VLDL-TG. However, the height of the plasma TG in FCHL patients also was influenced by individual clearance capacities for VLDL-TG, and fractional clearance rates in several seemed particularly low. Synthesis rates for cholesterol and\/or bile acids were high in several patients with FCHL, suggesting simultaneous overproduction of VLDL-TG and sterols; however, increased synthesis of both was not observed in all the patients. Most patients with poorly classified hypertriglyceridemia had over-production of VLDL-TG, but an apparent reduction in clearance was common. In these patients, increased synthesis of cholesterol and bile acids was infrequent. Our results indicate that abnormally high production of VLDL-TG seemed to be the major factor in causing primary hypertriglyceridemia, but that clearance capacity can play an important role in determining the the severity of the TG elevation.","subset":"pubmed_abstract"} +{"meta":{"pmid":874423,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":6,"2021-25":1,"2018-22":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2023-14":1,"2017-13":1}}},"text":"Activation of factor XII by tobacco glycoprotein.\nA glycoprotein of mol wt ca. 18,000 daltons isolated from cured tobacco leaves (TGP-L) and from cigarette smoke condensate (TGP-CSC) activated factor XII in normal human plasma in vitro as measured by (a) shortening of the partial thromboplastin time, (b) shortening of the lysis time of euglobulin clots, and (c) generation of kinin activity. These effects were not demonstrable in plasma deficient in factor XII. The capacity of TGP-L and TGP-CSC to activate factor XII was shown to depend on the presence of rutin, a substance chemically similar to quercetin and ellagic acid, which are known activators of factor XII. Rutin and rutin coupled to bovine serum albumin, but not bovine serum albumin alone, were also demonstrated to activate factor XII. The presence in cigarette smoke of material that is both allergenic and capable of activating factor XII of the intrinsic pathway of coagulatin may be important to the pathogenesis of cardiovascular and pulmonary disease associated with cigarette smoking.","subset":"pubmed_abstract"} +{"meta":{"pmid":12663991,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-06":1,"2022-40":1,"2022-21":1,"2021-39":1,"2021-25":1,"2021-21":1,"2021-04":1,"2020-50":1,"2020-40":1,"2020-24":2,"2019-43":1,"2023-23":1,"2024-22":1,"2024-26":1}}},"text":"Phosphorylation of the heat shock-related protein, HSP20, mediates cyclic nucleotide-dependent relaxation.\nCyclic nucleotide-dependent relaxation of vascular smooth muscle is associated with increases in the phosphorylation of the small heat shock-related protein, HSP20. To determine whether phosphorylated HSP20 directly mediates relaxation, we used gene transfection and protein transduction of HSP20 analogues. Rat mesangial cells were transfected with constructs containing wild-type HSP20-enhanced green fluorescent protein (EGFP), phosphorylation site mutated HSP20 (S16A-HSP20-EGFP), or EGFP alone. Contractile properties were determined on a silicone polymer substrata. In the presence of serum, EGFP-vector transfected control cells and S16A-HSP20 transfected cells formed wrinkles on the polymer (contracted). Activation of cyclic nucleotide signaling pathways in the EGFP-vector transfected control cells led to a time-dependent decrease in the wrinkles (relaxation). The S16A-HSP20 transfected cells were refractory to cyclic nucleotide-dependent relaxation. Cells overexpressing the wild-type HSP20 did not form wrinkles on the polymer in response to serum (refractory to contraction). Treatment of precontracted strips of intact bovine carotid artery smooth muscle with synthetic peptides containing HIV-trans-activating transcriptional activator and a phosphopeptide motif of HSP20 led to dose-dependent relaxation. These data provide evidence that phosphorylated HSP20 has a direct role in smooth muscle relaxation and that small phosphopeptide motifs of HSP20 can mimic the effects of the entire molecule.","subset":"pubmed_abstract"} +{"meta":{"pmid":29528360,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2023-06":1,"2022-49":1,"2021-21":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":3,"2023-14":1}}},"text":"Organic molecule-based photothermal agents: an expanding photothermal therapy universe.\nOver the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.","subset":"pubmed_abstract"} +{"meta":{"pmid":26944422,"dup_signals":{"dup_doc_count":16}},"text":"Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages.\nOxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroid responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratios of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90 l\/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumour necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages. This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced efficacy to control inflammation and oxidative stress in LPS-induced alveolar macrophages.","subset":"pubmed_abstract"} +{"meta":{"pmid":21512513,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Replication and extension of association between common genetic variants in SIM1 and human adiposity.\nHaplo-insufficiency of the bHLH (basic helix-loop-helix) transcription factor single-minded 1 (SIM1) causes severe obesity in mice and humans. We hypothesized that common genetic variations in\/near SIM1 could exert more subtle effects on its function and associate with human adiposity. First, SIM1 coding regions were sequenced in severely obese subjects, and two common nonsynonymous single-nucleotide polymorphisms (nsSNPs) in complete linkage disequilibrium (LD) were identified: Pro352Thr (rs3734354) and Ala371Val (rs3734355). We next carried out a SNP association study of five adiposity traits (BMI, % body fat, abdominal visceral and subcutaneous fat, and leptin concentrations) in 1,699 whites and 1,173 blacks. TagSNPs covering SIM1 and nearby conserved regions, and the only common nsSNP in SIM1's binding partner aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) (Gly679Ser\/rs4072568), were investigated. The effects of rs3734355\/4 on SIM1 activity were tested using an in vitro reporter assay. We replicated previous observations that homozygosity for the 371Val allele was associated with higher BMI in white males (P = 0.003). Together with previous findings in white males (combined n = 3,479), BMI was increased by 1.10 kg\/m(2) in 371Val homozygotes (95% confidence interval (CI): 0.25-1.95 kg\/m(2), P = 0.01). In vitro, the 352Thr-371Val haplotype impaired SIM1 transcriptional activity by 22% (P < 0.0001). TagSNP analysis of SIM1 revealed two SNPs in the 3' region (rs9390322 and rs7746743) and another in intron 5 (rs3734353) to be significantly associated with various adiposity measures in ethnicity- and sex-specific manners after multiple testing correction. In white males, rs4072568 in ARNT2 was also associated with BMI (P = 9 \u00d7 10(-4)) and % body fat (P = 0.001). Our findings implicate heritable defects of the SIM1-ARNT2 axis in the predisposition to human obesity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28770931,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"High performance asymmetric V2O5-SnO2 nanopore battery by atomic layer deposition.\nHere we report the high performance and cyclability of an asymmetric full cell nanopore battery, comprised of V2O5 as the cathode and prelithiated SnO2 as the anode, with integrated nanotubular Pt current collectors underneath each nanotubular storage electrode, confined within an anodized aluminium oxide (AAO) nanopore. Enabled by atomic layer deposition (ALD), this coaxial nanotube full cell is fully confined within a high aspect ratio nanopore (150 nm in diameter, 50 \u03bcm in length), with an ultra-small volume of about 1 fL. By controlling the amount of lithium ion prelithiated into the SnO2 anode, we can tune the full cell output voltage in the range of 0.3 V to 3 V. When tested as a massively parallel device (\u223c2 billion cm-2), this asymmetric nanopore battery array displays exceptional rate performance and cyclability: when cycled between 1 V and 3 V, capacity retention at the 200C rate is \u223c73% of that at 1C, and at 25C rate only 2% capacity loss occurs after more than 500 charge\/discharge cycles. With the increased full cell output potential, the asymmetric V2O5-SnO2 nanopore battery shows significantly improved energy and power density over the previously reported symmetric cell, 4.6 times higher volumetric energy and 5.2 times higher power density - an even more promising indication that controlled nanostructure designs employing nanoconfined environments with large electrode surface areas present promising directions for future battery technology.","subset":"pubmed_abstract"} +{"meta":{"pmid":23413013,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":11}}},"text":"Auditory imagery and the poor-pitch singer.\nThe vocal imitation of pitch by singing requires one to plan laryngeal movements on the basis of anticipated target pitch events. This process may rely on auditory imagery, which has been shown to activate motor planning areas. As such, we hypothesized that poor-pitch singing, although not typically associated with deficient pitch perception, may be associated with deficient auditory imagery. Participants vocally imitated simple pitch sequences by singing, discriminated pitch pairs on the basis of pitch height, and completed an auditory imagery self-report questionnaire (the Bucknell Auditory Imagery Scale). The percentage of trials participants sung in tune correlated significantly with self-reports of vividness for auditory imagery, although not with the ability to control auditory imagery. Pitch discrimination was not predicted by auditory imagery scores. The results thus support a link between auditory imagery and vocal imitation.","subset":"pubmed_abstract"} +{"meta":{"pmid":32264138,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Facile synthesis of magnetic covalent organic frameworks for the hydrophilic enrichment of N-glycopeptides.\nProtein glycosylations play important roles in various biological processes and in the disease progression of organisms. The development of specific enrichment materials and strategies before mass spectrometric analysis was a prerequisite to glycoproteomic analysis due to the difficulty caused by substoichiometric levels of glycoproteins. In this work, novel magnetic covalent organic frameworks (denoted as Fe3O4@TpPa-1) were first developed using only a two-step solvothermal reaction and then applied in the hydrophilic enrichment of glycopeptides. Sea urchin-type composites with super-paramagnetic properties were constructed by in situ growth of TpPa-1 covalent organic frameworks on the surface of magnetic nanoparticles. A total of 37 and 22 glycopeptides could be easily detected from IgG and HRP digests, respectively, by hydrophilic enrichment with the newly developed materials. An ultralow detection limit (28 fmol), satisfactory selectivity and high recovery could be achieved using Fe3O4@TpPa-1. The material's excellent enrichment performance was also demonstrated using glycopeptide analysis in real complex samples. Within three independent replicates, 228 glycopeptides corresponding to 114 glycoproteins could be detected from human serum digests, which is better than the performance obtained by commercial HILIC materials. The results suggest that covalent organic frameworks show potential for application in glycoproteomic studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":30157910,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-40":2,"2022-49":1,"2022-33":1,"2022-05":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2019-39":1,"2019-35":1,"2019-22":1,"2018-47":1,"2018-39":1,"2024-18":1}}},"text":"Zoledronic acid in the management of mesothelioma - a feasibility study (Zol-A Trial): study protocol for a randomised controlled trial.\nNitrogen containing bisphosphonates such as zoledronic acid (ZA) are known to contain certain anti-cancer properties. These have been investigated in the past in various cancers such as breast, prostate and colon. ZA in particular has shown promising results in pre-clinical studies. We propose a multicentre double-blind randomised controlled feasibility study to assess the recruitment and acceptability of ZA\/placebo alongside chemotherapy in malignant pleural mesothelioma (MPM). Patients will be recruited for a 13-month period from October 2016 to November 2017. Eligible patients will be identified via the regional mesothelioma multidisciplinary team meeting. Those who receive chemotherapy will be randomised to receive either ZA or placebo alongside their chemotherapy. Those who decline chemotherapy will be offered to join the trial on the non-randomised open-labelled arm of the trial. Patients will receive a maximum of six cycles of ZA\/placebo, at three-weekly cycles. All patients will be followed up for six months from randomisation. Semi-structured interviews to gather data on acceptability of trial procedures, tolerability of ZA and other relevant information will take place after the participants have completed their six cycles of treatment. For a better understanding about non-participation in mesothelioma trials we also aim to interview those who decline to take part in the trial. The qualitative and quantitative data gathered in this feasibility trial will hopefully pave the way to designing a robust full phase III trial to investigate the potential synergistic effect of ZA and current standard treatment for MPM, cisplatin-pemetrexed combination chemotherapy. ISRCTN Registry, ISRCTN45536692 . Registered on 9 August 2016. EudraCT no. 2015-004433-26.","subset":"pubmed_abstract"} +{"meta":{"pmid":16216025,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Alcohol septal ablation for hypertrophic cardiomyopathy: indications and technique.\nAlcohol septal ablation for the treatment of hypertrophic cardiomyopathy has been the subject of great interest, and the number of procedures performed is increasing despite an absence of randomized trial data. Although straightforward in concept, alcohol septal ablation may be considerably more difficult in actual practice. To optimize the results and prevent complications, the anatomy of the septal arcade architecture must be understood and the anatomic relationship between the septal artery and the specific portion of the septum to be ablated must be carefully delineated. For the latter, during the procedure, an echocardiographic contrast medium injection into the septal artery of interest is essential. Selection of the volume and amount of alcohol to be injected varies depending on the size and distribution of the septal artery. Specific complications such as conduction defects, hemodynamic compromise, ventricular arrhythmias, and inadequate gradient reduction can be minimized by specific technical approaches. After ablation, protocols are needed for periprocedural guidelines because some complications may occur late during the next several days. For optimal results, patients need to be selected after catheter assessment and combined echocardiography and angiography, and ablation techniques need to be scientific and rigorous.","subset":"pubmed_abstract"} +{"meta":{"pmid":10583735,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Effects of the solvents on bond strength of resin bonded porcelain.\nClinical trials of porcelain veneers for chairside colour modifications may require the use of a trial resin with various colours of tints. The bond strength effects of four different solvents used for removal of trial resin from etched porcelain specimens were investigated. Fifty-six porcelain specimens were fabricated, flattened by a metallurgically standard method, etched with hydrofluoric acid and silane treated. The specimens were divided into four groups at random. The trial resin material was cleaned with different solvents prior to bonding of a dual cure resin composite button. After bonding the specimens were stored in water at 37 degrees C for 7 days. Shear bond strength results were as follows: acetone (control) group, 12.9+\/-2.9 MPa; ethanol group, 15.1+\/-4.6 MPa; methanol group, 11.5+\/-2.9 MPa; methylene chloride group, 11.3+\/-2.4 MPa. No significant differences were measured (ANOVA, P>0.05). The results indicated that the resin-porcelain bond strengths were not affected by the type of solvent used to remove trial resin. This procedure is recommended for clinical cases when resin composite is used for the try-in of etched porcelain bonded restorations.","subset":"pubmed_abstract"} +{"meta":{"pmid":36297612,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"2024-30":1,"unknown":6}}},"text":"An Investigation of O-Demethyl Tramadol\/Tramadol Ratio for Cytochrome P450 2D6 Phenotyping: The CYTRAM Study.\nCytochrome P450 2D6 (CYP2D6) gene polymorphisms influence the exposure to tramadol (T) and its pharmacologically active metabolite, O-demethyl tramadol (O-dT). Tramadol has been considered as a candidate probe drug for CYP2D6 phenotyping. The objective of the CYTRAM study was to investigate the value of plasma O-dT\/T ratio for CYP2D6 phenotyping. European adult patients who received IV tramadol after surgery were included. CYP2D6 genotyping was performed and subjects were classified as extensive (EM), intermediate (IM), poor (PM), or ultra-rapid (UM) CYP2D6 metabolizers. Plasma concentrations of tramadol and O-dT were determined at 24 h and 48 h. The relationship between O-dT\/T ratio and CYP2D6 phenotype was examined in both a learning and a validation group. Genotype data were obtained in 301 patients, including 23 PM (8%), 117 IM (39%), 154 EM (51%), and 7 UM (2%). Tramadol trough concentrations at 24 h were available in 297 patients. Mean value of O-dT\/T ratio was significantly lower in PM than in non-PM individuals (0.061 \u00b1 0.031 versus 0.178 \u00b1 0.09, p < 0.01). However, large overlap was observed in the distributions of O-dT\/T ratio between groups. Statistical models based on O-dT\/T ratio failed to identify CYP2D6 phenotype with acceptable sensitivity and specificity. Those results suggest that tramadol is not an adequate probe drug for CYP2D6 phenotyping.","subset":"pubmed_abstract"} +{"meta":{"pmid":29147691,"dup_signals":{"dup_doc_count":12,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2018-43":1,"2018-34":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-09":1,"2017-51":3,"2018-47":1}}},"text":"A meta-selective-C-H alkenylation of phenol-derivatives employing a traceless organosilicon template.\nA traceless organosilicon template-directed meta-selective-C-H alkenylation of phenols was realized with good yields and high selectivities. The template was readily removable through F--promoted O-Si cleavage under extremely mild conditions or recyclable through a p-TSA catalyzed process. The product was successfully applied in the preparation of a series of meta-alkenylated aromatic compounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":26972603,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":1,"2024-18":1,"2024-10":2,"2024-30":1,"unknown":12}}},"text":"Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.\nIn the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":24354782,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Cross-cultural differences in processing of architectural ranking: evidence from an event-related potential study.\nVisual object identification is modulated by perceptual experience. In a cross-cultural ERP study we investigated whether cultural expertise determines how buildings that vary in their ranking between high and low according to the Western architectural decorum are perceived. Two groups of German and Chinese participants performed an object classification task in which high- and low-ranking Western buildings had to be discriminated from everyday life objects. ERP results indicate that an early stage of visual object identification (i.e., object model selection) is facilitated for high-ranking buildings for the German participants, only. At a later stage of object identification, in which object knowledge is complemented by information from semantic and episodic long-term memory, no ERP evidence for cultural differences was obtained. These results suggest that the identification of architectural ranking is modulated by culturally specific expertise with Western-style architecture already at an early processing stage.","subset":"pubmed_abstract"} +{"meta":{"pmid":36271298,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":5,"2024-26":1,"2024-10":1,"unknown":7}}},"text":"Deep learning-assisted co-registration of full-spectral autofluorescence lifetime microscopic images with H&E-stained histology images.\nAutofluorescence lifetime images reveal unique characteristics of endogenous fluorescence in biological samples. Comprehensive understanding and clinical diagnosis rely on co-registration with the gold standard, histology images, which is extremely challenging due to the difference of both images. Here, we show an unsupervised image-to-image translation network that significantly improves the success of the co-registration using a conventional optimisation-based regression network, applicable to autofluorescence lifetime images at different emission wavelengths. A preliminary blind comparison by experienced researchers shows the superiority of our method on co-registration. The results also indicate that the approach is applicable to various image formats, like fluorescence in-tensity images. With the registration, stitching outcomes illustrate the distinct differences of the spectral lifetime across an unstained tissue, enabling macro-level rapid visual identification of lung cancer and cellular-level characterisation of cell variants and common types. The approach could be effortlessly extended to lifetime images beyond this range and other staining technologies.","subset":"pubmed_abstract"} +{"meta":{"pmid":10365659,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":12}}},"text":"Persistent delivery of factor IX in mice: gene therapy for hemophilia using implantable microcapsules.\nSevere hemophilia B is a life-threatening, life long condition caused by absence of or defective coagulation factor IX. Gene therapy could provide an alternative treatment to repeated injection of plasma-derived concentrate or recombinant factor IX. We have previously described the use of implantable microcapsules containing recombinant myoblasts to deliver human factor IX in mice. This study reports the generation of improved myoblast-specific expression vectors. Mouse myoblast clones transfected with the various vectors secreted factor IX in vitro, at rates between 70 and 1000 ng\/10(6) cells\/day. The recombinant myoblast clones were then encapsulated and implanted into mice. Immunocompetent mice implanted with encapsulated myoblasts had up to 65 ng of factor IX per milliliter in their plasma for up to 14 days, after which antibodies to human factor IX became detectable, and this coincided with decreased factor IX in mouse plasma. In immunodeficient mice, however, factor IX delivery was maintained at a constant level for at least 6 weeks (end of experiment). Interestingly, the highest-secreting myoblast clone in vitro did not deliver the highest level of hFIX in vivo. This discrepancy observed between performance in vitro and in vivo may have important implications for the development of gene therapy protocols based on recombinant cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23461539,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":10}}},"text":"A concept analysis of nursing overtime.\nTo report a concept analysis of nursing overtime. Economic constraints have resulted in hospital restructuring with the aim of reducing costs. These processes often target nurse staffing (the largest organizational expense) by increasing usage of alternative staffing strategies including overtime hours. Overtime is a multifaceted, poorly defined, and indiscriminately used concept. Analysis of nursing overtime is an important step towards development and propagation of appropriate staffing strategies and rigorous research. Concept analysis. The search of electronic literature included indexes, grey literature, dictionaries, policy statements, contracts, glossaries and ancestry searching. Sources included were published between 1993-2012; dates were chosen in relation to increases in overtime hours used as a result of the healthcare structuring in the early 1990s. Approximately 65 documents met the inclusion criteria. Walker and Avant's methodology guided the analysis. Nursing overtime can be defined by four attributes: perception of choice or control over overtime hours worked; rewards or lack thereof; time off duty counts equally as much as time on duty; and disruption due to a lack of preparation. Antecedents of overtime arise from societal, organizational, and individual levels. The consequences of nursing overtime can be positive and negative, affecting organizations, nurses, and the patients they care for. This concept analysis clarifies the intricacies surrounding nursing overtime with recommendations to advance nursing research, practice, and policies. A nursing-specific middle-range theory was proposed to guide the understanding and study of nursing overtime.","subset":"pubmed_abstract"} +{"meta":{"pmid":30696420,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2023-06":1,"2021-39":1,"2021-17":1,"2020-40":1,"2020-16":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-13":1,"2023-40":1,"2024-18":1}}},"text":"Participatory development and pilot testing of iChoose: an adaptation of an evidence-based paediatric weight management program for community implementation.\nTo describe the identification, adaptation, and testing of an evidence-based pediatric weight management program for a health disparate community. A community advisory board (CAB) of decision-makers and staff from local health care, public health, and recreation organizations engaged with academic partners to select an evidence-based program (EBP) for local implementation. Three EBPs were identified (Traffic Light, Bright Bodies, Golan and colleagues Home Environmental Model) and each EBP was rated on program characteristics, implementation and adaptation, and adoptability. Following selection of the EBP that was rated highest, the POPS-CAB made adaptations based on the program principles described in peer-reviewed publications. The adapted intervention, iChoose, was then pilot tested in 3 iterative phases delivered initially by research partners, then co-delivered by research and community partners, then delivered by community partners. The RE-AIM framework was used to plan and evaluate the iChoose intervention across all waves with assessments at baseline, post program (3 months), and follow-up (6 months). Bright Bodies rated highest on program characteristics and adoptability (p's < 0.05), while Home Environmental Model rated highest on implementation factors (p < 0.05). Qualitatively, the selection focused on important program characteristics and on matching those characteristics to the potential to fit within the community partner services. The adapted program-iChoose-had 18% reach and with participants that were representative of the target population on age, gender, ethnicity, and race. Effectiveness was demonstrated by modest, but significant reductions in BMI z-scores at post-program compared to baseline (M\u0394 = - 0.047; t = - 2.11, p = 0.046). This decrease returned to values similar to baseline 3 months (M\u0394 = 0.009) after the program was completed. Implementation fidelity was high and implementation fidelity did not differ between community or research delivery agents. The process to help organizations identify and select evidence-based programs appropriate for their community led to consensus on a single EBP. While iChoose was successful in initiating changes in BMI z-scores, could be implemented in a low resource community with fidelity, it was insufficient to lead to sustained child BMI z-scores. In response to these data, maintenance of program effects and delivery are the current focus of the CBPR team.","subset":"pubmed_abstract"} +{"meta":{"pmid":31303294,"dup_signals":{"dup_doc_count":93,"dup_dump_count":36,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":4,"2023-23":1,"2023-14":7,"2023-06":2,"2022-49":2,"2022-40":3,"2022-27":2,"2022-21":4,"2022-05":1,"2021-49":1,"2021-43":6,"2021-39":3,"2021-31":3,"2021-25":1,"2021-21":3,"2021-17":4,"2021-10":3,"2021-04":3,"2020-50":2,"2020-45":4,"2020-40":5,"2020-34":2,"2020-24":1,"2020-16":1,"2020-10":3,"2020-05":2,"2019-51":2,"2019-43":2,"2019-39":1,"2019-35":2,"2024-30":2,"2024-26":2,"2024-22":1,"2024-18":1,"2024-10":1}}},"text":"Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis.\nInfluenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (\u226565 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5\u00b0 by 5\u00b0 grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0\u00b73 months [95% CI -0\u00b73 to 0\u00b79]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3\u00b78 months [3\u00b76 to 4\u00b70]) in temperate sites and longer duration (5\u00b72 months [4\u00b79 to 5\u00b75]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4\u00b76 months [4\u00b73 to 4\u00b78]), as it was for metapneumovirus (4\u00b78 months [4\u00b74 to 5\u00b71]). By comparison, parainfluenza virus had longer duration of epidemics (6\u00b73 months [6\u00b70 to 6\u00b77]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0\u00b72 months [-0\u00b76 to 0\u00b71]; respiratory syncytial virus 0\u00b71 months [-0\u00b72 to 0\u00b74]). This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).","subset":"pubmed_abstract"} +{"meta":{"pmid":28132596,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"* Comparison of Two Moldable Calcium Phosphate-Based Bone Graft Materials in a Noninstrumented Canine Interspinous Implantation Model.\nThere is a continuing search for novel synthetic materials as an alternative to autologous bone grafting. Different technologies are explored to promote bone formation, which include the addition of BioGlass\u2122 particles in calcium phosphate (CaP)-based materials and the use of surface modification in the form of submicron surface topographies. In this work, we aimed at comparing the bone formation in a noninstrumented canine interspinous model of moldable formulations of a submicron-surface structured tricalcium phosphate\/alkylene oxide copolymer (CaP\/AOC) or a tricalcium phosphate\/BioGlass\/collagen (CaP\/BG\/C) bone graft material. Intramuscular implantation was carried out as well to evaluate soft tissue responses. Eight mature male mongrel dogs underwent single-level, noninstrumented interspinous implantation, where the bone graft materials were implanted at either side of the spinous processes (L3-L4), with separation by the interspinous ligament ensuring comparison of both materials in each animal (n = 8 per material). The materials were also implanted in paraspinal muscle pouches. Animals were euthanized 12 weeks after surgery and the lumbar spines excised and intramuscular implants retrieved. Undecalcified sections were prepared for histological evaluation and histomorphometry was performed to quantify bone formation and material resorption. After 12 weeks, all submicron structured CaP\/AOC implants showed abundant bone formation in the (L3-L4) interspinous space (20.8% \u00b1 6.8%), whereas bone was not found in the CaP\/BG\/C implants (0% \u00b1 0%). Intramuscularly, the CaP\/AOC material triggered significant bone formation (12.0% \u00b1 7.8%), whereas CaP\/BG\/C did not form any bone. In both the spinal and muscular sites, resorption of the CaP\/AOC material was evident by a decrease in Feret diameter of the CaP granules as well as in their histological surface compared with the starting material, whereas CaP\/BG\/C material had a milder resorption. This study shows that a submicron-surface structured CaP\/AOC bone graft material has superior bone-forming properties in both an interspinous implantation model and intramuscularly, as compared with a CaP\/BG\/C bone graft material.","subset":"pubmed_abstract"} +{"meta":{"pmid":10925571,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":9}}},"text":"Control of idiopathic ventricular fibrillation by implantable cardioverter-defibrillator in a child who survived sudden death.\nIdiopathic ventricular fibrillation (VF) is extremely rare in children who have not previously undergone cardiac surgery. Patients resuscitated from idiopathic VF remain at risk for recurrence. The use of an implantable cardioverter-defibrillator (ICD) effectively prevents such recurrences. We report the case of a 12-year-old girl who had a history of recurrent syncope and had survived an episode of VF. Serial studies after prolonged but successful resuscitation, including echocardiography, an electrocardiogram (ECG), and coronary angiography failed to reveal abnormal cardiac structures responsible for VF. No abnormal conduction pathways or abnormal early or late after depolarization were found on electrophysiologic study. The ST segments of the 12-lead ECG remained normal after procainamide challenge. The patient underwent ICD implantation 2 weeks after admission and syncope did not recur during a follow-up of 14 months. This report emphasizes that idiopathic VF may be responsible for syncope in children. ICD therapy prevents the recurrence of idiopathic VF and the associated risk of sudden death.","subset":"pubmed_abstract"} +{"meta":{"pmid":19403228,"dup_signals":{"dup_doc_count":11}},"text":"Effect of sodium, amine and stannous fluoride at the same concentration and different pH on in vitro erosion.\nThis study aimed to compare the effects 0.5% and 1% sodium, amine and stannous fluoride at different pH on enamel erosion in vitro. Bovine enamel samples were submitted to a cyclic de- and remineralisation for 3 days. Each day, the samples were exposed for 120 min to pooled human saliva and subsequently treated with one of the fluoride solutions for 3 min: amine fluoride (AmF, 0.5% and 1% F(-)), sodium fluoride (NaF, 0.5% and 1% F(-)), each at pH 3.9 and 7.0, and stannous fluoride (SnF(2), 0.5% and 1% F(-)), at pH: 3.9. Additionally, two groups were treated with fluoride-free placebo solutions (pH: 3.9 and 7.0) and one group served as control (no fluoridation). Ten specimens each group were inserted in a so-called artificial mouth and eroded six times daily with hydrochloric acid (pH 2.6) for 90 s each intermitted by exposure to artificial saliva (1h). After 3 days, enamel loss was analyzed profilometrically and evaluated statistically by ANOVA. Only the acidic 0.5% and 1% SnF(2) and 1% AmF solutions were able to reduce erosive enamel loss significantly, while all other solutions and placebos did not differ significantly from the control. Between the acidic SnF(2) and the 1% AmF solutions no significant differences could be detected. At the same concentrations, acidic SnF(2) and AmF may be more effective than NaF to protect enamel against erosion.","subset":"pubmed_abstract"} +{"meta":{"pmid":26497478,"dup_signals":{"dup_doc_count":52,"dup_dump_count":38,"dup_details":{"curated_sources":4,"2023-40":1,"2023-23":2,"2023-14":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":2,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":4,"2019-35":1,"2019-26":1,"2019-22":1,"2019-13":1,"2019-04":2,"2018-47":1,"2018-43":1,"2018-39":1,"2018-30":2,"2018-22":1,"2018-17":1,"2018-13":1,"2018-05":2,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2023-50":1,"2024-26":2,"2024-10":2}}},"text":"Peripherally Restricted Cannabinoids for the Treatment of Pain.\nThe use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana. Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence). A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS. This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy). In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end.","subset":"pubmed_abstract"} +{"meta":{"pmid":30038779,"dup_signals":{"dup_doc_count":35,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2020-10":6,"2019-51":1,"2019-43":1,"2019-39":4,"2019-35":1,"2019-30":1,"2019-26":1,"2019-13":2,"2019-09":2,"2019-04":2,"2018-47":4,"2018-39":3,"2018-30":3,"2020-16":1}}},"text":"Cost-benefit analysis of acoustic recorders as a solution to sampling challenges experienced monitoring cryptic species.\nThe inferences that can be made from any study are limited by the quality of the sampling design. By bad luck, when monitoring species that are difficult to detect (cryptic), sampling designs become dictated by what is feasible rather than what is desired. We calibrated and conducted a cost-benefit analysis of four acoustic recorder options that were being considered as potential solutions to several sampling restrictions experienced while monitoring the Australasian bittern, a cryptic wetland bird. Such sampling restrictions are commonly experienced while monitoring many different endangered species, particularly those that are cryptic. The recorder options included mono and stereo devices, with two sound file processing options (visual and audible analysis). Recording devices provided call-count data similar to those collected by field observers but at a fraction of the cost, which meant that \"idealistic\" sampling regimes, previously thought to be too expensive, became feasible for bitterns. Our study is one of the few to assess the monetary value of recording devices in the context of data quality, allowing trade-offs (and potential solutions) commonly experienced while monitoring cryptic endangered species to be shown and compared more clearly. The ability to overcome challenges of monitoring cryptic species in this way increases research possibilities for data deficient species and is applicable to any species with similar monitoring challenges.","subset":"pubmed_abstract"} +{"meta":{"pmid":27767125,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":15}}},"text":"Marginal evidence for cosmic acceleration from Type Ia supernovae.\nThe 'standard' model of cosmology is founded on the basis that the expansion rate of the universe is accelerating at present - as was inferred originally from the Hubble diagram of Type Ia supernovae. There exists now a much bigger database of supernovae so we can perform rigorous statistical tests to check whether these 'standardisable candles' indeed indicate cosmic acceleration. Taking account of the empirical procedure by which corrections are made to their absolute magnitudes to allow for the varying shape of the light curve and extinction by dust, we find, rather surprisingly, that the data are still quite consistent with a constant rate of expansion.","subset":"pubmed_abstract"} +{"meta":{"pmid":26515560,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"EEG Correlates of Relative Motion Encoding.\nA large portion of the visual cortex is organized retinotopically, but perception is usually non-retinotopic. For example, a reflector on the spoke of a bicycle wheel appears to move on a circular or prolate cycloidal orbit as the bicycle moves forward, while in fact it traces out a curtate cycloidal trajectory. The moving bicycle serves as a non-retinotopic reference system to which the motion of the reflector is anchored. To study the neural correlates of non-retinotopic motion processing, we used the Ternus-Pikler display, where retinotopic processing in a stationary reference system is contrasted against non-retinotopic processing in a moving one. Using high-density EEG, we found similar brain responses for both retinotopic and non-retinotopic rotational apparent motion from the earliest evoked peak (around 120 ms) and throughout the rest of the visual processing, but only minor correlates of the motion of the reference system itself (mainly around 100-120 ms). We suggest that the visual system efficiently discounts the motion of the reference system from early on, allowing a largely reference system independent encoding of the motion of object parts.","subset":"pubmed_abstract"} +{"meta":{"pmid":29142995,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":3,"2019-09":1,"2018-43":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":1,"2018-09":1,"2017-51":3,"2017-47":2,"2019-18":1}}},"text":"Screening of novel RGD peptides to modify nanoparticles for targeted cancer therapy.\nNew targeted RGD peptides obtained by solid phase peptide synthesis (SPPS) were successfully screened by Molecular Operating Environment (MOE) and used for the building of the 6-O-carboxymethyl chitosan based carrier with an active target on the surface. CRGDYC-6-O-carboxymethyl chitosan based nanoparticles (NPs) loaded with doxorubicin hydrochloride (DOX) were successfully prepared by an ionic gelation method with the carrier synthesized before. Synthesis conditions and formulation parameters were optimized by determining the characteristics of nanoparticles including the particle size and drug encapsulation efficiency. 6-O-Carboxymethyl chitosan concentration, calcium chloride concentration and calcium chloride\/6-O-carboxymethyl chitosan ratio all had effects on the particle size and drug encapsulation efficiency. Nanoparticles with an average diameter of 193.4 nm, an average drug loading efficiency of up to 69.5% and an average drug loading of up to 0.395% were prepared successfully with the optimal formulation. Flow cytometry and confocal microscopy analyses showed that the cellular uptake of DOX in human breast cancer cell lines (MCF-7) was higher in the CRGDYC-modified nanoparticles compared with the unmodified nanoparticles. In vivo imaging showed that the distribution of CRGDYC-modified nanoparticles in the tumor site was higher compared with the unmodified nanoparticles. These results suggest that CRGDYC-6-O-carboxymethyl chitosan may be a promising cancer targeting carrier which can enhance the intracellular uptake and cytotoxicity of the drug-loaded nanoparticles.","subset":"pubmed_abstract"} +{"meta":{"pmid":28085301,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":2,"unknown":17}}},"text":"Thermalization of oscillator chains with onsite anharmonicity and comparison with kinetic theory.\nWe perform microscopic molecular dynamics simulations of particle chains with an onsite anharmonicity to study relaxation of spatially homogeneous states to equilibrium, and directly compare the simulations with the corresponding Boltzmann-Peierls kinetic theory. The Wigner function serves as a common interface between the microscopic and kinetic level. We demonstrate quantitative agreement after an initial transient time interval. In particular, besides energy conservation, we observe the additional quasiconservation of the phonon density, defined via an ensemble average of the related microscopic field variables and exactly conserved by the kinetic equations. On superkinetic time scales, density quasiconservation is lost while energy remains conserved, and we find evidence for eventual relaxation of the density to its canonical ensemble value. However, the precise mechanism remains unknown and is not captured by the Boltzmann-Peierls equations.","subset":"pubmed_abstract"} +{"meta":{"pmid":6603790,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":11}}},"text":"Associations among cataract prevalence, sunlight hours, and altitude in the Himalayas.\nThe relationship between cataract prevalence, altitude, and sunlight hours was investigated in a large national probability sample survey of 105 sites in the Himalayan kingdom of Nepal, December 1980 through April 1981. Cataract of senile or unknown etiology was diagnosed by ophthalmologists in 873 of 30,565 full-time life-long residents of survey sites. Simultaneously, the altitude of sites was measured using a standard mountain altimeter. Seasonally adjusted average daily duration of sunlight exposure for each site was calculated by a method which took into account latitude and obstructions along the skyline. Age- and sex-standardized cataract prevalence was 2.7 times higher in sites at an altitude of 185 meters or less than in sites over 1000 meters. Cataract prevalence was negatively correlated with altitude (r = -0.533, p less than 0.0001). However, a positive correlation between cataract prevalence and sunlight was observed (r = 0.563, p less than 0.0001). Sites with an average of 12 hours of sunlight exposure had 3.8 times as much cataract as sites with an average of only seven hours of exposure. Sunlight was blocked from reaching certain high altitude sites by tall neighboring mountains.","subset":"pubmed_abstract"} +{"meta":{"pmid":22717349,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1,"unknown":5}}},"text":"Analysis of lactation shapes in extended lactations.\nIn order to describe the temporal evolution of milk yield (MY) and composition in extended lactations, 21 658 lactations of Italian Holstein cows were analyzed. Six empirical mathematical models currently used to fit 305 standard lactations (Wood, Wilmink, Legendre, Ali and Schaeffer, quadratic and cubic splines) and one function developed specifically for extended lactations (a modification of the Dijkstra model) were tested to identify a suitable function for describing patterns until 1000 days in milk (DIM). Comparison was performed on individual patterns and on average curves grouped according to parity (primiparous and multiparous) and lactation length (standard \u2264305 days, and extended from 600 to 1000 days). For average patterns, polynomial models showed better fitting performances when compared with the three or four parameters models. However, LEG and spline regression, showed poor prediction ability at the extremes of the lactation trajectory. The Ali and Schaeffer polynomial and Dijkstra function were effective in modelling average curves for MY and protein percentage, whereas a reduced fitting ability was observed for fat percentage and somatic cell score. When individual patterns were fitted, polynomial models outperformed nonlinear functions. No detectable differences were observed between standard and extended patterns in the initial phase of lactation, with similar values of peak production and time at peak. A considerable difference in persistency was observed between 200 and 305 DIM. Such a difference resulted in an estimated difference between standard and extended cycle of about 7 and 9 kg\/day for daily yield at 305 DIM and of 463 and 677 kg of cumulated milk production at 305 DIM for the first- and second-parity groups, respectively. For first and later lactation animals, peak yield estimates were nearly 31 and 38 kg, respectively, and occurred at around 65 and 40 days. The asymptotic level of production was around 9 kg for multiparous cows, whereas the estimate was negative for first parity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28428557,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":16}}},"text":"The prognostic significance of Cdc6 and Cdt1 in breast cancer.\nDNA replication is a critical step in cell proliferation. Overexpression of MCM2-7 genes correlated with poor prognosis in breast cancer patients. However, the roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in breast cancers are largely unknown. In the present study, we have shown that the expression levels of Cdc6 and Cdt1 were both significantly correlated with an increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort (n = 1441). In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer, and was suppressed when ER signalling was inhibited either by tamoxifen in vitro or letrozole in human subjects. Importantly, breast cancer patients who responded to letrozole expressed significantly lower Cdc6 than those patients who did not respond. Our results suggest that Cdc6 is a potential prognostic marker and therapeutic target in breast cancer patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":18542569,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":1,"2024-10":1,"unknown":8}}},"text":"Anomalies in the disappearance of the extraordinary electromagnetic transmission in subwavelength hole arrays.\nWe studied the evolution of the Extraordinary Electromagnetic Transmission (EET) through subwavelength hole arrays versus hole size. Here, we show that for large holes EET vanishes and is replaced by another unusual transmission. A specific hole size is found where all the characteristics of the EET vanish and where most usual models fail to describe the transmission except full 3D simulations. The transition between these two domains is characterized by the discontinuity of parameters describing the transmission, in particular the resonance frequency. This transition exhibits a first order phase transition like behavior.","subset":"pubmed_abstract"} +{"meta":{"pmid":29377680,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Controlled Formation and Binding Selectivity of Discrete Oligo(methyl methacrylate) Stereocomplexes.\nThe triple-helix stereocomplex of poly(methyl methacrylate) (PMMA) is a unique example of a multistranded synthetic helix that has significant utility and promise in materials science and nanotechnology. To gain a fundamental understanding of the underlying assembly process, discrete stereoregular oligomer libraries were prepared by combining stereospecific polymerization techniques with automated flash chromatography purification. Stereocomplex assembly of these discrete building blocks enabled the identification of (1) the minimum degree of polymerization required for the stereocomplex formation and (2) the dependence of the helix crystallization mode on the length of assembling precursors. More significantly, our experiments resolved binding selectivity between helical strands with similar molecular weights. This presents new opportunities for the development of next-generation polymeric materials based on a triple-helix motif.","subset":"pubmed_abstract"} +{"meta":{"pmid":17324737,"dup_signals":{"dup_doc_count":31,"dup_dump_count":26,"dup_details":{"curated_sources":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":2,"2014-41":2,"2014-35":2,"2014-23":1,"2014-15":2,"2017-39":1}}},"text":"Pulse wave velocity in familial combined hyperlipidemia.\nIn the present cross-sectional study we investigated whether familial combined hyperlipidemia (FCH) is associated with an increased arterial wall stiffness, and whether measures of arterial wall stiffness in FCH family members could contribute to cardiovascular risk stratification. Ninety-eight subjects with FCH and 230 unaffected relatives filled out a questionnaire about their smoking habits, medical history, and medication use. Fasting venous blood was drawn after discontinuation of any lipid-lowering medication. Pulse wave velocity (PWV) and augmentation index (AIx) were determined by applanation tonometry as surrogate markers of arterial stiffness. Patients with FCH had a significantly increased PWV compared to their unaffected relatives (9.07 +\/- 2.75 v 8.28 +\/- 2.62 m\/sec, P = .005), whereas AIx was not increased (21.6 +\/- 12.7 v 15.6 +\/- 14.1, P = .96). Age- and gender-adjusted PWV was an equally good predictor of the presence of cardiovascular disease (CVD) in FCH family members as the most predictive combination of age- and gender-adjusted clinical and biochemical risk factors, including total cholesterol, HDL-cholesterol, and systolic blood pressure (area under the receiver operating curve (ROC) [AUC] 0.83 [0.76-0.90] v AUC 0.84 [0.78-0.91], P = .83). Addition of PWV to the multivariable prognostic model, including these age- and gender-adjusted traditional risk factors, did not increase the predictive ability for CVD (AUC 0.84 [0.79-0.89]). Patients with FCH are characterized by an increased arterial stiffness. The PWV predicts the presence of CVD equally well as any combination of clinical and traditional biochemical risk factors, but PWV has no additional value in addition to traditional risk factor screening in FCH families.","subset":"pubmed_abstract"} +{"meta":{"pmid":33839748,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Safety and feasibility of laparoscopic surgery for elderly rectal cancer patients in Japan: a nationwide study.\nThis study aimed to analyse the perioperative results from a national dataset of rectal cancer resections in elderly patients. The clinical records of patients undergoing rectal cancer surgery between 2012 and 2014 were retrieved from the Japanese National Clinical Database and analysed retrospectively. Patients were categorized according to age and those 80 years or older were defined as elderly. Subgroups were also defined according to the surgical approach (laparoscopy versus open surgery). The short-term outcomes, including mortality, anastomotic leak, surgical site infections and medical complications were compared between subgroups. Of 56 175 patients undergoing rectal cancer surgery, some 6717 patients were elderly and laparoscopy was performed in 46.8 per cent of the sample. When comparing laparoscopy and open surgery in elderly patients, the operative mortality rate (1.5 versus 2.8 per cent; P < 0.001), the incidence of anastomotic leakage (5.2 versus 6.5 per cent; P = 0.026), surgical site infections (6.0 versus 8.0 per cent; P = 0.001), pneumonia (1.4 versus 2.5 per cent; P = 0.001), renal failure (0.7 versus 1.3 per cent; P = 0.016) and cardiac events (0.3 versus 0.8 per cent; P = 0.008) were lower for laparoscopy than for open surgery. The overall complication rate in elderly patients (19.5 per cent) was comparable to that in the younger group (P = 0.07). However, incidence of systemic complications was significantly higher in elderly than in younger patients (all P < 0.001). Laparoscopy was safe and feasible in elderly patients compared with open surgery. However, the rates of systemic complications were significantly higher than in younger patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":21629783,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Changing patterns of malaria epidemiology between 2002 and 2010 in Western Kenya: the fall and rise of malaria.\nThe impact of insecticide treated nets (ITNs) on reducing malaria incidence is shown mainly through data collection from health facilities. Routine evaluation of long-term epidemiological and entomological dynamics is currently unavailable. In Kenya, new policies supporting the provision of free ITNs were implemented nationwide in June 2006. To evaluate the impacts of ITNs on malaria transmission, we conducted monthly surveys in three sentinel sites with different transmission intensities in western Kenya from 2002 to 2010. Longitudinal samplings of malaria parasite prevalence in asymptomatic school children and vector abundance in randomly selected houses were undertaken monthly from February 2002. ITN ownership and usage surveys were conducted annually from 2004 to 2010. Asymptomatic malaria parasite prevalence and vector abundances gradually decreased in all three sites from 2002 to 2006, and parasite prevalence reached its lowest level from late 2006 to early 2007. The abundance of the major malaria vectors, Anopheles funestus and An. gambiae, increased about 5-10 folds in all study sites after 2007. However, the resurgence of vectors was highly variable between sites and species. By 2010, asymptomatic parasite prevalence in Kombewa had resurged to levels recorded in 2004\/2005, but the resurgence was smaller in magnitude in the other sites. Household ITN ownership was at 50-70% in 2009, but the functional and effective bed net coverage in the population was estimated at 40.3%, 49.4% and 28.2% in 2010 in Iguhu, Kombewa, and Marani, respectively. The resurgence in parasite prevalence and malaria vectors has been observed in two out of three sentinel sites in western Kenya despite a high ownership of ITNs. The likely factors contributing to malaria resurgence include reduced efficacy of ITNs, insecticide resistance in mosquitoes and lack of proper use of ITNs. These factors should be targeted to avoid further resurgence of malaria transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":27510884,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":1,"2017-13":1,"2024-18":1,"unknown":15}}},"text":"In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography.\nMR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique. Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol\/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis. The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses. The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses.","subset":"pubmed_abstract"} +{"meta":{"pmid":16549372,"dup_signals":{"dup_doc_count":11}},"text":"Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes.\nCalcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes by assessing expression of the receptor and pharmacological effects on collagen type II degradation under ex vivo and in vivo conditions. Localization of the calcitonin receptor on articular chondrocytes was investigated by immunohistochemistry, and the expression by reverse transcriptase polymerase chain reaction (RT-PCR). In bovine articular cartilage explants, cartilage degradation was investigated by release of C-terminal telopeptides of collagen type II (CTX-II), induced by tumor necrosis factor-alpha (TNF-alpha) [20 ng\/ml] and oncostatin M (OSM) [10 ng\/ml], with salmon calcitonin [0.0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg\/kg calcitonin] for 9 weeks. The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration-dependently increased cAMP levels in isolated chondrocytes. Explants cultured with TNF-alpha and OSM showed a 100-fold increase in CTX-II release compared to vehicle-treated controls (P<0.001). The degradation of type II collagen in these explants was concentration-dependently inhibited by calcitonin, 65% protection at 10 nM calcitonin (P<0.01). TNF-alpha and OSM induced a pronounced increase in matrix metalloproteinase (MMP) activity, which was strongly inhibited by calcitonin. In vivo, administration of salmon calcitonin to OVX rats resulted in significant (P<0.001) decrease in CTX-II levels. These results are the first evidence of calcitonin receptor expression on articular chondrocytes and that the chondroprotective effects of calcitonin might involve the inhibition of MMP expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":14765981,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Progesterone induction of calcitonin expression in the murine mammary gland.\nProgesterone, via its nuclear receptor, is mandatory not only for the induction and specification of mammary gland ductal side-branching and lobuloalveologenesis but also for carcinogen-induced mammary tumorigenesis. Notwithstanding these recent advances, a more comprehensive molecular explanation of progesterone-induced mammary morphogenesis is contingent upon the identification and characterization of mammary molecular targets that are responsive to the progesterone signal. Toward this goal, we report that calcitonin, a 32 amino acid peptide hormone involved in calcium homeostasis, is exclusively expressed in, and secreted from, luminal epithelial cells within the mammary gland of the pregnant mouse, and, importantly, its expression is progesterone-dependent. Conversely, the calcitonin receptor is present during all stages of post-natal mammary development examined, is localized to the myoepithelial cell lineage, and is not regulated by progesterone. Because calcitonin induction spatiotemporally correlates with increases in progesterone-induced mammary gland proliferation and structural remodeling, we posit that calcitonin - through its receptor - may be involved in one or both of these progesterone-dependent processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":26749535,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Patient-reported outcomes of implant placement performed concomitantly with transcrestal sinus floor elevation or entirely in native bone.\nBased on the hypothesis that maxillary sinus floor elevation with a transcrestal approach (tSFE) does not increase the morbidity of implant surgery, the study evaluated the patient-reported outcomes as well as the type and incidence of complications when implants are placed either concomitantly with tSFE (performed according to Trombelli et al. 2008, 2010a,b) or entirely in native bone. Data from the record charts of patients undergone implant placement for single-tooth rehabilitation in the posterior maxilla were retrospectively obtained from four clinical centers. Cases for tSFE group were included if they showed an extent of sinus lift \u22654 mm concomitantly to implant placement. Cases for N group were included when implant placement was performed entirely in native bone. Patient-reported outcomes had been assessed using 100-mm visual analog scales (postoperative pain, VASpain ) and visual rating scales (level of discomfort, VRSdiscomfort ; willingness to undergo the same surgery, VRSwillingness ). The dose of analgesics had been self-recorded. A convenience sample of 14 patients and 17 patients (contributing with one implant site each) treated with tSFE and N, respectively, was obtained for this study. Membrane perforation occurred in 1 tSFE case, without compromising the completion of the procedure. VASpain remained low (<12) in both groups. A tendency of VASpain to decrease with time was observed in both groups. The area under the curve for VASpain (AUCpain ), indicating the level of pain experience through the first week following surgery, was 18.0 (IR: 8.5-85.0) and 11.5 (IR: 4.5-18.5) in tSFE and N groups, respectively, with no significant inter-group differences (P = 0.084). The dose of analgesics was similarly low between groups. No significant inter-group difference in VRSdiscomfort and VRSwillingness was observed. Implant placement performed either concomitantly with tSFE (according to Trombelli et al. 2008, 2010a,b) or entirely in native bone is associated with limited incidence of complications, low postoperative pain and medication and are both well tolerated.","subset":"pubmed_abstract"} +{"meta":{"pmid":30250952,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Ternary semiconductor ZnxAg1-xS nanocomposites for efficient photocatalytic degradation of organophosphorus pesticides.\nThe construction of ternary semiconductor nanostructures has attracted much attention in photocatalysis by virtue of their tunable elemental composition and band structure. Here, ternary semiconductor ZnxAg1-xS (0 \u2264 x \u2264 1) composites were successfully prepared by a simple and low-cost hydrothermal method without using any surfactant. Combined analyses using XRD, N2 sorption, SEM, TEM and UV-vis DRS revealed that the ternary composite semiconductor materials exhibited well-developed crystalline frameworks, large surface areas of 15-70 m2 g-1, sizes of 10-30 nm, and outstanding UV light absorption properties. Data from XRD and TEM indicate that photocatalysis might contribute to the formation of the strong interfacial interaction between ZnS and Ag2S nanoparticles. The photocatalytic activities were investigated via the degradation of organophosphorus pesticides, including malathion (MLT), monocrotophos (MCP) and chlorpyrifos (CPS), using the ZnxAg1-xS composites under UV light irradiation. The toxicity of MLT, MCP, and CPS was reduced by photocatalysis and photolysis; however, photocatalysis had a greater impact. Superior photocatalytic performance was exhibited by the Zn0.5Ag0.5S catalyst owing to its large surface area and the presence of Ag0 with improved charge transfer in comparison with that of bare ZnS and Ag2S. Assays of stability and reusability indicated that the Zn0.5Ag0.5S composite retained more than 85% of its activity after five cycles of use. On the basis of the results, a possible photocatalytic mechanism of the prepared samples was proposed. This study indicates a potential application of the ternary semiconductor materials in the efficient UV light-driven photocatalytic degradation of other pollutants that may cause environmental pollution.","subset":"pubmed_abstract"} +{"meta":{"pmid":32301484,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2023-23":2,"2023-14":1,"2022-49":1,"2022-27":1,"2021-43":2,"2021-17":1,"2021-04":1,"2020-40":1,"2020-34":1,"2024-22":1}}},"text":"Application of Selected Muscle Strength and Body Mass Cut Points for the Diagnosis of Sarcopenia in Men and Women With or at Risk for HIV Infection.\nPersons with HIV may experience greater mobility limitations than uninfected populations. Accurate tools are needed to identify persons at greatest risk of decline. We evaluated the performance of novel muscle weakness metrics (grip, grip\/body mass index [BMI], grip\/weight, grip\/total body fat, grip\/arm lean mass) and association with slowness and falls in older persons with or at risk for HIV infection as part of the work of the Sarcopenia Definitions and Outcomes Consortium (SDOC). We assessed the prevalence of sarcopenia among 398 men (200 HIV+, 198 HIV-) from the Multicenter AIDS Cohort Study and 247 women (162 HIV+, 85 HIV-) from the Women's Interagency HIV Study using previously validated muscle weakness metrics discriminative of slowness. Sensitivity and specificity were used to compare new muscle weakness and slowness criteria to previously proposed sarcopenia definitions. The prevalence of muscle weakness ranged from 16% to 66% among men and 0% to 47% among women. Grip\/BMI was associated with slowness among men with HIV only. Grip\/BMI had low sensitivity (25%-30%) with moderate to high specificity (68%-89%) for discriminating of slowness; all proposed metrics had poor performance in the discrimination of slowness (area under the curve [AUC] < 0.62) or fall status (AUC < 0.56). The combination of muscle weakness and slowness was not significantly associated with falls (p \u2265 .36), with a low sensitivity in identifying those sustaining one or more falls (sensitivity \u2264 16%). Clinical utility of new sarcopenia metrics for identification of slowness or falls in men and women with or at risk for HIV is limited, given their low sensitivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28819669,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":3,"unknown":18}}},"text":"Drastic difference between hole and electron injection through the gradient shell of CdxSeyZn1-xS1-y quantum dots.\nUltrafast fluorescence spectroscopy was used to investigate the hole injection in CdxSeyZn1-xS1-y gradient core-shell quantum dot (CSQD) sensitized p-type NiO photocathodes. A series of CSQDs with a wide range of shell thicknesses was studied. Complementary photoelectrochemical cell measurements were carried out to confirm that the hole injection from the active core through the gradient shell to NiO takes place. The hole injection from the valence band of the QDs to NiO depends much less on the shell thickness when compared to the corresponding electron injection to n-type semiconductor (ZnO). We simulate the charge carrier tunneling through the potential barrier due to the gradient shell by numerically solving the Schr\u00f6dinger equation. The details of the band alignment determining the potential barrier are obtained from X-ray spectroscopy measurements. The observed drastic differences between the hole and electron injection are consistent with a model where the hole effective mass decreases, while the gradient shell thickness increases.","subset":"pubmed_abstract"} +{"meta":{"pmid":26066093,"dup_signals":{"dup_doc_count":56,"dup_dump_count":37,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":1,"2022-21":1,"2021-43":3,"2021-31":2,"2021-21":2,"2021-17":2,"2021-04":3,"2020-45":1,"2020-40":1,"2020-34":3,"2020-29":2,"2020-24":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":2,"2019-47":1,"2019-43":2,"2019-35":3,"2019-26":1,"2019-22":2,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2024-22":1}}},"text":"Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair.\nHuman pluripotent stem cells (hPSCs) have emerged as an important source for cell therapy. However, to date, no studies demonstrated generation of purified hPSC-derived lymphatic endothelial cells (LECs) and tested their therapeutic potential in disease models. Here we sought to differentiate hPSCs into the LEC lineage, purify them with LEC markers, and evaluate their therapeutic effects. We found that an OP9-assisted culture system reinforced by addition of VEGF-A, VEGF-C, and EGF most efficiently generated LECs, which were then isolated via FACS-sorting with LYVE-1 and PODOPLANIN. These hPSC-derived LYVE-1(+)PODOPLANIN(+)cells showed a pure committed LEC phenotype, formed new lymphatic vessels, and expressed lymphangiogenic factors at high levels. These hPSC-derived LECs enhanced wound healing through lymphangiogenesis and lymphvasculogenesis. Here we report, for the first time, that LECs can be selectively isolated from differentiating hPSCs, and that these cells are potent for lymphatic vessel formation in vivo and wound healing. This system and the purified hPSC-derived LECs can serve as a new platform for studying LEC development as well as for cell therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":11954800,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Metabolic response against sulfur-containing heterocyclic compounds by the lignin-degrading basidiomycete Coriolus versicolor.\nThe fungal conversions of sulfur-containing heterocyclic compounds were investigated using the lignin-degrading basidiomycete Coriolus versicolor. The fungus metabolized a series of sulfur compounds--25 structurally related thiophene derivatives--via several different pathways. Under primary metabolic conditions, C. versicolor utilized thiophenes, such as 2-hydroxymethyl-, 2-formyl-, and 2-carboxyl-thiophenes, as a nutrient sulfur source for growth; thus, the fungus degraded these compounds more effectively in a non-sulfur-containing medium than in conventional medium. The product analysis revealed that several redox reactions, decarboxylation reactions, and C-S cleavage reactions were involved in the fungal conversion of non-aromatic thiophenes. On the other hand, benzothiophene (BT) and dibenzothiophene (DBT) skeletons were converted to water-soluble products. All the products and metabolic intermediates were more hydrophilic than the starting substrates. These metabolic actions seemed to be a chemical stress response against exogenously added xenobiotics. These metabolic reactions were optimized under ligninolytic conditions, also suggesting the occurrence of a fungal xenobiotic response. Furthermore, the fungus converted a series of BTs and DBTs via several different pathways, which seemed to be controlled by the chemical structure of the substrates. DBT, 4-methylDBT, 4, 6-dimethylDBT, 2-methylBT, and 7-methylBT were immediately oxidized to their S-oxides. BTs and DBTs with the hydroxymethyl substituent were converted to their xylosides without S-oxidation. Those with carboxyl and formyl substituents were reduced to form a hydroxymethyl group, then xylosidated. These observations strongly suggested the involvement of a fungal substrate-recognition and metabolic response mechanism in the metabolism of sulfur-containing heterocyclic compounds by C. versicolor.","subset":"pubmed_abstract"} +{"meta":{"pmid":23291387,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2017-13":1,"2024-30":1,"unknown":7}}},"text":"A systematic review of ultrasonography in gout and asymptomatic hyperuricaemia.\nGout is one of the most common inflammatory arthritides. The literature reveals that management of this condition is often suboptimal. Imaging techniques, such as ultrasound (US), may assist in the diagnosis and management of gout and asymptomatic hyperuricaemia (AH). To undertake a systematic review evaluating US as an outcome tool in gout and asymptomatic hyperuricaemia, articles published in Medline and PubMed (1975-February 2012) were identified. Data was extracted and categorised into four different groups namely tophi, articular cartilage, soft tissue pathologies and bony changes, with a focus on validity, responsiveness, reproducibility and feasibility. Lesions reported in the literature include tophi, cartilage abnormalities, soft tissue lesions and erosions. US is able to detect tophi, using MRI as the gold standard, and is sensitive to change. The double contour sign seen overlying cartilage is specific to gout and sensitive to change. Synovial pathology is identified in gout, with some reporting intrasynovial hyperechogeneicity is suggestive of gout. US was less sensitive than MRI to cortical erosions in gout, but better than conventional radiography. Interobserver reliability when assessed ranged from fair to substantial agreement for soft tissue changes and was very good for assessing tophi, double contour and erosions. US is a promising tool which could be used in the diagnosis and management of gout. More studies are needed to assess responsiveness, reliability and feasibility.","subset":"pubmed_abstract"} +{"meta":{"pmid":35020741,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Distilling the curriculum: An analysis of alcohol industry-funded school-based youth education programmes.\nFor decades, corporations such as the tobacco and fossil fuel industries have used youth education programmes and schools to disseminate discourses, ideas and values favourable to their positions, and to pre-empt regulation that threatens profits. However, there is no systematic research into alcohol industry-funded youth education programmes. This article serves to address this important gap in the literature. Using a discourse theoretical approach informed by poststructural discourse theory and critical discourse analysis, we analysed teaching materials from three school-based youth education initiatives which focus on alcohol consumption and health harms: Drinkaware for Education, The Smashed Project (funded by Diageo), and Talk About Alcohol (Alcohol Education Trust). These materials, some of which are disseminated internationally, are provided to schools through intermediary bodies in receipt of alcohol industry funding. The analysis found that these materials drew from and presented discourses of personal responsibility, moderate alcohol consumption, and involved a narrowing of the problem definition and causes. The locus of the problem is located by the discourses within individuals including youth, with causes of youth alcohol consumption repeatedly presented as peer pressure and 'poor choices', with little or no mention of alcohol industry marketing or other practices. All programmes promoted familiarisation and normalisation of alcohol as a 'normal' adult consumer product which children must learn about and master how to use responsibly when older. The discourses constructed in these materials closely align with those of other alcohol industry corporate social responsibility discourses which employ selective presentation of harms, including misinformation about cancer, and ambiguous terms such as \"responsible drinking\". Furthermore, the role of alcohol price, availability and access, and the impacts of alcohol and the industry on inequities were not articulated within the discourses. The research was limited to an analysis of teaching materials and further research is needed to explore their impact on youth, teachers and wider discourses and social norms. Alcohol industry-sponsored youth education programmes serve industry interests and promote moderate consumption while purportedly educating children about harms and influences of alcohol use. There are considerable conflicts of interest in the delivery of alcohol education programmes funded by the alcohol industry and intermediary bodies in receipt of such funding. Alcohol education materials should be developed independent from industry, including funding, and should empower children and young people to understand and think critically about alcohol, including harms and drivers of consumption, and effective interventions needed to protect them and others from alcohol-related harms. Independent organisations can use this analysis to critique their materials to strengthen alignment with meeting student and public health interests. The ongoing exposure of children and young people to such conflicted and misleading materials needs urgent attention from policymakers, practitioners, teachers and parents, and resources dependent on industry support should cease being used in schools.","subset":"pubmed_abstract"} +{"meta":{"pmid":22238083,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":12}}},"text":"Perceptual learning reduces crowding in amblyopia and in the normal periphery.\nAmblyopia is a developmental visual disorder of cortical origin, characterized by crowding and poor acuity in central vision of the affected eye. Crowding refers to the adverse effects of surrounding items on object identification, common only in normal peripheral but not central vision. We trained a group of adult human amblyopes on a crowded letter identification task to assess whether the crowding problem can be ameliorated. Letter size was fixed well above the acuity limit, and letter spacing was varied to obtain spacing thresholds for central target identification. Normally sighted observers practiced the same task in their lower peripheral visual field. Independent measures of acuity were taken in flanked and unflanked conditions before and after training to measure crowding ratios at three fixed letter separations. Practice improved the letter spacing thresholds of both groups on the training task, and crowding ratios were reduced after posttest. The reductions in crowding in amblyopes were associated with improvements in standard measures of visual acuity. Thus, perceptual learning reduced the deleterious effects of crowding in amblyopia and in the normal periphery. The results support the effectiveness of plasticity-based approaches for improving vision in adult amblyopes and suggest experience-dependent effects on the cortical substrates of crowding.","subset":"pubmed_abstract"} +{"meta":{"pmid":23912261,"dup_signals":{"dup_doc_count":35,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2021-10":1,"2021-04":1,"2020-16":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-18":1,"2019-09":2,"2018-47":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-13":2,"2018-05":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-25":1,"2017-13":1}}},"text":"Resource competition induces heterogeneity and can increase cohort survivorship: selection-event duration matters.\nDetermining when resource competition increases survivorship can reveal processes underlying population dynamics and reinforce the importance of heterogeneity among individuals in conservation. We ran an experiment mimicking the effects of competition in a growing season on survivorship during a selection event (e.g., overwinter starvation, drought). Using a model fish species (Poecilia reticulata), we studied how food availability and competition affect mass in a treatment stage, and subsequently survivorship in a challenge stage of increased temperature and starvation. The post-treatment mean mass was strongly related to the mean time to mortality and mass at mortality at all levels of competition. However, competition increased variance in mass and extended the right tail of the survivorship curve, resulting in a greater number of individuals alive beyond a critical temporal threshold ([Formula: see text]) than without competition. To realize the benefits from previously experienced competition, the duration of the challenge ([Formula: see text]) following the competition must exceed the critical threshold [Formula: see text] (i.e., competition increases survivorship when [Formula: see text]). Furthermore, this benefit was equivalent to increasing food availability by 20 % in a group without competition in our experiment. The relationship of [Formula: see text] to treatment and challenge conditions was modeled by characterizing mortality through mass loss in terms of the stochastic rate of loss of vitality (individual's survival capacity). In essence, when the duration of a selection event exceeds [Formula: see text], competition-induced heterogeneity buffers against mortality through overcompensation processes among individuals of a cohort. Overall, our study demonstrates an approach to quantify how early life stage heterogeneity affects survivorship.","subset":"pubmed_abstract"} +{"meta":{"pmid":7931574,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"The extent of adaptation in bullfrog saccular hair cells.\nPositive deflection of the sensory hair bundle of a vertebrate hair cell opens transduction channels to depolarize the cell. In bullfrog saccular hair cells, there is a subsequent adaptation process, whereby the proportion of transduction channels that are open, and thus the receptor current, declines toward the resting value. This occurs because the sensitivity curve, relating open probability to bundle deflection, shifts along the deflection axis in response to bundle deflections, in a manner consistent with a relaxation of mechanical tension on transduction channels. In this study we determined the extent of adaptation, measured as the shift of the sensitivity curve following deflection of the hair bundle. The shift was determined both by comparison of the receptor current in the adapted state to the resting sensitivity curve, and by comparison of pre- and postadapted sensitivity curves. The adaptive shift approached steady state with a time constant of 20-30 msec, and was at steady state within 150 msec. For all positive and for small negative deflections, both methods showed a shift that was approximately 80% of the deflection. For larger negative deflections, the shift reached a fixed limit that was 100-500 nm negative to the freestanding bundle position. The limited extent of adaptation confers a time-dependent sensitivity: the cell has an instantaneous or phasic sensitivity curve that is steep, and steady-state or tonic sensitivity curve that is about five times broader. It also suggests the existence of two additional structural elements within the transduction apparatus. A revised quantitative theory accommodates these elements.","subset":"pubmed_abstract"} +{"meta":{"pmid":30628536,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Severe Herpes Zoster Following Varicella Vaccination in Immunocompetent Young Children.\nVaricella vaccination is now virtually universal in North America, as well as in some European and Asian countries. Since varicella vaccine is a live attenuated virus, the virus replicates in the skin after administration and can travel via sensory nerves or viremia to become latent in the dorsal root ganglia. In some immunized children, virus reactivates within a few months to a few years to cause the dermatomal exanthem known as herpes zoster (shingles). Herpes zoster caused by vaccine virus often reactivates within the same dermatome as the site of the original varicella vaccine injection. We present evidence that occasional cases of herpes zoster following varicella vaccination in immunocompetent children can be as severe as herpes zoster following wild-type varicella. Analysis of the virus in one case disclosed that the vaccine virus causing herpes zoster was a wild-type variant with a mutation in ORF0. With regard to dermatomal localization of the viral eruption, we predict that herpes zoster of the lumbar dermatomes in children is likely to be caused by vaccine virus, because herpes zoster in those dermatomes is rare in children after wild-type varicella. One of the children with herpes zoster subsequently developed asthma, a known risk factor for herpes zoster, but none of the children had an autoimmune disease. Although postherpetic neuralgia is exceedingly rare, children who develop herpes zoster following varicella vaccination are at risk (albeit low) of developing meningoencephalitis and should be carefully observed for a few weeks.","subset":"pubmed_abstract"} +{"meta":{"pmid":31795854,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Long-Term Follow-Up of a Randomized Trial of Supported Employment for SSDI Beneficiaries With Mental Illness.\nIn this study, the authors assessed the long-term impact of the Mental Health Treatment Study (MHTS), a randomized controlled trial testing the effects of providing 2 years of employment services based on the evidence-based individualized placement and support model to Social Security Disability Insurance (SSDI) recipients with serious mental illness. Treatment recipients also received systematic medication management, supplemental health care supports, and short-term relief from medical continuing disability review by the Social Security Administration (SSA). MHTS site data for 2,160 participants were linked to SSA administrative data from 2011 to 2015, 1 to 5 years after the original study concluded. Univariate and multivariate models were used to assess the MHTS effects on employment, earnings, and disability benefit suspension-termination up to 7 years after services ended. The analyses showed that the treatment group was more likely than the control group to work, and average earnings among the treatment group increased more over time than earnings among the control group. Disability benefit suspension\/termination did not differ between groups. Providing the demonstration's package of services and support to SSDI beneficiaries with psychiatric disabilities for up to 2 years may have a long-term impact on employment and earnings. Under the SSDI program as currently structured, however, even after receiving 2 years of evidence-based supported employment and high-quality mental health services, SSDI beneficiaries with psychiatric conditions are unlikely to achieve economic independence within 5 years.","subset":"pubmed_abstract"} +{"meta":{"pmid":34972600,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Women Veterans' Attrition from the VA Health Care System.\nPatient attrition from the Veterans Health Administration (VA) health care system could undercut its mission to ensure care for eligible veterans. Attrition of women veterans could exacerbate their minority status and impede systemic efforts to provide high-quality care. We obtained women veterans' perspectives on why they left or continued to use VA health care. A sampling frame of new women veteran VA patients was stratified by those who discontinued (attriters) and those who continued (non-attriters) using VA care. Semistructured interviews were conducted from 2017 to 2018. Transcribed interviews were coded for women's decision-making, contexts, and recommendations related to health care use. Fifty-one women veterans (25 attriters and 26 non-attriters) completed interviews. Reasons for attrition included challenging patient care experiences (e.g., provider turnover, claim processing challenges) and the availability of private health insurance. Personal experiences with VA care (e.g., gender-specific care) were impactful in women's decision to use VA. The affordability of VA care was influential for both groups to stay connected to services. More than one-third of women originally categorized as attriters described subsequently reentering or planning to reenter VA care. Suggestions to decrease attrition included increasing outreach, improving access, and continuing to tailor care delivery to women veterans' needs. Understanding the drivers of patients' decisions to use or not use the VA is critical for the development of strategies to improve retention of current patients and optimize health outcomes for veterans. Women veterans described complex reasons why they left or continued using VA, with cost\/affordability playing an important role even in considerations of returning to VA after a long hiatus.","subset":"pubmed_abstract"} +{"meta":{"pmid":23297732,"dup_signals":{"dup_doc_count":62,"dup_dump_count":50,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":2,"2023-14":2,"2023-06":1,"2022-40":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-31":3,"2021-17":1,"2021-10":1,"2021-04":1,"2020-40":1,"2020-34":1,"2020-24":1,"2019-51":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":2,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-50":1,"2024-22":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1}}},"text":"Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years.\nOver the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya. Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates. Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90-0.98), with the density standing at low levels of an average 0.006 mosquitoes\/house in the year 2010. Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":26515434,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2019-30":1,"2019-26":3,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2020-34":1,"2017-13":1}}},"text":"Fast synthesis of platinum nanopetals and nanospheres for highly-sensitive non-enzymatic detection of glucose and selective sensing of ions.\nNovel methods to obtain Pt nanostructured electrodes have raised particular interest due to their high performance in electrochemistry. Several nanostructuration methods proposed in the literature use costly and bulky equipment or are time-consuming due to the numerous steps they involve. Here, Pt nanostructures were produced for the first time by one-step template-free electrodeposition on Pt bare electrodes. The change in size and shape of the nanostructures is proven to be dependent on the deposition parameters and on the ratio between sulphuric acid and chloride-complexes (i.e., hexachloroplatinate or tetrachloroplatinate). To further improve the electrochemical properties of electrodes, depositions of Pt nanostructures on previously synthesised Pt nanostructures are also performed. The electroactive surface areas exhibit a two order of magnitude improvement when Pt nanostructures with the smallest size are used. All the biosensors based on Pt nanostructures and immobilised glucose oxidase display higher sensitivity as compared to bare Pt electrodes. Pt nanostructures retained an excellent electrocatalytic activity towards the direct oxidation of glucose. Finally, the nanodeposits were proven to be an excellent solid contact for ion measurements, significantly improving the time-stability of the potential. The use of these new nanostructured coatings in electrochemical sensors opens new perspectives for multipanel monitoring of human metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":24001996,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-27":1,"2022-21":1,"2021-49":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-04":2,"2020-45":1,"2020-40":1,"2020-29":1,"2023-06":1}}},"text":"Probable nosocomial transmission of listeriosis in neonates.\nListeria monocytogenes was isolated in two neonates born consecutively in the same hospital in France. The isolates had indistinguishable pulsed-field electrophoresis profiles. Retrospective epidemiological investigations found no evidence of a food-borne or environmental source. Infection control protocols and decontamination processes were in accordance with standard recommendations. The timing of onset of these infections within the same maternity unit, and the similarity of pulsed-field gel electrophoresis profiles suggests cross-infection of L. monocytogenes between the two neonates.","subset":"pubmed_abstract"} +{"meta":{"pmid":25884426,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Endothelial cell self-fusion during vascular pruning.\nDuring embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":30397229,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Potential of Oryza officinalis to augment the cold tolerance genetic mechanisms of Oryza sativa by network complementation.\nOryza officinalis is an accessible alien donor for genetic improvement of rice. Comparison across a representative panel of Oryza species showed that the wild O. officinalis and cultivated O. sativa ssp. japonica have similar cold tolerance potentials. The possibility that either distinct or similar genetic mechanisms are involved in the low temperature responses of each species was addressed by comparing their transcriptional networks. General similarities were supported by shared transcriptomic signatures indicative of equivalent metabolic, hormonal, and defense status. However, O. officinalis has maintained an elaborate cold-responsive brassinosteroid-regulated BES1-network that appeared to have been fragmented in O. sativa. BES1-network is potentially important for integrating growth-related responses with physiological adjustments and defenses through the protection of photosynthetic machinery and maintenance of stomatal aperture, oxidative defenses, and osmotic adjustment. Equivalent physiological processes are functional in O. sativa but their genetic mechanisms are under the direct control of ABA-dependent, DREB-dependent and\/or oxidative-mediated networks uncoupled to BES1. While O. officinalis and O. sativa represent long periods of speciation and domestication, their comparable cold tolerance potentials involve equivalent physiological processes but distinct genetic networks. BES1-network represents a novel attribute of O. officinalis with potential applications in diversifying or complementing other mechanisms in the cultivated germplasm.","subset":"pubmed_abstract"} +{"meta":{"pmid":22179952,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"An extinct Eocene taxon of the daisy family (Asteraceae): evolutionary, ecological and biogeographical implications.\nMorphological, molecular and biogeographical information bearing on early evolution of the sunflower alliance of families suggests that the clade containing the extant daisy family (Asteraceae) differentiated in South America during the Eocene, although palaeontological studies on this continent failed to reveal conclusive support for this hypothesis. Here we describe in detail Raiguenrayun cura gen. & sp. nov., an exceptionally well preserved capitulescence of Asteraceae recovered from Eocene deposits of northwestern Patagonia, Argentina. The fossil was collected from the 47\u00b75 million-year-old Huitrera Formation at the Estancia Don Hip\u00f3lito locality, R\u00edo Negro Province, Argentina. The arrangement of the capitula in a cymose capitulescence, the many-flowered capitula with multiseriate-imbricate involucral bracts and the pappus-like structures indicate a close morphological relationship with Asteraceae. Raiguenrayun cura and the associated pollen Mutisiapollis telleriae do not match exactly any living member of the family, and clearly represent extinct taxa. They share a mosaic of morphological features today recognized in taxa phylogenetically close to the root of Asteraceae, such as Stifftieae, Wunderlichioideae and Gochnatieae (Mutisioideae sensu lato) and Dicomeae and Oldenburgieae (Carduoideae), today endemic to or mainly distributed in South America and Africa, respectively. This is the first fossil genus of Asteraceae based on an outstandingly preserved capitulescence that might represent the ancestor of Mutisioideae-Carduoideae. It might have evolved in southern South America some time during the early Palaeogene and subsequently entered Africa, before the biogeographical isolation of these continents became much more pronounced. The new fossil represents the first reliable point for calibration, favouring an earlier date to the split between Barnadesioideae and the rest of Asteraceae than previously thought, which can be traced back at least 47\u00b75 million years. This is the oldest well dated member of Asteraceae and perhaps the earliest indirect evidence for bird pollination in the family.","subset":"pubmed_abstract"} +{"meta":{"pmid":7153201,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Sensory reinforcement in the mentally handicapped and autistic child: a review.\nSensory reinforcement was first studied by learning theorists working with animals in the 1950s. Attempts to examine the phenomenon with children followed in the 1960s, and the studies demonstrated that sensory stimuli could act like any other reinforcers with normal young children. Similar work with the autistic and mentally handicapped child arose in relation to both the study of receptor development and more treatment-oriented research. It now seems that even profoundly handicapped children can learn to operate simple levers when reinforced by sensory stimuli, and some handicapped children have learned quite complex skills through sensory reinforcement. There also appears to be a close relationship between stereotyped behavior and sensory reinforcement. The clinical implications of the studies reviewed are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":29675171,"dup_signals":{"dup_doc_count":12}},"text":"Diphosphine-protected ultrasmall gold nanoclusters: opened icosahedral Au13 and heart-shaped Au8 clusters.\nDue to distinctive quantum confinement effects, ultrasmall gold nanoparticles usually exhibit interesting electronic structure and molecular-like properties. However, the lack of atomically-precise structural information makes the understanding of them almost impossible, such as understanding the relationships between their compositions and unique properties. Herein, by reducing a diphosphine AuI precursor (Au2(dppm)2Cl2; dppm = Ph2PCH2PPh2) with or without a S2- releasing reagent, we enriched our knowledge of the members in the families of Au13 and Au8 by the structural determinations of two new dppm-protected gold nanoclusters, [Au13(dppm)6]5+ (SD\/Au1) and [Au8(dppm)4S2]2+ (SD\/Au2), respectively. Within SD\/Au1, the Au13 kernel significantly deviates from the ideal Ih icosahedron by the elongation of three surface Au-Au bonds to \u223c3.5 \u00c5, giving it C3 symmetry, whereas SD\/Au2 has a novel heart-shaped C2 symmetric Au8S2 core (central Au4 tetrahedron + two Au2S units) protected by four \u03bc2-dppm ligands in the outer shell. Of note, SD\/Au1 represents a rare Au13 nanocluster with an opened icosahedral geometry, and SD\/Au2 shows a new edge-shared \"core + 4exo\" structure type that has never been observed before. The electronic structures and optical absorption spectra of these systems are correlated with time-dependent density functional theory (TDDFT) calculations. Based on the spherical jellium model, the stability of the Au13 and Au8 nanoclusters can be ascribed to 8- and 2-electron superatoms with 1S21P6 and 1S2 configurations, respectively. Interestingly, the cluster SD\/Au2 exhibits bright yellow luminescence with an emission maximum at 591 nm that slightly hypsochromically shifts to 581 nm upon cooling to 93 K. Our findings not only enrich the family of diphosphine-protected ultrasmall gold nanoclusters, but also demonstrate the rich variations of gold kernels during the transformation from a simple AuI precursor to Au nanoclusters.","subset":"pubmed_abstract"} +{"meta":{"pmid":18293041,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Potential chemosignals in the anogenital gland secretion of giant pandas, Ailuropoda melanoleuca, associated with sex and individual identity.\nWith a combination of dichloromethane extraction and analysis by gas chromatography-mass spectrometry (GC-MS), we found 39 compounds (corresponding to 38 GC peaks) in the anogenital gland secretion (AGS) of captive adult giant pandas, Ailuropoda melanoleuca, during the non-mating season. In addition to indole, squalene, and some of the straight-chain fatty acids that had been characterized previously from the AGS of giant pandas, we identified several new compounds such as decenal, two isomers of decadienal, phenylacetic acid, 5-methylhydantoin, hydroquinone, phenylpropanoic acid, and erucic acid. Quantitative comparison of the relative abundances of the 20 main GC peaks revealed that 5-methylhydantoin, indole, and erucic acid are putative female pheromones, whereas squalene and hydroquinone are putative male pheromones. In addition to the presence of a few individual-specific compounds, the relative abundances of most of the 21 constituents varied more among individuals than within individuals. This suggests that individual identity might be coded in both digital and analog form. The chemical composition of different AGS samples from the same pandas consistently displayed a minimum cluster distance, much smaller than that between samples from different individuals in a hierarchical linkage cluster (average linkage) dendrogram. Our results indicate that the AGS might contain an \"odor fingerprint.\" Although putative sex pheromones such as squalene and erucic acid should be assessed further by bioassay, our study suggests that synthetic chemosignals might be useful in modulating the behavior and physiology of giant pandas.","subset":"pubmed_abstract"} +{"meta":{"pmid":19578480,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":12}}},"text":"MICROPATTERNING OF GOLD SUBSTRATES BASED ON POLY(PROPYLENE SULFIDE-BL-ETHYLENE GLYCOL), (PPS-PEG) BACKGROUND PASSIVATION AND THE MOLECULAR-ASSEMBLY PATTERNING BY LIFT-OFF (MAPL) TECHNIQUE.\nPoly(propylene sulfide-bl-ethylene glycol (PPS-PEG) is an amphiphilic block copolymer that spontaneously adsorbs onto gold from solution. This results in the formation of a stable polymeric layer that renders the surface protein resistant when an appropriate architecture is chosen. The established molecular assembly patterning by lift-off (MAPL) technique can convert a prestructured resist film into a pattern of biointeractive chemistry and a noninteractive background. Employing the MAPL technique, we produced a micron-scale PPS-PEG pattern on a gold substrate, and then characterized the patterned structure with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) and Atomic Force Microscopy (AFM). Subsequent exposure of the PPS-PEG\/gold pattern to protein adsorption (full human serum) was monitored in situ; SPR-imaging (i-SPR) shows a selective adsorption of proteins on gold, but not on PPS-PEG areas. Analysis shows a reduction of serum adsorption up to 93% on the PPS-PEG areas as compared to gold, in good agreement with previous analysis of homogenously adsorbed PPS-PEG on gold. MAPL patterning of PPS-PEG block copolymers is straightforward, versatile and reproducible, and may be incorporated into biosensor-based surface analysis methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":27033198,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":8}}},"text":"Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?\nOxidative stress is a pathological feature common to a multitude of neurological diseases. The production of reactive oxygen species (ROS) is the main mechanism underlying this cellular redox imbalance. Antioxidants protect biological targets against ROS, therefore, they have been considered as attractive potential therapeutic agents to counteract ROS-mediated neuronal damage. However, despite encouraging in vitro and preclinical in vivo data, the clinical efficacy of antioxidant treatment strategies is marginal and most clinical trials using antioxidants as therapeutic agents in neurodegenerative diseases have yielded disappointing outcomes. This might in part be due to the need of adjustment in concentrations and time parameters between preclinical studies and clinical settings. Moreover new efficient delivery methods need to be investigated, particularly taking into account that a successful therapeutic agent for neurological diseases should readily cross the blood-brain barrier (BBB). In that sense, the use of compounds that cross the BBB and boost the endogenous antioxidant defense machinery, by activating for instance the Nrf2 pathway, or compounds that are able to modulate ROS production, such as NOX enzyme inhibitors, seems to represent a more promising approach to combat oxidative stress in the central nervous system (CNS). Here we present a brief overview of the main players in oxidative stress and outline evidences of their involvement in Parkinson's disease, Alzheimer's disease, Huntington's disease and multiple sclerosis. Finally, we review and critically discuss the potential of antioxidants as therapeutics for central nervous system disorders with a special focus on emerging novel therapeutic strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":31542088,"dup_signals":{"dup_doc_count":13}},"text":"A novel strategy of using corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol in unselected patients: A patient-friendly alternative.\nTo compare the outcomes of in vitro fertilization (IVF) and fresh embryo transfer (ET) using corifollitropin alfa in ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol and GnRH antagonist protocol. A total of 245 unselected patients undergoing IVF\/fresh ET were enrolled between January 1 and December 31, 2017, including 135 treated with ultrashort GnRHa protocol and 110 treated with antagonist protocol. The primary outcomes were number of total injections and outpatient department (OPD) visits before ovulation triggering. The secondary outcomes were the duration of stimulation, dosage of additional gonadotropin for ovarian hyperstimulation, rates of pregnancy, clinical pregnancy, live birth, ovarian response, and ovarian hyperstimulation syndrome (OHSS) rate. Patients treated with ultrashort GnRHa required less additional gonadotropin, fewer total injections, but had better ovarian responses, including more oocytes retrieved, more metaphase II oocytes, and more blastocysts than those treated with antagonist did. A premature LH surge occurred only in six patients treated with antagonist protocol. The rates of pregnancy (37.0% vs. 43.6%), clinical pregnancy (25.2% vs. 34.6%), and live birth (19.3% vs. 30.0%) did not differ significantly between the two groups. The OHSS rate was similar in the two groups. In unselected patients using corifollitropin alfa, the ultrashort GnRHa protocol needed lower dose of additional gonadotropin and fewer injections but produced similar pregnancy outcomes than antagonist protocol did, suggesting that the ultrashort GnRHa protocol could be an alternative.","subset":"pubmed_abstract"} +{"meta":{"pmid":24473194,"dup_signals":{"dup_doc_count":13}},"text":"Biasing GPCR signaling from inside.\nThe discovery of \"functional selectivity\" or \"biased signaling\" through G protein-coupled receptors (GPCRs) has redefined the classical GPCR signaling paradigm. Moreover, the therapeutic potential of biased signaling by and biased ligands for GPCRs is changing the landscape of GPCR drug discovery. The concept of biased signaling has primarily been developed and discussed in the context of ligands that bind to the extracellular regions of GPCRs. However, two recent reports demonstrate that it is also possible to bias GPCR signaling from inside the cell by targeting intracellular regions of these receptors. These findings present a novel handle for delineating the functional outcomes of biased signaling by GPCRs. Moreover, these approaches also uncover a previously unexplored framework for biasing GPCR signaling for drug discovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":28033384,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":18}}},"text":"Synchrony of Dengue Incidence in Ho Chi Minh City and Bangkok.\nHo Chi Minh City and Bangkok are highly dengue endemic. The extent to which disease patterns are attributable to local versus regional dynamics remains unclear. To address this gap we compared key transmission parameters across the locations. We used 2003-2009 age-stratified case data to inform catalytic transmission models. Further, we compared the spatial clustering of serotypes within each city. We found that annual case numbers were highly consistent across the two cities (correlation of 0.77, 95% CI: 0.74-0.79) as was the annual force of infection (correlation of 0.57, 95% CI: 0.46-0.68). Serotypes were less similar with serotype-specific correlations ranging from 0.65 for DENV1 to -0.14 for DENV4. Significant spatial clustering of serotypes was observed in HCMC at distances <500m, similar to previous observations from Bangkok. Dengue dynamics are comparable across these two hubs. Low correlation in serotype distribution suggests that similar built environments, vector populations and climate, rather than viral flow drives these observations.","subset":"pubmed_abstract"} +{"meta":{"pmid":27058877,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2017-13":1,"2024-30":1,"unknown":8}}},"text":"Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach.\nThere is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot. For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer \u22651:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis. Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot. These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives.","subset":"pubmed_abstract"} +{"meta":{"pmid":12232412,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2021-10":2,"2021-04":4,"2020-34":1,"2019-35":1,"2019-13":1,"2018-51":1}}},"text":"The rhd6 Mutation of Arabidopsis thaliana Alters Root-Hair Initiation through an Auxin- and Ethylene-Associated Process.\nRoot-hair initiation in Arabidopsis thaliana provides a model for studying cell polarity and its role in plant morphogenesis. Root hairs normally emerge at the apical end of root epidermal cells, implying that these cells are polarized. We have identified a mutant, rhd6, that displays three defects: (a) a reduction in the number of root hairs, (b) an overall basal shift in the site of root-hair emergence, and (c) a relatively high frequency of epidermal cells with multiple root hairs. These defects implicate the RHD6 gene in root-hair initiation and indicate that RHD6 is normally associated with the establishment of, or response to, root epidermal cell polarity. Similar alterations in the site of root-hair emergence, although less extreme, were also discovered in roots of the auxin-, ethylene-, abscisic acid-resistant mutant axr2 and the ethylene-resistant mutant etr1. All three rhd6 mutant phenotypes were rescued when either auxin (indoleacetic acid) or an ethylene precursor (1-aminocyclopropane-1-carboxylic acid) was included in the growth medium. The rhd6 root phenotypes could be phenocopied by treating wild-type seedlings with an inhibitor of the ethylene pathway (aminoethoxyvinylglycine). These results indicate that RHD6 is normally involved in directing the selection or assembly of the root-hair initiation site through a process involving auxin and ethylene.","subset":"pubmed_abstract"} +{"meta":{"pmid":20963508,"dup_signals":{"dup_doc_count":16}},"text":"Discrimination of n-3 rich oils by gas chromatography.\nExploring the capabilities of instrumental techniques for discriminating n-3 rich oils derived from animals is a very important though much neglected area that was emphasized more than 100 years ago. In this study the potential of gas chromatography (GC) for discriminating full fatty acid methyl ester (FAME) profiles from fish (cod liver and salmon) and marine mammal (seal and whale) oils is evaluated by means of principal component analysis (PCA). The FAME profiles from plant oils such as rapeseed, linseed and soy oils and seven different brands of n-3 supplements are also used in the discrimination process. The results from the PCA plots can reliably distinguish between plant, n-3 supplements, fish and marine mammal oils. By removing the contribution of the n-3 supplements and plant oils it is possible to discriminate between types of fish and marine animal oils. GC offers a rapid, simple and convenient means of discriminating oils from different species, brands and grades.","subset":"pubmed_abstract"} +{"meta":{"pmid":37880086,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2024-10":1,"unknown":5}}},"text":"Generation, characterization, and differentiation of induced pluripotent stem-like cells in the domestic cat.\nInduced pluripotent stem (iPS) cells are generated from somatic cells and can differentiate into various cell types. Therefore, these cells are expected to be a powerful tool for modeling diseases and transplantation therapy. Generation of domestic cat iPS cells depending on leukemia inhibitory factor has been reported; however, this strategy may not be optimized. Considering that domestic cats are excellent models for studying spontaneous diseases, iPS cell generation is crucial. In this study, we aimed to derive iPS cells from cat embryonic fibroblasts retrovirally transfected with mouse Oct3\/4, Klf4, Sox2, and c-Myc. After transfection, embryonic fibroblasts were reseeded onto inactivated SNL 76\/7 and cultured in a medium supplemented with basic fibroblast growth factor. Flat, compact, primary colonies resembling human iPS colonies were observed. Additionally, primary colonies were more frequently observed in the KnockOut Serum Replacement medium than in the fetal bovine serum (FBS) medium. However, enhanced maintenance and proliferation of iPS-like cells occurred in the FBS medium. These iPS-like cells expressed embryonic stem cell markers, had normal karyotypes, proliferated beyond 45 passages, and differentiated into all three germ layers in vitro. Notably, expression of exogenous Oct3\/4, Klf4, and Sox2 was silenced in these cells. However, the iPS-like cells failed to form teratomas. In conclusion, this is the first study to establish and characterize cat iPS-like cells, which can differentiate into different cell types depending on the basic fibroblast growth factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":22385436,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2014-10":1,"2013-48":3,"2013-20":1,"2015-11":1,"unknown":8}}},"text":"Therapy for metastatic melanoma: the past, present, and future.\nMetastatic melanoma is the most aggressive form of skin cancer with a median overall survival of less than one year. Advancements in our understanding of how melanoma evades the immune system as well as the recognition that melanoma is a molecularly heterogeneous disease have led to major improvements in the treatment of patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved two novel therapies for advanced melanoma: a BRAF inhibitor, vemurafenib, and an immune stimulatory agent, ipilimumab. The success of these agents has injected excitement and hope into patients and clinicians and, while these therapies have their limitations, they will likely provide excellent building blocks for the next generation of therapies. In this review we will discuss the advantages and limitations of the two new approved agents, current clinical trials designed to overcome these limitations, and future clinical trials that we feel hold the most promise.","subset":"pubmed_abstract"} +{"meta":{"pmid":33032398,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Nonlinear fluorescence spectroscopy of layered perovskite quantum wells.\nInterest in layered organohalide perovskites is motivated by their potential for use in optoelectronic devices. In these systems, the smallest and largest quantum wells are primarily concentrated near the glass and air interfaces of a film, thereby establishing a gradient in the average values of the bandgaps. It has been suggested that this layered architecture promotes the funneling of electronic excitations through space in a manner similar to light-harvesting processes in photosynthetic antennae. Whereas energy and charge transfer are difficult to distinguish by conventional transient absorption techniques, it has recently been shown that these competing relaxation mechanisms may be separately targeted with nonlinear fluorescence (NLFL) and photocurrent \"action spectroscopies.\" Here, we present perturbative rate functions to describe NLFL experiments conducted on layered perovskite systems. The formulas reproduce the patterns of resonances observed in experimental measurements and show how signatures of energy transfer manifest in two-dimensional spectra. Overall, this work suggests that NLFL spectroscopy may be used to fully reveal the trajectories of electronic excitations by correlating ultrafast energy transfer pathways to fluorescence emission from the thickest quantum wells.","subset":"pubmed_abstract"} +{"meta":{"pmid":21436277,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Adult donor rod photoreceptors integrate into the mature mouse retina.\nPrevious studies indicate that early postnatal mouse photoreceptors have the ability to integrate into the mature host retina after transplantation, while progenitors and fully differentiated photoreceptors do not. The authors sought to determine whether the decline in the ability of photoreceptors to integrate after transplantation with increasing age is related to a loss of migratory ability in the adult neurons or by a decrease in their survival. Dissociated retinal cells were transferred from green fluorescent protein-positive (GFP(+)) donor mice of ages ranging from embryonic day (E)12.5 to adults (>28 days postnatal [P]). Immunofluorescence was used to assess marker expression and the morphology of integrated cells. In vitro cultures of dissociated Nrl-GFP mice were used to assay survival. It was confirmed in previous reports that neonatal rods integrate into adult hosts. However, in contrast to previous reports, the age of the donor cell was not as critical as previously reported, because it was found that donor cells older than P11 effectively integrated into adult host retina. Although fully adult photoreceptors (P28 and older) show a higher transplant failure rate than immature ones (P5), successful transplants had very similar numbers of integrated cells for both mature and immature donors. Integrated cells from all ages were indistinguishable from those of the host in morphology and marker expression. Fully mature photoreceptors retain the ability to integrate into the mature retina. The authors propose that their potential for integration is limited primarily by their decreased survival after dissociation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27271196,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-50":2,"2023-23":1,"2022-40":1,"2021-39":1,"2020-34":1,"2019-35":1,"2019-18":1,"2019-09":1,"2018-26":1,"2018-09":1,"2017-47":1,"2017-39":1}}},"text":"An E3-ligase-based method for ablating inhibitory synapses.\nAlthough neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":7077747,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Effect of glycosylation inhibitors on the release of enveloped vaccinia virus.\nAddition of 1 to 10 mM 2-deoxy-D-glucose (2-dg) or glucosamine (gln) to the growth medium of vaccinia virus-infected cells inhibited the release of extracellular enveloped vaccinia virus (EEV) without affecting the production of intracellular naked vaccinia virus (INV) particles. In contrast, INV infectivity (particles per PFU) was decreased sevenfold by 50 mM 2-dg. Treatment with 2-dg reduced but did not eliminate glycosylation of the INV 37,000-molecular-weight glycoprotein. The kinetics of sensitivity to inhibitor addition experiments and inhibitor reversal experiments indicated that EEV release was dependent on glycosylation before 8 h postinfection. This was supported by polyacrylamide gel electrophoretic analysis of the synthesis kinetics for cell membrane-associated vaccinia glycoproteins in 2-dg-inhibited infected cells. The dependence of vaccinia protein glycosylation before 8 h postinfection for efficient EEV release was observed in spite of the fact that the period of greatest glycoprotein synthesis was 8 to 12 h postinfection. The presence of 2-dg resulted in an incompletely glycosylated 89,000-molecular-weight glycoprotein, as indicated by a reduction in the apparent glycoprotein molecular weight. The morphological event affected by the inhibitors was the acquisition by INV of a double-membrane structure from the Golgi apparatus. This morphological intermediate is necessary for release of EEV.","subset":"pubmed_abstract"} +{"meta":{"pmid":18267897,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":6}}},"text":"Interactions among Amazon land use, forests and climate: prospects for a near-term forest tipping point.\nSome model experiments predict a large-scale substitution of Amazon forest by savannah-like vegetation by the end of the twenty-first century. Expanding global demands for biofuels and grains, positive feedbacks in the Amazon forest fire regime and drought may drive a faster process of forest degradation that could lead to a near-term forest dieback. Rising worldwide demands for biofuel and meat are creating powerful new incentives for agro-industrial expansion into Amazon forest regions. Forest fires, drought and logging increase susceptibility to further burning while deforestation and smoke can inhibit rainfall, exacerbating fire risk. If sea surface temperature anomalies (such as El Ni\u00f1o episodes) and associated Amazon droughts of the last decade continue into the future, approximately 55% of the forests of the Amazon will be cleared, logged, damaged by drought or burned over the next 20 years, emitting 15-26Pg of carbon to the atmosphere. Several important trends could prevent a near-term dieback. As fire-sensitive investments accumulate in the landscape, property holders use less fire and invest more in fire control. Commodity markets are demanding higher environmental performance from farmers and cattle ranchers. Protected areas have been established in the pathway of expanding agricultural frontiers. Finally, emerging carbon market incentives for reductions in deforestation could support these trends.","subset":"pubmed_abstract"} +{"meta":{"pmid":8639864,"dup_signals":{"dup_doc_count":26,"dup_dump_count":22,"dup_details":{"curated_sources":4,"2021-39":1,"2021-04":1,"2019-35":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-36":1,"2022-49":1,"2017-13":1,"2015-18":1,"2024-18":1}}},"text":"Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.\nLong-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells\/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells\/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.","subset":"pubmed_abstract"} +{"meta":{"pmid":22045986,"dup_signals":{"dup_doc_count":31,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":6,"2013-48":4,"2013-20":16,"unknown":3}}},"text":"In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1\/2 study.\nWe have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.","subset":"pubmed_abstract"} +{"meta":{"pmid":11670028,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Ion-Pairing Interactions between Co(en)(3)(3+) and the (23)Na NMR Frequency Shift Reagent TmDOTP(5)(-).\nThree new formulations of TmDOTP(5)(-) (DOTP(8)(-) = 1,4,7,10-tetraazacyclododecane-1,4,7,11-tetrakis(methylenephosphonate)) have been prepared in an effort to develop a low-osmolality form of the (23)Na frequency shift reagent (SR). Equally concentrated (0.32 M) solutions of (MegH)(4)HTmDOTP (Meg = N-methylglucamine or meglumine), Na(4)HTmDOTP, and [Co(en)(3)](4\/3)HTmDOTP have solution osmolalities of 1245, 1040, and 707 mOsm\/kg, respectively, comparable to the ionic and non-ionic gadolinium-based MRI contrast agent preparations in clinical use. An analysis of (23)Na and (59)Co frequency shifts induced by TmDOTP(5)(-) indicated that Co(en)(3)(3+) can form both 1:1 and 2:1 adducts with TmDOTP(5)(-) with (log) binding constants of 3.1 +\/- 0.4 and 2.5 +\/- 0.4, respectively. These values were comparable with those obtained by analysis of the (1)H frequency shifts observed for Co(en)(3)(3+) upon binding to HoDOTP(5)(-). The (1)H shifts of Co(en)(3)(3+) signals induced by YbDOTP(5)(-) at pH 7.4 were fitted best by a 1:1 binding model with a conditional binding constant of 3.1 +\/- 0.2. The (59)Co and (1)H limiting frequency shifts of Co(en)(3)(3+) could be fitted with a dipolar shift model in which the Co atom of the Co(en)(3)(3+) cation is located 5.0 +\/- 0.3 \u00c5 from the Ln atom of the LnDOTP(5)(-) chelate, and with an angle of 40 +\/- 0.2 degrees between the Co-Ln vector and the 4-fold symmetry axis of the LnDOTP(5)(-) complex. Ion pairing of Co(en)(3)(3+) and TmDOTP(5)(-) was significant enough in both saline and human blood plasma to reduce the effectiveness of the (23)Na frequency SR. Comparisons between all formulations suggested that Na(4)HTmDOTP represents the best compromise of lower osmolality with minimal reduction of SR shift potency.","subset":"pubmed_abstract"} +{"meta":{"pmid":29648964,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"LC-MS\/MS-based determination of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in poultry meat from the Punjab-Pakistan.\nA simple, reliable and sensitive liquid chromatography-tandem mass spectrometry-based confirmatory method was redeveloped and validated for the simultaneous determination of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in chicken muscles. The analytes were extracted from minced chicken muscle with acetonitrile and ammoniated water mixture. A second extraction with ethyl acetate was followed by evaporation and dissolution of the residue in ammoniated methanol before defatting with n-hexane. Finally, the extract was further cleaned up by dispersive solid phase extraction using C-18 end-capped dispersive material. The validation protocol was adapted from the European Commission Decision 2002\/657\/EC and all the performance characteristics were successfully satisfied. The recoveries of all the analytes were found to be in the range of 86.4-108.1% and the precision values, within day and between days, ranged from 2.7% to 11% and 4.4% to 16.3%, respectively. The method was tested in various incurred samples and applied to analyse a wide range of random poultry market samples (n = 120) collected from three cities of the Punjab, Pakistan. Chloramphenicol and florfenicol residues were detected at low levels in less than 11% of the samples. Chloramphenicol was detected only in 4 samples with the concentration range of 0.17-0.477 \u00b5g kg-1, whereas the levels of florfenicol\/florfenicol amine residues detected in 9 samples ranged from 8.7 to 32.8 \u00b5g kg-1. Moreover, most of the florfenicol residues were identified as tissue bound, extractable only after strong acid hydrolysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24769911,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":3,"2022-40":1,"2022-21":1,"2022-05":1,"2021-39":1,"2021-31":1,"2021-21":1,"2019-47":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-22":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-14":1}}},"text":"Formation of cyanates in low-valent uranium chemistry: a synergistic experimental\/theoretical study.\nComputational studies on the reductive activation of a mixture of CO and NO by the U(iii) complex [U(\u03b7-C8H6{Si(i)Pr3-1,4}2)(\u03b7-Cp*)], which affords a mixture of [U(\u03b7-C8H6{Si(i)Pr3-1,4}2)(\u03b7-Cp*)]2(\u03bc-OCN)21 and [U(\u03b7-C8H6{Si(i)Pr3-1,4}2)(\u03b7-Cp*)]2(\u03bc-O) 2, show that the reaction proceeds via an initial attack of CO on a \u03bc-\u03b7(2):\u03b7(2) coordinated NO, side-on bridged between two uranium centres. This leads to the formation of the bridging oxo complex 2 and the cyanate radical; coordination of the latter to the starting complex and dimerisation affords 1. The DFT studies also predict the existence of the monocyanate-bridged, mixed valence species [U(\u03b7-C8H6{Si(i)Pr3-1,4}2)(\u03b7-Cp*)]2(\u03bc-OCN) 3, which has now been experimentally observed.","subset":"pubmed_abstract"} +{"meta":{"pmid":27527084,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":2,"unknown":13}}},"text":"A Novel RNase 3\/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.\nEradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and\/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.","subset":"pubmed_abstract"} +{"meta":{"pmid":26116576,"dup_signals":{"dup_doc_count":11}},"text":"Attractive and repulsive factors act through multi-subunit receptor complexes to regulate nerve fiber growth.\nIn the nervous system, attractive and repulsive factors guide neuronal growth, pathfinding and target innervation during development, learning and regeneration after injury. Repulsive and growth-inhibitory factors, such as some ephrins, semaphorins, netrins and myelin-associated growth inhibitors, restrict nerve fiber growth, whereas neurotrophins, and other ephrins, semaphorins and netrins attract fibers and promote neurite growth. Several of these guidance molecules also play crucial roles in vasculogenesis, and regulate cell migration and tissue formation in different organs. Precise and highly specific signal transduction in space and time is required in all these cases, which primarily depends on the presence and function of specific receptors. Interestingly, many of these ligands act through multi-subunit receptor complexes. In this Commentary, we review the current knowledge of how complexes of the receptors for attractive and repulsive neurite growth regulatory factors are reorganized in a spatial and temporal manner, and reveal the implications that such dynamics have on the signaling events that coordinate neurite fiber growth.","subset":"pubmed_abstract"} +{"meta":{"pmid":20207038,"dup_signals":{"dup_doc_count":49,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-23":3,"2023-14":1,"2023-06":1,"2021-49":1,"2016-26":2,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":1,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":2,"2014-42":1,"2014-41":3,"2014-35":3,"2014-23":4,"2014-15":2,"2024-30":2,"2024-10":1}}},"text":"Effect of changes in testing parameters on the cost-effectiveness of two pooled test methods to classify infection status of animals in a herd.\nMonte Carlo simulation was used to determine optimal fecal pool sizes for identification of all Mycobacterium avium subsp. paratuberculosis (MAP)-infected cows in a dairy herd. Two pooling protocols were compared: a halving protocol involving a single retest of negative pools followed by halving of positive pools and a simple protocol involving single retest of negative pools but no halving of positive pools. For both protocols, all component samples in positive pools were then tested individually. In the simulations, the distributions of number of tests required to classify all individuals in an infected herd were generated for various combinations of prevalence (0.01, 0.05 and 0.1), herd size (300, 1000 and 3000), pool size (5, 10, 20 and 50) and test sensitivity (0.5-0.9). Test specificity was fixed at 1.0 because fecal culture for MAP yields no or rare false-positive results. Optimal performance was determined primarily on the basis of a comparison of the distributions of numbers of tests needed to detect MAP-infected cows using the Mann-Whitney U test statistic. Optimal pool size was independent of both herd size and test characteristics, regardless of protocol. When sensitivity was the same for each pool size, pool sizes of 20 and 10 performed best for both protocols for prevalences of 0.01 and 0.1, respectively, while for prevalences of 0.05, pool sizes of 10 and 20 were optimal for the simple and halving protocols, respectively. When sensitivity decreased with increasing pool size, the results changed for prevalences of 0.05 and 0.1 with pool sizes of 50 being optimal especially at a prevalence of 0.1. Overall, the halving protocol was more cost effective than the simple protocol especially at higher prevalences. For detection of MAP using fecal culture, we recommend use of the halving protocol and pool sizes of 10 or 20 when the prevalence is suspected to range from 0.01 to 0.1 and there is no expected loss of sensitivity with increasing pool size. If loss in sensitivity is expected and the prevalence is thought to be between 0.05 and 0.1, the halving protocol and a pool size of 50 is recommended. Our findings are broadly applicable to other infectious diseases under comparable testing conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":15793101,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":10}}},"text":"Glycerol monolaurate inhibits virulence factor production in Bacillus anthracis.\nAnthrax, caused by Bacillus anthracis, has been brought to the public's attention because of the 2001 bioterrorism attacks. However, anthrax is a disease that poses agricultural threats in the United States as well as human populations in Europe, China, Africa, and Australia. Glycerol monolaurate (GML) is a compound that has been shown to inhibit exotoxin production by Staphylococcus aureus and other gram-positive bacteria. Here, we study the effects of GML on growth and toxin production in B. anthracis. The Sterne strain of B. anthracis was grown to post-exponential phase with 0-, 10-, 15-, or 20-microg\/ml concentrations of GML and then assayed quantitatively for protective antigen (PA) and lethal factor (LF). After 8 h, GML at concentrations greater than 20 microg\/ml was bacteriostatic to growth of the organism. However, a 10-microg\/ml concentration of GML was not growth inhibitory, but amounts of PA and LF made were greatly reduced. This effect was not global for all proteins when total secreted protein from culture fluids was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Through quantitative reverse transcription-PCR assays, this toxin-inhibitory effect was shown to occur at the transcriptional level, since amounts of mRNA for pagA (PA), lef (LF), and cya (edema factor) were reduced. Surprisingly, mRNA levels of atxA, a regulator of exotoxin gene expression, rose in the presence of GML. These data will be useful in developing therapeutic tools to treat anthrax disease, whether in animals or humans. These results also suggest that mechanisms of virulence regulation exist independent of atxA.","subset":"pubmed_abstract"} +{"meta":{"pmid":18626994,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Osteoblast migration on poly(alpha-hydroxy esters).\nWe investigated the migration of rat calvaria osteoblast populations on poly(alpha-hydroxy ester) films for up to 14 days to determine effects of substrate composition and culture conditions on the migratory characteristics of osteoblasts. Initial osteoblast culture conditions included cell colonies formed by seeding a high (84,000 cells\/cm(2)) or low (42,000 cells\/cm(2)) density of isolated osteoblasts on the polymer films, and bone tissue cultures formed by plating bone chips directly on the substrates. High density osteoblast colonies cultured and allowed to migrate and proliferate radially on 85:15 poly(DL-lactic-co-glycolic acid) (PLGA) films, 75:25 PLGA films, and tissue culture polystyrene controls demonstrated that the copolymer ratio in the polymer films did not affect the rate of increase in substrate surface area (or culture area) covered by the growing cell colony. However, the rate of increase in culture area was dependent on the initial osteoblast seeding density. Initial cell colonies formed with a lower osteoblast seeding density on 75:25 PLGA resulted in a lower rate of increase in culture area, specifically 4.9 +\/- 0.3 mm(2)\/day, versus 14.1 +\/- 0.7 mm(2)\/day for colonies seeded with a higher density of cells on the same polymer films. The proliferation rate for osteoblasts in the high and low density seeded osteoblast colonies did not differ, whereas the proliferation rate for the osteoblasts arising from the bone chips was lower than either of these isolated cell colonies. Confocal and light microscopy revealed that the osteoblast migration occurred as a monolayer of individual osteoblasts and not a calcified tissue front. These results demonstrated that cell seeding conditions strongly affect the rates of osteoblast migration and proliferation on biodegradable poly(alpha-hydroxy esters). (c) 1996 John Wiley & Sons, Inc.","subset":"pubmed_abstract"} +{"meta":{"pmid":23589803,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":14}}},"text":"A value-driven mechanism of attentional selection.\nAttention selects stimuli for cognitive processing, and the mechanisms that underlie the process of attentional selection have been a major topic of psychological research for over 30 years. From this research, it has been well documented that attentional selection can proceed both voluntarily, driven by visual search goals, and involuntarily, driven by the physical salience of stimuli. In this review, I provide a conceptual framework for attentional control that emphasizes the need for stimulus selection to promote the survival and wellbeing of an organism. I argue that although goal-driven and salience-driven mechanisms of attentional selection fit within this framework, a central component that is missing is a mechanism of attentional selection that is uniquely driven by learned associations between stimuli and rewards. I go on to review recent evidence for such a value-driven mechanism of attentional selection, and describe how this mechanism functions independently of the well-documented salience-driven and goal-driven mechanisms. I conclude by arguing that reward learning modifies the attentional priority of stimuli, allowing them to compete more effectively for selection even when nonsalient and task-irrelevant.","subset":"pubmed_abstract"} +{"meta":{"pmid":34257476,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2021-31":1,"2021-17":1,"2020-50":1,"2020-29":1,"2020-05":1,"2019-39":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2021-43":1}}},"text":"DISPOSITIONAL MINDFULNESS MODERATES THE RELATIONSHIP BETWEEN OCCUPATIONAL STRESSORS AND PERCEIVED STRESS AMONG LAW ENFORCEMENT PERSONNEL.\nLaw enforcement personnel (LEPs) experience occupational stressors that can result in poor health outcomes and have a negative impact on the communities they serve. Dispositional mindfulness, or receptive awareness and attention to present moment experience, has been shown to negatively predict perceived stress and to moderate the relationship between stressors and negative stress-related outcomes. The current study is an investigation of the moderating role of specific facets of dispositional mindfulness (i.e., nonreactivity, nonjudging, and acting with awareness) in the relationship between occupational stressors and perceived stress in a sample of LEPs. As hypothesized, nonreactivity significantly moderated the relationship between operational stressors and perceived stress, such that LEPs low in nonreactivity exhibited a significant relationship between stressors and perceived stress, whereas those high in nonreactivity did not. Nonjudging also moderated the relationship between organizational stressors and perceived stress; however, unexpectedly, LEPs high in nonjudging evidenced a significant relationship between stressors and perceived stress, whereas those low in nonjudging did not. Potential implications of these findings for LEP stress reduction interventions are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8317889,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Usefulness of fecal alpha-1-antitrypsin for detection of gastrointestinal bleeding in patients with gastric cancer.\nHemoglobin (Hb), albumin (Alb), immunoglobulin G (IgG) and alpha-1-antitrypsin (AAT) were measured in 87 fecal samples from 29 normal volunteers and 68 fecal samples from 33 patients with gastric cancer before surgery to evaluate the usefulness of fecal AAT as an indicator of gastrointestinal bleeding in patients with gastric cancer. Mean values and standard deviation of fecal Hb, Alb, IgG and AAT in normal volunteers were 0.13 +\/- 1.19 micrograms\/g, 6.96 +\/- 20.48 micrograms\/g, 17.52 +\/- 10.16 micrograms\/g, and 0.483 +\/- 0.315 mg\/g, respectively. These parameters in the patients with gastric cancer were significantly higher than those in the normal volunteers. No statistically significant correlations were observed between these fecal parameters, except between fecal Alb and IgG. Data obtained from peripheral blood also showed no significant correlation with these fecal parameters. When the cut-off levels of fecal Hb, Alb, IgG and AAT were set at M + 2SD of the values obtained from the normal volunteers, sensitivity, specificity and accuracy were 80.0%, 86.2% and 84.1% for fecal AAT, and 66.7%, 96.6% and 86.4% for fecal Hb in the patients with advanced gastric cancer in a cohort consisting of patients with advanced gastric carcinoma and normal volunteers. Since fecal AAT showed higher sensitivity in patients with advanced gastric cancer with a low number of false negative cases, we concluded that measurement of fecal AAT could be a promising method for assessment of gastrointestinal bleeding in patients with advanced gastric carcinoma instead of immunological detection of fecal Hb.","subset":"pubmed_abstract"} +{"meta":{"pmid":9516928,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Quantitative differences in telomerase activity among malignant, premalignant, and benign ovarian lesions.\nTelomerase activation has been demonstrated in both cancers and some noncancerous lesions. However, few studies have determined levels of telomerase activity in these lesions. In the present study, using a recently developed stretch PCR assay, telomerase activity was quantitatively determined in a variety of ovarian lesions including 36 ovarian cancers, 5 ovarian low potential malignancy (LPM) lesions, 10 ovarian cysts, and 12 normal ovaries. Telomerase activity was normalized to control activity (100 units) in C33A cell line and given in relative units. Telomerase activity in ovarian cancer (51 +\/- 7 units, mean +\/- SE) was significantly higher than that in LPM lesions, ovarian cysts, and normal ovaries (7 +\/- 3, 10 +\/- 2, and 10 +\/- 2 units, respectively; P < 0.001). Interestingly, all LPMs, ovarian cysts, and normal ovaries exhibited low telomerase activity less than 30 units, and no significant difference in level of telomerase activity was found among them. We also found a significant correlation between the level of telomerase activity and the clinical stage of ovarian cancer. Our quantitative telomerase assay thus clearly distinguished telomerase activity in ovarian cancers from that in LPM lesions and ovarian cysts. Significant levels of telomerase activation frequently occurred in cancer but rarely occurred in premalignant and benign lesions, suggesting that telomerase activation is a critical step in cancer development.","subset":"pubmed_abstract"} +{"meta":{"pmid":22739973,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Maintaining radiation exposures as low as reasonably achievable (ALARA) for dental personnel operating portable hand-held x-ray equipment.\nClinical experience indicates that newly available portable hand-held x-ray units provide advantages compared to traditional fixed properly installed and operated x-ray units in dental radiography. However, concern that hand-held x-ray units produce higher operator doses than fixed x-ray units has caused regulatory agencies to mandate requirements for use of hand-held units that go beyond those recommended by the manufacturer and can discourage the use of this technology. To assess the need for additional requirements, a hand-held x-ray unit and a pair of manikins were used to measure the dose to a simulated operator under two conditions: exposures made according to the manufacturer's recommendations and exposures made according to manufacturer's recommendation except for the removal of the x-ray unit's protective backscatter shield. Dose to the simulated operator was determined using an array of personal dosimeters and a pair of pressurized ion chambers. The results indicate that the dose to an operator of this equipment will be less than 0.6 mSv y\u207b\u00b9 if the device is used according to the manufacturer's recommendations. This suggests that doses to properly trained operators of well-designed, hand-held dental x-ray units will be below 1.0 mSv y\u207b\u00b9 (2% of the annual occupational dose limit) even if additional no additional operational requirements are established by regulatory agencies. This level of annual dose is similar to those reported as typical dental personnel using fixed x-ray units and appears to satisfy the ALARA principal for this class of occupational exposures.","subset":"pubmed_abstract"} +{"meta":{"pmid":9527715,"dup_signals":{"dup_doc_count":11}},"text":"[Tacrine].\nSignificant changes in cholinergic neurotransmission have been described in Alzheimer's disease (AD). These findings led to consider cholinergic deficit as the main disturbance in AD, due to degeneration of presynaptic cholinergic neurons, and that replacement of acetylcholine could restore the cognitive alterations characteristic of AD. Although it was soon demonstrated that cholinergic deficit was not the only change, cholinergic hypothesis has allowed to set several possible therapeutic strategies for these severe disease, the most promising is administration of acetylcholinesterase inhibitors. Of all the compounds investigated, tacrine (tetrahydroamineacridine) has shown in several clinical trials a positive effect on memory in patients with symptoms of slight to moderate severity. Although not all studies have given successful result, probably due to methodological differences, global clinical impression has justified the introduction of tacrine as the first palliative therapy in AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":9373291,"dup_signals":{"dup_doc_count":11}},"text":"Video-assisted thoracoscopic treatment of spinal lesions in the thoracolumbar junction.\nThe endoscopic treatment of spinal lesions in the thoracolumbar junction (T11-L2) poses a great challenge to the surgeon. From November 1, 1995 to December 31, 1996, we successfully used a combination of video-assisted thoracoscopy and conventional spinal instruments to treat 38 patients with anterior spinal lesions. Twelve of them had lesions in the thoracolumbar junction. The so-called extended manipulating channel method was used to perform vertebral biopsy, discectomy, decompressive corpectomy, interbody fusions, and\/or internal fixations in these patients. The size of the thoracoscopic portals was greater than usual in order to allow conventional spinal instruments and a thoracoscope to enter the chest cavity freely and be manipulated by techniques similar to those used in standard open surgical procedures. In this series, the procedures were performed by using either a three-portal approach (2. 5-3.5 cm) or a modified two-portal technique involving a 5-6 cm larger incision and a small one for introducing the scope. None of the operations resulted in injury to the great vessels, internal organs, or spinal cord. The total time for the operation ranged from 1.5 to 4.5 h (average, 3); and the total blood loss ranged from 50 to 3000 cc (average, 1050). One patient was converted to an open procedure due to severe pleural adhesion. Complications included two instances of transient intercostal neuralgia, one superfical wound infection, and one residual pneumothorax. The video-assisted technique with the extended manipulating channel method presented in this report simplifies thoracoscopic spinal surgery in the thoracolumbar junction and makes it easier. It avoids division of the diaphragm, removal of the rib, and wide spread of the intercostal space, and it allows greater control of intraoperative vessel bleeding. Using this technique, the number of portals required during the procedure can be reduced. In addition, the technique reduces the endoscopic materials required, thus lowering overall cost. It is an effective and promising approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":29440134,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":7}}},"text":"Interobserver variation in the diagnosis of fibroepithelial lesions of the breast: a multicentre audit by digital pathology.\nFibroepithelial lesions (FELs) of the breast span a morphological continuum including lesions where distinction between cellular fibroadenoma (FA) and benign phyllodes tumour (PT) is difficult. The distinction is clinically important with FAs managed conservatively while equivocal lesions and PTs are managed with surgery. We sought to audit core biopsy diagnoses of equivocal FELs by digital pathology and to investigate whether digital point counting is useful in clarifying FEL diagnoses. Scanned slide images from cores and subsequent excisions of 69 equivocal FELs were examined in a multicentre audit by eight pathologists to determine the agreement and accuracy of core needle biopsy (CNB) diagnoses and by digital point counting of stromal cellularity and expansion to determine if classification could be improved. Interobserver variation was high on CNB with a unanimous diagnosis from all pathologists in only eight cases of FA, diagnoses of both FA and PT on the same CNB in 15 and a 'weak' mean kappa agreement between pathologists (k=0.36). 'Moderate' agreement was observed on CNBs among breast specialists (k=0.44) and on excision samples (k=0.49). Up to 23% of lesions confidently diagnosed as FA on CNB were PT on excision and up to 30% of lesions confidently diagnosed as PT on CNB were FA on excision. Digital point counting did not aid in the classification of FELs. Accurate and reproducible diagnosis of equivocal FELs is difficult, particularly on CNB, resulting in poor interobserver agreement and suboptimal accuracy. Given the diagnostic difficulty, and surgical implications, equivocal FELs should be reported in consultation with experienced breast pathologists as a small number of benign FAs can be selected out from equivocal lesions.","subset":"pubmed_abstract"} +{"meta":{"pmid":27048246,"dup_signals":{"dup_doc_count":27,"dup_details":{"curated_sources":2,"unknown":25}}},"text":"BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy.\nNeuroendocrine tumors comprise a heterogeneous group of malignancies with a broad spectrum of clinical behavior. Poorly differentiated tumors follow an aggressive course with limited treatment options, and new approaches are needed. Oncogenic BRAF V600E (BRAF(V600E)) substitutions are observed primarily in melanoma, colon cancer, and non-small cell lung cancer, but have been identified in multiple tumor types. Here, we describe the first reported recurrent BRAF(V600E) mutations in advanced high-grade colorectal neuroendocrine tumors and identify a BRAF alteration frequency of 9% in 108 cases. Among these BRAF alterations, 80% were BRAF(V600E) Dramatic response to BRAF-MEK combination therapy occurred in two cases of metastatic high-grade rectal neuroendocrine carcinoma refractory to standard therapy. Urinary BRAF(V600E) circulating tumor DNA monitoring paralleled disease response. Our series represents the largest study of genomic profiling in colorectal neuroendocrine tumors and provides strong evidence that BRAF(V600E) is an oncogenic driver responsive to BRAF-MEK combination therapy in this molecular subset. BRAF(V600E) is an established oncogenic driver, but significant disparities in response exist among tumor types. Two patients with treatment-refractory high-grade colorectal neuroendocrine tumors harboring BRAF(V600E) exhibited rapid and durable response to combined BRAF-MEK inhibition, providing the first clinical evidence of efficacy in this aggressive tumor type. Cancer Discov; 6(6); 594-600. \u00a92016 AACR.This article is highlighted in the In This Issue feature, p. 561.","subset":"pubmed_abstract"} +{"meta":{"pmid":11869589,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Antibiotic regimens for endometritis after delivery.\nPost-partum endometritis, which is more common after cesarean section, occurs when vaginal organisms invade the endometrial cavity during labour and birth. Antibiotic treatment is warranted. The effect of different antibiotic regimens for the treatment of postpartum endometritis on failure of therapy and complications was systematically reviewed. We searched the Cochrane Pregnancy and Childbirth Group's trials register and the Cochrane Controlled Trials Register. Date of last search: June 2001. Randomised trials of different antibiotic regimens for postpartum endometritis, after cesarean section or vaginal birth, where outcomes of treatment failure or complications were reported were selected. Data were abstracted independently by the reviewers. Comparisons were made between different types of antibiotic regimen, based on type of antibiotic and duration and route of administration. Summary relative risks were calculated. Forty-seven trials were included. Overall the studies were methodologically poor. In the intent-to-treat analysis, fifteen studies comparing clindamycin and an aminoglycoside with another regimen showed more treatment failures with another regimen (relative risk (RR) 1.32; 95% confidence interval (CI) 1.09-1.60). Failures of those regimens with poor activity against penicillin resistant anaerobic bacteria were more likely (RR 1.53; 95% CI 1.10-2.13). In four studies that compared continued oral antibiotic therapy after intravenous therapy, no differences were found in recurrent endometritis or other outcomes. There was no evidence of difference in incidence of allergic reactions. Cephalosporins were associated with less diarrhea. The combination of gentamicin and clindamycin is appropriate for the treatment of endometritis. Regimens with activity against penicillin resistant anaerobic bacteria are better than those without. There is no evidence that any one regimen is associated with fewer side effects. Once uncomplicated endometritis has clinically improved with intravenous therapy, oral therapy is not needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23101533,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"A modification of the palmaris longus-to-extensor pollicis longus transfer for radial nerve palsy.\nThe standard palmaris longus (PL)-to-rerouted extensor pollicis longus (EPL) transfer was modified by taking the PL with an extension of the palmar aponeurosis (PA) and performing the transfer at the level of the thumb metacarpal. Our purpose was to evaluate whether this modified transfer could restore both the extension and the radial abduction of the thumb without rerouting the EPL. We restored thumb function of 5 patients with unrecovered radial nerve palsy (4 men and 1 women; mean age at surgery, 47 years; mean duration between onset of palsy and surgery, 13 months; and mean follow-up period after surgery, 17 months). The PA was dissected in continuity with the PL (PA\/PL) tendon, as is done in Camitz thumb opponensplasty. Another skin incision was made on the dorsal side of the thumb metacarpal, and the EPL tendon was exposed. The PA\/PL tendon was drawn into this skin incision, passing under the abductor pollicis longus and extensor pollicis brevis tendons. The PA\/PL tendon was woven into the undivided EPL tendon and immobilized for 3 weeks. The mean values of active hyperextension and flexion of the interphalangeal joint, radial abduction, palmar abduction of the thumb, grip strength, and tip pinch strength of the involved\/contralateral sides were 3\u00b0\/7\u00b0, 41\u00b0\/49\u00b0, 59\u00b0\/65\u00b0, 65\u00b0\/70\u00b0, 37 kg\/47 kg, and 4.0 kg\/5.2 kg, respectively. We used the PA to lengthen the PL tendon, to transfer it to the EPL at a level distal to the Lister tubercle. Because our procedure is based on the concept of standard transfer, it should yield similar long-term results. Our procedure should be a good alternative, especially in cases of closed radial nerve injury, because it preserves the paralyzed EPL for possible future recovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":23744626,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2019-47":1,"2019-43":2,"2019-35":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-30":1,"2018-22":1,"2017-51":1,"2017-43":1,"2019-51":1}}},"text":"First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing.\nTo define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. From singleton pregnancies undergoing screening for aneuploidies at three UK hospitals between March 2006 and May 2012, we analyzed prospectively collected data on the following biomarkers: fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free \u03b2-human chorionic gonadotropin (\u03b2-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cut-offs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing. In contingent screening, detection of 98% of fetuses with trisomy 21 at an overall invasive testing rate < 0.5% can be potentially achieved by offering cfDNA testing to about 36%, 21% and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum PlGF and AFP and using the combined test with the addition of PlGF, AFP and DV-PIV, respectively. Effective first-trimester screening for trisomy 21, with DR of 98% and invasive testing rate < 0.5%, can be potentially achieved by contingent screening incorporating biomarkers and cfDNA testing.","subset":"pubmed_abstract"} +{"meta":{"pmid":26739729,"dup_signals":{"dup_doc_count":11}},"text":"Clustered randomised controlled trial of two education interventions designed to increase physical activity and well-being of secondary school students: the MOVE Project.\nTo assess the effectiveness of 2 interventions in improving the physical activity and well-being of secondary school children. A clustered randomised controlled trial; classes, 1 per school, were assigned to 1 of 3 intervention arms or a control group based on a 2\u00d72 factorial design. The interventions were peer-mentoring and participative learning. Year 7 children (aged 11-12) in the peer-mentoring intervention were paired with year 9 children for 6 weekly mentoring meetings. Year 7 children in the participative learning arm took part in 6 weekly geography lessons using personalised physical activity and Global Positioning System (GPS) data. Year 7 children in the combined intervention received both interventions, with the year 9 children only participating in the mentoring sessions. 1494 year 7 students from 60 schools in the North of England took part in the trial. Of these, 43 students opted out of taking part in the evaluation measurements, 2 moved teaching group and 58 changed school. Valid accelerometry outcome data were collected for 892 students from 53 schools; and well-being outcome data were available for 927 students from 52 schools. The primary outcomes were mean minutes of accelerometer-measured moderate-to-vigorous intensity physical activity per day, and well-being as evaluated by the KIDSCREEN-27 questionnaire. These data were collected 6 weeks after the intervention; a 12-month follow-up is planned. No significant effects (main or interaction) were observed for the outcomes. However, small positive differences were found for both outcomes for the participative learning intervention. These findings suggest that the 2 school-based interventions did not modify levels of physical activity or well-being within the period monitored. Change in physical activity may require more comprehensive individual behavioural intervention, and\/or more system-based efforts to address wider environmental influences such as family, peers, physical environment, transport and educational policy. ISRCTN82956355.","subset":"pubmed_abstract"} +{"meta":{"pmid":24784334,"dup_signals":{"dup_doc_count":55,"dup_dump_count":45,"dup_details":{"curated_sources":4,"2023-40":1,"2023-14":1,"2022-49":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-05":1,"2017-51":1,"2017-43":2,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2023-50":1,"2015-06":1,"2015-18":1}}},"text":"Unintentional weight loss in older adults.\nUnintentional weight loss in persons older than 65 years is associated with increased morbidity and mortality. The most common etiologies are malignancy, nonmalignant gastrointestinal disease, and psychiatric conditions. Overall, nonmalignant diseases are more common causes of unintentional weight loss in this population than malignancy. Medication use and polypharmacy can interfere with taste or cause nausea and should not be overlooked. Social factors may contribute to unintentional weight loss. A readily identifiable cause is not found in 16% to 28% of cases. Recommended tests include a complete blood count, basic metabolic panel, liver function tests, thyroid function tests, C-reactive protein levels, erythrocyte sedimentation rate, glucose measurement, lactate dehydrogenase measurement, and urinalysis. Chest radiography and fecal occult blood testing should be performed. Abdominal ultrasonography may also be considered. When baseline evaluation is unremarkable, a three- to six-month observation period is justified. Treatment focuses on the underlying cause. Nutritional supplements and flavor enhancers, and dietary modification that takes into account patient preferences and chewing or swallowing disabilities may be considered. Appetite stimulants may increase weight but have serious adverse effects and no evidence of decreased mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":6847028,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Diet modification and the development of new food products.\nThe development of new food products to meet the needs of the 20th century American consumer offers a greater challenge to the innovativeness of the food industry scientist than ever before. The sequence of activities that leads to the introduction of a successful new food product into today's highly competitive marketplace has its beginnings and foundation in extensive and ongoing market research. This research elicits and defines the changing consumer needs and wants. The relation of diet to health is but one of many factors that influence food purchase decisions and, thus, the stimulus for developing new food products. In addition, the extent to which existing food products may be modified or new foods developed to meet dietary goals is subject to technologic and regulatory constraints. A commitment to ethical and responsible marketing strategies is essential to the evolution of food products for special dietary needs. Despite these complex restraints, many food products with altered nutrient or ingredient composition are currently available to consumers and others enter the marketplace each year.","subset":"pubmed_abstract"} +{"meta":{"pmid":30146565,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":9}}},"text":"Incidence and Characteristics of Bath-related Accidents.\nObjective Bath-related sudden cardiac arrests frequently occur in Japan. This study aimed to describe the actual incidence and characteristics of bath-related accidents, including non-fatal events, and to establish the etiology of bath-related sudden cardiac arrest. Methods This prospective cross-sectional observational study was conducted in Tokyo Metropolis and Saga and Yamagata Prefectures between October 2012 and March 2013. Emergency personnel enrolled events in this study when they recognized that activation of the emergency medical system was related to bathing. Surveillance cards were delivered and collected from the emergency personnel and attending physicians. Results In total, 4,593 events were enrolled (1,528 cardiac arrests, 935 survivors in need of help, 1,553 patients with acute illnesses, and 577 patients with injuries) in this study. In the group of survivors in need of help and with acute illness, consciousness disturbance and lethargy without any organic disease were recognized as the main symptoms. Acute coronary syndrome and stroke were infrequently diagnosed. Of the survivors, 30% had a body temperature above 38\u00b0C. Their consciousness level significantly correlated with their body temperature. Emergency personnel reported that 79% of sudden cardiac arrests were from victims whose faces were submerged in the tub water, while 18% of survivors had their faces submerged in the tub water. Conclusion This study revealed that accidents, including non-lethal events, frequently occur. The key symptoms were consciousness disturbance and lethargy characterized as a functional disorder and accompanied by an elevated body temperature. Those findings suggest that heat illness during hot water immersion causes drowning.","subset":"pubmed_abstract"} +{"meta":{"pmid":12470439,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-33":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-21":2,"2021-04":1,"2020-45":1,"2020-05":1,"2019-18":1,"2022-40":1}}},"text":"Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes).\nLentinan was extracted from shiitake mushrooms (Lentinus edodes) via a new cost-effective procedure that resulted in high purity (88%) and yield. Unlike previous reports whereby the lentinan was given parenterally, in this study the emphasis was on the oral administration of lentinan. The goal is to document whether the efficacy of the antitumor property is still expressed through this route of administration. Initial study on the action of lentinan was conducted using murine lymphoma (K36) cells in a AKR mouse model. Further investigation on the effectiveness of the extracted lentinan was then performed using human colon-carcinoma cell lines in mice. Six established human colon-carcinoma cell lines segregated into three groups of different degrees of differentiation were used in this study. One group was not fed (control) and the second group was prefed with lentinan for 7 days prior to inoculations with the cancer cells. The size of the tumors that developed was rated after 1 month. Significant regression in tumor formation was observed in prefed mice compared to control (unfed) mice when K36 or human colon-carcinoma cells were used. Significant reductions in the size of the tumors were observed in mice prefed with lentinan. Follow-up investigation proceeded with the use of nude mice (athymic). Lymphocytes extracted from AKR mice prefed with lentinan for 7 days were inoculated into the nude mice. This was then followed by inoculation of the human colon-carcinoma cell lines into these mice. Much smaller tumors were formed in nude mice inoculated with lymphocytes, in contrast to the larger tumor formed in nude mice without lymphocytes inoculation. This study showed that the antitumor property of lentinan was maintained with oral administration. In addition, \"primed\" lymphocytes, when given passively to immunodeficient mice, were able to retard the development of tumors in these mice.","subset":"pubmed_abstract"} +{"meta":{"pmid":16989553,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":14}}},"text":"Electrophysiological correlates of retrieval processing: effects of consistent versus inconsistent retrieval demands.\nStudies employing event-related potentials (ERPs) during tests of recognition memory have reported differences in neural activity elicited by new test items according to the specific demands of the retrieval task, such as retrieving studied words versus pictures. The present study investigated whether differential processing of new items is possible when retrieval demands vary unpredictably on a trial-by-trial basis. In separate study-test phases, subjects encoded lists of intermixed words and pictures, and undertook retrieval tests with words as test items. Each test item was preceded by a task cue that signaled whether subjects were to attempt to retrieve a word or a picture from the study list. In the \"blocked\"condition, the targeted study material remained constant throughout the test, whereas in the \"mixed\"condition, the targeted material varied unpredictably across trials. New-item ERPs were more positive-going when words rather than pictures were targeted in the \"blocked\" condition, replicating previous findings, but this effect was absent in the \"mixed\"condition. The findings are consistent with the hypothesis that differential processing of retrieval cues depends upon the adoption of different task sets (\"retrieval orientations\" that develop over multiple trials and cannot be adjusted merely in response to an instructional cue. Unlike the new-item ERPs, ERPs elicited by the task cues in the mixed condition differed according to targeted material, but only on trials when there was a switch between target material. The implications of these findings for understanding the different retrieval strategies engaged when retrieval demands are consistent versus inconsistent are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":31320817,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Examining the involvement of Slx5 in the apoptotic response to chronic activation of the spindle assembly checkpoint.\nMicrotubule-targeting agents represent one of the most successful groups of anticancer drugs used in cancer therapy today. These drugs induce a prolonged mitotic arrest through chronic spindle assembly checkpoint (SAC) activation. Apoptosis, an outcome of the prolonged mitotic arrest, is the main mechanism by which these anticancer drugs kill cancer cells. However, not much is known about the mechanism that directs chronic SAC activation to apoptosis among other possible outcomes. The aim of this study is to investigate whether Slx5, a sumo-targeted ubiquitin E3 ligase, is involved in directing chronic SAC activation to apoptosis. We show that chronic SAC activation triggered by a 10-h nocodazole incubation leads to a prolonged mitotic arrest in the slx5\u0394 strain similar to wild type (WT). However, the proportion of cells displaying apoptotic features such as nuclear fragmentation, DNA fragmentation, and reactive oxygen species (ROS) production were increased more in the WT strain during the chronic SAC activation compared to slx5\u0394, indicating that Slx5 may be involved in the chronic SAC-activation-apoptosis relation. We also showed that the possible role of Slx5 in the chronic SAC activation-apoptosis association was not through ubiquitin dependent degradation of 3 apoptosis-related and sumoylated candidate proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":31252576,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Amphidinol 22, a New Cytotoxic and Antifungal Amphidinol from the Dinoflagellate Amphidinium carterae.\nDue to the unique biodiversity and the physical-chemical properties of their environment, marine microorganisms have evolved defense and signaling compounds that often have no equivalent in terrestrial habitats. The aim of this study was to screen extracts of the dinoflagellate Amphidinium carterae for possible bioactivities (i.e., anticancer, anti-inflammatory, anti-diabetes, antibacterial and antifungal properties) and identify bioactive compounds. Anticancer activity was evaluated on human lung adenocarcinoma (A549), human skin melanoma (A2058), human hepatocellular carcinoma (HepG2), human breast adenocarcinoma (MCF7) and human pancreas carcinoma (MiaPaca-2) cell lines. Antimicrobial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus MRSA and MSSA), Gram-negative bacteria (i.e., Escherichia coli and Klebsiella pneumoniae), Mycobacterium tuberculosis and the fungus Aspergillus fumigatus. The results indicated moderate biological activities against all the cancer cells lines and microorganisms tested. Bioassay-guided fractionation assisted by HRMS analysis allowed the detection of one new and two known amphidinols that are potentially responsible for the antifungal and cytotoxic activities observed. Further isolation, purification and structural elucidation led to a new amphidinol, named amphidinol 22. The planar structure of the new compound was determined by analysis of its HRMS and 1D and 2D NMR spectra. Its biological activity was evaluated, and it displayed both anticancer and antifungal activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":23678414,"dup_signals":{"dup_doc_count":21,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2022-49":2,"2022-40":1,"2022-21":2,"2022-05":1,"2021-39":1,"2021-25":1,"2019-51":1,"2019-39":2,"2019-26":1,"2018-43":1,"2018-22":1,"2017-51":1,"2017-43":1,"2017-34":1}}},"text":"Investigation into alternative sugars as potential carriers for dry powder formulation of budesonide.\nDry powder inhaler (DPI) formulations are so far being used for pulmonary drug delivery, mainly for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Currently most of DPI formulations rely on lactose as a carrier in the drug powder blend. However, due to reducing sugar function of lactose which makes it incompatible with some drugs such as budesonide, it is realistic to investigate for alternative sugars that would overcome the concerned drawback but still have the positive aspects of lactose. The study was conducted by characterizing carriers for their physico-chemical properties and preparing drug\/carrier blends with concentration of 5% and 10% drug with the carrier. The mixing uniformity (homogeneity) of Budesonide in the blends was analyzed using spectrophotometer. The blend was then filled into NB7\/2 Airmax inhaler device and the deposition profiles of the drug were determined using multi stage liquid impinger (MSLI) after aerosolization at 4 kPa via the inhaler. The morphology of the carriers conducted using the scanning electron microscope. The results determined that the mean fine particle fraction (FPF) of 5% and 10% blends of mannitol was 61%, possibly due to fine elongated particles. Dextrose exhibited excellent flowability. Scanning electron microscope illustrated mannitol with fine elongated particles and dextrose presenting larger and coarse particles. It was found out that type of carriers, particle size distribution, and morphology would influence the FPF of budesonide. It may be concluded that mannitol could be suitable as a carrier on the basis of its pharmaceutical performance and successful achievement of FPF whereas the more hygroscopic sugars such as sorbitol or xylitol showed poor dispersibility leading to lower FPF.","subset":"pubmed_abstract"} +{"meta":{"pmid":27185800,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis.\nThe novel ATP synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. In a limited number of bedaquiline-treated patients reported to date, \u22654-fold upward shifts in bedaquiline MIC during treatment have been attributed to non-target-based mutations in Rv0678 that putatively increase bedaquiline efflux through the MmpS5-MmpL5 pump. These mutations also confer low-level clofazimine resistance, presumably by a similar mechanism. Here, we describe a new non-target-based determinant of low-level bedaquiline and clofazimine cross-resistance in Mycobacterium tuberculosis: loss-of-function mutations in pepQ (Rv2535c), which corresponds to a putative Xaa-Pro aminopeptidase. pepQ mutants were selected in mice by treatment with clinically relevant doses of bedaquiline, with or without clofazimine, and were shown to have bedaquiline and clofazimine MICs 4 times higher than those for the parental H37Rv strain. Coincubation with efflux inhibitors verapamil and reserpine lowered bedaquiline MICs against both mutant and parent strains to a level below the MIC against H37Rv in the absence of efflux pump inhibitors. However, quantitative PCR (qPCR) revealed no significant differences in expression of Rv0678, mmpS5, or mmpL5 between mutant and parent strains. Complementation of a pepQ mutant with the wild-type gene restored susceptibility, indicating that loss of PepQ function is sufficient for reduced susceptibility both in vitro and in mice. Although the mechanism by which mutations in pepQ confer bedaquiline and clofazimine cross-resistance remains unclear, these results may have clinical implications and warrant further evaluation of clinical isolates with reduced susceptibility to either drug for mutations in this gene.","subset":"pubmed_abstract"} +{"meta":{"pmid":33175130,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":15}}},"text":"Guidelines for Opioid Prescribing in Children and Adolescents After Surgery: An Expert Panel Opinion.\nOpioids are frequently prescribed to children and adolescents after surgery. Prescription opioid misuse is associated with high-risk behavior in youth. Evidence-based guidelines for opioid prescribing practices in children are lacking. To assemble a multidisciplinary team of health care experts and leaders in opioid stewardship, review current literature regarding opioid use and risks unique to pediatric populations, and develop a broad framework for evidence-based opioid prescribing guidelines for children who require surgery. Reviews of relevant literature were performed including all English-language articles published from January 1, 1988, to February 28, 2019, found via searches of the PubMed (MEDLINE), CINAHL, Embase, and Cochrane databases. Pediatric was defined as children younger than 18 years. Animal and experimental studies, case reports, review articles, and editorials were excluded. Selected articles were graded using tools from the Oxford Centre for Evidence-based Medicine 2011 levels of evidence. The Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument was applied throughout guideline creation. Consensus was determined using a modified Delphi technique. Overall, 14 574 articles were screened for inclusion, with 217 unique articles included for qualitative synthesis. Twenty guideline statements were generated from a 2-day in-person meeting and subsequently reviewed, edited, and endorsed externally by pediatric surgical specialists, the American Pediatric Surgery Association Board of Governors, the American Academy of Pediatrics Section on Surgery Executive Committee, and the American College of Surgeons Board of Regents. Review of the literature and guideline statements underscored 3 primary themes: (1) health care professionals caring for children who require surgery must recognize the risks of opioid misuse associated with prescription opioids, (2) nonopioid analgesic use should be optimized in the perioperative period, and (3) patient and family education regarding perioperative pain management and safe opioid use practices must occur both before and after surgery. These are the first opioid-prescribing guidelines to address the unique needs of children who require surgery. Health care professionals caring for children and adolescents in the perioperative period should optimize pain management and minimize risks associated with opioid use by engaging patients and families in opioid stewardship efforts.","subset":"pubmed_abstract"} +{"meta":{"pmid":30657873,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":11}}},"text":"A Novel Olfactometer for Efficient and Flexible Odorant Delivery.\nUnderstanding how sensory space maps to neural activity in the olfactory system requires efficiently and flexibly delivering numerous odorants within single experimental preparations. Such delivery is difficult with current olfactometer designs, which typically include limited numbers of stimulus channels and are subject to intertrial and interchannel contamination of odorants. Here, we present a novel olfactometer design that is easily constructed, modular, and capable of delivering an unlimited number of odorants in air with temporal precision and no detectable intertrial or interchannel contamination. The olfactometer further allows for the flexible generation of odorant mixtures and flexible timing of odorant sequences. Odorant delivery from the olfactometer is turbulent but reliable from trial to trial, supporting operant conditioning of mice in an odorant discrimination task and permitting odorants and concentrations to be mapped to neural activity with a level of precision equivalent to that obtained with a flow dilution olfactometer. This novel design thus provides several unique advantages for interrogating olfactory perception and for mapping sensory space to neural activity in the olfactory system.","subset":"pubmed_abstract"} +{"meta":{"pmid":16669779,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Vitamin synthesis in plants: tocopherols and carotenoids.\nCarotenoids and tocopherols are the two most abundant groups of lipid-soluble antioxidants in chloroplasts. In addition to their many functional roles in photosynthetic organisms, these compounds are also essential components of animal diets, including humans. During the past decade, a near complete set of genes required for the synthesis of both classes of compounds in photosynthetic tissues has been identified, primarily as a result of molecular genetic and biochemical genomics-based approaches in the model organisms Arabidopsis thaliana and Synechocystis sp. PCC6803. Mutant analysis and transgenic studies in these and other systems have provided important insight into the regulation, activities, integration, and evolution of individual enzymes and are already providing a knowledge base for breeding and transgenic approaches to modify the types and levels of these important compounds in agricultural crops.","subset":"pubmed_abstract"} +{"meta":{"pmid":29296774,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis.\nSecondary acute myeloid leukemia (s-AML) includes therapy-related AML and AML evolving from antecedent hematological disorder (AHD). s-AML arising after treating AHD likely represents a prognostically distinct, high-risk disease category. In this study, treated s-AML (ts-AML) was defined by: (1) prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and (2) at least 1 therapy for that diagnosis. ts-AML was categorized by age (< or \u226560 years), and each cohort assessed for response rates and overall survival (OS) on various treatment regimens. Survival outcomes were compared against other high-risk prognostic subsets. Results showed that complete response and 8-week mortality rates were 32% and 27% in the younger, and 24% and 19% in the older age groups, respectively. There was a significant OS difference within s-AML based on prior treatment of AHD (ie, ts-AML vs s-AML with untreated AHD, 4.2 vs 9.2 months; P < .001). Survival in ts-AML was poor across both cohorts (younger and older, 5 and 4.7 months, respectively). In younger AML, survival was significantly inferior in ts-AML when compared with deletion 5\/7, TP53, 3q abnormality, and therapy-related AML groups (median, 5 vs 7.9, 7.8, 7.9, and 11.2 months, respectively; P < .01). Additional adverse karyotype within ts-AML was associated with even worse outcomes (OS range, 1.6-2.8 months). ts-AML represents a very high-risk category, even in younger AML patients. s-AML should be further classified to describe ts-AML, an entity less responsive to currently applied treatment approaches. Future AML trial designs should accommodate ts-AML as a distinct subgroup.","subset":"pubmed_abstract"} +{"meta":{"pmid":35632025,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Improving the Quality of Measurements Made by Alphasense NO2 Non-Reference Sensors Using the Mathematical Methods.\nConventional NO2 monitoring devices are relatively cumbersome, expensive, and have a relatively high-power consumption that limits their use to fixed sites. On the other hand, they offer high-quality measurements. In contrast, the low-cost NO2 sensors offer greater flexibility, are smaller, and allow greater coverage of the area with the measuring devices. However, their disadvantage is much lower accuracy. The main goal of this study was to investigate the measurement data quality of NO2-B43F Alphasense sensors. The measurement performance analysis of Alphasense NO2-B43F sensors was conducted in two research areas in Poland. Sensors were placed near fixed, professional air quality monitoring stations, carrying out measurements based on reference methods, in the following periods: July-November, and December-May. Results of the study show that without using sophisticated correction methods, the range of measured air pollution concentrations may be greater than their actual values in ambient air-measured in the field by fixed stations. In the case of summer months (with air temperature over 30 \u00b0C), the long-term mean absolute percentage error was over 150% and the sensors, using the methods recommended by the manufacturer, in the case of high temperatures could even show negative values. After applying the mathematical correction functions proposed in this article, it was possible to significantly reduce long-term errors (to 40-70% per month, regardless of the location of the measurements) and eliminate negative measurement values. The proposed method is based on the recalculation of the raw measurement, air temperature, and air RH and does not require the use of extensive analytical tools.","subset":"pubmed_abstract"} +{"meta":{"pmid":2995535,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2017-13":1,"2024-26":1,"unknown":10}}},"text":"Pig interleukin 1. Purification of two immunologically different leukocyte proteins that cause cartilage resorption, lymphocyte activation, and fever.\nTwo forms of interleukin 1 (IL-1) were purified to homogeneity from the culture supernatants of pig buffy coat leukocytes stimulated with concanavalin A. The two proteins had identical Mr of 21,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but one, which had previously been purified as a cartilage-resorbing protein, had pI 5 (IL-1\/5) and the other, pI 8.3 (IL-1\/8). After initial gel filtration and separation by chromatofocusing IL-1\/5 was purified by chromatography on hydroxyapatite and the ion exchangers, Mono S and Mono Q; IL-1\/8 was purified by chromatography at pH 4.0 and pH 6.4 on Mono S. Purification was monitored by a cartilage proteoglycan release assay and both proteins had a final specific activity approximately 10(5) times that of the leukocyte culture medium. Medium conditioned by cells from 200 L of blood yielded approximately 15 micrograms of IL-1\/5 and 50 micrograms IL-1\/8. IL-1\/8 augmented mouse thymocyte proliferation, stimulated synovial fibroblasts to produce prostaglandin E and latent collagenase, and was pyrogenic upon intracerebroventricular injection into rabbits. IL-1\/5 has previously been shown to possess all these activities. An antiserum to each IL-1 was raised in rabbits. Each antiserum inhibited its respective IL-1 in a cartilage bioassay and stained it upon Western blotting. Neither antiserum inhibited or stained the other IL-1. We conclude that pig leukocytes make two immunologically distinct forms of IL-1 that have identical Mr, demonstrate the same range of biological activity, but differ in isoelectric point.","subset":"pubmed_abstract"} +{"meta":{"pmid":2317789,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Pharmacokinetics of recombinant interleukin 2 in humans.\nThis report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an i.v. bolus, i.v. or i.p. infusion, and i.m. or s.c. injection. Immediately after an i.v. bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units\/ml for a dose of 10(6) units\/m2. The level initially decreases with a half-life of 12.9 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus. The median steady state level during an i.v. infusion of 10(6) units\/m2 over 6 h is 41 units\/ml. A clearance rate of approximately 120 ml\/min is obtained from either the i.v. bolus or infusion data and is consistent with the renal filtration being the major route of clearance. Serum levels remain fairly constant for about 8 h after s.c. or i.m. injection but are approximately 2% of the level seen immediately after an i.v. bolus. The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an i.m. injection to the blood. After i.p. infusion IL-2 is only slowly transported to the blood. The median serum IL-2 levels are 430-fold lower than levels in the i.p. fluid and decrease with a median half-life of 6.3 h.","subset":"pubmed_abstract"} +{"meta":{"pmid":15782944,"dup_signals":{"dup_doc_count":28,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2018-30":3,"2018-26":1,"2018-22":1,"2018-17":3,"2018-13":2,"2018-09":1,"2018-05":4,"2017-47":2,"2017-39":2,"2017-30":2,"2017-22":1,"2017-17":1,"2018-34":1,"2017-13":2}}},"text":"Chromatographic media for bioseparation.\nBioseparation processes are dominated by chromatographic steps. Even primary recovery is sometimes accomplished by chromatographic separation, using a fluidized bed instead of a fixed bed. In this review, the action principles, features of chromatography media regarding physical and chemical properties will be described. An attempt will be made to establish categories of different media. Characteristics for bioseparation are the large pores and particle sizes. To achieve sufficient capacity for ultralarge molecules, such as plasmids or nanoparticles, such as viruses monoliths are the media of choice. In these media, the mass transport is accomplished by convection, and thus, the low diffusivity can be overcome. Common to all modern chromatography media is the fast operation. There are examples where a residence time of less then 3 min, is sufficient to reach the full potential of the adsorbent.","subset":"pubmed_abstract"} +{"meta":{"pmid":22300646,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":14}}},"text":"Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure.\nChronic liver failure leads to hyperammonemia, a central component in the pathogenesis of hepatic encephalopathy (HE); however, a correlation between blood ammonia levels and HE severity remains controversial. It is believed oxidative stress plays a role in modulating the effects of hyperammonemia. This study aimed to determine the relationship between chronic hyperammonemia, oxidative stress, and brain edema (BE) in two rat models of HE: portacaval anastomosis (PCA) and bile-duct ligation (BDL). Ammonia and reactive oxygen species (ROS) levels, BE, oxidant and antioxidant enzyme activities, as well as lipid peroxidation were assessed both systemically and centrally in these two different animal models. Then, the effects of allopurinol (xanthine oxidase inhibitor, 100mg\/kg for 10days) on ROS and BE and the temporal resolution of ammonia, ROS, and BE were evaluated only in BDL rats. Similar arterial and cerebrospinal fluid ammonia levels were found in PCA and BDL rats, both significantly higher compared to their respective sham-operated controls (p<0.05). BE was detected in BDL rats (p < 0.05) but not in PCA rats. Evidence of oxidative stress was found systemically but not centrally in BDL rats: increased levels of ROS, increased activity of xanthine oxidase (oxidant enzyme), enhanced oxidative modifications on lipids, as well as decreased antioxidant defense. In PCA rats, a preserved oxidant\/antioxidant balance was demonstrated. Treatment with allopurinol in BDL rats attenuated both ROS and BE, suggesting systemic oxidative stress is implicated in the pathogenesis of BE. Analysis of ROS and ammonia temporal resolution in the plasma of BDL rats suggests systemic oxidative stress might be an important \"first hit\", which, followed by increases in ammonia, leads to BE in chronic liver failure. In conclusion, chronic hyperammonemia and oxidative stress in combination lead to the onset of BE in rats with chronic liver failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":21630013,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-39":1,"2020-40":1,"2020-05":1,"2019-18":1,"2018-39":1,"2018-17":1,"2017-51":1,"2017-43":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-14":1,"2017-13":1}}},"text":"Outcomes of antiretroviral therapy in the Swiss HIV Cohort Study: latent class analysis.\nAn in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":21860911,"dup_signals":{"dup_doc_count":24,"dup_dump_count":8,"dup_details":{"curated_sources":3,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2013-20":1,"2024-18":1,"unknown":12}}},"text":"Association between alcohol abuse during pregnancy and birth weight.\nTo assess the association between alcohol abuse during gestation and low birth weight. Cross-sectional, population-based nested study from a cohort of 957 pregnant women who received prenatal assistance through Sistema \u00danico de Sa\u00fade (National Health System) in the city of Pelotas, Southern Brazil, and delivered their babies between September 2007 and September 2008. The mothers were interviewed at two distinct moments: prenatal and postpartum periods. In order to verify alcohol abuse, the CAGE (Cut down, Annoyed by criticism, Guilty and Eye-opener) scale was used. Bivariate analyses were carried out, as well as multiple logistic regression adjusted by the variables prematurity and alcohol abuse. The level of significance that was adopted was 95%. Of the women who participated in the study, 2.1% abused alcohol during pregnancy and, among these, 26.3% had low birth weight children. There was an association between alcohol abuse and low birth weight (p<0.038). The findings indicate that alcohol abuse during pregnancy is associated with low birth weight.","subset":"pubmed_abstract"} +{"meta":{"pmid":28660869,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A reliability and readability analysis of silicosis-related Italian websites: implications for occupational health.\nSilicosis represents a \"classical\" occupational disease characterized by a renewed interest. New risk factors are emerging, such as sandblasting in the jeans industry or hydrofracking, leading to clusters of acute or massive cases. Given that the Internet could represent a worker education and empowerment tool, and considering the increase in popularity of silicosis-related information, we aimed at systematically analyzing the reliability and readability of online silicosis-relevant information. The search term \"silicosi\" was used to query 5 top search engines. The first 3 pages of results were screened using two validated readability tools: namely, the Gulpease and the ReadIt DyLanLab grade level scores. Seventy sites were analyzed. The Gulpease score differed among the types of websites: academic websites differed from institutional websites, as well as encyclopedia\/dictionary pages from institutional sites. The Lexical Model - ReadIt DyLanLab grade level differed among the types of websites. Encyclopedia\/dictionary pages differed from academic, commercial, health-related, institutional and news sites. Approximately, half of the websites were intended\/designed for workers. Only the Global Model - Read-It DyLanLab grade level differed according to the intended\/designed target. Only 1.4% of websites adhered to Health on the Net Foundation Code of Conduct. Our findings may have important practical implications for occupational physicians and health agencies\/authorities. They should make efforts in strengthening their online presence, and producing appropriate material. This could lead to positive outcomes in term of occupational health promotion, potentially enabling workers to increase and to improve their work-related health and its determinants.","subset":"pubmed_abstract"} +{"meta":{"pmid":17611984,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation.\nTo investigate whether 14-3-3 proteins were detectable in synovial fluid (SF) of patients with inflamed joints, and if so, what isoform(s); and to examine whether there was a correlation between the levels of these proteins and those of MMP-1 and MMP-3 in the same samples. In general, 2 sets of synovial and serum samples were analyzed. The first set of 17 SF -samples from patients with inflamed joints were analyzed for 14-3-3 eta isoform by Western blot. The second set of 12 matching serum and SF samples were analyzed for 14-3-3 eta, gamma, MMP-1, and MMP-3 by the same procedure. The MMP-1 stimulatory effect of various concentrations of 14-3-3 eta in cultured fibroblasts was then evaluated. We found that of the seven 14-3-3 isoforms tested (beta, gamma, epsilon, eta, sigma, Theta, and zeta), the levels of only 2 isoforms, eta and gamma, were easily detectable in SF samples from patients with inflammatory joint diseases. The levels of these proteins were significantly higher in inflammatory SF and serum samples relative to controls. The values of these proteins correlated strongly with the levels of MMP-1 and MMP-3, 2 biomarkers for rheumatoid arthritis, detected in sera. Further, the level of 14-3-3 eta was significantly higher in a pool of 12 serum samples from patients with inflammatory joint disease than those from healthy individuals. Detection of only 2 (14-3-3 eta and gamma) out of 7 different isoforms in SF suggests they are specific to the site of inflammation, and that distinguishes them from barely detectable levels of these isoforms found in normal serum. The MMP-1 stimulatory effect of the eta isoform explains its correlation with MMP-1 levels seen in these samples.","subset":"pubmed_abstract"} +{"meta":{"pmid":10518921,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"The suitability of five liquid scintillation cocktails for use with a continuous flow-through mucosal perfusion system.\nContinuous flow-through perfusion systems can be successfully used to study the permeability of small mucosal samples to various permeants. The latter often need to be radiolabelled to enable detection by means of liquid scintillation counting. However, the efficacy of the latter is dependent on the liquid scintillation cocktail used. The present study was conducted to evaluate five liquid scintillation cocktails commercially available in South Africa. Although four out of the five cocktails had similar efficacies in the concentration range 0.05 to 50 nCi, this was not the case in the low range (0.01 to 0.5 nCi). Overall Ready Protein+ was the most efficacious and has the added advantage that this cocktail has protein solubilising properties. The latter is important when we extend our permeability studies to include small proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":33225206,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Universal Screening of Gastrointestinal Malignancies for Mismatch Repair Deficiency at Stanford.\nIn light of recent Food and Drug Administration (FDA) approval of immune checkpoint inhibitors for mismatch repair deficient (dMMR) malignancies, identifying patients with dMMR malignancies has become increasingly important. Although screening for dMMR in colorectal cancer (CRC) is recommended, it is less common for extracolonic gastrointestinal (GI) malignancies. At Stanford Comprehensive Cancer Institute (SCCI), all GI malignancies have been screened for dMMR via immunohistochemistry since January 2016. In this study, we conducted a retrospective review of all patients with GI malignancies screened for dMMR between January 2016 and December 2017. Tumor sequencing was performed on cases negative for germline pathogenic variants where tumor material was available. A total of 1425 consecutive GI malignancies were screened for dMMR at SCCI during the study period, and 1374 were included for analysis. dMMR was detected in 7.2% of all GI malignancies. We detected the highest prevalence of dMMR in gastric (15 of 150, 10.0%) followed by colorectal (63 of 694, 9.1%), pancreatic (13 of 244, 5.3%), and gastroesophageal malignancy (6 of 132, 4.5%) patients. Lynch syndrome was the most common etiology for dMMR in colorectal cancer (41.5%), double somatic (confirmed or possible) pathogenic variants the most common etiology in pancreatic cancer (44.4%), and somatic MLH1 hypermethylation the most common etiology in gastric (73.3%) and gastroesophageal cancer (83.3%). Given the relatively high incidence of dMMR in GI malignancies, we recommend screening all GI malignancies. Our results suggest that although a rare occurrence, double somatic pathogenic variants may be a biologically significant pathway causing dMMR in pancreatic cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":27570294,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Antihypercholesterolemic and antioxidant effect of sterol rich methanol extract of stem of Musa sapientum (banana) in cholesterol fed wistar rats.\nMusa sapientum Linn. (English 'Banana' family Musaceae), is a plant with nutritive, as well as medicinal value. Antihypercholesterolemic and antioxidant effect of methanolic extract of stem of this plant was investigated in hypercholesterolemic rats. Rats were made hypercholesterolemic by feeding cholesterol (100 mg\/kg\/day) suspended in soya oil. Treatment groups received extract at a dose of 10, 20 and 40 mg\/kg\/day in addition to cholesterol orally once daily. Fasting blood samples were collected before and after 6 weeks treatment. Animals were sacrificed and liver stored at -80 \u00b0C. Total cholesterol, HDL-cholesterol and triacylglycerol were estimated in blood. Malondialdehyde, reduced glutathione, superoxide dismutase and catalase were measured in blood and liver. Total lipids, HMG CoA redutase and lipoprotein lipase were investigated in liver. Most effective dose was found to be 20 mg\/kg\/day. Rise in total cholesterol, LDL + VLDL-cholesterol and triacylglycerol in animals receiving only cholesterol was 179 %, 417 % and 74 % respectively, while in animals receiving 20 mg\/kg dose rise in these parameters was restricted to 40 %, 106 % and 24 %. HDL-cholesterol decreased by 12 % in extract treated group, while it decreased to 36 % in untreated hypercholesterolemic rats. Malonaldialdehyde, marker of lipid peroxidation decreased while reduced glutathione and enzymes superoxide dismutase and catalase increased significantly in blood and liver (p < 0.01). Total lipids in liver decreased and enzymes of lipid metabolism viz. HMG CoA redutase and lipoprotein lipase were restored to near normal. Gas chromatography mass spectroscopy indicated high content of sterols in extract. Study demonstrated that methanol extract of stem of Musa sapientum has significant antihypercholesterolemic and antioxidant effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":33125716,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies.\nTo conduct a systematic review of modern-era (post-millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective drug experiences were also reviewed and presented. A systematic literature search (1 Jan 2000 to 1 May 2020) was conducted in PubMed and PsychINFO for studies of patients undergoing treatment with a serotonergic psychedelic. Data from 16 papers, representing 10 independent psychedelic-assisted therapy trials (psilocybin = 7, ayahuasca = 2, LSD = 1), were extracted, presented in figures and tables, and narratively synthesized and discussed. Across these studies, a total of 188 patients suffering either cancer- or illness-related anxiety and depression disorders (C\/I-RADD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD) or substance use disorder (SUD) were included. The reviewed studies established feasibility and evidence of safety, alongside promising early data of efficacy in the treatment of depression, anxiety, OCD, and tobacco and alcohol use disorders. For a majority of patients, the therapeutic effects appeared to be long-lasting (weeks-months) after only 1 to 3 treatment session(s). All studies were conducted in line with guidelines for the safe conduct of psychedelic therapy, and no severe adverse events were reported. The resurrection of clinical psychedelic research provides early evidence for treatment efficacy and safety for a range of psychiatric conditions, and constitutes an exciting new treatment avenue in a health area with major unmet needs.","subset":"pubmed_abstract"} +{"meta":{"pmid":23583268,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2020-40":1,"2023-23":1,"2024-10":1,"2024-26":1}}},"text":"Targeting ATR in DNA damage response and cancer therapeutics.\nThe ataxia telangiectasia and Rad3-related (ATR) plays an important role in maintaining genome integrity during DNA replication through the phosphorylation and activation of Chk1 and regulation of the DNA damage response. Preclinical studies have shown that disruption of ATR pathway can exacerbate the levels of replication stress in oncogene-driven murine tumors to promote cell killing. Additionally, inhibition of ATR can sensitise tumor cells to radiation or chemotherapy. Accumulating evidence suggests that targeting ATR can selectively sensitize cancer cells but not normal cells to DNA damage. Furthermore, in hypoxic conditions, ATR blockade results in overloading replication stress and DNA damage response causing cell death. Despite the attractiveness of ATR inhibition in the treatment of cancer, specific ATR inhibitors have remained elusive. In the last two years however, selective ATR inhibitors suitable for in vitro and - most recently - in vivo studies have been identified. In this article, we will review the literature on ATR function, its role in DDR and the potential of ATR inhibition to enhance the efficacy of radiation and chemotherapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":11869681,"dup_signals":{"dup_doc_count":56,"dup_dump_count":28,"dup_details":{"curated_sources":2,"2023-40":5,"2023-23":1,"2023-14":2,"2023-06":1,"2022-40":1,"2022-33":2,"2022-27":1,"2022-21":3,"2022-05":2,"2021-43":2,"2021-39":1,"2021-31":2,"2021-17":3,"2021-04":3,"2020-45":3,"2019-51":1,"2019-35":1,"2018-43":1,"2018-34":2,"2018-22":2,"2018-13":2,"2018-05":1,"2017-51":1,"2017-43":2,"2017-34":2,"2024-30":2,"2024-18":4,"2024-10":1}}},"text":"WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation.\nWIP stabilizes actin filaments and is important for filopodium formation. To define the role of WIP in immunity, we generated WIP-deficient mice. WIP(minus sign\/minus sign) mice have normal lymphocyte development, but their T cells fail to proliferate, secrete IL-2, increase their F-actin content, polarize and extend protrusions following T cell receptor ligation, and are deficient in conjugate formation with superantigen-presenting B cells and anti-CD3 bilayers. In contrast, WIP-deficient B lymphocytes have enhanced proliferation and CD69 expression following B cell receptor ligation and mount normal antibody responses to T-independent antigens. Both WIP-deficient T and B cells show a profound defect in their subcortical actin filament networks. These results suggest that WIP is important for immunologic synapse formation and T cell activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":30975016,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Objective and Self-Reported Measures of Physical Activity and Sex Hormones: Women's Lifestyle Validation Study.\nBackground: The relationship between specific characteristics of physical activity (PA) (eg, intensity, type, frequency) with sex hormones is uncertain. The authors evaluated the association between characteristics of PA and circulating sex hormones. Methods: This was a cross-sectional analysis of the Women's Lifestyle Validation Study (n = 493). Total PA, light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA) were assessed by accelerometry (a) and self-report (sr). Self-report was used to assess PA type (ie, aerobic, weight training) and exercise frequency. Dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin (SHBG) were assayed among all women; estradiol was assayed in postmenopausal women not currently on hormone therapy. Results: Estradiol was inversely associated and SHBG positively associated with MVPA and LPA (estradiol: \u03b2 = -0.15 per SD increase, P \u2264 .01 for a-MVPA and a-LPA; SHBG: a-MVPA \u03b2 = 0.20 per SD increase, P \u2264 .01, a-LPA \u03b2 = 0.15, P < .01). By type, aerobic activity and weight training were each independently associated with estradiol and SHBG. Controlling for body mass index attenuated all associations for estradiol, and to a lesser extent SHBG. PA was not associated with testosterone levels. Conclusions: Multiple aspects of PA were independently associated with sex hormones; associations varied some by activity intensity and type, and were attenuated after accounting for body mass index.","subset":"pubmed_abstract"} +{"meta":{"pmid":22348055,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"The effect of surface wave propagation on neural responses to vibration in primate glabrous skin.\nBecause tactile perception relies on the response of large populations of receptors distributed across the skin, we seek to characterize how a mechanical deformation of the skin at one location affects the skin at another. To this end, we introduce a novel non-contact method to characterize the surface waves produced in the skin under a variety of stimulation conditions. Specifically, we deliver vibrations to the fingertip using a vibratory actuator and measure, using a laser Doppler vibrometer, the surface waves at different distances from the locus of stimulation. First, we show that a vibration applied to the fingertip travels at least the length of the finger and that the rate at which it decays is dependent on stimulus frequency. Furthermore, the resonant frequency of the skin matches the frequency at which a subpopulation of afferents, namely Pacinian afferents, is most sensitive. We show that this skin resonance can lead to a two-fold increase in the strength of the response of a simulated afferent population. Second, the rate at which vibrations propagate across the skin is dependent on the stimulus frequency and plateaus at 7 m\/s. The resulting delay in neural activation across locations does not substantially blur the temporal patterning in simulated populations of afferents for frequencies less than 200 Hz, which has important implications about how vibratory frequency is encoded in the responses of somatosensory neurons. Third, we show that, despite the dependence of decay rate and propagation speed on frequency, the waveform of a complex vibration is well preserved as it travels across the skin. Our results suggest, then, that the propagation of surface waves promotes the encoding of spectrally complex vibrations as the entire neural population is exposed to essentially the same stimulus. We also discuss the implications of our results for biomechanical models of the skin.","subset":"pubmed_abstract"} +{"meta":{"pmid":7449099,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Measurement of near-normal concentrations of erythrocyte protoporphyrin with the hematofluorometer: influence of plasma on \"front-surface illumination\" assay.\nZinc protoporphyrin in erythrocytes increases in iron depletion. Because the hematofluorometer directly measures zinc protoporphyrin in whole blood, it may therefore be a useful screening instrument for detecting iron deficiency. We evaluated its performance with normal to slightly above-normal zinc protoporphyrin concentrations (0.2 to 2.0 mg\/L) in erythrocytes, because this is a critical range for differentiating normal and iron-deficient individuals. There was excellent correlation (r2 = 0.900) between erythrocyte protoporphyrin as measured by an extraction procedure and as measured directly with the hematofluorometer. However, at these concentrations, plasma caused hematofluorometer readings to be spuriously high, by 2.4 to 89.4%, an effect due to the instrument's optical design. The effect can be eliminated by washing the cells free of plasma or by allowing erythrocytes to displace plasma by settling to the illuminated surface before the measurement. The interference does not affect the hematofluorometer's sensitivity, but abnormal results obtained for whole blood should be confirmed with more-specific tests, and interlaboratory precision may be influenced if whole-blood samples are used. A 1-min delay from sample placement to measurement decreased zinc protoporphyrin values by 2.6 to 36.9%. We also describe the use of cryopreserved control erythrocytes, for which the CV is 2.3% for a concentration of 0.96 mg per liter of erythrocytes, which are not affected by time of measurement, and which are stable for three months.","subset":"pubmed_abstract"} +{"meta":{"pmid":30606745,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-16":1,"2019-39":1,"2019-22":1,"2019-13":1,"2023-40":1,"2024-18":1}}},"text":"Leveraging Evidence-Based Public Policy and Advocacy to Advance Newborn Screening in California.\nIn 2016, the EveryLife Foundation for Rare Diseases, in partnership with Dr Pan, who is a pediatrician and state senator in California, launched legislation to advance and expand newborn screening. Researchers have shown that newborn screening can be cost-effective and can greatly improve health outcomes for patients with rare diseases. However, adding additional diseases in newborn screening is a long process, requiring legislative approval in addition to new state funding. Such process delays can lead to protracted diagnostic odysseys for patients, especially those with rare diseases. These delays can result in irreversible morbidity and, in some cases, early mortality for patients. To improve this process, legislation known as Senate Bill 1095 was introduced to require California to adhere to the latest federal recommendations for newborn screening within 2 years. We provide insight and describe the process of advancing state legislation, coalition building, and managing opposition. Senate Bill 1095 would become law in 2016, requiring California to screen for 2 new rare diseases by August 2018: mucopolysaccharidosis type I and Pompe disease. This case study can serve as a model for advocates looking to expand state newborn-screening programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":22001751,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":2,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Identification of serum proteins bound to industrial nanomaterials.\nNanoparticles (NPs) are decorated with proteins and other biomolecules when they get into contact with biological systems. The presence of proteins in cell culture medium can therefore have effects on the biological outcome in cell-based tests. In this study, the manufactured nanomaterials silicon dioxide (SiO(2)), titanium dioxide (TiO(2)), iron-III-oxide (Fe(2)O(3)), and carbon black (CB) were used to study their interaction with single proteins from bovine and human plasma (albumin, fibrinogen and IgG) as well as with complete human serum. The protein binding capacity of the material was investigated and 1D gel electrophoresis was used to separate the bound proteins and to identify the bands by matrix-assisted laser desorption\/ionisation-time-of-flight (MALDI-TOF) mass spectrometry. We found that the NP surface chemistry had a great impact on the amount of bound protein with distinct ligands for each of the tested particles. The hydrophobic CB NPs bound much more protein than the hydrophilic metal oxide NPs. Among the single proteins investigated, fibrinogen showed the strongest affinity for SiO(2), TiO(2) and CB NPs. The identified proteins from human serum adsorbed to these NPs were very different. Only apolipoprotein A1 was found to be adsorbed to all NPs. These studies will help to explain the different degree of biological responses observed after in vitro exposure of cells in the absence or presence of serum and might also support the interpretation of in vivo experiments were NPs come directly into contact with blood plasma.","subset":"pubmed_abstract"} +{"meta":{"pmid":15861138,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2015-14":1,"2016-40":1,"2015-18":1}}},"text":"Mot1-mediated control of transcription complex assembly and activity.\nMot1 is an essential Snf2\/Swi2-related ATPase and TATA-binding protein (TBP)-associated factor (TAF). In vitro, Mot1 utilizes ATP hydrolysis to disrupt TBP-DNA complexes, but the relationship of this activity to Mot1's in vivo function is unclear. Chromatin immunoprecipitation was used to determine how Mot1 affects the assembly of preinitiation complexes (PICs) at Mot1-controlled promoters in vivo. We find that the Mot1-repressed HSP26 and INO1 promoters are both regulated by TBP recruitment; inactivation of Mot1 leads to increased PIC formation coincident with derepression of transcription. For the Mot1-activated genes BNA1 and URA1, inactivation of Mot1 also leads, remarkably, to increased TBP binding to the promoters, despite the fact that transcription of these genes is obliterated in mot1 cells. In contrast, levels of Taf1, TFIIB, and RNA polymerase II are reduced at Mot1-activated promoters in mot1 cells. These results suggest that Mot1-mediated displacement of TBP underlies its mechanism of repression and activation at these genes. We suggest that at activated promoters, Mot1 disassembles transcriptionally inactive TBP, thereby facilitating the formation of a TBP complex that supports functional PIC assembly.","subset":"pubmed_abstract"} +{"meta":{"pmid":32110988,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Impact of Cover Crops on the Soil Microbiome of Tree Crops.\nIncreased concerns associated with interactions between herbicides, inorganic fertilizers, soil nutrient availability, and plant phytotoxicity in perennial tree crop production systems have renewed interest in the use of cover crops in the inter-row middles or between trees as an alternative sustainable management strategy for these systems. Although interactions between the soil microbiome and cover crops have been examined for annual cropping systems, there are critical differences in management and growth in perennial cropping systems that can influence the soil microbiome and, therefore, the response to cover crops. Here, we discuss the importance of cover crops in tree cropping systems using multispecies cover crop mixtures and minimum tillage and no-tillage to not only enhance the soil microbiome but also carbon, nitrogen, and phosphorus cycling compared to monocropping, conventional tillage, and inorganic fertilization. We also identify potentially important taxa and research gaps that need to be addressed to facilitate assessments of the relationships between cover crops, soil microbes, and the health of tree crops. Additional evaluations of the interactions between the soil microbiome, cover crops, nutrient cycling, and tree performance will allow for more effective and sustainable management of perennial cropping systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":21329559,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Suppressive effect of asbestos on cytotoxicity of human NK cells.\nAsbestos, a naturally occurring fibrous mineral, causes malignant mesothelioma (MM). However, it takes a very long time to develop MM, which suggests that effects other than tumorigenicity of asbestos might contribute to the development of MM, and one of the possible targets is anti-tumor immunity. Therefore, we examined the effect of asbestos exposure on human natural killer (NK) cells using the cell line of YT-A1, Peripheral blood mononuclear cells (PBMCs) cultures and specimens from patients with MM. In particular, we focused on expression of NK cell-activating receptors, including NKG2D, 2B4 and NKp46. Analysis of the YT-CB5 subline of YT-A1, cultured with CB for over 5 months, showed a decrease in cytotoxicity with low expressions of NKG2D and 2B4, although there were no decreases after about one month. YT-CB5 showed decreases in phosphorylation of extracellular signal-regulated kinase (ERK) and degranulation stimulated by antibodies to NKG2D. Peripheral blood (PB-) NK cells from MM patients also showed decreased cytotoxicity compared with healthy volunteers (HV), and was accompanied with low expression of NKp46 unlike YT-CB5. PBMCs cultured with CB resulted in decreased expression of NKp46 on NK cells, although this did not occur when using glass wool, an asbestos substitute. These results indicate that asbestos has the potential to suppress cytotoxicity of NK cells. In particular, it is noteworthy that both NK cells from MM patients and those from a culture of PBMCs derived from HVs with asbestos showed the same characteristic of decreased cytotoxicity with low expression of NKp46.","subset":"pubmed_abstract"} +{"meta":{"pmid":16966412,"dup_signals":{"dup_doc_count":89,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2023-40":4,"2023-23":6,"2023-14":5,"2023-06":2,"2022-49":6,"2022-40":2,"2022-33":1,"2022-27":6,"2022-21":4,"2022-05":2,"2021-49":1,"2021-43":3,"2021-39":1,"2021-31":4,"2021-25":1,"2021-21":2,"2021-17":7,"2021-10":2,"2021-04":3,"2020-50":2,"2020-45":1,"2020-40":3,"2023-50":1,"2024-30":5,"2024-22":4,"2024-18":4,"2024-10":3}}},"text":"Early gamma interferon and interleukin-2 responses to vaccination predict the late resting memory in malaria-na\u00efve and malaria-exposed individuals.\nTwo different cell populations respond to potent T-cell-inducing vaccinations. The induction and loss of effector cells can be seen using an ex vivo enzyme-linked immunospot (ELISPOT) assay, but the more durable resting memory response is demonstrable by a cultured ELISPOT assay. The relationship of the early effector response to durable resting memory is incompletely understood. Effector phenotype is usually identified by gamma interferon (IFN-gamma) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-gamma- and IL-2-secreting effector cells were identified by an ex vivo ELISPOT assay 1 week after vaccination and compared with the resting memory responses detected by a cultured ELISPOT assay 3 months later. The different kinetics and induction of IL-2 by different vaccines and natural exposure are described. Furthermore, both early IFN-gamma and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-na\u00efve volunteers, but only IFN-gamma predicted memory in malaria-exposed volunteers. However, dual ELISPOT assays were also performed on malaria-exposed volunteers to identify cells producing both cytokines simultaneously. This demonstrated that double-cytokine-producing cells were highly predictive of memory. This assay may be useful in predicting vaccinations most likely to generate stable, long-term memory responses.","subset":"pubmed_abstract"} +{"meta":{"pmid":22192879,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Communicating oscillatory networks: frequency domain analysis.\nConstructing predictive dynamic models of interacting signalling networks remains one of the great challenges facing systems biology. While detailed dynamical data exists about individual pathways, the task of combining such data without further lengthy experimentation is highly nontrivial. The communicating links between pathways, implicitly assumed to be unimportant and thus excluded, are precisely what become important in the larger system and must be reinstated. To maintain the delicate phase relationships between signals, signalling networks demand accurate dynamical parameters, but parameters optimised in isolation and under varying conditions are unlikely to remain optimal when combined. The computational burden of estimating parameters increases exponentially with increasing system size, so it is crucial to find precise and efficient ways of measuring the behaviour of systems, in order to re-use existing work. Motivated by the above, we present a new frequency domain-based systematic analysis technique that attempts to address the challenge of network assembly by defining a rigorous means to quantify the behaviour of stochastic systems. As our focus we construct a novel coupled oscillatory model of p53, NF-kB and the mammalian cell cycle, based on recent experimentally verified mathematical models. Informed by online databases of protein networks and interactions, we distilled their key elements into simplified models containing the most significant parts. Having coupled these systems, we constructed stochastic models for use in our frequency domain analysis. We used our new technique to investigate the crosstalk between the components of our model and measure the efficacy of certain network-based heuristic measures. We find that the interactions between the networks we study are highly complex and not intuitive: (i) points of maximum perturbation do not necessarily correspond to points of maximum proximity to influence; (ii) increased coupling strength does not necessarily increase perturbation; (iii) different perturbations do not necessarily sum and (iv) overall, susceptibility to perturbation is amplitude and frequency dependent and cannot easily be predicted by heuristic measures.Our methodology is particularly relevant for oscillatory systems, though not limited to these, and is most revealing when applied to the results of stochastic simulation. The technique is able to characterise precisely the distance in behaviour between different models, different systems and different parts within the same system. It can also measure the difference between different simulation algorithms used on the same system and can be used to inform the choice of dynamic parameters. By measuring crosstalk between subsystems it can also indicate mechanisms by which such systems may be controlled in experiments and therapeutics. We have thus found our technique of frequency domain analysis to be a valuable benchmark systems-biological tool.","subset":"pubmed_abstract"} +{"meta":{"pmid":16341225,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":1,"2024-30":1,"unknown":14}}},"text":"Crystal structure and functional analysis of Dcp2p from Schizosaccharomyces pombe.\nDecapping is a key step in both general and nonsense-mediated 5' --> 3' mRNA-decay pathways. Removal of the cap structure is catalyzed by the Dcp1-Dcp2 complex. The crystal structure of a C-terminally truncated Schizosaccharomyces pombe Dcp2p reveals two distinct domains: an all-helical N-terminal domain and a C-terminal domain that is a classic Nudix fold. The C-terminal domain of both Saccharomyces cerevisiae and S. pombe Dcp2p proteins is sufficient for decapping activity, although the N-terminal domain can affect the efficiency of Dcp2p function. The binding of Dcp2p to Dcp1p is mediated by a conserved surface on its N-terminal domain, and the N-terminal domain is required for Dcp1p to stimulate Dcp2p activity. The flexible nature of the N-terminal domain relative to the C-terminal domain suggests that Dcp1p binding to Dcp2p may regulate Dcp2p activity through conformational changes of the two domains.","subset":"pubmed_abstract"} +{"meta":{"pmid":18828412,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":2,"unknown":7}}},"text":"Place matters: variation in the black\/white very preterm birth rate across U.S. metropolitan areas, 2002-2004.\nWe reported on the distribution of very preterm (VPT) birth rates by race across metropolitan statistical areas (MSAs). Rates of singleton VPT birth for non-Hispanic white, non-Hispanic black, and Hispanic women were calculated with National Center for Health Statistics 2002-2004 natality files for infants in 168 MSAs. Subanalysis included stratification by parity, age, smoking, maternal education, metropolitan size, region, proportion of MSA that was black, proportion of black population living below the poverty line, and indices of residential segregation. The mean metropolitan-level VPT birth rate was 12.3, 34.8, and 15.7 per 1,000 live births for white, black, and Hispanic women, respectively. There was virtually no overlap in the white and black distributions. The variation in mean risk across cities was three times greater for black women compared with white women. The threefold disparity in mean rate, and two- to threefold increased variation as indicated by standard deviation, was maintained in all subanalyses. Compared with white women, black women have three times the mean VPT birth risk, as well as three times the variance in city-level rates. The racial disparity in VPT birth rates was composed of characteristics that were constant across MSAs, as well as factors that varied by MSA. The increased sensitivity to place for black women was unexplained by measured maternal and metropolitan factors. Understanding determinants of differences in both the mean risk and the variation of risk among black and white women may contribute to reducing the disparity in risk between races.","subset":"pubmed_abstract"} +{"meta":{"pmid":8568599,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Angiotensin converting enzyme inhibition prevents polyploidization of cardiomyocytes in spontaneously hypertensive rats with left ventricular hypertrophy.\nPolyploidization of cardiomyocyte nuclei is a physiological phenomenon that increases in pathological conditions such as myocardial hypertrophy. The purpose of this study was to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the polyploidization of cardiomyocyte nuclei in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH). Sixteen week-old male SHR were treated with oral quinapril (average dose 10 mg\/kg per day) for 20 weeks. Sixteen- and 36-week-old untreated SHR and 16- and 36-week-old normotensive Wistar-Kyoto (WKY) rats were used as controls. Nuclear polyploidization was determined by DNA flow cytometry of frozen tissues from the left ventricle, at least 20,000 nuclei being measured in each sample. The rates of tetraploidy in the 16- and 36-week-old SHR groups were 2.8 per cent (range 2.16-3 per cent) and 5.4 per cent (range 4.9-5.9 per cent), respectively. Treated SHR had a similar rate of DNA tetraploidy to the 16- and 36-week-old WKY rat groups: 1.8 per cent (range 1.5-2.3 per cent), 1.55 per cent (range 1.5-1.6 per cent), and 1.5 per cent (range 1.4-1.6 per cent), respectively. The differences in the percentage of tetraploid cardiomyocytes between the SHR untreated groups and the SHR treated group were statistically significant (P < 0.05). Regression of LVH and normalization of blood pressure were observed in treated rats. These results indicate that DNA tetraploidy in the myocardium of SHR increases with hypertrophy and decreases on quinapril treatment. It is suggested that ACE inhibition modifies nuclear processes involved in myocyte growth in arterial hypertension.","subset":"pubmed_abstract"} +{"meta":{"pmid":30746314,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Study of silica-based intrinsically emitting nanoparticles produced by an excimer laser.\nWe report an experimental study demonstrating the feasibility to produce both pure and Ge-doped silica nanoparticles (size ranging from tens up to hundreds of nanometers) using nanosecond pulsed KrF laser ablation of bulk glass. In particular, pure silica nanoparticles were produced using a laser pulse energy of 400 mJ on pure silica, whereas Ge-doped nanoparticles were obtained using 33 and 165 mJ per pulse on germanosilicate glass. The difference in the required energy is attributed to the Ge doping, which modifies the optical properties of the silica by facilitating energy absorption processes such as multiphoton absorption or by introducing absorbing point defects. Defect generation in bulk pure silica before nanoparticle production starts is also suggested by our results. Regarding the Ge-doped samples, scanning electron microscopy (SEM) and cathodoluminescence (CL) investigations revealed a good correspondence between the morphology of the generated particles and their emission signal due to the germanium lone pair center (GLPC), regardless of the energy per pulse used for their production. This suggests a reasonable homogeneity of the emission features of the samples. Similarly, energy dispersive X-ray spectroscopy (EDX) data showed that the O, Ge and Si signals qualitatively correspond to the particle morphology, suggesting a generally uniform chemical composition of the Ge-doped samples. No significant CL signal could be detected in pure silica nanoparticles, evidencing the positive impact of Ge for the development of intrinsically emitting nanoparticles. Transmission electron microscope (TEM) data suggested that the Ge-doped silica nanoparticles are amorphous. SEM and TEM data evidenced that the produced nanoparticles tend to be slightly more spherical in shape for a higher energy per pulse. Scanning transmission electron microscope (STEM) data have shown that, regardless of size and applied energy per pulse, in each nanoparticle, some inhomogeneity is present in the form of brighter (i.e., more dense) features of a few nanometers.","subset":"pubmed_abstract"} +{"meta":{"pmid":19028145,"dup_signals":{"dup_doc_count":32,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2022-33":2,"2022-21":1,"2022-05":1,"2021-49":2,"2021-43":1,"2021-39":2,"2021-31":1,"2021-25":2,"2021-21":2,"2021-17":1,"2021-04":1,"2020-50":1,"2020-40":1,"2019-43":1,"2019-18":2,"2018-47":1,"2018-26":1,"2018-17":1,"2017-47":1,"2017-39":1,"2023-23":1,"2014-10":2,"2013-48":1}}},"text":"Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway.\nCellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 g broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts. Oral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress. This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease. A placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":25494097,"dup_signals":{"dup_doc_count":24,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2020-16":6,"2020-10":4,"2020-05":4,"2019-51":4,"2019-47":1,"2021-04":1,"2024-10":1}}},"text":"Clustering of Physical Inactivity in Leisure, Work, Commuting, and Household Domains: Data From 47,477 Industrial Workers in Brazil.\nPhysical inactivity in each domain (leisure, work, commuting, and household) is not completely independent. This study aimed to describe the clustering of physical inactivity in different domains and its association with sociodemographic factors among Brazilian industrial workers. This was a cross-sectional, population-based study using data from 23 Brazilian states and the Federal District collected via questionnaires between 2006 and 2008. Physical inactivity in each domain was defined as nonparticipation in specific physical activities. Clustering of physical inactivity was identified using the ratio of the observed (O) and expected (E) percentages of each combination. Multinomial logistic regression was used to identify sociodemographic factors with the outcome. Among the 44,477 interviewees, most combinations exceeded expectations, particularly the clustering of physical inactivity in all domains among men (O\/E = 1.37; 95% CI: 1.30; 1.44) and women (O\/E = 1.47; 95% CI: 1.36; 1.60). Physical inactivity in 2 or more domains was observed more frequently in women, older age groups, individuals living without a partner, and those with higher education and income levels. Physical inactivity tends to be observed in clusters regardless of gender. Women and workers with higher income levels were the main factors associated with to be physically inactive in 2 or more domains.","subset":"pubmed_abstract"} +{"meta":{"pmid":8249058,"dup_signals":{"dup_doc_count":92,"dup_dump_count":38,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":3,"2023-23":4,"2023-14":5,"2023-06":1,"2022-49":2,"2022-40":2,"2022-27":2,"2022-21":3,"2022-05":2,"2021-43":4,"2021-39":3,"2021-31":5,"2021-25":1,"2021-21":1,"2021-17":4,"2021-10":2,"2021-04":4,"2020-50":2,"2020-45":1,"2020-40":5,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-05":2,"2017-51":1,"2017-43":3,"2017-34":2,"2024-30":3,"2024-22":4,"2024-18":6,"2024-10":2}}},"text":"Periodicity and space-time clustering of severe childhood malaria on the coast of Kenya.\nTraditionally malaria epidemiology has focused on factors such as parasite rates and vector dynamics without specific reference to disease. There are limited comprehensive data on malaria as a life-threatening event in African children. We have identified, through hospital surveillance, 581 episodes of severe malaria in residents of a defined area on the Kenya coast over a period of 3 years. This represents an absolute minimum risk of developing severe malaria by the fifth birthday of 1 in 15. The presentation of severe malaria showed marked seasonality, but the timing and magnitude of these fluctuations varied considerably between years. A satellite navigational system was used to define the exact location of the home of each severe malaria case. Space-time clustering of severe malaria was evident in this community. Seasonal peaks in incidence of severe malaria may comprise discrete mini-epidemics. In contrast, parasite rates in the community varied little during the course of the surveillance. The monitoring of disease, as opposed to parasitization, in children may result in more effective targeting of intervention resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":16504726,"dup_signals":{"dup_doc_count":11}},"text":"Application of sulforaphane: histopathological study of intraportal transplanted pancreatic islets into livers of diabetic rats.\nIslet cell transplantation is a promising method to restore insulin independence to patients with type 1 diabetes mellitus. A main problem in clinical islet transplantation is the fact that only a small percentage of allogeneic islet-transplanted type 1 diabetic patients can completely omit insulin injections after transplantation. One reason for the impaired survival of islet grafts is aberration of the function of islets due to toxic agents, including oxygen radicals and nitric oxide, which arise during warm or cold ischemic time. Therefore, in clinical islet transplantation, islets have been preserved with a mixture of antioxidants to reduce free radical-mediated damage of transplanted beta cells. Our aim was to examine hepatic tissue after metabolic normalization following intraportal islet transplantation after application of sulforaphane. Islets were isolated from pancreata of WAG rats. Sulforaphane (24 mg\/kg) was administered 24 hours before isolated islets were transplanted into the liver through the portal vein (1200 +\/- 100 per rat). At 9 months after transplantation the animals were killed and liver tissue removed for morphological examination. This report indicated that the intrahepatic portal vein site was indeed an excellent locus for implantation of free pancreatic islets. The islet grafts developed rich vascularization derived from both venous and arterial sources. The islet cells maintained their structural and functional integrity after implantation. Our results showed that sulforaphane improved islet function in vivo, indicating that combination of a free radical scavenger and an antioxidant (sulforaphane) may be used to increase the effectiveness of islet transplantation.","subset":"pubmed_abstract"} +{"meta":{"pmid":24872594,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":15}}},"text":"Deciphering thylakoid sub-compartments using a mass spectrometry-based approach.\nPhotosynthesis has shaped atmospheric and ocean chemistries and probably changed the climate as well, as oxygen is released from water as part of the photosynthetic process. In photosynthetic eukaryotes, this process occurs in the chloroplast, an organelle containing the most abundant biological membrane, the thylakoids. The thylakoids of plants and some green algae are structurally inhomogeneous, consisting of two main domains: the grana, which are piles of membranes gathered by stacking forces, and the stroma-lamellae, which are unstacked thylakoids connecting the grana. The major photosynthetic complexes are unevenly distributed within these compartments because of steric and electrostatic constraints. Although proteomic analysis of thylakoids has been instrumental to define its protein components, no extensive proteomic study of subthylakoid localization of proteins in the BBY (grana) and the stroma-lamellae fractions has been achieved so far. To fill this gap, we performed a complete survey of the protein composition of these thylakoid subcompartments using thylakoid membrane fractionations. We employed semiquantitative proteomics coupled with a data analysis pipeline and manual annotation to differentiate genuine BBY and stroma-lamellae proteins from possible contaminants. About 300 thylakoid (or potentially thylakoid) proteins were shown to be enriched in either the BBY or the stroma-lamellae fractions. Overall, present findings corroborate previous observations obtained for photosynthetic proteins that used nonproteomic approaches. The originality of the present proteomic relies in the identification of photosynthetic proteins whose differential distribution in the thylakoid subcompartments might explain already observed phenomenon such as LHCII docking. Besides, from the present localization results we can suggest new molecular actors for photosynthesis-linked activities. For instance, most PsbP-like subunits being differently localized in stroma-lamellae, these proteins could be linked to the PSI-NDH complex in the context of cyclic electron flow around PSI. In addition, we could identify about a hundred new likely minor thylakoid (or chloroplast) proteins, some of them being potential regulators of the chloroplast physiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":32375972,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":8}}},"text":"Genomic analysis of 40 prophages located in the genomes of 16 carbapenemase-producing clinical strains of Klebsiella pneumoniae.\nKlebsiella pneumoniae is the clinically most important species within the genus Klebsiella and, as a result of the continuous emergence of multi-drug resistant (MDR) strains, the cause of severe nosocomial infections. The decline in the effectiveness of antibiotic treatments for infections caused by MDR bacteria has generated particular interest in the study of bacteriophages. In this study, we characterized a total of 40 temperate bacteriophages (prophages) with a genome range of 11.454-84.199 kb, predicted from 16 carbapenemase-producing clinical strains of K. pneumoniae belonging to different sequence types, previously identified by multilocus sequence typing. These prophages were grouped into the three families in the order Caudovirales (27 prophages belonging to the family Myoviridae, 10 prophages belonging to the family Siphoviridae and 3 prophages belonging to the family Podoviridae). Genomic comparison of the 40 prophage genomes led to the identification of four prophages isolated from different strains and of genome sizes of around 33.3, 36.1, 39.6 and 42.6 kb. These prophages showed sequence similarities (query cover >90 %, identity >99.9 %) with international Microbe Versus Phage (MVP) (http:\/\/mvp.medgenius.info\/home) clusters 4762, 4901, 3499 and 4280, respectively. Phylogenetic analysis revealed the evolutionary proximity among the members of the four groups of the most frequently identified prophages in the bacterial genomes studied (33.3, 36.1, 39.6 and 42.6 kb), with bootstrap values of 100 %. This allowed the prophages to be classified into three clusters: A, B and C. Interestingly, these temperate bacteriophages did not infect the highest number of strains as indicated by a host-range assay, these results could be explained by the development of superinfection exclusion mechanisms. In addition, bioinformatic analysis of the 40 identified prophages revealed the presence of 2363 proteins. In total, 59.7 % of the proteins identified had a predicted function, mainly involving viral structure, transcription, replication and regulation (lysogenic\/lysis). Interestingly, some proteins had putative functions associated with bacterial virulence (toxin expression and efflux pump regulators), phage defence profiles such as toxin-antitoxin modules, an anti-CRISPR\/Cas9 protein, TerB protein (from terZABCDE operon) and methyltransferase proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":17998620,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Advantages of multiple algorithm support in treatment planning system for external beam dose calculations.\nThe complexity of interactions and the nature of the approximations made in the formulation of the algorithm require that the user be familiar with the limitations of various models. As computer power keeps growing, calculation algorithms are tending more towards physically based models. The nature and quantity of the data required varies according to the model which may be either measurement based models or physical based models. Multiple dose calculation algorithm support found in XiO Treatment Planning System can be used to advantage when choice is to be made between speed and accuracy. Thus XiO allows end users generate plans accurately and quickly to optimize the delivery of radiation therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":17652054,"dup_signals":{"dup_doc_count":12}},"text":"Molecular biology of rhabdomyosarcoma.\nRhabdomyosarcoma (RMS) is one of the most common extracranial solid tumours in children. Embryonal and alveolar subtypes of RMS present completely different genetic abnormalities. Embryonal RMS (eRMS) is characterised by loss of heterozygosity on the short arm of chromosome 11 (11p15.5), suggesting inactivation of a tumour-suppressor gene. In contrast, the majority (80-85%) of the alveolar RMS (aRMS) have the reciprocal chromosomal translocations 't(2;13)(q35;q14) or t(1;13)(p36;q14). t(2;13) appears in approximately 70% of patients with the alveolar subtype. The molecular counterpart of this translocation consists of the generation of a chimeric fusion gene involving the \/PAX3\/ gene located in chromosome 2 and a member of the fork-head family, \/FOXO1\/ (formerly \/FKHR\/), located in chromosome 13. A less frequent variant translocation t(1;13) involves another PAX family gene, \/PAX7\/, located in chromosome 1 and \/FOXO1\/ and is present in 10-15% of cases of the alveolar subtype in RMS. Recently, many studies focused on cancer have demonstrated the great potential of the genomic approach based on tumour expression profiles. These technologies permit the identification of new regulatory pathways. Molecular detection of minimal disease by a sensitive method could contribute to better treatment stratification in these patients. In RMS, the advances in the knowledge of the biological characteristics of the tumour are slowly translated into the clinical management of children with this tumour.","subset":"pubmed_abstract"} +{"meta":{"pmid":29258755,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-21":1,"2021-17":1,"2020-34":1,"2020-05":1,"2019-43":1,"2019-26":1,"2022-49":1}}},"text":"Effects of dietary dandelion extract on intestinal morphology, antioxidant status, immune function and physical barrier function of juvenile golden pompano Trachinotus ovatus.\nIntestinal morphology, antioxidant status, immune function and tight junction proteins mRNA expression were examined in golden pompano (Trachinotus ovatus) that fed respectively six diets containing dandelion extracts (DE) at 0, 0.5, 1, 2, 4 and 10 g kg-1 after 8 weeks feeding. The study indicated that dietary DE significantly improved intestinal antioxidant abilities by increasing SOD, CAT, T-AOC activities and up-regulating intestinal cat, gpx mRNA levels, but by decreasing MDA content and down-regulating intestinal keap1 mRNA levels in golden pompano. Meanwhile, dietary DE improved intestinal morphology, suggesting that enhances intestinal digestion and absorption, by increasing muscle thickness, villus length, villus width and villus number in the foregut and hindgut; as well as villus number, villus width and muscle thickness in the midgut (P < .05). Dietary DE enhanced intestinal barrier function by increasing intestinal zo-1 and occludin mRNA levels, but by decreasing the mRNA levels of claudin-12 and claudin-15. Furthermore, dietary DE improved intestinal immunity via increasing goblet cells numbers and regulating expression of immune-related genes. In conclusion, dietary DE supplementation promoted intestine health by improving intestine morphology, immunity, antioxidant abilities and intestinal barrier in golden pompano.","subset":"pubmed_abstract"} +{"meta":{"pmid":32779779,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"A new method for protein characterization and classification using geometrical features for 3D face analysis: An example of tubulin structures.\nThis article reports on the results of research aimed to translate biometric 3D face recognition concepts and algorithms into the field of protein biophysics in order to precisely and rapidly classify morphological features of protein surfaces. Both human faces and protein surfaces are free-forms and some descriptors used in differential geometry can be used to describe them applying the principles of feature extraction developed for computer vision and pattern recognition. The first part of this study focused on building the protein dataset using a simulation tool and performing feature extraction using novel geometrical descriptors. The second part tested the method on two examples, first involved a classification of tubulin isotypes and the second compared tubulin with the FtsZ protein, which is its bacterial analog. An additional test involved several unrelated proteins. Different classification methodologies have been used: a classic approach with a support vector machine (SVM) classifier and an unsupervised learning with a k-means approach. The best result was obtained with SVM and the radial basis function kernel. The results are significant and competitive with the state-of-the-art protein classification methods. This leads to a new methodological direction in protein structure analysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":11724897,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":10}}},"text":"In vivo transduction of central neurons using recombinant Sindbis virus: Golgi-like labeling of dendrites and axons with membrane-targeted fluorescent proteins.\nA new recombinant virus which labeled the infected neurons in a Golgi stain-like fashion was developed. The virus was based on a replication-defective Sindbis virus and was designed to express green fluorescent protein with a palmitoylation signal (palGFP). When the virus was injected into the ventrobasal thalamic nuclei, many neurons were visualized with the fluorescence of palGFP in the injection site. The labeling was enhanced by immunocytochemical staining with an antibody to green fluorescent protein to show the entire configuration of the dendrites. Thalamocortical axons of the infected neurons were also intensely immunostained in the somatosensory cortex. In contrast to palGFP, when DsRed with the same palmitoylation signal (palDsRed) was introduced into neurons with the Sindbis virus, palDsRed neither visualized the infected neurons in a Golgi stain-like manner nor stained projecting axons in the cerebral cortex. The palDsRed appeared to be aggregated or accumulated in some organelles in the infected neurons. Anterograde labeling with palGFP Sindbis virus was very intense, not only in thalamocortical neurons but also in callosal, striatonigral, and nigrostriatal neurons. Occasionally there were retrogradely labeled neurons that showed Golgi stain-like images. These results indicate that palGFP Sindbis virus can be used as an excellent anterograde tracer in the central nervous system.","subset":"pubmed_abstract"} +{"meta":{"pmid":24727072,"dup_signals":{"dup_doc_count":13,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2022-21":1,"2021-43":1,"2020-34":1,"2020-24":1,"2019-51":1,"2019-43":2,"2019-39":1,"2019-35":1,"2019-30":2,"2023-14":1}}},"text":"Hypertensive disorders of pregnancy and gestational diabetes mellitus among French Caribbean women chronically exposed to chlordecone.\nFew studies have explored the consequences of environmental exposure to organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE) and gestational diabetes mellitus (GDM). Chlordecone is a persistent organochlorine pesticide that was used intensively, and almost exclusively, in the French West Indies until 1993. We investigated the impact of prenatal exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779 pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying maternal plasma and information about pregnancy complications was obtained from midwives, pediatricians and hospital medical records after delivery. The risks of GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic regression including potential confounders. Levels of chlordecone plasma concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically significant decrease in the risk of GH. A log10 increase in chlordecone concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI: 0.2, 0.6). No significant associations were observed between the chlordecone exposure and the risk of PE or GDM. This study suggests an inverse association between chlordecone exposure during pregnancy and GH. Further studies are required to determine the underlying mechanism, or the potential unknown confounding factors, resulting in this association.","subset":"pubmed_abstract"} +{"meta":{"pmid":22275514,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2014-10":1,"unknown":13}}},"text":"Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells.\nOxidative protein folding in the endoplasmic reticulum (ER) requires strict regulation of redox homeostasis. Disruption of the lumenal redox balance induces an integrated ER stress response that is associated with reduced protein translation, increased chaperone activity, and ultimately cell death. Imexon is a small-molecule chemotherapeutic agent that has been shown to bind glutathione (GSH) and induce oxidative stress in tumor cells; however, the mechanism of cytotoxicity is not well understood. In this report, we investigate the effects of imexon on the integrated ER stress response in pancreatic carcinoma cells. Acute exposure to imexon induces an ER stress response characterized by accumulation of the oxidized form of the oxidoreductase Ero1\u03b1, phosphorylation of eIF2\u03b1, and inhibition of protein synthesis. An RNA interference chemosensitization screen identified the eukaryotic translation initiation factor eIF2B5 as a target that enhanced imexon-induced growth inhibition of MiaPaCa-2 pancreatic cancer cells, but did not significantly augment the effects of imexon on protein synthesis. Concurrent reduction of intracellular thiols with N-acetyl cysteine reversed imexon activity, however cotreatment with superoxide scavengers had no effect, suggesting thiol binding may be a primary component of the oxidative effects of imexon. Moreover, the data suggest that disruption of the redox balance in the ER is a potential therapeutic target.","subset":"pubmed_abstract"} +{"meta":{"pmid":22341373,"dup_signals":{"dup_doc_count":34,"dup_dump_count":28,"dup_details":{"curated_sources":1,"2022-33":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":2,"2020-45":1,"2020-34":2,"2020-29":2,"2020-16":2,"2020-05":1,"2019-47":1,"2019-35":1,"2019-26":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2022-49":1}}},"text":"Viability and function of the cryopreserved whole rat ovary: comparison between slow-freezing and vitrification.\nTo investigate four different protocols for cryopreservation of the whole rat ovary with intact vasculature to evaluate whether differences exist in post-thawing viability of the ovary after either vitrification or slow freezing. Experimental study. Obstetrics and gynecology department. Immature Sprague-Dawley female rats. Ovaries were isolated with the vascular tree intact up to the bifurcation of the abdominal aorta and were subsequently cannulated. The ovaries were flushed with increasing concentrations of the cryoprotectant dimethyl sulfoxide (DMSO) to either 1.5 or 7 M. The ovaries underwent cryopreservation by vitrification or passive slow freezing. After thawing, the ovaries were subjected to neutral red viability staining to assess the density of viable small follicles and for long-term (48 hours) incubation evaluation of steroid secretion, histology, and apoptosis assay. The follicular viability was decreased in both vitrification groups and in the slow-freezing group with the high concentration of DMSO, as compared with fresh controls. Estradiol levels in the incubation medium followed the same pattern. Light microscopy revealed well-preserved morphology in all groups after 48 hours' incubation. Apoptosis was increased in both vitrified and cryopreserved ovaries. We have developed a new method that can be used in basic studies to improve cryopreservation protocols. Our initial findings suggest that a moderate concentration of the cryoprotectant DMSO is superior to a high DMSO concentration for both vitrification and slow freezing.","subset":"pubmed_abstract"} +{"meta":{"pmid":28334943,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Effects of prefrontal cortex damage on emotion understanding: EEG and behavioural evidence.\nHumans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others' actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others' actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation-execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others' emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others' emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor cortex.","subset":"pubmed_abstract"} +{"meta":{"pmid":27780243,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Local Electrical Dyssynchrony during Atrial Fibrillation: Theoretical Considerations and Initial Catheter Ablation Results.\nElectrogram-based identification of the regions maintaining persistent Atrial Fibrillation (AF) is a subject of ongoing debate. Here, we explore the concept of local electrical dyssynchrony to identify AF drivers. Local electrical dyssynchrony was calculated using mean phase coherence. High-density epicardial mapping along with mathematical model were used to explore the link between local dyssynchrony and properties of wave conduction. High-density mapping showed a positive correlation between the dyssynchrony and number of fibrillatory waves (R2 = 0.68, p<0.001). In the mathematical model, virtual ablation at high dyssynchrony regions resulted in conduction regularization. The clinical study consisted of eighteen patients undergoing catheter ablation of persistent AF. High-density maps of left atrial (LA) were constructed using a circular mapping catheter. After pulmonary vein isolation, regions with the top 10% of the highest dyssynchrony in LA were targeted during ablation and followed with ablation of complex atrial electrograms. Catheter ablation resulted in termination during ablation at high dyssynchrony regions in 7 (41%) patients. In another 4 (24%) patients, transient organization was observed. In 6 (35%) there was no clear effect. Long-term follow-up showed 65% AF freedom at 1 year and 22% at 2 years. Local electrical dyssynchrony provides a reasonable estimator of regional AF complexity defined as the number of fibrillatory waves. Additionally, it points to regions of dynamical instability related with action potential alternans. However, despite those characteristics, its utility in guiding catheter ablation of AF is limited suggesting other factors are responsible for AF persistence.","subset":"pubmed_abstract"} +{"meta":{"pmid":22747654,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-48":3,"unknown":8}}},"text":"Variation of chemosensory receptor content of Campylobacter jejuni strains and modulation of receptor gene expression under different in vivo and in vitro growth conditions.\nChemotaxis is crucial for the colonisation\/infection of hosts with Campylobacter jejuni. Central to chemotaxis are the group A chemotaxis genes that are responsible for sensing the external environment. The distribution of group A chemoreceptor genes, as found in the C. jejuni sequenced strains, tlp1-4, 7, 10 and 11 were determined in 33 clinical human and avian isolates. Group A tlp gene content varied among the strains with genes encoding tlp1 (aspartate receptor, ccaA) and tlp7 present in all strains tested, where as tlp11 was present in only one of our international collection clinical isolates, C. jejuni 520, but was more prevalent (9\/13) in the freshly isolated clinical stains from patients who required hospitalisation due to C. jejuni infection (GCH1-17). Relative expression levels of the group A tlp genes were also determined in C. jejuni reference strains NCTC 11168-GS, 11168-O and 81116 using cells grown in vitro at 37\u00b0C, 42\u00b0C and maintained at room temperature and with cells isolated directly from murine and avian hosts by immune magnetic separation without subsequent culture. Gene expression of tlp genes was varied based on strain, growth conditions and in vivo isolation source. Tlp1, although the most conserved, showed the lowest and most varied mRNA expression and protein production under laboratory conditions. Tlp7 was highly expressed at most conditions tested, and gene expression was not influenced by the tlp7 gene encoding a full length protein or one expressed as separate periplasmic and cytoplasmic domains. We have shown that chemosensory receptor set variation exists among C. jejuni strains, but is not dependent on the isolation source.","subset":"pubmed_abstract"} +{"meta":{"pmid":32601174,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease.\nPathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) are the predominant genetic cause of Parkinson's disease (PD). They increase its activity, resulting in augmented Rab10-Thr73 phosphorylation and conversely, LRRK2 inhibition decreases pRab10 levels. Currently, there is no assay to quantify pRab10 levels for drug target engagement or patient stratification. To meet this challenge, we developed an high accuracy and sensitivity targeted mass spectrometry (MS)-based assay for determining Rab10-Thr73 phosphorylation stoichiometry in human samples. It uses synthetic stable isotope-labeled (SIL) analogues for both phosphorylated and nonphosphorylated tryptic peptides surrounding Rab10-Thr73 to directly derive the percentage of Rab10 phosphorylation from attomole amounts of the endogenous phosphopeptide. The SIL and the endogenous phosphopeptides are separately admitted into an Orbitrap analyzer with the appropriate injection times. We test the reproducibility of our assay by determining Rab10-Thr73 phosphorylation stoichiometry in neutrophils of LRRK2 mutation carriers before and after LRRK2 inhibition. Compared with healthy controls, the PD predisposing mutation carriers LRRK2 G2019S and VPS35 D620N display 1.9-fold and 3.7-fold increased pRab10 levels, respectively. Our generic MS-based assay further establishes the relevance of pRab10 as a prognostic PD marker and is a powerful tool for determining LRRK2 inhibitor efficacy and for stratifying PD patients for LRRK2 inhibitor treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":27510041,"dup_signals":{"dup_doc_count":20,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2021-31":2,"2019-22":3,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-30":2,"2017-26":1,"2017-22":1,"2017-17":1}}},"text":"Recent advances in the biomimicry of structural colours.\nNature has mastered the construction of nanostructures with well-defined macroscopic effects and purposes. Structural colouration is a visible consequence of the particular patterning of a reflecting surface with regular structures at submicron length scales. Structural colours usually appear bright, shiny, iridescent or with a metallic look, as a result of physical processes such as diffraction, interference, or scattering with a typically small dissipative loss. These features have recently attracted much research effort in materials science, chemistry, engineering and physics, in order to understand and produce structural colours. In these early stages of photonics, researchers facing an infinite array of possible colour-producing structures are heavily inspired by the elaborate architectures they find in nature. We review here the recent technological strategies employed to artificially mimic the structural colours found in nature, as well as some of their current and potential applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":28265635,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Cellular structures arising from viscoelastic phase separation in binary mixtures of thermotropic liquid crystals.\nViscoelastic effects are known to influence pattern formation during phase separation in dynamically asymmetric mixtures. Evidence is shown for such an effect in some binary mixtures composed of liquid crystals made of rod-like (R) and bent-core (BC) molecules. The difference in dynamics at phase separation manifests itself in the form of cellular structures (CSs). This is mainly driven by dissimilarities in flow and rotational viscosities of the two types of molecules which differ in size and shape. The heterogeneous structure has been characterized by optical and confocal microscopy along with X-ray diffraction studies and found to be composed of coexisting liquid crystalline phases. The striking resemblance to CSs of biological systems further enriched by topological defects is unique to this system. The morphology and stability of the CSs are dictated by the smectic ordering influenced by the relative concentration and mutual orientation of the R and BC molecules. This type of phase separation process can also be utilized to form functional ordered assemblies of nanoparticles embedded in a liquid crystal matrix.","subset":"pubmed_abstract"} +{"meta":{"pmid":32860230,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Clinical response to antibiotic regimens in lower limb cellulitis: a systematic review.\nThere is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen. Many patients with cellulitis fail to respond to first-line antibiotics. This can negatively affect patient care and result in unnecessary hospital admissions. The aim of this systematic review was to determine the clinical response and safety of antibiotic regimens for the management of LLC. A systematic review for randomized controlled trials (RCTs) was conducted using OVID MEDLINE, Ovid Embase and Cochrane Central Register of Controlled Trials in January 2019. Outcomes of interest included the clinical response to antibiotic regimens (type, dose, route, duration) and the safety of antibiotics in LLC. Trial quality was identified using the Cochrane Risk of Bias tool. Four RCTs were included. All included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration or dose. LLC may be overtreated and shorter courses of oral antibiotics, possibly with lower doses, may be more suitable. There is a lack of published data on the clinical response and safety of antibiotics in LLC. Three studies were high risk for bias overall. Further high-quality studies may help determine whether less intensive antibiotic regimens can effectively treat LLC.","subset":"pubmed_abstract"} +{"meta":{"pmid":22726629,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":2,"2024-10":1,"unknown":7}}},"text":"Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults.\nThis study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. A baseline cohort of 115,746 participants without a history of thyroid disease, \u226520 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU\/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU\/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death.","subset":"pubmed_abstract"} +{"meta":{"pmid":28754506,"dup_signals":{"dup_doc_count":28,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":2,"2021-39":2,"2021-31":1,"2021-17":1,"2020-50":1,"2020-24":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-26":1,"2018-17":1,"2018-13":1,"2017-51":2,"2017-43":2,"2017-34":2,"2023-40":1,"2024-26":1}}},"text":"The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.\nThe dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar - but not cerebral - coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.","subset":"pubmed_abstract"} +{"meta":{"pmid":19299614,"dup_signals":{"dup_doc_count":35,"dup_dump_count":22,"dup_details":{"curated_sources":4,"2020-45":1,"2020-10":1,"2019-35":1,"2019-09":1,"2018-51":1,"2018-43":2,"2018-34":1,"2018-30":1,"2018-13":1,"2017-39":1,"2017-34":1,"2017-22":1,"2017-09":3,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":2,"2016-07":2,"2021-31":1,"2013-20":1}}},"text":"Alfv\u00e9n waves in the lower solar atmosphere.\nThe flow of energy through the solar atmosphere and the heating of the Sun's outer regions are still not understood. Here, we report the detection of oscillatory phenomena associated with a large bright-point group that is 430,000 square kilometers in area and located near the solar disk center. Wavelet analysis reveals full-width half-maximum oscillations with periodicities ranging from 126 to 700 seconds originating above the bright point and significance levels exceeding 99%. These oscillations, 2.6 kilometers per second in amplitude, are coupled with chromospheric line-of-sight Doppler velocities with an average blue shift of 23 kilometers per second. A lack of cospatial intensity oscillations and transversal displacements rules out the presence of magneto-acoustic wave modes. The oscillations are a signature of Alfv\u00e9n waves produced by a torsional twist of +\/-22 degrees. A phase shift of 180 degrees across the diameter of the bright point suggests that these torsional Alfv\u00e9n oscillations are induced globally throughout the entire brightening. The energy flux associated with this wave mode is sufficient to heat the solar corona.","subset":"pubmed_abstract"} +{"meta":{"pmid":8324431,"dup_signals":{"dup_doc_count":25,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":4,"2024-22":1,"2024-10":1,"unknown":17}}},"text":"Factors associated with suicide after parasuicide in young people.\nTo determine factors associated with completed suicide in young parasuicide patients. Case-control study. Regional poisoning treatment centre in a teaching general hospital. Patients who, between 1968 and 1985 when aged 15-24 years, were admitted to the regional poisoning treatment centre because of deliberate self poisoning or self injury. Cases (n = 62) consisted of those who by the end of 1985 had died locally from either suicide (n = 41) or possible suicide (n = 21). Controls (n = 124) were patients who were known not to have died locally during the study period. Two controls were selected for each case, matched by sex, age (within two years), and length of follow up. Possible predictors of completed suicide. Univariate analysis (conditional logistic regression) showed that risk of death due to suicide and possible suicide was associated with six factors: social class V (odds ratio 2.7, 95% confidence interval 1.1 to 6.7), unemployment (2.8, 1.4 to 5.8), previous inpatient psychiatric treatment (4.9, 2.2 to 10.9), substance misuse (3.3, 1.6 to 6.8), personality disorder (2.1, 1.03 to 4.4), and previous attempted suicide (2.3, 1.2 to 4.4). Multivariate analysis identified two factors as significantly contributing to the model that best discriminated between the cases and controls: substance misuse (alcohol or drugs, or both) (adjusted odds ratio 3.9) and previous inpatient psychiatric treatment (3.7). These factors seemed to be associated with suicide after attempted suicide in both the short term (less than 12 months) and the long term (one year or more) and were also identified when the analysis was restricted to subjects who definitely died by suicide and their controls. Suicide after parasuicide in young people is associated with substance misuse. This suggests that prevention of suicide in young people who attempt suicide might be improved by close liaison between general hospital services for patients who have attempted suicide and services for young substance misusers and by measures aimed at preventing substance misuse in young people.","subset":"pubmed_abstract"} +{"meta":{"pmid":22465817,"dup_signals":{"dup_doc_count":12}},"text":"Ivermectin reduces alcohol intake and preference in mice.\nThe high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL\/6 mice. Overall, IVM (1.25-10 mg\/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (C(max)) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs.","subset":"pubmed_abstract"} +{"meta":{"pmid":9721103,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate.\nA large protein complex mediates the phosphorylation of the inhibitor of kappaB (IkappaB), which results in the activation of nuclear factor kappaB (NF-kappaB). Two subunits of this complex, IkappaB kinase alpha (IKKalpha) and IkappaB kinase beta (IKKbeta), are required for NF-kappaB activation. Purified recombinant IKKalpha and IKKbeta expressed in insect cells were used to demonstrate that each protein can directly phosphorylate IkappaB proteins. IKKalpha and IKKbeta were found to form both homodimers and heterodimers. Both IKKalpha and IKKbeta phosphorylated IkappaB bound to NF-kappaB more efficiently than they phosphorylated free IkappaB. This result explains how free IkappaB can accumulate in cells in which IKK is still active and thus can contribute to the termination of NF-kappaB activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28339184,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":19}}},"text":"MXene Ti3C2: An Effective 2D Light-to-Heat Conversion Material.\nMXene, a new series of 2D material, has been steadily advancing its applications to a variety of fields, such as catalysis, supercapacitor, molecular separation, electromagnetic wave interference shielding. This work reports a carefully designed aqueous droplet light heating system along with a thorough mathematical procedure, which combined leads to a precise determination of internal light-to-heat conversion efficiency of a variety of nanomaterials. The internal light-to-heat conversion efficiency of MXene, more specifically Ti3C2, was measured to be 100%, indicating a perfect energy conversion. Furthermore, a self-floating MXene thin membrane was prepared by simple vacuum filtration and the membrane, in the presence of a rationally chosen heat barrier, produced a light-to-water-evaporation efficiency of 84% under one sun irradiation, which is among the state of art energy efficiency for similar photothermal evaporation system. The outstanding internal light-to-heat conversion efficiency and great light-to-water evaporation efficiency reported in this work suggest that MXene is a very promising light-to-heat conversion material and thus deserves more research attention toward practical applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":25906193,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Oxidative stress in aging human skin.\nOxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, \u03b1-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.","subset":"pubmed_abstract"} +{"meta":{"pmid":15872087,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Structural and functional dissection of the Abp1 ADFH actin-binding domain reveals versatile in vivo adapter functions.\nAbp1 is a multidomain protein that regulates the Arp2\/3 complex and links proteins involved in endocytosis to the actin cytoskeleton. All of the proposed cellular functions of Abp1 involve actin filament binding, yet the actin binding site(s) on Abp1 have not been identified, nor has the importance of actin binding for Abp1 localization and function in vivo been tested. Here, we report the crystal structure of the Saccharomyces cerevisiae Abp1 actin-binding actin depolymerizing factor homology (ADFH) domain and dissect its activities by mutagenesis. Abp1-ADFH domain and ADF\/cofilin structures are similar, and they use conserved surfaces to bind actin; however, there are also key differences that help explain their differential effects on actin dynamics. Using point mutations, we demonstrate that actin binding is required for localization of Abp1 in vivo, the lethality caused by Abp1 overexpression, and the ability of Abp1 to activate Arp2\/3 complex. Furthermore, we genetically uncouple ABP1 functions that overlap with SAC6, SLA1, and SLA2, showing they require distinct combinations of activities and interactions. Together, our data provide the first structural and functional view of the Abp1-actin interaction and show that Abp1 has distinct cellular roles as an adapter, linking different sets of ligands for each function.","subset":"pubmed_abstract"} +{"meta":{"pmid":35735439,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Sunitinib-Induced Elevation of Mean Corpuscular Volume (MCV)-Exploring Its Possible Clinical Relevance in Cancer Patients.\nSunitinib is a broad-spectrum multitargeted tyrosine kinase inhibitor mainly used as second-line therapy for non-resectable gastrointestinal stromal or first-line treatment option of metastatic renal cell carcinoma (mRCC), and as an \"off-label\" option in pediatric oncology. It has been previously reported that sunitinib elevates the mean corpuscular volume of erythrocytes (MCV) in treated subjects. The aim of this study was to assess time-dependent changes of this effect and evaluate its possible clinical relevance. In this study, 179 adult and 21 pediatric patients with solid tumors treated with sunitinib were retrospectively analyzed. The laboratory and treatment-related data were collected for each treatment period. The regression model with a broken-line relationship was used to fit time dependence of the MCV. In the adult group, the MCV was increasing during the first 21.6 weeks (median) of treatment in a median level of 99.8 fL, where it stabilized. MCV increase was faster in the patients who suffered from treatment-related adverse events (21.3 vs. 24.6 weeks, p = 0.010). In the pediatric cohort, the MCV dynamics were similar to adults. In conclusion, MCV changes during sunitinib treatment in pediatric and adult patients may be of clinical utility in monitoring sunitinib treatment course.","subset":"pubmed_abstract"} +{"meta":{"pmid":12091403,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Associations of human crystalline lens retrodots and waterclefts with visual impairment: an observational study.\nTo investigate the relationships between visual acuity, contrast sensitivity, and 11 clinicopathologic classes of opacity in the human crystalline lens. The Somerset and Avon Eye Study is an observational population study of age-related sight-threatening eye disease, based in Bristol, UK. After excluding eyes with other visually relevant disease, data from 902 individuals aged 55 years or older were analyzed. The associations of lens features (posterior subcapsular cataract, nuclear color, nuclear white scatter, cortical spokes, anterior subcapsular cataract, vacuoles, waterclefts, coronary flakes, focal dots, retrodots, fiber folds), with refracted log minimum angle of resolution (MAR) distance acuity and Pelli-Robson contrast sensitivity, were investigated. Multivariable linear regression models using data from both eyes and taking account of the intraclass correlation between eyes were used for analysis, with the lens features and age included as potential explanatory variables. As anticipated from earlier studies, posterior subcapsular, nuclear, and cortical cataracts were associated with visual impairment. In addition, retrodots were strongly and independently associated in the multivariable models with both impaired visual acuity (P < 0.001) and contrast sensitivity (P < 0.001). Waterclefts were strongly associated with impaired visual acuity (P < 0.001). Retrodots and waterclefts are associated with visual impairment. A causal relationship between these lens features and retinal image degradation is plausible.","subset":"pubmed_abstract"} +{"meta":{"pmid":18264702,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2021-25":1,"2020-10":1,"2019-43":1,"2019-13":1,"2019-09":1,"2018-39":1,"2018-17":1,"2017-47":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2022-33":1,"2017-13":1,"2024-10":1}}},"text":"Catalytic diesel particulate filters reduce the in vitro estrogenic activity of diesel exhaust.\nAn in vitro reporter gene assay based on human breast cancer T47D cells (ER-CALUX) was applied to examine the ability of diesel exhaust to induce or inhibit estrogen receptor (ER)-mediated gene expression. Exhaust from a heavy-duty diesel engine was either treated by iron- or copper\/iron-catalyzed diesel particulate filters (DPFs) or studied as unfiltered exhaust. Collected samples included particle-bound and semivolatile constituents of diesel exhaust. Our findings show that all of the samples contained compounds that were able to induce ER-mediated gene expression as well as compounds that suppressed the activity of the endogenous hormone 17beta-estradiol (E2). Estrogenic activity prevailed over antiestrogenic activity. We found an overall ER-mediated activity of 1.63 +\/- 0.31 ng E2 CALUX equivalents (E2-CEQs) per m(3) of unfiltered exhaust. In filtered exhaust, we measured 0.74 +\/- 0.07 (iron-catalyzed DPF) and 0.55 +\/- 0.09 ng E2-CEQ m(-3) (copper\/iron-catalyzed DPF), corresponding to reductions in estrogenic activity of 55 and 66%, respectively. Our study demonstrates that both catalytic DPFs lowered the ER-mediated endocrine-disrupting potential of diesel exhaust.","subset":"pubmed_abstract"} +{"meta":{"pmid":29028899,"dup_signals":{"dup_doc_count":21,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":2,"2024-22":4,"2024-18":2,"2024-10":1,"unknown":7}}},"text":"Phandango: an interactive viewer for bacterial population genomics.\nFully exploiting the wealth of data in current bacterial population genomics datasets requires synthesizing and integrating different types of analysis across millions of base pairs in hundreds or thousands of isolates. Current approaches often use static representations of phylogenetic, epidemiological, statistical and evolutionary analysis results that are difficult to relate to one another. Phandango is an interactive application running in a web browser allowing fast exploration of large-scale population genomics datasets combining the output from multiple genomic analysis methods in an intuitive and interactive manner. Phandango is a web application freely available for use at www.phandango.net and includes a diverse collection of datasets as examples. Source code together with a detailed wiki page is available on GitHub at https:\/\/github.com\/jameshadfield\/phandango.","subset":"pubmed_abstract"} +{"meta":{"pmid":9372930,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":9}}},"text":"Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions.\nSaccharomyces cerevisiae contains eight members of a novel and fungus-specific family of bZIP proteins that is defined by four atypical residues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistance. Although initially described as AP-1 factors, at least four Yap proteins bind most efficiently to TTACTAA, a sequence that differs at position +\/-2 from the optimal AP-1 site (TGACTCA); further, a Yap-like derivative of the AP-1 factor Gcn4 (A239Q S242F) binds efficiently to the Yap recognition sequence. Molecular modeling suggests that the Yap-specific residues make novel contacts and cause physical constraints at the +\/-2 position that may account for the distinct DNA-binding specificities of Yap and AP-1 proteins. To various extents, Yap1, Yap2, Yap3, and Yap5 activate transcription from a promoter containing a Yap recognition site. Yap-dependent transcription is abolished in strains containing high levels of protein kinase A; in contrast, Gcn4 transcriptional activity is stimulated by protein kinase A. Interestingly, Yap1 transcriptional activity is stimulated by hydrogen peroxide, whereas Yap2 activity is stimulated by aminotriazole and cadmium. In addition, unlike other yap mutations tested, yap4 (cin5) mutations affect chromosome stability, and they suppress the cold-sensitive phenotype of yap1 mutant strains. Thus, members of the Yap family carry out overlapping but distinct biological functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":34064413,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Patchy Micelles with a Crystalline Core: Self-Assembly Concepts, Properties, and Applications.\nCrystallization-driven self-assembly (CDSA) of block copolymers bearing one crystallizable block has emerged to be a powerful and highly relevant method for the production of one- and two-dimensional micellar assemblies with controlled length, shape, and corona chemistries. This gives access to a multitude of potential applications, from hierarchical self-assembly to complex superstructures, catalysis, sensing, nanomedicine, nanoelectronics, and surface functionalization. Related to these applications, patchy crystalline-core micelles, with their unique, nanometer-sized, alternating corona segmentation, are highly interesting, as this feature provides striking advantages concerning interfacial activity, functionalization, and confinement effects. Hence, this review aims to provide an overview of the current state of the art with respect to self-assembly concepts, properties, and applications of patchy micelles with crystalline cores formed by CDSA. We have also included a more general discussion on the CDSA process and highlight block-type co-micelles as a special type of patchy micelle, due to similarities of the corona structure if the size of the blocks is well below 100 nm.","subset":"pubmed_abstract"} +{"meta":{"pmid":28574078,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Confining the spin between two metal atoms within the carbon cage: redox-active metal-metal bonds in dimetallofullerenes and their stable cation radicals.\nLanthanide-lanthanide bonds are exceptionally rare, and dimetallofullerenes provide a unique possibility to stabilize and study these unusual bonding patterns. The presence of metal-metal bonds and consequences thereof for the electronic properties of M2@C82 (M = Sc, Er, Lu) are addressed by electrochemistry, electron paramagnetic resonance, SQUID magnetometry and other spectroscopic techniques. A simplified non-chromatographic separation procedure is developed for the isolation of Er2@C82 (Cs(6) and C3v(8) cage isomers) and Sc2@C82 (C3v(8) isomer) from fullerene mixtures. Sulfide clusterfullerenes Er2S@C82 with Cs(6) and C3v(8) fullerene cages are synthesized for the first time. The metal-metal bonding orbital of the spd hybrid character in M2@C82 is shown to be the highest occupied molecular orbital, which undergoes reversible single-electron oxidation with a metal-dependent oxidation potential. Sulfide clusterfullerenes with a fullerene-based HOMO have more positive oxidation potentials. The metal-based oxidation of Sc2@C82-C3v is confirmed by the EPR spectrum of the cation radical [Sc2@C82-C3v]+ generated by chemical oxidation in solution. The spectrum exhibits an exceptionally large a(45Sc) hyperfine coupling constant of 199.2 G, indicating a substantial 4s contribution to the metal-metal bonding orbital. The cationic salt [Er2@C82-C3v]+SbCl6- is prepared, and its magnetization behavior is compared to that of pristine Er2@C82-C3v and Er2S@C82-C3v. The formation of the single-electron Er-Er bond in the cation dramatically changes the coupling between magnetic moments of Er ions.","subset":"pubmed_abstract"} +{"meta":{"pmid":22373422,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":14}}},"text":"Comparative studies on single-layer reduced graphene oxide films obtained by electrochemical reduction and hydrazine vapor reduction.\nThe comparison between two kinds of single-layer reduced graphene oxide (rGO) sheets, obtained by reduction of graphene oxide (GO) with the electrochemical method and hydrazine vapor reduction, referred to as E-rGO and C-rGO, respectively, is systematically studied. Although there is no morphology difference between the E-rGO and C-rGO films adsorbed on solid substrates observed by AFM, the reduction process to obtain the E-rGO and C-rGO films is quite different. In the hydrazine vapor reduction, the nitrogen element is incorporated into the obtained C-rGO film, while no additional element is introduced to the E-rGO film during the electrochemical reduction. Moreover, Raman spectra show that the electrochemical method is more effective than the hydrazine vapor reduction method to reduce the GO films. In addition, E-rGO shows better electrocatalysis towards dopamine than does C-rGO. This study is helpful for researchers to understand these two different reduction methods and choose a suitable one to reduce GO based on their experimental requirements.","subset":"pubmed_abstract"} +{"meta":{"pmid":29136123,"dup_signals":{"dup_doc_count":37,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-23":2,"2023-14":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":2,"2020-34":1,"2020-24":2,"2019-51":1,"2019-43":2,"2019-35":3,"2019-26":2,"2019-18":1,"2019-09":1,"2018-51":2,"2018-43":2,"2018-34":1,"2018-26":1,"2023-40":1,"2024-10":1}}},"text":"Amyloid Network Topology Characterizes the Progression of Alzheimer's Disease During the Predementia Stages.\nThere is increasing evidence showing that the accumulation of the amyloid-\u03b2 (A\u03b2) peptide into extracellular plaques is a central event in Alzheimer's disease (AD). These abnormalities can be detected as lowered levels of A\u03b242 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage A\u03b2 accumulation, defined as abnormal CSF A\u03b242 levels and normal Florbetapir PET (CSF+\/PET-), and more advanced A\u03b2 accumulation, defined as both abnormal CSF A\u03b242 and Florbetapir PET (CSF+\/PET+). The amyloid networks were built using correlations in the mean 18F-florbetapir PET values between 72 brain regions and analyzed using graph theory analyses. Our findings showed an association between early amyloid stages and increased covariance as well as shorter paths between several brain areas that overlapped with the default-mode network (DMN). Moreover, we found that individuals with more advanced amyloid accumulation showed more widespread changes in brain regions both within and outside the DMN. These findings suggest that amyloid network topology could potentially be used to assess disease progression in the predementia stages of AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":2054627,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Calcimycin potentiates responses of rat hippocampal neurons to N-methyl-D-aspartate.\nWe examined the effect of elevating intracellular calcium ([Ca2+]i) on responses to iontophoretically applied N-methyl-D-aspartate (NMDA), and quisqualate in CA1 neurons of the hippocampal slice. Topical application of calcimycin (A23187), a calcium ionophore, potentiated responses to NMDA but not to quisqualate. This potentiation was prevented by loading cells with the calcium chelator, BAPTA, suggesting that the action of calcimycin on NMDA receptors was mediated by an elevation of [Ca2+]i in the recorded cell. The potentiation was also recorded in voltage-clamped and in cesium-loaded cells, suggesting that it was not mediated by non-specific changes in voltage or input resistance of the cell that may have resulted from the rise in [Ca2+]i. We propose that intracellular calcium plays a crucial role in regulating the activity of the NMDA subtype of L-glutamate receptor.","subset":"pubmed_abstract"} +{"meta":{"pmid":7639441,"dup_signals":{"dup_doc_count":13}},"text":"Relapsing invasive group B streptococcal infection in adults.\nTo study recurrent group B streptococcal infection in adults. Patients with more than one reported group B streptococcal infection were identified through active surveillance for this infection. Sterile-site group B streptococcal isolates were evaluated for serotype and molecular subtyping using restriction endonuclease analysis of chromosomal DNA (REAC). All acute-care hospitals in Maryland. Nonpregnant residents of Maryland 18 years of age or older. 22 adults had at least two group B streptococcal episodes that were separated by 2 to 95 weeks (mean, 24 weeks). Of 395 patients with invasive group B streptococcal infection who survived the first episode and were followed for at least 1 year, 17 (4.3% [95% CI, 2.6% to 6.9%]) had more than one episode. Several patients were found to have endocarditis or osteomyelitis during the second episode. Group B streptococcal isolates from both episodes were obtained from 18 of 22 patients. Of the 18 isolate pairs, 13 (72% [CI, 46% to 90%]) had identical REAC patterns; the probability that at least 13 matches would be found by chance alone was less than 0.000001. Among patients with recurrent infection caused by the same strain, the interval between episodes was shorter (mean, 14 weeks) than that among patients with recurrent infection caused by another strain (mean, 43 weeks; P = 0.05). Recurrent group B streptococcal infection is common among adults and in most cases appears to be caused by relapse. The optimal management of adults with a first episode of group B streptococcal infection needs to be further defined to minimize the likelihood of recurrent disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":22568995,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"The effect of noise exposure on the cervical vestibular evoked myogenic potential.\nThe purpose of this study was to investigate the effects of noise exposure on the cervical vestibular evoked myogenic potential (cVEMP) in individuals with asymmetric noise-induced sensorineural hearing loss (NIHL). A cross-sectional observational study was used to compare cVEMP characteristics in 43 individuals with a history of noise exposure greater in one ear (e.g., the left ear of a right-handed rifle shooter) and asymmetric sensorineural hearing loss consistent with the history of noise exposure and in 14 age-matched controls. The characteristics of hearing loss were examined further for the noise-exposed participants with abnormal cVEMPs and the noise-exposed participants with normal cVEMPs. Thirty-three percent of the noise-exposed participants had abnormal cVEMPs, whereas cVEMPs were present and symmetrical in 100% of the age-matched controls, and cVEMP threshold was greater in the noise-exposed group than in the control group. Abnormal cVEMPs occurred most often in the ears with poorer hearing (or greater NIHL), and the noise-exposed participants who had abnormal cVEMPs had poorer high-frequency pure-tone thresholds (greater NIHL) and greater interaural high-frequency pure-tone threshold differences than the noise-exposed participants with normal cVEMPs. These findings are consistent with previous studies that suggest that the sacculocollic pathway may be susceptible to noise-related damage. There is emerging evidence that the severity of NIHL is associated with the presence or absence of cVEMPs.","subset":"pubmed_abstract"} +{"meta":{"pmid":23735162,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2021-10":1,"2019-51":1,"2019-13":1,"2018-39":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-27":1}}},"text":"Can axillary reverse mapping avoid lymphedema in node positive breast cancer patients?\nTracing lymphatic drainage of the ipsilateral arm of node positive breast cancer patients, termed \"axillary reverse mapping\" (ARM), has recently been described in several reports. We analyzed our experience with this new technique in patients scheduled for axillary lymph node dissection (ALND) and evaluated its usefulness for reducing the incidence of lymphedema. Blue dye was injected subcutaneously along the intermuscular groove of the upper inner arm; radioisotope was injected subcutaneously in the interdigital webspace of the hand. All blue and radioactive lymph vessels and lymph nodes were recorded. Only unsuspicious \"ARM lymph nodes\" located in the lateral part of the axillary basin were preserved. All other level I and II axillary lymph nodes were removed. Resected ARM nodes were immediately separated from all other lymph nodes. ARM was performed in 143 patients subsequently undergoing ALND. ARM lymph nodes were successfully identified in 112 cases (78%). In 55 patients at least one ARM lymph node had to be removed. In 14 of these, tumor involvement was confirmed. In 71 patients one or more ARM nodes were preserved. During a median follow-up time of 19 months no axillary recurrence was noted. 35 of 114 evaluated patients developed lymphedema. Preservation of ARM lymph nodes did not significantly decrease the incidence of lymphedema. ARM is feasible for patients with node positive breast cancer. However, we found no evidence that it reduces the incidence of lymphedema.","subset":"pubmed_abstract"} +{"meta":{"pmid":1464761,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":2,"2024-26":1,"unknown":8}}},"text":"Lesions of the perirhinal cortex but not of the frontal, medial prefrontal, visual, or insular cortex block fear-potentiated startle using a visual conditioned stimulus.\nThe present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and 1-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory.","subset":"pubmed_abstract"} +{"meta":{"pmid":11314153,"dup_signals":{"dup_doc_count":21,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2024-22":1,"unknown":9}}},"text":"Is it in a neonate's best interest to enter a randomised controlled trial?\nClinicians are required to act in the best interest of neonates. However, it is not obvious that entry into a randomised controlled trial (RCT) is in a neonate's best interest because such trials often involve additional onerous procedures (such as intramuscular injections) in return for which the neonate receives unproven treatment or a placebo. On the other hand, neonatology needs to develop its evidence base, and RCTs are central to this task. The solution posited here is based on two points. First, \"best interest\" is not equivalent to \"the best possible interest\" only to \"best interest within a certain realm\". The realm of deliberation when asking the title question is the neonate's health. Deliberating in this realm may involve the exclusion from consideration of some factors that might be thought relevant (such as parental wealth). Furthermore, circumstances may dictate the need to deliberate on other factors that might be thought irrelevant (such as health care resources). Second, deciding on a neonate's best interest does not involve \"putting oneself in its shoes\". Rather, it involves asking in what it has an interest, or stake. These will include some things in which we all, as human beings, have a stake, such as medical progress. Putting these two points together, in the realm of health the answer to whether RCT entry is in a neonate's best interest is usually very finely balanced. Where this is the case, it is reasonable to invoke a broader notion of best interest and include a broader range of elements in which the neonate has a stake, including medical progress. In this way RCT entry can, usually, be said to be in a neonate's best interest.","subset":"pubmed_abstract"} +{"meta":{"pmid":21982028,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2017-13":1,"unknown":10}}},"text":"Arsenic in North Carolina: public health implications.\nArsenic is a known human carcinogen and relevant environmental contaminant in drinking water systems. We set out to comprehensively examine statewide arsenic trends and identify areas of public health concern. Specifically, arsenic trends in North Carolina private wells were evaluated over an eleven-year period using the North Carolina Department of Health and Human Services database for private domestic well waters. We geocoded over 63,000 domestic well measurements by applying a novel geocoding algorithm and error validation scheme. Arsenic measurements and geographical coordinates for database entries were mapped using Geographic Information System techniques. Furthermore, we employed a Bayesian Maximum Entropy (BME) geostatistical framework, which accounts for geocoding error to better estimate arsenic values across the state and identify trends for unmonitored locations. Of the approximately 63,000 monitored wells, 7712 showed detectable arsenic concentrations that ranged between 1 and 806\u03bcg\/L. Additionally, 1436 well samples exceeded the EPA drinking water standard. We reveal counties of concern and demonstrate a historical pattern of elevated arsenic in some counties, particularly those located along the Carolina terrane (Carolina slate belt). We analyzed these data in the context of populations using private well water and identify counties for targeted monitoring, such as Stanly and Union Counties. By spatiotemporally mapping these data, our BME estimate revealed arsenic trends at unmonitored locations within counties and better predicted well concentrations when compared to the classical kriging method. This study reveals relevant information on the location of arsenic-contaminated private domestic wells in North Carolina and indicates potential areas at increased risk for adverse health outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22221171,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2023-50":1,"2024-18":1}}},"text":"The efficacy of mirtazapine in the treatment of cocaine dependence with comorbid depression.\nPrior findings concerning the use of mirtazapine in the treatment of a variety of substance use disorders and its antagonistic actions at the serotonin 5-HT(2A) receptor suggest that this drug may have efficacy in the treatment of cocaine dependence in the presence of a depressive disorder. Depressed cocaine-dependent subjects received either mirtazapine (target dose 45 mg daily) or placebo for 12 weeks. Urine concentrations of benzoylecgonine and self-report were used to assess cocaine consumption. Depression and sleep quality were evaluated using the Hamilton Depression Rating Scale (HAM-D) and the Pittsburgh Sleep Quality Index, respectively. Cocaine consumption during the treatment period did not differ significantly between the mirtazapine (n = 11) and placebo (n = 13) groups in this study. In week 4 sleep latency was significantly lower in the active medication than in the placebo group. Positive effects of mirtazapine treatment on early insomnia were suggested by an item analysis of the HAM-D. The results of this study suggest that mirtazapine is superior to placebo in improving sleep in patients with comorbid depression and cocaine dependence, but is not more effective than placebo in reducing cocaine use.","subset":"pubmed_abstract"} +{"meta":{"pmid":12591677,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":8}}},"text":"Radiofrequency ablation of hepatic tumors adjacent to the gallbladder: feasibility and safety.\nThis study was performed to assess the feasibility and safety of radiofrequency ablation of hepatic tumors adjacent to the gallbladder. Of the 83 patients who underwent radiofrequency ablation of hepatic tumors at our institution between December 1997 and August 2000, we identified eight patients--four men and four women who were 42-85 years old (mean age, 67 years)--who had tumors adjacent to the gallbladder. All ablations were performed with curative intent. We reviewed the patients' preablation imaging, radiofrequency ablation parameters, and course after ablation. Follow-up ranged from 3 to 22 months (mean, 8 months). Six patients with colorectal carcinoma and two with hepatocellular carcinoma had a total of 14 tumors adjacent to the gallbladder. Of the 14 tumors, nine (64%) were metastases and five (36%) were hepatocellular carcinoma. Eleven tumors (79%) were located directly adjacent to the gallbladder and three (21%) were located within 1 cm of the gallbladder. Tumor size ranged from 0.9 to 4.5 cm (mean, 3.6 cm). The number of radiofrequency ablations performed on each tumor ranged between one and six (mean, three ablations). Right upper quadrant pain developed in the immediate postablation period (within 7 days after the ablation) in six patients (75%) and ranged in duration from 5 to 21 days (mean, 7 days). Fever developed in four patients (50%), with a mean duration of 5 days. Arthralgia and right shoulder pain developed in one patient (12%). No deaths were noted in the immediate period after ablation. Complete ablation of all tumors visible on CT was achieved in seven patients. Of these, one patient (14%) had local tumor recurrence after 11 months. Radiofrequency ablation of tumors adjacent to the gallbladder is feasible and appears to be safe. Self-limited morbidity after ablation is noted in most patients and is probably related to a mild iatrogenic cholecystitis.","subset":"pubmed_abstract"} +{"meta":{"pmid":7916481,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells.\nIndirect evidence implicates gamma delta T cells in the cross-regulation of CD4 alpha beta T cell responses. Adoptive transfer of small numbers of gamma delta T cells from ovalbumin (OVA)-tolerant mice selectively suppressed TH2-dependent immunoglobulin E (IgE) antibody production without affecting parallel IgG responses. Challenge of these gamma delta T cells in vitro with specific antigen resulted in production of high levels of interferon gamma. The effects of the gamma delta T cells may be mediated by direct inhibition of OVA-specific CD4+ TH2 cell proliferation or selection for specific CD4 TH2 cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":21850205,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":18}}},"text":"RNA granules present only in extracellular toxoplasma gondii increase parasite viability.\nToxoplasma gondii is an obligate intracellular parasite. When searching for a new cell to invade, the parasites have to confront the stress of being exposed to the extracellular environment. The mechanisms by which T. gondii survives outside the host cells are poorly understood. In this work we show that extracellular parasites form mRNA aggregates with characteristics of stress granules. Intracellular tachyzoites or bradyzoites do not form mRNA granules. We tested different stimuli that trigger granule formation in vitro and discovered that a buffer that mimics the host cell cytosol ionic composition (high potassium) strongly induces granule formation, suggesting that the granules arise when the parasites come in contact with the host cell cytosol during egress. We examined the importance of granule formation for parasite viability and show that the parasite populations that are able to form granules have a growth advantage, increased invasion, and decreased apoptosis in the extracellular environment. Overall, granule formation improves the fitness of extracellular parasites and increases the efficiency of the lytic cycle.","subset":"pubmed_abstract"} +{"meta":{"pmid":28830440,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":12}}},"text":"Cross-sectional association between soda consumption and body mass index in a community-based sample of twins.\nConsumption of sugar-sweetened beverages, such as soda, have been shown to play an important role in weight gain. Although soda consumption has been associated with body mass index (BMI) in many studies, it has been difficult to ascertain a true causal relationship between soda consumption and BMI for two reasons. First, findings have been based largely on observational and cross-sectional studies, with much less evidence from randomized controlled trials. Second, the reported relationships may be confounded by genetic and shared environmental factors that affect both soda consumption and BMI. In the present study, we used the twin design to better understand the relationship between soda consumption and BMI by accounting for measured and unmeasured confounds in non-experimental data. Associations from genetically informed tests in twins are considered \"quasi-causal,\" suggesting that our confidence in the causal underpinning of the association between soda consumption and BMI has been strengthened. We hypothesized that the association between soda consumption and BMI would be significant both between and within twins. This was a cross sectional study of 5787 same sex adult twin pairs (18-97 years, 66% female) from the community based Washington State Twin Registry. Structural equation modeling (SEM) was employed to investigate associations between soda consumption and BMI in the population (the phenotypic association between exposure and outcome among all twins treated as individuals) and within pairs of identical and fraternal twins (the quasi-causal association controlling for between pair genetic and environmental confounds). Among all twins, there was a significant phenotypic association between soda consumption and BMI that held when controlling for age, sex, race, annual household income, and education level (P < 0.05). In the quasi-causal model, however, the effect of soda consumption on BMI was greatly reduced and no longer significant, with a large genetic confound in both men and women (P < 0.05). Among a large group of adult twin pairs, increased soda consumption was associated with increased BMI; however, the observed association was mediated by a genetic background common to both.","subset":"pubmed_abstract"} +{"meta":{"pmid":25047639,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"The neutral self-assembling peptide hydrogel SPG-178 as a topical hemostatic agent.\nConventional self-assembling peptide hydrogels are effective as topical hemostatic agents. However, there is a possibility to harm living tissues due to their low pH. The aim of the present study was to demonstrate the efficacy of SPG-178, a neutral self-assembling peptide hydrogel, as a topical hemostatic agent. First, we measured the bleeding duration of incisions made on rat livers after application of SPG-178 (1.0% w\/v), SPG-178 (1.5% w\/v), RADA16 (1.0% w\/v), and saline (n = 12\/group). Second, we observed the bleeding surfaces by transmission electron microscopy immediately after hemostasis. Third, we measured the elastic and viscous responses (G' and G\u2033, respectively) of the hydrogels using a rheometer. Our results showed that bleeding duration was significantly shorter in the SPG-178 group than in the RADA16 group and that there were no significant differences in transmission electron microscopy findings between the groups. The greater the G' value of a hydrogel, the shorter was the bleeding duration. We concluded that SPG-178 is more effective and has several advantages: it is non-biological, transparent, nonadherent, and neutral and can be sterilized by autoclaving.","subset":"pubmed_abstract"} +{"meta":{"pmid":32544900,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Spin-chain correlations in the frustrated triangular lattice material CuMnO2.\nThe Ising triangular lattice remains the classic test-case for frustrated magnetism. Here we report neutron scattering measurements of short range magnetic order in CuMnO2, which consists of a distorted lattice of Mn3+ spins with single-ion anisotropy. Physical property measurements on CuMnO2 are consistent with 1D correlations caused by anisotropic orbital occupation. However the diffuse magnetic neutron scattering seen in powder measurements has previously been fitted by 2D Warren-type correlations. Using neutron spectroscopy, we show that paramagnetic fluctuations persist up to \u223c25 meV above T N = 65 K. This is comparable to the incident energy of typical diffractometers, and results in a smearing of the energy integrated signal, which hence cannot be analysed in the quasi-static approximation. We use low energy XYZ polarised neutron scattering to extract the purely magnetic (quasi)-static signal. This is fitted by reverse Monte Carlo analysis, which reveals that two directions in the triangular layers are perfectly frustrated in the classical spin-liquid phase at 75 K. Strong antiferromagnetic correlations are only found along the b-axis, and our results hence unify the pictures seen by neutron scattering and macroscopic physical property measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":15910113,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2017-30":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2018-05":1,"2013-20":1,"2013-48":1}}},"text":"Decision-making deficits of korsakoff patients in a new gambling task with explicit rules: associations with executive functions.\nDecision-making deficits reflected by risky decisions in gambling tasks have been associated with frontal lobe dysfunctions in various neurologic and psychiatric populations. The question remains whether decision-making impairments are related to executive functions. The authors developed a new gambling task, the Game of Dice Task, with explicit and stable rules for reinforcement and punishment, to investigate relations between executive functions and risk-taking behavior in an explicit decision-making situation. A sample of 35 alcoholic Korsakoff patients and 35 healthy controls was examined with the Game of Dice Task and a neuropsychological test battery. Results show that Korsakoff patients are strongly impaired in this explicit decision-making task and that these disturbances are correlated with specific executive functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":18313770,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2014-10":1,"unknown":11}}},"text":"Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection.\nSubregional analyses of the hippocampus suggest CA1-dependent memory processes rely heavily upon interactions between the CA1 subregion and entorhinal cortex. There is evidence that the direct perforant path (pp) projection to CA1 is selectively modulated by dopamine while having little to no effect on the Schaffer collateral (SC) projection to CA1. The current study takes advantage of this pharmacological dissociation to demonstrate that local infusion of the non-selective dopamine agonist, apomorphine (10, 15 microg), into the CA1 subregion of awake animals produces impairments in working memory at intermediate (5 min), but not short-term (10 s) delays within a delayed non-match-to-place task on a radial arm maze. Sustained impairments were also found in a novel context with similar object-space relationships. Infusion of apomorphine into CA1 is also shown here to produce deficits in spatial, but not non-spatial novelty detection within an object exploration paradigm. In contrast, apomorphine produces no behavioral deficits when infused into the CA3 subregion or overlying cortex. These behavioral studies are supported by previous electrophysiological data that demonstrate local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a fundamental role for EC-CA1 synaptic transmission in terms of detection of spatial novelty, and intermediate-term, but not short-term spatial working memory or object-novelty detection.","subset":"pubmed_abstract"} +{"meta":{"pmid":26479250,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"[Somatic screening in child and adolescent psychiatry: a descriptive pilot study].\nSomatic disorders occur more often in psychiatric patients than in the general population. Somatic symptoms can cause or increase psychiatric symptoms. Psychiatric symptoms and their treatment can have an effect on the physical state of the patient. A pilot study involving an adult outpatient population has demonstrated that 62% of the patients studied had new clinically relevant symptoms. So far, no other data are available relating to somatic screening in child and adolescent psychiatry. To assess whether somatic screening of children and adolescents newly referred to a department of child and adolescent psychiatry in the Netherlands gives added value to the diagnosis and treatment policy. In a pilot study 43 newly referred patients aged between 6 and 18 were screened by means of somatic history, a physical examination and blood parameters. On this basis we could calculate the percentage of somatic symptoms and , where necessary, follow-up treatment could be applied. One or more clinically relevant disorders were found in almost 56% of the children and adolescents investigated. The disorders included dysmorphic anomalies, weight and height deviations, raised thyroid hormone levels, dyslipidaemia, anaemia and vitamin D and B12 deficiency. Advice about a healthy lifestyle was given to 44% of the patients. An antipsychotic medication in 25% of the patients was changed, in the case of 16% of the patients a family doctor was contacted about subsequent treatment and 19% of the patients were referred to a medical specialist. Although the results of the pilot study indicate that somatic screening does provide added value, more research is needed in order to optimise the screening procedure.","subset":"pubmed_abstract"} +{"meta":{"pmid":26030442,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Differential CARM1 Isoform Expression in Subcellular Compartments and among Malignant and Benign Breast Tumors.\nCoactivator-associated arginine methyltransferase 1 (CARM1) is a coactivator for ER\u03b1 and cancer-relevant transcription factors, and can methylate diverse cellular targets including histones. CARM1 is expressed in one of two alternative splice isoforms, full-length CARM1 (CARM1FL) and truncated CARM1 (CARM1\u0394E15). CARM1FL and CARM1\u0394E15 function differently in transcriptional regulation, protein methylation, and mediation of pre-mRNA splicing in cellular models. To investigate the functional roles and the prognosis potential of CARM1 alternative spliced isoforms in breast cancer, we used recently developed antibodies to detect differential CARM1 isoform expression in subcellular compartments and among malignant and benign breast tumors. Immunofluorescence in MDA-MB-231 and BG-1 cell lines demonstrated that CARM1\u0394E15 is the dominant isoform expressed in the cytoplasm, and CARM1FL is more nuclear localized. CARM1\u0394E15 was found to be more sensitive to Hsp90 inhibition than CARM1FL, indicating that the truncated isoform may be the oncogenic form. Clinical cancer samples did not have significantly higher expression of CARM1FL or CARM1\u0394E15 than benign breast samples at the level of mRNA or histology. Furthermore neither CARM1FL nor CARM1\u0394E15 expression correlated with breast cancer molecular subtypes, tumor size, or lymph node involvement. The analysis presented here lends new insights into the possible oncogenic role of CARM1\u0394E15. This study also demonstrates no obvious association of CARM1 isoform expression and clinical correlates in breast cancer. Recent studies, however, have shown that CARM1 expression correlates with poor prognosis, indicating a need for further studies of both CARM1 isoforms in a large cohort of breast cancer specimens.","subset":"pubmed_abstract"} +{"meta":{"pmid":29311642,"dup_signals":{"dup_doc_count":14,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2022-21":2,"2022-05":1,"2021-17":1,"2021-10":1,"2020-40":1,"2020-34":1,"2019-47":1,"2019-35":1,"2019-26":1,"2023-23":1,"2024-22":1}}},"text":"HSP90 inhibition alters the chemotherapy-driven rearrangement of the oncogenic secretome.\nAdaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP). Thus, administration of a clinical trial grade, HSP90, inhibitor blunted the release of several cytokines by the chemotherapy-treated MPM cells, including interleukin (IL)-8. Reduction of IL-8 levels hampered the FAK-AKT signaling and inhibited 3D growth and migration. This correlated with downregulation of key EMT and chemoresistance genes and affected the survival of chemoresistant ALDHbright cell subpopulations. Altogether, inhibition of HSP90 provoked a switch from a pro-tumorigenic SASP to a pro-apoptotic senescence status, thus resulting in chemosensitizing effects. In mouse xenografts treated with first-line agents, inhibiting HSP90 blunted FAK activation and reduced the expression of ALDH1A3 and the levels of circulating human IL-8, these latter strongly correlating with the effect on tumor growth. We validated the above findings in primary mesothelioma cultures, a more clinically relevant model. We unveiled here a key contribution of the chaperone HSP90 at assisting the secretory stress in chemotherapy-treated cells, which may warrant further investigation in combinatorial therapeutic settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":8398904,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extracellular matrix.\nTo examine whether the expression of retinoblastoma (RB) protein could mediate tumor suppression in a lung carcinoma cell line carrying multiple genetic defects, we transfected the Rb gene into a non-small cell lung cancer cell line with absent RB protein. We observed that the stable expression of a functional RB product was associated with a decreased efficiency of soft agar cloning and partial suppression of tumorigenicity in nude mice. The suppression of tumorigenicity was marked when 10(6) cells were injected into the flanks of nude mice but was less prominent when 10(7) cells were injected. RB-mediated tumor suppression, however, was consistently blocked by preincubation of the transfected cells with an extract enriched with an extracellular matrix (Matrigel). Analysis of tumors harvested from nude mice showed that they continued to express detectable levels of human RB protein which retained functional E1A binding activity and nuclear localization. RB-mediated inhibition of soft agar cloning was also blocked in a dose-dependent manner by the addition of Matrigel. These observations demonstrate that the expression of wild-type RB may suppress certain parameters of tumorigenicity in lung carcinoma cells that contain multiple genetic alterations. In addition, the reversal of tumor suppression by an extract enriched in basement membrane components may offer clues for further investigations into the mechanism of RB-mediated tumor suppression.","subset":"pubmed_abstract"} +{"meta":{"pmid":29156921,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Sexual healthcare for cancer patients receiving palliative care: a narrative review.\nPalliative care aims to improve quality of life (QoL) for patients and families and does so by addressing issues not limited to pathology, but other symptoms that may be debilitating to patient experience and QoL. Despite sexual health being an important aspect of life for many patients, it is often omitted in clinical practice. This review summarizes published primary studies to explore the prevalence and importance of incorporating sexual health in the symptom screening and assessments of palliative patients, to identify current interventions that are implemented to address sexual health issues, and identify the barriers that health care professionals (HCPs) and patients may encounter which may prevent sexual health discussions. A literature review was conducted on Medline and Embase databases using keywords including \"cancer\", \"sexual health\", \"intimacy\", and \"palliative care\". Eleven papers focusing on the sexual health and intimacy of terminally ill patients in hospice, palliative or terminal care settings were identified for inclusion. Discussions about sexual health, functioning, and intimacy were not common in patient care, despite being a service that both patients and their partners desired. Referrals to sexologists, or discussions with patients and partners about intimacy and sexuality over the course of the disease trajectory were shown to improve QoL as well as alleviate some of the stress of receiving palliative care services. HCPs cited a lack of training, their own life experiences, or discomfort with the topic as barriers to initiating conversations with patients. In conclusion, sexuality and intimacy remain important parts of many people's lives regardless of their health, and should be incorporated into the care of all patients including those in palliative care. There is a need for further research to evaluate different methods or procedures for educating and counselling patients and their partners on sexual health issues. HCPs should have specific training and education in sexual health care to enable them to initiate and direct these discussions.","subset":"pubmed_abstract"} +{"meta":{"pmid":29184073,"dup_signals":{"dup_doc_count":16,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2020-50":1,"2020-05":1,"2019-43":1,"2019-26":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-13":1,"2018-05":1,"2021-21":1}}},"text":"Simple spatial scaling rules behind complex cities.\nAlthough most of wealth and innovation have been the result of human interaction and cooperation, we are not yet able to quantitatively predict the spatial distributions of three main elements of cities: population, roads, and socioeconomic interactions. By a simple model mainly based on spatial attraction and matching growth mechanisms, we reveal that the spatial scaling rules of these three elements are in a consistent framework, which allows us to use any single observation to infer the others. All numerical and theoretical results are consistent with empirical data from ten representative cities. In addition, our model can also provide a general explanation of the origins of the universal super- and sub-linear aggregate scaling laws and accurately predict kilometre-level socioeconomic activity. Our work opens a new avenue for uncovering the evolution of cities in terms of the interplay among urban elements, and it has a broad range of applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":21344145,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Investigation and analysis of a human orf outbreak among people living on the same farm.\nHuman orf is a viral zoonotic infection caused by Parapoxvirus. The skin lesions of human orf can be misdiagnosed as cutaneous anthrax leading to overtreatment and also fear. This study was conducted to analyze an outbreak which led to deaths among kids and lambs in the same flock, and skin lesions in some persons who were living on the same farm that were initially diagnosed as cutaneous anthrax by a practitioner. Eight patients with skin lesions and eleven persons who had no skin lesion were considered as patients and control groups, respectively. The cultures obtained from the lesions of all patients were negative for Bacillus anthracis. The diagnosis of skin lesions was done by clinical findings, histopathological examination and PCR as human orf. To be under 20 years of age, direct contact with the animals, and contact with flayed skin of sick animals were the risk factors for human orf (Odds Ratio 7.5; 95% Confidence Interval 1.02-54.54, OR 12.25; 95% CI:1.3-100.9, OR 16.67; 95% CI:1.65-148.20, respectively). Orf should be kept in mind in the differential diagnosis of skin lesions resembling anthrax. For control and prevention of orf, transmission routes should be known; good hand hygiene and other personal protective measures have to be implemented.","subset":"pubmed_abstract"} +{"meta":{"pmid":23677316,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":4,"unknown":9}}},"text":"Do TNF inhibitors reduce the risk of myocardial infarction in psoriasis patients?\nTo assess whether patients with psoriasis treated with tumor necrosis factor (TNF) inhibitors have a decreased risk of myocardial infarction (MI) compared with those not treated with TNF inhibitors. Retrospective cohort study. Kaiser Permanente Southern California health plan. Patients with at least 3 International Classification of Diseases, Ninth Revision, Clinical Modification, codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI) between January 1, 2004, and November 30, 2010. Incident MI. Of 8845 patients included, 1673 received a TNF inhibitor for at least 2 months (TNF inhibitor cohort), 2097 were TNF inhibitor naive and received other systemic agents or phototherapy (oral\/phototherapy cohort), and 5075 were not treated with TNF inhibitors, other systemic therapies, or phototherapy (topical cohort). The median duration of follow-up was 4.3 years (interquartile range, 2.9, 5.5 years), and the median duration of TNF inhibitor therapy was 685 days (interquartile range, 215, 1312 days). After adjusting for MI risk factors, the TNF inhibitor cohort had a significantly lower hazard of MI compared with the topical cohort (adjusted hazard ratio, 0.50; 95% CI, 0.32-0.79). The incidence of MI in the TNF inhibitor, oral\/phototherapy, and topical cohorts were 3.05, 3.85, and 6.73 per 1000 patient-years, respectively. Use of TNF inhibitors for psoriasis was associated with a significant reduction in MI risk and incident rate compared with treatment with topical agents. Use of TNF inhibitors for psoriasis was associated with a non-statistically significant lower MI incident rate compared with treatment with oral agents\/phototherapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":34369592,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"A fresh scientific look at transfer and persistence: From a materials science and tribology perspective.\nKnowledge of the mechanisms governing transfer, persistence, and recovery of trace evidence, together with background prevalence in the population of interest, and other task relevant information, is key for the forensic interpretation and reconstruction of what happened at the activity level. Up to now, this informational \"toolkit\" has largely been developed through empirical forensic studies on specific trace materials such as glass, textile fibers, and soil. Combined with the identified systemic siloing between disciplines, while valuable, such research tends to be very material-dependent, introducing specific parameters and interpretations that may have actually impeded the recognition of underlying foundational factors applicable to most material types. In Australia, there has been a renewed interest in developing a discipline-independent framework for the interpretation and\/or reconstruction of trace evidence to interpret specific circumstances in casework. In this paper, we present a discipline agnostic \"way of thinking\" that has been anchored in foundational science underpinning the trace evidence discipline. Physical and mechanical material properties such as material geometry and surface topography, strength, stiffness, and hardness collectively influence contact interactions through underlying friction, wear, and lubrication cause and effect mechanisms. We discuss how these fundamental factors and parameters stemming from materials science and tribology may be adopted and adapted by forensic practitioners and researchers to contribute to a better understanding of transfer, persistence, and recovery mechanisms irrespective of evidence discipline and material type. Examples are provided to demonstrate the practical significance to real-life casework and academic research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22276127,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2022-21":1,"2021-21":1,"2020-24":1,"2019-30":1,"2018-47":1,"2018-26":1,"2018-05":2,"2017-39":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-23":1,"2017-13":1}}},"text":"Multiparameter telemetry as a sensitive screening method to detect vaccine reactogenicity in mice.\nRefined vaccines and adjuvants are urgently needed to advance immunization against global infectious challenges such as HIV, hepatitis C, tuberculosis and malaria. Large-scale screening efforts are ongoing to identify adjuvants with improved efficacy profiles. Reactogenicity often represents a major hurdle to the clinical use of new substances. Yet, irrespective of its importance, this parameter has remained difficult to screen for, owing to a lack of sensitive small animal models with a capacity for high throughput testing. Here we report that continuous telemetric measurements of heart rate, heart rate variability, body core temperature and locomotor activity in laboratory mice readily unmasked systemic side-effects of vaccination, which went undetected by conventional observational assessment and clinical scoring. Even minor aberrations in homeostasis were readily detected, ranging from sympathetic activation over transient pyrogenic effects to reduced physical activity and apathy. Results in real-time combined with the potential of scalability and partial automation in the industrial context suggest multiparameter telemetry in laboratory mice as a first-line screen for vaccine reactogenicity. This may accelerate vaccine discovery in general and may further the success of vaccines in combating infectious disease and cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":29385959,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":12}}},"text":"Reducing Frequent Utilization of Psychiatric Emergency Services Among Veterans While Maintaining Quality of Care.\nUse of psychiatric emergency services in emergency departments (EDs) and inpatient psychiatry units contributes substantially to the cost of mental health care. Among patients who utilize psychiatric emergency services, a small percentage (\"high utilizers\") contributes a disproportionate share of the total cost, yet little is known about the context of care for these patients. This study employed qualitative methods to identify barriers to and facilitators of reducing use of psychiatric emergency services among high utilizers. Semistructured phone interviews were conducted with 31 directors of mental health services and providers of psychiatric emergency services across 22 Veterans Health Administration medical centers. The Consolidated Framework for Implementation Research was used to guide the interviews to evaluate the context of care for high utilizers. Thematic coding was used to identify barriers to and facilitators of reducing utilization. Barriers emerged at the patient level (for example, treatment nonadherence and transiency), provider level (for example, stigma toward high utilizers and lack of expertise and training in the management of psychiatric issues among ED staff), and system level (for example, lack of specialized services to address short- and long-term care needs). Facilitators included recovery-oriented care; interdisciplinary care coordination and case management, with emphasis on the role of psychiatric social workers; and predictive analytics to flag high utilizers. The findings lay the groundwork for the design of novel approaches to care for high utilizers of psychiatric emergency services while limiting provider burnout, managing costs, and optimizing treatment outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29191434,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":18}}},"text":"The gendered effects of foreign investment and prolonged state ownership on mortality in Hungary: an indirect demographic, retrospective cohort study.\nResearch on the health outcomes of globalisation and economic transition has yielded conflicting results, partly due to methodological and data limitations. Specifically, the outcomes of changes in foreign investment and state ownership need to be examined using multilevel data, linking macro-effects and micro-effects. We exploited the natural experiment offered by the Hungarian economic transition by means of a multilevel study designed to address these gaps in the scientific literature. For this indirect demographic, retrospective cohort study, we collected multilevel data related to Hungary between 1995 and 2004 from the PrivMort database and other sources at the town, company, and individual level to assess the relation between the dominant company ownership of a town and mortality. We grouped towns into three ownership categories: dominant state, domestic private, and foreign ownership. We did population surveys in these towns to collect data on vital status and other characteristics of survey respondents' relatives. We assessed the relation between dominant ownership and mortality at the individual level. We used discrete-time survival modelling, adjusting for town-level and individual-level confounders, with clustered SEs. Of 83 eligible towns identified, we randomly selected 52 for inclusion in the analysis and analysed ownership data from 262 companies within these towns. Additionally, between June 16, 2014, and Dec 22, 2014, we collected data on 78 622 individuals from the 52 towns, of whom 27 694 were considered eligible. After multivariable adjustment, we found that women living in towns with prolonged state ownership had significantly lower odds of dying than women living in towns dominated by domestic private ownership (odds ratio [OR] 0\u00b774, 95% CI 0\u00b761-0\u00b790) or by foreign investment (OR 0\u00b780, 0\u00b769-0\u00b792). Prolonged state ownership was associated with protection of life chances during the post-socialist transformation for women. The indirect economic benefits of foreign investment do not translate automatically into better health without appropriate industrial and social policies. The European Research Council.","subset":"pubmed_abstract"} +{"meta":{"pmid":32365137,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":15}}},"text":"Better together: Elements of successful scientific software development in a distributed collaborative community.\nMany scientific disciplines rely on computational methods for data analysis, model generation, and prediction. Implementing these methods is often accomplished by researchers with domain expertise but without formal training in software engineering or computer science. This arrangement has led to underappreciation of sustainability and maintainability of scientific software tools developed in academic environments. Some software tools have avoided this fate, including the scientific library Rosetta. We use this software and its community as a case study to show how modern software development can be accomplished successfully, irrespective of subject area. Rosetta is one of the largest software suites for macromolecular modeling, with 3.1 million lines of code and many state-of-the-art applications. Since the mid 1990s, the software has been developed collaboratively by the RosettaCommons, a community of academics from over 60 institutions worldwide with diverse backgrounds including chemistry, biology, physiology, physics, engineering, mathematics, and computer science. Developing this software suite has provided us with more than two decades of experience in how to effectively develop advanced scientific software in a global community with hundreds of contributors. Here we illustrate the functioning of this development community by addressing technical aspects (like version control, testing, and maintenance), community-building strategies, diversity efforts, software dissemination, and user support. We demonstrate how modern computational research can thrive in a distributed collaborative community. The practices described here are independent of subject area and can be readily adopted by other software development communities.","subset":"pubmed_abstract"} +{"meta":{"pmid":21880868,"dup_signals":{"dup_doc_count":20,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-40":1,"2021-49":2,"2021-25":1,"2021-21":1,"2020-45":1,"2020-29":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-22":1,"2023-50":1,"2024-10":3,"2024-22":1}}},"text":"Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum.\nMutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial diseases in children and adults. This study sequenced the exons and flanking intronic regions of the POLG gene from 2697 unrelated patients with clinical presentations suggestive of POLG deficiency. Informative mutations have been identified in 136 unrelated individuals (5%), including 92 patients with two recessive pathogenic alleles and three patients harbouring a dominant mutation. Twenty-four novel recessive mutations and a novel possible dominant mutation, p.Y951N, were identified. All missense mutations occurred at evolutionarily conserved amino acids within functionally important regions identified by molecular modelling analyses. Oligonucleotide array comparative genomic hybridisation analyses performed on DNA samples from 81 patients with one mutant POLG allele identified a large intragenic deletion in only one patient, suggesting that large deletions in POLG are rare. The 92 patients with two mutant alleles exhibited a broad spectrum of disease. Almost all patients in all age groups had some degree of neuropathy. Seizures, hepatopathy, and lactic acidaemia were predominant in younger patients. By comparison, patients who developed symptoms in adulthood had a higher percentage of myopathy, sensory ataxia, and chronic progressive external ophthalmoplegia (CPEO)\/ptosis. In conclusion, POLG mutations account for a broad clinical spectrum of mitochondrial disorders. Sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders, even in the absence of apparent mitochondrial DNA abnormalities.","subset":"pubmed_abstract"} +{"meta":{"pmid":30161166,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Dissociable psychosocial profiles of adolescent substance users.\nAlcohol, tobacco and cannabis use in adolescence is associated with adverse outcomes. Characterizing adolescent substance misusers, however, is difficult due to the wide range of risk and protective factors linked to substance use. The aim of the present study was to examine the role of the Individual, Family, School, Peer, and Social Environment on alcohol (lifetime and risky), tobacco (risky only), and cannabis use (lifetime and riskiness). Data were analyzed from a national sample of 5,680 adolescents, capturing substance use behavior alongside risk and protective factors across Individual, Family, School, Peer and Social domains. We applied a sophisticated machine learning classifier to develop models of alcohol, tobacco and cannabis initiation and misuse. We found highly accurate (area under curve of receiver-operator-characteristic for out-of-sample performance was > .88) and replicable (over multiple iterations and in comparison with permuted outcomes) dissociable psychosocial profiles of alcohol, tobacco and cannabis use. Alongside common predictors (peer relations and externalizing behavior), dissociable risk and resilience factors were observed. Adolescent profiles of alcohol use were distinguished by the contribution of multiple domains. In contrast, tobacco use was characterized by a small number of individual variables, including female gender and poor perceived academic position. Cannabis use was differentiated by the distinct contribution of Individual risk factors, in particular male gender and feelings of anger. Differential associations were also evident, with the strength and direction of association differing substantially across substances. This study indicates that the relationship between the environment and substance use is more complex than previously thought.","subset":"pubmed_abstract"} +{"meta":{"pmid":22647633,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":1,"2013-20":1,"unknown":5}}},"text":"Differential effects of extracellular ATP on chloride transport in cortical collecting duct cells.\nExtracellular ATP in the cortical collecting duct can inhibit epithelial sodium channels (ENaC) but also stimulate calcium-activated chloride channels (CACC). The relationship between ATP-mediated regulation of ENaC and CACC activity in cortical collecting duct cells has not been clearly defined. We used the mpkCCD(c14) cortical collecting duct cell line to determine effects of ATP on sodium (Na(+)) and chloride (Cl(-)) transport with an Ussing chamber system. ATP, at a concentration of 10(-6) M or less, did not inhibit ENaC-mediated short-circuit current (I(sc)) but instead stimulated a transient increase in I(sc). The macroscopic current-voltage relationship for ATP-inducible current demonstrated that the direction of this ATP response changes from positive to negative when transepithelial voltage (V(te)) is clamped to less than -10 mV. We hypothesized that this negative V(te) might be found under conditions of aldosterone stimulation. We next stimulated mpkCCD(c14) cells with aldosterone (10(-6) M) and then clamped the V(te) to -50 mV, the V(te) of aldosterone-stimulated cells under open-circuit conditions. ATP (10(-6) M) induced a transient increase in negative clamp current, which could be inhibited by flufenamic acid (CACC inhibitor) and BAPTA-AM (calcium chelator), suggesting that ATP stimulates Cl(-) absorption through CACC. Together, our findings suggest that the status of ENaC activity, by controlling V(te), may dictate the direction of ATP-stimulated Cl(-) transport. This interplay between aldosterone and purinergic signaling pathways may be relevant for regulating NaCl transport in cortical collecting duct cells under different states of extracellular fluid volume.","subset":"pubmed_abstract"} +{"meta":{"pmid":15941415,"dup_signals":{"dup_doc_count":30,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":3,"2020-24":1,"2019-47":1,"2024-30":3,"2024-26":1,"2024-10":2}}},"text":"Clinical algorithms for malaria diagnosis lack utility among people of different age groups.\nWe conducted a study to determine whether clinical algorithms would be useful in malaria diagnosis among people living in an area of moderate malaria transmission within Kilifi District in Kenya. A total of 1602 people of all age groups participated. We took smears and recorded clinical signs and symptoms (prompted or spontaneous) of all those presenting to the study clinic with a history of fever. A malaria case was defined as a person presenting to the clinic with a history of fever and concurrent parasitaemia. A set of clinical signs and symptoms (algorithms) with the highest sensitivity and specificity for diagnosing a malaria case was selected for the age groups <\/=5 years, 6-14 years and >\/=15 years. These age-optimized derived algorithms were able to identify about 66% of the cases among those <15 years of age but only 23% of cases among adults. Were these algorithms to be used as a basis for a decision on treatment among those presenting to the clinic, 16% of children <\/=5 years, 44% of those 6-14 years of age and 66% of the adults who had a history of fever and parasitaemia >\/=5000 parasites\/microl of blood would be sent home without treatment. Clinical algorithms therefore appear to have little utility in malaria diagnosis, performing even worse in the older age groups, where avoiding unnecessary use of anti-malarials would make more drugs available to the really needy population of children under 5 years of age.","subset":"pubmed_abstract"} +{"meta":{"pmid":31215580,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Late stage functionalization of heterocycles using hypervalent iodine(iii) reagents.\nLate stage functionalization (LSF) through direct X-H manipulations (X = C, N) enables synthetic chemists to accelerate the diversification of natural products, agrochemicals and pharmaceuticals allowing rapid access to novel bioactive molecules without resorting to arduous de novo synthesis. LSF does not only allow tapping of the hitherto unexplored chemical space but also renders the synthetic sequence more straightforward, atom economical and cost-effective. In this regard, the recent decade has witnessed the emergence of hypervalent iodine(iii) reagents as a powerful synthetic tool owing to their easy availability, mild reaction conditions, remarkable oxidizing properties and high functional group tolerance. Iodine(iii) reagents have tremendous applications in the regio- and chemo-selective late-stage functionalization of a diverse variety of heterocycles through an exciting range of transformations, such as oxidative amination, cross-dehydrogenative coupling (CDC), fluoroalkylation, azidation, halogenation and oxidation. The present review, classified according to the types of synthetic methods involved, encompasses all these recent developments in the field of transition-metal-free iodine(iii)-catalyzed\/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.","subset":"pubmed_abstract"} +{"meta":{"pmid":18813484,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"[Social spending in Brazil: income transfer programs versus social investments].\nThis paper compares the dynamics of social spending in Brazil, with lower outlays on basic services and more direct monetary transfers through means-test programs, highlighting the fact that as Brazil's social safety net concentrates on cash transfer programs without simultaneously increasing per capita outlays on education, basic sanitation and housing, it is not resolving the issue of inequality. This paper works with secondary data from the National Household Sampling Survey, together with Federal, State and Municipal budgets.","subset":"pubmed_abstract"} +{"meta":{"pmid":19723417,"dup_signals":{"dup_doc_count":24,"dup_dump_count":11,"dup_details":{"curated_sources":3,"2023-50":2,"2023-23":4,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-21":3,"2022-05":1,"2024-18":2,"2024-10":4,"2024-30":1}}},"text":"Ethicolegal aspects of genetics in surgical practice.\nGenetic medicine can pose ethical and legal dilemmas or both. This short review highlights some of the ethicolegal issues in disclosure of genetic information to family members and considers whether the availability, or not, of a medical intervention is relevant in communication of risk information.","subset":"pubmed_abstract"} +{"meta":{"pmid":21747869,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":9}}},"text":"Industrial fungal enzymes: an occupational allergen perspective.\nOccupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":31817802,"dup_signals":{"dup_doc_count":85,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-25":2,"2021-04":9,"2020-50":1,"2020-45":12,"2020-40":2,"2020-34":2,"2020-29":13,"2020-24":8,"2020-16":24,"2020-10":7,"2020-05":1}}},"text":"Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration.\nBone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and\/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.","subset":"pubmed_abstract"} +{"meta":{"pmid":16770577,"dup_signals":{"dup_doc_count":15}},"text":"Uptake and speciation of selenium in garlic cultivated in soil amended with symbiotic fungi (mycorrhiza) and selenate.\nThe scope of the work was to investigate the influence of selenate fertilisation and the addition of symbiotic fungi (mycorrhiza) to soil on selenium and selenium species concentrations in garlic. The selenium species were extracted from garlic cultivated in experimental plots by proteolytic enzymes, which ensured liberation of selenium species contained in peptides or proteins. Separate extractions using an aqueous solution of enzyme-deactivating hydroxylamine hydrochloride counteracted the possible degradation of labile selenium species by enzymes (such as alliinase) that occur naturally in garlic. The selenium content in garlic, which was analysed by ICP-MS, showed that addition of mycorrhiza to the natural soil increased the selenium uptake by garlic tenfold to 15 microg g(-1) (dry mass). Fertilisation with selenate and addition of mycorrhiza strongly increased the selenium content in garlic to around one part per thousand. The parallel analysis of the sample extracts by cation exchange and reversed-phase HPLC with ICP-MS detection showed that gamma-glutamyl-Se-methyl-selenocysteine amounted to 2\/3, whereas methylselenocysteine, selenomethionine and selenate each amounted to a few percent of the total chromatographed selenium in all garlic samples. Se-allyl-selenocysteine and Se-propyl-selenocysteine, which are selenium analogues of biologically active sulfur-containing amino acids known to occur in garlic, were searched for but not detected in any of the extracts. The amendment of soil by mycorrhiza and\/or by selenate increased the content of selenium but not the distribution of detected selenium species in garlic. Finally, the use of two-dimensional HPLC (size exclusion followed by reversed-phase) allowed the structural characterisation of gamma-glutamyl-Se-methyl-selenocysteine and gamma-glutamyl-Se-methyl-selenomethionine in isolated chromatographic fractions by quadrupole time-of-flight mass spectrometry.","subset":"pubmed_abstract"} +{"meta":{"pmid":15811483,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-50":1}}},"text":"Impact of an adherence clinic on behavioral outcomes and virologic response in treatment of HIV infection: a prospective, randomized, controlled pilot study.\nThe aim of this randomized, controlled pilot study was to examine the impact of a pharmacist operated adherence clinic on adherence to highly active antiretroviral therapy (HAART) and viral suppression in patients with HIV over 28 weeks. Consecutive eligible patients initiating HAART at an indigent-care clinic were randomized to an adherence clinic or to standard care (information provided by physician or nurse practitioner) for education and monitoring. Group assignment was stratified before randomization according to regimen complexity and potential tolerability. Adherence (electronic monitoring and patient self-report) and viral load (reverse-transcription polymerase chain reaction) were assessed at weeks 4, 16, and 28. Thirty-three randomized patients (adherence clinic, n = 16; standard care, n = 17) comprised the intent-to-treat population. The groups were well-matched for demographics and antiretroviral regimen. The median age was 38.0 years in both groups. Most patients were male (85%), had previously used HAART (78%), and had an AIDS diagnosis (79%). Mean (SD) adherence at weeks 4, 16, and 28 was 86% (27%), 77% (28%), and 74% (31%) in the adherence clinic group versus 73% (32%), 56% (39%), and 51% (41%) in the standard care group (week-16 difference, 21% [90% CI, 1%-42%]; week-28 difference, 23% [90% CI, 1%-44%]). Sixty-nine percent of patients in the adherence clinic group took their medication on schedule versus 42% in the standard care group (P = 0.025); mean decline in adherence from weeks 4 to 28 was 12% in the adherence clinic group (P = 0.15) versus 22% in the standard care group (P = 0.002). HIV-1 RNA levels were <400 copies\/mL at weeks 4, 16, and 28 in 63%, 100%, and 94% of the adherence clinic group and 29% (P = NS), 71% (P = 0.04), and 65% (P = NS) of the standard care group. In this preliminary trial, an adherence clinic model improved adherence to HAART and virologic response over 28 weeks in the patients studied.","subset":"pubmed_abstract"} +{"meta":{"pmid":27644870,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Revenge Pornography: Mental Health Implications and Related Legislation.\nRevenge pornography, also known as nonconsensual pornography, is a subtype of cyberharassment\/cyberstalking, and a serious problem facing society in the Internet age. Revenge pornography can result in lifelong mental health consequences for victims, damaged relationships, and social isolation. Recently, a growing number of states have recognized the importance of this phenomenon and have enacted legislation that criminalizes it. The technology industry has also taken steps to assist victims of revenge pornography by creating web forms to request removal of links leading to the explicit content. The Cyber Civil Rights Initiative (CCRI) has been instrumental in promoting public awareness of this often overlooked problem and in providing services for victims. Although important steps have been made, greater recognition of the gravity of this problem and the mental health implications of revenge pornography is needed to expand legislation criminalizing such acts. A federal criminal law, in particular, is much overdue. Mental health professionals must understand the dimensions of revenge pornography to be able to identify and address the consequences in both forensic and clinical settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":23034740,"dup_signals":{"dup_doc_count":17,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-11":1,"unknown":10}}},"text":"Multifaceted prismatic silver nanoparticles: synthesis by chloride-directed selective growth from thiolate-protected clusters and SERS properties.\nWe describe the synthetic preparation of well-defined symmetric multifaceted prismatic silver nanoparticles with chemically controlled faceting advantageous for strong and tunable surface-enhanced Raman scattering, SERS. These silver nanoparticles, that have been termed nanoflowers, AgNFls for their characteristic morphologies, have been prepared by a one-pot aqueous reaction under ambient conditions. AgNFl faceting is synthetically controlled by selective nanoparticle growth driven by chloride ions. Selective chloride binding to the surface of growing AgNFls results in nanoparticle enlargement predominantly at the points of their highest energy. These growth points are located at the tips of prismatic polygons in precursor prismatic morphologies that have been produced from thiolate-protected silver clusters whose coalescence is triggered with a strong base. For the practical aspects of AgNFl synthesis, concentrations of thiol and a strong base were found to be the key variables reliably controlling the extent of AgNFl faceting, as well as the kinetics of AgNFl formation and their stability. The selective growth of AgNFls progresses slower compared to that of non-faceted prisms: fewer nuclei can form leading to larger AgNFls with the diameter ranging from 130 to 2250 nm and asperity sizes on the order of 20 to 100 nm. Self-assembly of AgNFls yields columnar stacking. AgNFls were demonstrated to function as a promising substrate for surface-enhanced Raman scattering. SERS measurements were performed for a series of AgNFls with variable faceting, where the enhancement factors of 4.6 \u00d7 10(8) and 425 have been achieved for dry solid films and aqueous dispersions of non-aggregated AgNFls with single-particle enhancement, respectively. These SERS results are promising, especially in combination with that AgNFl nanoscale asperities can be conveniently tailored synthetically. Overall, AgNFls offer valuable opportunities for a system with synthetically variable nanoscale asperities.","subset":"pubmed_abstract"} +{"meta":{"pmid":27908181,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Defining and assessing an anisotropic delineation margin for modern radiotherapy.\nUncertainty in target volume delineation for modern radiotherapy impacts dosimetry and patient outcomes. Delineation uncertainty is generally overlooked in practice as a source of error, potentially since historically, other uncertainties have been the main focus. This work defined and assessed an anisotropic delineation margin in both polar and spherical coordinate systems in order to account for the spatially varying nature of this uncertainty using a whole breast radiotherapy cohort as a proof of concept. A cohort of 21 whole breast radiotherapy patient datasets with clinical target volumes delineated by eight independent observers was utilized. Patients were divided into categories based on target volume and laterality. An anisotropic delineation margin for each category was determined by multiplying the average standard deviation in observer contours in each category by a factor of two. Standard deviation was determined in both polar and spherical coordinates at angular increments. This anisotropic approach was compared to a conventional clinical approach, where the delineation margin was applied in the cardinal directions only. The assessment of the delineation margin was undertaken by comparing the encompassment of the observer volumes by the target volume with added margin. The extra, presumed healthy tissue included in the margin and the malignant tissue missed by the margin were determined. The proposed delineation margin is effective at accounting for inter-observer variation, producing >95% coverage of all CTVs for polar, spherical, and Cartesian margins in 82%, 79%, and 92% of cases, respectively. Additionally, <1% malignant tissue was missed for 65%, 70%, and 91% of cases and <37% healthy tissue was included in 95%, 89%, and 97% of cases. A conventional delineation margin approach is most appropriate for small and gold standard target volumes. However, for large target volumes, an anisotropic margin is necessary, producing significantly greater coverage of CTVs, including significantly less presumed healthy tissue and missing significantly less malignant tissue. All delineation margin methods that account for target volume and laterality proved to be adequate, with appropriate encompassment of interobserver variation and minimal inclusion of extra excess healthy tissue and exclusion of possible malignant tissue. The anisotropic approach was found to be superior to a conventional approach for target volumes >1400 cm3 only with significantly greater encompassment of interobserver variation, less missed malignant tissue and less included healthy tissue. This methodology has been validated for a whole breast radiotherapy cohort as a proof of concept, however could be applied to other anatomical sites.","subset":"pubmed_abstract"} +{"meta":{"pmid":15829810,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Flipped scleral flap surgery for reduction of ocular pigmentation in oculodermal melanosis.\nTo report on surgical reduction of oculodermal melanosis in 6 patients presenting with severe episcleral pigmentation. After informed consent was obtained, surgical reduction of ocular pigmentation with ocular dermal melanosis was performed on 3 children, 2 girls and 1 boy male, who were cosmetically handicapped. After conjunctival peritomy, rectangular scleral free flaps were created using lamellar dissection, usually in the nasal or temporal quadrants. The rectangles extended from just posterior to the rectus muscle insertion. These free flaps were flipped over and reattached to the scleral bed, hiding the episcleral pigmentation internally and resulting in a less pigmented surface being visible. The superficial scleral nevus and the nevus adjacent to the limbus were peeled using a blade. In all cases, episcleral pigmentation was reduced with satisfactory cosmetic improvement, but mild scleral pigmentation and conjunctival scarring remained. During the 37-month mean follow-up period, no complications were observed. Patients with oculodermal melanosis often complain of globe pigmentation as well as face pigmentation. Serial follow-up was needed because some reports indicate development of choroidal melanoma occurs in oculodermal melanosis. To the best of our knowledge, this is the first report of successful surgical reduction of ocular pigmentation in oculodermal melanosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":32264332,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-14":1,"2022-27":1,"2022-05":1,"2019-43":1,"2018-47":1,"2018-30":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-34":3,"2023-40":1}}},"text":"Hyperbranched polyesters as biodegradable and antibacterial additives.\nHerein, we present novel hyperbranched poly(amino-ester)s functionalized with quaternary ammonium salts (QAS-HPAEs). These materials can be used as antibacterial and biodegradable additives for mixing with non-active polymers. The chemical structure and thermal properties of the HPAEs were studied. All QAS-HPAEs were stable until 192 \u00b0C, which makes their thermal blending with other polymers possible. Blending polycaprolactone (PCL) as a biodegradable polymer with QAS-HPAEs improved its surface and bulk hydrophilicity, while partially decreasing its elastic modulus and tensile strength. Mixing 10 wt% of QAS-HPAEs in PCL resulted in a film with high contact-killing activity against E. coli and B. subtilis and faster degradability in the presence and absence of esterase. The activity of esterase was inhibited in the presence of a higher content of QAS-HPAEs (20 wt%).","subset":"pubmed_abstract"} +{"meta":{"pmid":7919129,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-10":1,"2018-17":2,"2018-05":2,"2022-49":1,"2024-10":1}}},"text":"Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody and the protein-bound polysaccharide PSK in mice bearing a human cancer cell line.\nThe antitumor effects of a monoclonal antibody against a human cancer cell line and a protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined. The IgG2a monoclonal antibody against the human colon cancer cell line colo 205 induced in vitro antibody-dependent macrophage-mediated cytotoxicity against the cancer cells, but only slightly suppressed the in vivo growth of the cancer cells. Concurrent use of PSK with the antibody enhanced the in vitro antibody-dependent macrophage-mediated cytotoxicity as well as the in vivo antitumor activity. These findings suggest that the combined use of a monoclonal antibody and PSK, which have different modes of action, may be useful in the treatment of cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":26076376,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"FlexiQule (Boswellia extract) in the supplementary management of osteoarthritis: a supplement registry.\nThe aim of the present pilot, registry study was an assessment in a supplement study of FlexiQule (standardized Boswellia extract) capsules in the supplementary management of patients with symptomatic knee osteoarthritis (OA) also treated with the \"standard management\" (SM) in comparison with a group of patients only managed with SM. This 4-week study included patients with symptomatic knee arthrosis (X-ray). Registry subjects were able to perform a treadmill walking test and to understand questions from the WOMAC questionnaire. Exclusion criteria were conditions requiring drug treatment, Body Mass Index >25, metabolic disorders, surgery within three months prior to inclusion, oncological condition or inability to walk. Twenty-seven registry subjects using the supplement+SM and 28 using only SM completed the registry; at inclusion, the two groups were comparable including Karnofsky scale, WOMAC Score and the Treadmill Test. Of the subjects completing the registry 24 preferred to use the combination SM and the supplement. Safety evaluation: no problems - indicating the suspension of the supplementation \u2011 were observed. Routine blood tests were normal at inclusion and did not significantly vary at 4 weeks. The Karnofski Scale at 4 weeks was improved in both groups: from 74.3;3.1 to 88.9;5.3 (P<0.05) in the Boswellia group in comparison with a variation from 75.3;5.2 to 79.4;3.3 (P<0.05) in the SM. The effects of the supplement were significantly higher (P<0.05). The WOMAC Score was decreased significantly more in the supplement+SM group in comparison with controls considering pain, stiffness and physical functions (P<0.05). Social\/emotional functions improved better with the supplement (P<0.05). Both groups improved their walking distance at 4 weeks. The improvement was higher (P<0.05) in the Boswellia group. The need for other drugs or tests during the registry period was reduced more in the supplement group (P<0.05). The difference between SM and the supplementation associated to SM was significant) in favor of the supplementation with Boswellia for all target measurements evaluated in the registry at 4 weeks.","subset":"pubmed_abstract"} +{"meta":{"pmid":18253988,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2024-22":3,"unknown":8}}},"text":"Chest radiograph in acute respiratory infections.\nChest radiography is widely used during the management of acute lower respiratory infections, but the benefits are unknown. To assess the effects of chest radiography on clinical outcome in acute lower respiratory infections. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1950 to January 2007) and EMBASE (January 1976 to February 2007). Randomised or quasi-randomised trials of chest radiography in acute respiratory infections. Both review authors independently applied the inclusion criteria, extracted data and assessed trial quality. We identified two trials. One, of 522 outpatient children (and performed by the review authors), found that 46% of both radiography and control participants had recovered by seven days (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.31). Thirty-three per cent of radiography participants and 32% of control participants made a subsequent hospital visit within four weeks (RR 1.02, 95% CI 0.79 to 1.30) and 3% of both radiography and control participants were subsequently admitted to hospital within four weeks (RR 1.02, 95% CI 0.41 to 2.52). The other trial involving 1502 adults attending an emergency department found no significant difference in length of illness, the single outcome prespecified for this review (mean of 16.9 days in radiograph group versus 17.0 days in control group, P > 0.05). There is no evidence that chest radiography improves outcome in outpatients with acute lower respiratory infection. The findings do not exclude a potential effect of radiography, but the potential benefit needs to be balanced against the hazards and expense of chest radiography. The findings apply to outpatients only.","subset":"pubmed_abstract"} +{"meta":{"pmid":30034686,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2022-21":1,"2021-10":2,"2021-04":1,"2020-40":1,"2020-24":1,"2019-18":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-06":1}}},"text":"Crystal engineering of a family of hybrid ultramicroporous materials based upon interpenetration and dichromate linkers.\nA new family of 2-fold interpenetrated primitive cubic (pcu) networks of formula [M(L)2(Cr2O7)] n (M = Co2+, Ni2+, Cu2+ and Zn2+; L = 4,4'-azopyridine), DICRO-3-M-i, has been synthesised and their structures, permanent porosity and gas sorption properties were comprehensively characterised. Molecular simulations indicate that CO2 molecules occupy both of the two distinct ultramicropores that run through this isostructural series. The orientation of the Cr2O72- pillars is thought to contribute to high isosteric enthalpy of adsorption (Qst) towards CO2 and temperature programmed desorption experiments reveal that DICRO-3-Ni-i selectively adsorbs CO2 from gas mixtures that simulate flue gas. Performance in this context is among the highest for physisorbents measured to date and these materials are readily regenerated at 50 \u00b0C.","subset":"pubmed_abstract"} +{"meta":{"pmid":18006737,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Mobile robots: motor challenges and materials solutions.\nBolted-down robots labor in our factories, performing the same task over and over again. Where are the robots that run and jump? Equaling human performance is very difficult for many reasons, including the basic challenge of demonstrating motors and transmissions that efficiently match the power per unit mass of muscle. In order to exceed animal agility, new actuators are needed. Materials that change dimension in response to applied voltage, so-called artificial muscle technologies, outperform muscle in most respects and so provide a promising means of improving robots. In the longer term, robots powered by atomically perfect fibers will outrun us all.","subset":"pubmed_abstract"} +{"meta":{"pmid":28754723,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":3,"unknown":14}}},"text":"A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis.\nThe chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B\/Ipl1 in association with its activator (INCENP\/Sli15) and two additional proteins (Survivin\/Bir1 and Borealin\/Nbl1). Here, we report a genome-wide genetic interaction screen in Saccharomyces cerevisiae using the bir1-17 mutant, identifying through quantitative fitness analysis deletion mutations that act as enhancers and suppressors. Gene knockouts affecting the Ctf19 kinetochore complex were identified as the strongest enhancers of bir1-17, while mutations affecting the large ribosomal subunit or the mRNA nonsense-mediated decay pathway caused strong phenotypic suppression. Thus, cells lacking a functional Ctf19 complex become highly dependent on Bir1 function and vice versa. The negative genetic interaction profiles of bir1-17 and the cohesin mutant mcd1-1 showed considerable overlap, underlining the strong functional connection between sister chromatid cohesion and chromosome biorientation. Loss of some Ctf19 components, such as Iml3 or Chl4, impacted differentially on bir1-17 compared with mutations affecting other CPC components: despite the synthetic lethality shown by either iml3\u2206 or chl4\u2206 in combination with bir1-17, neither gene knockout showed any genetic interaction with either ipl1-321 or sli15-3 Our data therefore imply a specific functional connection between the Ctf19 complex and Bir1 that is not shared with Ipl1.","subset":"pubmed_abstract"} +{"meta":{"pmid":30035448,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-22":1,"unknown":11}}},"text":"[Between old and new targets: blood pressure control in hypertensive outpatients].\nIn developed countries, blood pressure (BP) control has increased over the past few decades and is now approaching 70% of patients. Herewith we report the results of a cross-sectional study carried out on hypertensive outpatients. In a cohort of 1,412 consecutive hypertensive outpatients (790 females, 622 males; mean age: 60.3\u00b112.2 years) evaluated from January 2015 to December 2016, the following parameters were assessed: age, gender, body mass index (BMI), waist circumference (WC), smoking habits, BP in the sitting position, estimated glomerular filtration rate (eGFR), serum glucose, lipid profile, antihypertensive drugs prescribed. In agreement with the European guidelines, hypertension was defined as sitting BP \u2265140\/90 mmHg or use of antihypertensive drugs. Patients whose BP was <140\/90 mmHg were considered as having achieved BP control. Furthermore, in compliance with the redefinition of hypertension suggested by the American College of Cardiology\/American Heart Association (ACC\/AHA), a second level of BP control (BP <130\/80 mmHg) was evaluated. Overall, 75.7% of hypertensive patients achieved BP levels <140\/90 mmHg, while 50.5% achieved BP levels <130\/80 mmHg. In both contexts, compared with patients whose BP was not controlled, those achieving the BP targets were mainly younger and females with a lower prevalence of obesity, diabetes and chronic kidney disease. Furthermore, they also had a lower WC and a higher eGFR. Nearly 76% of patients achieved the BP target of <140\/90 mmHg, a result which is higher than the 70% achieved in Europe, and 50.6% achieved that of <130\/80 mmHg, a result which is slightly higher than the 47% recently reported in USA.","subset":"pubmed_abstract"} +{"meta":{"pmid":17651490,"dup_signals":{"dup_doc_count":30,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2022-21":1,"2020-40":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":1,"2014-15":2,"2023-14":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-10":1}}},"text":"A systematic review on the impact of leg ulceration on patients' quality of life.\nA systematic review was conducted to analyse journal articles that describe or measure the impact of leg ulceration on patients' quality of life (QoL) in order to improve the content of an educational programme that aims to enhance self-care agency in leg ulcer patients. Original articles published in English and German between 1990 and 2006 were included if the findings were analysed at the level of patients. Articles were excluded if (1) they investigated the impact of specific treatments or settings on QoL or (2) focused mainly on arterial ulcers or diabetic foot ulcers. Twenty-four original research articles met the inclusion criteria; 11 studies used a quantitative, 11 studies a qualitative, and 2 used a mixed method approach. The findings were collapsed into 5 core domains. Quantitative studies commonly investigated the parameters of pain, sleep, social isolation, and physical mobility. Patients had significantly more pain, more restrictions regarding social functioning, less vitality, and limitations with respect to emotional roles compared to the respective controls. Other problem areas identified were restrictions in work capacity, recreation, social interaction, psychological well-being, as well as problems caused by treatment regimes. Inconclusive results were obtained regarding pain intensity, physical restrictions, and gender effects. Numerous original studies neither undertook a differentiation of participants by ulcer aetiology nor did they analyse the results according to gender differences. As leg ulceration has an impact on QoL, national guidelines on the treatment of leg ulceration need to more specifically address these far-ranging effects identified in this review.","subset":"pubmed_abstract"} +{"meta":{"pmid":16510630,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Dimensions of the local health care environment and use of care by uninsured children in rural and urban areas.\nDespite concerted policy efforts, a sizeable percentage of children lack health insurance coverage. This article examines the impact of the health care safety net and health care market structure on the use of health care by uninsured children. We used the Medical Expenditure Panel Survey linked with data from multiple sources to analyze health care utilization among uninsured children. We ran analyses separately for children who lived in rural and urban areas and assessed the effects on utilization of the availability of safety net providers, safety net funding, supply of primary care physicians, health maintenance organization penetration, and the percentage of people who are uninsured, controlling for other factors that influence use. Fewer than half of uninsured children had office-based visits to health care providers during the year, 8% of rural and 10% of urban children visited the emergency department at least once, and just over half of children had medical expenditures or charges during the year. Among uninsured children in rural areas, living closer to a safety net provider and living in an area with a higher supply of primary care physicians were positively associated with higher use and medical expenditures. In urban areas, the supply of primary care physicians and the level of safety net funding were positively associated with uninsured children's medical expenditures, whereas the percentage of the population that was uninsured was negatively associated with use of the emergency department. Uninsured children had low levels of utilization over a range of different health care provider types and settings. The availability of safety net providers in the local area and the safety net's capacity to serve the uninsured influence access to care among children. Possible measures for ensuring access to health care among uninsured children include increasing the density of safety net providers in rural areas, enhancing funding for the safety net, and policies to increase primary care physician supply.","subset":"pubmed_abstract"} +{"meta":{"pmid":21299793,"dup_signals":{"dup_doc_count":26,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-10":2,"2020-24":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2024-18":1,"2024-30":1}}},"text":"A systematic review of dermal fillers for age-related lines and wrinkles.\nDermal fillers are gaining popularity for rapid aesthetic improvement. Long-term efficacy and safety have not been well documented. The aim of this systematic review was to assess the safety and efficacy of injectable dermal fillers compared with other facial augmentation techniques for the management of age-related lines and wrinkles. Studies including patients receiving injectable semi-permanent or permanent dermal fillers for age-related lines and wrinkles were included in this review. Efficacy outcomes (including changes in skin thickness and patient satisfaction) and safety outcomes (including mortality, lumps and infections) were examined. Three randomized control trials and six case series were included. Permanent and semi-permanent dermal fillers improved subjective ratings of appearance and resulted in higher patient satisfaction than temporary fillers. Long-term efficacy appeared good in the few studies that reported it. Short-term safety appeared favourable. Lumps were reported in all but one study but received little follow-up. Long-term safety data were limited. The treatment of age-related lines and wrinkles with permanent and semi-permanent dermal fillers is more efficacious compared with temporary fillers in those studies that compared them. Case series evidence suggests that these fillers achieve their objective, which is to decrease the visible effects of age-related changes. These fillers appear at least as safe as temporary fillers in the short term in those studies that compared them. Long-term safety could not be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":6654468,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Effects of anterior hypothalamic disconnection on the evolution of Goldblatt renal hypertension. A dual response.\nThe role of the central nervous system, in general, and of the hypothalamus, in particular, in the genesis of various forms of experimental hypertension has been the object of increased investigation. Lesions of the anteroventral area of the third ventricle (AV3V) in rats seem to block the development of various forms of hypertension. In the present experiments, AV3V was kept intact but its connections with the caudal neuroaxis were severed by means of a curved knife (2 mm radius), stereotaxically placed at the level of the arcuate nucleus. This disconnection, per se, induces polydipsia, and a reduction of the pressor effect of i.v.-infused angiotensin II. The interactions of simultaneously performed hypothalamic disconnection (HD) and Goldblatt one-kidney, one clip, (1K1C) or two-kidney, one clip (2K1C) hypertensions was studied. It was found that HD retards and attenuates the development of 1K1C hypertension but does not materially affect the evolution of the 2K1C model. Rats with established 1K1C or 2K1C hypertensions were not affected by HD, whereas rats with chronic HD (4 weeks) showed slight and slow developing hypertension in response to clipping. The possible significance of these results with respect to the neural connections of AV3V is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26849405,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line.\nOver the past several years, investigations in both low-dose hyper-radiosensitivity and increased radioresistance have been a focus of radiation oncology and biology research, since both conditions occur primarily in tumor cell lines. There has been significant progress in elucidating their signaling pathways, however uncertainties exist when they are studied together with radiation-induced bystander effects. Therefore, the aim of this work was to further investigate this relationship using the T98G glioma and HaCaT cell lines. T98G glioma cells have demonstrated a strong transition from hyper-radiosensitivity to induced radioresistance, and HaCaT cells do not show low-dose hypersensitivity. Both cell lines were paired using a mix-and-match protocol, which involved growing nonirradiated cells in culture media from irradiated cells and covering all possible combinations between them. The end points analyzed were clonogenic cell survival and live calcium measurements through the cellular membrane. Our data demonstrated that T98G cells produced bystander signals that decreased the survival of both reporter T98G and HaCaT cells. The bystander effect occurred only when T98G cells were exposed to doses below 1 Gy, which was corroborated by the induction of calcium fluxes. However, when bystander signals originated from HaCaT cells, the survival fraction increased in reporter T98G cells while it decreased in HaCaT cells. Moreover, the corresponding calcium data showed no calcium fluxes in T98G cells, while HaCaT cells displayed a biphasic calcium profile. In conclusion, our findings indicate a possible link between low-dose hyper-radiosensitivity and bystander effects. This relationship varies depending on which cell line functions as the source of bystander signals. This further suggests that the bystander mechanisms are more complex than previously expected and caution should be taken when extrapolating bystander results across all cell lines and all radiation doses.","subset":"pubmed_abstract"} +{"meta":{"pmid":22262460,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":10}}},"text":"A secreted MMP is required for reepithelialization during wound healing.\nMatrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaster, whose genome encodes only two MMPs-one secreted type (Mmp1) and one membrane-anchored type (Mmp2)-to study the function and regulation of the secreted class of MMPs in vivo. In the absence of redundancy, we found that the Drosophila secreted MMP, Mmp1, is required in the epidermis to facilitate reepithelialization by remodeling the basement membrane, promoting cell elongation and actin cytoskeletal reorganization, and activating extracellular signal-regulated kinase signaling. In addition, we report that the jun N-terminal kinase (JNK) pathway upregulates Mmp1 expression after wounding, but that Mmp1 is expressed independent of the JNK pathway in unwounded epidermis. When the JNK pathway is ectopically activated to overexpress Mmp1, the rate of healing is accelerated in an Mmp1-dependent manner. A primary function of Mmp1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue.","subset":"pubmed_abstract"} +{"meta":{"pmid":16513003,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":14}}},"text":"Single-dose levodopa administration and aging independently disrupt time production.\nWe tested the hypothesis that age-related time production deficits are dopamine-mediated. The experiment was conducted double-blind, and with random assignment of 32 healthy aged and 32 healthy young participants to either inert placebo or levodopa (200 mg) groups. The procedure included training participants to produce two target time intervals (6 and 17 sec) in separate blocks, drug\/placebo administration, a 1-hr delay, and then delayed free-recall time production retesting without feedback. Participants also performed a speeded choice reaction time (RT) task, as a control for potential dopaminergic and aging effects on attention and psychomotor speed. Results indicate that during retesting, aged participants show duration-dependent timing errors that are larger than those shown by the young participants. Levodopa administration yielded lengthened time production of both target intervals. The aging and levodopa effects did not interact. Also, aging slowed RT and increased RT variability, but levodopa had no effect on the RT. These results suggest that at this dosage and under these specific conditions, timing is dopamine-mediated but the effect of aging on time production is not. Moreover, the levodopa timing effect cannot be attributed to the effects of dopaminergic function on psychomotor speed.","subset":"pubmed_abstract"} +{"meta":{"pmid":15909148,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-14":3,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":2,"2021-21":1,"2021-10":1,"2020-50":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-22":1}}},"text":"The formation and patterning of leaves: recent advances.\nLeaves, the plant's major photosynthetic organs, form through the activity of groups of pluripotent cells, termed shoot apical meristems (SAMs), located at the growing tips of plants. Leaves develop with a dorso-ventral asymmetry, with the adaxial surface adjacent to the meristem and the abaxial surface developing at a distance from it. Molecular genetic studies have shown that the correct specification of adaxial\/abaxial polarity requires communication between the incipient leaf and the meristem, and that the juxtaposition of adaxial\/abaxial fates is necessary for lamina outgrowth (Waites and Hudson 1995; McConnell et al. 2001). Over the last few years, a number of factors that control cell fate specification in the apex have been identified. This review will focus on recent advances on distinct but overlapping aspects of leaf development, namely, the transition from meristem to leaf fate and the specification of abaxial\/adaxial polarity and its possible role in leaf growth.","subset":"pubmed_abstract"} +{"meta":{"pmid":24491520,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2020-24":2,"2020-05":1,"2019-43":1,"2019-35":2,"2019-09":2,"2019-04":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-34":2,"2018-22":1,"2018-13":1,"2017-39":1}}},"text":"A longitudinal study of gait function and characteristics of gait disturbance in individuals with Alzheimer's disease.\nWalking in daily life places high demands on the interplay between cognitive and motor functions. A well-functioning dual-tasking ability is thus essential for walking safely. The aims were to study longitudinal changes in gait function during single- and dual-tasking over a period of two years among people with initially mild AD (n=21). Data were collected on three occasions, twelve months apart. An optical motion capture system was used for three-dimensional gait analysis. Gait parameters were examined at comfortable gait speed during single-tasking, dual-tasking naming names, and naming animals. The dual-task cost for gait speed was pronounced at baseline (names 26%, animals 35%), and remained so during the study period. A significant (p<0.05) longitudinal decline in gait speed and step length during single- and dual-tasking was observed, whereas double support time, step width and step height showed inconsistent results. Systematic visual examination of the motion capture files revealed that dual-tasking frequently resulted in gait disturbances. Three main characteristics of such disturbances were identified: Temporal disturbance, Spatial disturbance and Instability in single stance. These aberrant gait performances may affect gait stability and increase the risk of falling. Furthermore, the observed gait disturbances can contribute to understanding and explaining previous reported gait variability among individuals with AD. However, the role that dual-task testing and aberrant dual-task gait performance play in the identification of individuals with early signs of cognitive impairment and in predicting fall risk in AD remains to be studied.","subset":"pubmed_abstract"} +{"meta":{"pmid":20826077,"dup_signals":{"dup_doc_count":30,"dup_dump_count":25,"dup_details":{"curated_sources":1,"2023-14":1,"2022-21":1,"2021-21":1,"2021-10":1,"2020-40":1,"2020-34":1,"2020-29":2,"2020-16":2,"2020-05":2,"2019-51":1,"2019-43":1,"2019-39":2,"2019-30":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-23":1}}},"text":"Slow wave sleep deficits as a trait marker in patients with schizophrenia.\nAmong the sleep abnormalities found in schizophrenia, slow wave sleep deficits have been found to persist even after the resolution of active psychotic symptoms. Further, such abnormalities are observed in young healthy individuals at high risk of schizophrenia, which suggest that slow wave sleep deficits might be trait marker in schizophrenia. Sleep EEG was recorded in 20 right handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14 first degree relatives and 20 age and sex matched controls. Patients were rated on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) for assessment of psychopathology. There was significant difference between the three groups in total sleep period (p<.01), total sleep time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant positive correlation of REM percentage of total sleep time with BPRS total score (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas significant negative correlation of REM latency was found with BPRS total score (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the patients. Slow wave sleep deficits are a possible trait marker in patients with schizophrenia, which needs replication in further studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":24731950,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Polyploidy and hybridization as main factors of speciation: complex reticulate evolution within the grass genus Helictochloa.\nTo study the origin and evolution of naturally occurring polyploids, we performed phylogenetic analyses of nuclear ribosomal DNA spacers combined with molecular cytogenetics in 55 accessions of 27 taxa of the oat genus Helictochloa. A complex pattern of reticulate evolution was revealed with many diploid species and extensive polyploidy up to 20x. Altogether 11 groups of internal transcribed spacer (ITS) sequences can be distinguished. Sequences from 1-3 different ITS lineages were detected in polyploids. Cytogenetic data allow reconstruction of 8 basic monoploid chromosome sets. Six of these genomes occur in different combinations in the polyploid species. Two genomes are only found in diploids. Our sequence and karyological data highlight the occurrence of autopolyploidy and allopolyploidy, provide new information about the evolutionary history of taxa, and allow a more accurate systematic treatment of the concerned species. The geographical distribution of the 11 ITS lineages distinguished is highly structured and points to an origin of the genus in western Asia, presumably in grasslands like steppes or mountain steppes and meadows. The evolutionary basal lineages are of Asian, Minor Asian and east Mediterranean distribution and are present also in North America. The western and central parts of the Mediterranean and northern Europe harbor the modern lineages.","subset":"pubmed_abstract"} +{"meta":{"pmid":9788621,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":3,"unknown":11}}},"text":"Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes.\nTransgenic mice expressing the oncogene SV40 T antigen (Tag) in the insulin-producing beta cells of the pancreas develop islet cell carcinomas. Expression of the oncogene beginning in adult life leads to autoimmunity and lymphocytic infiltration of premalignant lesions. Nevertheless, Tag-expressing solid tumors escape the immune surveillance and are devoid of infiltrating lymphocytes. Attempting to elicit a tumor inflammatory response, we have both expressed a potent costimulator in oncogene-expressing beta cells and increased the abundance of reactive T cells. Coexpression of the costimulator B7.1 and the Tag oncoprotein leads to destruction of normal and premalignant islets and severe diabetes. Nevertheless, Tag+ tumors eventually develop, evidencing significantly reduced B7.1 expression and no infiltration. Another approach, whereby the abundance of reactive T cells was increased in double transgenic mice expressing Tag and a Tag-specific, CD4+-restricted T-cell receptor, was similarly unable to elicit tumor infiltration and destruction. Thus, neither costimulatory tumor cells nor hyperactivated antitumor lymphocytes were sufficient to produce an effective tumor immune response. In contrast, adoptive transfer of lymphocytes activated ex vivo did result in modest tumor infiltration with a limited induction of high endothelial venules on tumor vasculature, provided that T cells were transferred into irradiated recipients. However, adoptive transfer of ex vivo activated lymphocytes did not produce the dramatic inflammation seen in premalignant lesions. Thus, in addition to the parameters of activation and abundance of antitumor lymphocytes, the tumor microenvironment is evidently a critical parameter that can suppress lymphocyte extravasation and\/or function inside tumors, likely in part via distinctive properties of the tumor vasculature.","subset":"pubmed_abstract"} +{"meta":{"pmid":19053351,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Dimensional caging of polyiodides.\nTwo series of iodide and polyiodide chain structures have been synthesized through the employment of secondary interactions between polycation, long-chain, hydrocarbon cations. These compounds represent examples of crystal engineering, employing a simple strategy of synthesis. The two series are related, and the capacity to incorporate polyiodide ions dependent on the length of the hydrocarbon chains is indicated.","subset":"pubmed_abstract"} +{"meta":{"pmid":23801823,"dup_signals":{"dup_doc_count":23,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-10":4,"2019-39":4,"2019-35":2,"2019-18":1,"2018-47":1,"2018-26":1,"2017-47":1,"2023-50":1,"2024-22":3,"2024-18":1}}},"text":"International comparison of treatment and long-term outcomes for acute myocardial infarction in the elderly: Minneapolis\/St. Paul, MN, USA and Goteborg, Sweden.\nInternational studies provide an opportunity to compare treatment approaches and outcomes. The present study compares elderly hospitalized acute myocardial infarction (AMI) patients in Minneapolis\/St. Paul, USA (MSP) and G\u00f6teborg, Sweden (GB). A population-based sample of hospitalized AMI (ICD-9 410) patients aged \u226575 in MSP and GB in 2001-02 was abstracted by trained nurses. Mortality was ascertained from medical records and death certificates. Demographics, cardiovascular procedures, and prescription medications were compared using sex-specific generalized linear models. Adjusted hazard ratios (HR) were calculated with Cox regression. In MSP 839 (387 men, 452 women) and in GB 564 (275 men, 289 women) patients were identified. Age was similar (men: MSP 83 \u00b1 7, GB 82 \u00b1 5; women: MSP 84 \u00b1 6, GB 84 \u00b1 6) yet MSP patients had more previous cardiovascular comorbidities and procedures (PCI\/CABG). Guideline-based medication use was high in both locations. MSP patients were significantly more likely to undergo PCI (men: MSP 33%, GB 7%; women: MSP 30%, GB 7%). Survival at 7.5 years was 27.8% among MSP patients (men: 26.6%, women: 28.8%) and 17.2% among GB patients (men: 17.5%, women: 17.0%). After adjustment for baseline characteristics and guideline-based therapies, survival was higher among MSP men [HR: 0.66, 95% confidence interval (CI): 0.50-0.88] and women (HR: 0.49, 95% CI: 0.36-0.67) compared with GB. In MSP and GB, guideline-based therapy use was high. However, PCI use was markedly higher in MSP. Long-term survival was better among elderly men and women in MSP compared with GB possibly related to greater utilization of PCI.","subset":"pubmed_abstract"} +{"meta":{"pmid":22977225,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study.\nAtrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice. We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height. Independent from sex, increased height is significantly associated with the risk of AF.","subset":"pubmed_abstract"} +{"meta":{"pmid":17582092,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Ultrafiltered milk reduces bitterness in reduced-fat Cheddar cheese made with an exopolysaccharide-producing culture.\nThe objectives were to reduce bitterness in reduced-fat Cheddar cheese made with an exopolysaccharide (EPS)-producing culture and study relationships among ultra-filtration (UF), residual chymosin activity (RCA), and cheese bitterness. In previous studies, EPS-producing cultures improved the textural, melting, and viscoelastic properties of reduced-fat Cheddar cheese. However, the EPS-positive cheese developed bitterness after 2 to 3 mo of ripening due to increased RCA. We hypothesized that the reduced amount of chymosin needed to coagulate UF milk might result in reduced RCA and bitterness in cheese. Reduced-fat Cheddar cheeses were manufactured with EPS-producing and nonproducing cultures using skim milk or UF milk (1.2x) adjusted to a casein:fat ratio of 1.35. The EPS-producing culture increased moisture and RCA in reduced-fat Cheddar cheese. Lower RCA was found in cheese made from UF milk compared with that in cheese made from control milk. Ultrafiltration at a low concentration rate (1.2x) produced EPS-positive, reduced-fat cheese with similar RCA to that in the EPS-negative cheese. Slower proteolysis was observed in UF cheeses compared with non-UF cheeses. Panelists reported that UF EPS-positive cheese was less bitter than EPS-positive cheese made from control milk. This study showed that UF at a low concentration factor (1.2x) could successfully reduce bitterness in cheese containing a high moisture level. Because this technology reduced the RCA level (per g of protein) to a level similar to that in the control cheeses, the contribution of chymosin to cheese proteolysis would be similar in both cheeses.","subset":"pubmed_abstract"} +{"meta":{"pmid":25870160,"dup_signals":{"dup_doc_count":11}},"text":"Do bimanual coordination, tool use, and body posture contribute equally to hand preferences in bonobos?\nApproximately 90% of the human population is right-handed. The emergence of this hand preference in humans is thought to be linked to the ability to execute complex tasks and habitual bipedalism. In order to test these hypotheses, the present study explored, for the first time, hand preference in relation to both body posture (seated and bipedal) and task complexity (bimanual coordination and two tool use tasks of different complexity) in bonobos (Pan paniscus). Few studies have explored the effects of both posture and task complexity on handedness, and investigations with bonobos are scarce, particularly studies on tool use. Our study aims to overcome such a gap by addressing two main questions: 1) Does a bipedal posture increase the strength of hand preference and\/or create a directional bias to the use of the right hand? 2) Independent of body posture, does task complexity increase the strength of the hand preference and\/or create a directional bias to the use of the right hand? Our results show that independent of body posture, the more complex the task, the more lateralization occurred. Moreover, subjects tended to be right-handed for tasks involving tool use. However, posture had no significant effect on hand preference in the tasks tested here. Therefore, for a given task, bonobos were not more lateralized in a bipedal posture than in a seated one. Task complexity might thus have contributed more than bipedal posture to the emergence of human lateralization and the preponderance of right-handedness, although a larger sample size and more data are needed to be conclusive.","subset":"pubmed_abstract"} +{"meta":{"pmid":8987358,"dup_signals":{"dup_doc_count":46,"dup_dump_count":25,"dup_details":{"curated_sources":6,"2021-10":1,"2020-50":1,"2020-45":1,"2020-40":2,"2020-34":2,"2020-29":1,"2020-24":3,"2020-16":3,"2020-10":1,"2020-05":4,"2019-51":2,"2019-43":2,"2019-39":2,"2019-35":1,"2019-30":1,"2019-18":2,"2019-13":2,"2019-04":1,"2018-47":2,"2016-07":1,"2015-35":1,"2015-32":1,"2014-23":1,"2021-21":1,"2014-10":1}}},"text":"Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS, N2O, and NO).\nProduction and consumption processes in soils contribute to the global cycles of many trace gases (CH4, CO, OCS, H2, N2O, and NO) that are relevant for atmospheric chemistry and climate. Soil microbial processes contribute substantially to the budgets of atmospheric trace gases. The flux of trace gases between soil and atmosphere is usually the result of simultaneously operating production and consumption processes in soil: The relevant processes are not yet proven with absolute certainty, but the following are likely for trace gas consumption: H2 oxidation by abiontic soil enzymes; CO cooxidation by the ammonium monooxygenase of nitrifying bacteria; CH4 oxidation by unknown methanotrophic bacteria that utilize CH4 for growth; OCS hydrolysis by bacteria containing carbonic anhydrase; N2O reduction to N2 by denitrifying bacteria; NO consumption by either reduction to N2O in denitrifiers or oxidation to nitrate in heterotrophic bacteria. Wetland soils, in contrast to upland soils are generally anoxic and thus support the production of trace gases (H2, CO, CH4, N2O, and NO) by anaerobic bacteria such as fermenters, methanogens, acetogens, sulfate reducers, and denitrifiers. Methane is the dominant gaseous product of anaerobic degradation of organic matter and is released into the atmosphere, whereas the other trace gases are only intermediates, which are mostly cycled within the anoxic habitat. A significant percentage of the produced methane is oxidized by methanotrophic bacteria at anoxic-oxic interfaces such as the soil surface and the root surface of aquatic plants that serve as conduits for O2 transport into and CH4 transport out of the wetland soils. The dominant production processes in upland soils are different from those in wetland soils and include H2 production by biological N2 fixation, CO production by chemical decomposition of soil organic matter, and NO and N2O production by nitrification and denitrification. The processes responsible for CH4 production in upland soils are completely unclear, as are the OCS production processes in general. A problem for future research is the attribution of trace gas metabolic processes not only to functional groups of microorganisms but also to particular taxa. Thus, it is completely unclear how important microbial diversity is for the control of trace gas flux at the ecosystem level. However, different microbial communities may be part of the reason for differences in trace gas metabolism, e.g., effects of nitrogen fertilizers on CH4 uptake by soil; decrease of CH4 production with decreasing temperature; or different rates and modes of NO and N2O production in different soils and under different conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":17986009,"dup_signals":{"dup_doc_count":41,"dup_dump_count":36,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-34":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-09":2,"2017-51":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2023-40":1,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Crystal structure of human DAAM1 formin homology 2 domain.\nReorganization of the actin filament is an essential process for cell motility, cell-cell attachment and intracellular transport. Formin proteins promote nucleation and elongation of the actin filament, and thus are key regulators for this process. The formin homology 2 (FH2) domain forms a head-to-tail ring-shaped dimer, and processively moves towards the barbed end. Dishevelled-associated activator of morphogenesis (DAAM) is a Rho-regulated formin implicated in neuronal development. Here, we present the crystal structure of human DAAM1 FH2 dimer at 2.8 A resolution. This is the first dimeric structure of the mammalian formin. The core structure of human DAAM1 is similar to those of mouse mDia1 and yeast Bni1p, whereas the orientations of the FH2 dimeric rings are different between human DAAM1 and yeast Bni1p, despite their similar dimer interactions. This difference supports the previous prediction that the dimer architecture of the formin is highly flexible in the actin-free state. The results of the actin assembly assays using the DAAM1 mutants demonstrated that the length of the linker connecting the N-terminal domain and the core region is crucial for the activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":27253322,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Interfacial rheometry of polymer at a water-oil interface by intra-pair magnetophoresis.\nWe describe an interfacial rheometry technique based on pairs of micrometer-sized magnetic particles at a fluid-fluid interface. The particles are repeatedly attracted and repelled by well-controlled magnetic dipole-dipole forces, so-called interfacial rheometry by intra-pair magnetophoresis (IPM). From the forces (\u223cpN), displacements (\u223c\u03bcm) and velocities (\u223c\u03bcm s(-1)) of the particles we are able to quantify the interfacial drag coefficient of particles within a few seconds and over very long timescales. The use of local dipole-dipole forces makes the system insensitive to fluid flow and suited for simultaneously recording many particles in parallel over a long period of time. We apply IPM to study the time-dependent adsorption of an oil-soluble amino-modified silicone polymer at a water-oil interface using carboxylated magnetic particles. At low polymer concentration the carboxylated particles remain on the water side of the water-oil interface, while at high polymer concentrations the particles transit into the oil phase. Both conditions show a drag coefficient that does not depend on time. However, at intermediate polymer concentrations data show an increase of the interfacial drag coefficient as a function of time, with an increase over more than three orders of magnitude (10(-7) to 10(-4) N s m(-1)), pointing to a strong polymer-polymer interaction at the interface. The time-dependence of the interfacial drag appears to be highly sensitive to the polymer concentration and to the ionic strength of the aqueous phase. We foresee that IPM will be a very convenient technique to study fluid-fluid interfaces for a broad range of materials systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":17310052,"dup_signals":{"dup_doc_count":13}},"text":"Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.\nUnderutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis prevents clinically important outcomes in hospitalized medical patients at risk for venous thromboembolism. To assess the effects of anticoagulant prophylaxis in reducing clinically important outcomes in hospitalized medical patients. MEDLINE, EMBASE, and Cochrane databases were searched to September 2006 without language restrictions. Randomized trials comparing anticoagulant prophylaxis with no treatment in hospitalized medical patients. Any symptomatic pulmonary embolism (PE), fatal PE, symptomatic deep venous thrombosis, all-cause mortality, and major bleeding. Pooled relative risks and associated 95% CIs were calculated. For treatment effects that were statistically significant, the authors determined the absolute risk reduction and the number needed to treat for benefit (NNT(B)) to prevent an outcome. 9 studies (n = 19 958) were included. During anticoagulant prophylaxis, patients had significant reductions in any PE (relative risk, 0.43 [CI, 0.26 to 0.71]; absolute risk reduction, 0.29%; NNT(B), 345) and fatal PE (relative risk, 0.38 [CI, 0.21 to 0.69]; absolute risk reduction, 0.25%; NNT(B), 400), a nonsignificant reduction in symptomatic deep venous thrombosis (relative risk, 0.47 [CI, 0.22 to 1.00]), and a nonsignificant increase in major bleeding (relative risk, 1.32 [CI, 0.73 to 2.37]). Anticoagulant prophylaxis had no effect on all-cause mortality (relative risk, 0.97 [CI, 0.79 to 1.19]). 2 of 9 included studies were not double-blind. Anticoagulant prophylaxis is effective in preventing symptomatic venous thromboembolism during anticoagulant prophylaxis in at-risk hospitalized medical patients. Additional research is needed to determine the risk for venous thromboembolism in these patients after prophylaxis has been stopped.","subset":"pubmed_abstract"} +{"meta":{"pmid":32845907,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":1,"2024-18":1,"unknown":7}}},"text":"Non-invasive prenatal testing (NIPT) by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions.\nTo study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi\/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes. We used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts. The in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples. Our results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening\/diagnostics procedure, however, accuracy and reliability depends on several specific factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":16043849,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The controlled-environment chamber: a new mouse model of dry eye.\nTo develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. Eight- to 12-week-old BALB\/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +\/- 5.1%, AF = 15 L\/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.","subset":"pubmed_abstract"} +{"meta":{"pmid":17348056,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Theoretical study of the reaction of vitamin B6 with 1O2.\nSinglet oxygen is known to cause oxidative stress in cells, leading to severe damage (e.g., lipid peroxidation, membrane degradation, mutagenic alterations to DNA, protein misfunctionality). Recently, pyridoxine has been discovered to be capable of quenching singlet oxygen, however, the mechanism of this reaction remains essentially unknown. In this work, we have investigated four sets of reactions: 1) 1,3-addition to a double bond connected to a hydrogen-carrying group, resulting in the formation of allylic hydroperoxides; 2) [pi2+pi2] 1,2-cycloaddition to an isolated double bond, resulting in the formation of 1,2-peroxides; 3) 1,4-cycloaddition to a system containing at least two conjugated double bonds, resulting in the formation of the so-called 1,4-peroxides; 4) 1,4-addition to phenols and naphthols with the formation of hydroperoxide ketones. Thermodynamically, reaction 4 and the 6(9), 3(8), and 5(8) cases of reaction 1 are the most exergonic ones, with energies ranging from -16 to -18 kcal mol(-1). Furthermore, reaction 4 shows the lowest barrier through the reaction path, and is predicted to be the preferred mechanism for the pyridoxine + singlet-oxygen reaction, which is in agreement with previous experimental results.","subset":"pubmed_abstract"} +{"meta":{"pmid":31461487,"dup_signals":{"dup_doc_count":23,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-30":1,"unknown":18}}},"text":"The economic burden of endoscopic treatment for anastomotic leaks following oncological Ivor Lewis esophagectomy.\nComplications after surgery for esophageal cancer are associated with significant resource utilization. The aim of this study was to analyze the economic burden of two frequently used endoscopic treatments for anastomotic leak management after esophageal surgery: Treatment with a Self-expanding Metal Stent (SEMS) and Endoscopic Vacuum Therapy (EVT). Between January 2012 and December 2016, we identified 60 German-Diagnosis Related Group (G-DRG) cases of patients who received a SEMS and \/ or EVT for esophageal anastomotic leaks. Direct costs per case were analyzed according to the Institute for Remuneration System in Hospitals (InEK) cost-accounting approach by comparing DRG payments on the case level, including all extra fees per DRG catalogue. In total, 60 DRG cases were identified. Of these, 15 patients were excluded because they received a combination of SEMS and EVT. Another 6 cases could not be included due to incomplete DRG data. Finally, N = 39 DRG cases were analyzed from a profit-center perspective. A further analysis of the most frequent DRG code -G03- including InEK cost accounting, revealed almost twice the deficit for the EVT group (N = 13 cases, \u20ac - 9.282 per average case) compared to that for the SEMS group (N = 9 cases, \u20ac - 5.156 per average case). Endoscopic treatments with SEMS and EVT for anastomotic leaks following oncological Ivor Lewis esophagectomies are not cost-efficient for German hospitals. Due to longer hospitalization and insufficient reimbursements, EVT is twice as costly as SEMS treatment. An adequate DRG cost compensation is needed for SEMS and EVT.","subset":"pubmed_abstract"} +{"meta":{"pmid":12684526,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":19}}},"text":"Dynamic imaging in living cells: windows into local signaling.\nHighly localized changes in intracellular calcium concentration [Ca2+]i play a critical role in regulating numerous cellular functions, ranging from muscle contraction to neurotransmitter and hormone secretion to gene transcription. Fluorescent Ca2+ indicators have been invaluable tools in elucidating the role of localized changes in [Ca2+]i in regulating ion channels and other key proteins in various signaling pathways. Other techniques used to investigate localized changes in [Ca2+]i include approaches based on fluorescence resonance energy transfer, and electrophysiological measurements of ionic flux through Ca2+-sensitive channels. This Perspective discusses research using fluorescent Ca2+ indicators to study excitation-contraction coupling in cardiac myocytes, presenting both key findings and limitations of this approach. Complementary approaches useful in studying localized changes in Ca2+ and other second messengers (such as cyclic adenosine monophosphate) are also discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":9007234,"dup_signals":{"dup_doc_count":31,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2021-39":1,"2020-45":1,"2020-34":1,"2020-29":1,"2020-10":1,"2020-05":1,"2019-43":2,"2019-39":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-47":1,"2017-43":1,"2017-34":2,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-49":1,"2017-13":1,"2024-10":1}}},"text":"Mutations affecting development of the notochord in zebrafish.\nThe notochord is critical for the normal development of vertebrate embryos. It serves both as the major skeletal element of the embryo and as a signaling source for the establishment of pattern within the neurectoderm, the paraxial mesoderm and other tissues. In a large-scale systematic screen of mutations affecting embryogenesis in zebrafish we identified 65 mutations that fall into 29 complementation groups, each leading to a defect in the formation and\/or maintenance of the notochord. These mutations produce phenotypic abnormalities at numerous stages of notochord development, thereby establishing a phenotypic pathway, which in turn suggests a genetic pathway for the development of the notochord. Perturbations within adjacent tissues in mutant embryos further indicate the importance of notochord-derived signals for patterning within the embryo and suggest that these mutations will yield additional insight into the cues that regulate these patterning processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":32680325,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Measurement Issues: Review of four patient reported outcome measures: SDQ, RCADS, C\/ORS and GBO - their strengths and limitations for clinical use and service evaluation.\nThere is an international drive for routine use of Patient Reported Outcome Measures (PROMs) across all health services including in relation to Child and Adolescent Mental Health Services (CAMHS). A number of reviews have summarized the validity and reliability of well-being and mental health measures for children but there are fewer attempts to consider utility for routine use. This review considers four child self-report measures: the Strengths and Difficulties Questionnaire (SDQ), the Revised Child Anxiety and Depression Scale (RCADS), (Child) Outcomes Rating Scale (C\/ORS) and Goals Based Outcomes (GBOs). It explores the strengths and limitations of each and considers how they can be used to support both clinical practice and service evaluation. There is evidence for the clinical utility of RCADS, C\/ORS and GBOs, although the utility of the SDQ as a feedback measure remains unclear. For service evaluation, the SDQ has the greatest evidence for norms making it useful for comparison and there is evidence that the RCADS may be the most sensitive to change of the measures reviewed; C\/ORS has issues around ceiling effect, data error and data manipulation. More research is required around GBOs before their use for service evaluation can be determined. In summary, these different measures may be viewed as complementary tools and determining the best way to make use of them severally and individually in clinical and community settings is a current focus for child mental health practitioners.","subset":"pubmed_abstract"} +{"meta":{"pmid":38009683,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children.\nAllergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16\u00b12.88 years old) and 51 healthy children (control group, 8.22\u00b13.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type (P = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group (P = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk (P < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.","subset":"pubmed_abstract"} +{"meta":{"pmid":12404079,"dup_signals":{"dup_doc_count":25,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2022-40":1,"2019-35":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-47":2,"2017-39":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2014-23":1,"2023-23":1}}},"text":"Orphanin FQ\/nociceptin blocks cocaine-induced behavioral sensitization in rats.\nOrphanin FQ\/nociceptin (OFQ\/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1-17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization. The present study was designed to examine the ability of OFQ\/N to block cocaine-induced behavioral sensitization. Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ\/N (15 nmol) followed by saline or cocaine (20 mg\/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ\/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg\/kg) in the absence of OFQ\/N on day 8. The specificity of OFQ\/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ\/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1-3. Finally, the effect of intra-VTA OFQ\/N administration on cocaine sensitization was examined. Sensitization did not develop in rats repeatedly treated with OFQ\/N, via either route of administration, prior to cocaine administration on days 1-3. The inhibitory effect of OFQ\/N was not dependent on context and was blocked by pretreatment with J-113397. Our results indicate that OFQ\/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ\/N.","subset":"pubmed_abstract"} +{"meta":{"pmid":30744031,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":17}}},"text":"PPCS: A Progressive Popularity-Aware Caching Scheme for Edge-Based Cache Redundancy Avoidance in Information-Centric Networks.\nThis article proposes a novel chunk-based caching scheme known as the Progressive Popularity-Aware Caching Scheme (PPCS) to improve content availability and eliminate the cache redundancy issue of Information-Centric Networking (ICN). Particularly, the proposal considers both entire-object caching and partial-progressive caching for popular and non-popular content objects, respectively. In the case that the content is not popular enough, PPCS first caches initial chunks of the content at the edge node and then progressively continues caching subsequent chunks at upstream Content Nodes (CNs) along the delivery path over time, according to the content popularity and each CN position. Therefore, PPCS efficiently avoids wasting cache space for storing on-path content duplicates and improves cache diversity by allowing no more than one replica of a specified content to be cached. To enable a complete ICN caching solution for communication networks, we also propose an autonomous replacement policy to optimize the cache utilization by maximizing the utility of each CN from caching content items. By simulation, we show that PPCS, utilizing edge-computing for the joint optimization of caching decision and replacement policies, considerably outperforms relevant existing ICN caching strategies in terms of latency (number of hops), cache redundancy, and content availability (hit rate), especially when the CN's cache size is small.","subset":"pubmed_abstract"} +{"meta":{"pmid":12799354,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-50":2,"2020-45":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2022-40":1}}},"text":"eVOC: a controlled vocabulary for unifying gene expression data.\nExpression data contribute significantly to the biological value of the sequenced human genome, providing extensive information about gene structure and the pattern of gene expression. ESTs, together with SAGE libraries and microarray experiment information, provide a broad and rich view of the transcriptome. However, it is difficult to perform large-scale expression mining of the data generated by these diverse experimental approaches. Not only is the data stored in disparate locations, but there is frequent ambiguity in the meaning of terms used to describe the source of the material used in the experiment. Untangling semantic differences between the data provided by different resources is therefore largely reliant on the domain knowledge of a human expert. We present here eVOC, a system which associates labelled target cDNAs for microarray experiments, or cDNA libraries and their associated transcripts with controlled terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal controlled vocabularies suitable for describing the domains of human gene expression data including Anatomical System, Cell Type, Pathology and Developmental Stage. We have curated and annotated 7016 cDNA libraries represented in dbEST, as well as 104 SAGE libraries,with expression information,and provide this as an integrated, public resource that allows the linking of transcripts and libraries with expression terms. Both the vocabularies and the vocabulary-annotated libraries can be retrieved from http:\/\/www.sanbi.ac.za\/evoc\/. Several groups are involved in developing this resource with the aim of unifying transcript expression information.","subset":"pubmed_abstract"} +{"meta":{"pmid":31523514,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data.\nMycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicin-resistant (RR)-TB. However, as next-generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low- and middle-income high TB-burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance. We developed the Python-based MycTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs-Xpert MTB\/RIF, XpertMTB\/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data. The MTBGT tool correctly transformed the single nucleotide polymorphism (SNP) data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin-susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda. Overall, the MTBGT tool allows low- and middle-income countries to make sense of the increasingly generated WGS in light of the readily available RDT results, and assess whether currently implemented RDTs adequately detect RR-TB in their setting. With its feature to transform WGS to RDT results and facilitate continuous RR-TB data analysis, the MTBGT tool may bridge the gap between and among data from periodic surveys, continuous surveillance, research, and routine tests, and may be integrated within the national information system for use by the NTP and epidemiologists to improve setting-specific RR-TB control. The MTBGT source code and accompanying documentation are available at https:\/\/github.com\/KamelaNg\/MTBGT.","subset":"pubmed_abstract"} +{"meta":{"pmid":17580082,"dup_signals":{"dup_doc_count":34,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-14":2,"2022-33":1,"2021-31":1,"2021-21":1,"2021-17":1,"2020-45":1,"2019-22":1,"2019-18":1,"2018-51":1,"2018-47":1,"2018-39":2,"2018-30":1,"2018-17":2,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-26":2,"2017-22":1,"2017-17":1,"2017-09":1,"2023-50":1,"2024-30":2,"2024-18":1,"2017-13":1}}},"text":"Cargo transport: two motors are sometimes better than one.\nMolecular motor proteins are crucial for the proper distribution of organelles and vesicles in cells. Much of our current understanding of how motors function stems from studies of single motors moving cargos in vitro. More recently, however, there has been mounting evidence that the cooperation of multiple motors in moving cargos and the regulation of motor-filament affinity could be key mechanisms that cells utilize to regulate cargo transport. Here, we review these recent advances and present a picture of how the different mechanisms of regulating the number of motors moving a cargo could facilitate cellular functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":32284326,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":15}}},"text":"Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency.\nEffective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. Here, we expressed and purified active SARS-CoV-2 RdRp composed of the nonstructural proteins nsp8 and nsp12. Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA. Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2'-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.","subset":"pubmed_abstract"} +{"meta":{"pmid":25264848,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation.\nAlthough the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL\/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.","subset":"pubmed_abstract"} +{"meta":{"pmid":26518354,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":14}}},"text":"Adult pancreatic hemangioma in pregnancy--concerns and considerations of a rare case.\nPancreatic tumors in pregnancy are rare but clinically challenging. Careful diagnostic workup, including appropriate imaging examinations, should be performed to evaluate surgery indications and timing . In the present case a diagnosis of an adult pancreatic hemangioma was made. We were not able to identify a similar case in the very sparse literature on this rare disease. A 30-year-old woman at 12 weeks of gestation was diagnosed with a large pancreatic tumor having a cystic pattern based on imaging. Although the preoperative diagnosis was uncertain, patient preference and clinical symptoms and signs suggested surgery. Open distal pancreatic resection including splenectomy was performed, and complete resection of the large cystic tumor was successfully achieved, with no postoperative complications. Although a solid pseudopapillary epithelial neoplasm (SPEN) was suspected, specimen morphology, including immunohistochemistry, supported the diagnosis of an adult benign pancreatic hemangioma. Although mucinous cystic neoplasm (MCN) and adenocarcinoma are the most common pancreatic tumors during pregnancy, various other malignant and benign lesions can be encountered. This report adds to the very small number of pancreatic hemangiomas reported in the literature and involves the first patient diagnosed with this rare condition during pregnancy. Careful clinical considerations regarding diagnostic workup and treatments are required to ensure that mother and child receive the best possible care.","subset":"pubmed_abstract"} +{"meta":{"pmid":36220816,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":2,"2024-22":2,"2024-10":3,"unknown":9}}},"text":"Whole genome sequence analysis of blood lipid levels in >66,000 individuals.\nBlood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.","subset":"pubmed_abstract"} +{"meta":{"pmid":18628218,"dup_signals":{"dup_doc_count":93,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2018-05":1,"2017-51":1,"2017-47":2,"2017-43":3,"2017-39":3,"2017-34":4,"2017-30":3,"2017-26":7,"2017-22":7,"2017-17":8,"2017-09":9,"2017-04":10,"2016-50":10,"2016-44":8,"2016-40":1,"2018-13":1,"2017-13":11}}},"text":"Improving handoff communications in critical care: utilizing simulation-based training toward process improvement in managing patient risk.\nA patient admitted to the medical step-down unit experienced severe hypoglycemia due to an infusion of a higher-than-ordered insulin dose. The event could have been prevented if the insulin syringe pump was checked during the nursing shift handoff. Risk management exploration included direct observations of nursing shift handoffs, which highlighted common deficiencies in the process. This led to the development and implementation of a handoff protocol and the incorporation of handoff training into a simulation-based teamwork and communication workshop. A second round of observations took place 6 to 8 weeks following training. The intervention demonstrated an increase in the incidence of nurses communicating crucial information during handoffs, including patient name, events that had occurred during the previous shift, and treatment goals for the next shift. However, there was no change in the incidence of checking the monitor alarms and the mechanical ventilator. Simulation-based training can be incorporated into the risk management process and can contribute to patient safety practice.","subset":"pubmed_abstract"} +{"meta":{"pmid":21499342,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":12}}},"text":"Quality-factor enhancement of supermodes in coupled microdisks.\nWe investigate the optical modes in a coupled pair of semiconductor microdisks in symmetric and asymmetric configurations both experimentally and theoretically. While the quality factors of coupled first- and second-order whispering gallery modes (WGMs) show a conventional crossing, the quality factors of the same-order WGMs reveal an interesting splitting behavior, leading to the formation of high- and low-quality supermodes. Our results are reproduced by numerical simulations, and an explanation based on optical interference is suggested. Quality-factor splitting is a subtle phenomenon that might help to design microarchitectures for efficient optical coupling in cavity quantum electrodynamic experiments.","subset":"pubmed_abstract"} +{"meta":{"pmid":28302974,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Effect of the Chain Length of a Modified Layer and Surface Roughness of an Electrode on Impedimetric Immunosensors.\nAn ultrasensitive label-free impedimetric immunosensor is constructed by modifying a 3-mercaptoproponic acid (MPA) monolayer on highly rough gold nanostructure (AuNS)-electrodeposited screen printed carbon electrodes (SPCEs) for the detection of small molecular weight drugs (SMWDs), such as salbutamol (SAL). The SPCEs preoxidized in a 0.1 M H2SO4 solution (called po-SPCEH2SO4) are electrodeposited with the AuNS to increase the roughness factor to 23.64 \u00b1 1.76, larger than the AuNS\/po-SPCENaOH or the AuNS\/po-SPCEPBS. Furthermore, the MPA modified layer as a link for the anti-SAL immobilization to give the immunosensors an impedimetric signal-to-noise ratio larger than the 11-mercapto-undecanoic acid- and 16-mercaptohexadecanoic acid-modified layer, due to the lower interfacial impedance of the MPA monolayer. The MPA\/AuNS\/po-SPCEH2SO4-based immunosensors have a wide linear range of 1 fg mL-1 to 1 ng mL-1 and a limit of detection of 0.6 fg mL-1. Moreover, the immunosensors can practically quantify the SAL concentrations in 1000 times-diluted serum samples with good recovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":11290790,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-27":2,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-26":1}}},"text":"Relaxed DM requirements during class II peptide loading and CD4+ T cell maturation in BALB\/c mice.\nCurrent ideas about DM actions have been strongly influenced by studies of mutant strains expressing the H-2(b) haplotype. To evaluate DM contributions to class II activities in BALB\/c mice, we generated a novel mutation at the DMa locus via embryonic stem cell technology. Unlike long-lived A(b)\/class II-associated invariant chain-derived peptide (CLIP) complexes, mature A(d) and E(d) molecules are loosely occupied by class II-associated invariant chain-derived peptide and are SDS unstable. BALB\/c DM mutants weakly express BP107 conformational epitopes and toxic shock syndrome toxin-1 superantigen-binding capabilities, consistent with partial occupancy by wild-type ligands. Near normal numbers of mature CD4(+) T cells fail to undergo superantigen-mediated negative selection, as judged by TCR Vbeta usage. Ag presentation assays reveal consistent differences for A(d)- and E(d)-restricted T cells. Indeed, the mutation leads to decreased peptide capture by A(d) molecules, and in striking contrast causes enhanced peptide loading by E(d) molecules. Thus, DM requirements differ for class II structural variants coexpressed under physiological conditions in the intact animal.","subset":"pubmed_abstract"} +{"meta":{"pmid":28850030,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":11}}},"text":"Increasing suppression of saccade-related transients along the human visual hierarchy.\nA key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3\u00b0-3.7\u00b0) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.","subset":"pubmed_abstract"} +{"meta":{"pmid":10756616,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":11}}},"text":"Iron deficiency anaemia and aspirin use in old age.\nAspirin is being increasingly prescribed for cardiovascular protection, but is also recognized to have significant gastrointestinal side-effects. Whether chronic aspirin consumption causes iron deficiency is undetermined, and there is little information available regarding iron deficiency and aspirin use in old age. We studied the relationship between iron deficiency anaemia and regular aspirin prescription in old age.","subset":"pubmed_abstract"} +{"meta":{"pmid":10613155,"dup_signals":{"dup_doc_count":34,"dup_dump_count":26,"dup_details":{"curated_sources":6,"2022-40":2,"2022-21":2,"2022-05":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2024-22":1,"2024-30":1}}},"text":"The shoulder in patients with muscular dystrophy.\nShoulder weakness and instability are not usually a major part of the clinical picture of muscular dystrophies. Problems usually do not arise until the patient is wheelchair bound, at which time assistive appliances may be required. The majority of orthopaedic intervention is confined to the rare facioscapulohumeral dystrophy. Facioscapulohumeral dystrophy causes muscular weakness of the face, shoulder girdle, and upper arm with selective sparing of the deltoid muscle. This leads to scapular winging and a marked decrease in flexion and abduction of the shoulder. As the muscles stabilizing the scapula become involved, the scapula starts to wing. The deltoid is spared, but its action is wasted because of the unstable scapula. The deltoid contracts and the arm attempts to move in a normal fashion, but because the scapula is no longer stable, it wings and rotates under the forces of the long lever arm of the upper limb and scapula complex. Mechanical fixation of the scapula to the thoracic wall provides a stable fulcrum on which the deltoid can exert its powerful action on the humerus and abduct the arm without rotation of the scapula. Twenty thoracoscapular fusions were performed on 13 patients. Ten patients (14 shoulders) were available for long term followup. The long term results showed that this operation is successful in achieving stability of the scapula, while greatly improving function and cosmesis. Although the course of this type of muscular dystrophy is variable, the benefits of surgery have not deteriorated with progression of the disease during a maximum followup of 44 years.","subset":"pubmed_abstract"} +{"meta":{"pmid":6334714,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-30":1,"unknown":7}}},"text":"Purification and characterization of a mannose-containing disaccharide obtained from human pregnancy urine. A new immunoregulatory saccharide.\nEndogenous mammalian lectin-like sugar-binding molecules have been previously described that have immunoregulatory properties. Further, the addition of defined simple saccharides to lymphocyte cultures has been shown to inhibit a variety of in vitro lymphocyte functions, presumably because these sugars are able to compete with the binding of endogenous lectins to critical membrane receptors. In this report, we describe the isolation and characterization of a D-mannose-containing disaccharide in human pregnancy urine that inhibits the proliferative response of human T lymphocytes. The inhibitory disaccharide was purified to homogeneity by sequential steps including affinity chromatography on immobilized concanavalin A and molecular sizing on Sephadex G-75 and then Fractogel 40S columns, with final purification on high-performance thin-layer chromatography. By mass spectrometry of the purified material as its permethylated derivative, the deduced structure of this compound was alpha-D-Manp 1-6-D-Man. To confirm that this disaccharide was in fact immunosuppressive, an identical disaccharide was prepared by sequential digestion of yeast cell wall polysaccharide. The urinary and yeast disaccharides had identical immunosuppressive properties. It has been previously reported that D-mannose is inhibitory for antigen-specific proliferative assays in the range of 10-50 mM. The purified alpha-D-Manp 1-6-D-Man disaccharide was inhibitory at 100-fold-lower concentrations. Further, while D-mannose inhibits T cell proliferation when added at anytime up to 24 h before harvest of a 6-d lymphocyte culture, alpha-D-Manp 1-6-D-Man disaccharide was inhibitory only if added at the initiation of culture and had no inhibitory effect if added just 24 h later. These data support the concept that simple sugar compounds can exhibit marked immunoregulatory activity in vitro. The impact of these molecules on the regulation of immune responses in vivo is unknown, as is their precise mechanism of action, but structural and chemical identification should now permit a detailed analysis of these issues.","subset":"pubmed_abstract"} +{"meta":{"pmid":11471135,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Upper Paleolithic triple burial of Doln\u00ed Vestonice: pathology and funerary behavior.\nThis work focuses on paleopathological analysis of one of the skeletons from the Gravettian triple burial of Doln\u00ed Vestonice (Moravia) and addresses issues of Upper Paleolithic funerary behavior. The burial includes the well-preserved skeletons of three young individuals. The skeleton in the middle (DV 15) is pathological and very problematic to sex; the other two (DV 13 and DV 14) are males and lie in an unusual position. The young age, the possibility of a simultaneous interment, and the position of the three specimens have given rise to speculations about the symbolic significance of this spectacular and intriguing funerary pattern. The pathological condition of the skeleton in the middle further emphasizes its peculiarity. Main pathological changes of the DV 15 skeleton include: asymmetric shortening of the right femur and of left forearm bones, bowing of the right femur, right humerus, and left radius, elongation of fibulae, dysplasias of the vertebral column, and very marked enamel hypoplasias. Scrutiny of the medical literature suggests that the most likely etiology is chondrodysplasia calcificans punctata (CCP) complicated by trauma and early fractures of the upper limbs. CCP is a rare inherited disorder characterized by stippled ossification of the epiphyses. The cartilaginous stippling is a transient phenomenon that disappears during infancy, leaving permanent deformities on affected bones. Among the different forms of CCP, the X-linked dominant form is that resulting in asymmetric shortening and is lethal during early infancy in males. Thus, survival of DV 15 until young adult age would require the specimen to be a female. Clinical findings often associated with the disease (erythemas, ichthyosis, alopecia, cataracts, and joint contractures, among others) would emphasize the singular aspect of this individual, pointing to a condition that should be carefully taken into account when speculating on the significance of that peculiar burial.","subset":"pubmed_abstract"} +{"meta":{"pmid":29322002,"dup_signals":{"dup_doc_count":11}},"text":"Complementary and alternative medicine use in thalassemia patients in Shiraz, southern Iran: A cross-sectional study.\nThis study aimed to determine the frequency and pattern of complementary and alternative medicine (CAM) use in thalassemia patients in south of Iran. The survey was done using a validated questionnaire which was distributed among 122 thalassemia patients. Only 108 questionnaires were completed and turned back (response rate 88.5%). Patients referred to an outpatient thalassemia clinic in Shiraz, southern Iran for blood transfusion. The mean age of the patients was 22.9 \u00b1 7.9 years (range 4-45 years) with female\/male ratio 1.84. Seventy four (68.5%) of the responders used CAM at least once during their life, and about half of them used it concurrently with their conventional treatments. The most reported CAM product was mint juice (50%). The most common reason of CAM use was increased general health. The most common information source about CAM was physicians who were the most trusted source as well. CAM is frequently being used in thalassemia patients to ensure their sense of well-being and help them overcome the complications of their illnesses.","subset":"pubmed_abstract"} +{"meta":{"pmid":28758018,"dup_signals":{"dup_doc_count":46,"dup_dump_count":26,"dup_details":{"curated_sources":1,"2023-50":2,"2020-40":2,"2020-29":1,"2020-16":3,"2020-05":4,"2019-51":2,"2019-47":1,"2019-43":2,"2019-35":2,"2019-26":2,"2019-18":1,"2019-09":3,"2018-51":2,"2018-47":1,"2018-43":2,"2018-39":1,"2018-34":2,"2018-30":1,"2018-26":2,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-43":2,"2017-34":2}}},"text":"The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries.\nHepatitis C (HCV) can only be eradicated if annual rates of cure (SVR) are consistently and significantly higher than new HCV infections, across many countries. In 2016, the WHO called for a 90% reduction in new HCV infection by 2030. Direct-acting antivirals (DAA) can cure the majority of those treated, at around 90% in most populations, at potentially very low prices. We compared the net annual change in epidemic size across 91 countries using data on SVR, new HCV infections, and deaths. In a further 109 countries, we projected this figure using regional averages of epidemic size. Epidemiological data for 2016 were extracted from national reports, publications and the Polaris Observatory. There were 91\/210 countries with data on SVR, HCV-related deaths and new infections available for analysis; 109 countries had net change in epidemic size projected from the regional prevalence of HCV, extrapolated to their population size. 'Net cure' was defined as the number of people with SVR, minus new HCV infections, plus HCV-related deaths in 2016. For the 91 countries analysed, there were 57.3 million people with chronic HCV infection in 2016. In the remaining 109 countries, the projected epidemic size was 12.2 million, giving a global epidemic size of 69.6 million. Across the 91 countries, there was a fall from 57.3 to 56.9 million people in 2017, a 0.7% reduction. The projected global net change was from 69.6 to 69.3 million, a 0.4% reduction. Ten countries had at least five times more people reaching SVR than new HCV infections, including Egypt and USA. In 47\/91 countries, there were more HCV infections than SVR in 2016. Very few countries are on target to achieve elimination of HCV as a public health problem by 2030. While the North American, North African\/Middle East and Western European regions have shown small declines in prevalence, the epidemic is growing in sub-Saharan Africa and Eastern Europe. Far higher rates of DAA treatment are required for worldwide elimination of HCV.","subset":"pubmed_abstract"} +{"meta":{"pmid":28576949,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Trends and Correlates of Hookah Use Among High School Students in North Carolina.\nOBJECTIVES Although youth cigarette smoking has declined in the United States, use of alternative tobacco products, such as hookah, has increased. This study assesses changes in prevalence of use from 2011 to 2013, and examines factors associated with current hookah use among North Carolina high school students in 2013.METHODS Data came from the North Carolina Youth Tobacco Survey in 2011 (n = 4,791) and 2013 (n = 4,092). STATA (StataCorp LLC) logistic regression survey procedures account for the complex survey design and sampling weights.RESULTS Prevalence of reported current hookah use significantly increased from 3.6% (95% CI: 2.8-4.5) in 2011 to 6.1% (95% CI: 4.9-7.5) in 2013 while reported lifetime hookah use increased from 9.8% (95% CI: 8.0-12.0) in 2011 to 12.6% (95% CI: 11.0-14.4) in 2013. Correlates of current hookah use included having a weekly disposable income over $50 (adjusted odds ratio (AOR) = 2.05, 95% CI: 1.25-3.35), currently smoking cigarettes (AOR = 4.57, 95% CI: 1.80-11.62), and living with hookah users (AOR = 6.45, 95% CI: 3.21-12.93). Participant self-reports of \"liking\" or positively commenting on tobacco products on social media were associated with current hookah use (AOR = 1.83, 95% CI: 1.84-4.52). Frequent exposure to online tobacco advertisements (AOR = 1.61, 95% CI: 1.13-2.28) were also associated with current hookah use.CONCLUSIONS Comprehensive product specific communication and policy interventions are needed to educate youth about the dangers of hookah use and reduce social acceptability among youth. To decrease hookah use in North Carolina, policymakers should consider restoring funding for comprehensive tobacco prevention and control programs, and equalizing tobacco tax rates for all tobacco product types.","subset":"pubmed_abstract"} +{"meta":{"pmid":8406158,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.\nPeptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":11453473,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Development of a technique for the in vivo assessment of flatulence in dogs.\nTo develop a noninvasive method for the in vivo assessment of flatulence in dogs. 8 adult dogs. Rectal gases were collected via a perforated tube held close to each dog's anus and attached to a monitoring pump fitted with a sensor that recorded hydrogen sulfide concentrations every 20 seconds. Patterns of flatulence were monitored for 14 hours after feeding on 4 days, and within- and between-dog variation was assessed over 4 hours on 4 consecutive days. Rate of hydrogen sulfide production (flatulence index) and frequency and number of emissions were evaluated as potential indicators of flatus characteristics. An odor judge assigned an odor rating to each flatulence episode, and the relationship between that rating and hydrogen sulfide concentration was determined. Flatulence patterns varied within and between dogs. Variation was most pronounced for flatulence index; mean coefficients of variance within dogs over time and between dogs on each day were 75 and 103%, respectively. Flatus with hydrogen sulfide concentrations > 1 parts per million could be detected by the odor judge, and severity of malodor was highly correlated with hydrogen sulfide concentration. Odor ratings were accurately predicted by use of the equation 1.51 X hydrogen sulfide concentration(0.28). The technique described in this report appears to provide sensitive, reliable, and relevant data and will enable further studies of the factors that influence flatulence in dogs. Use of this technique also has the potential to aid in investigations of colonic physiology and pathology.","subset":"pubmed_abstract"} +{"meta":{"pmid":19060099,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"De novo synthesis and degradation of Lx and V cycle pigments during shade and sun acclimation in avocado leaves.\nThe photoprotective role of the universal violaxanthin cycle that interconverts violaxanthin (V), antheraxanthin (A), and zeaxanthin (Z) is well established, but functions of the analogous conversions of lutein-5,6-epoxide (Lx) and lutein (L) in the selectively occurring Lx cycle are still unclear. We investigated carotenoid pools in Lx-rich leaves of avocado (Persea americana) during sun or shade acclimation at different developmental stages. During sun exposure of mature shade leaves, an unusual decrease in L preceded the deepoxidation of Lx to L and of V to A+Z. In addition to deepoxidation, de novo synthesis increased the L and A+Z pools. Epoxidation of L was exceptionally slow, requiring about 40 d in the shade to restore the Lx pool, and residual A+Z usually persisted overnight. In young shade leaves, the Lx cycle was reversed initially, with Lx accumulating in the sun and declining in the shade. De novo synthesis of xanthophylls did not affect alpha- and beta-carotene pools on the first day, but during long-term acclimation alpha-carotene pools changed noticeably. Nonetheless, the total change in alpha- and beta-branch carotenoid pools was equal. We discuss the implications for regulation of metabolic flux through the alpha- and beta-branches of carotenoid biosynthesis and potential roles for L in photoprotection and Lx in energy transfer to photosystem II and explore physiological roles of both xanthophyll cycles as determinants of photosystem II efficiency.","subset":"pubmed_abstract"} +{"meta":{"pmid":30473728,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2023-23":2,"2023-06":1,"2022-27":2,"2021-25":1,"2021-17":2,"2021-04":2,"2020-45":1,"2023-50":1,"2024-18":1,"2024-26":1}}},"text":"Treatment recommendation differences for schizophrenia and major depression: a population-based study in a Vietnamese cohort.\nIn Vietnam, the mental health care infrastructure is on the verge of transformation with an increase in the demand for access to adequate and effective mental health care services. Public attitudes towards mental illness, as well as corresponding treatment options influence help-seeking behaviors of patients and caregivers, affecting the course of their treatment. This study assesses attitudes towards treatment options for depression and schizophrenia, as the two most common psychiatric disorders in Vietnam, accounting for at least 75% of all psychiatric inpatients. A general population-based survey was conducted in Hanoi, Vietnam between April and August 2013. Participants received a description of a person with symptoms of either depression (n = 326) or schizophrenia (n = 403) and were asked to give recommendations for adequate sources of mental health support and treatment options. Multiple analyses on a single item level compared the likelihood of recommendation between schizophrenia and depression. Overall, respondents recommended health care services, ranging from seeking mental health care professionals, psychotherapists, and psychiatrists for both disorders. Psychotherapy was the most favored treatment method, whereas further treatment options, such as concentration and relaxation exercises, meditation or yoga and psychotropic medication were also endorsed as helpful. For the schizophrenia vignette condition, psychotherapy, visiting a psychiatrist or psychotherapist received stronger endorsement rates as compared to the depression vignette. Furthermore, ECT, Feng Shui-based practices, praying and visiting natural healers were recommended less by respondents for the depression vignette in comparison with the schizophrenia vignette. The Vietnamese public endorsed evidence-based treatment recommendations from a variety of treatments options. Differences in the treatment recommendations between depression and schizophrenia reflected the perceived severity of each disorder. Further developments of the Vietnamese mental health care system concerning mental health care providers, as well as the legal regulations surrounding the provision of psychotherapy are needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26748261,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2022-49":1,"2022-33":1,"2021-31":1,"2021-21":1,"2020-45":1,"2020-40":1,"2018-43":1,"2018-34":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2023-06":1,"2024-26":1}}},"text":"In-situ polymerisation of fully bioresorbable polycaprolactone\/phosphate glass fibre composites: In vitro degradation and mechanical properties.\nFully bioresorbable composites have been investigated in order to replace metal implant plates used for hard tissue repair. Retention of the composite mechanical properties within a physiological environment has been shown to be significantly affected due to loss of the integrity of the fibre\/matrix interface. This study investigated phosphate based glass fibre (PGF) reinforced polycaprolactone (PCL) composites with 20%, 35% and 50% fibre volume fractions (Vf) manufactured via an in-situ polymerisation (ISP) process and a conventional laminate stacking (LS) followed by compression moulding. Reinforcing efficiency between the LS and ISP manufacturing process was compared, and the ISP composites revealed significant improvements in mechanical properties when compared to LS composites. The degradation profiles and mechanical properties were monitored in phosphate buffered saline (PBS) at 37\u00b0C for 28 days. ISP composites revealed significantly less media uptake and mass loss (p<0.001) throughout the degradation period. The initial flexural properties of ISP composites were substantially higher (p<0.0001) than those of the LS composites, which showed that the ISP manufacturing process provided a significantly enhanced reinforcement effect than the LS process. During the degradation study, statistically higher flexural property retention profiles were also seen for the ISP composites compared to LS composites. SEM micrographs of fracture surfaces for the LS composites revealed dry fibre bundles and poor fibre dispersion with polymer rich zones, which indicated poor interfacial bonding, distribution and adhesion. In contrast, evenly distributed fibres without dry fibre bundles or polymer rich zones, were clearly observed for the ISP composite samples, which showed that a superior fibre\/matrix interface was achieved with highly improved adhesion.","subset":"pubmed_abstract"} +{"meta":{"pmid":18808239,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":5,"2021-17":1,"2020-05":1,"2018-39":1,"2018-17":1,"2018-05":2,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-21":1}}},"text":"Me against myself: motivational conflicts and emotional development in adulthood.\nTwo studies investigated adult age differences in the frequency and emotional consequences of motivational conflicts (i.e., feeling that one wants to or should do something else in a given situation). Study 1 compared younger and older adults. Study 2 included a more age-heterogeneous sample ranging from 20 to 70 years. Data were obtained using diary and experience-sampling methods. Multilevel regression showed that motivational conflict was associated with lower emotional well-being. With age, the frequency of motivational conflict decreased, while emotional well-being increased. Importantly, the age-related decrease in motivational conflicts partly accounted for the age-related increase in emotional well-being. Findings were consistent across studies and robust after the authors controlled for age differences in a number of control variables including time use. The authors conclude that an age-related decrease in motivational conflicts in daily life may be among the factors underlying the positive development of emotional well-being into older adulthood.","subset":"pubmed_abstract"} +{"meta":{"pmid":8604041,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Localization of synaptotagmin-binding domains on syntaxin.\nSynaptotagmin, an abundant calcium- and phospholipid-binding protein of synaptic vesicles, has been proposed to regulate neurotransmitter release at the nerve terminal. To understand better the biochemical mechanism of neurotransmitter release, we have investigated the calcium-dependent and -independent protein-protein interactions between synaptotagmin I and syntaxin 1a, a subunit of the receptor for synaptic vesicles on the presynaptic plasma membrane. Soluble syntaxin 1a binds to synaptotagmin glutathione S-transferase (GST) fusion protein, and the binding was decreased in the presence of calcium. A synaptotagmin fragment containing the second C2 repeat (Syt3-5) had the same binding profile as the whole cytoplasmic domain; however, fragments containing the first C2 repeat (Syt1-3 and Syt2-3) showed calcium-dependent binding to syntaxin. In addition, the soluble full-length cytoplasmic domain of synaptotagmin binds to a syntaxin GST fusion protein in a calcium-dependent manner. Syntaxin domains required for calcium-dependent and -independent synaptotagmin-binding were localized using syntaxin deletion mutants. Amino acids 241-266 of the syntaxin C terminus were required for calcium-independent binding of synaptotagmin. The minimal domain required for calcium-dependent binding of synaptotagmin to syntaxin was localized to amino acids 220-266. The syntaxin domains required for synaptotagmin binding overlap with the domains for vesicle-associated membrane protein (or VAMP) and alpha-soluble N-ethyl-maleimide-sensitive fusion protein attachment protein (or alphaSNAP) interactions. The data suggest both calcium-dependent and -independent roles of synaptotagmin in regulating synaptic vesicle release and\/or recycling.","subset":"pubmed_abstract"} +{"meta":{"pmid":19958538,"dup_signals":{"dup_doc_count":42,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2020-16":1,"2020-10":2,"2019-13":1,"2018-43":1,"2018-26":1,"2018-05":2,"2017-43":1,"2017-34":1,"2017-30":1,"2017-17":1,"2015-48":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":2,"2014-15":2,"2021-25":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":2,"2013-20":2,"2015-18":1}}},"text":"Cannabis as a substitute for alcohol and other drugs.\nSubstitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Anonymous survey data were collected at the Berkeley Patient's Group (BPG), a medical cannabis dispensary in Berkeley, CA. (N = 350) The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal), 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and\/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%) with cannabis. The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":14871532,"dup_signals":{"dup_doc_count":48,"dup_dump_count":30,"dup_details":{"curated_sources":2,"2023-40":1,"2023-14":3,"2023-06":2,"2022-49":2,"2022-40":1,"2022-27":3,"2022-21":2,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-25":1,"2021-17":3,"2021-10":1,"2021-04":4,"2020-50":1,"2020-45":2,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-18":2,"2024-30":1}}},"text":"The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo.\nAssessment of cell-mediated toxicity has traditionally been achieved by measuring the specific activity of enriched effector cell populations against antigen-loaded target cells labeled with radioactive isotopes in vitro. Fluorometric techniques are viewed as a promising alternative to the use of radioactive isotopes for these analyses. Direct assessment of cytotoxicity in vivo can be achieved by monitoring survival of injected fluorescent targets relative to a differentially labeled internal control population without specific antigen. We have developed this approach, incorporating the use of multiple target cell populations labeled with different dyes so that cytotoxicity can be assessed against titrated doses of a given antigen, or against a range of different antigens, simultaneously. We show that this assay, referred to as the VITAL assay, can be used to assess cytotoxic activity of CTL and iNKT cells in vivo and in vitro. CTL responses measured in vivo could be correlated with antigen doses used in immunization strategies, and also with the size of specific CTL populations enumerated in the blood with fluorescent MHC\/peptide tetramers. The VITAL assay is, therefore, a sensitive technique allowing analysis of complex multi-epitope responses.","subset":"pubmed_abstract"} +{"meta":{"pmid":20965911,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":13}}},"text":"Promoting critical consciousness and social mobilization in HIV\/AIDS programmes: lessons and curricular tools from a South African intervention.\nThe development of critical consciousness is seen as a key stage in communities increasing levels of dialogue about priority problems and effecting structural change for health. However, relatively little research identifies concrete methods for programmes to build critical consciousness. We examined how a South African structural intervention used critical consciousness as a tool for prevention of intimate partner violence and HIV infection. We collected qualitative data in the form of in-depth interviews with managers, trainers, and participants of the Intervention with Microfinance for AIDS and Gender Equity intervention (IMAGE) in rural South Africa. The data were analysed through a coding structure developed in QSR NVivo. We draw practical lessons from IMAGE to guide other HIV programmes aiming to promoting critical consciousness and social mobilization. This research suggests that specific curricular tools can work towards critical consciousness and that mobilization efforts in future programmes can be strengthened by including individual and collective efforts by participants.","subset":"pubmed_abstract"} +{"meta":{"pmid":21750009,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2021-39":1,"2020-40":1,"2018-51":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-51":2,"2017-34":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-14":1,"2017-13":1}}},"text":"Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study.\nPrevious studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. We computed person-years at risk for children aged 0-15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place of residence at birth and calculated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing the risk of cancer in children born <5 km, 5-10 km and 10-15 km from the nearest NPP with children born >15 km away, using Poisson regression models. We included 2925 children diagnosed with cancer during 21 117 524 person-years of follow-up; 953 (32.6%) had leukaemia. Eight and 12 children diagnosed with leukaemia at ages 0-4 and 0-15 years, and 18 and 31 children diagnosed with any cancer were born <5 km from a NPP. Compared with children born >15 km away, the IRRs (95% CI) for leukaemia in 0-4 and 0-15 year olds were 1.20 (0.60-2.41) and 1.05 (0.60-1.86), respectively. For any cancer, corresponding IRRs were 0.97 (0.61-1.54) and 0.89 (0.63-1.27). There was no evidence of a dose-response relationship with distance (P > 0.30). Results were similar for residence at diagnosis and at birth, and when adjusted for potential confounders. Results from sensitivity analyses were consistent with main results. This nationwide cohort study found little evidence of an association between residence near NPPs and the risk of leukaemia or any childhood cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":26923351,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":8}}},"text":"Dietary fiber and blood pressure control.\nIn the past few years, new strategies to control blood pressure levels are emerging by developing new bioactive components of foods. Fiber has been linked to the prevention of a number of cardiovascular diseases and disorders. \u03b2-Glucan, the main soluble fiber component in oat grains, was initially linked to a reduction in plasma cholesterol. Several studies have shown afterward that dietary fiber may also improve glycaemia, insulin resistance and weight loss. The effect of dietary fiber on arterial blood pressure has been the subject of far fewer studies than its effect on the above-mentioned variables, but research has already shown that fiber intake can decrease arterial blood pressure in hypertensive rats. Moreover, certain fibers can improve arterial blood pressure when administered to hypertensive and pre-hypertensive subjects. The present review summarizes all those studies which attempt to establish the antihypertensive effects of dietary fiber, as well as its effect on other cardiovascular risk factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":8283246,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Aggregation of vasopressin mRNA in a subset of axonal swellings of the median eminence and posterior pituitary: light and electron microscopic evidence.\nThe mRNA encoding vasopressin has recently been documented within the magnocellular hypothalamo-neurohypophyseal projections of the rat such as the median eminence (ME) and the posterior pituitary (PP), suggesting the possibility of its axonal transport. To address the origin of this mRNA and to investigate the functional significance of this unexpected axonal transport of mRNA, we have examined its subcellular localization within both magnocellular perikarya and their axonal projections. For this purpose, we have used nonradioactive in situ hybridization techniques in order to localize the vasopressin mRNA with precision at the ultrastructural level in magnocellular perikarya, dendrites, and axons from control, salt-loaded, and lactating rats. This approach permitted us to demonstrate directly the axonal localization of vasopressin mRNA. Moreover, we were able to obtain novel information concerning vasopressin mRNA compartmentation within both perikarya and axons. At both light and electron microscopic levels, we observed vasopressin mRNA-containing cells in the hypothalamic magnocellular cell body groups, but not in the ME or in the PP. When vasopressin mRNA was detected in medium-size dendrites, it was always associated with the rough endoplasmic reticulum (RER). Within the labeled magnocellular perikarya, the abundant vasopressin mRNA was mainly associated with discrete areas of the RER. However, vasopressin mRNA was never detected in the Golgi apparatus or in association with neurosecretory granules, in perikarya or axons. These data suggest that vasopressin mRNA translation is restricted to certain segments within the RER, and that axonal transport of vasopressin mRNA does not involve the classical neurosecretory pathway, via the Golgi apparatus and the neurosecretory granules, as has been proposed. Within the magnocellular neuron axons, vasopressin mRNA could be detected only in a subset of axonal swellings, all of which were confined to the internal layer of the ME and the PP. The mRNA-containing swellings were numerous in 7 d salt-loaded animals, less abundant in lactating animals, and almost undetectable in control animals. In all groups of animals, no vasopressin mRNA was detectable in any other region of the magnocellular neuron axons, including undilated axonal segments or varicose swellings. These results strongly suggest that, under physiological activation such as chronic salt loading, axonal vasopressin mRNA is increased and becomes aggregated in a selected subset of swellings of the ME and the PP. Furthermore, these data indicate that along the magnocellular neuron axons, the swellings may differ in their biochemical and functional features. Further analysis focused on the mRNA-accumulating swellings may illuminate the function of RNA within the axonal compartment.","subset":"pubmed_abstract"} +{"meta":{"pmid":25775586,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-30":1,"unknown":20}}},"text":"A 17-My-old whale constrains onset of uplift and climate change in east Africa.\nTiming and magnitude of surface uplift are key to understanding the impact of crustal deformation and topographic growth on atmospheric circulation, environmental conditions, and surface processes. Uplift of the East African Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to constrain plateau evolution and subsequent vertical motions associated with rifting. Here, we assess the paleotopographic implications of a beaked whale fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the present-day coastline of the Indian Ocean at an elevation of 620 m. The specimen is \u223c 17 My old and represents the oldest derived beaked whale known, consistent with molecular estimates of the emergence of modern strap-toothed whales (Mesoplodon). The whale traveled from the Indian Ocean inland along an eastward-directed drainage system controlled by the Cretaceous Anza Graben and was stranded slightly above sea level. Surface uplift from near sea level coincides with paleoclimatic change from a humid environment to highly variable and much drier conditions, which altered biotic communities and drove evolution in east Africa, including that of primates.","subset":"pubmed_abstract"} +{"meta":{"pmid":29452665,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"Novel agents for relapsed and refractory follicular lymphoma.\nFollicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although current frontline regimens are associated with high response rates, most patients still relapse. When progression is discovered, re-establishing the diagnosis and ruling out transformation in paramount. The outcomes following relapse have been improving due to the activity and increasing availability of novel agents with various mechanisms of action. Despite these advances, single agent activity is limited and the disease remains incurable in the majority of cases. Examples of drug classes with promising activity in relapsed disease include anti-CD20 monoclonal antibodies, immunomodulatory drugs (IMiDs), small molecule tyrosine kinase inhibitors, bcl2 inhibitors, epigenetic modifiers, conjugated antibodies, and checkpoint inhibitors. Many drugs in each class are associated with unique, variable and often surprising toxicity profiles. Combination studies are currently underway with novel-novel combinations and with traditional chemotherapy regimens. This overview will discuss the results of several recent studies exploring activity of novel drugs in relapsed follicular lymphoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":11228162,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Programmed cell death of keratinocytes culminates in apoptotic secretion of a humectant upon secretagogue action of acetylcholine.\nThe programmed cell death of the stratified squamous epithelial cells comprising human epidermis culminates in abrupt transition of viable granular keratinocytes (KC) into dead corneocytes sloughed by the skin. The granular cell-corneocyte transition is associated with a loss in volume and dry cell weight but the mechanism for and biological significance of this form of keratinocyte apoptosis remain obscure. We show that terminally differentiated KC extrude into the intercellular spaces of living epidermis the cytoplasmic buds containing randomly congregated components of the cytosol as well as filaggrin, a precursor of the natural moisturizing factor. The discharge of secretory product is reminiscent of holocrine secretion, suggesting the term 'apoptotic secretion' for this novel, essential step in the process of cornification. The secretory product may become a part of the glycocalyx (a.k.a. 'intercellular cement substance' of epidermis) and serve as a humectant that counterbalances the osmotic pressure imposed by the natural moisturizing factor located in the stratum corneum comprised by corneocytes. The apoptotic secretion commences upon secretagouge action of acetylcholine which is synthesized and released by KC. A combination of a cholinergic nicotinic agonist and a muscarinic antagonist which increases intracellular calcium levels is required to trigger the apoptotic secretion. Analysis of the relative amounts of cholinergic enzymes and receptors expressed by KC capable of secretion and the pharmacological profiles of secretion regulation revealed an upward concentration gradient of free acetylcholine in epidermis which may provide for its unopposed secretagogue action via the m1 muscarinic and the alpha7, and alpha9 nicotinic receptor types expressed by KC at the latest stage of their development in the epidermis.","subset":"pubmed_abstract"} +{"meta":{"pmid":27637250,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2017-47":1,"2017-13":1}}},"text":"Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness.\nIntrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance running distance and body fat, blood glucose, other health indicators, and natural life span. To understand the interplay among genetic differences, chronological age, and acute exercise we performed microarray-based gene expression analyses in skeletal muscle with a 2\u00d72\u00d72 design to simultaneously compare HCR and LCR, old and young animals, and rest and exhaustion. Transcripts for mitochondrial function are expressed higher in HCRs than LCRs at both rest and exhaustion and for both age groups. Expression of cell adhesion and extracellular matrix genes tend to decrease with age. This and other age effects are more prominent in LCRs than HCRs, suggesting that HCRs have a slower aging process and this may be partly due to their better metabolic health. Strenuous exercise mainly affects transcription regulation and cellular response. The effects of any one factor often depend on the other two. For example, there are \u223c140 and \u223c110 line-exercise \"interacting\" genes for old and young animals, respectively. Many genes highlighted in our study are consistent with prior reports, but many others are novel. The gene- and pathway-level statistics for the main effects, either overall or stratified, and for all possible interactions, represent a rich reference dataset for understanding the interdependence among lines, aging, and exercise.","subset":"pubmed_abstract"} +{"meta":{"pmid":23977721,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Eccentric exercise-induced delayed-onset muscle soreness and changes in markers of muscle damage and inflammation.\nThe purpose of this study was to determine the relationships among delayed-onset muscle soreness (DOMS), muscle damage and inflammatory responses to eccentric exercise and investigate the underlying mechanisms. Nine healthy males performed one-leg calf-raise exercise with their right leg on a force plate. They performed 10 sets of 40 repetitions of exercise at 0.5 Hz by the load corresponding to the half of their body weight, with a rest for 3 min between sets. DOMS was evaluated by a visual analogue scale (VAS). Blood and urine samples were collected before and 2, 4, 24, 48, 72 and 96 h post-exercise. Blood samples were analyzed for leucocyte differential counts and neutrophil functions (migratory activity and oxidative burst activity). We also determined a serum marker of muscle damage, myoglobin (Mb), and plasma and urinary prostaglandin E2 as an algesic substance. As for the inflammatory mediators, plasma and urine were analyzed for cytokines (interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, tumour necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and granulocyte macrophage colony-stimulating factor), leucocyte activation markers (calprotectin and myeloperoxidase), and neutrophil chemotactic factor complement 5a. All subjects reported muscle soreness on subsequent days and VAS peaked at 72 h after exercise. Serum Mb concentration significantly increased (p < 0.05) at 72 h after exercise as compared with the pre-exercise values which was correlated with the increases in VAS at 72 h (r = 0.73, p < 0.05). Circulating neutrophil count and migratory activity increased significantly (p < 0.01, and p < 0.05, respectively) at 4 h after exercise, whereas there were no significant changes in the other plasma and urinary inflammatory mediators. These results suggest that neutrophils can be mobilized into the circulation and migrate to the muscle tissue several hours after the eccentric exercise. There were also positive correlations between the exercise-induced increases in neutrophil migratory activity at 4 h and the increases in Mb at 48 h (r = 0.67, p < 0.05). These findings suggest that neutrophil mobilization and migration after exercise may be involved in the muscle damage and inflammatory processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27458067,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-21":1,"2020-45":1,"2020-16":1,"2020-05":1,"2018-39":1,"2018-26":1,"2018-09":1,"2018-05":1,"2017-47":1,"2017-34":1,"2022-27":1}}},"text":"Variation in blood pressure among adolescent schoolchildren in an urban slum of Kolkata, West Bengal.\nHigh blood pressure in childhood is a potential risk factor for cardiovascular and cerebrovascular diseases. The roots of essential hypertension in adults may be initiated in childhood. This study was conducted to investigate blood pressure profiles of adolescent schoolchildren in the practice field area of the Urban Health Centre, Chetla, Kolkata. This cross-sectional study was carried out to determine the prevalence of hypertension in adolescent schoolchildren, to compare the blood pressure between boys and girls, and to study the association between selected variables and blood pressure. The study was conducted among adolescent schoolchildren aged 10-19 years in two randomly selected secondary schools situated in the practice field area of the Urban Health Centre, Chetla, Kolkata. All students aged 10-19 years present on the day of the visit were included in the study; the sample was 129. A predesigned questionnaire was used to carry out the study. Measurements of height, weight, body mass index (BMI) and blood pressure were made using standardised physical instruments following standard operative guidelines. The data were collected and analysed using appropriate statistical methods. The prevalence of hypertension was found to be 10.1% (11.1% in boys and 8.8% in girls). The prevalence of pre-hypertension was 20.2% (16.7% in boys and 24.6% in girls). Hypertension was found to be significantly associated with physical exercise (p<0.05) and salt intake (p<0.05); BMI was also significantly associated with both systolic blood pressure (p<0.05) and diastolic blood pressure (p<0.05). There was a significant (p<0.05) positive correlation of systolic blood pressure and diastolic blood pressure with BMI (r=0.303, p<0.05; r=0.262, p<0.05), age (r=0.326, p<0.05; r=0.267, p<0.05) and height (r=0.322, p<0.05; r=0.174, p<0.05). There was a negative correlation between hypertension and physical exercise (r=-0.313, p<0.05) and a positive correlation between hypertension and salt intake (r=0.298, p<0.05). The prevalence of pre-hypertension and hypertension together in adolescents was 30.3%. To avoid the consequences and sequelae of hypertension, prevention should start from childhood by encouraging physical exercise, promoting low salt intake, advising on maintaining normal body weight, and checking up on blood pressure at regular intervals.","subset":"pubmed_abstract"} +{"meta":{"pmid":23100581,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Effect of dietary acids on growth performance of nursery pigs: a cooperative study.\nAn experiment involving 854 crossbred pigs (20 replicate pens of 4 to 8 pigs per pen) was conducted at 8 experiment stations to determine the effects of acids in nursery pig diets and their inclusion amounts on growth performance using diets and weaning ages typical of those used in the United States commercial pork industry. Diets were formulated to have constant a ME and contain 1.45, 1.45, and 1.30% standardized ileal digestible Lys for phases 1, 2, and 3, respectively. The basal diets were supplemented with various types and concentrations of acid at the expense of corn (Zea mays). Treatment diets included 0% acid (control), 0.1 or 0.2% phosphoric acid, 1 or 2% organic acids, and 0.1% phosphoric acid plus 1% organic acids with or without an antibiotic. The organic acids consisted of 50% citric acid and 50% fumaric acid by weight. All but the final diet contained the antibiotic carbadox. All diets contained 3,000 mg of Zn\/kg diet from zinc oxide during phases 1 and 2 and had limited acid buffering capacity, ranging from 142, 127, and 122 mEq\/kg of feed for phases 1, 2, and 3, respectively. At each participating station, pigs were randomly allotted to dietary treatments on the basis of their initial BW. Sex and ancestry were equally distributed across the treatments. Results indicated that treatment effects on pig performance were observed in phases 1 and 2 but not in phase 3. In phase 1, ADG of pigs fed 0.2% phosphoric acid was greater than that of pigs fed the combination of acids with no antibiotic (P = 0.041). In phase 2, pigs fed treatments containing an antibiotic had a greater ADG than those fed the combination of acids without antibiotic (P < 0.05). Addition of acids to diets did not affect growth performance during any phase or the overall period. Over the 4-wk study, growth rate was slowest on the treatment without antibiotic, with specific differences that were often statistically significant (P < 0.05). In summary, under the conditions of this experiment, the acid treatments had no effect but the antibiotic improved growth performance.","subset":"pubmed_abstract"} +{"meta":{"pmid":7651402,"dup_signals":{"dup_doc_count":19,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-40":1,"2020-24":2,"2020-16":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-43":3,"2019-39":1,"2019-26":1,"2019-22":1,"2021-04":1}}},"text":"Functional differences and interactions among the putative RecA homologs Rad51, Rad55, and Rad57.\nThe genes of the Saccharomyces cerevisiae RAD52 epistasis group are required for the repair of ionizing radiation-induced DNA damage. Three of these genes, RAD51, RAD55, and RAD57, have been identified as putative RecA homologs. An important feature of RecA is its ability to bind and hydrolyze ATP. RAD55 and RAD57 contain putative nucleotide binding motifs, and the importance of these motifs was determined by constructing site-directed mutations of the conserved lysine residue within the Walker A-box. Changing the lysine residue to arginine or alanine resulted in a mutant phenotype in DNA repair and sporulation for Rad55 but not for Rad57. Protein-protein interactions among Rad51, Rad55, and Rad57 were tested for by the two-hybrid system. Rad55 was shown to interact with Rad51 and Rad57 but not with itself. Additionally, no interaction between Rad57 and Rad51 or between Rad57 and itself was detected. Consistent with the hypothesis that Rad55 and Rad57 may function within, or stabilize, a protein complex, we found that RAD51 expressed from a high-copy-number plasmid suppresses the DNA repair defect of strains carrying rad55 and rad57 mutations. These data, in conjunction with other reports, demonstrate the importance of protein-protein interactions in the process of DNA repair.","subset":"pubmed_abstract"} +{"meta":{"pmid":24956792,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Optimal cultivation of simultaneous ammonium and phosphorus removal aerobic granular sludge in A\/O\/A sequencing batch reactor and the assessment of functional organisms.\nIn this study, sequencing batch reactor (SBR) with an anaerobic\/aerobic\/anoxic operating mode was used to culture granular sludge. Optimal adjustment of cycle duration was achieved by the direction ofpH, oxidation reduction potential and dissolved oxygen parameters. The results showed that the treating efficiency was significantly improved as the cycle was shortened from 450 to 360 min and further to 200 min. Nitrogen and phosphorus removal were nearly quantitative after 50 days operation and maintained stable to the end of the study period. The typical cycle tests revealed that simultaneous denitrification and phosphorus removal occurred when aerobic granules were gradually formed. The nitrite effect tests showed that less than 4.8 mg N\/L of the nitrite could enhance superficial specific aerobic phosphate uptake rate (SAPUR) under aerobic condition, indicating that the traditional method to evaluate the capability of total phosphate-accumulating organisms (PAOs) was inaccurate. Additionally, a high level of nitrite was detrimental to PAOs. A novel method was developed to determine the activity of each kind of PAOs and other denitrifying organisms. The results showed that (1) nitrate, besides nitrite, could also enhance SAPUR and (2) aerobic granular sludge could perform denitrification even when phosphate was not supplied under anoxic condition, suggesting that other denitrifying organisms besides denitrifying phosphate-accumulating organisms also contributed to denitrification.","subset":"pubmed_abstract"} +{"meta":{"pmid":22226254,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":9}}},"text":"Safe glycemic management during closed-loop treatment of type 1 diabetes: the role of glucagon, use of multiple sensors, and compensation for stress hyperglycemia.\nPatients with type 1 diabetes mellitus (T1DM) must make frequent decisions and lifestyle adjustments in order to manage their disorder. Automated treatment would reduce the need for these self-management decisions and reduce the risk for long-term complications. Investigators in the field of closed-loop glycemic control systems are now moving from inpatient to outpatient testing of such systems. As outpatient systems are developed, the element of safety increases in importance. One such concern is the risk for hypoglycemia, due in part to the delayed onset and prolonged action duration of currently available subcutaneous insulin preparations. We found that, as compared to an insulin-only closed-loop system, a system that also delivers glucagon when needed led to substantially less hypoglycemia. Though the capability of glucagon delivery would mandate the need for a second hormone chamber, glucagon in small doses is tolerated very well. People with T1DM often develop hyperglycemia from emotional stress or medical stress. Automated closed-loop systems should be able to detect such changes in insulin sensitivity and adapt insulin delivery accordingly. We recently verified the adaptability of a model-based closed-loop system in which the gain factors that govern a proportional-integral-derivative-like system are adjusted according to frequently measured insulin sensitivity. Automated systems can be tested by physical exercise to increase glucose uptake and insulin sensitivity or by administering corticosteroids to reduce insulin sensitivity. Another source of risk in closed-loop systems is suboptimal performance of amperometric glucose sensors. Inaccuracy can result from calibration error, biofouling, and current drift. We found that concurrent use of more than one sensor typically leads to better sensor accuracy than use of a single sensor. For example, using the average of two sensors substantially reduces the proportion of large sensor errors. The use of more than two allows the use of voting algorithms, which can temporarily exclude a sensor whose signal is outlying. Elements such as the use of glucagon to minimize hypoglycemia, adaptation to changes in insulin sensitivity, and sensor redundancy will likely increase safety during outpatient use of closed-loop glycemic control systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":30465898,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":14}}},"text":"Preventive role of Pycnogenol\u00ae against the hyperglycemia-induced oxidative stress and DNA damage in diabetic rats.\nDiabetes mellitus, a complex progressive metabolic disorder, leads to some oxidative stress related complications. Pycnogenol\u00ae (PYC), a plant extract obtained from Pinus pinaster, has been suggested to be effective in many diseases including diabetes, cancer, inflammatory and immune system disorders. The mechanisms underlying the effects of PYC in diabetes need to be elucidated. The aim of this study was to determine the effects of PYC treatment (50 mg\/kg\/day, orally, for 28 days) on the DNA damage and biochemical changes in the blood, liver, and kidney tissues of experimental diabetic rats. Changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase enzymes, and the levels of 8-hydroxy-2'-deoxyguanosine, total glutathione, malondialdehyde, insulin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, high density lipoprotein, low density lipoprotein, total cholesterol, and triglyceride were evaluated. DNA damage was also determined in the whole blood cells and the liver and renal tissue cells using the alkaline comet assay. PYC treatment significantly ameliorated the oxidative stress, lipid profile, and liver function parameters as well as DNA damage in the hyperglycemic rats. The results show that PYC treatment might improve the hyperglycemia-induced biochemical and physiological changes in diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":12458816,"dup_signals":{"dup_doc_count":34,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-30":1,"unknown":26}}},"text":"Visceral leishmaniasis and Coombs' positive hemolytic anemia: a rare association in an infant treated with liposomal amphotericin B.\nVisceral leishmaniasis is a worldwide, disseminated intracellular protozoal infection that usually manifests by fever, hepatosplenomegaly, anemia, thrombocytopenia, leukopenia and hypergammaglobulinemia. Although anemia is a usual finding, Coombs' positive hemolytic anemia has rarely been reported in association with this disease. Pentavalent antimonials have been the preferred treatment for this disease for decades, but increasing numbers of treatment failure with antimony are being reported. Liposomal amphotericin B is a new drug which is highly efficacious in the treatment of visceral leishmaniasis and produces minimal toxicity. Here we report an infant with visceral leishmaniasis associated with Coombs' positive hemolytic anemia who was successfully treated with liposomal amphotericin B.","subset":"pubmed_abstract"} +{"meta":{"pmid":18350131,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"Canonical source reconstruction for MEG.\nWe describe a simple and efficient solution to the problem of reconstructing electromagnetic sources into a canonical or standard anatomical space. Its simplicity rests upon incorporating subject-specific anatomy into the forward model in a way that eschews the need for cortical surface extraction. The forward model starts with a canonical cortical mesh, defined in a standard stereotactic space. The mesh is warped, in a nonlinear fashion, to match the subject's anatomy. This warping is the inverse of the transformation derived from spatial normalization of the subject's structural MRI image, using fully automated procedures that have been established for other imaging modalities. Electromagnetic lead fields are computed using the warped mesh, in conjunction with a spherical head model (which does not rely on individual anatomy). The ensuing forward model is inverted using an empirical Bayesian scheme that we have described previously in several publications. Critically, because anatomical information enters the forward model, there is no need to spatially normalize the reconstructed source activity. In other words, each source, comprising the mesh, has a predetermined and unique anatomical attribution within standard stereotactic space. This enables the pooling of data from multiple subjects and the reporting of results in stereotactic coordinates. Furthermore, it allows the graceful fusion of fMRI and MEG data within the same anatomical framework.","subset":"pubmed_abstract"} +{"meta":{"pmid":17981560,"dup_signals":{"dup_doc_count":33,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-49":2,"2021-39":4,"2021-31":3,"2021-17":1,"2021-04":1,"2020-45":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-10":1,"2024-30":1}}},"text":"Macrophage activation and polarization.\nMacrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.","subset":"pubmed_abstract"} +{"meta":{"pmid":28254844,"dup_signals":{"dup_doc_count":34,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-06":1,"2022-27":1,"2021-39":1,"2021-04":1,"2020-34":1,"2020-16":1,"2017-43":7,"2017-34":8,"2017-26":8,"2023-50":1}}},"text":"VEGF-A-Expressing Adipose Tissue Shows Rapid Beiging and Enhanced Survival After Transplantation and Confers IL-4-Independent Metabolic Improvements.\nAdipocyte-derived vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation, and beiging of subcutaneous adipose tissue. Using a doxycycline-inducible adipocyte-specific VEGF-A-overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observed a rapid appearance of beige fat cells in subcutaneous white adipose tissue as early as 2 days postinduction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A-induced beiging is independent of interleukin-4. We subjected metabolically healthy VEGF-A-overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A-overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing white adipose tissue beiging and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.","subset":"pubmed_abstract"} +{"meta":{"pmid":28151820,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Associations Between Impaired Cerebral Blood Flow Autoregulation, Cerebral Oxygenation, and Biomarkers of Brain Injury and Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.\nIncreasing evidence links postoperative cognitive dysfunction (POCD) to surgery and anesthesia. POCD is recognized as an important neuropsychological adverse outcome in surgical patients, particularly the elderly. This prospective cohort study aimed to investigate whether POCD is associated with impaired intraoperative cerebral autoregulation and oxygenation, and increased levels of biomarkers of brain injury. Study subjects were patients \u226565 years of age scheduled for major noncardiac surgery. Cognitive function was assessed before and 1 week after surgery. POCD was diagnosed if a decline of >1 standard deviation of z-scores was present in \u22652 variables of the test battery. The incidence of POCD 1 week after surgery was modeled as a multivariable function of the index of autoregulation (MxA) and tissue oxygenation index (TOI), adjusting for baseline neuropsychological assessment battery (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery [CERAD-NAB]) total score and the maximum C-reactive protein (CRP) concentration. The biomarkers of brain injury neuron-specific enolase and S100\u03b2 protein, age, and level of education were included in secondary multivariable logistic regression analyses. Of the 82 patients who completed the study, 38 (46%) presented with POCD 1 week after surgery. In the multivariable regression analysis, higher intraoperative MxA (odds ratio [OR; 95% confidence interval (CI)], 1.39 [1.01-1.90] for an increase of 0.1 units, P = .08 after Bonferroni adjustment), signifying less effective autoregulation, was not associated with higher odds of POCD. The univariable logistic regression model for MxA yielded an association with POCD (OR [95% CI], 1.44 [1.06-1.95], P = .020). Tissue oxygenation index (1.12 [0.41-3.01] for an increase of 10%, P = 1.0 after Bonferroni adjustment) and baseline CERAD-NAB total score (0.80 [0.45-1.42] for an increase of 10 points, P = .45) did not affect the odds of POCD. POCD was associated with elevated CRP on postoperative day 2 (median [interquartile range]; 175 [81-294] vs 112 [62-142] mg\/L, P = .033); however, the maximum CRP value (OR [95% CI], 1.35 [0.97-1.87] for a 2-fold increase, P = .07) had no distinct effect on POCD. Impairment of intraoperative cerebral blood flow autoregulation is not predictive of early POCD in elderly patients, although secondary analyses indicate that an association probably exists.","subset":"pubmed_abstract"} +{"meta":{"pmid":35619518,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":12}}},"text":"Segmental Rearrangements Relax Stresses in Nonequilibrated Polymer Films.\nWe probed the relaxation of preparation-induced residual stresses in nonequilibrated polymer films through dewetting experiments. While we observed fast relaxations at temperatures close to or below the glass transition, at elevated temperatures these relaxation times were orders of magnitude longer than the reptation time. Intriguingly, applying appropriate scaling of preparation conditions allowed us to present all relaxation times, including published data, from various complementary experiments on a single master curve exhibiting an Arrhenius-type behavior. The corresponding activation energy (75 \u00b1 10 kJ\/mol) is similar to values obtained for the relaxation of segments in polystyrene. The observed long relaxation times suggest that residual stresses, a consequence of nonequilibrium conformations inherited from preparation, relax via concerted rearrangements of many segments.","subset":"pubmed_abstract"} +{"meta":{"pmid":24808419,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":8}}},"text":"MRI of hepatocellular carcinoma: an update of current practices.\nHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and liver transplantation is the optimal treatment for selected patients with HCC and chronic liver disease (CLD). Accurate selection of patients for transplantation is essential to maximize patient outcomes and ensure optimized allocation of donor organs. Magnetic resonance imaging (MRI) is a powerful tool for the detection, characterization, and staging of HCC. In patients with CLD, the MRI findings of an arterial-enhancing mass with subsequent washout and enhancing capsule on delayed interstitial phase images are diagnostic for HCC. Major organizations with oversight for organ donor distribution, such as The Organ Procurement and Transplantation Network (OPTN), accept an imaging diagnosis of HCC, no longer requiring tissue biopsy. In patients that are awaiting transplantation, or are not candidates for liver transplantation, localized therapies such as transarterial chemoembolization and radiofrequency ablation may be offered. MRI can be used to monitor treatment response. The purpose of this review article is to describe the role of imaging methods in the diagnosis, staging, and follow-up of HCC, with particular emphasis on established and evolving MRI techniques employing nonspecific gadolinium chelates, hepatobiliary contrast agents, and diffusion weighted imaging. We also briefly review the recently developed Liver Imaging Reporting and Data System (LI-RADS) formulating a standardized terminology and reporting structure for evaluation of lesions detected in patients with CLD.","subset":"pubmed_abstract"} +{"meta":{"pmid":27425255,"dup_signals":{"dup_doc_count":22,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":18}}},"text":"Stimulatory effects of advanced glycation endproducts (AGEs) on fibronectin matrix assembly.\nAdvanced glycation endproducts (AGEs) are a heterogeneous group of compounds that form via non-enzymatic glycation of proteins throughout our lifespan and at a higher rate in certain chronic diseases such as diabetes. AGEs contribute to the progression of fibrosis, in part by stimulating cellular pathways that affect gene expression. Long-lived ECM proteins are targets for non-enzymatic glycation but the question of whether the AGE-modified ECM leads to excess ECM accumulation and fibrosis remains unanswered. In this study, cellular changes due to AGE accretion in the ECM were investigated. Non-enzymatic glycation of proteins in a decellularized fibroblast ECM was achieved by incubating the ECM in a solution of methylglyoxal (MGO). Mass spectrometry of fibronectin (FN) isolated from the glycated matrix identified twenty-eight previously unidentified MGO-derived AGE modification sites including functional sites such as the RGD integrin-binding sequence. Mesangial cells grown on the glycated, decellularized matrix assembled increased amounts of FN matrix. Soluble AGE-modified bovine serum albumin (BSA) also stimulated FN matrix assembly and this effect was reduced by function-blocking antibodies against the receptor for AGE (RAGE). These results indicate that cells respond to AGEs by increasing matrix assembly and that RAGE is involved in this response. This raises the possibility that the accumulation of ECM during the progression of fibrosis may be enhanced by cell interactions with AGEs on a glycated ECM.","subset":"pubmed_abstract"} +{"meta":{"pmid":8306968,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-21":2,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2023-50":1,"2024-26":1,"2024-10":2,"2024-30":1}}},"text":"The chromatin-associated protein H-NS alters DNA topology in vitro.\nH-NS is one of the two most abundant proteins in the bacterial nucleoid and influences the expression of a number of genes. We have studied the interaction of H-NS with DNA; purified H-NS was demonstrated to constrain negative DNA supercoils in vitro. This provides support for the hypothesis that H-NS influences transcription via changes in DNA topology, and is evidence of a structural role for H-NS in bacterial chromatin. The effects of H-NS on topology were only observed at sub-saturating concentrations of the protein. In addition, a preferred binding site on DNA was identified by DNase I footprinting at sub-saturating H-NS concentrations. This site corresponded to a curved sequence element which we previously showed, by in vivo studies, to be a site at which H-NS influences transcription of the proU operon. When present in saturating concentrations, H-NS did not constrain supercoils and bound to DNA in a sequence-independent fashion, covering all DNA molecules from end to end, suggesting that H-NS may form distinct complexes with DNA at different H-NS:DNA ratios. The data presented here provide direct support for the hypothesis that H-NS acts at specific sites to influence DNA topology and, hence, transcription.","subset":"pubmed_abstract"} +{"meta":{"pmid":16516581,"dup_signals":{"dup_doc_count":11}},"text":"Use of stress testing early after coronary artery bypass graft surgery.\nThe American College of Cardiology\/American Heart Association guidelines for exercise testing do not take a position regarding the utility of routine stress testing after coronary artery bypass grafting (CABG). Our purposes were (1) to document the patterns of use of stress testing after CABG and (2) to establish whether the choice of stress testing strategy is associated with clinical characteristics of patients. The Routine versus Selective Exercise Treadmill Testing after Coronary Artery Bypass Graft Surgery (ROSETTA-CABG) Registry is a prospective multicenter study that examined the use of stress testing after CABG among 395 patients at 16 clinical centers in 6 countries. During the 12 months after CABG, 37% of patients underwent stress testing (range across centers 0% to 100%). Among patients who underwent stress testing, 24% had a clinical indication and 76% had it as a routine follow-up. A total of 65% of stress tests involved exercise treadmill testing alone, 17% involved stress nuclear perfusion imaging, 13% involved stress echocardiographic imaging, and 5% involved other types of stress tests, such as positron emission tomographic scans. The first stress test was performed at a median of 13 weeks after CABG, with 20% of patients having second tests at a median of 28 weeks and 6% having additional tests at a median of 34 weeks. Univariate and multivariate analyses demonstrated that the chief determinant of using routine stress testing was the clinical center. In conclusion, these results suggest that there is little consensus on the appropriate use of stress testing soon after CABG. Practice patterns vary widely; poorly diagnostic tests are used routinely; and the clinical center at which the procedure is performed, rather than the clinical characteristics of the patient, determines the use of stress testing after CABG.","subset":"pubmed_abstract"} +{"meta":{"pmid":25776532,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":1,"unknown":7}}},"text":"Trial of early, goal-directed resuscitation for septic shock.\nEarly, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).","subset":"pubmed_abstract"} +{"meta":{"pmid":15784565,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":18}}},"text":"Elucidation of the monoclonal antibody 5G8-reactive, virulence-associated lipopolysaccharide epitope of Haemophilus influenzae and its role in bacterial resistance to complement-mediated killing.\nThe phase-variable locus lex2 is required for expression of a Haemophilus influenzae lipopolysaccharide (LPS) epitope of previously unknown structure. This epitope, which is reactive with monoclonal antibody (MAb) 5G8, has been associated with virulence of type b strains. When strain RM118 (from the same source as strain Rd), in which the lex2 locus and MAb 5G8 reactivity are absent, was transformed with lex2 DNA, transformants that were reactive with MAb 5G8 were obtained. Surprisingly, the 5G8 reactivity of these transformants was phase variable, although the lex2 locus lacked tetrameric repeats and was constitutively expressed. This phase variation was shown to be the result of phase-variable expression of phosphorylcholine (PCho) such that MAb 5G8 reacted only in the absence of PCho. Structural analysis showed that, compared to RM118, the lex2 transformant had acquired a tetrasaccharide, Gal-alpha1,4-Gal-beta1,4-Glc-beta1,4-Glc-beta1,4, linked to the proximal heptose (HepI). A terminal GalNAc was detected in a minority of glycoforms. LPS derived from a mutant of RM7004, a virulent type b strain which naturally expresses lex2 and has LPS containing the same tetrasaccharide linked to HepI as the sole oligosaccharide extension from the inner core, confirmed that GalNAc is not a part of the MAb 5G8-reactive epitope. Thus, MAb 5G8 specifically binds to the structure Gal-alpha1,4-Gal-beta1,4-Glc-beta1,4-Glc-beta attached via a 1,4 linkage to HepI of H. influenzae LPS, and we show that the ability to synthesize this novel tetrasaccharide was associated with enhanced bacterial resistance to complement-mediated killing.","subset":"pubmed_abstract"} +{"meta":{"pmid":30327479,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Structural basis for arginine glycosylation of host substrates by bacterial effector proteins.\nThe bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-\u03baB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens.","subset":"pubmed_abstract"} +{"meta":{"pmid":11912212,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":2,"2013-20":1,"unknown":6}}},"text":"Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation.\nPIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function. We now report that PIMT strongly interacts with transcriptional coactivators, CBP, p300, and PBP but not with SRC-1 and PGC-1alpha under in vitro and in vivo conditions. The PIMT binding sites on CBP and p300 are located in the cysteine-histidine-rich C\/H1 and C\/H3 domains, and the PIMT binding site on PBP is in the region encompassing amino acids 1101-1560. The N-terminal of PIMT (residues 1-369) containing the RNA binding domain interacts with both C\/H1 and C\/H3 domains of CBP and p300 and with the C-terminal portion of PBP that encompasses amino acids 1371-1560. The C-terminal of PIMT (residues 611-852), which binds S-adenosyl-l-methionine, interacts respectively with the C\/H3 domain of CBP\/p300 and with a region encompassing amino acids 1101-1370 of PBP. Immunoprecipitation data showed that PIMT forms a complex in vivo with CBP, p300, PBP, and PRIP. PIMT appeared to be co-localized in the nucleus with CBP, p300, and PBP. PIMT enhanced PBP-mediated transcriptional activity of the PPARgamma, as it did for PRIP, indicating synergism between PIMT and PBP. In contrast, PIMT functioned as a repressor of CBP\/p300-mediated transactivation of PPARgamma. Based on these observations, we suggest that PIMT bridges the CBP\/p300-anchored coactivator complex with the PBP-anchored coactivator complex but differentially modulates coactivator function such that inhibition of the CBP\/p300 effect may be designed to enhance the activity of PBP and PRIP.","subset":"pubmed_abstract"} +{"meta":{"pmid":21785622,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"New perspectives on chinese herbal medicine (zhong-yao) research and development.\nSynthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":12185772,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":4,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"'A systematic overview--a decade of research'. The information and counselling needs of people with epilepsy.\nThis paper explores the background to epilepsy in terms of medical impact and psychosocial effects. The argument that information and counselling may be central to the person with epilepsy is explored. The evidence from primary research published between 1990 and 2000 investigating the information and counselling needs of people with epilepsy is appraised and synthesized. This paper seeks to answer the following questions: What are the information and counselling needs of people with epilepsy? What are the preferred formats, timing and delivery of information and counselling? What are the outcomes of information giving and counselling for people with epilepsy? The review suggests that there are unmet needs for personal and general information about epilepsy which may include individual or group education and counselling. Information related to gaining control for people with epilepsy and targeted public education may contribute to improved quality of life for people with epilepsy. Information is required which is individually relevant and could be delivered in small groups or as part of an individual counselling service. Specialist epilepsy clinics and specialist nurses can improve patient knowledge and communication and provide an effective and high quality service for people with epilepsy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28572671,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Interaction studies of carbon nanomaterials and plasma activated carbon nanomaterials solution with telomere binding protein.\nMost cancer cells have telomerase activity because they can express the human telomerase reverse transcriptase (hTERT) gene. Therefore, the inhibition of the hTERT expression can play an important role in controlling cancer cell proliferation. Our current study aims to inhibit hTERT expression. For this, we synthesized graphene oxide (GO) and a functionalized multiwall carbon nanotube (f-MWCNT), latter treated them with cold atmospheric pressure plasma for further analysis of the hTERT expression. The inhibition of hTERT expression by GO, f-MWCNT, plasma activated GO solution (PGOS), and plasma activated f-MWCNT solution (PCNTS), was studied using two lung cancer cell lines, A549 and H460. The hTERT experimental results revealed that GO and PGOS sufficiently decreased the hTERT concentration, while f-MWCNT and PCNTS were unable to inhibit the hTERT concentration. Therefore, to understand the inhibition mechanism of hTERT, we studied the binding properties of GO and PGOS with telomere binding protein (AtTRB2). The interaction studies were carried out using circular dichroism, fluorescence, 1H-15N NMR spectroscopy, and size-exclusion chromatography (SEC) binding assay. We also used docking simulation to have an better understanding of the interactions between GO nanosheets and AtTRB2 protein. Our results may provide new insights that can benefit in biomedical treatments.","subset":"pubmed_abstract"} +{"meta":{"pmid":31602463,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-21":1,"2020-50":1,"2020-24":1,"2023-50":1,"2024-18":1}}},"text":"Bereaved Family Cancer Caregivers' Unmet Needs: Measure Development and Validation.\nAccumulating evidence shows that bereaved family caregivers report elevated distress for an extended period, which compromises their quality of life. A first step in the development of programs to enhance bereaved caregivers' quality of life should be determining the needs they experience to manage the loss, and the needs that are not being satisfied. Thus, this study aimed to develop a new measure to assess unmet needs among bereaved family caregivers. The 20-item Needs Assessment of Family Caregivers-Bereaved to Cancer measure was developed and validated with bereaved cancer caregivers 5 (n = 159) and 8 (n = 194) years after the initial cancer diagnosis of the index patient, when stress in providing care to the patient was assessed. Exploratory factor analysis yielded two primary factors: unmet needs for reintegration and unmet needs for managing the loss. Bereaved caregivers who were younger and ethnic minority, and who had greater earlier perceived stress of caregiving, reported their needs were more poorly met (t > 2.33, p < .05). The extent to which bereaved caregivers' needs to manage the loss were not perceived as being met was a consistent and strong predictor of poor adjustment to bereavement at both 5- and 8-year marks (t > 1.96, p < .05), beyond the effects of a host of demographic and earlier caregiving characteristics. Findings support the validity of the Needs Assessment of Family Caregivers-Bereaved to Cancer and suggest that interventions to help bereaved caregivers manage the loss by assisting their transition to re-engagement in daily and social activities will benefit caregivers by mitigating bereavement-related distress years after the loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":30243556,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-14":3,"2023-06":1,"2022-21":1,"2021-43":2,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Cartilage-sparing surgery for melanoma of the external ear.\nThe excision of melanoma of the external ear poses a challenge to surgeons, who must achieve adequate oncological control while minimising impact on form and function. Cartilage-preserving surgery is an attractive option, as it leaves behind a scaffold for immediate reconstruction with a variety of techniques including full-thickness skin grafts (FTSGs) and local flaps. This manuscript will review the literature comparing cartilage-sparing surgery with composite excision of the skin and the cartilage for the treatment of auricular melanoma. We report the results of a 17 year experience of using both techniques, together with sentinel node biopsy at our centre. A structured review of MEDLINE and EMBASE was conducted to evaluate all studies reporting local recurrence or survival rates for melanoma of the external ear treated with cartilage-preserving surgery. A retrospective review of all patients undergoing wide local excision (WLE) and sentinel lymph node biopsy (SLNB) for auricular melanoma at our centre between 2000 and 2017 was performed. Of 40 patients identified, 29 underwent cartilage-preserving surgery with no local recurrences or evidence of perichondral involvement. There was one local recurrence out of 11 patients who had their cartilage excised. There were no significant differences in recurrence rates or melanoma-specific survival rates when comparing cartilage-preserving and cartilage-sparing surgery. Our results are supported by the literature review, which suggests that cartilage-sparing surgery is gaining acceptance as a safe practice.","subset":"pubmed_abstract"} +{"meta":{"pmid":20957113,"dup_signals":{"dup_doc_count":32,"dup_dump_count":24,"dup_details":{"curated_sources":1,"2022-05":2,"2021-49":1,"2021-43":1,"2021-39":2,"2021-21":1,"2020-16":2,"2020-10":1,"2019-43":1,"2019-30":1,"2019-26":2,"2019-18":1,"2019-13":1,"2019-09":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-17":2,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":2,"2017-39":1,"2022-40":1}}},"text":"Exposure to sodium fluoride produces signs of apoptosis in rat leukocytes.\nFluoride is naturally present in the earth's crust and can be found in rocks, coal, and clay; thus, it can be found in small quantities in water, air, plants, and animals. Therefore, humans are exposed to fluoride through food, drinking water, and in the air they breathe. Flouride is essential to maintain bone strength and to protect against dental decay, but if it is absorbed too frequently, it can cause tooth decay, osteoporosis, and damage to kidneys, bones, nerves, and muscles. Therefore, the present work was aimed at determining the effect of intake of sodium fluoride (NaF) as an apoptosis inducer in leukocytes of rats treated for eight weeks with 1 or 50 parts per million (ppm) NaF. Expression of p53, bcl-2, and caspade-3 were used as apoptotic and general metabolism indicators of leukocyte-like indicators of the (INT) oxidation system. Male rats were exposed to NaF (1 and 500 ppm) for eight weeks, and then sacrificed weekly to obtain blood samples. Expression of p53, bcl-2, and caspase-3 were determined in leukocytes by Western blot, and general metabolism of leukocytes was analyzed with a commercial kit. We found changes in the expression of the proteins described, especially when the animals received 50 ppm of NaF. These results indicate that NaF intoxication can be an apoptosis inducer in rat leukocytes treated with the compound for eight weeks.","subset":"pubmed_abstract"} +{"meta":{"pmid":21359211,"dup_signals":{"dup_doc_count":32,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2018-30":1,"2018-26":4,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":2,"2017-39":3,"2017-34":1,"2017-30":2,"2017-26":2,"2017-22":1,"2017-17":2,"2023-23":1,"2024-18":1,"2013-20":1,"2024-22":1}}},"text":"Earliest directly-dated human skull-cups.\nThe use of human braincases as drinking cups and containers has extensive historic and ethnographic documentation, but archaeological examples are extremely rare. In the Upper Palaeolithic of western Europe, cut-marked and broken human bones are widespread in the Magdalenian (\u223c15 to 12,000 years BP) and skull-cup preparation is an element of this tradition. Here we describe the post-mortem processing of human heads at the Upper Palaeolithic site of Gough's Cave (Somerset, England) and identify a range of modifications associated with the production of skull-cups. New analyses of human remains from Gough's Cave demonstrate the skilled post-mortem manipulation of human bodies. Results of the research suggest the processing of cadavers for the consumption of body tissues (bone marrow), accompanied by meticulous shaping of cranial vaults. The distribution of cut-marks and percussion features indicates that the skulls were scrupulously 'cleaned' of any soft tissues, and subsequently modified by controlled removal of the facial region and breakage of the cranial base along a sub-horizontal plane. The vaults were also 'retouched', possibly to make the broken edges more regular. This manipulation suggests the shaping of skulls to produce skull-cups. Three skull-cups have been identified amongst the human bones from Gough's Cave. New ultrafiltered radiocarbon determinations provide direct dates of about 14,700 cal BP, making these the oldest directly dated skull-cups and the only examples known from the British Isles.","subset":"pubmed_abstract"} +{"meta":{"pmid":16765501,"dup_signals":{"dup_doc_count":14}},"text":"Proposal to improve vertebrate cell cultures to establish them as substitutes for the regulatory testing of chemicals and effluents using fish.\nCultures of vertebrate cells are widely applied in mechanistic studies in human toxicology as well as in toxicity identification in ecotoxicology. As in vitro models, they display many advantages over whole animal experimentation, pertaining to such characteristics as availability, reproducibility and costs. As well, they satisfy the societal desire to reduce the number of animals in toxicology. For these reasons vertebrate cell models also appear to be a desirable replacement for animals in regulatory tests. Several vertebrate cell models are now accepted for regulatory purposes in human health sciences, with the test for photocytotoxicity using the 3T3 mouse cell line being one example. However, an in vitro alternative to whole animal tests has not yet been established for regulatory risk assessment in ecotoxicology. This review sets out to outline why such a replacement has not yet been possible and explores avenues to improve vertebrate cell cultures so that a replacement of whole animal tests could more likely be achieved. Inasmuch as fish is the most widely used non-mammalian vertebrate in risk assessment and regulation, focus will be on the replacement, by in vitro vertebrate models, of fish.","subset":"pubmed_abstract"} +{"meta":{"pmid":26344924,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Minor Elevation in C-Reactive Protein Levels Predicts Incidence of Erythropoiesis-Stimulating Agent Hyporesponsiveness among Hemodialysis Patients.\nHemodialysis (HD) patients occasionally experience minor asymptomatic elevation in C-reactive protein (CRP) levels, which may be associated with difficulty in managing renal anemia using erythropoiesis-stimulating agents (ESAs). Here, we assessed whether elevation of CRP predicts future incidences of ESA hyporesponsiveness. A total of 2,956 HD patients lacking ESA hyporesponsiveness and infectious diseases were enrolled, and the association between CRP levels and incidence of ESA hyporesponsiveness was assessed. CRP levels were divided into 4 categories (normal [<1.0 mg\/l], mild [1.0 \u2264 CRP <3.0 mg\/l], moderate [3.0 \u2264 CRP <10.0 mg\/l] and high [\u2265 10.0 mg\/l]). The primary outcome was the cumulative incidence of ESA hyporesponsiveness, defined as a failure to achieve hemoglobin level \u2265 10 g\/dl despite receiving high doses of ESAs (\u2265 9,000 U\/week recombinant human epoetin [rHuEPO]-\u03b1 or rHuEPO-\u03b2 and \u2265 60 \u03bcg\/week darbepoetin-\u03b1) during 12 months of follow-up. The cumulative incidence of ESA hyporesponsiveness was 134 (4.8%) occurrences over 4 months and 300 (12.4%) over 12 months. The elevated CRP groups had significantly higher incidence of ESA hyporesponsiveness over 4 months of follow-up than the normal reference group (adjusted relative risk [RR] 1.6, 95% CI 1.0-2.6 for moderate; adjusted RR 2.5, 95% CI 1.5-4.1 for high). Furthermore, the association remained consistent even over 12 months (adjusted RR 1.4, 95% CI 1.0-1.8 for moderate; adjusted RR 1.6, 95% CI 1.1-2.4 for high). Elevated CRP levels were associated with future incidence of ESA hyporesponsiveness from low-grade inflammation (3.0 \u2264 CRP <10.0 mg\/l).","subset":"pubmed_abstract"} +{"meta":{"pmid":27542302,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-23":1,"2022-33":1,"2022-21":2,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2019-39":1,"2023-50":1}}},"text":"Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial.\nNon-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids. We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged \u226518 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg\/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838. Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8\u00b73 months; hazard ratio 0\u00b757, 95% CI 0\u00b739-0\u00b784; p=0\u00b7004). The 40th percentile for time to treatment failure was 4\u00b78 months in the placebo group and 10\u00b72 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group). Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis. AbbVie.","subset":"pubmed_abstract"} +{"meta":{"pmid":32805014,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":15}}},"text":"Habitual Coffee and Tea Consumption and Cardiometabolic Biomarkers in the UK Biobank: The Role of Beverage Types and Genetic Variation.\nMechanisms linking habitual consumption of coffee and tea to the development of type 2 diabetes and cardiovascular diseases remain unclear. We leveraged dietary, genetic, and biomarker data collected from the UK Biobank to investigate the role of different varieties of coffee and tea in cardiometabolic health. We included data from \u2264447,794 participants aged 37-73 y in 2006-2010 who provided a blood sample and completed questionnaires regarding sociodemographic factors, medical history, diet, and lifestyle. Multivariable linear regression was used to examine the association between coffee or tea consumption and blood concentrations of glycated hemoglobin, fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, fasting triglycerides (TGs), apoA-1, apoB, lipoprotein-a, and C-reactive protein (CRP). Lifestyle and genetic factors affecting caffeine metabolism, responses, or intake were tested for interactions with beverage intake in relation to biomarker concentrations. Compared with coffee nonconsumers, each additional cup of coffee was significantly associated with higher total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations and lower TG and CRP concentrations in both men and women (P-trend < 0.002). Higher consumption of espresso coffee (\u22652 compared with 0 cups\/d) was associated with higher LDL cholesterol in men (\u03b2: 0.110 mmol\/L; 95% CI: 0.058, 0.163 mmol\/L) and women (\u03b2: 0.161 mmol\/L; 95% CI: 0.088, 0.234 mmol\/L), whereas no substantial association was observed for instant coffee. Compared with tea nonconsumers, higher tea consumption was associated with lower total and LDL cholesterol and apoB and higher HDL cholesterol (P-trend < 0.002); these associations were similar for black and green tea. Associations were not modified by genetics. In the UK Biobank, consumption of certain coffee brews such as espresso had unfavorable associations with blood lipids, whereas consumption of tea had favorable associations. Findings were not modified by genetic variants affecting caffeine metabolism, suggesting a role of noncaffeine constituents of these beverages in cardiometabolic health.","subset":"pubmed_abstract"} +{"meta":{"pmid":30863108,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-22":1,"unknown":15}}},"text":"First-line tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer: a network meta-analysis.\nEGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA). A systematic review was performed, aiming to find eligible literature. Data of PFS, overall survival (OS), objective response rate (ORR), and adverse events were extracted. An NMA based on Bayesian statistics was established to synthesize the efficacy and toxicity of all treatments. Thirteen randomized controlled trials, including data from 3,539 patients with EGFR-mutated NSCLC, were analyzed. Rank probabilities showed that osimertinib had a potentially better efficacy in terms of PFS and OS compared to all other TKIs. For ORR, afatinib and osimertinib showed a trend of superiority compared to the other four TKIs. Furthermore, there was a high risk of diarrhea and rash for patients treated with afatinib or dacomitinib as well as a moderate risk for treatment with erlotinib, gefitinib, and osimertinib. Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations. Furthermore, gefitinib, erlotinib, and osimertinib were associated with fewer toxicities compared to the other TKIs. Therefore, osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC.","subset":"pubmed_abstract"} +{"meta":{"pmid":23006970,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":12}}},"text":"Sexual dysfunction in Assyrian\/Syrian immigrants and Swedish-born persons with type 2 diabetes.\nFew studies have investigated sexual dysfunction in immigrant patients with type 2 diabetes in Sweden. The aim of this study was to examine the association between ethnicity and sexual dysfunction and to analyze if this association remains after adjusting for explanatory variables including age, marital status, HbA1c, triglycerides, and hypertension. This cross-sectional study was conducted at four primary health care centers in the Swedish town of S\u00f6dert\u00e4lje. A total of 354 persons with type 2 diabetes (173 Assyrians\/Syrians and 181 Swedish-born patients) participated in the survey. The main outcome measure was the self-reported presence of sexual dysfunction based on two questions, one regarding loss of ability to have sexual intercourse and the other loss of sexual desire. Response rates were 78% and 86%, respectively. The total prevalence of loss of ability to have intercourse was 29.5%. In the multivariate models, the odds of loss of ability to have intercourse was significantly higher in the oldest age group (OR = 5.80; 95% CI, 2.33-14.40), in men (OR = 3.33; 95% CI, 1.33-8.30), and in unmarried individuals (OR = 2.40; 95% CI, 1.02-5.70). The odds of reporting loss of sexual desire was higher in Assyrians\/Syrians than in Swedish-born patients and increased from 2.00 in the age- and gender-adjusted model to 2.70 in the fully adjusted model when all confounders were taken into account. Sexual dysfunction appears to be more common in Assyrians\/Syrians than in Swedish-born patients. Health care workers should actively ask about sexual function in their patients with type 2 diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":10218242,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-06":1,"2014-10":1,"2013-48":2,"2013-20":1,"2015-11":1,"unknown":3}}},"text":"Back problems. Neuroanatomy and neurological examination.\nComponents of the equine nervous system are described including classical anatomy and newer sensory innervation maps that are useful for localizing lesions to and within the nervous system. The key components in a neurological examination that help differentiate primary neurologic disease from musculoskeletal disorders are explained. Gait deficits associated with neurologic dysfunction are listed as well as diagnostic aids and an overview of differential diagnoses.","subset":"pubmed_abstract"} +{"meta":{"pmid":20974833,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Computational prediction of type III and IV secreted effectors in gram-negative bacteria.\nIn this review, we provide an overview of the methods employed in four recent studies that described novel methods for computational prediction of secreted effectors from type III and IV secretion systems in Gram-negative bacteria. We present the results of these studies in terms of performance at accurately predicting secreted effectors and similarities found between secretion signals that may reflect biologically relevant features for recognition. We discuss the Web-based tools for secreted effector prediction described in these studies and announce the availability of our tool, the SIEVE server (http:\/\/www.sysbep.org\/sieve). Finally, we assess the accuracies of the three type III effector prediction methods on a small set of proteins not known prior to the development of these tools that we recently discovered and validated using both experimental and computational approaches. Our comparison shows that all methods use similar approaches and, in general, arrive at similar conclusions. We discuss the possibility of an order-dependent motif in the secretion signal, which was a point of disagreement in the studies. Our results show that there may be classes of effectors in which the signal has a loosely defined motif and others in which secretion is dependent only on compositional biases. Computational prediction of secreted effectors from protein sequences represents an important step toward better understanding the interaction between pathogens and hosts.","subset":"pubmed_abstract"} +{"meta":{"pmid":963839,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon.\nThe effect of chronic renovascular hypertension on the autoregulation of cerebral blood flow was studied in anesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe clearance method. Six baboons with renal hypertension of 8-12 weeks' duration were compared with six normotensive controls. The lower limit of autoregulation was determined following controlled hemorrhage. In the initially normotensive baboons, cerebral blood flow remained constant until mean arterial pressure had decreased to the range of 45-59 mm Hg. Thereafter, cerebral blood flow decreased with each further decrease in mean arterial pressure. In the chronically hypertensive baboons cerebral blood flow autoregulated until the mean arterial pressure had decreased to the range of 75-89 mm Hg. Therefore, the lower limit of autoregulation of cerebral blood flow was shifted to higher absolute levels of mean arterial pressure in baboons with chronic renovascular hypertension presumably due to adaptive changes in the cerebral circulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":32176703,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial.\nLymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for control of lymphatic filariasis and other neglected tropical diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":30961031,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Effect of Morphological Changes due to Increasing Carbon Nanoparticles Content on the Quasi-Static Mechanical Response of Epoxy Resin.\nMechanical failure in epoxy polymer and composites leads them to commonly be referred to as inherently brittle due to the presence of polymerization-induced microcrack and microvoids, which are barriers to high-performance applications, e.g., in aerospace structures. Numerous studies have been carried out on epoxy's strengthening and toughening via nanomaterial reinforcement, e.g., using rubber nanoparticles in the epoxy matrix of new composite aircraft. However, extremely cautious process and functionalization steps must be taken in order to achieve high-quality dispersion and bonding, the development of which is not keeping pace with large structures applications. In this article, we report our studies on the mechanical performance of an epoxy polymer reinforced with graphite carbon nanoparticles (CNPs), and the possible effects arising from a straightforward, rapid stir-mixing technique. The CNPs were embedded in a low viscosity epoxy resin, with the CNP weight percentage (wt %) being varied between 1% and 5%. Simplified stirring embedment was selected in the interests of industrial process facilitation, and functionalization was avoided to reduce the number of parameters involved in the study. Embedment conditions and timing were held constant for all wt %. The CNP filled epoxy resin was then injected into an aluminum mold and cured under vacuum conditions at 80 \u00b0C for 12 h. A series of test specimens were then extracted from the mold, and tested under uniaxial quasi-static tension, compression, and nanoindentation. Elementary mechanical properties including failure strain, hardness, strength, and modulus were measured. The mechanical performance was improved by the incorporation of 1 and 2 wt % of CNP but was degraded by 5 wt % CNP, mainly attributed to the morphological change, including re-agglomeration, with the increasing CNP wt %. This change strongly correlated with the mechanical response in the presence of CNP, and was the major governing mechanism leading to both mechanical improvement and degradation.","subset":"pubmed_abstract"} +{"meta":{"pmid":17363237,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"The phylogenetic placement of Ostropales within Lecanoromycetes (Ascomycota) revisited.\nResults of molecular studies regarding the phylogenetic placement of the order Ostropales and related taxa within Lecanoromycetes were thus far inconclusive. Some analyses placed the order as sister to the rest of Lecanoromycetes, while others inferred a position nested within Lecanoromycetes. We assembled a data set of 101 species including sequences from nuLSU rDNA, mtSSU rDNA, and the nuclear protein-coding RPB1 for each species to examine the cause of incongruencies in previously published phylogenies. MP, minimum evolution, and Bayesian analyses were performed using the combined three-region data set and the single-gene data sets. The position of Ostropales nested in Lecanoromycetes is confirmed in all single-gene and concatenated analyses, and a placement as sister to the rest of Lecanoromycetes is significantly rejected using two independent methods of alternative topology testing. Acarosporales and related taxa (Acarosporaceae group) are basal in Lecanoromycetes. However, if the these basal taxa are excluded from the analyses, Ostropales appear to be sister to the rest of Lecanoromycetes, suggesting different ingroup rooting as the cause for deviating topologies in previously published phylogenies.","subset":"pubmed_abstract"} +{"meta":{"pmid":9414070,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":3,"2022-33":1,"2022-27":2,"2022-21":1,"2021-10":1,"2020-10":1,"2019-43":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-40":1}}},"text":"Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review.\nCreatine supplementation has become a common practice among competition athletes participating in different sports over the last few years. The mechanism by which supplementary creatine could have potential ergogenic effects would be an increased muscle creatine and phosphocreatine concentration, leading to a higher rate of ATP resynthesis, a delay in the onset of muscular fatigue and a facilitated recovery during repeated bouts of high-intensity exercise. A critical review of the literature reveals that these ergogenic effects, when found, have been generally shown in untrained subjects performing several exercise bouts under laboratory conditions. The limited body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population does not benefit from creatine supplementation. Therefore, the widespread use of creatine ingestion to improve competition performance does not seem to be justified. The potential interest of creatine supplementation for elite athletes could be related to an increased ability to perform repeated high-intensity exercise bouts, either during training or during competition in sports in which repeated efforts are required (e.g. soccer, basketball), but this possibility needs scientific confirmation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21438645,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review.\nTo evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES\/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. A number of herbal medicines show promise in the management of mild-to-moderate depression.","subset":"pubmed_abstract"} +{"meta":{"pmid":32288994,"dup_signals":{"dup_doc_count":12,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":2,"2018-51":2,"2018-26":1,"2018-17":1,"2018-05":1,"2023-50":1}}},"text":"The relationship between obsessive compulsive beliefs and symptoms, anxiety and disgust sensitivity, and Swine Flu fears.\nUsing the 2009 Swine Flu outbreak as a contemporary example of pandemic fears, this study examined the relationship between various symptoms related to anxiety sensitivity and Swine Flu fears. It was hypothesized that both obsessive-compulsive (OC) beliefs and OC symptoms would significantly predict Swine Flu fears. It was also hypothesized that symptoms of anxiety, including measures of anxiety sensitivity and disgust sensitivity would significantly mediate the relationship between both OC beliefs and OC symptoms and Swine Flu fears. A total of 393 undergraduate students completed measures of Swine Flu fears, anxiety sensitivity, OC beliefs and symptoms, and disgust sensitivity. It was found that both OC beliefs and OC symptoms significantly predicted Swine Flu fears. While disgust sensitivity significantly mediated the relationship between both OC beliefs and OC symptoms and Swine Flu fears using the Sobel test, anxiety sensitivity was a significant mediator only for OC symptoms. Additionally, path modeling showed that anxiety sensitivity mediated the relationship between OC symptoms and Swine Flu fears best. The results of this study may be useful for treating individuals suffering from anxiety in light of future pandemics, as well as continuing to research the role of anxiety symptoms in predicting pandemic fears.","subset":"pubmed_abstract"} +{"meta":{"pmid":22980021,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2013-20":1,"2024-22":1,"unknown":12}}},"text":"Bacteriological survey of ready-to-eat lettuce, fresh-cut fruit, and sprouts collected from the Swiss market.\nThe consumption of ready-to-eat fresh vegetables has increased significantly in the recent decades. So far, no data are available on the bacteriological burden and the prevalence of foodborne pathogens in ready-to-eat lettuce, fresh-cut fruit, and sprouts on the Swiss market. This study was based on investigations carried out during 2 months of the summer season in 2011. Samples of 142 salads, 64 fresh-cut fruit, and 27 sprouts were included in this study. Escherichia coli, an indicator microorganism for fecal contamination, was only found in 5 lettuce samples, with amounts ranging between 2 and 3 log CFU\/g. No Salmonella spp. were detected from any of the 233 samples analyzed in this study, and a low occurrence was found for contamination with L. monocytogenes, Shiga toxin-producing E. coli, enteropathogenic E. coli, and Cronobacter. From the results of the present study, we conclude that even in a country where the use of chlorine solutions to sanitize fruits and vegetables in the fresh-cut industry is not allowed, it is possible to produce ready-to-eat lettuce, fresh-cut fruit, and sprouts with high microbiological standards. Strict maintenance of good practices of hygiene at preharvest, harvest, and postharvest levels is of central importance to ensure both public health protection and product quality.","subset":"pubmed_abstract"} +{"meta":{"pmid":17071782,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Efficient production of L-lactic acid from xylose by Pichia stipitis.\nMicrobial conversion of renewable raw materials to useful products is an important objective in industrial biotechnology. Pichia stipitis, a yeast that naturally ferments xylose, was genetically engineered for l-(+)-lactate production. We constructed a P. stipitis strain that expressed the l-lactate dehydrogenase (LDH) from Lactobacillus helveticus under the control of the P. stipitis fermentative ADH1 promoter. Xylose, glucose, or a mixture of the two sugars was used as the carbon source for lactate production. The constructed P. stipitis strain produced a higher level of lactate and a higher yield on xylose than on glucose. Lactate accumulated as the main product in xylose-containing medium, with 58 g\/liter lactate produced from 100 g\/liter xylose. Relatively efficient lactate production also occurred on glucose medium, with 41 g\/liter lactate produced from 94 g\/liter glucose. In the presence of both sugars, xylose and glucose were consumed simultaneously and converted predominantly to lactate. Lactate was produced at the expense of ethanol, whose production decreased to approximately 15 to 30% of the wild-type level on xylose-containing medium and to 70 to 80% of the wild-type level on glucose-containing medium. Thus, LDH competed efficiently with the ethanol pathway for pyruvate, even though the pathway from pyruvate to ethanol was intact. Our results show, for the first time, that lactate production from xylose by a yeast species is feasible and efficient. This is encouraging for further development of yeast-based bioprocesses to produce lactate from lignocellulosic raw material.","subset":"pubmed_abstract"} +{"meta":{"pmid":25564809,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Early introduction of complementary foods in preterm infants.\nThe aim of the present study was to determine the odds of early introduction of solid foods in a nationally representative sample of preterm infants when compared with term infants and to examine whether factors associated with early introduction are the same for preterm and term infants. Our sample of 7650 came from the first wave of the Early Childhood Longitudinal Study, Birth Cohort (2001-2002). We performed multivariable logistic regression to determine whether preterm infants were introduced to solid foods more frequently before 4 months than term infants using adjusted age for preterm infants and chronological age for term infants. In a separate analysis in preterm infants, we used multivariable logistic regression to determine whether the factors associated with early introduction in term infants were the same in the preterm sample. Infants born 22 to 32 weeks' gestation had a 9.90 (95% confidence interval 5.54-18.0) odds of being fed solid food before 4 months compared with term infants, and infants born 33 to 36 weeks' gestation had a 6.19 (95% confidence interval 4.58-8.36) odds. Race\/ethnicity and maternal smoking were the only factors that predicted early solid feeding in both preterm and term infants; the remaining predictors differed. Preterm infants are significantly more likely to be introduced to complementary foods early compared with term infants. The predictors of early solid feeding differ for preterm infants. Given the health implications, specific guidelines for preterm infants should be developed and future research should examine predictors of early introduction in preterm infants.","subset":"pubmed_abstract"} +{"meta":{"pmid":21807456,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2020-40":1,"2018-43":1,"2018-22":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-39":1,"2017-13":1}}},"text":"Antegrade perfusion with bacillus Calmette-Gu\u00e9rin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit?\nThere is paucity of data on bacillus Calmette-Gu\u00e9rin (BCG) perfusion in patients with non-muscle-invasive urothelial carcinoma (NMIUC) of the upper urinary tract (UUT). To assess the long-term results of BCG perfusion in patients with UUT NMIUC in terms of efficacy and tolerability. Retrospective analysis of 55 consecutive patients (64 renal units [RUs]) with UUT NMIUC prospectively followed according to a standardised protocol for a median of 42 mo (range: 2-237 mo). Our series includes negatively selected patients, most of whom were not eligible for radical surgery, with additional invasive urothelial carcinoma of the urinary tract in roughly one-third of the cases. Antegrade BCG perfusion of the UUT was performed either with curative intent for carcinoma in situ (Tis; 42 RUs) or with adjuvant intent after ablation of Ta\/T1 tumours (22 RUs). Primary outcome measures were recurrence-free, progression-free, and nephroureterectomy-free survival. The secondary outcome measure was treatment tolerability. Recurrence occurred in 30 of 64 RUs (47%), 17 of 42 (40%) with Tis and 13 of 22 (59%) with Ta\/T1 tumours. Progression occurred in 11 of 64 RUs (17%), 2 of 42 (5%) with Tis and 9 of 22 (41%) with Ta\/T1 tumours. Nephroureterectomy was eventually performed in 7 of 64 RUs (11%), 2 of 42 (5%) with Tis and 5 of 22 (23%) with Ta\/T1 tumours. Patients treated with curative intent for Tis tended to have better recurrence-free survival (p=0.42) and significantly better progression-free survival (p<0.01) and nephroureterectomy-free survival (p=0.05) compared with those treated with adjuvant intent after ablation of Ta\/T1 tumours. Adverse events, mostly minor, occurred in a total of 11 patients (20%), with one case of fatal Escherichia coli septicaemia. In our patients with UUT NMIUC, antegrade BCG perfusion resulted in a high kidney-preservation rate. Patients treated with curative intent for Tis apparently benefited in terms of local disease control more than those treated with adjuvant intent after ablation of Ta\/T1 tumours. Treatment tolerability was good.","subset":"pubmed_abstract"} +{"meta":{"pmid":28845370,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Seismocardiography-Based Cardiac Computed Tomography Gating Using Patient-Specific Template Identification and Detection.\nTo more accurately trigger cardiac computed tomography angiography (CTA) than electrocardiography (ECG) alone, a sub-system is proposed as an intermediate step toward fusing ECG with seismocardiography (SCG). Accurate prediction of quiescent phases is crucial to prospectively gating CTA, which is susceptible to cardiac motion and, thus, can affect the diagnostic quality of images. The key innovation of this sub-system is that it identifies the SCG waveform corresponding to heart sounds and determines their phases within the cardiac cycles. Furthermore, this relationship is modeled as a linear function with respect to heart rate. For this paper, B-mode echocardiography is used as the gold standard for identifying the quiescent phases. We analyzed synchronous ECG, SCG, and echocardiography data acquired from seven healthy subjects (mean age: 31; age range: 22-48; males: 4) and 11 cardiac patients (mean age: 56; age range: 31-78; males: 6). On average, the proposed algorithm was able to successfully identify 79% of the SCG waveforms in systole and 68% in diastole. The simulated results show that SCG-based prediction produced less average phase error than that of ECG. It was found that the accuracy of ECG-based gating is more susceptible to increases in heart rate variability, while SCG-based gating is susceptible to high cycle to cycle variability in morphology. This pilot work of prediction using SCG waveforms enriches the framework of a comprehensive system with multiple modalities that could potentially, in real time, improve the image quality of CTA.","subset":"pubmed_abstract"} +{"meta":{"pmid":722276,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Calcium efflux from squid axons under constant sodium electrochemical gradient.\nThe effect of varying Nao and Nai on Ca efflux while maintaining the ratio Nao\/Nai constant was explored in squid giant axons dialyzed with and without ATP. In the absence of ATP, the Ca efflux increased 3.4 +\/- 0.2-fold when the Nao\/Nai concentrations were reduced from 440\/80 to 110\/20 mM. In the presence of ATP a similar change did not have an appreciable effect. The inhibition of Ca efflux produced by Nai was studied in the presence and in the absence of ATP. In the absence of ATP, inhibition is very marked and is reminiscent of a unimolecular noncompetitive reaction (inactivation constant [KI] of 34 +\/- 5 mM of Nai) whereas in the presence of ATP, the slight inhibition observed indicates that ATP probably increases the KI to 200mM. From the inhibition of the Ca efflux produced by Nai in the presence or absence of ATP a curve describing the dependence of Nai of the ATP-promoted fraction of Ca efflux was constructed. The effect of Nao on the Ca efflux was studied as a function of [Na]i: at low Nai, an activation constant (KA) of 41 mM for Nao was obtained either in the presence of in the absence of ATP. As the intracellular Na is increased in the presence of ATP, Nai seems to have no effect on the apparent half-activation constant. However, in the absence of ATP, the KA for activation increases along a sigmoid curve reaching a value of 112 mM at 100 mM Nai. It is concluded that the Ca efflux system uses the energy of the Na electrochemical gradient. The action of Nai appears to be such that the interaction of a single Na+ is sufficient to block Ca extrusion whereas several Naps externally are necessary to activate Ca extrusion.","subset":"pubmed_abstract"} +{"meta":{"pmid":21629526,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Rectal metastasis of prostate cancer: about a case.\nProstate adenocarcinomas present a high risk of metastasis. We report a case of an atypical prostate cancer metastasis. A male patient presented a prostatic adenocarcinoma treated by surgery. A biological recurrence was discovered during the follow-up by an increased rate of Prostate Specific Antigen (PSA) and was treated by hormonotherapy. Several months later, there was a re-increase of the PSA rate. The CT scan showed a radiation proctitis aspect. An intermittent hormonotherapy was decided. Six months later, he presented abdominal pain. Examinations were performed and showed a rectal carcinosarcoma with prostate origins. A surgical management was realised. The outcomes were an early recurrence. A symptomatic treatment was decided. There are not any rectal localisations reported in the literature. Only loco-regional invasions of the rectum are described and no histological modification of metastasis compared to the primitive tumor has been reported. So, we report a metastasis of a prostate adenocarcinoma which transformed into a carcinosarcoma. Adenocarcinoma; Carcinosarcoma; Metastasis; Prostate; Rectal neoplasm.","subset":"pubmed_abstract"} +{"meta":{"pmid":23377209,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Vitamin D deficiency and depression in adults: systematic review and meta-analysis.\nThere is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. To determine the relationship, if any, between vitamin D deficiency and depression. A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.","subset":"pubmed_abstract"} +{"meta":{"pmid":24362078,"dup_signals":{"dup_doc_count":19}},"text":"Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya.\nTraditional medicine plays a critical role in treatment of chronic debilitating and life threatening conditions and diseases. Cancer is one such condition whose therapeutic intervention is commonly through inexpensive traditional herbal remedies. Increasingly industrialised societies are developing drugs and chemotherapeutics from these traditional herbal plants. Plant biogeography determines the abundance and availability of medicinal plants which in turn determine their use by local communities. The present study was carried out in Kakamega County of Kenya to identify and document medicinal plants used for treatment and management of cancer states by communities living adjacent to Kakamega Tropical rainforest of Kakamega County, Kenya. An ethnobotanical survey was done using semi-structured questionnaires administered to 32 randomly selected herbalists from Kakamega County. Sixty five (65) plants of 59 genera and 32 families were identified as candidates in therapeutic intervention against cancer states. Most commonly cited plant species were Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Microglossa pyrifolia (Lam.) Kuntze, Harungana madagascariensis Lam. ex poir, Prunus africana (Hook. f.) kalkman, Cyphostemma serpens (A. Rich), Catharanthus roseus (L.) G. Don and Aloe volkensii Engl. The following were documented for the first time; Aeschynomene abyssinica (A. Rich.) Vatke, Synsepalum cerasiferum (welw.) T. D penn., Albizia coriaria Welw. ex Oliv., Aloe volkensii Engl. Bridelia micrantha (Hochst.) Baill, Croton macrostachyus Delile, Cyphostemma serpens (A. Rich), Dicliptera laxata C.B. Clarke, Ekebergia capensis Sparrm., Gardenia volkensii K. schum. ssp. volkensii, Glycine wightii (wight & Arn.), Ocimum gratissimum Suave, Olea hotcsh spp. hochstetteri, Pavetta abyssinica Fresen., Phyllanthus fischeri Pax, Psydrax schimperiana (A. Rich), Rhus vulgaris Meikle, Senna didymobotyra (Fresen.) Irwin and Barneby, Solanecio nandensis (S. Moore) C. Jeffrey, Solanum mauritianum Scop, Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Spermacoce princea (K. Schum.) Verdc., Tabernaemontana stapfiana Britten, Tragia brevipes Pax and Zanthoxylum gilletii (De Wild.) P.G.Waterman. The most frequently used plant parts were fresh or dried leaves and stem barks. Administration to patients was almost exclusively oral, with the exceptions being topical application especially for breast cancer and skin sarcomas. This study identified diverse medicinal plants used in therapeutic and management intervention against cancer by communities living adjacent to Kakamega Tropical Rainforest. The primary mode of administration was oral.","subset":"pubmed_abstract"} +{"meta":{"pmid":29325066,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Toppar: an interactive browser for viewing association study results.\nData integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http:\/\/mccarthy.well.ox.ac.uk\/toppar\/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study anthropometric waist and body mass index data (Locke et al., 2015; Shungin et al., 2015) from the Genetic Investigation of ANthropometric Traits consortium. email@example.com.","subset":"pubmed_abstract"} +{"meta":{"pmid":26919991,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"The mediation effect of individual eating behaviours on the relationship between socioeconomic status and dietary quality in children: the Korean National Health and Nutrition Examination Survey.\nAlthough it has been suggested that socioeconomic status is associated with dietary quality, the possible mediation effects of eating behaviours on dietary quality are unclear. Thus, we investigated the causal chain by which socioeconomic status influences the quality of the diets consumed by children through their eating behaviours using data from the Korean National Health and Nutrition Examination Survey. The study focused on persons from 2 to 18 years of age who completed the 24-h dietary recall survey (n = 3158). Using causal mediation analysis, we assessed the relationship between socioeconomic status and poor dietary quality in children and examined the mediation effects of eating behaviours. Socioeconomic indicators included household income, parental education, and parental occupation. Dietary quality was defined by the number of key nutrients, protein, calcium, phosphorous, iron, vitamin A, vitamin B1, vitamin B2, niacin, and vitamin C, consumed at insufficient levels. In the present study, more than half the children did not consume the recommended amounts of vitamin A, vitamin C, iron, and calcium. Eating breakfast had a significant impact on poor dietary quality regardless of socioeconomic indicators. On the other hand, children from lower-middle-income households consumed insufficient amounts of more nutrients than their counterparts regardless of eating behaviours. Through the mediation model, we found that lower-middle household incomes were associated with poor dietary quality, but that dietary quality was significantly mediated by eating breakfast. We found that poor dietary quality among children in lower-income households was partially explained by their being less likely to eat breakfast, but that eating breakfast did not entirely mediate these effects. Thus, to reduce differences in dietary quality among children, those who are economically vulnerable must be prioritized.","subset":"pubmed_abstract"} +{"meta":{"pmid":22361011,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":2,"2013-20":1,"2015-18":1,"unknown":11}}},"text":"Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis.\nmicroRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense. This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes. Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families.","subset":"pubmed_abstract"} +{"meta":{"pmid":30938417,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Genetic variants in CYP and GST genes, smoking and risk for head and neck cancers: a gene-environment interaction hospital-based case-control study among Canadian Caucasians.\nThe evidence for genetic polymorphisms in genes encoding cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada. The study involved 389 incident SCCHN cases and 429 controls, frequency-matched by age and sex, recruited from four main hospitals between 2005 and 2013. Life-course-based interviews collected information on tobacco smoking history and other risk behaviors. DNA was isolated from oral exfoliated cells and genotyped for genetic variants. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for main, joint effect, stratum-specific and interaction estimates among non-, moderate and heavy smokers. Carriers of GSTP1 105Val (versus non-carriers) had a lower risk of SCCHN (OR = 0.71, 95% CI: 0.53, 0.95), which was observed for heavy smokers (OR = 0.59, 95% CI: 0.36, 0.95) and non-smokers alike (OR = 0.49, 95% CI: 0.24, 0.98). The decreased risk associations were also conserved among human papillomavirus negative individuals. There was no evidence for statistical interaction with smoking on additive or multiplicative scales for any of the variants analyzed. Of CYP and GST polymorphisms detected in Canadian Caucasians, only GSTP1 105Val was associated with a decreased risk for SCCHN.","subset":"pubmed_abstract"} +{"meta":{"pmid":20851511,"dup_signals":{"dup_doc_count":12}},"text":"Electrophysiological correlates of the composite face illusion: disentangling perceptual and decisional components of holistic face processing in the human brain.\nWhen the bottom halves of two faces differ, people's behavioral judgment of the identical top halves of those faces is impaired: they report that the top halves are different, and\/or take more time than usual to provide a response. This behavioral measure is known as the composite face effect (CFE) and has traditionally been taken as evidence that faces are perceived holistically. Recently, however, it has been claimed that this effect is driven almost entirely by decisional, rather than perceptual, factors (Richler, Gauthier, Wenger, & Palmeri, 2008). To disentangle the contribution of perceptual and decisional brain processes, we aimed to obtain an event-related potential (ERP) measure of the CFE at a stage of face encoding (Jacques & Rossion, 2009) in the absence of a behavioral CFE effect. Sixteen participants performed a go\/no-go task in an oddball paradigm, lifting a finger of their right or left hand when the top half of a face changed identity. This change of identity of the top of the face was associated with an increased ERP signal on occipito-temporal electrode sites at the N170 face-sensitive component (\u223c160 ms), the later decisional P3b component, and the lateralized readiness potential (LRP) starting at \u223c350 ms. The N170 effect was observed equally early when only the unattended bottom part of the face changed, indicating that an identity change was perceived across the whole face in this condition. Importantly, there was no behavioral response bias for the bottom change trials, and no evidence of decisional biases from electrophysiological data (no P3b and LRP deflection in no-go trials). These data show that an early CFE can be measured in ERPs in the absence of any decisional response bias, indicating that the CFE reflects primarily the visual perception of the whole face.","subset":"pubmed_abstract"} +{"meta":{"pmid":21504536,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":9}}},"text":"Iron isotope fractionation during microbial dissimilatory iron oxide reduction in simulated Archaean seawater.\nThe largest Fe isotope excursion yet measured in marine sedimentary rocks occurs in shales, carbonates, and banded iron formations of Neoarchaean and Paleoproterozoic age. The results of field and laboratory studies suggest a potential role for microbial dissimilatory iron reduction (DIR) in producing this excursion. However, most experimental studies of Fe isotope fractionation during DIR have been conducted in simple geochemical systems, using pure Fe(III) oxide substrates that are not direct analogues to phases likely to have been present in Precambrian marine environments. In this study, Fe isotope fractionation was investigated during microbial reduction of an amorphous Fe(III) oxide-silica coprecipitate in anoxic, high-silica, low-sulphate artificial Archaean seawater at 30 \u00b0C to determine if such conditions alter the extent of reduction or isotopic fractionations relative to those observed in simple systems. The Fe(III)-Si coprecipitate was highly reducible (c. 80% reduction) in the presence of excess acetate. The coprecipitate did not undergo phase conversion (e.g. to green rust, magnetite or siderite) during reduction. Iron isotope fractionations suggest that rapid and near-complete isotope exchange took place among all Fe(II) and Fe(III) components, in contrast to previous work on goethite and hematite, where exchange was limited to the outer few atom layers of the substrate. Large quantities of low-\u03b4(56)Fe Fe(II) (aqueous and solid phase) were produced during reduction of the Fe(III)-Si coprecipitate. These findings shed new light on DIR as a mechanism for producing Fe isotope variations observed in Neoarchaean and Paleoproterozoic marine sedimentary rocks.","subset":"pubmed_abstract"} +{"meta":{"pmid":23440027,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":20}}},"text":"The physician assistant: Shifting the Paradigm of European medical practice?\nPhysician Assistants are medical care providers working under supervision and\/or in collaboration with a medical doctor. The Physician Assistant profession has its origin in the United States, but in the last decade has also reached other nations to overcome medical staffing issues. With little summarized literature available, the aim of this study is to portray the Physician Assistant movement in Europe. A literature search was conducted in Academic Search Premier, CINAHL, ERIC and MEDLINE databases. In addition, European PA educational programs, professional associations, and local experts on the PA profession were queried. Currently, in Europe there are three countries in which physician assistants are trained and are working. The educational models of physician assistant training in the United Kingdom, Germany and the Netherlands differ, as do the degrees offered by the training institutions. There is scant literature about physician assistant training and practice in Europe available in the common scientific databases. The paucity of literature makes it difficult for an outsider to observe the developments and to value the impact of a new profession on national health systems. Further high-quality research is needed to adequately characterize physician assistant education and implementation across Europe.","subset":"pubmed_abstract"} +{"meta":{"pmid":29677125,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.\nThe space radiation environment includes helium (\u2074He) ions that may impact brain function. As little is known about the effects of exposures to \u2074He ions on the brain, we assessed the behavioral and cognitive performance of C57BL\/6J \u00d7 DBA2\/J F1 (B6D2F1) mice three months following irradiation with \u2074He ions (250 MeV\/n; linear energy transfer (LET) = 1.6 keV\/\u03bcm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. \u2074He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear conditioning tests. Taken together, the results indicate that some aspects of cognitive performance are altered in male mice exposed to \u2074He ions, but that the response is task-dependent. Furthermore, the sensitive doses can vary within each task in a non-linear fashion. This highlights the importance of assessing the cognitive and behavioral effects of charged particle exposure with a variety of assays and at multiple doses, given the possibility that lower doses may be more damaging due to the absence of induced compensatory mechanisms at higher doses.","subset":"pubmed_abstract"} +{"meta":{"pmid":3032788,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Red blood cell Na+,K+-ATPase in men with newly diagnosed or previously treated essential hypertension.\nAlterations of cellular function of Na+,K+-adenosine triphosphatase (ATPase; Na+-K+ pump) have been implicated in the pathophysiology of essential hypertension. Therefore, this aspect of red blood cell (RBC) Na metabolism was studied in black men with newly diagnosed, untreated essential hypertension (NEH) and a normotensive control group. RBC Na content, Na+-K+ pump number (ouabain binding sites), and pump activity were measured. No statistically significant differences were found between the two groups for any of these three parameters. However, a group of previously treated essential hypertensive subjects (PEH) who had been withdrawn from therapy in the preceding 6 weeks were also studied. This group differed significantly from the NEH subjects in regard to all RBC Na+-K+ pump parameters. Their RBC Na content (10.27 +\/- 3.23 vs 7.77 +\/- 2.52 mmol Na\/LRBC; p = 0.006) was higher, and their Na+-K+ pump activity (166 +\/- 50 vs 221 +\/- 87 nmol inorganic phosphate\/mg membrane protein\/hr; p = 0.03) and Na+-K+ pump number (213 +\/- 40 vs 284 +\/- 85 binding sites\/RBC; p = 0.001) were lower compared with those in NEH subjects. Although the PEH subjects were older and somewhat less hypertensive than their NEH counterparts, these factors were not found to influence the Na+-K+ pump parameters. These results indicate that chronic diuretic therapy of patients with essential hypertension is associated with a reduced number of RBC Na+-K+ pumps. Since RBCs are not considered target cells for diuretics, the effects of these drugs on RBC electrolyte metabolism may occur at the time of erythropoiesis by the production of RBCs with fewer Na+-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":23278386,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-18":1,"2015-06":1,"2013-20":2,"2024-26":1,"unknown":6}}},"text":"Genetic markers of comorbid depression and alcoholism in women.\nAlcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1-9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression. Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females. We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics. Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism\/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":15592069,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Health related quality of life before and after laparoscopic radical prostatectomy.\nThe viability of laparoscopic radical prostatectomy (LRP) as a surgical treatment for prostate cancer depends on oncological and health related quality of life (HRQOL) outcomes. We present a prospective assessment of HRQOL in 122 patients before and after LRP using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire. EPIC data were collected preoperatively, and at 3, 6 and 12 months after LRP, and all were normalized to patient preoperative baseline responses. Using traditional single question responses, 93.4% of patients were continent (0 to 1 pads) at postoperative month 12. Of previously potent men who underwent bilateral nerve sparing 78.9% reported engaging in sexual intercourse within postoperative year 1. However, EPIC domain scores provided a more comprehensive assessment of functional outcomes. For the urinary incontinence subdomain, the majority of functional recovery was achieved by postoperative month 6, reaching a 74% return to baseline on average. In contrast, recovery of the sexual function subdomain continued throughout postoperative year 1 (to a mean of 64%). Recovery of sexual function was not significantly affected by age or preoperative potency status, although the extent of nerve sparing was a significant predictor of outcome (mean recovery to 75% of baseline for bilateral vs 36% for no nerve sparing at 12 months, p = 0.005). Nerve sparing LRP provides satisfactory first year HRQOL outcomes when assessed with a validated instrument. The time course and extent of functional recovery documented in this prospective study may prove useful for patient counseling before LRP.","subset":"pubmed_abstract"} +{"meta":{"pmid":31257031,"dup_signals":{"dup_doc_count":15}},"text":"Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner.\nImmune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":12672860,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Memantine in moderate-to-severe Alzheimer's disease.\nOverstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis). Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases). Memantine was not associated with a significant frequency of adverse events. Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available.","subset":"pubmed_abstract"} +{"meta":{"pmid":22768189,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":9}}},"text":"The role of turtles as coral reef macroherbivores.\nHerbivory is widely accepted as a vital function on coral reefs. To date, the majority of studies examining herbivory in coral reef environments have focused on the roles of fishes and\/or urchins, with relatively few studies considering the potential role of macroherbivores in reef processes. Here, we introduce evidence that highlights the potential role of marine turtles as herbivores on coral reefs. While conducting experimental habitat manipulations to assess the roles of herbivorous reef fishes we observed green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) showing responses that were remarkably similar to those of herbivorous fishes. Reducing the sediment load of the epilithic algal matrix on a coral reef resulted in a forty-fold increase in grazing by green turtles. Hawksbill turtles were also observed to browse transplanted thalli of the macroalga Sargassum swartzii in a coral reef environment. These responses not only show strong parallels to herbivorous reef fishes, but also highlight that marine turtles actively, and intentionally, remove algae from coral reefs. When considering the size and potential historical abundance of marine turtles we suggest that these potentially valuable herbivores may have been lost from many coral reefs before their true importance was understood.","subset":"pubmed_abstract"} +{"meta":{"pmid":19648736,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome.\nRecessive mutations in the SLC26A4 gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between SLC26A4 genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the SLC26A4 coding regions, the SLC26A4 promoter and the FOXI1 transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the SLC26A4 coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different SLC26A4 genotypes. Specifically, probands heterozygous for SLC26A4 mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.-2554G>A of SLC26A4) with possible pathological consequences, no definite mutation was detected after extensive screening in the SLC26A4 promoter and FOXI1. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of SLC26A4 by FOXI1. Meanwhile, exploration of undetected mutations in the SLC26A4 noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected SLC26A4 alleles of the c.919-2A>G heterozygotes, indicating that there might be no common and predominant mutations in the SLC26A4 introns.","subset":"pubmed_abstract"} +{"meta":{"pmid":35172866,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":2,"2024-22":1,"unknown":14}}},"text":"Challenges and improvement needs in the care of patients with central diabetes insipidus.\nCentral diabetes insipidus (CDI) is a rare condition, with significant impact on patient health and well-being. It is a chronic condition which usually requires meticulous long-term care. It can affect both children and adults. There is limited literature considering the needs and challenges inherent in providing high quality care to patients with CDI, across the care pathway. This paper seeks to address this gap by providing a unique and well-rounded understanding of clinical and healthcare systems-related challenges. It draws on insights from the literature, from direct clinical experience contributed by five clinicians as co-authors (providing insights from France, Ireland, Italy, Spain and the United Kingdom), and from patient perspectives provided through interviews with patient representatives from three patient organisations. We identify clinical challenges related to the diagnosis of CDI, including differentiating between other similar conditions and determining the underlying aetiology. Treatment is challenging, given the need to tailor medication to each patient's needs and ongoing management is required to ensure that patients continue to respond adequately to treatment. Ongoing support is required when patients switch between formulations. We also identify healthcare systems challenges related to limited awareness of CDI amongst primary care physicians and general paediatricians, and the need for highly skilled specialist care and appropriate workforce capacity. There is also a significant need for raising awareness and for the education of both healthcare professionals and patients about different aspects of CDI, with the aim of supporting improved care and effective patient engagement with healthcare professionals. We reflect on this information and highlight improvement opportunities. These relate to developing guidance to support patients, carers, primary care physicians and general paediatricians to identify clinical features earlier, and to consider CDI as a possible diagnosis when a patient presents with suggestive symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":27001545,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-22":1,"2017-13":1,"2024-22":1}}},"text":"An automated microreactor for semi-continuous biosensor measurements.\nLiving bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter (\"bactosensors\"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 \u03bcgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 \u03bcg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments.","subset":"pubmed_abstract"} +{"meta":{"pmid":22464713,"dup_signals":{"dup_doc_count":31,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":10,"2013-48":5,"unknown":15}}},"text":"Applying a structured innovation process to interventional radiology: a single-center experience.\nTo determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice. The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session. Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories. This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27560619,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-14":1,"2022-27":1,"2022-21":2,"2021-49":1,"2021-31":1,"2021-21":1,"2021-04":1,"2020-29":1,"2020-24":1,"2019-43":1,"2017-22":1,"2017-17":1,"2023-50":1,"2024-10":1}}},"text":"Prevention and Control of Seasonal Influenza with Vaccines.\nThis report updates the 2015-16 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season. MMWR Morb Mortal Wkly Rep 2015;64:818-25). Routine annual influenza vaccination is recommended for all persons aged \u22656 months who do not have contraindications. For the 2016-17 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013-14 and 2015-16 seasons, for the 2016-17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Vaccine virus strains included in the 2016-17 U.S. trivalent influenza vaccines will be an A\/California\/7\/2009 (H1N1)-like virus, an A\/Hong Kong\/4801\/2014 (H3N2)-like virus, and a B\/Brisbane\/60\/2008-like virus (Victoria lineage). Quadrivalent vaccines will include an additional influenza B virus strain, a B\/Phuket\/3073\/2013-like virus (Yamagata lineage).Recommendations for use of different vaccine types and specific populations are discussed. A licensed, age-appropriate vaccine should be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. Information in this report reflects discussions during public meetings of ACIP held on October 21, 2015; February 24, 2016; and June 22, 2016. These recommendations apply to all licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (http:\/\/www.cdc.gov\/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.","subset":"pubmed_abstract"} +{"meta":{"pmid":19501914,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2022-40":1,"2022-21":1,"2022-05":2,"2021-49":1,"2021-31":1,"2021-17":1,"2020-50":1,"2020-34":1,"2020-29":1,"2023-06":1}}},"text":"Maternal bipolar disorder increased low birthweight and preterm births: a nationwide population-based study.\nTo investigate pregnancy outcomes, including low birthweight, preterm births, and small-for-gestational-age (SGA) among women with bipolar disorder, schizophrenia compared with women with no history of mental illness using nationwide population-based data. This study linked the Taiwan National Health Insurance Research Dataset with the national birth certificate registry. A total of 528,398 singleton births between 2001 and 2003 were included; 337 were diagnosed with bipolar disorder. Multivariate logistic regression analyses were carried out to examine the relationship between maternal bipolar disorder, schizophrenia and the odds of low birthweight, preterm births, and SGA, after adjusting for characteristics of infant, mother and father. It shows that pregnant women with bipolar disorder were more likely to have LBW infants (9.8% vs. 5.7%), preterm births (14.2% vs. 6.9%) and SGA (22.3% vs. 15.7%) than pregnant women with no history of mental illness. The adjusted odds of low birthweight for women with bipolar disorder was 1.66 times (95% CI, 1.16-2.38) that of women with no history of mental illness. In terms of preterm births and SGA, the adjusted odds ratios were 2.08 (95% CI, 1.53-2.83) and 1.47 (95% CI, 1.14-1.91) respectively, for women with bipolar disorder, compared to their counterparts with no history of mental illness. We conclude that women with bipolar disorder had increased risk of low birthweight, preterm births, and SGA than women without a history of mental illness. More active monitoring and early intervention to counter potential adverse pregnancy outcomes for pregnant women with bipolar disorder should be initiated.","subset":"pubmed_abstract"} +{"meta":{"pmid":12675847,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Differential gene expression following early renal ischemia\/reperfusion.\nAcute renal failure from ischemia\/reperfusion injury is associated with tubule cell apoptosis, the molecular mechanisms of which remain under active investigation. The purpose of this study was to identify apoptosis-related genes that are differentially expressed in the early periods following renal ischemia. Mice underwent unilateral renal artery clamping for 45 minutes and were sacrificed at 0, 3, 12, or 24 hours of reperfusion. Tubule cell apoptosis was confirmed by DNA laddering and terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. We employed cDNA microarrays to define global changes in renal gene expression. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used as confirmatory tools. By microarray analysis, we identified consistent patterns of altered gene expression, including transcription factors, growth factors, signal transduction molecules, and apoptotic factors. Prominent among the last category included FADD, DAXX, BAD, BAK, and p53. Up-regulation of these proapoptotic genes was confirmed by semiquantitative RT-PCR and immunohistochemistry. The results indicate that apoptosis may represent an important mechanism for the early loss of tubule cells following ischemia\/reperfusion injury. Both the death receptor-dependent (FADD-DAXX) and mitochondrial (BAD-BAK) pathways are activated. The results also provide a molecular basis for the previous findings that significant intrarenal mechanisms exist to enable tubule cell repair and regeneration, as evidenced by the up-regulation of genes such as growth, proliferation, transcription, and cytoskeletal factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":15828683,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2023-23":1}}},"text":"Transcriptional analysis of the Azospirillum brasilense indole-3-pyruvate decarboxylase gene and identification of a cis-acting sequence involved in auxin responsive expression.\nExpression of the Azospirillum brasilense ipdC gene, encoding an indole-3-pyruvate decarboxylase, a key enzyme in the production of indole-3-acetic acid (IAA) in this bacterium, is upregulated by IAA. Here, we demonstrate that the ipdC gene is the promoter proximal gene in a bicistronic operon. Database searches revealed that the second gene of this operon, named iaaC, is well conserved evolutionarily and that the encoded protein is homologous to the Escherichia coli protein SCRP-27A, the zebrafish protein ES1, and the human protein KNP-I\/GT335 (HES1), all of unknown function and belonging to the DJ-1\/PfpI superfamily. In addition to this operon structure, iaaC is also transcribed monocistronically. Mutation analysis of the latter gene indicated that the encoded protein is involved in controlling IAA biosynthesis but not ipdC expression. Besides being upregulated by IAA, expression of the ipdC-iaaC operon is pH dependent and maximal at acidic pH. The ipdC promoter was studied using a combination of deletion analyses and site-directed mutagenesis. A dyadic sequence (ATTGTTTC(GAAT)GAAACAAT), centered at -48 was demonstrated to be responsible for the IAA inducibility. This bacterial auxin-responsive element does not control the pH-dependent expression of ipdC-iaaC.","subset":"pubmed_abstract"} +{"meta":{"pmid":2164721,"dup_signals":{"dup_doc_count":25,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-14":2,"2022-49":1,"2022-27":2,"2022-05":1,"2021-39":3,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":2,"2019-26":1,"2019-18":1,"2023-50":1,"2024-26":2,"2024-22":1}}},"text":"Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I.\nEvidence has been presented that herpes simplex virus (HSV) immunoglobulin (IgG) Fc receptors are composed of a complex of two glycoproteins, gE and gI. In previous studies, cells infected with HSV-1 mutants lacking either gE or gI bound lower levels of soluble IgG than cells infected with wild-type viruses suggesting that both gE and gI were required for IgG binding. We have reevaluated the Fc receptor activity of these mutants using a more sensitive assay involving IgG-coated erythrocytes and have found that cells infected with a gE- mutant HSV-1 did not bind IgG-coated erythrocytes whereas cells infected with a gI- mutant retained some Fc binding activity. To further study HSV-induced Fc receptors recombinant adenovirus vectors expressing gE or gI were constructed. Cells expressing gE alone bound both soluble IgG and IgG-coated red cells, although the binding was consistently lower than that observed with HSV-infected cells or cells expressing both gE and gI. Cells expressing only gI were unable to bind either soluble IgG or IgG-coated erythrocytes. These results support the conclusion that both gE and gI are required for full Fc receptor activity, although gE alone can bind IgG to a lesser extent.","subset":"pubmed_abstract"} +{"meta":{"pmid":224831,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Day treatment and psychotropic drugs in the aftercare of schizophrenic patients. A Veterans Administration cooperative study.\nSchizophrenic patients referred for day treatment at the time of discharge from ten hospitals were randomly assigned to receive day treatment plus drugs or to receive drugs alone. They were tested before assignment and at 6, 12, 18, and 24 months on social functioning, symptoms, and attitudes. Community tenure and costs were also measured. The ten day centers were described on process variables every six months for the four years of the study. Some centers were found to be effective in treating chronic schizophrenic patients and others were not. All centers improved the patients' social functioning. Six of the centers were found to significantly delay relapse, reduce sumptoms, and change some attitudes. Costs for patients in these centers were not significantly different from the group receiving only drugs. More professional staff hours, group therapy, and a high patient turnover treatment philosophy were associated with poor-result centers. More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers.","subset":"pubmed_abstract"} +{"meta":{"pmid":17926928,"dup_signals":{"dup_doc_count":58,"dup_dump_count":39,"dup_details":{"curated_sources":4,"2023-14":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":2,"2021-49":1,"2021-39":1,"2021-25":1,"2021-17":2,"2021-04":1,"2020-45":2,"2020-34":3,"2020-24":1,"2020-16":2,"2020-10":2,"2020-05":2,"2019-51":1,"2019-43":1,"2019-39":3,"2019-35":1,"2019-30":3,"2019-26":1,"2019-22":2,"2019-18":1,"2019-13":2,"2019-09":1,"2019-04":2,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2014-35":1,"2023-40":1}}},"text":"Artistic edge and corner enhancing smoothing.\nTwo important visual properties of paintings and painting-like images are the absence of texture details and the increased sharpness of edges as compared to photographic images. Painting-like artistic effects can be achieved from photographic images by filters that smooth out texture details, while preserving or enhancing edges and corners. However, not all edge preserving smoothers are suitable for this purpose. We present a simple nonlinear local operator that generalizes both the well known Kuwahara filter and the more general class of filters known in the literature as \"criterion and value filter structure.\" This class of operators suffers from intrinsic theoretical limitations which give rise to a dramatic instability in presence of noise, especially on shadowed areas. Such limitations are discussed in the paper and overcome by the proposed operator. A large variety of experimental results shows that the output of the proposed operator is visually similar to a painting. Comparisons with existing techniques on a large set of natural images highlight conditions on which traditional edge preserving smoothers fail, whereas our approach produces good results. In particular, unlike many other well established approaches, the proposed operator is robust to degradations of the input image such as blurring and noise contamination.","subset":"pubmed_abstract"} +{"meta":{"pmid":28851253,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Pedicled Transplantation of Axially Vascularized Bone Constructs in a Critical Size Femoral Defect.\nAxial vascularization represents a mandatory requirement for clinically applied larger scale vascularized bone grafts. The aim of this study was to combine the arteriovenous (AV) loop model in the rat with a critically sized femoral bone defect and to successfully transplant axially vascularized bone constructs into the defect. In Groups A and C, an AV loop together with a clinically approved hydroxyapatite and beta-tricalcium phosphate (HA\/\u03b2-TCP) matrix, mesenchymal stem cells, and recombinant human bone morphogenetic protein 2 were implanted into a newly designed porous titanium chamber with an integrated osteosynthesis plate in the thighs of rats, whereas in Groups B and D, the same matrix composition without AV loop and, in Group E, only the HA\/\u03b2-TCP matrix were implanted. After 6 weeks, the constructs were transplanted into a 10 mm femoral defect created in the same leg, in Groups A and C, under preservation of the AV loop pedicle. Group F served as a control group with an empty chamber. Ten days (Groups A and B) and 12 weeks (Groups C-F) after transplantation, the femora together with the constructs were explanted and investigated using computed tomography (CT), micro-CT, X-ray, histology, and real-time polymerase chain reaction (RT-PCR). Ten days after transplantation, Group A showed a maintained vascular supply leading to increased vascularization, cell survival in the scaffold center, and bone generation compared to Group B. After 12 weeks, there was no difference detectable among all groups regarding total vessel number, although Group C, using the AV loop, still showed increased vascularization of the construct center compared to Groups D and E. In Group C, there was still enhanced bone generation detectable compared to the other groups and increased bony fusion rate at the proximal femoral stump. This study shows the combination of the AV loop model in the rat with a critically sized femoral defect. By maintenance of the vascular supply, the constructs initially showed increased vascularization, leading to increased bone formation and bony fusion in the long term.","subset":"pubmed_abstract"} +{"meta":{"pmid":8231231,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-04":1}}},"text":"Hypoxaemia in patients with hyperleukocytosis: true or spurious, and clinical implications.\nIt has been suggested that in asymptomatic patients with leukaemias and very high white blood cell counts, the apparent hypoxaemia found using routine blood gas analysis is spurious, the result of excessive O2 metabolism by leukocytes. Pulse oximetry has been suggested as a means of overcoming the shortcomings of blood gas analysis in the assessment of these patients. We present the findings of two patients with extremely high white cell counts, which show that the hypoxaemia found is in fact true hypoxaemia, even in asymptomatic patients, and that met-haemoglobinaemia may be at least in part responsible for the low PaO2. We also showed that pulse oximetry was completely unreliable in our patients due to the elevated met-haemoglobin levels. We recommend that all patients with markedly elevated white cell counts should undergo blood gas analysis with no delay between sampling and processing and that patients with low PaO2 should undergo urgent cytoreduction.","subset":"pubmed_abstract"} +{"meta":{"pmid":18306379,"dup_signals":{"dup_doc_count":30,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":2,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":2,"2018-34":1,"2018-26":1,"2018-22":1,"2017-51":1,"2017-26":1,"2016-44":1,"2023-50":1,"2024-10":1,"2024-22":1}}},"text":"Active surveillance for early-stage prostate cancer: review of the current literature.\nThe natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":31532436,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Graphene-based wearable sensors.\nThe human body is a \"delicate machine\" full of sensors such as the fingers, nose, and mouth. In addition, numerous physiological signals are being created every moment, which can reflect the condition of the body. The quality and the quantity of the physiological signals are important for diagnoses and the execution of therapies. Due to the incompact interface between the sensors and the skin, the signals obtained by commercial rigid sensors do not bond well with the body; this decreases the quality of the signal. To increase the quantity of the data, it is important to detect physiological signals in real time during daily life. In recent years, there has been an obvious trend of applying graphene devices with excellent performance (flexibility, biocompatibility, and electronic characters) in wearable systems. In this review, we will first provide an introduction about the different methods of synthesis of graphene, and then techniques for graphene patterning will be outlined. Moreover, wearable graphene sensors to detect mechanical, electrophysiological, fluid, and gas signals will be introduced. Finally, the challenges and prospects of wearable graphene devices will be discussed. Wearable graphene sensors can improve the quality and quantity of the physiological signals and have great potential for health-care and telemedicine in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":8996593,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Combinations of paclitaxel and etoposide in the treatment of lung cancer.\nPaclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and etoposide are two chemotherapy agents with broad cytotoxic activity but different mechanisms of action and resistance. Previous in vitro studies of their combined cytotoxicity have yielded conflicting results. We evaluated the effects of drug scheduling in cell growth inhibition in lung and breast human cancer cell lines. A clonogenic assay with either simultaneous or sequential 24-hour incubation of paclitaxel and etoposide was used to assess growth inhibition, and the combination index was used to evaluate drug interactions. In these studies, including the A549 human lung cancer cell line, mild antagonism (combination index, > 1) was observed with concurrent exposure of paclitaxel and etoposide, but synergism (combination index, < 1) was observed when the drugs were incubated sequentially. In view of the wide range of antitumor activity of both paclitaxel and etoposide, and the potential importance and clinical impact of optimizing drug doses and schedules, we recently completed a phase I study with the following objectives: (1) to determine the maximum tolerated dose of paclitaxel given intravenously on day 10 after 10 days of oral etoposide and (2) to investigate the toxicity profile of this combination of agents. Three consecutive cohorts consisting of a total of 29 patients with various measurable or assessable tumors were treated with paclitaxel by intravenous infusion over 3 hours after receiving 10 days of etoposide 50 mg orally twice daily. Conclusions for this clinical study were that the combination was feasible and tolerable and had demonstrated antitumor activity in a group of mostly pretreated patients. The recommended doses for phase II studies were etoposide 50 mg twice daily for 10 days followed by paclitaxel 150 mg\/m2 intravenously over 3 hours. A phase II study in patients with extensive small cell lung cancer, with appropriate translational studies, has been initiated.","subset":"pubmed_abstract"} +{"meta":{"pmid":15616072,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"The impact of the joint commission for accreditation of healthcare organizations pain initiative on perioperative opiate consumption and recovery room length of stay.\nThe enhanced organizational emphasis on the management of pain in hospitalized patients mandated by the Joint Commission for Accreditation of Health Care Organizations (JCAHO) pain initiative precipitated a number of changes by the perioperative services at our facility. In October 2002, a numeric pain scale became mandatory in our postanesthesia care unit (PACU). Response to analgesia in the PACU was recorded using this scale. In addition, an acceptable pain score was required for discharge from the PACU. We evaluated the effects of these changes in the pain management of 1082 patients undergoing general, orthopedic, neurosurgical, urologic, and gynecologic surgeries. We detected an overall increase in the average consumption of opiates (morphine equivalents) in 2002 compared with 2000 (46.6 +\/- 20.4 mg versus 40.4 +\/- 13.2 mg, P <0.001). This increase was most significant in the PACU (10.5 +\/- 10.4 mg versus 6.5 +\/- 7.3 mg, P <0.001 between the 2 periods, respectively). This increase in opiate use was not associated with an increased length of stay, an increase in the requirement for naloxone, or an increase in treatment for postoperative nausea and vomiting. We conclude that the increase in opiate use, which could be explained by compliance with the JCAHO pain initiative, was not associated with additional opiate-induced morbidity in the immediate postoperative period.","subset":"pubmed_abstract"} +{"meta":{"pmid":25270892,"dup_signals":{"dup_doc_count":21,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2019-35":2,"2019-30":4,"2019-26":1,"2019-22":3,"2019-18":3,"2019-13":2,"2019-09":1,"2018-51":1,"2018-43":1}}},"text":"Sleep in the intensive care unit - nurses' documentation and patients' perspectives.\nInability to sleep is one of the most distressing factors for patients in the intensive care unit (ICU). Sleep is perceived as light and awakenings are numerous. Nurses' documentations of sleep are narrow, mainly concentrating on the quantity and general quality. Nurses should diversely evaluate, document and promote sleep to provide patient centered care. To investigate the content of nurses' documentation about the sleep of ICU patients, patients' own perceptions of sleep, and the correspondence of the two. Nurses' documentations (n = 90) were analysed retrospectively with quantitative content analysis. A cross-sectional survey of patients' (n = 114) perspectives was collected with the five-item Richards-Campbell Sleep Questionnaire (RCSQ), on a visual analogue scale from 0 (the poorest quality sleep) to 100 (optimum sleep). The data was analysed statistically. Correspondence was tested with cross-tabulation. Nurses documented sleep quantity for 71% and quality for 27% of patients, along with the needs assessment, used interventions and their effect on sleep. Patients' perspectives varied widely. Sleep depth was rated the lowest and falling asleep highest of the RCSQ sleep domains. Age of the patients correlated positively with general quality of sleep, sleep depth and falling asleep. Nurses' documentations and patients' perceptions correlated in over half of the cases. Nurses' documentation of ICU patients' sleep is not systematic or comprehensive and corresponds only partially with patients' own perception. The sleep of non-intubated patients is light and awakenings are frequent. Documentation of ICU patients' sleep should include the whole nursing process, i.e. needs assessment, interventions used, and evaluation of sleep and the effects of the interventions, along with patients' own perspective to promote patient-centered care. Evaluation and documentation of patients' sleep must include patients' own perception to be comprehensive. Nurses' documentation should include all elements of nursing process.","subset":"pubmed_abstract"} +{"meta":{"pmid":23608077,"dup_signals":{"dup_doc_count":33,"dup_dump_count":30,"dup_details":{"curated_sources":2,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-15":2,"2018-26":1,"2015-18":1,"2015-11":1,"2014-10":1,"2017-13":1}}},"text":"White matter integrity and executive abilities in individuals with phenylketonuria.\nPrevious studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes are poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU.","subset":"pubmed_abstract"} +{"meta":{"pmid":19899223,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Reprint of mutation of the fucose-specific beta1,3 N-acetylglucosaminyltransferase LFNG results in abnormal formation of the spine.\nNotch signaling is an evolutionarily conserved mechanism that determines cell fate in a variety of contexts during development. This is achieved through different modes of action that are context dependent. One mode involves boundary formation between two groups of cells. With this mode of action, Notch signaling is central to vertebrate evolution as it drives the segmentation of paraxial mesoderm in the formation of somites, which are the precursors of the vertebra. In this case, boundary formation facilitates a mesenchymal to epithelial transition, leading to the creation of a somite. In addition, the boundary establishes a signaling center that patterns the somite, a feature that directly impacts on vertebral column formation. Studies in Xenopus, zebrafish, chicken and mouse have established the importance of Notch signaling in somitogenesis, and indeed in mouse how perturbations in somitogenesis affect vertebral column formation. Spondylocostal dysostosis is a congenital disorder characterized by formation of abnormal vertebrae. Here, mutation in Notch pathway genes demonstrates that Notch signaling is also required for normal somite formation and vertebral column development in humans; of particular interest here is mutation of the LUNATIC FRINGE (LFNG) gene, which causes SCD type 3. LUNATIC FRINGE encodes for a fucose-specific beta1,3-N-acetylglucosaminyltransferase, which modifies Notch receptors and alters Notch signaling activity. This review will focus on Notch glycolsylation, and the role of LUNATIC FRINGE in somite formation and vertebral column development in mice and humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":10969970,"dup_signals":{"dup_doc_count":24,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2021-04":1,"2020-40":1,"2020-16":1,"2020-10":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2023-06":1,"2017-13":1,"2024-30":1}}},"text":"Synthesis and properties of 2'-O-methyl-2-thiouridine and oligoribonucleotides containing 2'-O-methyl-2-thiouridine.\nA new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in thermophilic bacterial tRNA was developed. Structural properties of s2Um and s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability of s2Um in formation of RNA-RNA and RNA DNA duplexes. The UV melting experiments revealed that RNA*-RNA and RNA*-DNA duplexes having an s2U-A base pair are more stable than those having a U-A base pair. On the contrary, the thermal stability of RNA*-RNA and RNA*-DNA duplexes having an s2U-G wobble base pair was much lower than that of the unmodified duplexes having a natural U-G base pair. It is concluded that s2Um has higher selectivity toward A over G than unmodified U.","subset":"pubmed_abstract"} +{"meta":{"pmid":11169965,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-22":1,"2024-30":1,"unknown":14}}},"text":"Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2\/M cell cycle arrest in human colorectal cancer cells.\nIn this study, we demonstrate that apoptosis and G2\/M cell cycle arrest were easily induced by treatment with the oral-antifungal agent, griseofulvin (GF). The mechanisms of GF-induced G2\/M arrest were characterized as (a) induction of abnormal mitotic spindle formation, (b) elevation of cyclin B1\/cdc2 kinase activity and (c) down-regulation of myt-1 protein expression. On the other hand, caspase 3 activation, Bcl-2 hyperphosphorylation and inhibition of the normal function of Bcl-2 associated with Bax were demonstrated to be the mechanisms of GF-induced apoptosis. DNA fragmentation and flow cytometry analyses demonstrated that combined treatment of GF with the cancer chemotherapeutic agent, nocodazole (ND), strongly potentiates the apoptotic effect and arrest of the G2\/M cell cycle in 5 types of human cancer cells, but not in normal human keratinocytes (#76 KhGH). The combined treatment of GF and ND triggered the polymerization of purified tubulin in HT 29 but not in #76 KhGH cells. To further confirm these observations, the therapeutic efficacy was further examined in vivo by treating athymic mice bearing COLO 205 tumor xenografts, with GF (50 mg\/kg), ND (5 mg\/kg) or GF + ND. Combined treatment of GF and ND significantly enhanced the effect of ND, and led to cessation of tumor growth. These results suggest that chemotherapeutic agents (such as ND) administered in the presence of GF might provide a novel therapy for colorectal cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":24043998,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The Predicaments of People Whose Suicide was Captured on Film.\nAlthough suicide is commonly linked with mental disorder, the notion that suicide may occur in response to predicaments has been the subject of much recent study and attention. A predicament in this context refers to an uncomfortable situation from which escape is difficult. We aimed to examine the predicaments of people whose suicide was captured on film and displayed on the public record. The authors' extensive private library and the web were explored for examples of suicide on film. The authors viewed the films and associated records, and extracted and listed details of the suicides. Six individual cases and two groups (totalling 2200 plus individuals) were identified. The individual cases were Thich Quang Duc (1963), Christine Chubbuck (1974), Budd Dwyer (1987), Daniel Victor Jones (1998), Michael Marin (2012) and Jordon Romero (2012). The two groups were the Japanese Kamikaze pilots of 1944\/1995, and those who jumped from the burning \"Twin Towers\" on September 11, 2001. One of the six individuals has evidence of a mental disorder, and all (individual and group cases) were in potent social\/environmental predicaments. Both psychological autopsies and our clinical experience suggest that suicide is often associated with mental disorder. Nevertheless, social\/environmental predicaments may lead to suicide. This study suggests that individuals whose suicide is captured on film are often seeking public exposure of their fatal act.","subset":"pubmed_abstract"} +{"meta":{"pmid":8339811,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":13}}},"text":"The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.\nThe case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.","subset":"pubmed_abstract"} +{"meta":{"pmid":2466556,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Effects of heat shock proteins (Mr 70,000) on protein and DNA synthesis at elevated temperatures in vitro.\nThe protective effect of Mr 70,000 heat shock protein (HSP-70) during thermotolerance has been previously observed. However, it is not known what cellular processes or components may be protected by this protein during the tolerance state. In the studies reported here, the protective effects of purified HSP-70, the nonspecific heat-stable proteins fetuin and trypsin inhibitor (ovomucoid), and other proteins and agents such as bovine serum albumin, D2O, or glycerol on protein and DNA synthesis during heating were investigated in vitro. In vitro protein synthesis at 30, 40, and 42 degrees C was measured by globin mRNA translation. Protein synthesis was inhibited 40 to 70% when incubated for 60 min at 40 and 42 degrees C. However, protein synthesis was protected when either fetuin or ovomucoid was present during protein synthesis at elevated temperatures. The protection was concentration dependent. The HSP-70 purified from Chinese hamster (HA-1) cells was also able to confer protection to the translation system, but at much lower concentrations than either fetuin or ovomucoid. Other proteins, such as bovine serum albumin, or other agents, such as D2O or glycerol which are known protectors of cellular survival during heating, did not protect the translation system. Similar experiments were performed with DNA synthesis in vitro. Purified DNA polymerase alpha was added to the activated calf thymus DNA in an in vitro replication system. A temperature of 46 degrees C for 60 min inhibited replication by 40%. Addition of heat-stable proteins, purified HSP-70, bovine serum albumin, D2O, or glycerol did not confer protection to the replication system. These studies provide new evidence that HSP-70 may confer protection to a component of the protein synthesis machinery during thermotolerance.","subset":"pubmed_abstract"} +{"meta":{"pmid":29209859,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2021-10":1,"2020-50":1,"2020-29":1,"2019-51":1,"2019-39":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2021-21":1}}},"text":"Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind, randomised clinical trial.\nThe trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia, as compared to placebo in adult patients with acute bronchitis. Patients with uncomplicated acute bronchitis (bronchitis severity score [BSS] \u2265 5 score points) were randomly assigned to treatment with Spicae ae. or placebo in a double-blind, parallel-group design. No additional treatment was admitted. The primary objective was the mean difference of a defined total BSS of 25% between the Spicae ae. and the placebo group after 7 days of full medication dose. Secondary endpoints included the BSS at day 10, additional signs and symptoms of bronchitis, quality of life (QoL) and safety. The mean decrease in BSS at day 7 and day 10 was significant with 4.79 vs. 3.20 (p < 0.005 for a 25% difference) and 6.47 vs. 4.32 (p < 0.009 for a 25% difference) score points respectively in the Spicae ae. (n = 119) vs. placebo group (n = 110). Accordingly, most additional signs and symptoms of acute bronchitis as well as the patients' QoL improved significantly with Spicae ae. as compared to placebo. In all, 258 patients were eligible for safety analysis. The treatment with Spicae ae. was well tolerated; no serious adverse events occurred. The defined objectives both for the primary and secondary endpoints have been met. The results of this study provide evidence that Spicae ae. is well tolerated, effective and superior to placebo in the symptomatic treatment of uncomplicated acute bronchitis in adult patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":19041967,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":2,"2017-22":1,"2021-43":1}}},"text":"Direct retroperitoneal pelvic packing versus pelvic angiography: A comparison of two management protocols for haemodynamically unstable pelvic fractures.\nTo evaluate the outcomes of haemodynamically unstable cases of pelvic ring injury treated with a protocol focused on either direct retroperitoneal pelvic packing or early pelvic angiography and embolisation. A retrospective review of a prospectively collected database in an academic level I trauma centre, treating matched haemodynamically unstable cases of pelvic fracture with either pelvic packing (PACK group, n=20) or early pelvic angiography (ANGIO group, n=20). Physiological markers of haemorrhage, time to intervention, transfusion requirements, complications and early mortality were recorded. The PACK group underwent operative packing at a median of 45min from admission; the median time to angiography in the ANGIO group was 130min. The PACK group, but not the ANGIO group, demonstrated a significant decrease in blood transfusions over the next 24h post intervention. In the ANGIO group, ten people required embolisation and six died, two from acute haemorrhage; in the PACK group, three people required embolisation; four died, none due to uncontrolled haemorrhage. Pelvic packing is as effective as pelvic angiography for stabilising haemodynamically unstable casualties with pelvic fractures, decreases need for pelvic embolisation and post-procedure blood transfusions, and may reduce early mortality due to exsanguination from pelvic haemorrhage.","subset":"pubmed_abstract"} +{"meta":{"pmid":21497048,"dup_signals":{"dup_doc_count":25,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-04":1,"2018-43":2,"2018-34":2,"2018-30":1,"2018-22":1,"2018-17":2,"2018-13":1,"2018-09":1,"2018-05":2,"2017-47":2,"2017-39":2}}},"text":"In vivo evaluation of blue-light attenuation with tinted and untinted intraocular lenses.\nTo evaluate blue-light attenuation in eyes with a tinted intraocular lens (IOL) or an untinted IOL. Department of Ophthalmology, University Hospital of Crete, Crete, Greece. Comparative case series. Patients had lens extraction and implantation of an Acrysof Natural tinted or Tecnis ZA9003 or Softec III untinted acrylic IOL. The luminance ratio of green (530 nm) and blue (465 nm) light (green:blue ratio) required for isoluminant perception was determined by heterochromatic flicker photometry. Patients were tested preoperatively and 20 days postoperatively. The parafoveal measure of the green:blue ratio, expressed in decibels, is proportional to the blue-light attenuation by the lens. Twenty-two patients received the tinted IOL and 21 the untinted IOL. Preoperatively, age was strongly linearly correlated with the green:blue ratio (r = 0.59, P < .001). The mean postoperative decrease in the green:blue ratio was greater in the untinted IOL group (P = .003). Postoperatively, the tinted IOL group had a significantly higher green:blue ratio than the untinted IOL group (P < .001). In the tinted IOL group, the green:blue ratio was linearly related to IOL dioptric power. Less blue light reached the retina with tinted IOLs than with untinted IOLs. The absorption properties of tinted IOLs seemed to resemble those of the aging human crystalline lens, while untinted IOLs resembled the lower levels of blue-light attenuation of younger lenses. Thus, tinted IOLs may protect against the presumed blue-light hazard. No author has a financial or proprietary interest in any material or method mentioned.","subset":"pubmed_abstract"} +{"meta":{"pmid":11305035,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"[Influence of acupuncture and moxibustion on QOL of the elderly living in nursing home and care house].\nTo clarify the influence of acupuncture therapy on the quality of life (QOL) of the elderly, the acupuncture and moxibustion were performed on 35 elderly subjects (8 men and 27 women) with a mean age 79.1 living in nursing homes and elderly care houses. The acu-points were chosen according to their symptoms. Changes in pain and other complaints, body condition, appetite, sleep, bowel movement and activity of daily living (ADL) were evaluated by questionnaires. A total of 38 symptoms were reported. A high rate of improvement was seen in pain and stiffness. For example, there was 86% improvement in low back pain, 84% in knee joint pain and 82% in shoulder stiffness. Concerning body conditions, decrease of fatigue, relaxed of feeling, improvement in appetite, sleep and bowel movement were observed. Furthermore, gait and ADL were also improved. These results suggested that acupuncture and moxibustion are useful to improve QOL in the elderly.","subset":"pubmed_abstract"} +{"meta":{"pmid":23300915,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Standardization of diagnostic biomarker concentrations in urine: the hematuria caveat.\nSensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers. Our objective was therefore to characterize the effects of standardizing urinary levels of IL-6, IL-8, and VEGF using the commonly applied standards namely urinary creatinine, osmolarity and protein. First, we report results based on the biomarker levels measured in 120 hematuric patients, 80 with pathologically confirmed bladder cancer, 27 with confounding pathologies and 13 in whom no underlying cause for their hematuria was identified, designated \"no diagnosis\". Protein levels were related to final diagnostic categories (p = 0.022, ANOVA). Osmolarity (mean = 529 mOsm; median = 528 mOsm) was normally distributed, while creatinine (mean = 10163 \u00b5mol\/l, median = 9350 \u00b5mol\/l) and protein (0.3297, 0.1155 mg\/ml) distributions were not. When we compared AUROCs for IL-6, IL-8 and VEGF levels, we found that protein standardized levels consistently resulted in the lowest AUROCs. The latter suggests that protein standardization attenuates the \"true\" differences in biomarker levels across controls and bladder cancer samples. Second, in 72 hematuric patients; 48 bladder cancer and 24 controls, in whom urine samples had been collected on recruitment and at follow-up (median = 11 (1 to 20 months)), we demonstrate that protein levels were approximately 24% lower at follow-up (Bland Altman plots). There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients. Collectively, our findings identify caveats intrinsic to the common practice of protein standardization in biomarker discovery studies conducted on urine, particularly in patients with hematuria.","subset":"pubmed_abstract"} +{"meta":{"pmid":24754542,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Relationship between menopausal symptoms and sexual dysfunction among married Turkish women in 40-65 age group.\nThis was a cross-sectional study to analyse the relationship between menopausal symptoms and sexual dysfunction among 229 married Turkish women in the 40-65 age group. The study was carried out at a menopause clinic of a state hospital between 1 October and 31 December 2010. Data were collected with Personal Characteristics Form, Menopause Rating Scale (MRS) and the Arizona Sexual Experience Scale (ASEX). The average age of the women was 52.33 (SD = 4.80) years. The average MRS total score was 20.13(SD = 9.20). The ASEX mean score was 19.97 (SD = 5.44). It was determined that there is a positive meaningful relationship between ASEX mean score, MRS total mean score and the sub-score of women. From the results obtained from this study, it can be said that women have differing levels of menopausal symptoms, and as the severity of menopausal symptoms increases, there is an increase in sexual dysfunction.","subset":"pubmed_abstract"} +{"meta":{"pmid":16960552,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Locally acquired mosquito-transmitted malaria: a guide for investigations in the United States.\nRecent outbreaks of locally acquired mosquito-transmitted malaria in the United States demonstrate the continued risk for reintroduction of the disease. Since 1957, when CDC's Malaria Branch started conducting malaria surveillance, 63 outbreaks have occurred, constituting 156 cases (annual range: 1-32) that were a result of locally acquired mosquitoborne transmission. This report describes the steps that should be taken to 1) investigate a case that might have been acquired locally, 2) prevent a small focus of malaria cases from becoming a source of sustained transmission, and 3) inform clinicians regarding the process of an investigation so they can effectively address concerns and questions from patients. Although these locally acquired mosquito-transmitted outbreaks frequently involve only a limited number of infected persons, they frequently raise concerns in the community and require substantial public health resources. For example, as a result of the most recent local outbreak of eight malaria cases in Florida in 2003, reverse 911 telephone calls (a community notification system) were made to approximately 300,000 residents; insect repellent, postcards, flyers, and posters in multiple languages were distributed; public announcements were made through the media and to schools and homeless shelters; and notifications were sent to local hospitals and physicians to inform residents of that community. When a local health department investigates a potential locally acquired mosquito-transmitted case, the systematic inquiry should include epidemiologic, environmental, and laboratory components. Local and state health departments inquiring about the proper approach to investigate and control a potential locally acquired case frequently request urgent assistance and tools from CDC. This report provides a starting point for such investigations to local and state health departments by providing them with the tools necessary to initiate an investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28851683,"dup_signals":{"dup_doc_count":31,"dup_details":{"curated_sources":3,"unknown":28}}},"text":"Delayed extrusion of embolic coils into the airway after embolization of an external carotid artery pseudoaneurysm.\nCarotid blowout syndrome (CBS) is a known devastating complication of head and neck surgery. The risk of developing CBS increases in the setting of radiation therapy, wound breakdown, or tumor recurrence. Traditionally, the treatment of choice for CBS is surgical ligation of the bleeding artery; however, recently, endovascular occlusion has become a more common option. If a pseudoaneurysm is present, treatment consists of trapping with endovascular coils or occlusion with a liquid embolic agent. Delayed migration of embolization coils into the airway causing acute respiratory distress is a rare occurrence. This report presents a case of a 57-year-old woman who presented to her otolaryngologist after experiencing an episode of acute respiratory distress which resolved when she expectorated embolization coil material from her tracheostomy tube. Three months prior to the episode she underwent coil embolization of an external carotid artery pseudoaneurysm for life-threatening hemorrhage.","subset":"pubmed_abstract"} +{"meta":{"pmid":23023591,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":12}}},"text":"Reoperation rate after surgery for lumbar herniated intervertebral disc disease: nationwide cohort study.\nRetrospective cohort study using national health insurance data. To provide a longitudinal reoperation rate after surgery for lumbar herniated intervertebral disc (HIVD) disease, and to compare the reoperation rates of surgical methods. Herniated intervertebral disc disease is the most common cause of lumbar spinal surgery. Despite improved surgical techniques and instrumentation, reoperation cannot be avoided. The reoperation rates were in the range of 6% to 24% in previous studies. A population-based study is less subject to bias; hence, a nationwide longitudinal analysis was warranted. A national health insurance database was used to identify a cohort of patients who underwent first surgery for herniated intervertebral disc disease in 2003 and 18,590 patients were selected. Individual patients were followed for at least 5 years through their encrypted unique resident registration number. The primary endpoint was any type of second lumbar surgery. After adjusting for confounding factors, 5 surgical methods (fusion, laminectomy, open discectomy, endoscopic discectomy, and nucleolysis [including mechanical nucleus decompression]) were compared. Open discectomy was used as the reference method. Open discectomy was the most common procedure (68.9%) followed by endoscopic discectomy (16.1%), laminectomy (7.9%), fusion (3.9%), and nucleolysis (3.2%). The cumulative reoperation rate was 5.4% at 3 months, 7.4% at 1 year, 9% at 2 years, 10.5% at 3 years, 12.1% at 4 years, and 13.4% at 5 years. The reoperation rates were 18.6%, 14.7%, 13.8%, 12.4%, and 11.8% after laminectomy, nucleolysis, open discectomy, endoscopic discectomy, and fusion, respectively. Compared with open discectomy, the reoperation rate was higher after laminectomy at 3 months, whereas the other surgical methods had similar rates. The cumulative reoperation rate after 5 years was 13.4% and half of the reoperations occurred during the first postoperative year. With the exception of laminectomy, the reoperation rates of the other procedures were not different from that of open discectomy.","subset":"pubmed_abstract"} +{"meta":{"pmid":29471925,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-23":2,"2023-06":2,"2022-40":2,"2022-21":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1}}},"text":"Cost and cost-effectiveness of computerized vs. in-person motivational interventions in the criminal justice system.\nAlthough substance use is common among probationers in the United States, treatment initiation remains an ongoing problem. Among the explanations for low treatment initiation are that probationers are insufficiently motivated to seek treatment, and that probation staff have insufficient training and resources to use evidence-based strategies such as motivational interviewing. A web-based intervention based on motivational enhancement principles may address some of the challenges of initiating treatment but has not been tested to date in probation settings. The current study evaluated the cost-effectiveness of a computerized intervention, Motivational Assessment Program to Initiate Treatment (MAPIT), relative to face-to-face Motivational Interviewing (MI) and supervision as usual (SAU), delivered at the outset of probation. The intervention took place in probation departments in two U.S. cities. The baseline sample comprised 316 participants (MAPIT = 104, MI = 103, and SAU = 109), 90% (n = 285) of whom completed the 6-month follow-up. Costs were estimated from study records and time logs kept by interventionists. The effectiveness outcome was self-reported initiation into any treatment (formal or informal) within 2 and 6 months of the baseline interview. The cost-effectiveness analysis involved assessing dominance and computing incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Implementation costs were used in the base case of the cost-effectiveness analysis, which excludes both a hypothetical license fee to recoup development costs and startup costs. An intent-to-treat approach was taken. MAPIT cost $79.37 per participant, which was ~$55 lower than the MI cost of $134.27 per participant. Appointment reminders comprised a large proportion of the cost of the MAPIT and MI intervention arms. In the base case, relative to SAU, MAPIT cost $6.70 per percentage point increase in the probability of initiating treatment. If a decision-maker is willing to pay $15 or more to improve the probability of initiating treatment by 1%, estimates suggest she can be 70% confident that MAPIT is good value relative to SAU at the 2-month follow-up and 90% confident that MAPIT is good value at the 6-month follow-up. Web-based MAPIT may be good value compared to in-person delivered alternatives. This conclusion is qualified because the results are not robust to narrowing the outcome to initiating formal treatment only. Further work should explore ways to improve access to efficacious treatment in probation settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":23288533,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":15}}},"text":"Negative absolute temperature for motional degrees of freedom.\nAbsolute temperature is usually bound to be positive. Under special conditions, however, negative temperatures-in which high-energy states are more occupied than low-energy states-are also possible. Such states have been demonstrated in localized systems with finite, discrete spectra. Here, we prepared a negative temperature state for motional degrees of freedom. By tailoring the Bose-Hubbard Hamiltonian, we created an attractively interacting ensemble of ultracold bosons at negative temperature that is stable against collapse for arbitrary atom numbers. The quasimomentum distribution develops sharp peaks at the upper band edge, revealing thermal equilibrium and bosonic coherence over several lattice sites. Negative temperatures imply negative pressures and open up new parameter regimes for cold atoms, enabling fundamentally new many-body states.","subset":"pubmed_abstract"} +{"meta":{"pmid":20950451,"dup_signals":{"dup_doc_count":22,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2021-04":1,"2020-24":1,"2019-39":1,"2019-22":1,"2018-47":1,"2018-34":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2021-17":1,"2017-13":1,"2024-30":1}}},"text":"Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models.\nAmyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1G93A mutant mice. Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1G93A animal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1G93A mice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-\u03b1 antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting. BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 \u00b1 3.5 days) was 18% greater than control group (117 \u00b1 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1G93A mice at the symptomatic stage. From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.","subset":"pubmed_abstract"} +{"meta":{"pmid":25534867,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Sodium Excretion and Cardiovascular Structure and Function in the Nonhypertensive Population: The Korean Genome and Epidemiology Study.\nThe effect of sodium intake on the cardiovascular system remains controversial. The purpose of this study is to investigate the relation between sodium intake and cardiovascular structure and function in the nonhypertensive population. We performed a cross-sectional analysis in 1,586 nonhypertensive subjects who participated in the Korean Genome Epidemiology Study (2007-2008). Sodium intake was assessed by estimating the 24-hour urinary sodium excretion from a spot urine sample. Changes in cardiovascular structure and function were assessed by using tissue Doppler echocardiography, the carotid intima-media thickness (CIMT), and the brachial-ankle pulse wave velocity (baPWV). Systolic and diastolic blood pressures increased with increasing tertiles of estimated 24-hour urinary sodium excretion. In multivariate analyses adjusting for covariates, there were stepwise decreases in the baPWV (P = 0.003) and CIMT (P = 0.001) values as the estimated 24-hour urinary sodium excretion increased, whereas no significant differences in left ventricular (LV) structural and functional parameters were observed across the tertiles of estimated 24-hour urinary sodium excretion. Multiple linear regression analyses revealed that the estimated 24-hour urinary sodium excretion was independently and inversely associated with baPWV (P < 0.001) and CIMT (P = 0.001), but not with LV parameters. In the nonhypertensive population, urinary sodium excretion was inversely related to baPWV and CIMT. However, there were no associations between urinary sodium excretion and LV structure or function.","subset":"pubmed_abstract"} +{"meta":{"pmid":10473404,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Phylogenetic affiliation and quantification of psychrophilic sulfate-reducing isolates in marine Arctic sediments.\nThirteen psychrophilic sulfate-reducing isolates from two permanently cold fjords of the Arctic island Spitsbergen (Hornsund and Storfjord) were phylogenetically analyzed. They all belonged to the delta subclass of Proteobacteria and were widely distributed within this group, indicating that psychrophily is a polyphyletic property. A new 16S rRNA-directed oligonucleotide probe was designed against the largest coherent cluster of these isolates. The new probe, as well as a set of available probes, was applied in rRNA slot blot hybridization to investigate the composition of the sulfate-reducing bacterial community in the sediments. rRNA related to the new cluster of incompletely oxidizing, psychrophilic isolates made up 1.4 to 20.9% of eubacterial rRNA at Storfjord and 0.6 to 3. 5% of eubacterial rRNA at Hornsund. This group was the second-most-abundant group of sulfate reducers at these sites. Denaturing gradient gel electrophoresis and hybridization analysis showed bands identical to those produced by our isolates. The data indicate that the psychrophilic isolates are quantitatively important in Svalbard sediments.","subset":"pubmed_abstract"} +{"meta":{"pmid":28657988,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Vaginal Uterosacral Ligament Suspension: A Retrospective Cohort of Absorbable and Permanent Suture Groups.\nThe aim of this study was to compare anatomic results after vaginal uterosacral ligament suspension with absorbable versus permanent suture. We performed a retrospective cohort study of women who underwent vaginal uterosacral ligament suspension, from 2006 to 2015. We compared 2 groups: (1) absorbable suspension suture and (2) permanent suspension suture (even if accompanied by absorbable suture). Our primary outcome was composite anatomic failure defined as (1) recurrent prolapse in any compartment past the hymen or (2) retreatment for prolapse. Continuous variables were analyzed using the Student t test or Mann-Whitney U test, and categorical variables were analyzed using \u03c7 or Fisher exact test. Multivariable logistic regression analysis was performed to control for confounders. P < 0.05 was considered significant. Of the 242 patients with medium-term follow-up (3 months to 2 years after surgery), 188 underwent vaginal uterosacral ligament suspension with only absorbable suture, and 54 underwent suspension with permanent suture. Compared with the absorbable suture cohort, the permanent suture cohort was more likely to have had advanced preoperative prolapse (P = 0.01), less likely to have had a prior hysterectomy (P = 0.01), and less likely to have undergone a concomitant posterior colporrhaphy\/perineoplasty (P < 0.01). Overall, there were no differences in composite anatomic failure between the absorbable and permanent suture groups (17.0% vs 20.4%, P = 0.41). In multivariable logistic regression analyses, when controlling for covariates, there remained no difference in composite anatomic failure between permanent and absorbable suture groups. Completion of vaginal uterosacral ligament suspension using only absorbable suture affords similar anatomic outcomes in the medium term as compared with suspension with additional permanent suture.","subset":"pubmed_abstract"} +{"meta":{"pmid":21796370,"dup_signals":{"dup_doc_count":11}},"text":"Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), \u0394\u2079-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.\nPhytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), \u0394(9)-tetrahydrocannabivarin (\u0394(9)-THCV) and cannabigerol (CBG). We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg\/kg, ip and oral) was further assessed using a marble burying test in mice. All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg\/kg) and CBDV (60 mg\/kg), but not for \u0394(9)-THCV (30 mg\/kg) and CBG (120 mg\/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile. These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":32180952,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":3,"unknown":11}}},"text":"Normal variations in personality predict eating behavior, oral health, and partial syndrome bulimia nervosa in adolescent girls.\nEating disorders are among the most prevalent disorders in adolescence and can have negative consequences including poor quality of life, medical complications, and even death. This study addresses whether normal variations in personality relate to eating behavior and eating disorder symptomatology in adolescent girls. Participants were a near-representative sample of Australian adolescent girls (n = 1,676). Three personality traits (neuroticism, extraversion, and conscientiousness) were assessed at age 12 and again at age 14, and self-reported eating and weight management behaviors were assessed at age 14. After controlling for sociodemographic factors, higher levels of conscientiousness at age 12, and increases in conscientiousness between ages 12 and 14, were associated with greater fruit and vegetable consumption, a lower intake of high fat foods and high sugar drinks, less frequent meal skipping, better oral health, and decreased risk of partial syndrome bulimia nervosa at age 14. Higher neuroticism at age 12 was associated with more frequent meal skipping, and increases in neuroticism between ages 12 and 14 were associated with more frequent meal skipping and increased risk of partial syndrome bulimia nervosa at age 14. Extraversion was generally unrelated to eating and weight management behaviors. These findings provide evidence that normal variations in personality are related to eating behavior, oral health, and eating disorder symptoms during midadolescence.","subset":"pubmed_abstract"} +{"meta":{"pmid":24596327,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Iron(III)-quantity-dependent aggregation-dispersion conversion of functionalized gold nanoparticles.\nDeveloping gold nanoparticles (AuNPs) with well-designed functionality is highly desirable for boosting the performance and versatility of inorganic-organic hybrid materials. In an attempt to achieve ion recognition with specific signal expressions, we present here 4-piperazinyl-1,8-naphthalimide-functionalized AuNPs for the realization of quantitative recognition of Fe(III) ions with dual (colorimetric and fluorescent) output. The research takes advantage of 1) quantity-controlled chelation-mode transformation of the piperazinyl moiety on the AuNPs towards Fe(III), thereby resulting in an aggregation-dispersion conversion of the AuNPs in solution, and 2) photoinduced electron transfer of a naphthaimide fluorophore on the AuNPs, thus leading to reversible absorption and emission changes. The functional AuNPs are also responsive to pH variations. This strategy for realizing the aggregation-dispersion conversion of AuNPs with returnable signal output might exhibit application potential for advanced nanoscale chemosensors.","subset":"pubmed_abstract"} +{"meta":{"pmid":28680119,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-30":3,"2024-26":1,"2024-22":2,"2024-18":2,"unknown":10}}},"text":"Increased Stability and Breakdown of Brain Effective Connectivity During Slow-Wave Sleep: Mechanistic Insights from Whole-Brain Computational Modelling.\nRecent research has found that the human sleep cycle is characterised by changes in spatiotemporal patterns of brain activity. Yet, we are still missing a mechanistic explanation of the local neuronal dynamics underlying these changes. We used whole-brain computational modelling to study the differences in global brain functional connectivity and synchrony of fMRI activity in healthy humans during wakefulness and slow-wave sleep. We applied a whole-brain model based on the normal form of a supercritical Hopf bifurcation and studied the dynamical changes when adapting the bifurcation parameter for all brain nodes to best match wakefulness and slow-wave sleep. Furthermore, we analysed differences in effective connectivity between the two states. In addition to significant changes in functional connectivity, synchrony and metastability, this analysis revealed a significant shift of the global dynamic working point of brain dynamics, from the edge of the transition between damped to sustained oscillations during wakefulness, to a stable focus during slow-wave sleep. Moreover, we identified a significant global decrease in effective interactions during slow-wave sleep. These results suggest a mechanism for the empirical functional changes observed during slow-wave sleep, namely a global shift of the brain's dynamic working point leading to increased stability and decreased effective connectivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":21979475,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Centipede bite victims: a review of patients presenting to two emergency departments in Hong Kong.\nOBJECTIVE. To review the clinical characteristics of patients presenting after centipede bites in Hong Kong. DESIGN. Descriptive case series. SETTING. Emergency departments of two public hospitals in Hong Kong. PATIENTS. Patients presenting after centipede bites between 2006 and 2010. MAIN OUTCOME MEASURES. Demographics, time and locations of bites, symptoms and signs, treatments and outcomes. RESULTS. A total of 46 relevant patient records were retrieved. The bites were frequently at night, indoors, on lower limbs, and consistently resulted in pain. The majority of the victims were treated with analgesia, anti-histamines, and antibiotics. One patient developed necrosis and five re-attended for delayed pruritus and relapsed\/recurrent swelling. CONCLUSIONS. Centipede bites are usually uncomplicated, but may lead to necrosis or delayed hypersensitive reactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30157765,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-06":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-21":1,"2021-10":1,"2020-45":1,"2020-34":1,"2020-10":1,"2019-47":1,"2019-39":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Temperature responses of mutation rate and mutational spectrum in an Escherichia coli strain and the correlation with metabolic rate.\nTemperature is a major determinant of spontaneous mutation, but the precise mode, and the underlying mechanisms, of the temperature influences remain less clear. Here we used a mutation accumulation approach combined with whole-genome sequencing to investigate the temperature dependence of spontaneous mutation in an Escherichia coli strain. Experiments were performed under aerobic conditions at 25, 28 and 37 \u00b0C, three temperatures that were non-stressful for the bacterium but caused significantly different bacterial growth rates. Mutation rate did not differ between 25 and 28 \u00b0C, but was higher at 37 \u00b0C. Detailed analyses of the molecular spectrum of mutations were performed; and a particularly interesting finding is that higher temperature led to a bias of mutation to coding, relative to noncoding, DNA. Furthermore, the temperature response of mutation rate was extremely similar to that of metabolic rate, consistent with an idea that metabolic rate predicts mutation rate. Temperature affects mutation rate and the types of mutation supply, both being crucial for the opportunity of natural selection. Our results help understand how temperature drives evolutionary speed of organisms and thus the global patterns of biodiversity. This study also lend support to the metabolic theory of ecology for linking metabolic rate and molecular evolution rate.","subset":"pubmed_abstract"} +{"meta":{"pmid":27043165,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":18}}},"text":"Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.\nAntiarrhythmic drugs are used commonly in out-of-hospital cardiac arrest for shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, but without proven survival benefit. In this randomized, double-blind trial, we compared parenteral amiodarone, lidocaine, and saline placebo, along with standard care, in adults who had nontraumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia after at least one shock, and vascular access. Paramedics enrolled patients at 10 North American sites. The primary outcome was survival to hospital discharge; the secondary outcome was favorable neurologic function at discharge. The per-protocol (primary analysis) population included all randomly assigned participants who met eligibility criteria and received any dose of a trial drug and whose initial cardiac-arrest rhythm of ventricular fibrillation or pulseless ventricular tachycardia was refractory to shock. In the per-protocol population, 3026 patients were randomly assigned to amiodarone (974), lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%, respectively, survived to hospital discharge. The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], -0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points (95% CI, -1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7 percentage points (95% CI, -3.2 to 4.7; P=0.70). Neurologic outcome at discharge was similar in the three groups. There was heterogeneity of treatment effect with respect to whether the arrest was witnessed (P=0.05); active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing than did recipients of lidocaine or placebo. Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT01401647.).","subset":"pubmed_abstract"} +{"meta":{"pmid":24964172,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity.\nMethotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient's white blood cell count was found to be 0.9 \u00d7 10(9)\/L (4-10 \u00d7 10(9)\/L). The patient developed fever exceeding 40 \u00b0C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3 \u00d7 10(9)\/L and the patient's fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":25895531,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":6,"2022-40":1,"2022-27":1,"2021-43":1,"2021-39":1,"2021-21":2,"2021-10":1,"2021-04":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-16":1,"2023-23":1}}},"text":"B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.\nB cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part as a result of the success of B cell-depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B cell Ag presentation was suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support Ag-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHC class II, we reported previously that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole APC. In this study, we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of Ag-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuroinflammation at later stages of disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":30025141,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Optic Nerve Sheath Tethering in Adduction Occurs in Esotropia and Hypertropia, But Not in Exotropia.\nRepetitive strain to the optic nerve (ON) due to tethering in adduction has been recently proposed as an intraocular pressure-independent mechanism of optic neuropathy in primary open-angle glaucoma. Since strabismus may alter adduction, we investigated whether gaze-related ON straightening and associated globe translation differ in horizontal and vertical strabismus. High-resolution orbital magnetic resonance imaging was obtained in 2-mm thick quasi-coronal planes using surface coils in 25 subjects (49 orbits) with esotropia (ET, 19 \u00b1 3.6\u0394 SEM), 11 (15 orbits) with exotropia (XT, 33.7 \u00b1 7.3\u0394), 7 (12 orbits) with hypertropia (HT, 14.6 \u00b1 3.2\u0394), and 31 normal controls (62 orbits) in target-controlled central gaze, and in maximum attainable abduction and adduction. Area centroids were used to determine ON path sinuosity and globe positions. Adduction angles achieved in ET (30.6\u00b0 \u00b1 0.9\u00b0) and HT (27.2\u00b0 \u00b1 2.3\u00b0) did not significantly differ from normal (28.3\u00b0 \u00b1 0.7\u00b0), but significantly less adduction was achieved in XT (19.0\u00b0 \u00b1 2.5\u00b0, P = 0.005). ON sheath tethering in adduction occurred in ET and HT similarly to normal, but did not in XT. The globe translated significantly less than normal, nasally in adduction in XT and temporally in abduction in ET and HT (P < 0.02, for all). Globe retraction did not occur during abduction or adduction in any group. Similar to normal subjects, the ON and sheath become tethered without globe retraction in ET and HT. In XT, adduction tethering does not occur, possibly due to limited adduction angle. Thus, therapeutic limitation of adduction could be considered as a possible treatment for ON sheath tethering.","subset":"pubmed_abstract"} +{"meta":{"pmid":23956920,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Simultaneous right retroperitoneal schwannoma and left renal hydatid cyst.\nRetroperitoneal schwannomas are quite rare tumors. Isolated renal hydatid cyst is also rare, and it forms 2-4% of hydatid disease. Because of their infrequent occurrence, nonspecific signs and symptoms, and lack of distinguishing radiologic features, we report herein a case of right retroperitoneal mass in a 26-year-old woman which was found to be benign schwannoma following a percutaneous core needle biopsy and a large cortical cyst in the lower pole of the left kidney which was diagnosed as isolated renal hydatid cyst following exploration.","subset":"pubmed_abstract"} +{"meta":{"pmid":30702093,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Unraveling structural dynamics in isoenergetic excited S1 and multi-excitonic 1(TT) states of 9,10-bis(phenylethynyl)anthracene (BPEA) in solution via ultrafast Raman loss spectroscopy.\nPolyacenes, such as anthracene, tetracene, pentacene etc., have been identified as potential candidates for singlet fission (SF) and triplet-triplet annihilation (TTA) processes in their crystalline and thin film forms as they possess significant singlet and triplet exciton couplings. Interestingly, phenyl-ethynyl substitution to anthracene at the 9,10 positions (9,10-bis(phenylethynyl)anthracene\/BPEA) enhances the transverse \u03c0-electron conjugation and retains the planar structure even in the excited state. The excited singlet state S1 and the multi-excitonic state 1(TT) in BPEA are separated by \u223c30 meV (\u223c250 cm-1) making it an ideal system for both SF and TTA applications. BPEA is very effective in photon up-conversion even for low input intensities. Transient absorption measurements of BPEA in n-hexane solution are inadequate for distinguishing the S1 state and the multi-excitonic state 1(TT), since the spectroscopic features are complex (mixed) due to the isoenergetic nature and the existence of an equilibrium between these states. However, ultrafast Raman loss spectroscopy reveals a systematic red shift and a blue shift in the central frequencies of the Raman modes corresponding to C[double bond, length as m-dash]C and C[triple bond, length as m-dash]C vibrational frequencies with time constants of \u223c2.0 and \u223c20 ps, respectively. Such a shift in the Raman frequencies is direct evidence of the structural changes that take place while changing from excited singlet state S1 to the multi-excitonic state on the potential surface.","subset":"pubmed_abstract"} +{"meta":{"pmid":23815109,"dup_signals":{"dup_doc_count":31,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":3,"2024-10":1,"2017-13":1,"2024-30":1,"unknown":21}}},"text":"The Child PTSD Symptom Scale: an update and replication of its psychometric properties.\nThe psychometric properties of the child PTSD Symptom Scale (CPSS) were examined in 2 samples. Sample 1 (N = 185, ages 6-17 years) consisted of children recruited from hospitals after accidental injury, assault, and road traffic trauma, and assessed 6 months posttrauma. Sample 2 (N = 68, ages 6-17 years) comprised treatment-seeking children who had experienced diverse traumas. In both samples psychometric properties were generally good to very good (internal reliability for total CPSS scores = .83 and .90, respectively). The point-biserial correlation of the CPSS with posttraumatic stress disorder (PTSD) diagnosis derived from structured clinical interview was .51, and children diagnosed with PTSD reported significantly higher symptoms than non-PTSD children. The CPSS demonstrated applicability to be used as a diagnostic measure, demonstrating sensitivity of 84% and specificity of 72%. The performance of the CPSS Symptom Severity Scale to accurately identify PTSD at varying cutoffs is reported in both samples, with a score of 16 or above suggested as a revised cutoff.","subset":"pubmed_abstract"} +{"meta":{"pmid":2613953,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Some ambiguities of the student's role in undergraduate nurse training.\nProposed changes in the way in which nurses are educated and trained will lead to stronger links between the academic and practical worlds of nursing. However, little or no attention has been focused on the potential difficulties associated with such a move for the student in this new and changing role. Important ambiguities of the student's role need to be addressed if the degree nursing student is to make the most of available opportunities for learning. In this paper we draw a distinction between two kinds of ambiguity in the role of nursing degree student during clinical placements. The first type is essential to the very nature of degree education in nursing, since the ambiguities here all entail problems in bridging the gap between the world of practical nursing and that of education. They include whether he or she is to regard the role as one of learner or producer of work; whether to become unreflectively acculturated to the organization or to reflect on its norms and values; and the student function within the organization. A second kind of ambiguity is not essential to nurse education, but is an unintended consequence of placement arrangements. The student is thrust into the clinical field as a short-term member of an organization; their position is anomalous and the motive for their involvement is largely different from that of permanent employees. These ambiguities of the role are also the source of important learning opportunities.","subset":"pubmed_abstract"} +{"meta":{"pmid":31383959,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-22":1,"unknown":7}}},"text":"Challenges with colorectal cancer staging: results of an international study.\nChallenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study.","subset":"pubmed_abstract"} +{"meta":{"pmid":30954305,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":13}}},"text":"Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.\nSuboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity. By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of disease-specific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome. In 2017, 11 million (95% uncertainty interval [UI] 10-12) deaths and 255 million (234-274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1-5] deaths and 70 million [34-118] DALYs), low intake of whole grains (3 million [2-4] deaths and 82 million [59-109] DALYs), and low intake of fruits (2 million [1-4] deaths and 65 million [41-92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates. This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually. Bill & Melinda Gates Foundation.","subset":"pubmed_abstract"} +{"meta":{"pmid":30975531,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2020-05":3,"2019-51":2,"2019-47":1,"2019-43":6,"2019-39":2,"2023-23":1}}},"text":"Kinetic models of migration of melamine and formaldehyde from melamine kitchenware with data of liquid chromatography.\nEuropean legislation has established a specific migration limit (SML) of 15 mg kg-1 for formaldehyde and 2.5 mg kg-1 for melamine. Formaldehyde resins are used in the manufacture of melamine kitchenware. Formaldehyde is listed in group 1 of the IARC list of carcinogenic compounds. To determine the quantity of formaldehyde and melamine as potential migrants from different types of melamine kitchenware (glass, mug, cutlery, big cup and bowl), a HPLC-DAD method has been implemented. This method is an alternative to the ones proposed in technical guidelines to determine formaldehyde by UV-vis spectrophotometry and melamine by HPLC. The final objective was to fit the migration kinetic curves of these two analytes in melamine kitchenware. After the method was validated, decision limit (CC\u03b1) and detection capability (CC\u03b2) were calculated for both analytes, when the probabilities of false positive (\u03b1) and false negative (\u03b2) were fixed at 0.05; being CC\u03b2 0.269 mg L-1 and 0.311 mg L-1 for melamine and formaldehyde respectively. CC\u03b1 and CC\u03b2 were also calculated at the SML of both analytes. The migration testing were conducted with simulant B (3% acetic acid (w\/v) in aqueous solution), the conditions of each exposure being 70 \u00b0C for 2 h. The quantities of melamine and formaldehyde found in the third exposure of the total kitchenware analysed were between 0.21 and 1.09 mg L-1 and between 0.55 and 3.86 mg L-1, respectively. Migration kinetic curves were built for each type of kitchenware with the data of sixteen consecutive migration cycles (70 \u00b0C each 30 min). The SML for melamine was surpassed in the mug, in the big cup and in the bowl after eleven, thirteen and one cycles, respectively. When more cycles were carried out in the mug, the values of the accumulated quantity of formaldehyde and melamine were 15.30 and 6.79 mg L-1, respectively, after thirty-two cycles. Both concentrations exceeded the corresponding SML.","subset":"pubmed_abstract"} +{"meta":{"pmid":27531449,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2019-35":2,"2019-18":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2017-13":1}}},"text":"Advance Care Planning in Norwegian nursing homes-Who is it for?\nAdvance care planning (ACP) is an international concept for improving patient autonomy and communication in the context of anticipated deterioration and end-of-life care. In a preparatory conversation, health care professionals facilitate one or more conversations where nursing home residents are invited to reflect on, and articulate wishes and preferences concerning future medical treatment and end-of-life care. Our aim with this study was to increase knowledge of existing ACP practices in Norwegian nursing homes. We wanted to know how nursing home residents, relatives and nursing home staff take part in the conversations, and to what extent these conversations can be regarded as promoting autonomy, legal rights and individual needs for the residents. We conducted participant observation of seven preparatory conversations, followed by interviews with health care staff (together) and resident and relative (together). In the result section, we present an informative case example of an ACP conversation where common and important characteristics running through our data are present. These are further elaborated under the following headings: Life critical questions, Residents' quiet participation in the conversations, the Dying phase - a clinical issue, Nurses and physicians; different domains and Timing. We find that nursing home staff in our study wants to contribute to open awareness, autonomy and a good death, but there are little reflections about the purpose and content of the conversations, how they should be carried out and when, and what frail nursing home residents are able to understand and express in ACP conversations.","subset":"pubmed_abstract"} +{"meta":{"pmid":3492786,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Reduction in regional cerebral metabolic rate of oxygen during human aging.\nTo investigate changes in cerebral circulation and oxygen metabolism during aging, regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2) and regional cerebral blood volume (rCBV) were measured using the 15O labelled gas inhalation technique and a multi-slice positron emission tomograph (PET) in 22 healthy volunteers, aged from 26 to 64 years old. The measurements were performed with subjects at rest, without sensory deprivation. The values of rCBF, rOEF, rCMRO2 and rCBV in more than 40 anatomical structures of the brain were evaluated by studying a large series of scans in each region of interest after the functional PET image had been anatomically identified using x-ray computed tomographic images corresponding to the PET. In mean gray values, only CMRO2 showed significant reduction with age. rCMRO2 significantly decreased with age only in the supratentrium, and much more in the left hemisphere. Especially remarkable was rCMRO2 reduction in the left caudate region. Both CBF and OEF were variable and less age-dependent. It was concluded that CMRO2 could be reflecting healthy brain aging most properly.","subset":"pubmed_abstract"} +{"meta":{"pmid":16765249,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits.\nRho kinase plays an important role in vascular smooth muscle cell (VSMC) contraction and other cellular functions, such as proliferation, migration, and apoptosis. Recent studies have demonstrated that long-term inhibition of Rho kinase suppresses coronary artery spasm and vascular lesion formation after arterial injury. In the cardiovascular surgery field, intimal thickening in vein grafts is the major cause of late graft failure, for which no effective treatment has yet been developed. In this study, we examined whether long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. Male rabbits were randomly divided into two groups and received normal chow (control group) or a special chow containing 0.09% fasudil (fasudil group). After oral administration, fasudil is metabolized to a specific Rho kinase inhibitor, hydroxyfasudil. Each group underwent reversed autologous vein graft surgery with the internal jugular vein into the left common carotid artery. At 1, 2, and 4 weeks after the operation, we examined the extent of intimal thickening of the graft and VSMC proliferation and apoptosis. The intimal thickening was significantly suppressed in the fasudil group compared with the control group at 2 and 4 weeks after the operation. In the fasudil group, VSMC proliferation was suppressed at 1 and 2 weeks after the operation, whereas VSMC apoptosis was enhanced at 2 weeks after the procedure. These results indicate that Rho kinase is substantially involved in the pathogenesis of intimal thickening of vein grafts and that it is an important therapeutic target for the prevention of graft failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":35638387,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"Land-based climate solutions for the United States.\nMeeting end-of-century global warming targets requires aggressive action on multiple fronts. Recent reports note the futility of addressing mitigation goals without fully engaging the agricultural sector, yet no available assessments combine both nature-based solutions (reforestation, grassland and wetland protection, and agricultural practice change) and cellulosic bioenergy for a single geographic region. Collectively, these solutions might offer a suite of climate, biodiversity, and other benefits greater than either alone. Nature-based solutions are largely constrained by the duration of carbon accrual in soils and forest biomass; each of these carbon pools will eventually saturate. Bioenergy solutions can last indefinitely but carry significant environmental risk if carelessly deployed. We detail a simplified scenario for the United States that illustrates the benefits of combining approaches. We assign a portion of non-forested former cropland to bioenergy sufficient to meet projected mid-century transportation needs, with the remainder assigned to nature-based solutions such as reforestation. Bottom-up mitigation potentials for the aggregate contributions of crop, grazing, forest, and bioenergy lands are assessed by including in a Monte Carlo model conservative ranges for cost-effective local mitigation capacities, together with ranges for (a) areal extents that avoid double counting and include realistic adoption rates and (b) the projected duration of different carbon sinks. The projected duration illustrates the net effect of eventually saturating soil carbon pools in the case of most strategies, and additionally saturating biomass carbon pools in the case of forest management. Results show a conservative end-of-century mitigation capacity of 110 (57-178) Gt CO2 e for the U.S., ~50% higher than existing estimates that prioritize nature-based or bioenergy solutions separately. Further research is needed to shrink uncertainties, but there is sufficient confidence in the general magnitude and direction of a combined approach to plan for deployment now.","subset":"pubmed_abstract"} +{"meta":{"pmid":22712786,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":2,"2013-48":2,"unknown":8}}},"text":"Effect of scheduled monitoring of liver function during anti-Tuberculosis treatment in a retrospective cohort in China.\nData on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment. A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis. 33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001). Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":8333551,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Expression of human Mn SOD in Chinese hamster ovary cells confers protection from oxidant injury.\nManganese superoxide dismutase (Mn SOD) is an important component of antioxidant defense in aerobic cells because of its location in the mitochondria, a significant source of oxygen radicals and an important target of oxidant injury. To test the hypothesis that increased mitochondrial Mn SOD protects from oxidant injury, Chinese hamster ovary (CHO) cells were transfected with a eukaryotic expression vector containing the human Mn SOD cDNA. In recombinant CHO cells, Mn SOD activity was increased threefold over wild-type controls. Acute survival during paraquat exposure (0-500 microM) was significantly improved in CHO cells expressing human Mn SOD, with 71% of recombinant CHO cells surviving at the 50% lethal dose (LD50) for wild-type CHO controls. Cell growth following exposure to paraquat (100 microM) was also significantly improved in recombinant CHO cells. CHO cells expressing human Mn SOD continued to grow and divide after paraquat exposure, whereas growth of wild-type CHO cells was negligible. Protection against oxidant-induced injury was directly related to increased Mn SOD, occurring in the absence of changes in other antioxidant enzymes including catalase, Cu,Zn SOD, and glutathione associated cellular antioxidant mechanisms. We conclude that increased expression of human Mn SOD in vitro directly confers protection against oxidant injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":9539919,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2023-23":1,"2021-25":1,"2019-13":1,"2018-43":1,"2018-26":1,"2018-05":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2023-50":1}}},"text":"Post circumcision meatal stenosis: 12 years' experience.\nTo study the presentation of meatal stenosis as a complication of circumcision done in boys of neonatal or nappy age. A total of 50 patients were studied. These patients had meatotomy performed to treat meatal stenosis. All the patients had circumcision during the neonatal period or in the nappy age. Meatal stenosis was defined as change in the appearance of the delicate lips of the urinary meatus, with loss of elliptical shape to a circular shape because of fibrosis or scarring, with visually apparent narrowing. Patients with this appearance and no symptoms, but who had presented with a hernia, undescended testes or some other unassociated condition and had meatotomy were for the purpose of this study classed as the incidental group. Patients who were symptomatic and had the meatal stenosis as defined above were classed as the symptomatic group. Sixteen patients (total n = 50) had the diagnosis of meatal stenosis made incidentally. Thirty four patients, (68% of the total treated by meatotomy) presented to the clinic, being symptomatic due to meatal stenosis. The median age at presentation of the symptomatic group was 48 months (range 3 months-13 years) following circumcision. In all the symptomatic patients meatotomy alleviated the symptoms. All the operated patients were seen between one to three months following the operation and discharged. There were no late presentations with recurrence of meatal stenosis or complications of the treatment. Meatal stenosis is an under recognised complication of circumcision done in neonatal and nappy aged boys. Symptomatic presentation from meatal stenosis can be very late.","subset":"pubmed_abstract"} +{"meta":{"pmid":24804018,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-10":1,"2015-18":1,"2024-30":1,"unknown":5}}},"text":"\u03b2-Glucan supplementation, allergy symptoms, and quality of life in self-described ragweed allergy sufferers.\nThis randomized, placebo-controlled, double-blind study compared the effects of daily supplementation for 4 week with 250 mg Wellmune WGP\u00ae \u03b2-1,3\/1,6-Glucan (WGP) with placebo 250 mg\/day (rice flour) on physical and psychological health attributes of self-described \"moderate\" ragweed allergy sufferers. Study participants (mean age = 36 \u00b1 9 year; range 18-53 year) were recruited before the beginning of ragweed season (September) in Northeastern Ohio. Serum IgE concentration, allergy symptoms [via self-report, Visual Analog Scale (VAS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)], psychological well-being [Profile of Mood States (POMS)], and physical function (RAND SF-36 Medical Outcomes Study) were measured immediately prior to and after supplementation with WGP (n = 24) or placebo (n = 24) for 4 weeks. Data were analyzed using repeated measures analyses of variance (ANOVA). Compared with placebo, WGP reduced total allergy symptoms (28%), symptom severity (52%), and symptom rating on the VAS (37%) (P < 0.05), but had no effect on serum IgE levels. As measured by the POMS, WGP increased participants' rating of vigor (10%), but reduced tension (34%), depression (45%), anger (41%), fatigue (38%), and confusion (34%) (P < 0.05). Study participants given WGP reported increased physical health (11%), energy (19%), and emotional well-being (7%) compared with study participants given the placebo (RAND SF-36 Medical Outcomes Study). The WGP group also reported decreased sleep problems (53%), reduced nasal symptoms (59%), eye symptoms (57%), non-nasal symptoms (50%), activities (53%), emotions (57%), and improved quality of life (QOL) (56%), as well as improved global mood state (13%). Supplementation with WGP for 4 weeks improved allergy symptoms, overall physical health, and emotional well-being compared with placebo in self-described \"moderate\" ragweed allergy sufferers during ragweed allergy season.","subset":"pubmed_abstract"} +{"meta":{"pmid":34249016,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Metabolic Control of Smoldering Neuroinflammation.\nCompelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation.","subset":"pubmed_abstract"} +{"meta":{"pmid":10211173,"dup_signals":{"dup_doc_count":60,"dup_dump_count":31,"dup_details":{"curated_sources":4,"2018-05":2,"2017-51":2,"2017-47":2,"2017-43":2,"2017-39":2,"2017-34":2,"2017-30":2,"2017-26":2,"2017-22":2,"2017-17":2,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":2,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":2,"2015-22":2,"2015-14":2,"2017-13":2,"2015-18":2,"2015-11":2}}},"text":"Stalking: false claims of victimisation.\nFalse allegations of victimisation although uncommon are important to recognise. This paper examines those who falsely claim to have been the victims of stalking. To highlight the phenomenon of false victims of stalking. Twelve individuals who falsely claimed to be victims of stalking were compared with a group of 100 true stalking victims. False stalking victims presented for help earlier than real victims and were less likely to claim harassment via letters. They reported equivalent levels of violence directed at themselves but seldom claimed others were attacked. Five types of false claimants were recognisable. False victims consumed more medical services than genuine stalking victims and they were more likely to be embroiled in legal action. They reported similar levels of distress with suicidal ruminations in over 40%. The current interest in stalking is promoting false claims of being stalked. Early identification of these cases and appropriate intervention are essential to both minimising abuses of resources available to true victims and equally to ensure appropriate care for those who express their own disordered state in false claims of victimisation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21330785,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-40":1,"2022-21":1,"2021-17":1,"2021-04":1,"2020-40":1,"2018-51":1,"2018-34":1,"2018-13":1,"2017-39":1,"2017-22":1,"2017-17":1,"2023-06":1}}},"text":"Effect of drought and rewatering on the cellular status and antioxidant response of Medicago truncatula plants.\nEffects of water stress on plants have been well-documented. However, the combined responses to drought and rewatering and their underlying mechanisms are relatively unknown. The present study attempts to describe spatiotemporal alterations in the physiology and cellular status of Medicago truncatula tissues that result from and subsequently follow a period of moderate water deficit. Physiological processes and cellular damage levels were monitored in roots and leaves by determining lipid peroxidation levels, as well as nitric oxide and hydrogen peroxide content, further supported by stomatal conductance and chlorophyll fluorescence measurements in leaves. During water stress, cells in both organs displayed increased damage levels and reactive oxygen and nitrogen species content, while leaves showed reduced stomatal conductance. Furthermore, both tissues demonstrated increased proline content. Upon rewatering, plants recovered displaying readings similar to pre-stress control conditions. Furthermore, molecular analysis of antioxidant gene expression by quantitative real-time RT-PCR revealed differential spatiotemporal regulation in a number of genes examined (including catalase, cytosolic ascorbate peroxidase, copper\/zinc and iron superoxide dismutase and alternative oxidase). Overall, M. truncatula plants demonstrated increased sensitivity to drought-induced oxidative damage; however, this was reversed following rewatering indicating a great elasticity in the plant's capacity to cope with free oxygen radicals.","subset":"pubmed_abstract"} +{"meta":{"pmid":28585956,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Engineering the exchange bias and bias temperature by modulating the spin glassy state in single phase Bi9Fe5Ti3O27.\nExchange anisotropy is normally observed at ferromagnetic (FM)\/anti-ferromagnetic (AFM) interfaces and also usually at low temperatures. An effective way to find new single-phase materials with strong exchange bias (EB) and high operation temperatures is required for making them useful in practical applications of future spintronic devices. In this work, the exchange bias behaviors of single phase Bi9Fe5Ti3O27 (BFT) were found able to be manipulated by altering its spin glassy state, when the material was intentionally prepared in the nanobelt format. A core-shell model has been proposed to explain the controllable behavior of both exchange bias and bias temperature, in which the AFM domain could be effectively reduced within the nanobelts when changing their particle sizes. A direct observation of two spin glassy behaviors corresponding to two distinct peaks in the zero field cooling (ZFC) curves manifests the validity of the proposed core-shell model.","subset":"pubmed_abstract"} +{"meta":{"pmid":2524348,"dup_signals":{"dup_doc_count":15,"dup_dump_count":7,"dup_details":{"curated_sources":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2024-18":1,"unknown":4}}},"text":"Drug-induced immune-complex disease.\nA range of drugs including hydralazine, isoniazid, procainamide and penicillamine cause toxic side effects which resemble systemic lupus erythematosus (SLE). Deficiencies of C1, C4 and C2 are associated with idiopathic SLE, and these defects may compromise the ability of the patient to deal with immune complexes. Immune complexes with protein as antigen, such as has been reported to be diagnostic of procainamide-induced SLE, interact more with the C4A isotype of C4 than the C4B isotype. It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4. For each of these drugs, C4A is inhibited more than C4B, and it is suggested that this is an important contributory factor in the development of the toxic side effects to these drugs involving immune-complex deposition. For procainamide, it is shown that the hydroxylamine metabolite rather than the drug itself inhibits the covalent binding reaction of C4. Hydralazine, isoniazid and procainamide are metabolised by the polymorphic N-acetyltransferase, and slow acetylators are at increased risk of drug-induced lupus. For procainamide, oxidation to the hydroxylamine form is an alternative metabolic route of increased importance in slow acetylators, and it is suggested that investigation of C4 type in susceptible patients could provide a means of identifying those at greatest risk of immunotoxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":10954735,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2017-51":1,"2017-13":1}}},"text":"Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes.\nPlasmodium falciparum requires glucose as its energy source to multiply within erythrocytes but is separated from plasma by multiple membrane systems. The mechanism of delivery of substrates such as glucose to intraerythrocytic parasites is unclear. We have developed a system for robust functional expression in Xenopus oocytes of the P. falciparum asexual stage hexose permease, PfHT1, and have analyzed substrate specificities of PfHT1. We show that PfHT1 (a high-affinity glucose transporter, K(m) approximately 1.0 mM) also transports fructose (K(m) approximately 11.5 mM). Fructose can replace glucose as an energy source for intraerythrocytic parasites. PfHT1 binds fructose in a furanose conformation and glucose in a pyranose form. Fructose transport by PfHT1 is ablated by mutation of a single glutamine residue, Q169, which is predicted to lie within helix 5 of the hexose permeation pathway. Glucose transport in the Q169N mutant is preserved. Comparison in oocytes of transport properties of PfHT1 and human facilitative glucose transporter (GLUT)1, an archetypal mammalian hexose transporter, combined with studies on cultured P. falciparum, has clarified hexose permeation pathways in infected erythrocytes. Glucose and fructose enter erythrocytes through separate permeation pathways. Our studies suggest that both substrates enter parasites via PfHT1.","subset":"pubmed_abstract"} +{"meta":{"pmid":28797606,"dup_signals":{"dup_doc_count":13}},"text":"Plasma creatine kinase B correlates with injury severity and symptoms in professional boxers.\nEach year in the United States, approximately 1.7 million people sustain a traumatic brain injury (TBI). Of these TBI events, about 75 percent are characterized as being mild brain injuries. Immediately following TBI, a secondary brain damage persists for hours, days, and even months. Previously, detection of neuronal and glial biomarkers have proven to be useful to predict neurological outcomes. Here, we hypothesized that creatine kinase, brain (CKBB) is a sensitive biomarker for acute secondary brain injury in professional boxers. Blood (8cc) was collected from the boxing athletes (n=18) prior to and after competition (\u223c30min). The plasma levels of CKBB were measured using the Meso Scale Diagnostic (MSD) electrochemiluminescence (ECL) array-based multiplex format. Additional data such as number of blows to the head and symptom score (Rivermead Post Concussion Symptoms Questionnaire) were collected. At approximately 30min after the competition, the plasma levels of CKBB were significantly elevated in concussed professional boxers and correlated with the number of blows to the head and symptom scores. Additionally, receiver operating curve (ROC) analysis yielded a 77.8% sensitivity and a specificity of 82.4% with an area under the curve (AUC) of 90% for CKBB as an identifier of secondary brain injury within this population. This study describes the detection of CKBB as a brain biomarker to detect secondary brain injury in professional athletes that have experienced multiple high impact blows to the head. This acute biomarker may prove useful in monitoring secondary brain injury after injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":28002179,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Game Profile-Based Training in Soccer: A New Field Approach.\nDello Iacono, A, Martone, D, Cular, D, Milic, M, and Padulo, J. Game profile-based training in soccer: a new field approach. J Strength Cond Res 31(12): 3333-3342, 2017-The aim of the study was to profile and compare the time-motion, physiological, and neuromuscular responses of both National Youth League (NYL) and UEFA Youth League (UYL) matches with those of an experimental game profile-based training (GPBT) protocol. Time-motion traits and physiological, perceptual, and neuromuscular responses were investigated in 24 male soccer players across 14 matches and 6 GPBT training sessions, for a total of 420 samples. The GPBT had a greater influence on time-motion traits and perceptual responses than the NYL and UYL matches (all p < 0.001). No significant GPBT vs. match differences were found for mean heart rate or blood lactate (F = 1.228, p = 0.304, and F = 0.978, p = 0.385, respectively). Finally, the GPBT protocol led to greater impairment of the neuromuscular explosive performances when compared with those of the postmatch scores (squat jump: F = 19.991, p < 0.001; countermovement jump: F = 61.703, p < 0.001). Results identified the GPBT protocol as characterized by relatively greater high-intensity workloads than official NYL and UYL matches, requiring increased demanding efforts. In light of these outcomes, the GPBT protocol can be considered an advantageous training method for elite soccer players, capable of stimulating the physical effort and physiological capabilities required during a match. This approach is favorable when designing a training intervention according to the principle of sport specificity, as it is based on the specific metabolic demands.","subset":"pubmed_abstract"} +{"meta":{"pmid":29665103,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Health and Care Related Risk Factors for Suicide Among Nursing Home Residents: A Data Linkage Study.\nThis study aimed to examine associations between health status and care needs of nursing home residents and risk of death from suicide compared to other causes through a retrospective data linkage cohort study examining nursing home resident deaths in Australia between 2000 and 2013. Data linkage was performed between aged care assessment tools-Resident Classification System and Aged Care Funding Instrument-and the National Coronial Information System. A competing risks survival analysis was performed to determine the association between care assessment variables (activities of daily living (ADL), behavior, and complex health care) and the risk of death from suicide and any other cause. Of the 146 nursing home residents who died from suicide, 130 (89%) were matched to their assessment data, with comparable information available for 95 residents (65%). Residents who required high levels of care with ADL, physical health care, and cognitive and behavioral issues had a higher risk of dying from all other causes, yet lower risk of dying from suicide. The study findings demonstrate the feasibility and value of linking these two data sets; highlight a need for improved data collection processes; and support a person-centered care approach for prevention of suicide among nursing home residents.","subset":"pubmed_abstract"} +{"meta":{"pmid":24974612,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"[Living with responsibility: Max Born and Carl Friedrich von Weizs\u00e4cker as philosophers with distance].\nBoth Carl Friedrich von Weizs\u00e4cker und Max Born belong to the most active scientists, which have raised their voice for peace in the 1950s. While Born, senior to Weizs\u00e4cker by one generation, engaged in peace movements at an early stage, which was also due to his emigration, and was a driving force for the Einstein-Russell memorandum, Weizs\u00e4cker entered the stage essentially with the G\u00f6ttingen declaration but quickly dominated the discourse. The comparison of their different engagements for peace sheds new light on Weizs\u00e4cker. Unlike the German emigrant with a British passport, who was mainly influenced by EInstein and Russell as well as some socialist thoughts he had encountered at an early age, the son of a noble diplomat and the physicist, who was saved from military duties because of his work in the German wartime nuclear project, had quite a different perspective on the postwar atomic threat. The relation of Born and Weizs\u00e4cker remained marked by a certain distance even when both took up very similar roles of 'public scientists' active for peace, be it as delegates at Pugwash conferences, on the air, or as speakers in the Frankfurt Paulskirche.","subset":"pubmed_abstract"} +{"meta":{"pmid":20038922,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Value of amniotic fluid interleukin-8 for the prediction of histological chorioamnionitis in preterm premature rupture of membranes.\nTo determine whether amniotic fluid levels of interleukin-8 (IL-8) are of value in the antenatal diagnosis of acute histological chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM). Department of Obstetrics and Gynaecology, Charles University, Medical School and University Hradec Kralove, Czech Republic. We compared amniotic fluid IL-8 levels in twenty-nine pregnant women with preterm premature rupture of membranes between 24th and 36th gestational weeks with presence and absence acute histological chorioamnionitis or\/and microbial invasion in the amniotic cavity using nonparametric tests (Mann-Whitney test), given the non-normal distribution of analyte. Comparisons of proportions were performed with Shapiro-Wilk normality test. Patients with HCA had a significantly higher median amniotic fluid IL-8 concentration than patients without the histological signs of chorioamnionitis (1867 pg\/mL, 826-5577 versus 1045 pg\/mL, 60-4133, p=0.013). Patients with MIAC had a significantly higher median amniotic fluid level than patients without invasion (1888 pg\/mL, 519-5577 versus 1225 pg\/mL, 60-2766, p= 0.017). Women with HCA and MIAC had a significantly higher median amniotic fluid IL-8 level than women without histological signs of chorioamnionitis and microbial invasion (3117 pg\/mL, 826-5577 versus 1468 pg\/mL, 394-2766, p=0.034). HCA or\/and MIAC are associated with a significant increase of amniotic fluid interleukin-8 levels. Amniotic fluid IL-8 seems to be a marker of intraamniotic inflammation.","subset":"pubmed_abstract"} +{"meta":{"pmid":25994085,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Different polyamine pathways from bacteria have replaced eukaryotic spermidine biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia.\nThe polyamine spermidine is absolutely required for growth and cell proliferation in eukaryotes, due to its role in post-translational modification of essential translation elongation factor eIF5A, mediated by deoxyhypusine synthase. We have found that free-living ciliates Tetrahymena and Paramecium lost the eukaryotic genes encoding spermidine biosynthesis: S-adenosylmethionine decarboxylase (AdoMetDC) and spermidine synthase (SpdSyn). In Tetrahymena, they were replaced by a gene encoding a fusion protein of bacterial AdoMetDC and SpdSyn, present as three copies. In Paramecium, a bacterial homospermidine synthase replaced the eukaryotic genes. Individual AdoMetDC-SpdSyn fusion protein paralogues from Tetrahymena exhibit undetectable AdoMetDC activity; however, when two paralogous fusion proteins are mixed, AdoMetDC activity is restored and spermidine is synthesized. Structural modelling indicates a functional active site is reconstituted by sharing critical residues from two defective protomers across the heteromer interface. Paramecium was found to accumulate homospermidine, suggesting it replaces spermidine for growth. To test this concept, a budding yeast spermidine auxotrophic strain was found to grow almost normally with homospermidine instead of spermidine. Biosynthesis of spermidine analogue aminopropylcadaverine, but not exogenously provided norspermidine, correlated with some growth. Finally, we found that diverse single-celled eukaryotic parasites and multicellular metazoan Schistosoma worms have lost the spermidine biosynthetic pathway but retain deoxyhypusine synthase.","subset":"pubmed_abstract"} +{"meta":{"pmid":10220591,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1.\nTo clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes. The chondrocytes were exposed to CTF using a Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen, and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro- and active-MMP-9. The degradation of proteoglycan was inhibited by and MMP inhibitor, indicating that MMPs are involved in the degradation of proteoglycans induced by high frequency CTF. Moreover, reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this CTF magnitude causes only minor changes in the cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -9 proteins, suggesting that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27922741,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?\nDecreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and\/or severity, and others have shown that combinations of long-acting \u03b22-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA\/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA\/LAMA combinations over single long-acting bronchodilators or LABA\/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA\/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":18826829,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-22":3,"2024-18":1,"2024-10":1,"unknown":2}}},"text":"Extended sequence typing of Campylobacter spp., United Kingdom.\nSupplementing Campylobacter spp. multilocus sequence typing with nucleotide sequence typing of 3 antigen genes increased the discriminatory index achieved from 0.975 to 0.992 among 620 clinical isolates from Oxfordshire, United Kingdom. This enhanced typing scheme enabled identification of clusters and retained data required for long-range epidemiologic comparisons of isolates.","subset":"pubmed_abstract"} +{"meta":{"pmid":32278932,"dup_signals":{"dup_doc_count":12,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2022-33":1,"2021-39":2,"2021-17":1,"2021-10":2,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2022-49":1}}},"text":"COVID-19: Initial experience of an international group of hand surgeons.\nThe emergence of the COVID-19 pandemic has severely affected medical treatment protocols throughout the world. While the pandemic does not affect hand surgeons at first glance, they have a role to play. The purpose of this study was to describe the different measures that have been put in place in response to the COVID-19 pandemic by hand surgeons throughout the world. The survey comprised 47 surgeons working in 34 countries who responded to an online questionnaire. We found that the protocols varied in terms of visitors, health professionals in the operating room, patient waiting areas, wards and emergency rooms. Based on these preliminary findings, an international consensus on hand surgery practices for the current viral pandemic, and future ones, needs to be built rapidly.","subset":"pubmed_abstract"} +{"meta":{"pmid":2071354,"dup_signals":{"dup_doc_count":25,"dup_details":{"curated_sources":2,"unknown":23}}},"text":"Morphologic and ultrastructural examination of I-A+ cells in the murine iris.\nThe surface membrane expression of major histocompatibility (MHC) class II antigens is an important prerequisite for presentation of foreign antigens to the immune system. Because particular antigens that are placed within the anterior chamber of the eye elicit a deviant form of immunity in which effector delayed-type hypersensitivity responses are suppressed, it has been proposed that novel MHC class II antigen-bearing cells exist in the tissues that line the anterior chamber. Class II MHC antigen expression has been identified within the iris, but the detailed morphologic description of these cells is incomplete. With the use of in situ immunoperoxidase and immunoelectron microscopic techniques, we examined the morphologic and ultrastructural characteristics of resident MHC-positive class II (I-A+) cells in murine irises. A significant number of these cells was found in the connective tissue of BALB\/c irises. The majority showed extensive dendritic morphologic characteristics and formed a network throughout the iris that did not overlap. Ultrastructurally, I-A+ cells had an indented nucleus, some vacuoles, lysosomes, mitochondria, and an occasional phagosome within their cytoplasm and an absence of desmosomes or other intercellular junctions. Based on these features, it is unlikely that these cells are epithelial or endothelial in origin, but rather are similar to cells of the monocyte\/macrophage\/dendritic cell lineage. These results show the presence of an I-A+ dendritic cell population, within the murine iris, distributed in a pattern that is similar to that of Langerhans cells in the skin. Due to their compartmentalization within the eye, this cell population may represent a novel antigen-presenting cell that contributes to the immunologic privilege of the anterior chamber.","subset":"pubmed_abstract"} +{"meta":{"pmid":27565301,"dup_signals":{"dup_doc_count":90,"dup_dump_count":52,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":2,"2022-27":2,"2022-21":1,"2022-05":2,"2021-49":1,"2021-43":1,"2021-39":3,"2021-31":1,"2021-25":2,"2021-21":1,"2021-17":2,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":3,"2020-40":1,"2020-24":2,"2020-16":1,"2019-35":1,"2019-22":1,"2019-09":1,"2019-04":2,"2018-51":1,"2018-43":3,"2018-34":2,"2018-26":3,"2018-22":2,"2018-17":1,"2018-13":2,"2018-09":2,"2018-05":1,"2017-51":3,"2017-43":3,"2017-34":4,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":1,"2017-04":1,"2023-50":1,"2024-30":3,"2024-26":1,"2024-22":1,"2024-18":3,"2024-10":1,"2017-13":2}}},"text":"White matter integrity as a marker for cognitive plasticity in aging.\nAge-related differences in white matter (WM) integrity are substantial, but it is unknown whether between-subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging.","subset":"pubmed_abstract"} +{"meta":{"pmid":21212791,"dup_signals":{"dup_doc_count":21,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2024-22":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"unknown":13}}},"text":"Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study.\nWe report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.","subset":"pubmed_abstract"} +{"meta":{"pmid":28025390,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.\nThe landscape of HPV infection in racial\/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial\/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16\/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16\/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16\/18 status and p16 expression, White patients had the highest proportion of HPV16\/18+\/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16\/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.","subset":"pubmed_abstract"} +{"meta":{"pmid":2823128,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Protein-DNA cross-linking reveals dramatic variation in RNA polymerase II density on different histone repeats of Drosophila melanogaster.\nIn Drosophila melanogaster the five histone genes are within a 5-kilobase region which is repeated 100 times at a single chromosomal site. These 5-kilobase repeats are of two distinct classes, short and long, that differ by approximately 200 base pairs of DNA in the spacer region between the H1 and H3 genes. Since the mRNA-homologous regions of the repeats are highly conserved, one cannot examine differential expression of the repeats by classical hybridization methods. In this study, we assessed their transcriptional activity by measuring in vivo the relative amounts of RNA polymerase II that were cross-linked by UV irradiation to the two different histone repeats. The RNA polymerase II density on the long repeat in Schneider line 2 cells was strikingly lower (10-fold) than the density on the short repeat. The magnitude of this difference cannot be accounted for by reduced transcription of only one or two genes of the repeat. The density of topoisomerase I, an indicator of transcriptional activity, was also much higher on the short repeat than on the long repeat of line 2 cells. In contrast, the RNA polymerase II density was slightly higher on the long repeat than on the short repeat in a second cell line, KcH. The major difference between active (KcH) and inactive (S2) long repeats resides in the H1-H3 nontranscribed spacer. This portion of the spacer may contain a component necessary for expression that can act over a moderate distance and affect multiple genes of the repeat.","subset":"pubmed_abstract"} +{"meta":{"pmid":18185667,"dup_signals":{"dup_doc_count":24,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":21}}},"text":"Laser-diode wavelength tuning based on butt coupling into an optical fiber.\nAn extremely short external cavity that is realized when a Fabry-Perot laser diode is butt coupled to a waveguide or a fiber produces feedback that is effective for controlled wavelength tuning. We used butt coupling to tune a high-output-power laser diode over a wide range (as great as 15 nm) while maintaining constant driving current and temperature. Single-mode or multimode operation repeatedly occurred at specific points throughout the tuning range. An analytical model that includes the effect of multiple reflections from the external cavity, each attenuated by a modal overlap integral, and which is based on phenomenological principles, shows good agreement with the experimental results.","subset":"pubmed_abstract"} +{"meta":{"pmid":2913195,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Life-style changes in a cardiac rehabilitation program: the client perspective.\nMajor life-style changes are required after an acute coronary event, although the vast majority of patients are unsuccessful in maintaining these changes. This study examines factors clients view as enabling or disabling their life-style changes for health promotion. Ten patients in a cardiac rehabilitation program were interviewed using grounded theory methodology. Both health protection and health promotion stimulated life-style change, as did instructions from the physician and life enjoyment. Enabling and disabling factors affecting the process of repatterning were individually defined, but changes in beliefs, attitudes, and plans facilitated repatterning. Specific precipitants to change, forces influencing change, and methods of repatterning life style are discussed, as are nursing implications.","subset":"pubmed_abstract"} +{"meta":{"pmid":16670086,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Differential gel electrophoresis and transgenic mitochondrial calcium reporters demonstrate spatiotemporal filtering in calcium control of mitochondria.\nMitochondria must adjust both their intracellular location and their metabolism in order to balance their output to the needs of the cell. Here we show by the proteomic technique of time series difference gel electrophoresis that a major result of neuroendocrine stimulation of the Drosophila renal tubule is an extensive remodeling of the mitochondrial matrix. By generating Drosophila that were transgenic for both luminescent and fluorescent mitochondrial calcium reporters, it was shown that mitochondrial calcium tracked the slow (minutes) but not the rapid (<1 s) changes in cytoplasmic calcium and that this resulted in both increased mitochondrial membrane polarization and elevated cellular ATP levels. The selective V-ATPase inhibitor, bafilomycin, further enhanced ATP levels, suggesting that the apical plasma membrane V-ATPase is a major consumer of ATP. Both the mitochondrial calcium signal and the increase in ATP were abolished by the mitochondrial calcium uniporter blocker Ru360. By using both mitochondrial calcium imaging and the potential sensing dye JC-1, the apical mitochondria of principal cells were found to be selectively responsive to neuropeptide signaling. As the ultimate target is the V-ATPase in the apical plasma membrane, this selective activation of mitochondria is clearly adaptive. The results highlight the dynamic nature and both spatial and temporal heterogeneity of calcium signaling possible in differentiated, organotypic cells and provide a new model for neuroendocrine control of V-ATPase.","subset":"pubmed_abstract"} +{"meta":{"pmid":11768327,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":2,"unknown":8}}},"text":"New developments: chloroquine-resistance in Plasmodium falciparum.\nChloroquine-resistance is associated with higher malaria mortality in children in Africa where the drug is still widely used. In sensitive strains the drug attacks hemoglobin digestion in the lysosome and prevents detoxification of hemin to hemozoin. Reduced drug uptake is responsible for resistance, which is incompletely associated with changes in lysosome membrane protein PGH1. The report discussed here gives evidence for the role of another lysosome membrane protein, PfCRT, where a change from lysine to threonine in a transmembrane domain determines the change to resistance. Other changes in PfCRT, and to some extent change(s) in PGH1, are believed to compensate for loss of fitness of the modified PfCRT.","subset":"pubmed_abstract"} +{"meta":{"pmid":10964998,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":3,"2024-30":1,"unknown":12}}},"text":"SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer.\nWe describe a protocol for disclosing unfavorable information-\"breaking bad news\"-to cancer patients about their illness. Straightforward and practical, the protocol meets the requirements defined by published research on this topic. The protocol (SPIKES) consists of six steps. The goal is to enable the clinician to fulfill the four most important objectives of the interview disclosing bad news: gathering information from the patient, transmitting the medical information, providing support to the patient, and eliciting the patient's collaboration in developing a strategy or treatment plan for the future. Oncologists, oncology trainees, and medical students who have been taught the protocol have reported increased confidence in their ability to disclose unfavorable medical information to patients. Directions for continuing assessment of the protocol are suggested.","subset":"pubmed_abstract"} +{"meta":{"pmid":30134152,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2022-49":1,"2022-27":1,"2020-40":1,"2020-10":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-39":1,"2023-23":1}}},"text":"Benefit-risk analysis for foods (BRAFO): Evaluation of exposure to dietary nitrates.\nDietary nitrate has been associated with health benefits as well as potential risks, thus presenting a paradox for consumers and health professionals. To address the issue, we applied the Benefit-Risk Analysis for Foods (BRAFO) framework to evaluate dietary exposure to nitrate by considering how the risks and benefits might vary under the reference scenario of the acceptable daily intake (ADI) set forth by JECFA (3.7 mg\/kg-day), or under an alternative scenario of a higher ADI (independently developed herein). Results demonstrated that risk, as conservatively characterized by various toxicological benchmarks, was present at levels ranging from the current ADI value of 3.7 mg\/kg-day (lowest end of the range) to >15 mg\/kg-day. When these ADI values, both established by regulatory bodies as well as independently herein were compared to intakes associated with benefits (decreased blood pressure observed following repeated exposure to nitrates \u223c4-18 mg\/kg-day), along with considerations of current dietary exposures associated with healthy diets, the alternative scenario allowed for benefits without incurring additional risk. For consumers aged 12 weeks and older, ADI values \u223c12-17 mg\/kg-day-based on more reliable data than used to derive the current ADI-allow benefits to be realized while still protecting public health. The assessment serves as a case study in how benefits can be considered in a risk assessment paradigm for foods, thus providing useful information to decision makers.","subset":"pubmed_abstract"} +{"meta":{"pmid":17902265,"dup_signals":{"dup_doc_count":86,"dup_dump_count":33,"dup_details":{"curated_sources":4,"2020-29":5,"2020-24":3,"2019-35":2,"2019-26":1,"2019-04":1,"2018-30":1,"2017-04":3,"2016-50":3,"2016-44":3,"2016-40":3,"2016-36":3,"2016-30":3,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":3,"2015-35":1,"2015-32":2,"2015-14":1,"2014-52":3,"2014-49":2,"2014-42":5,"2014-41":4,"2014-35":4,"2014-23":6,"2014-15":3,"2015-11":1,"2015-06":3,"2014-10":2,"2013-48":3,"2013-20":2,"2015-18":1}}},"text":"Improving the education of children living in poverty.\nRichard Murnane observes that the American ideal of equality of educational opportunity has for years been more the rhetoric than the reality of the nation's political life. Children living in poverty, he notes, tend to be concentrated in low-performing schools staffed by ill-equipped teachers. They are likely to leave school without the skills needed to earn a decent living in a rapidly changing economy. Murnane describes three initiatives that the federal government could take to improve the education of these children and increase their chances of escaping poverty. All would strengthen the standards-based reforms at the heart of the No Child Left Behind Act of 2001 (NCLB) by bracing the three legs on which the reforms rest: accountability, incentives, and capacity. Congress, says Murnane, should improve accountability by amending NCLB to make performance goals more attainable. The goals should emphasize growth in children's skills rather than whether children meet specific test score targets. Congress should also amend NCLB to develop meaningful goals for high school graduation rates. Congress should strengthen states' incentives to improve the education of low-income students. It should also encourage states to develop effective voluntary school choice programs to enable students who attend failing public schools to move to more successful schools in other districts. Finally, Congress should use competitive matching grants to build the capacity of schools to educate low-income children and the capacity of state departments of education to boost the performance of failing schools and districts. The grants would help develop effective programs to improve teaching and to serve students who do not fare well in conventional high school programs. Murnane estimates the annual cost of these three initiatives to be approximately $2.5 billion.","subset":"pubmed_abstract"} +{"meta":{"pmid":22470415,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"The SpikerBox: a low cost, open-source bioamplifier for increasing public participation in neuroscience inquiry.\nAlthough people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle\/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience.","subset":"pubmed_abstract"} +{"meta":{"pmid":11301519,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":1,"2015-06":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":7}}},"text":"Neurobiology of the structure of personality: dopamine, facilitation of incentive motivation, and extraversion.\nExtraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation. Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system. Individual differences in the functioning of this network arise from functional variation in the ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, \"experience-expectant,\" and \"experience-dependent.\" Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive context and incentive motivation and behavior. Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":22276178,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Aristolochic acid I induced autophagy extenuates cell apoptosis via ERK 1\/2 pathway in renal tubular epithelial cells.\nAutophagy is a lysosomal degradation pathway that is essential for cell survival and tissue homeostasis. However, limited information is available about autophagy in aristolochic acid (AA) nephropathy. In this study, we investigated the role of autophagy and related signaling pathway during progression of AAI-induced injury to renal tubular epithelial cells (NRK52E cells). The results showed that autophagy in NRK52E cells was detected as early as 3-6 hrs after low dose of AAI (10 \u00b5M) exposure as indicated by an up-regulated expression of LC3-II and Beclin 1 proteins. The appearance of AAI-induced punctated staining of autophagosome-associated LC3-II upon GFP-LC3 transfection in NRK52E cells provided further evidence for autophagy. However, cell apoptosis was not detected until 12 hrs after AAI treatment. Blockade of autophagy with Wortmannin or 3-Methyladenine (two inhibitors of phosphoinositede 3-kinases) or small-interfering RNA knockdown of Beclin 1 or Atg7 sensitized the tubular cells to apoptosis. Treatment of NRK52E cells with AAI caused a time-dependent increase in extracellular signal-regulated kinase 1 and 2 (ERK1\/2) activity, but not c-Jun N-terminal kinase (JNK) and p38. Pharmacological inhibition of ERK1\/2 phosphorylation with U0126 resulted in a decreased AAI-induced autophagy that was accompanied by an increased apoptosis. Taken together, our study demonstrated for the first time that autophagy occurred earlier than apoptosis during AAI-induced tubular epithelial cell injury. Autophagy induced by AAI via ERK1\/2 pathway might attenuate apoptosis, which may provide a protective mechanism for cell survival under AAI-induced pathological condition.","subset":"pubmed_abstract"} +{"meta":{"pmid":23972021,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Modulation of Spontaneous Brain Activity during Mental Imagery.\nMagnetic measurements of average power of human alpha and beta activity over the occipital and parietal areas of the scalp reveal spatially selective suppression of the activity of the occipital cortex when abstract figures are briefly presented visually and subjects simply indicate that they saw the figure. However, the duration of the suppression increases markedly when subjects must indicate whether or not they had previously seen the figure. The reaction time is similarly prolonged during the search of visual memory, and is commensurate with the duration of selective suppression of brain activity. It is also demonstrated that alpha activity is not replaced by beta activity during this suppression, but that power in the beta band is also diminished during memory search. Low correlations between the scalp distributions of power in the beta and alpha bands indicate that partly different neuronal populations give rise to activity of these different frequency bands. Since magnetic fields are negligibly affected by intervening bone tissues, dramatic asymmetries in the distribution of alpha activity across the scalps of individuals and the differences in distribution between individuals cannot be ascribed to differences in skull thickness but are due instead to differences in underlying brain anatomy or function. Nevertheless, a common pattern of suppression of alpha activity is observed across subjects during well-controlled cognitive tasks. This implies that the visual system is involved in mental imagery.","subset":"pubmed_abstract"} +{"meta":{"pmid":31638045,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Comparison of flanged intrascleral intraocular lens fixation versus iris claw intraocular lens fixation: A retrospective study.\nTo compare the visual outcome and complications of retropupillary fixated iris claw intraocular lens (IOL) and sutureless intrascleral IOL fixation using the flanged fixation technique at 1 year. In this retrospective study, eyes that underwent either iris claw or flanged SFIOL from January 2016 to July 2017 with a minimum of 1-year follow-up were enrolled. Improvement in visual acuity, intraocular pressure measurements, endothelial cell count, central macular thickness, and complications were compared between and within groups at 6 weeks, 3 months, and 1 year postoperatively. Data from 150 eyes were analyzed (n = 90 in the iris claw group and n = 60 in the flanged SFIOL group). Posterior capsular rent was the most common indication for IOL implantation (n = 51, 34%). The iris claw and SFIOL groups were comparable in terms of demographics and baseline characteristics. There was significant improvement in uncorrected distance visual acuity (UCDVA) at 6 weeks in both groups (P = 0.77), and at 1 year, the UCDVA was comparable between groups (0.36 \u00b1 0.32 in the iris claw group and 0.30 \u00b1 0.28 in the SFIOL, P= 0.75). Transient elevation of intraocular pressure was seen slightly more in eyes with SFIOL (17%), while ovalization of the pupil was the main sequelae seen in the iris claw group (20%). Both iris claw IOL fixation and SFIOL using flange are viable options for surgical correction of aphakia. Visual outcomes are excellent at 6 weeks and are maintained till 1-year follow-up, and complication rates are acceptably low, although ovalization of pupil is common with iris claw IOLs.","subset":"pubmed_abstract"} +{"meta":{"pmid":31300680,"dup_signals":{"dup_doc_count":15,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-10":1,"2020-05":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2021-43":1}}},"text":"In vivo two-photon microscopy of the human eye.\nTwo-photon (2P) microscopy is a powerful tool for imaging and exploring label-free biological tissues at high resolution. Although this type of microscopy has been demonstrated in ex vivo ocular tissues of both humans and animal models, imaging the human eye in vivo has always been challenging. This work presents a novel compact 2P microscope for non-contact imaging of the anterior part of the living human eye. The performance of the instrument was tested and the maximum permissible exposure to protect ocular tissues established. To the best of our knowledge, 2P images of the in vivo human cornea, the sclera and the trabecular meshwork are shown for the very first time. Acquired images are of enough quality to visualize collagen arrangement and morphological features of clinical interest. Future implementations of this technique may constitute a potential tool for early diagnosis of ocular diseases at submicron scale.","subset":"pubmed_abstract"} +{"meta":{"pmid":15870046,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"The incidence of emboli during cardiac surgery: a histopathologic analysis of 2297 patients.\nManipulation of the atherosclerotic aorta during cardiac surgery is assumed to cause embolization, which can contribute to adverse outcomes. Recently, as a result of worldwide trials deploying the Embol-X intraaortic filter during cardiac surgery, such emboli were captured and processed for histopathologic analysis. Filters with a pore size of 120 microns were placed in 2297 patients who underwent the following operations: coronary artery bypass grafting (CABG) (70%), valve (17%), combination CABG\/valve (11%), and other (2%). The filters captured at least one embolus in 98% of the patients. An average of 8.3 particles was captured per filter (range of 0-74). The surface area of the emboli was on an average 5.8 mm2 (range of 0-188 mm2). Histologic analysis of the captured particles indicated that in 79% of the filters fibrous atheromata were noted, in 44% there were platelets and fibrin, 8% had red blood cell thrombus, 3% had fibro-fatty\/adventitial tissue, 2% had other material including cartilage, myocardium, lung, suture, and a teflon pledget. Of the patients enrolled, 1569 were high-risk. The average number of particles captured in the high-risk patients was 8.5 versus 5.8 for the low- to moderate-risk patients (P < .0001). Concomitantly,there was an increase in the embolic burden between the higher- and lower-risk patients (surface area 6.6 vs. 4.0 mm2, P < .0001). These data show the ubiquitous incidence of emboli during cardiac procedures. Intraaortic filtration should reduce adverse outcomes as was demonstrated for the high-risk patients in this study. Aortic manipulation during cardiac surgery can cause embolization and increase morbidity. The use of an intraaortic filter can decrease the embolic burden. We now report the histopathologic analysis of these emboli.","subset":"pubmed_abstract"} +{"meta":{"pmid":19836927,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":15}}},"text":"Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study.\n22q11.2 deletion syndrome (22q11DS) is associated with an increased susceptibility to develop schizophrenia. Despite a large body of literature documenting abnormal brain structure in 22q11DS, cerebral changes associated with brain maturation in 22q11DS remained largely unexplored. To map cortical maturation from childhood to adulthood in 22q11.2 deletion syndrome, we used cerebral MRI from 59 patients with 22q11DS, aged 6 to 40, and 80 typically developing controls; three year follow-up assessments were also available for 32 patients and 31 matched controls. Cross-sectional cortical thickness trajectories during childhood and adolescence were approximated in age bins. Repeated-measures were also conducted with the longitudinal data. Within the group of patients with 22q11DS, exploratory measures of cortical thickness differences related to COMT polymorphism, IQ, and schizophrenia were also conducted. We observed deviant trajectories of cortical thickness changes with age in patients with 22q11DS. In affected preadolescents, larger prefrontal thickness was observed compared to age-matched controls. Afterward, we observed greater cortical loss in 22q11DS with a convergence of cortical thickness values by the end of adolescence. No compelling evidence for an effect of COMT polymorphism on cortical maturation was observed. Within 22q11DS, significant differences in cortical thickness were related to cognitive level in children and adolescents, and to schizophrenia in adults. Deviant trajectories of cortical thickness from childhood to adulthood provide strong in vivo cues for a defect in the programmed synaptic elimination, which in turn may explain the susceptibility of patients with 22q11DS to develop psychosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":30854485,"dup_signals":{"dup_doc_count":56,"dup_dump_count":26,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":4,"2023-14":1,"2023-06":2,"2022-40":2,"2022-27":3,"2022-21":3,"2022-05":1,"2021-49":2,"2021-43":3,"2021-39":2,"2021-31":4,"2021-21":1,"2021-17":3,"2021-10":1,"2021-04":3,"2020-50":1,"2020-45":5,"2020-40":3,"2020-34":1,"2020-29":1,"2020-24":1,"2023-50":1,"2024-22":1,"2024-18":2,"2024-30":1}}},"text":"Cytoskeletal actin patterns shape mast cell activation.\nActivation of immune cells relies on a dynamic actin cytoskeleton. Despite detailed knowledge of molecular actin assembly, the exact processes governing actin organization during activation remain elusive. Using advanced microscopy, we here show that Rat Basophilic Leukemia (RBL) cells, a model mast cell line, employ an orchestrated series of reorganization events within the cortical actin network during activation. In response to IgE antigen-stimulation of FC\u03b5 receptors (FC\u03b5R) at the RBL cell surface, we observed symmetry breaking of the F-actin network and subsequent rapid disassembly of the actin cortex. This was followed by a reassembly process that may be driven by the coordinated transformation of distinct nanoscale F-actin architectures, reminiscent of self-organizing actin patterns. Actin patterns co-localized with zones of Arp2\/3 nucleation, while network reassembly was accompanied by myosin-II activity. Strikingly, cortical actin disassembly coincided with zones of granule secretion, suggesting that cytoskeletal actin patterns contribute to orchestrate RBL cell activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29256213,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"\"Evita Una Muerte, Esta en Tus Manos\" Program: Bystander First Aid Training for Terrorist Attacks.\nThe latest terrorist attacks in Europe and in the rest of the world, and the military experience in the most recent conflicts leave us with several lessons learned. The most important is that the fate of the wounded rests in the hands of the one who applies the first dressing, because the victims usually die within the first 10 minutes, before professional care providers or police personnel arrive at the scene. A second lesson is that the primary cause of preventable death in these types of incidents involving explosives and firearms is massive hemorraghe. There is a need to develop a training oriented to citizens so they can identify and use available resources to avoid preventable deaths that occur in this kind of incidents, especially massive hemorrhage. A 7-hour training intervention program was developed and conducted between January and May 2017. Data were collected from participants' answers on a multiple-choice test before and after undertaking the training. Improved mean score for at least 75% of a group's members on the posttraining test was considered reflective of adequate knowledge. A total of 173 participants (n = 74 men [42.8%]; n = 99 women [57.2%]) attended the training. They were classified into three groups: a group of citizens\/ first responders with no prior health training, a group of health professionals, and a group of nursing students. Significant differences (\u03c1 < .05) between mean pre- and post-training test scores occurred in each of the three groups. There was a clear improvement in the knowledge of the students after the training when pre- and post-training test scores were compared within the three groups. The greatest improvement was seen in the citizens\/first responders group.","subset":"pubmed_abstract"} +{"meta":{"pmid":22192981,"dup_signals":{"dup_doc_count":43,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2018-17":2,"2018-09":2,"2017-51":2,"2017-43":2,"2017-26":2,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2016-36":2,"2016-30":2,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":2,"2015-18":1,"2017-13":1}}},"text":"Three-dimensional imaging with simultaneous reproduction of two image elements in one display pixel by linearization of intensity ratio of two images formed by any physical gear.\nFull spatial resolution in stereo image is reached if each (left and right) view of a three-dimensional scene is reproduced by all pixels of the display matrix. It is attractive for this purpose to simultaneously reproduce two image resolvable elements (corresponding to image elements of left and right views) in one display pixel. This paper shows how information-dependent linearization of the optical intensity ratio of left and right image elements (whose sum is submitted in the form of common optical intensity on the input of the display pixel) can be used to present corresponding elements separately in left and right observation windows. Such a linearization principle is valid regardless of the concrete physical gear of optical separation and demonstrated on the examples of optical separators on the basis of polarization, spectral, diffractive, and real amplitude modulation of light.","subset":"pubmed_abstract"} +{"meta":{"pmid":23041628,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":2,"unknown":6}}},"text":"Cross-presenting CD103+ dendritic cells are protected from influenza virus infection.\nCD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103+ DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103+ DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103+ DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":21630273,"dup_signals":{"dup_doc_count":60,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":5,"2023-14":2,"2023-06":2,"2022-49":2,"2022-40":1,"2022-27":3,"2022-21":1,"2022-05":4,"2021-49":3,"2021-43":2,"2021-39":4,"2021-31":4,"2021-21":1,"2021-17":3,"2021-10":1,"2021-04":3,"2020-50":3,"2020-40":4,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Expression of hypoxia-associated proteins in sporadic medullary thyroid cancer is associated with desmoplastic stroma reaction and lymph node metastasis and may indicate somatic mutations in the VHL gene.\nMedullary thyroid carcinomas (MTCs) are mostly aggressive but slowly growing malignant tumours that metastasize early to loco-regional lymph nodes. Desmoplastic stroma reaction is a strong risk factor associated with lymph node metastases. We evaluated immunohistochemically the expression of two hypoxia-associated proteins, carbonic anhydrase IX (CAIX) and hypoxia-induced factor 1\u03b1 (HIF1\u03b1), and ki-67, intercellular matrix adhesion molecule E-cadherin and the stroma remodelling marker tenascin C in a series of 100 sporadic MTCs and corresponding lymph node metastases, if present. Moderate to strong expression of CAIX was seen in 53 cases, and of HIF1\u03b1 in 51 cases, showing a strong correlation (p < 0.001; Spearman's coefficient of correlation, 0.59). Expression correlated with the degree of desmoplasia (pCAIX = 0.001 and pHIF1\u03b1 = 0.001), with tenascin C expression (pCAIX = 0.001,pHIF1\u03b1 = 0.038), with the ki-67 proliferation index (pCAIX = 0.001, pHIF1\u03b1 = 0.001) and with the presence of lymph node metastases (pCAIX < 0.001 and pHIF1\u03b1 = 0.007). The absence of membranous E-cadherin staining was significantly associated with the grade of desmoplasia, tenascin expression and lymph node metastases(p \u2264 0.05) but not with ki67 proliferation index or expression of hypoxia-associated factors. Expression of hypoxia-associated proteins was in most cases identical between primary tumours and lymph node metastases.Two cases showed strong uniform expression of CAIX and HIF1\u03b1 in the primary tumour as well as in the lymph node metastases, and sequencing revealed mutations in the coding regions of the Von-Hippel\u2013Lindau gene (VHL ).Our findings suggest that despite of the fact that MTCs have only slowly growth, tumour hypoxia plays an important role in the development of loco-regional metastases. Since traditional cytotoxic chemotherapy has only little effect on MTCs, targeting hypoxia-associated and -regulated proteins might be of benefit for patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":15458581,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":10}}},"text":"The \"schola medica salernitana\": the forerunner of the modern university medical schools.\nThe schola medica salernitana is considered the oldest medical school of modern civilization. Salerno's long medical tradition began during the Greco-Roman period in a Greek colony named Elea, where Parmenides decided to found a medical school. The fame of the school became more and more important during the 10th century, and it was best known in the 11th century. In the middle of 12th century, the school was at its apogee, and Salerno provided a notable contribution to the formulation of a medical curriculum for medieval universities. The most famous work of the Salernitan School was the Regimen Sanitatis Saleritanum, a Latin poem of rational, dietetic, and hygienic precepts, many of them still valid today. The school also produced a physician's reference book, with advice on how to treat a patient, a sort of code of conduct to help the physician to respect the patient and his or her relatives. The first science-based surgery appeared on the scene of the discredited medieval practice in Salerno, thanks to Roger of Salerno and his fellows. He wrote a book on surgery, called Rogerina or Post Mundi Fabricam, in which surgery from head to toe is described, with surprising originality. The important contribution to the School of Salerno made by women as female practitioners is outlined, and among them, Trotula de Ruggiero was the most renowned. The period when the School of Salerno, universally recognized as the forerunner of the modern universities, became a government academy was when Frederick II reigned over the Kingdom of the Two Sicilies, as Emperor of the Holy Roman Empire.","subset":"pubmed_abstract"} +{"meta":{"pmid":22721720,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats.\nThe Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 \u00d7 44 \u00d7 600 \u03bcm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":22768200,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"MED12 alterations in both human benign and malignant uterine soft tissue tumors.\nThe relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously reported but also in 11% of STUMP and 20% of leiomyosarcomas. The mutated allele is predominantly expressed in leiomyomas and STUMP. Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12. All these tumors without protein expression exhibit complex genomic profiles. No mutations and no expression loss were identified in an additional series of 38 non-uterine leiomyosarcomas. MED12 mutations are not exclusive to leiomyomas but seem to be specific to uterine malignancies. A previous study has suggested that MED12 mutations in leiomyomas could lead to Wnt\/\u03b2-catenin pathway activation however our immunohistochemistry results show that there is no association between MED12 status and \u03b2-catenin nuclear\/cytoplasmic localization. Collectively, our results show that subgroups of benign and malignant tumors share a common genetics. We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors.","subset":"pubmed_abstract"} +{"meta":{"pmid":9012859,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":1,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-26":1}}},"text":"A homolog of the mammalian GTPase Rab2 is present in Arabidopsis and is expressed predominantly in pollen grains and seedlings.\nVesicle traffic between the endoplasmic reticulum and the Golgi apparatus in mammals requires the small GTP-binding protein Rab2, but Saccharomyces cerevisiae appears not to have a Rab2 homolog. Here it is shown that the higher plant, Arabidopsis thaliana, contains a gene, At-RAB2, whose predicted product shares 79% identity with human Rab2 protein. Transgenic plants containing fusions between beta-glucuronidase and sequences upstream of At-RAB2 demonstrated histochemical staining predominantly in maturing pollen and rapidly growing organs of germinating seedlings. beta-glucuronidase activity in pollen is first detectable at microspore mitosis and increases thereafter. In this respect, the promoter of At-RAB2 behaves like those of class II pollen-specific genes, whose products are often required after germination for pollen tube growth. Seedling germination and pollen tube growth are notable for their unusually high rates of cell wall and membrane biosynthesis. These results are consistent with a role for At-RAB2 in secretory activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":24205186,"dup_signals":{"dup_doc_count":30,"dup_dump_count":22,"dup_details":{"curated_sources":4,"2022-27":1,"2021-25":1,"2020-29":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-39":2,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":2,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":2,"2017-34":2,"2017-30":1,"2017-26":1,"2017-17":1,"2023-50":1}}},"text":"Multiplex PageRank.\nMany complex systems can be described as multiplex networks in which the same nodes can interact with one another in different layers, thus forming a set of interacting and co-evolving networks. Examples of such multiplex systems are social networks where people are involved in different types of relationships and interact through various forms of communication media. The ranking of nodes in multiplex networks is one of the most pressing and challenging tasks that research on complex networks is currently facing. When pairs of nodes can be connected through multiple links and in multiple layers, the ranking of nodes should necessarily reflect the importance of nodes in one layer as well as their importance in other interdependent layers. In this paper, we draw on the idea of biased random walks to define the Multiplex PageRank centrality measure in which the effects of the interplay between networks on the centrality of nodes are directly taken into account. In particular, depending on the intensity of the interaction between layers, we define the Additive, Multiplicative, Combined, and Neutral versions of Multiplex PageRank, and show how each version reflects the extent to which the importance of a node in one layer affects the importance the node can gain in another layer. We discuss these measures and apply them to an online multiplex social network. Findings indicate that taking the multiplex nature of the network into account helps uncover the emergence of rankings of nodes that differ from the rankings obtained from one single layer. Results provide support in favor of the salience of multiplex centrality measures, like Multiplex PageRank, for assessing the prominence of nodes embedded in multiple interacting networks, and for shedding a new light on structural properties that would otherwise remain undetected if each of the interacting networks were analyzed in isolation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29327008,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"An upconversion nanoparticle-based fluorescence resonance energy transfer system for effectively sensing caspase-3 activity.\nWe report a new fluorescence resonance energy transfer (FRET) sensing platform for the sensitive detection of caspase-3 activity in vitro and in cells using NaGdF4:Yb3+,Er3+@NaGdF4 upconversion nanoparticles (UCNPs) as the energy donor and Rhodamine B (RB) as the energy acceptor. The phosphorylated RB-modified peptide containing a caspase-3 cleavage site and cell-penetrating peptide (CPP) motif (sequence, (RB)-DEVDGGS(p)GCGT(p)GRKKRRQRRRPQ) is immobilized on the UCNP surface via the strong coordination interaction between Gd3+ ions with phosphate. After the cleavage of DEVD by caspase-3, the RB is released from the UCNP surface and the reduced upconversion luminescence (UCL) is recovered. Under the optimum conditions, the recovery ratio of the UCL is linearly dependent on the caspase-3 concentration within the range of 0.01 to 1000 pg mL-1 and with a limit of detection (LOD) of 0.01 pg mL-1 (S\/N = 3). In particular, the as-proposed UCNP-based FRET sensing platform has reasonable selectivity which is successfully employed to monitor caspase-3 activity in drug-induced apoptosis of HeLa cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":28570871,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-39":2,"2018-26":2,"2018-13":1,"2018-09":1,"2017-47":2,"2017-26":1,"2019-26":1}}},"text":"Influence of dissolved organic matter concentration and composition on the removal efficiency of perfluoroalkyl substances (PFASs) during drinking water treatment.\nDrinking water treatment plants (DWTPs) are constantly adapting to a host of emerging threats including the removal of micro-pollutants like perfluoroalkyl substances (PFASs), while concurrently considering how background levels of dissolved organic matter (DOM) influences their removal efficiency. Two adsorbents, namely anion exchange (AE) and granulated active carbon (GAC) have shown particular promise for PFAS removal, yet the influence of background levels of DOM remains poorly explored. Here we considered how the removal efficiency of 13 PFASs are influenced by two contrasting types of DOM at four concentrations, using both AE (Purolite A-600\u00ae) and GAC (Filtrasorb 400\u00ae). We placed emphasis on the pre-equilibrium conditions to gain better mechanistic insight into the dynamics between DOM, PFASs and adsorbents. We found AE to be very effective at removing both PFASs and DOM, while largely remaining resistant to even high levels of background DOM (8 mg carbon L-1) and surprisingly found that smaller PFASs were removed slightly more efficiently than longer chained counterparts, In contrast, PFAS removal efficiency with GAC was highly variable with PFAS chain length, often improving in the presence of DOM, but with variable response based on the type of DOM and PFAS chain length.","subset":"pubmed_abstract"} +{"meta":{"pmid":15914776,"dup_signals":{"dup_doc_count":30,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2019-26":1,"2019-18":1,"2019-04":2,"2018-47":2,"2018-43":3,"2018-34":3,"2018-30":2,"2018-22":3,"2018-17":1,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":2,"2017-47":1,"2019-30":1}}},"text":"A region-based mathematical model of the urine concentrating mechanism in the rat outer medulla. I. Formulation and base-case results.\nWe have developed a highly detailed mathematical model for the urine concentrating mechanism (UCM) of the rat kidney outer medulla (OM). The model simulates preferential interactions among tubules and vessels by representing four concentric regions that are centered on a vascular bundle; tubules and vessels, or fractions thereof, are assigned to anatomically appropriate regions. Model parameters, which are based on the experimental literature, include transepithelial transport properties of short descending limbs inferred from immunohistochemical localization studies. The model equations, which are based on conservation of solutes and water and on standard expressions for transmural transport, were solved to steady state. Model simulations predict significantly differing interstitial NaCl and urea concentrations in adjoining regions. Active NaCl transport from thick ascending limbs (TALs), at rates inferred from the physiological literature, resulted in model osmolality profiles along the OM that are consistent with tissue slice experiments. TAL luminal NaCl concentrations at the corticomedullary boundary are consistent with tubuloglomerular feedback function. The model exhibited solute exchange, cycling, and sequestration patterns (in tubules, vessels, and regions) that are generally consistent with predictions in the physiological literature, including significant urea addition from long ascending vasa recta to inner-stripe short descending limbs. In a companion study (Layton AT and Layton HE. Am J Physiol Renal Physiol 289: F1367-F1381, 2005), the impact of model assumptions, medullary anatomy, and tubular segmentation on the UCM was investigated by means of extensive parameter studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":26929248,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Effects of Naringenin on Oxidative Stress and Histopathological Changes in the Liver of Lead Acetate Administered Rats.\nLead has several adverse effects on the body due to one of the environmental pollutants. We aimed to determine the effects of naringenin on the oxidative stress and the hepatic damage against lead acetate treatment in the liver of male rats. Naringenin was administered by orogastric gavage (50 mg\/kg) and lead acetate was given as daily 500 parts per million in drinking water for 4 weeks. Lead and antioxidant activities were measured, and histopathological evaluation was performed in the liver. Lead concentrations, malondialdehyde, and antioxidant activity were restored by the naringenin. The grade of necrosis, hydropic degeneration, and hepatic cord disorganization was decreased by the naringenin. However, there were no differences in the degree of sinusoidal congestion, hepatic steatosis, and capsular fibrosis between lead acetate and naringenin + lead acetate groups. We can suggest that naringenin has antioxidant and chelating effects in the liver. Nevertheless, this effect is not enough against the lead acetate induced hepatic injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":24799190,"dup_signals":{"dup_doc_count":21,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2020-16":2,"2020-10":1,"2020-05":1,"2019-51":3,"2019-47":1,"2019-39":4,"2019-35":1,"2018-22":1,"2017-51":1,"2016-44":1,"2020-24":1}}},"text":"Peptidoglycan remodeling by the coordinated action of multispecific enzymes.\nThe peptidoglycan (PG) cell wall constitutes the main defense barrier of bacteria against environmental insults and acts as communication interface. The biochemistry of this macromolecule has been well characterized throughout the years but recent discoveries have unveiled its chemical plasticity under environmental stresses. Non-canonical D-amino acids (NCDAA) are produced and released to the extracellular media by diverse bacteria. Such molecules govern cell wall adaptation to challenging environments through their incorporation into the polymer, a widespread capability among bacteria that reveals the inherent catalytic plasticity of the enzymes involved in the cell wall metabolism. Here, we analyze the recent structural and biochemical characterization of Bsr, a new family of broad spectrum racemases able to generate a wide range of NCDAA. We also discuss the necessity of a coordinated action of PG multispecific enzymes to generate adequate levels of modification in the murein sacculus. Finally, we also highlight how this catalytic plasticity of NCDAA-incorporating enzymes has allowed the development of new revolutionary methodologies for the study of PG modes of growth and in vivo dynamics.","subset":"pubmed_abstract"} +{"meta":{"pmid":33196672,"dup_signals":{"dup_doc_count":70,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-40":5,"2023-23":5,"2023-14":1,"2023-06":2,"2022-49":2,"2022-40":2,"2022-27":1,"2022-21":5,"2022-05":1,"2021-49":1,"2021-43":4,"2021-39":5,"2021-31":3,"2021-25":3,"2021-21":3,"2021-17":3,"2021-10":4,"2021-04":4,"2020-50":3,"2024-26":1,"2024-18":4,"2024-10":3,"2024-30":1}}},"text":"A Bayesian phase 2 model based adaptive design to optimise antivenom dosing: Application to a dose-finding trial for a novel Russell's viper antivenom in Myanmar.\nFor most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined 'optimal dose'. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell's viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified '3+3' design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar.","subset":"pubmed_abstract"} +{"meta":{"pmid":10948181,"dup_signals":{"dup_doc_count":82,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-40":5,"2023-23":1,"2023-14":2,"2022-49":3,"2022-27":4,"2022-21":3,"2022-05":1,"2021-49":3,"2021-43":2,"2021-31":4,"2021-25":1,"2021-17":5,"2021-10":1,"2021-04":3,"2020-50":1,"2020-45":5,"2020-40":3,"2019-18":1,"2019-13":1,"2019-04":2,"2018-51":1,"2018-47":1,"2018-43":2,"2018-39":1,"2018-34":1,"2018-30":2,"2018-22":2,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2024-30":3,"2024-26":2,"2024-18":2,"2024-10":2,"2017-13":2}}},"text":"Direct evidence for involvement of NF-kappaB in transcriptional activation of tumor necrosis factor by a spirochetal lipoprotein.\nVariable major lipoprotein (Vmp) is a major tumor necrosis factor (TNF)-inducing component of Borrelia recurrentis, the agent of louse-borne relapsing fever. B. recurrentis Vmp rapidly stimulates nuclear translocation of NF-kappaB and proinflammatory cytokine gene expression in the human monocyte-like cell line MonoMac 6. By overexpressing disabled mutant IkappaBalpha in MonoMac 6 cells cotransfected with a reporter gene, we provide evidence that NF-kappaB is essential for the transcriptional activation of TNF in this system.","subset":"pubmed_abstract"} +{"meta":{"pmid":11999966,"dup_signals":{"dup_doc_count":25,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2016-44":3,"2016-36":2,"2016-30":3,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":3,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":2,"2015-22":1,"2017-39":1}}},"text":"Light scattering from self-affine fractal silver surfaces with nanoscale cutoff: far-field and near-field calculations.\nWe study the light scattered from randomly rough, one-dimensional, self-affine fractal silver surfaces with nanoscale lower cutoff illuminated by s- or p-polarized Gaussian beams a few micrometers wide. By means of rigorous numerical calculations based on the Green's theorem integral equation formulation (GTIEF), we obtain both the far- and near-field scattered intensities. The influence of diminishing the size of the fractal lower-scale irregularities (from approximately 50 nm to a few nanometers) is analyzed in the case of both single realization and ensemble-average magnitudes. For s polarization, variations are small in the far field, being significant only in the higher-spatial-frequency components of evanescent character in the near field. In the case of p polarization, however, the nanoscale cutoff has remarkable effects stemming from the roughness-induced excitation of surface-plasmon polaritons. In the far field, the effect is noticed both in the speckle pattern variation and in the decrease of the total reflected energy upon ensemble averaging, as a result of increased absorption. In the near field, more efficient excitation of localized optical modes is achieved with smaller cutoff, which in turn leads to huge surface electric field enhancements.","subset":"pubmed_abstract"} +{"meta":{"pmid":17267443,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesis.\nIn rodents, the formation of ovarian follicles occurs after birth. In recent years, several factors required for follicular assembly and the growth of the newly formed follicles have been identified. We now describe a novel gene, Fxna, identified by differential display in the neonatal rat ovary. Fxna encodes an mRNA of 5.4 kb, and a protein of 898 amino acids. Fxna is a transmembrane metallopeptidase from family M28, localized to the endoplasmic reticulum. In the ovary, Fxna mRNA is expressed in granulosa cells; its abundance is maximal 48 hours after birth, i.e. during the initiation of follicular assembly. Reducing Fxna mRNA levels via lentiviral-mediated delivery of short hairpin RNAs to neonatal ovaries resulted in substantial loss of primordial, primary and secondary follicles, and structural disorganization of the ovary, with many abnormal follicles containing more than one oocyte and clusters of somatic cells not associated with any oocytes. These abnormalities were not attributable to either increased apoptosis or decreased proliferation of granulosa cells. The results indicate that Fxna is required for the organization of somatic cells and oocytes into discrete follicular structures. As an endoplasmic reticulum-bound peptidase, Fxna may facilitate follicular organization by processing precursor proteins required for intraovarian cell-to-cell communication.","subset":"pubmed_abstract"} +{"meta":{"pmid":29500807,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2022-27":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2023-50":1,"2024-22":1}}},"text":"Effect of Physical Rehabilitation on Echocardiographic Parameters in Patients with Acute Coronary Syndrome.\nEchocardiographic parameters were assessed in patients with non-ST segment elevation acute coronary syndrome, who underwent emergency percutaneous coronary intervention followed by various outpatient physical cardiac rehabilitation programs. The patients underwent physical rehabilitation for 3 months under conditions of diagnostic centre in the rehabilitation unit according to the standard program including in treadmill or bicycle exercise in the exercise therapy room or with Nordic walking in the main training block. After rehabilitation course, the left ventricular mass index significantly decreased and systolic volume and left ventricular ejection fraction significantly increased in both groups. Nordic walking training for 3 months non-ST segment elevation acute coronary syndrome induced similar positive shifts in the parameters of intracardiac hemodynamics, as standard treadmill or bicycle training program, which allows considering it as an alternative cardiac rehabilitation method.","subset":"pubmed_abstract"} +{"meta":{"pmid":22763459,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":14}}},"text":"Clinical profile, quality of care, and recurrence in Arab-American and Caucasians prostate cancer patients in Michigan.\nProstate cancer is the most common cancer among men in the United States with striking differences in incidence and mortality among ethnic groups. Michigan has one of the largest concentrations of Arab Americans (AAs) in the U.S. and little is known about this ethnic minority with respect to prostate cancer. This study investigated differences in clinical profile, quality of care, and recurrence among prostate cancer survivors comparing AAs and Caucasian Americans (CAs). Participants in this study included 2499 prostate cancer survivors from the Michigan Cancer Registry from 1985 to 2004. Participants completed surveys regarding health-seeking behavior, post-treatment symptoms, quality of care and recurrence. Ethnicity was self-reported and AAs and CAs were compared with respect to clinical profile, quality of care, and recurrence. There were 52 AAs and 1886 CAs patients with AAs being younger ([Formula: see text] age 68.3 \u00b1 SD 21.4 years, [Formula: see text] age 72.3 \u00b1 SD 14.1 years, for AAs and CAs, respectively) (P = 0.05). AAs had lower socioeconomic standard than CAs (34 vs. 10.6 %, <$20,000 yearly income\/year; for AAs vs. CAs, respectively) (P < 0.0001). AAs reported poorer health than AAs (7.7 vs. 3.0 % for AAs vs. CAs, respectively) (P < 0.0001). AAs were more likely to visit specialists for prostate follow-up (44.5 vs. 19.7 % visited a specialist, for AAs vs. CAs respectively) (P < 0.0001) and received supplementary healthcare workers (13 % of AAs vs. 3.1 % CAs) (P = 0.032). In addition, AAs reported higher occurrence of urinary incontinence compared to CAs (67.4 vs. 60.4 %, for AAs vs. CAs, respectively) (P = 0.001). Ethnic background was not a predictor of recurrence [(Odds ratio (OR) = 1.1 (95 % confidence intervals CI = 0.40, 2.9)] (P = 0.873) even after adjusting for age, PSA levels within the last 2 years, metastasis and hormonal therapy. While AAs prostate cancer patients were different from CAs in age, income, seeking medical care, and health reporting, ethnic background was not a predictor of recurrence. Future studies of the impact of socioeconomic, demographic and cultural factors, and health care seeking behavior on long-term survival of prostate cancer in AAs and other ethnic minorities are warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":11444415,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":17}}},"text":"A comparison of intakes of breast-fed and bottle-fed infants during the first two days of life.\nIn the first days of life, breast-fed infants consume minimal amounts of milk; this may be explained by substrate limitation (limited milk output) and\/or by self-limitation (through low appetite and\/or suck-swallow competency). The spontaneous milk intake of unrestricted formula-fed infants has not been studied to date. We compared the spontaneous formula intake of unrestricted formula-fed infants to that of breast-fed infants over the first 48 hours of life. We hypothesized that 1) spontaneous formula intake of unrestricted infants is much higher than that of breast-fed infants and 2) spontaneous formula intake correlates positively with gestational age or birthweight. We studied 43 healthy, term infants. By maternal choice, 15 infants were exclusively breast-fed and 28 were formula-fed ad libitum every four hours. Breast-fed infants were weighed before and one hour after initiation of feeding, and intake was calculated from the difference between the measurements and corrected individually for the infant's normal postnatal decrease in body weight. Bottles offered to formula-fed infants contained 60 cc, and the remainder was carefully measured. Intakes were expressed as cc\/kg\/d, and weight changes as % of birthweight. Statistical methods included Student's t tests and stepwise regression analysis. Breast feeding on Day I was 9.6 +\/- 10.3 (mean +\/- SD) vs. 18.5 +\/- 9.6 cc\/kg\/d in formula-fed infants (p=0.011); on Day 2 it was 13.0 +\/- 11.3 vs. 42.2 +\/- 14.2 cc\/kg\/d (p<0.001). Breast-fed infants lost significantly more weight on Day 2 (p=0.015). In multiple regression, when the dependent variable was the second-day intake, the significant independent variables were group (higher intake in the formula-fed group), weight loss (the higher the weight loss, the lower the intake), and first-day intake (the higher the first-day intake, the higher the second-day intake). Newborn infants offered formula ad libitum every four hours consumed much larger amounts than breast-fed infants fed according to the same schedule. In addition, weight loss was more marked in breast-fed infants on Day 2 of life.","subset":"pubmed_abstract"} +{"meta":{"pmid":26749373,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2022-21":1,"2020-10":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-26":1,"2017-51":1,"2022-49":1}}},"text":"Functioning and disability in autism spectrum disorder: A worldwide survey of experts.\nThis study is the second of four to prepare International Classification of Functioning, Disability and Health (ICF; and Children and Youth version, ICF(-CY)) Core Sets for Autism Spectrum Disorder (ASD).The objective of this study was to survey the opinions and experiences of international experts on functioning and disability in ASD. Using a protocol stipulated by the World Health Organization (WHO) and monitored by the ICF Research Branch, an email-based questionnaire was circulated worldwide among ASD experts, and meaningful functional ability and disability concepts were extracted from their responses. These concepts were then linked to the ICF(-CY) by two independent researchers using a standardized linking procedure. N = 225 experts from 10 different disciplines and all six WHO-regions completed the survey. Meaningful concepts from the responses were linked to 210 ICF(-CY) categories. Of these, 103 categories were considered most relevant to ASD (i.e., identified by at least 5% of the experts), of which 37 were related to Activities and Participation, 35 to Body functions, 22 to Environmental factors, and 9 to Body structures. A variety of personal characteristics and ASD-related functioning skills were provided by experts, including honesty, loyalty, attention to detail and creative talents. Reported gender differences in ASD comprised more externalizing behaviors among males and more internalizing behaviors in females. The ICF(-CY) categories derived from international expert opinions indicate that the impact of ASD on functioning extends far beyond core symptom domains. Autism Res 2016, 9: 959-969. \u00a9 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.","subset":"pubmed_abstract"} +{"meta":{"pmid":20450993,"dup_signals":{"dup_doc_count":35,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":1,"2014-23":2,"2014-15":3,"2017-34":1,"2015-06":1,"2014-10":2,"2013-48":2,"2015-18":1}}},"text":"A common variant in fibroblast growth factor binding protein 1 (FGFBP1) is associated with bone mineral density and influences gene expression in vitro.\nWe previously detected strong evidence for linkage of forearm bone mineral density (BMD) to chromosome 4p (lod=4.3) in a set of 29 large Mexican American families. Fibroblast growth factor binding protein 1 (FGFBP1) is a strong candidate gene for bone homeostasis in this region. We sequenced the coding region of FGFBP1 in a subset of our Mexican American study population and performed association studies with BMD on SNPs genotyped in the entire cohort. We then attempted to replicate these findings in an independent study cohort and performed in vitro functional studies on replicated, potentially functional polymorphisms using a luciferase reporter construct to evaluate influence on gene expression. Several SNPs spanning the gene, all in one large block of linkage disequilibrium, were significantly associated with BMD at various skeletal sites (n=872, p=0.001-0.04). The associations were then replicated in an independent population of European ancestry (n=972; p=0.02-0.04). Sex-stratified association analyses in both study populations suggest this association is much stronger in men. Subsequent luciferase reporter gene assays revealed marked differences in FGFBP1 expression among the three common haplotypes. Further experiments revealed that a promoter polymorphism, rs12503796, results in decreased expression of FGFBP1 and inhibits upregulation of the gene by testosterone in vitro. Collectively, these findings suggest that sequence variation in FGFBP1 may contribute to variation in BMD, possibly influencing osteoporosis risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":29772765,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Protein Carbamylation: A Marker Reflecting Increased Age-Related Cell Oxidation.\nCarbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a \"hallmark of aging\". The molecular mechanisms associated with aging are related to an increased release of free radicals. We have studied whether carbamylated proteins from the peripheral blood of healthy subjects are related to oxidative damage and aging, taking into account the gender and the immune profile of the subjects. The study was performed in healthy human volunteers. The detection of protein carbamylation and malondialdehyde (MDA) levels was evaluated using commercial kits. The immune profile was calculated using parameters of immune cell function. The results show that the individuals from the elderly group (60\u207b79 years old) have increased carbamylated protein and MDA levels. When considered by gender, only men between 60 and 79 years old showed significantly increased carbamylated proteins and MDA levels. When those subjects were classified by their immune profile, the carbamylated protein levels were higher in those with an older immune profile. In conclusion, the carbamylation of proteins in peripheral blood is related to age-associated oxidative damage and to an aging functional immunological signature. Our results suggest that carbamylated proteins may play an important role at the cellular level in the aging process.","subset":"pubmed_abstract"} +{"meta":{"pmid":3030680,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The human growth hormone gene locus: structure, evolution, and allelic variations.\nGenomic clones containing the closely related genes for human growth hormone (hGH) and chorionic somatomammotropin (hCS) were obtained from genomic bacteriophage lambda and cosmid libraries. The entire GH\/CS chromosomal locus was reconstructed utilizing overlapping restriction fragments characterized from the isolated clones. The hGH\/hCS locus contains two GH genes and three CS genes spanning 48 kb of DNA in the order: 5'-(hGH-1\/hCS-5\/hCS-1\/hGH-2\/hCS-2)-3', confirming analysis of cosmid clones obtained from a different human library (Barsh et al., 1983). To complete the characterization of the hCS genes, the nucleotide sequence of the hCS-5 gene was determined. Sequence analysis revealed a mutation of the 5' splice site at the exon II-intron B boundary, suggesting that the hCS-5 gene is a pseudogene. The nucleotide sequence of an allelic variant of the hCS-2 gene was determined and found to contain a single amino acid substitution and the deletion of a single codon. The hGH\/hCS gene locus was further characterized by the localization of at least 27 Alu-type repetitive sequences and identification of three unique sequences in the vicinity of several hGH and hCS genes which define the probable breakpoints of the evolutionary duplication units. These data, combined with the nucleotide sequences of all five GH and CS genes, indicate that the hGH\/hCS gene locus has evolved by duplication mechanisms. Evidence for the occurrence of at least one gene conversion event involving the hCS-1 gene precursor and the hCS-2 gene was found, indicating that the hGH\/hCS gene locus has evolved by concerted mechanisms. The structure of the hCS genes is discussed in light of recent studies of CS genes from other mammalian species.","subset":"pubmed_abstract"} +{"meta":{"pmid":30753137,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Genetics of aldosterone-producing adenomas with pathogenic KCNJ5 variants.\nSomatic variants in genes that regulate intracellular ion homeostasis have been identified in aldosterone-producing adenomas (APA). Although the mechanisms leading to an increased aldosterone production in APA cells has been well studied, the molecular events that cause cell proliferation and tumor formation are poorly understood. In the present study, we have performed whole exome sequencing (WES) to characterize the landscape of somatic alterations in a homogeneous series of APA with pathogenic KCNJ5 variants. In the WES analysis on eleven APA, 84 exonic somatic events were called by 3 different somatic callers. Besides the KCNJ5 gene, only two genes (MED13 and ZNF669) harbored somatic variants in more than one APA. Unlike adrenocortical carcinomas, no chromosomal instability was observed by the somatic copy-number alteration and loss of heterozygosity analyses. The estimated tumor purity ranged from 0.35 to 0.67, suggesting a significant proportion of normal cell infiltration. Based on the results of PureCN analysis, the KCNJ5 variants appear to be clonal. In conclusion, in addition to KCNJ5 somatic pathogenic variant, no significant somatic event that would obviously explain proliferation or tumor growth was observed in our homogeneous cohort of KCNJ5-mutated APA. The molecular mechanisms causing APA growth and tumorigenesis remain to be elucidated.","subset":"pubmed_abstract"} +{"meta":{"pmid":32740356,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.\nThrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.","subset":"pubmed_abstract"} +{"meta":{"pmid":23331676,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":10}}},"text":"Characterization of canine filaggrin: gene structure and protein expression in dog skin.\nFilaggrin (FLG) is a key protein for skin barrier formation and hydration of the stratum corneum. In humans, a strong association between FLG gene mutations and atopic dermatitis has been reported. Although similar pathogenesis and clinical manifestation have been argued in canine atopic dermatitis, our understanding of canine FLG is limited. The aim of this study was to determine the structure of the canine FLG gene and to raise anti-dog FLG antibodies, which will be useful to detect FLG protein in dog skin. The structure of the canine FLG gene was determined by analysing the publicly available canine genome DNA sequence. Polyclonal anti-dog FLG antibodies were raised based on the canine FLG sequence analysis and used for defining the FLG expression pattern in dog skin by western blotting and immunohistochemistry. Genomic DNA sequence analysis revealed that canine FLG contained four units of repeated sequences corresponding to FLG monomer protein. Western blots probed with anti-dog FLG monomer detected two bands at 59 and 54 kDa, which were estimated sizes. The results of immunohistochemistry showed that canine FLG was expressed in the stratum granulosum of the epidermis as a granular staining pattern in the cytoplasmic region. This study revealed the unique gene structure of canine FLG that results in production of FLG monomers larger than those of humans or mice. The anti-dog FLG antibodies raised in this study identified FLG in dog skin. These antibodies will enable us to screen FLG-deficient dogs with canine atopic dermatitis or ichthyosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":18249140,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2022-33":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-25":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-29":1,"2020-24":1,"2020-10":1,"2022-49":1,"2024-26":1}}},"text":"Influence of additional load on the moments of the agonist and antagonist muscle groups at the knee joint during closed chain exercise.\nThe present study investigated the influence of additional loads on the knee net joint moment, flexor and extensor muscle group moments, and cocontraction index during a closed chain exercise. Loads of 8, 28, or 48 kg (i.e., respectively, 11.1+\/-1.5%, 38.8+\/-5.3%, and 66.4+\/-9.0% of body mass) were added to subjects during dynamic half squats. The flexor and extensor muscular moments and the amount of cocontraction were estimated at the knee joint using an EMG-and-optimization model that includes kinematics, ground reaction, and EMG measurements as inputs. In general, our results showed a significant influence of the Load factor on the net knee joint moment, the extensor muscular moment, and the flexor muscle group moment (all Anova p<.05). Hence we confirmed an increase in muscle moments with increasing load and moreover, we also showed an original \"more than proportional\" evolution of the flexor and extensor muscle group moments relative to the knee net joint moment. An influence of the Phase (i.e., descent vs. ascent) factor was also seen, revealing different activation strategies from the central nervous system depending on the mode of contraction of the agonist muscle group. The results of the present work could find applications in clinical fields, especially for rehabilitation protocols.","subset":"pubmed_abstract"} +{"meta":{"pmid":21523250,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":2,"2024-10":1,"2024-26":1,"unknown":6}}},"text":"The dynamics of the impact and coalescence of droplets on a solid surface.\nA simple experimental setup to study the impact and coalescence of deposited droplets is described. Droplet impact and coalescence have been investigated by high-speed particle image velocimetry. Velocity fields near the liquid-substrate interface have been observed for the impact and coalescence of 2.4 mm diameter droplets of glycerol\u2215water striking a flat transparent substrate in air. The experimental arrangement images the internal flow in the droplets from below the substrate with a high-speed camera and continuous laser illumination. Experimental results are in the form of digital images that are processed by particle image velocimetry and image processing algorithms to obtain velocity fields, droplet geometries, and contact line positions. Experimental results are compared with numerical simulations by the lattice Boltzmann method.","subset":"pubmed_abstract"} +{"meta":{"pmid":22040144,"dup_signals":{"dup_doc_count":33,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2019-51":1,"2019-04":1,"2018-47":1,"2018-26":1,"2018-22":1,"2017-47":1,"2017-39":2,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2021-49":1,"2024-22":2,"2024-18":1,"2024-10":1,"2013-48":1,"2024-26":1}}},"text":"Prevention of urinary tract infections in nursing homes: lack of evidence-based prescription?\nUrinary tract infections (UTIs, including upper and lower symptomatic) are the most common infections in nursing homes and prevention may reduce patient suffering, antibiotic use and resistance. The spectre of agents used in preventing UTIs in nursing homes is scarcely documented and the aim of this study was to explore which agents are prescribed for this purpose. We conducted a one-day, point-prevalence study in 44 Norwegian nursing homes during April-May 2006. Nursing home residents prescribed any agent for UTI prophylaxis were included. Information recorded was type of agent and dose, patient age and gender, together with nursing home characteristics. Appropriateness of prophylactic prescribing was evaluated with references to evidence in the literature and current national guidelines. The study included 1473 residents. 18% (n = 269) of the residents had at least one agent recorded as prophylaxis of UTI, varying between 0-50% among the nursing homes. Methenamine was used by 48% of residents prescribed prophylaxis, vitamin C by 32%, and cranberry products by 10%. Estrogens were used by 30% but only one third was for vaginal administration. Trimethoprim and nitrofurantoin were used as prophylaxis by 5% and 4%, respectively. The agents frequently prescribed to prevent UTIs in Norwegian nursing homes lack documented efficacy including methenamine and vitamin C. Recommended agents like trimethoprim, nitrofurantoin and vaginal estrogens are infrequently used. We conclude that prescribing of prophylactic agents for UTIs in nursing homes is not evidence-based.","subset":"pubmed_abstract"} +{"meta":{"pmid":7281088,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Pulmonary involvement in primary biliary cirrhosis.\nThe association of pulmonary fibrosis and primary biliary cirrhosis (PBC) remains controversial. To determine the frequency of pulmonary fibrosis in PBC, a carefully selected series of 14 PBC patients, seven patients with Sicca complex, and 14 control subjects have been studied. Seven of the 14 patients with PBC had Sj\u00f6gren's syndrome, four of whom had some clinical evidence of pulmonary disease. Evaluation of ventilatory capacity, gas transfer factor, arterial blood gases, and lung mechanics were performed. Gas transfer was reduced in patients with PBC associated with Sj\u00f6gen's syndrome and in patients with the Sicca complex. These results suggest that the respiratory, clinical, ad functional abnormalities found in PBC are related to the presence of an associated Sj\u00f6gen's syndrome.","subset":"pubmed_abstract"} +{"meta":{"pmid":23041167,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-33":1,"2022-05":2,"2021-39":1,"2021-17":1,"2021-04":1,"2020-16":1,"2023-50":1}}},"text":"Very long-term outcomes following drug-eluting stent implantation for unprotected left main coronary artery stenosis: a single center experience.\nEncouraging results at long-term follow-up have been reported from non-randomized registries and randomized trials following percutaneous coronary intervention with drug-eluting stent implantation for unprotected left main stenosis. However, information on very long-term (>5-year) outcomes is limited. The aim of this study was to assess the very long-term outcomes (6-years) following drug-eluting stent implantation for left main disease. All consecutive patients with unprotected left main stenosis electively treated with drug-eluting stent implantation, between March 2002 and May 2005, were analyzed according to the location of the left main lesion (distal bifurcation vs ostial\/body). The study included 149 patients: 113 with distal bifurcation and 36 with ostial\/body lesion. Triple-vessel disease was significantly higher in the distal than in the ostial\/body group (52.2% vs 33.2%, P=.05). At 6-years of follow-up, the cumulative major adverse cardiovascular event rate was 41.6% (45.1% distal vs 30.6% ostial\/body, P=0.1), including 18.8% any death (22.1% distal vs 8.3% ostial\/body, P=.08), 3.4% myocardial infarction (3.5% distal vs 2.8% ostial\/body, P=1), and 15.4% target lesion revascularization (18.6% distal vs 5.6% ostial\/body, P=.06). The composite of cardiac death and myocardial infarction was 10.7% (13.3% distal vs 2.8% ostial\/body, P=.1) while the definite\/probable stent thrombosis rate was 1.4% (all in the distal group). At 6-year clinical follow-up, percutaneous coronary intervention with drug-eluting stent implantation for unprotected left main disease was associated with acceptable rates of cardiac death, myocardial infarction and stent thrombosis. Favorable long-term outcomes in ostial\/body lesions compared to distal bifurcation lesions were confirmed at long-term clinical follow-up.","subset":"pubmed_abstract"} +{"meta":{"pmid":18362978,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The gas-phase ozonolysis of unsaturated volatile organic compounds in the troposphere.\nThe gas-phase reactions of ozone with unsaturated hydrocarbons are significant sources of free radical species (including *OH) and particulate material in the Earth's atmosphere. In this tutorial review, the kinetics, products and mechanisms of these reactions are examined, starting with a discussion of the original mechanism proposed by Criegee and following with a summary presentation of the complex, free radical-mediated reactions of carbonyl oxide (Criegee) intermediates. The contribution of ozone-terpene reactions to the atmospheric burden of secondary organic aerosol material is also discussed from the viewpoint of the formation of non-volatile organic acid products from the complex chemistry of ozone with alpha-pinene. Throughout the article, currently accepted understanding is supported through the presentation of key experimental results, and areas of persistent or new uncertainty are highlighted.","subset":"pubmed_abstract"} +{"meta":{"pmid":3598645,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Recycling of plasmalemma in chick tectal growth cones.\nGrowth cones from freeze-substituted intact chick optic tectum were analyzed in serial reconstructions of thin-section electron micrographs in order to determine which internal organelles might contribute membrane for plasmalemmal expansion. These growth cones contain numerous stacked and single lumenless membrane-limited disks; the stacks are arrays of single disks interconnected, and possibly organized, by intervening electron-dense cross-links. The single and stacked disks together account for 80% of the total intracellular membrane in the growth cones. Single disks frequently lie close to and occasionally contact the filopodial plasmalemma; regularly spaced electron-dense cross-links also occur at these juxtapositions between single disks and the plasmalemma. Some of the juxtaposed disk membranes contact the growth cone plasmalemma, and images of some of these contacts appear to indicate fusion of the disk membrane with the plasmalemma. When excised optic tecta are exposed to cationized ferritin for various times, ferritin micelles appear sequentially in coated pits, coated vesicles, smooth vesicles, vacuoles, and then in stacked and single disks, including some of those contacting the plasmalemma. Because the cytoplasmic disks filled only at the longest times after exposure to ferritin, the membrane continuities between the disks and the plasmalemma are thought to be indicative of exocytosis rather than endocytosis. We propose, therefore, that components of the plasma membrane are recycled through the stacks of lumenless disks in the chick tectal growth cones; the disks therefore represent a pool of internal membrane waiting to be added to the growth cone plasmalemma that could be used for filopodial extension or neuritic extension.","subset":"pubmed_abstract"} +{"meta":{"pmid":7053900,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-40":1,"2021-31":1,"2020-34":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":1,"2016-50":1,"2023-50":1,"2017-13":1}}},"text":"Late survival and symptoms after repair of tetralogy of Fallot.\nThe long-term results of 414 patients who underwent repair of tetralogy of Fallot between 1967 and 1977 were studied and correlated with the results of others. There were nine late deaths (8-year actuarial survival 95.8%). Six of the deaths wee directly related to the malformation or its treatment. Eight patients (2.4%) required reoperation. Ten patients (4.8%) had arrhythmic symptoms. Eight (3.1%) had congestive heart failure that required treatment. The risk factors associated with late events of all types, including death, were: older age at repair, a high mean ratio of peak systolic right-to-left ventricular pressures (PLV\/RV) immediately after repair, and the presence of a Potts anastomosis. Neither a transannular patch nor a previous Blalock-Taussig or Waterson anastomosis was an incremental risk factor. Bacterial endocarditis was not observed. Three hundred seven patients underwent repair primarily or after a single Blalock-Taussig or Waterston shunt and had a PRV\/LV of 0.85 or less after repair. Among these selected patients, the actuarial survival was 98.1%, which is still lower than that for the general population (p = 0.12), and freedom from events was 95.9%. Late after repair, PRV\/LV was lower by 6 +\/- 28% (+\/- SD) than PRV\/LV immediately after repair (p = 0.03) in the 33 restudied patients with such data. The higher the PRV\/LV immediately after repair, the greater the percent reduction.","subset":"pubmed_abstract"} +{"meta":{"pmid":24885524,"dup_signals":{"dup_doc_count":38,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2022-05":1,"2021-43":2,"2021-39":2,"2021-31":1,"2021-21":1,"2021-17":3,"2021-10":3,"2020-45":1,"2020-29":1,"2020-24":1,"2020-16":1,"2019-18":2,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2018-05":1,"2017-39":2,"2023-06":1,"2024-30":4,"2024-26":2,"2024-18":1}}},"text":"Patients with persistent medically unexplained physical symptoms: a descriptive study from Norwegian general practice.\nFurther research on effective interventions for patients with peristent Medically Unexplained Physical Symptoms (MUPS) in general practice is needed. Prevalence estimates of such patients are conflicting, and other descriptive knowledge is needed for development and evaluation of effective future interventions. In this study, we aimed to estimate the consultation prevalence of patients with persistent MUPS in general practice, including patients' characteristics and symptom pattern, employment status and use of social benefits, and the general practitioners' (GPs) management strategy. During a four-week period the participating Norwegian GPs (n=84) registered all consultations with patients who met a strict definition of MUPS (>3 months duration and function loss), using a questionnaire with simple tick-off questions. Analyses were performed with descriptive statistics for all variables and split analysis on gender and age. The GPs registered 526 patients among their total of 17 688 consultations, giving a consultation prevalence of persistent MUPS of 3%. The mean age of patients was 46 years, and 399 (76%) were women. The most frequent group of symptoms was musculoskeletal problems, followed by asthenia\/fatigue. There was no significant gender difference in symptom pattern. Almost half of the patients were currently working (45%), significantly more men. The major GP management strategy was supportive counseling. A consultation prevalence rate of 3% implies that patients with persistent MUPS are common in general practice. Our study disclosed heterogeneity among the patients such as differences in employment status, which emphasizes the importance of personalized focus rather than unsubstantiated stereotyping of \"MUPS patients\" as a group.","subset":"pubmed_abstract"} +{"meta":{"pmid":8366872,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-26":1,"unknown":12}}},"text":"Language comprehension in ape and child.\nPrevious investigations of the linguistic capacities of apes have focused on the ape's ability to produce words, and there has been little concern for comprehension. By contrast, it is increasingly recognized that comprehension precedes production in the language development of normal human children, and it may indeed guide production. It has been demonstrated that some species can process speech sounds categorically in a manner similar to that observed in humans. Consequently, it should be possible for such species to comprehend language if they have the cognitive capacity to understand word-referent relations and syntactic structure. Popular theories of human language acquisition suggest that the ability to process syntactic information is unique to humans and reflects a novel biological adaptation not seen in other animals. The current report addresses this issue through systematic experimental comparisons of the language comprehension skills of a 2-year-old child and an 8 year-old bonobo (Pan paniscus) who was raised in a language environment similar to that in which children are raised but specifically modified to be appropriate for an ape. Both subjects (child and bonobo) were exposed to spoken English and lexigrams from infancy, and neither was trained to comprehend speech. A common caretaker participated in the rearing of both subjects. All language acquisition was through observational learning. Without prior training, subjects were asked to respond to the same 660 novel sentences. All responses were videotaped and scored for accuracy of comprehension of the English language. The results indicated that both subjects comprehended novel requests and simple syntactic devices. The bonobo decoded the syntactic device of word recursion with higher accuracy than the child; however, the child tended to do better than the bonobo on the conjunctive, a structure that places a greater burden on short-term memory. Both subjects performed as well on sentences that required the ability to reverse work order as they did on sentences that did not require this capacity. These results are discussed in light of a model of the evolution of language that suggests that the potential for language comprehension preceded the appearance of speech by several million years at minimum. The onset of speech is linked to the appearance of fully adapted bipedalism, which necessitated reorientation of the laryngeal tract and made closure of the soft palate possible. For the first time, such closure permitted mammals to easily produce sounds that could be interpreted by the mammalian auditory system in a categorical manner. When these sounds were paired with the previously extant capacity to produce vowels, it became possible to form \"bounded vowels\" or sound units that could readily be discriminated as units by the auditory system. It is suggested that this physical adaptation allowed the extant cognitive capacity of the hominids to embark on a speech-like mode of communication.","subset":"pubmed_abstract"} +{"meta":{"pmid":15165413,"dup_signals":{"dup_doc_count":30,"dup_dump_count":27,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2023-40":1,"2017-13":1,"2024-18":1}}},"text":"Electrophysiological evidence of intuition: Part 2. A system-wide process?\nThis study aims to contribute to a scientific understanding of intuition, a process by which information normally outside the range of conscious awareness is perceived by the body's psychophysiological systems. The first objective, presented in two empirical reports (Part 1 and Part 2), was to replicate and extend the results of previous experiments demonstrating that the body can respond to an emotionally arousing stimulus seconds before it is actually experienced. The second objective, to be presented in a forthcoming publication (Part 3), is to develop a theory that explains how the body receives and processes information involved in intuitive perception. The study used a counterbalanced crossover design, in which 30 calm and 15 emotionally arousing pictures were presented to 26 participants under two experimental conditions: a baseline condition of \"normal\" psychophysiologic function and a condition of physiological coherence. Primary measures included: skin conductance; the electroencephalogram (EEG), from which cortical event-related potentials (ERP) and heartbeatevoked potentials (HBEP) were derived; and the electrocardiogram (ECG), from which cardiac decelerations\/ accelerations were derived. These measures were used to investigate where and when in the brain and body intuitive information is processed. The main findings presented here are: (1) surprisingly, both the heart and brain appear to receive and respond to intuitive information; (2) even more surprisingly, there is compelling evidence that the heart appears to receive intuitive information before the brain; (3) there were significant differences in prestimulus ERPs for calm versus emotional stimuli; (4) the frontal cortex, temporal, occipital, and parietal areas appear to be involved in the processing of prestimulus information; (5) there were significant differences in prestimulus calm\/emotional HBEPs, primarily in the coherent mode; (6) there were significant gender differences in the processing of prestimulus information. Especially noteworthy is the apparent interaction between the HBEPs and ERPs in the females, which suggests that the heart modulates the ERP and that females are more attuned to intuitive information from the heart. Overall, our data suggest that the heart and brain, together, are involved in receiving, processing, and decoding intuitive information. On the basis of these results and those of other research, it would thus appear that intuitive perception is a system-wide process in which both the heart and brain (and possibly other bodily systems) play a critical role. To account for the study's results, Part 3 will develop a theory based on holographic principles explaining how intuitive perception accesses a field of energy into which information about \"future\" events is spectrally enfolded.","subset":"pubmed_abstract"} +{"meta":{"pmid":22339626,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":13}}},"text":"Varenicline potentiates alcohol-induced negative subjective responses and offsets impaired eye movements.\nVarenicline (VAR) is a partial nicotinic receptor agonist that is an effective smoking cessation medication. Preliminary evidence indicates that it may also reduce alcohol consumption, but the underlying mechanism is not clear. For example, VAR may reduce alcohol consumption by attenuating its subjectively rewarding properties or by enhancing its aversive effects. In this study, we examined the effects of an acute dose of VAR upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers. Healthy men and women (N = 15) participated in 6 randomized sessions; 3 sessions each with 2 mg VAR and placebo (PL) followed 3 hours later by a beverage containing PL, low-dose alcohol (0.4 g\/kg), or high-dose alcohol (0.8 g\/kg). Subjective mood and drug effects (i.e., stimulation, drug liking), physiological measures (heart rate, blood pressure), and eye tracking tasks were administered at various intervals before and after drug and alcohol administration. VAR acutely increased blood pressure, heart rate, ratings of dysphoria and nausea, and also improved eye tracking performance. After alcohol drinking (vs. PL), VAR increased dysphoria and tended to reduce alcohol liking ratings. It also attenuated alcohol-induced eye-tracking impairments. These effects were independent of the drug's effects on nausea before drinking. Our data support the theory that VAR may reduce drinking by potentiating aversive effects of alcohol. VAR also offsets alcohol-induced eye movement impairment. The evidence suggests that VAR may decrease alcohol consumption by producing effects, which oppose the rewarding efficacy of alcohol.","subset":"pubmed_abstract"} +{"meta":{"pmid":17296760,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Influence of neutropenia on the course of serotype 8 pneumococcal pneumonia in mice.\nPolymorphoneutrophils (PMNs) are important effector cells in host defense against pneumonia. However, PMNs can also induce inflammation and tissue damage. To investigate the contribution of PMNs to host defense against pneumococcal pneumonia, we determined the effect of the PMN-depleting rat monoclonal antibody RB6-8C5 (RB6) on survival and inflammatory and cellular response in the lungs to a lethal intranasal infection with a serotype 8 pneumococcus in BALB\/c mice. Control mice received rat immunoglobulin G (rIgG). Strikingly, the survival of RB6-treated mice was significantly prolonged compared to that of rIgG-treated mice. Although the numbers of CFU in the lungs were statistically similar in both groups 4, 24, and 32 h after infection, rIgG-treated mice developed higher levels of bacteremia, and histopathological examination of the lungs of infected mice revealed marked differences between RB6- and rIgG-treated mice. RB6-treated mice had focal, perivascular lesions without accompanying parenchymal inflammation, and rIgG-treated mice had diffuse, interstitial parenchymal inflammation. Lung homogenates from the rIgG-treated mice had more leukocytes and significantly more total and apoptotic PMNs as determined by fluorescence-activated cell sorter analysis with Annexin V and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining of lung tissue samples. Studies with a pneumolysin-deficient mutant of the serotype 8 strain we used also demonstrated the prolonged survival of RB6- compared to rIgG-treated mice. Taken together, our findings suggest that PMNs enhance the likelihood of early death and alter the pathological response to pneumococcal lung infection in BALB\/c mice with serotype 8 pneumonia without significantly affecting bacterial clearance or the cytokine response.","subset":"pubmed_abstract"} +{"meta":{"pmid":15145146,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":4,"2013-48":2,"unknown":5}}},"text":"Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes?\nThe long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy. Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng\/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS. The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively). Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.","subset":"pubmed_abstract"} +{"meta":{"pmid":26120062,"dup_signals":{"dup_doc_count":23,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2022-49":2,"2022-40":1,"2020-45":1,"2020-40":1,"2019-18":1,"2019-13":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-06":1,"2024-22":1}}},"text":"Capillary droplet propulsion on a fibre.\nA viscous liquid film coating a fibre becomes unstable and decays into droplets due to the Rayleigh-Plateau instability (RPI). Here, we report on the generation of uniform droplets on a hydrophobized fibre by taking advantage of this effect. In the late stages of liquid column breakup, a three-phase contact line can be formed at one side of the droplet by spontaneous rupture of the thinning film. The resulting capillary imbalance leads to droplet propulsion along the fibre. We study the dynamics and the dewetting speed of the droplet as a function of molecular weight as well as temperature and compare to a force balance model based on purely viscous dissipation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27605366,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2018-05":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2018-13":1,"2017-13":1}}},"text":"Prevalence of HIV Infection and Risk Factors Among Female Sex Workers in a Southeast Province of Vietnam.\nFemale sex workers (FSWs) are at heightened risk of HIV infection. This research aims to determine the prevalence of HIV and relevant risk factors and related behavior among FSWs in Ba Ria - Vung Tau, a southeast province of Vietnam. 420 FSWs were interviewed using a structured questionnaire and biological samples tested for HIV. 2.6 % were found to be HIV positive. HIV infection was significantly higher in FSWs who had low income (\u2264AUD 200 per month), have had anal sex, have had sex with injecting drug users, and had a low level of HIV\/AIDS-related knowledge. Improved employment opportunities and income are important to reduce the pressure for young women to engage in sex work for income purposes, but in public health terms, existing HIV treatment, prevention and intervention programs needs better targeting and improvements to reduce the risk of HIV infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":24347564,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2021-04":1,"2020-40":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2024-22":1}}},"text":"A screen for bacterial endosymbionts in the model organisms Tribolium castaneum, T. confusum, Callosobruchus maculatus, and related species.\nReproductive parasites such as Wolbachia are extremely widespread amongst the arthropods and can have a large influence over the reproduction and fitness of their hosts. Undetected infections could thus confound the results of a wide range of studies that focus on aspects of host behavior, reproduction, fitness, and degrees of reproductive isolation. This potential problem has already been underlined by work investigating the incidence of Wolbachia infections in stocks of the model system Drosophila melanogaster. Here we survey a range of lab stocks of further commonly used model arthropods, focusing especially on the flour beetles Tribolium castaneum and Tribolium confusum, the cowpea weevil Callosobruchus maculatus and related species (Coleoptera: Tenebrionidae and Bruchidae). These species are widespread stored product pests so knowledge of infections with symbionts further has potential use in informing biocontrol measures. Beetles were assessed for infection with 3 known microbial reproductive parasites: Wolbachia, Rickettsia, Spiroplasma. Infections with some of these microbes were found in some of the lab stocks studied, although overall infections were relatively rare. The consequences of finding infections in these or other species and the type of previous studies likely to be affected most are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":33768971,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":6,"2024-22":1,"2024-30":1,"unknown":2}}},"text":"Methylomes in Vegans versus Pescatarians and Nonvegetarians.\nEpigenetic studies in animal models have demonstrated that diet affects gene regulation by altering methylation patterns. We interrogated methylomes in humans who have different sources of protein in their diet. We compared methylation of DNA isolated from buffy coat in 38 vegans, 41 pescatarians and 68 nonvegetarians. Methylation data were obtained using Infinium HumanMethylation450 arrays and analyzed using the Partek Genomic software. Differences in differentially methylated sites were small, though with the use of relaxed statistical tests we did identify diet-associated differences. To further test the validity of these observations, we performed separate and independent comparisons of the methylation differences between vegans and nonvegetarians, and between vegans and pescatarians. The detected differences were then examined to determine if they were enriched in specific pathways. Pathway analysis revealed enrichment of several specific processes, including homeobox transcription and glutamate transport. The detected differences in DNA methylation patterns between vegans, pescatarians, and nonvegetarians enabled us to identify 77 CpG sites that may be sensitive to diet and\/or lifestyle, though high levels of individual-specific differences were also noted.","subset":"pubmed_abstract"} +{"meta":{"pmid":31484832,"dup_signals":{"dup_doc_count":41,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2023-14":10,"2020-45":2,"2020-24":1,"2020-10":5,"2020-05":1,"2019-47":5,"2019-39":10,"2023-50":1,"2024-18":2}}},"text":"High-fat diet-induced vagal afferent dysfunction via upregulation of 2-pore domain potassium TRESK channel.\nResearch shows that rats and humans on a high-fat diet (HFD) are less sensitive to satiety signals known to act via vagal afferent pathways. We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ganglia (NG) and decreased vagal response to satiety signals, which contribute to hyperphagia. We show that a 2-week HFD caused an upregulation of 2-pore domain TWIK-related spinal cord K+ (TRESK) and TWIK-related acid-sensitive K+ 1 (TASK1) channels by 330% \u00b1 50% and 60% \u00b1 20%, respectively, in NG. Patch-clamp studies of isolated NG neurons demonstrated a decrease in excitability. In vivo single-unit NG recordings showed that a 2-week HFD led to a 55% reduction in firing frequency in response to CCK-8 or leptin stimulation. NG electroporation with TRESK siRNA restored NG responsiveness to CCK-8 and leptin. Rats fed a 2-week HFD consumed ~40% more calories compared with controls. Silencing NG TRESK but not TASK1 channel expression in HFD-fed rats restored normal calorie consumption. In conclusion, HFD caused upregulation of TRESK channels, resulting in NG hyperpolarization and decreased vagal responsiveness to satiety signals. This finding provides a pharmacological target to prevent or treat HFD-induced hyperphagia.","subset":"pubmed_abstract"} +{"meta":{"pmid":20458324,"dup_signals":{"dup_doc_count":14}},"text":"Differential effects of high MUFA with high or low P\/S ratio (polyunsaturated to saturated fatty acids) on improving hepatic lipolytic enzymes and mediating PPAR\u03b3 related with lipoprotein lipase and hormone-sensitive lipase of white adipose tissue in diet-induced obese hamster.\nThe aim of this study was to assess the relationship between high monounsaturated fatty acids (MUFAs) with different levels of polyunsaturated-to-saturated fatty acid (P\/S) ratios and body fat loss in diet-induced obesity (DIO) models. Male Golden Syrian hamsters were randomly assigned to the control group (n=12) and obesity group (n=24) for 4 weeks of the high-fat DIO period; afterward, six hamsters from each group were killed. The remaining control hamsters were still fed a low-fat diet. For an additional 8 weeks, the remaining obesity hamsters were switched to a low-fat diet and subdivided into three subgroups (n=6\/group): the obesity-control (ObC) group, high MUFA with high P\/S ratio oil (HMHR) group and olive oil (OO) group. Serum insulin and leptin concentrations were measured, and hepatic fatty acid metabolic enzymes and adipose differentiation markers were determined using enzyme activities analysis, western blot and semiquantification reverse-transcription PCR. No difference was observed in the mean energy intake through all study periods. After the DIO period, the obesity group increased in weight gain and epididymal fat weight compared with the control group. DIO hamsters in the HMLR group had significant reductions in white adipose tissue deposition and plasma leptin levels, suppression in adipose peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) and lipoprotein lipase (LPL) mRNA expressions and increases in hepatic acyl-CoA oxidase and carnitine palmitoyltransferase-I activities and mRNA levels compared with those in the ObC group. The HMHR group had upregulated phosphorylation of hormone-sensitive lipase (HSL) relative to total HSL protein levels compared with the OO group. However, the OO group had significantly elevated hepatic de novo lipogenesis compared with the HMHR group. HMHR seemed to be beneficial in depleting white adipose tissue accumulation by decreasing adipose PPAR\u03b3 and LPL mRNA expressions and mediating phosphorylation of HSL, and by improving hepatic lipolytic enzyme activities and mRNA expressions involved in \u03b2-oxidation in DIO hamsters.","subset":"pubmed_abstract"} +{"meta":{"pmid":25563650,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":13}}},"text":"Synergistic effect of angiotensin II on vascular endothelial growth factor-A-mediated differentiation of bone marrow-derived mesenchymal stem cells into endothelial cells.\nIncreased levels of angiotensin II (Ang II) and activity of Ang II receptor type 1 (AT1R) elicit detrimental effects in cardiovascular disease. However, the role of Ang II receptor type 2 (AT2R) remains poorly defined. Mesenchymal stem cells (MSCs) replenish and repair endothelial cells in the cardiovascular system. Herein, we investigated a novel role of angiotensin signaling in enhancing vascular endothelial growth factor (VEGF)-A-mediated differentiation of MSCs into endothelial cells (ECs). Bone marrow was aspirated from the femurs of Yucatan microswine. MSCs were extracted via ficoll density centrifugation technique and were strongly immunopositive for MSC markers, CD44, CD90, and CD105, but negative for hematopoietic markers, CD14 and CD45. Subsequently, na\u00efve MSCs were differentiated for 10 days in varying concentrations and combinations of VEGF-A, Ang II, and AT1R or AT2R antagonists. Markers specific to ECs were determined by FACS analysis. AT1R and AT2R expression and cellular localization was demonstrated in MSCs stimulated with VEGF-A and Ang II via quantitative RT-PCR and immunofluorescence, respectively. Differentiation of na\u00efve MSCs in media containing Ang II (2 ng\/ml) plus low-dose VEGF-A (2 ng\/ml) produced a significantly higher percentage of cells that were positive for expression of EC markers (for example, platelet endothelial cell adhesion molecule, vascular endothelial Cadherin and von Willebrand factor) compared to VEGF-A alone. Ang II alone failed to induce EC marker expression. MSCs differentiated with the combination of Ang II and VEGF-A were capable of forming capillary tubes using an in vitro angiogenesis assay. Induction of EC marker expression was greatly attenuated by co-treatment of Ang II\/VEGF-A with the AT2R antagonist PD123319, but not the AT1R antagonist telmisartan. We report the presence of functional AT2R receptor on porcine bone marrow-derived MSCs, where it positively regulates EC differentiation. These findings have significant implications toward therapeutic approaches based on activation of AT2R, which could be a means to stimulate regeneration of damaged endothelium and prevent vascular thrombosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":2380794,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Long-term consistency of nutrient intakes in humans.\nConsistency of intake over time for calcium, phosphorus, protein and energy, as estimated from diet diaries, was studied prospectively in two groups of women. One group provided short-term data (n = 165), and the other, data spanning intervals of up to 20 y (n = 164). Although group average intakes changed little, there was a great deal of individual variation. Even at intervals as short as 6 m, current intake estimates accounted for only about 40% of the variance of intakes at an earlier time. Over longer intervals, the predictive value of one estimate in respect to a second deteriorated even further. Thus, across 5 y, less than 25% of the variance of all four nutrient intakes could be accounted for by current intake. The 95% confidence interval for an estimate of earlier intake based upon a later measurement was more than +\/- 700 mg for calcium, the least consistent nutrient. The other three nutrients showed nearly identical interstudy consistency, with uncertainties relative to their respective means being about half as large as for calcium. These data show that accurate longitudinal estimates of intake require continuous, prospective monitoring and that current intake is not a good estimator of past intake for most nutrients, especially for calcium.","subset":"pubmed_abstract"} +{"meta":{"pmid":28297706,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Phytoplankton can actively diversify their migration strategy in response to turbulent cues.\nMarine phytoplankton inhabit a dynamic environment where turbulence, together with nutrient and light availability, shapes species fitness, succession and selection. Many species of phytoplankton are motile and undertake diel vertical migrations to gain access to nutrient-rich deeper layers at night and well-lit surface waters during the day. Disruption of this migratory strategy by turbulence is considered to be an important cause of the succession between motile and non-motile species when conditions turn turbulent. However, this classical view neglects the possibility that motile species may actively respond to turbulent cues to avoid layers of strong turbulence. Here we report that phytoplankton, including raphidophytes and dinoflagellates, can actively diversify their migratory strategy in response to hydrodynamic cues characteristic of overturning by Kolmogorov-scale eddies. Upon experiencing repeated overturning with timescales and statistics representative of ocean turbulence, an upward-swimming population rapidly (5-60 min) splits into two subpopulations, one swimming upward and one swimming downward. Quantitative morphological analysis of the harmful-algal-bloom-forming raphidophyte Heterosigma akashiwo together with a model of cell mechanics revealed that this behaviour was accompanied by a modulation of the cells' fore-aft asymmetry. The minute magnitude of the required modulation, sufficient to invert the preferential swimming direction of the cells, highlights the advanced level of control that phytoplankton can exert on their migratory behaviour. Together with observations of enhanced cellular stress after overturning and the typically deleterious effects of strong turbulence on motile phytoplankton, these results point to an active adaptation of H. akashiwo to increase the chance of evading turbulent layers by diversifying the direction of migration within the population, in a manner suggestive of evolutionary bet-hedging. This migratory behaviour relaxes the boundaries between the fluid dynamic niches of motile and non-motile phytoplankton, and highlights that rapid responses to hydrodynamic cues are important survival strategies for phytoplankton in the ocean.","subset":"pubmed_abstract"} +{"meta":{"pmid":38069729,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Spin-Mapping Methods for Simulating Ultrafast Nonadiabatic Dynamics.\nMany chemical reactions exhibit nonadiabatic effects as a consequence of coupling between electronic states and\/or interaction with light. While a fully quantum description of nonadiabatic reactions is unfeasible for most realistic molecules, a more computationally tractable approach is to combine a classical description of the nuclei with a quantum description of the electronic states. Combining the formalisms of quantum and classical dynamics is however a difficult problem for which standard methods (such as Ehrenfest dynamics and surface hopping) may be insufficient. In this article, we review a new trajectory-based approach developed in our group that is able to describe nonadiabatic dynamics with a higher accuracy than previous approaches but for a similar level of computational effort. This method treats the electronic states with a phase-space representation for discrete-level systems, which in the two-level case is analogous to a spin-\u00bd. We point out the key features of the method and demonstrate its use in a variety of applications, including ultrafast transfer through conical intersections, damped coherent excitation under coupling to a strong light field, and nonlinear spectroscopy of light-harvesting complexes.","subset":"pubmed_abstract"} +{"meta":{"pmid":23035854,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2015-11":1,"unknown":8}}},"text":"Subcutaneous mastectomy in female-to-male transsexuals: a retrospective cohort-analysis of 202 patients.\nSubcutaneous mastectomy is the first surgical procedure to be completed by female to male transsexuals after appropriate mental health and endocrine therapy. Objectives of subcutaneous mastectomy in this group are to masculinize the chest by the removal of breast tissue and skin excess, reduction and proper positioning of the nipple-areola complex, obliteration of the infra-mammary fold, and ideally with a minimal of chest wall scars. In this study, the largest series of subcutaneous mastectomies in female-to-male transsexuals to date is presented. Our aim was to determine relations between surgical technique, risk factors, complications, reoperations and secondary corrections in female-to-male transsexuals. We performed a retrospective survey study on 404 mastectomies in 202 female-to-male transsexuals during the period of 2000-2011. Primary outcomes for this study were complication rate, acute reoperations, secondary corrections, surgical time, and length of hospital stay in relation to the surgical technique used. The average age of these patients at time of the intervention was 31 years (\u00b110) with an average BMI of 25 kg\/m(2) (\u00b14). The chosen technique depended strongly on breast volume, which, in turn, was strongly related to BMI and age. The number of acute reoperations and secondary corrections depended on the surgical technique. The total rate of acute complications was 5.0%. This percentage was highest in surgeries without skin resection (10.5%). To improve overall aesthetic results, the following secondary corrections were performed: nipple and\/or areola corrections (8.9%), scar revisions (12.6%), and chest contouring (17.8%). This study shows a correlation between the surgical technique, complication rate, and length of hospital stay. In general, the larger the breast, the larger the scars that remain after the operation. On the other hand, the smaller the scars resulting from the operation, the higher the risk of hematoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":29316357,"dup_signals":{"dup_doc_count":28,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":26}}},"text":"Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.\nTo determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic\/racial inception cohort of patients with systemic lupus erythematosus (SLE). A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid\/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics\/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE. CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.","subset":"pubmed_abstract"} +{"meta":{"pmid":18368531,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Internalization and desensitization of adenosine receptors.\nUntil now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A(1), A(2A), A(2B) and A(3) receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A(1)Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A(2A)R and A(2B)R undergo much faster downregulation, usually shorter than 1 h. The A(3)R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A(3)R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23573489,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Timing of nephrology referral: influence on mortality and morbidity in chronic kidney disease.\nFew studies in India as well as in most developing countries have compared the mortality and morbidity rates between chronic kidney disease patients who were referred early to nephrologists and those who were referred late. To study the mortality and morbidity patterns and to compare the various clinical parameters between the abovementioned early and late referrals. Fifty consecutive chronic kidney disease patients were followed up for one year. They were then classified as early referral (patients who underwent dialysis more than three months after the referral) and late referral (patients who underwent dialysis within three months of the referral). Clinical, laboratory parameters, and mortality patterns were compared between the two groups. The blood pressure, hemoglobin, glomerular filtration rate, and calcium and phosphate values were better in the early referral group. Among the 24 complications that occurred, 17 (70.8%) were seen among the patients who were referred late. Among the 13 deaths that occurred, only one belonged to the early referral group. We observed that the mortality rate and clinical parameters were better in patients who were referred early to nephrologists.","subset":"pubmed_abstract"} +{"meta":{"pmid":2203726,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-22":1,"unknown":11}}},"text":"Effect of an acute bout of exercise on glucose disposal in human obesity.\nThe effect of acute exercise on insulin action has been studied in six obese (150-250% ideal body weight) non-insulin-dependent diabetics (OD), seven obese normoglycemics (ON), and six lean healthy controls (LC). Using a three-stage euglycemic clamp, the metabolic clearance rate (MCR) of glucose under increasing insulin concentrations was measured. The insulin dose-response curve was assessed on two separate occasions: 1) a base-line test and 2) 1 h after aerobic treadmill exercise at a steady-state heart rate of 150-160 beats\/min. In the base-line test, under all insulin levels, glucose MCR was significantly lower in obese compared with lean individuals (P less than 0.01). Exercise increased glucose MCR at the highest hormonal concentrations applied to 124 and 134% of base line in OD and in ON, respectively (P less than 0.05); the insulin concentration required for one-half of the maximal clearance rate of glucose achieved in this study decreased from 200 to 130 and from 160 to 95 microU\/ml in OD and ON, respectively (P less than 0.05). The changes in these parameters were insignificant in LC. It is suggested that acute exercise affected the insulin dose-response curve in OD and in ON but not in LC; although enhanced by exercise, glucose MCR remained significantly lower in both obese groups compared with control subjects. We concluded that insulin resistance, which accompanies extreme obesity, could be markedly decreased but not completely reversed by one bout of exercise.","subset":"pubmed_abstract"} +{"meta":{"pmid":11904177,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2023-14":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":2,"2021-39":1,"2021-21":1,"2021-10":1,"2020-50":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-50":1}}},"text":"Cysteinyl-tRNA formation and prolyl-tRNA synthetase.\nAminoacyl-tRNA (AA-tRNA) formation is a key step in protein biosynthesis. This reaction is catalyzed with remarkable accuracy by the AA-tRNA synthetases, a family of 20 evolutionarily conserved enzymes. The lack of cysteinyl-tRNA (Cys-tRNA) synthetase in some archaea gave rise to the discovery of the archaeal prolyl-tRNA (Pro-tRNA) synthetase, an enzyme capable of synthesizing Pro-tRNA and Cys-tRNA. Here we review our current knowledge of this fascinating process.","subset":"pubmed_abstract"} +{"meta":{"pmid":8189058,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell.\nTCR-gamma delta cells, a T cell subset present in the epithelial and lymphoid tissues, have been implicated in viral and bacterial infections. We have identified a TCR-gamma delta clone (TgI4.4) that, unlike TCR-alpha beta cells, recognizes a herpes simplex virus type 1 transmembrane glycoprotein, gI, in an MHC class I- and class II-independent fashion. The TCR of TgI4.4 is composed of rearranged V delta 8 (a V alpha 2 family member) and V gamma 1.2 variable genes, a heterodimeric pair not previously described. Furthermore, anti-V alpha 2 mAbs are sufficient to block recognition of the gI ligand. Strikingly, anti-gI Abs also are capable of blocking recognition, a phenomena that is very rare in TCR-alpha beta Ag recognition. Therefore, to dissect the mechanism involved in this unique form of Ag recognition, we constructed a mutant of gI, gIt, that lacks cell surface expression upon transfection into APCs. This form of gI was not sufficient for Ag presentation. In contrast, wild-type gI expressed in the Ag-processing mutant cell, RMA-S, is recognized by TgI4.4, suggesting that gI presentation occurs independently of classical Ag-processing pathways. In fact, through the use of a soluble recombinant gI molecule, gI-Ig, we show that TgI4.4 can recognize whole, unprocessed gI protein in the absence of any APCs. These results suggest that there exist alternate and novel forms of TCR Ag recognition, and that the TCR-gamma delta clone, TgI4.4, may represent a novel T cell subset that, during pathogenic challenge, may respond directly to Ags on the surfaces of bacteria and viruses.","subset":"pubmed_abstract"} +{"meta":{"pmid":2522498,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells.\nThe activation of highly purified murine peripheral T cells in vitro by Con A is dependent on a co-stimulatory signal that is not IL-1 or IL-2. Previous evidence has demonstrated that the recently defined lymphokine IL-6 could provide costimulatory activity for purified T cells cultured with Con A. In this report we demonstrate that IL-7 also has potent co-stimulatory activity for purified murine T cells, as well as its previously described ability to support the growth of pre-B cells in Witte-Whitlock cultures. When rIL-7 was added to cultures of purified T cells together with Con A, it induced the expression of IL-2 receptors, IL-2 production, and consequently proliferation. In addition, IL-7 exhibited the same magnitude of activity in this assay as IL-6. Also, anti-IL-6 antibody which inhibited the IL-6-induced response had no effect on the IL-7 response. Thus, IL-7 does not act by inducing IL-6. These results demonstrate that IL-7, a potent growth stimulus for pre-B cells, also has a role in T cell activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29434080,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"Exploring peptide hormones in plants: identification of four peptide hormone-receptor pairs and two post-translational modification enzymes.\nThe identification of hormones and their receptors in multicellular organisms is one of the most exciting research areas and has lead to breakthroughs in understanding how their growth and development are regulated. In particular, peptide hormones offer advantages as cell-to-cell signals in that they can be synthesized rapidly and have the greatest diversity in their structure and function. Peptides often undergo post-translational modifications and proteolytic processing to generate small oligopeptide hormones. In plants, such small post-translationally modified peptides constitute the largest group of peptide hormones. We initially explored this type of peptide hormone using bioassay-guided fractionation and later by in silico gene screening coupled with biochemical peptide detection, which led to the identification of four types of novel peptide hormones in plants. We also identified specific receptors for these peptides and transferases required for their post-translational modification. This review summarizes how we discovered these peptide hormone-receptor pairs and post-translational modification enzymes, and how these molecules function in plant growth, development and environmental adaptation.","subset":"pubmed_abstract"} +{"meta":{"pmid":17732248,"dup_signals":{"dup_doc_count":40,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2018-47":1,"2018-39":1,"2018-13":1,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":1,"2017-39":3,"2017-34":1,"2017-30":2,"2017-26":1,"2017-22":1,"2017-17":3,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":1,"2016-40":2,"2016-36":2,"2016-30":1,"2016-22":1,"2016-07":1,"2019-04":1,"2017-13":2}}},"text":"Simple systems that exhibit self-directed replication.\nBiological experience and intuition suggest that self-replication is an inherently complex phenomenon, and early cellular automata models support that conception. More recently, simpler computational models of self-directed replication called sheathed loops have been developed. It is shown here that \"unsheathing\" these structures and altering certain assumptions about the symmetry of their components leads to a family of nontrivial self-replicating structures, some substantially smaller and simpler than those previously reported. The dependence of replication time and transition function complexity on initial structure size, cell state symmetry, and neighborhood are examined. These results support the view that self-replication is not an inherently complex phenomenon but rather an emergent property arising from local interactions in systems that can be much simpler than is generally believed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8731618,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-21":1,"2021-04":1,"2020-34":1,"2020-10":1,"2019-47":1,"2019-22":1,"2018-05":1,"2017-30":1,"2014-23":1,"2022-33":1,"2024-22":1}}},"text":"Which smokers are helped to give up smoking using transdermal nicotine patches? Results from a randomized, double-blind, placebo-controlled trial.\nNicotine replacement therapy is effective in helping people to give up smoking. The three forms now available--transdermal patches, chewing gum and nasal spray--deliver nicotine at different rates and to different levels. Therefore, it might be expected that smokers with different characteristics, and at different levels of nicotine dependence, will be helped more by one or other method. The aim of the study was to examine whether the effectiveness of transdermal patches is related to nicotine dependence or to other smoker characteristics and to investigate factors predicting smoking cessation using patches. Data from a randomized, double-blind, placebo-controlled trial of nicotine transdermal patches were analysed retrospectively. The trial, conducted in 1990-1992, involved 1686 patients recruited from 19 general practices in Oxfordshire. The main outcome measure was continuous smoking cessation from 8 to 52 weeks after the start of patch use, biochemically validated at 12, 24 and 52 weeks. The effectiveness of the patches was measured by the relative odds of sustained cessation using nicotine patches compared with placebo patches. Nicotine transdermal patches were more effective in smokers with moderate nicotine dependence [odds ratio (OR) 1.94; 95% confidence interval (CI) 1.24-3.04] than in mildly or highly dependent smokers (OR 0.98; 95% CI 0.58-1.65) (difference in ORs P < 0.05) and more effective in those aged 24-49 years (OR 1.89; 95% CI 1.24-2.87) than in older smokers aged 50-65 years (OR 0.88; 95% CI 0.49-1.59) (difference in ORs P < 0.05). Abstinence from smoking in the first week of the trial was the strongest predictor of sustained cessation and was more common among smokers using nicotine patches than those using placebo patches (33% of 842 compared with 22% of 844; P < 0.001). Of first-week abstainers, 25 and 28% of 277 and 182 in the nicotine and placebo groups, respectively, achieved sustained cessation compared with 4% of 565 and 2% of 662 first-week smokers. Nicotine transdermal patches were most effective for smokers with moderate nicotine dependence and for younger smokers. Early abstinence from smoking was the strongest predictor of sustained cessation. A week's trial of the patch proceeding to longer term use if abstinence is achieved may be an effective policy.","subset":"pubmed_abstract"} +{"meta":{"pmid":30612219,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2022-05":1,"2021-49":1,"2021-25":1,"2020-29":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-22":2,"2019-18":1,"2019-13":1,"2019-04":2,"2022-40":1}}},"text":"Gene Expression Profiles of Two Coral Species with Varied Resistance to Ocean Acidification.\nRecent studies have indicated that various corals might have different degrees of resistance to elevated CO2 levels. However, the underlying molecular mechanism accounting for these differences is still poorly understood. In this study, RNA-seq data were analyzed to identify differentially expressed genes in two coral species (Acropora austera and Acropora cerealis) in response to high CO2 levels. The calcification rates were higher in high CO2 treatment than the control in A. austera, but was not significantly different in A. cerealis. A KEGG database search revealed that in both coral species, most Ca2+ transporters were present in the calcium signaling pathway, which could be important in the CO2 regulation of coral calcification. The gene expression levels of many CO2 and HCO3- transporters were not affected by elevated CO2. Nevertheless, high CO2 levels did have an effect on the expression of certain Ca2+ transporters. The upregulation of Ca2+ transporters likely explained the higher resistance of A. austera to high CO2 than A. cerealis.","subset":"pubmed_abstract"} +{"meta":{"pmid":28406813,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in Mechanically Ventilated Patients.\nLung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of hypercapnia and hypercapnic acidosis in patients requiring mechanical ventilation. Multicenter, binational, retrospective study aimed to assess the impact of compensated hypercapnia and hypercapnic acidosis in patients receiving mechanical ventilation. Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database over a 14-year period where 171 ICUs contributed deidentified data. Patients were classified into three groups based on a combination of pH and carbon dioxide levels (normocapnia and normal pH, compensated hypercapnia [normal pH with elevated carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay. Logistic regression analysis was used to identify the independent association of hypercapnia and hypercapnic acidosis with hospital mortality. Nil. A total of 252,812 patients (normocapnia and normal pH, 110,104; compensated hypercapnia, 20,463; and hypercapnic acidosis, 122,245) were included in analysis. Patients with compensated hypercapnia and hypercapnic acidosis had higher Acute Physiology and Chronic Health Evaluation III scores (49.2 vs 53.2 vs 68.6; p < 0.01). The mortality was higher in hypercapnic acidosis patients when compared with other groups, with the lowest mortality in patients with normocapnia and normal pH. After adjusting for severity of illness, the adjusted odds ratio for hospital mortality was higher in hypercapnic acidosis patients (odds ratio, 1.74; 95% CI, 1.62-1.88) and compensated hypercapnia (odds ratio, 1.18; 95% CI, 1.10-1.26) when compared with patients with normocapnia and normal pH (p < 0.001). In patients with hypercapnic acidosis, the mortality increased with increasing PCO2 until 65 mm Hg after which the mortality plateaued. Hypercapnic acidosis during the first 24 hours of intensive care admission is more strongly associated with increased hospital mortality than compensated hypercapnia or normocapnia.","subset":"pubmed_abstract"} +{"meta":{"pmid":17002767,"dup_signals":{"dup_doc_count":34,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2022-05":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-43":1,"2018-30":1,"2018-13":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2023-06":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Using scalar models for precautionary assessments of threatened species.\nScalar population models, commonly referred to as count-based models, are based on time-series data of population sizes and may be useful for screening-level ecological risk assessments when data for more complex models are not available. Appropriate use of such models for management purposes, however, requires understanding inherent biases that may exist in these models. Through a series of simulations, which compared predictions of risk of decline of scalar and matrix-based models, we examined whether discrepancies may arise from different dynamics displayed due to age structure and generation time. We also examined scalar and matrix-based population models of 18 real populations for potential patterns of bias in population viability estimates. In the simulation study, precautionary bias (i.e., overestimating risks of decline) of scalar models increased as a function of generation time. Models of real populations showed poor fit between scalar and matrix-based models, with scalar models predicting significantly higher risks of decline on average. The strength of this bias was not correlated with generation time, suggesting that additional sources of bias may be masking this relationship. Scalar models can be useful for screening-level assessments, which should in general be precautionary, but the potential shortfalls of these models should be considered before using them as a basis for management decisions.","subset":"pubmed_abstract"} +{"meta":{"pmid":24204887,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Characterization of the Viable but Nonculturable (VBNC) State in Saccharomyces cerevisiae.\nThe Viable But Non Culturable (VBNC) state has been thoroughly studied in bacteria. In contrast, it has received much less attention in other microorganisms. However, it has been suggested that various yeast species occurring in wine may enter in VBNC following sulfite stress.In order to provide conclusive evidences for the existence of a VBNC state in yeast, the ability of Saccharomyces cerevisiae to enter into a VBNC state by applying sulfite stress was investigated. Viable populations were monitored by flow cytometry while culturable populations were followed by plating on culture medium. Twenty-four hours after the application of the stress, the comparison between the culturable population and the viable population demonstrated the presence of viable cells that were non culturable. In addition, removal of the stress by increasing the pH of the medium at different time intervals into the VBNC state allowed the VBNC S. cerevisiae cells to \"resuscitate\". The similarity between the cell cycle profiles of VBNC cells and cells exiting the VBNC state together with the generation rate of cells exiting VBNC state demonstrated the absence of cellular multiplication during the exit from the VBNC state. This provides evidence of a true VBNC state. To get further insight into the molecular mechanism pertaining to the VBNC state, we studied the involvement of the SSU1 gene, encoding a sulfite pump in S. cerevisiae. The physiological behavior of wild-type S. cerevisiae was compared to those of a recombinant strain overexpressing SSU1 and null \u0394ssu1 mutant. Our results demonstrated that the SSU1 gene is only implicated in the first stages of sulfite resistance but not per se in the VBNC phenotype. Our study clearly demonstrated the existence of an SO2-induced VBNC state in S. cerevisiae and that the stress removal allows the \"resuscitation\" of VBNC cells during the VBNC state.","subset":"pubmed_abstract"} +{"meta":{"pmid":28718811,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Tissue Specific Labeling in Proteomics.\nMass spectrometry-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples. While it is routinely used for the characterization of simple cell line systems, the analysis of the cell specific proteome in multicellular organisms and tissues poses a significant challenge. Isolating a subset of cells from tissues requires mechanical and biochemical separation or sorting, a process which can alter cellular signaling, and thus, the composition of the proteome. Recently, several approaches for cell selective labeling of proteins, that include bioorthogonal amino acids, biotinylating enzymes, and genetic tools, have been developed. These tools facilitate the selective labeling of proteins, their interactome, or of specific cell types within a tissue or an organism, while avoiding the difficult and contamination-prone biochemical separation of cells from the tissue. In this review, we give an overview of existing techniques and their application in cell culture models and whole animals.","subset":"pubmed_abstract"} +{"meta":{"pmid":30950783,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Pseudomonas urumqiensis sp. nov., isolated from rhizosphere soil of Alhagi sparsifolia.\nA motile, Gram-stain-negative, fusiform-shaped bacterium, designated strain T3T, was isolated from rhizosphere soil of Alhagi sparsifolia, collected from Xinjiang, PR China. Strain T3T grew at 15-42 \u00b0C, pH 4-9 and 1-6 % (w\/v) NaCl concentrations. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain T3T belonged to the genus Pseudomonas and showed highest similarity of 98.6 % to Pseudomonas azotifigens JCM 12708T, followed by Pseudomonas balearica DSM 6083T (97.8 %), Pseudomonas matsuisoli JCM 30078T (97.7 %), Pseudomonas furukawaii KF707T (97.7 %), Pseudomonas tarimensis CCTCC AB 2013065T (97.3 %) and Pseudomonas indica DSM 14015T (97.1 %). Analysis based on concatenated gene sequences of 16S rRNA, rpoB and gyrB further confirmed the phylogenetic assignment of strain T3T. The Genome-to-Genome Distance Calculator results for P. azotifigens JCM12708T and P. balearica DSM 6083T were 28.7\u00b14.4% and 24.1\u00b12.4 %, and the average nucleotide identity scores were 81.3 and 78.1 %. The major polar lipids of strain T3T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The predominant quinone was Q-9. The major fatty acids comprised summed feature 8 (C18 : 1\u03c96c\/C18 : 1\u03c97c; 37.7 %), summed feature 3 (C16 : 1\u03c96c\/C16 : 1\u03c97c; 28.2 %), C16 : 0 (15.6 %), C12 : 0 (7.8 %), C10 : 03-OH (3.0 %) and C12 : 03-OH (2.6 %). The G+C content of the genomic DNA of the type strain was 65.3 mol%. It is obvious from the phylogenetic, phenotypic and chemotaxonomic data that strain T3T represents a novel species of the genus Pseudomonas, for which the name Pseudomonasurumqiensis sp. nov., is proposed. The type strain is T3T (=ACCC 60124T=JCM 32830T).","subset":"pubmed_abstract"} +{"meta":{"pmid":31377695,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A protocol for a discrete choice experiment: understanding patient medicine preferences for managing chronic non-cancer pain.\nHigh rates of chronic non-cancer pain (CNCP), concerns about adverse effects including dependence among those prescribed potent pain medicines, the recent evidence supporting active rather than passive management strategies and a lack of funding for holistic programme have resulted in challenges around decision making for treatment among clinicians and their patients. Discrete choice experiments (DCEs) are one way of assessing and valuing treatment preferences. Here, we outline a protocol for a study that assesses patient preferences for CNCP treatment. A final list of attributes (and their levels) for the DCE was generated using a detailed iterative process. This included a literature review, a focus group and individual interviews with those with CNCP and clinicians who treat people with CNCP. From this process a list of attributes was obtained. Following a review by study investigators including pain and addiction specialists, pharmacists and epidemiologists, the final list of attributes was selected (number of medications, risk of addiction, side effects, pain interference, activity goals, source of information on pain, provider of pain care and out-of-pocket costs). Specialised software was used to construct an experimental design for the survey. The survey will be administered to two groups of participants, those from a longitudinal cohort of patients receiving opioids for CNCP and a convenience sample of patients recruited through Australia's leading pain advocacy body (Painaustralia) and their social media and website. The data from the two participant groups will be initially analysed separately, as their demographic and clinical characteristics may differ substantially (in terms of age, duration of pain and current treatment modality). Mixed logit and latent class analysis will be used to explore heterogeneity of responses. Ethics approval was obtained from the University of New South Wales Sydney Human Ethics committee HC16511 (for the focus group discussions, the one-on-one interviews and online survey) and HC16916 (for the cohort). A lay summary will be made available on the National Drug and Alcohol Research Centre website and Painaustralia's website. Peer review papers will be submitted, and it is expected the results will be presented at relevant pain management conferences nationally and internationally. These results will also be used to improve understanding of treatment goals between clinicians and those with CNCP.","subset":"pubmed_abstract"} +{"meta":{"pmid":24920659,"dup_signals":{"dup_doc_count":61,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2021-10":3,"2020-40":1,"2020-16":3,"2019-51":1,"2019-47":2,"2019-43":1,"2019-30":2,"2019-22":4,"2019-18":1,"2019-13":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":2,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":1,"2017-17":2,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":2,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-27":1,"2021-25":1,"2017-13":2}}},"text":"Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs.\nGaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis of bacteria but reduced production of intracellular reactive oxygen species and impaired chemotaxis. The disease phenotype was reversed with a noninhibitory small-molecule chaperone drug that enhanced glucocerebrosidase activity in the macrophages, reduced glycolipid storage, and normalized chemotaxis and production of reactive oxygen species. Macrophages differentiated from patient monocytes or patient-derived iPSCs provide cellular models that can be used to investigate disease pathogenesis and facilitate drug development.","subset":"pubmed_abstract"} +{"meta":{"pmid":19705318,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"A longitudinal study of the effect of an interprofessional education curriculum on student satisfaction and attitudes towards interprofessional teamwork and education.\nThere has been limited research on the effect of interprofessional education (IPE) over time on the attitudes of undergraduate health and human service professional students. Previous research in this area has suggested that students from different professions report differing attitudes towards IPE and interprofessional teamwork, and such attitudes may also be influenced by other background characteristics of the students themselves (e.g., gender, age). The purpose of this study was to evaluate the longitudinal effect of the introduction of an IPE curriculum on students' attitudes towards IPE and teamwork. A time series study design was conducted to assess the attitudes of undergraduate health and human service professional students towards IPE and teamwork, and students were also asked to complete satisfaction surveys after IPE curriculum activities. Significant differences in the attitudes of students from different professions and their satisfaction with participation in IPE were reported over the duration of the study. Overall, student satisfaction with IPE participation was relatively positive; however the introduction of IPE curriculum during their undergraduate education did not appear to have a significant longitudinal effect on attitudes towards IPE or interprofessional teamwork. The findings have implications for the design and integration of IPE curriculum within existing uni-professional curriculum.","subset":"pubmed_abstract"} +{"meta":{"pmid":23862977,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Formulation and characterization of ethylcellulose microparticles containing .L-alanyl- L-glutamine peptide.\nThe L-alanyl-L-glutamine peptide (AGP) has been effective to promote acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and the oral administration of AGP is suggested to prevent prolonged hypoglycemia, such as nocturnal hypoglycemia. Considering the ability of AGP on glycemia recovery and AGP's fast metabolism, the aim of current study was to obtain and characterize ethylcellulose microparticles to deliver the drug for a prolonged time. Microparticles were prepared by simple and double emulsification\/hardening method and characterized by scanning electron microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro release. Spherical structures with a mean diameter between 9.30 \u00b5m and 13.19 \u00b5m were formed. TG analysis showed that the thermal stability of AGP was even more increased by encapsulation with ethylcellulose. In addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in a molecular way. Higher values of encapsulation efficiency were observed for the microparticles prepared by double emulsification (57.83-83.67%) than for those prepared by simple emulsification (18.37%). However, the last ones could release the peptide in a quicker and more extensive manner than those prepared by double emulsification. For the first time, microparticles containing AGP were developed and exhibited prolonged in vitro release as well as protection to the drug, and it could be considered as a dosage form for patients who suffer from insulin-induced hypoglycemia and\/or nocturnal hypoglycemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":12582642,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":4}}},"text":"Transpecific microsatellites for hard pines.\nMicrosatellites are difficult to recover from large plant genomes so cross-specific utilisation is an important source of markers. Fifty microsatellites were tested for cross-specific amplification and polymorphism to two New World hard pine species, slash pine ( Pinus elliottii var. elliottii) and Caribbean pine ( P. caribaea var. hondurensis). Twenty-nine (58%) markers amplified in both hard pine species, and 23 of these 29 were polymorphic. Soft pine (subgenus Strobus) microsatellite markers did amplify, but none were polymorphic. Pinus elliottii var. elliottii and P. caribaea var. hondurensis showed mutational changes in the flanking regions and the repeat motif that were informative for Pinus spp. phylogenetic relationships. Most allele length variation could be attributed to variability in repeat unit number. There was no evidence for ascertainment bias.","subset":"pubmed_abstract"} +{"meta":{"pmid":29424386,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-50":2,"2023-23":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2018-09":1,"2024-22":1}}},"text":"The effect of Agaricus brasiliensis extract supplementation on honey bee colonies.\nThis study was done to discover any beneficial effect of a medicinal mushroom Agaricus brasiliensis extract on the honey bee. Firstly, a laboratory experiment was conducted on 640 bees reared in 32 single-use plastic rearing cups. A. brasiliensis extract proved safe in all doses tested (50, 100 and 150 mg\/kg\/day) irrespective of feeding mode (sugar syrup or candy). Secondly, a three-year field experiment was conducted on 26 colonies treated with a single dose of A. brasiliensis extract (100 mg\/kg\/day) added to syrup. Each year the colonies were treated once in autumn and twice in spring. The treatments significantly increased colony strength parameters: brood rearing improvement and adult population growth were noticed more often than the increase in honey production and pollen reserves. These positive effects were mainly observed in April. In conclusion, A. brasiliensis extract is safe for the bees and helps maintaining strong colonies, especially in spring.","subset":"pubmed_abstract"} +{"meta":{"pmid":16156350,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2019-13":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-17":1,"2016-30":1,"2021-17":1}}},"text":"Spatio-temporal nonrigid registration for ultrasound cardiac motion estimation.\nWe propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method.","subset":"pubmed_abstract"} +{"meta":{"pmid":14977671,"dup_signals":{"dup_doc_count":13}},"text":"Intra-articular knee temperature changes: ice versus cryotherapy device.\nCryotherapy is commonly applied without research documenting the intra-articular (IA) temperature changes or subject discomfort between ice and a cryotherapy device. The null hypothesis is that no difference would be observed in IA temperature decline or subject tolerance between ice and the cryotherapy device in normal knees. Prospective, within-subject controlled clinical trial. Twelve subjects had IA temperature in suprapatellar pouch and skin recorded bilaterally after application of cryotherapy versus ice. Subject tolerance was recorded by 10-cm visual analog scale (VAS). Statistical evaluation was by Spearman's correlation analysis and paired, nonparametric Wilcoxon's signed rank test. Both significantly lowered (P < 0.001) skin and IA temperature with median decreases (ice\/cryotherapy) at 30 (3.3 degrees C\/2.2 degrees C), 60 (12.8 degrees C\/7.1 degrees C), and 90 (15.2 degrees C\/9.7 degrees C) minutes. However, ice lowered the IA temperature significantly more than the cryotherapy device (P < 0.001) and was more painful by VAS at 30 and 60 minutes (P < 0.01). Both methods produced large declines in skin and IA temperatures. However, ice was more effective yet resulted in higher pain scores. The authors hypothesize that IA temperatures below a threshold are associated with increased perceived pain.","subset":"pubmed_abstract"} +{"meta":{"pmid":35467925,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":1,"2024-10":1,"unknown":6}}},"text":"Are leaders still presumed white by default? Racial bias in leader categorization revisited.\nIn the United States, leaders of the highest valued companies, best-ranked universities, and most-consumed media outlets are more likely to be White than what would be expected based on White people's representation in the U.S. population. One explanation for this racial gap is that U.S. respondents' prototype of a leader is White by default-which is, in turn, what causes White (vs. non-White) people to be promoted up the organizational ladder more quickly. Although this explanation has empirical support, its central premise was recently challenged by experimental evidence documenting that U.S. respondents no longer associate leaders, more than nonleaders, with being White. To reconcile these contradictory findings, we conducted three preregistered experiments (N = 1,316) on the topic of whether leaders, more than nonleaders, continue to be associated with Whiteness (i.e., being categorized as White or being represented with stereotypically White qualities). Results suggest that associations between leaders and Whiteness hold up to scrutiny, but that detecting them may depend on what methods researchers employ. In particular, when researchers use direct methods of detecting racial assumptions (e.g., self-report measures), there appears to be no evidence of an association between leaders and Whiteness (Experiment 1). Yet, when researchers use more indirect methods of detecting racial assumptions (e.g., a Princeton trilogy task), an association between leaders and Whiteness readily emerges (Experiments 2 and 3). In short, although respondents refrain from freely expressing associations they may harbor between leaders and Whiteness, these associations do not appear to have dissipated with time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).","subset":"pubmed_abstract"} +{"meta":{"pmid":20824204,"dup_signals":{"dup_doc_count":25,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-39":1,"2018-51":1,"2018-09":1,"2017-30":1,"2017-04":1,"2023-40":1}}},"text":"From sea to sea: Canada's three oceans of biodiversity.\nEvaluating and understanding biodiversity in marine ecosystems are both necessary and challenging for conservation. This paper compiles and summarizes current knowledge of the diversity of marine taxa in Canada's three oceans while recognizing that this compilation is incomplete and will change in the future. That Canada has the longest coastline in the world and incorporates distinctly different biogeographic provinces and ecoregions (e.g., temperate through ice-covered areas) constrains this analysis. The taxonomic groups presented here include microbes, phytoplankton, macroalgae, zooplankton, benthic infauna, fishes, and marine mammals. The minimum number of species or taxa compiled here is 15,988 for the three Canadian oceans. However, this number clearly underestimates in several ways the total number of taxa present. First, there are significant gaps in the published literature. Second, the diversity of many habitats has not been compiled for all taxonomic groups (e.g., intertidal rocky shores, deep sea), and data compilations are based on short-term, directed research programs or longer-term monitoring activities with limited spatial resolution. Third, the biodiversity of large organisms is well known, but this is not true of smaller organisms. Finally, the greatest constraint on this summary is the willingness and capacity of those who collected the data to make it available to those interested in biodiversity meta-analyses. Confirmation of identities and intercomparison of studies are also constrained by the disturbing rate of decline in the number of taxonomists and systematists specializing on marine taxa in Canada. This decline is mostly the result of retirements of current specialists and to a lack of training and employment opportunities for new ones. Considering the difficulties encountered in compiling an overview of biogeographic data and the diversity of species or taxa in Canada's three oceans, this synthesis is intended to serve as a biodiversity baseline for a new program on marine biodiversity, the Canadian Healthy Ocean Network. A major effort needs to be undertaken to establish a complete baseline of Canadian marine biodiversity of all taxonomic groups, especially if we are to understand and conserve this part of Canada's natural heritage.","subset":"pubmed_abstract"} +{"meta":{"pmid":32369188,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Spiral valve parasites of blue and common thresher sharks as indicators of shark feeding behaviour and ecology.\nThis study documented the parasite faunas of the spiral valves of blue sharks Prionace glauca (L. 1758) and common thresher sharks Alopias vulpinus (Bonnaterre, 1788) caught in the California Current Large Marine Ecosystem (CCLME) north of the Mexican border. The spiral valves of 18 blue and 19 thresher sharks caught in the CCLME from 2009 to 2013 were examined for parasites. Seven parasite taxa were found in blue sharks and nine in threshers. The tetraphyllidean cestode Anthobothrium sp. (78% prevalence) was the most common parasite in blue sharks, and the phyllobothriid cestode Paraorygmatobothrium sp. (90% prevalence) was the most common in threshers. An adult nematode of the genus Piscicapillaria was found in threshers for the first time and may be a new species. Adult individuals of Hysterothylacium sp. were found in both shark species. The adult acanthocephalan Rhadinorhynchus cololabis and remains of the parasitic copepod Pennella sp. - both parasites of Pacific saury, Cololabis saira - were found in the intestines of threshers, indicating recent feeding on saury. This study paves the way for a more comprehensive examination, including more samples and a wider variety of shark species, to provide a greater understanding of shark feeding behaviour and possibly provide information on shark population biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":29741192,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":2,"2022-05":2,"2021-39":2,"2021-25":2,"2021-17":1,"2021-04":1,"2020-45":1,"2023-40":1,"2024-30":2,"2024-18":1,"2024-10":1}}},"text":"Seasonal Variation in Vitamin D Status among Frail Older Hospitalized Patients.\nSeasonal variation in 25-hydroxyvitamin D [25(OH)D] levels is the result of sunlight dependent skin synthesis of vitamin D. However, its presence is not studied in frail older hospitalized patients. We sought to investigate whether seasonal variation in 25(OH)D levels is evident among these patients. This study investigated older participants who were consecutively admitted between February 2015 and December 2016 to the geriatric acute care ward. Results of routine measurements of 25(OH)D at hospital admission were retrospectively analyzed and stratified according to months and seasons. Previous intake of vitamin D supplementation was derived from the patients' medical records. The study group comprised 679 participants (mean age 82.1\u00b18.2; 457 females), of which 78% had vitamin D deficiency. Older individuals not taking vitamin D supplements had a lower mean serum 25(OH)D than those receiving supplements. Of those patients with no vitamin D supplementation, 87.0% were vitamin D deficient and only 5% showing sufficient vitamin 25(OH)D. Further, there were neither monthly nor seasonal variations in vitamin 25(OH)D levels among these patients and their vitamin D levels stayed far below the recommended threshold of 20 ng\/ml across the seasons. Vitamin D deficiency was very prevalent in the subgroup of older hospitalized patients without vitamin D supplementation, irrespective of season. Since no seasonal variations in mean 25(OH)D levels was observed, sunlight dependent skin synthesis is unlikely to contribute to vitamin D status in these patients. Supplementation seems to be necessary to maintain desirable vitamin D levels among this population throughout the year.","subset":"pubmed_abstract"} +{"meta":{"pmid":23031662,"dup_signals":{"dup_doc_count":23,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":19}}},"text":"Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.\nThe effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level.","subset":"pubmed_abstract"} +{"meta":{"pmid":32027752,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK\/NF-\u03baB Signaling and Modulating Metabolome in the Piglet Intestine.\nProbiotic Lactobacillius rhamnosus GG (LGG) shows beneficial immunomodulation on cultured cell lines in vitro and in mouse models. The aim was to investigate the effects of LGG on intestinal injury and the underlying mechanisms by elucidating inflammatory signaling pathways and metabolomic response to LPS stimulation in the piglet intestine. Piglets (Duroc \u00d7 Landrace \u00d7 Large White, including males and female; 8.6 \u00b1 1.1 kg) aged 28 d were assigned to 3 groups (n = 6\/group): oral inoculation with PBS for 2 wk before intraperitoneal injection of physiological saline [control (CON)] or LPS (25 \u03bcg\/kg body weight; LPS) or oral inoculation with LGG for 2 wk before intraperitoneal injection of LPS (LGG+LPS). Piglets were killed 4 h after LPS injection. Systemic inflammation, intestinal integrity, inflammation signals, and metabolomic characteristics in the intestine were determined. Compared with CON, LPS stimulation significantly decreased ileal zonula occludens 1 (ZO-1; 44%), claudin-3 (44%), and occludin (41%) expression; increased serum diamineoxidase (73%), D-xylose (19%), TNF-\u03b1 (43%), and IL-6 (55%) concentrations; induced p38 mitogen-activated protein kinase (p38 MAPK; 85%), extracellular signal-regulated kinase (ERK; 96%), and NF-\u03baB p65 phosphorylation (37%) (P < 0.05). Compared with LPS stimulation alone, LGG pretreatment significantly enhanced the intestinal barrier by upregulating expressions of tight junction proteins (ZO-1, 73%; claudin-3, 55%; occludin, 67%), thereby decreasing serum diamineoxidase (26%) and D-xylose (28%) concentrations, and also reduced serum TNF-\u03b1 expression (16%) and ileal p38 MAPK (79%), ERK (43%) and NF-\u03baB p65 (37%) phosphorylation levels (P < 0.05). Metabolomic analysis showed clear separation between each group. The concentrations of caprylic acid [fold-change (FC) = 2.39], 1-mono-olein (FC = 2.68), erythritol (FC = 4.62), and ethanolamine (FC = 4.47) significantly increased in the intestine of LGG + LPS piglets compared with the LPS group (P < 0.05). These data suggest that LGG alleviates gut inflammation, improves intestinal barrier function, and modulates the metabolite profile of piglets challenged with LPS. This trial was registered at the Zhejiang University (http:\/\/www.lac.zju.edu.cn) as ZJU20170529.","subset":"pubmed_abstract"} +{"meta":{"pmid":30576570,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":3,"2024-22":1,"2024-30":1,"unknown":7}}},"text":"Early diagnosis and management of dementia in general practice - how do Swiss GPs meet the challenge?\nIn general practice, the diagnosis of dementia is often delayed. Therefore, the Swiss National Dementia Strategy 2014 concluded that action was needed to improve patient care. Little is known about GPs' confidence in and approach to the diagnosis, disclosure and post-diagnostic management of individuals with dementia in Switzerland. The aim of this survey is to assess these elements of dementia care and GPs' views on the adequacy of health care services regarding dementia. Cross-sectional postal survey in Switzerland in 2017 supported by all academic institutes of general practice in Swiss universities. Members of the Swiss Association of General Practitioners (n = 4460) were asked to participate in the survey. In addition to the GPs' demographic characteristics, the survey addressed the following issues: GPs' views on the adequacy of health care services, clinical approach and confidence in the management of dementia. The survey response rate was 21%. The majority of GPs (64%) felt confident diagnosing dementia, but not in patients with a migration background (15%). For neuropsychological testing, three-quarters of GPs collaborated with memory clinics and were satisfied with the access to diagnostic services. At the time of first diagnosis, 62% of GPs diagnosed the majority of their patients with a mild stage of dementia, and 31% with a mild cognitive impairment. The most frequent actions taken by GPs after the diagnosis of mild dementia were giving advice to relatives (71%), testing fitness-to-drive (66%) and minimising cardiovascular risk factors (63%). While 65% of GPs felt confident taking care of patients with dementia, fewer (53%) felt confident in pharmacological treatment, coping with suicidal ideation (44%) or caring for patients with a migration background (16%). Half of GPs preferred to delegate the assessment of fitness-to-drive to an official authority. One in four GPs was not satisfied with the local provision of care and support facilities for patients with dementia. Overall, GPs reported confidence in establishing a diagnosis of dementia and sufficient access to diagnostic services. Post-diagnostic management primarily focused on counselling and harm reduction rather than pharmacological treatment. Future educational support for GPs should be developed, concentrating on coping with their patients' suicidal ideation and caring for patients with a migration background.","subset":"pubmed_abstract"} +{"meta":{"pmid":11907055,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The use of ground-borne vibrations for prey localization in the Saharan sand vipers (Cerastes).\nSand vipers of the genus Cerastes are specialized semi-fossorial snakes that launch predatory strikes at rodents and lizards while partially buried in the soft sand of the Saharan desert. This study attempted to document which environmental stimuli are used by these snakes as a trigger for the ambush behavior. Denervating the olfactory and vomeronasal organs produced no changes in prey capture behavior in Cerastes cerastes. Occluding the eyes of the denervated specimens resulted in significant decreases in strike distance, diversity of strike angle and strike accuracy, demonstrating the importance of visual stimuli for target acquisition in this species. Nevertheless, every olfactory-denervated, temporarily blinded specimen succeeded in capturing free-ranging mice in every trial. Presentation of chemosensory-neutral targets to the olfactory-denervated, temporarily blinded specimens resulted in similar predatory behaviors, whether the target was isothermic to the environment or heated to mammalian body temperature. Collectively, these results provide evidence for the importance of visual stimuli during foraging in C. cerastes, the first experimental evidence for foraging by vibration detection in snakes and the strongest evidence to date that snakes are capable of 'hearing' vibrational stimuli.","subset":"pubmed_abstract"} +{"meta":{"pmid":28550016,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":3,"unknown":20}}},"text":"Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior.\nHuman psychiatric disorders such as schizophrenia, bipolar disorder, and attention-deficit\/hyperactivity disorder often include adverse behaviors including increased aggressiveness. Individuals with psychiatric disorders often exhibit social withdrawal, which can further increase the probability of conducting a violent act. Here, we used the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP) to investigate the genetic basis of variation in male aggressive behavior for flies reared in a socialized and socially isolated environment. We identified genetic variation for aggressive behavior, as well as significant genotype-by-social environmental interaction (GSEI); i.e., variation among DGRP genotypes in the degree to which social isolation affected aggression. We performed genome-wide association (GWA) analyses to identify genetic variants associated with aggression within each environment. We used genomic prediction to partition genetic variants into gene ontology (GO) terms and constituent genes, and identified GO terms and genes with high prediction accuracies in both social environments and for GSEI. The top predictive GO terms significantly increased the proportion of variance explained, compared to prediction models based on all segregating variants. We performed genomic prediction across environments, and identified genes in common between the social environments that turned out to be enriched for genome-wide associated variants. A large proportion of the associated genes have previously been associated with aggressive behavior in Drosophila and mice. Further, many of these genes have human orthologs that have been associated with neurological disorders, indicating partially shared genetic mechanisms underlying aggression in animal models and human psychiatric disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":14597789,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Distal tibial transphyseal osteotomy for ankle varus deformity in an operated case of clubfoot.\nAnkle varus deformity arises due to a number of congenital and acquired causes leading to significant functional debility in the patients, especially children. We report a less commonly used technique, the transphyseal osteotomy of distal tibia, for the correction of varus deformity of the ankle joint in a thirteen-year-old boy. Full correction of the deformity could be achieved using this technique. The patient is fully functional with normal gait. No recurrence was detected at follow-up visit 26 months later.","subset":"pubmed_abstract"} +{"meta":{"pmid":22547422,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation.\nSeveral reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy. We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women. We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations. The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation. In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.","subset":"pubmed_abstract"} +{"meta":{"pmid":23282976,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-30":2,"2024-26":1,"unknown":9}}},"text":"Frequency of HER-2 positivity in rectal cancer and prognosis.\nIn patients with advanced rectal cancer (cUICC II and III) multimodality therapy resulted in better long-term local tumor control. Ongoing clinical trials are focusing on therapy intensification to improve disease-free (DFS) and cancer-specific survival (CSS), the integration of biomarkers for prediction of individual recurrence risk, and the identification of new targets. In this context, we investigated HER-2, a member of the epidermal growth factor receptor family, whose expression pattern and role was unclear in rectal cancer. A total of 264 patients (192 male, 72 female; median age 64 y) received standardized multidisciplinary treatment according to protocols of phase II\/III trials of the German Rectal Cancer Study Group. HER-2 status was determined in pretherapeutic biopsies and resection specimens using immunohistochemistry scoring and detection of silver in situ hybridization amplification. Tumors with an immunohistochemistry score of 3 or silver in situ hybridization ratios of \u22652.0 were classified HER-2 positive; these results were correlated with clinicopathologic parameters [eg, resection (R) status, nodal status ((y)pN)], DFS, and CSS. Positive HER-2 status was found in 12.4% of biopsies and in 26.7% of resected specimens. With a median follow-up of 46.5 months, patients with HER-2 positivity showed in trend a better DFS (P=0.1) and a benefit in CSS (P=0.03). The 5-year survival rate was 96.0% (HER-2 positive) versus 80.0% (HER-2 negative). In univariate and multivariate analyses, HER-2 was an independent predictor for CSS (0.02) along with the (y)pN status (P<0.00001) and R status (P=0.011). HER-2 amplification is detectable in a relevant proportion (26.7%) of rectal cancer patients. For the development of innovative new therapies, HER-2 may represent a promising target and should be further assessed within prospective clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":27450643,"dup_signals":{"dup_doc_count":31,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":2,"2021-10":1,"2020-45":1,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":2,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2024-22":1}}},"text":"Antibody-associated epilepsies: Clinical features, evidence for immunotherapies and future research questions.\nThe growing recognition of epilepsies and encephalopathies associated with autoantibodies against surface neuronal proteins (LGI1, NMDAR, CASPR2, GABABR, and AMPAR) means that epileptologists are increasingly asking questions about mechanisms of antibody-mediated epileptogenesis, and about the use of immunotherapies. This review summarizes clinical and paraclinical observations related to autoimmune epilepsies, examines the current evidence for the effectiveness of immunotherapy, and makes epilepsy-specific recommendations for future research. Systematic literature search with summary and review of the identified publications. Studies describing the clinical characteristics of autoantibody-associated epilepsies and treatments are detailed in tables. Literature describing the clinical manifestations and treatment of autoimmune epilepsies associated with neuronal cell-surface autoantibodies (NSAbs) is largely limited to retrospective case series. We systematically summarize the features of particular interest to epileptologists dividing patients into those with acute or subacute encephalopathies associated with epilepsy, and those with chronic epilepsy without encephalopathy. Available observational studies suggest that immunotherapies are effective in some clinical circumstances but outcome data collection methods require greater standardization. The clinical experience captured suggests that clusters of clinical features associate well with specific NSAbs. Intensive and early immunotherapy is indicated when patients present with autoantibody-associated encephalopathies. It remains unclear how patients with chronic epilepsy and the same autoantibodies should be assessed and treated. Tables in this paper provide a comprehensive resource for systematic descriptions of both clinical features and treatments, and highlight limitations of current studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":22657926,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"A survey of Tennessee veterinarian and physician attitudes, knowledge, and practices regarding zoonoses prevention among animal owners with HIV infection or AIDS.\nTo examine the attitudes, knowledge, and practices of Tennessee veterinarians and physicians engaged in clinical practice regarding the risk for and prevention of zoonoses in people with HIV infection or AIDS. Cross-sectional survey. Licensed Tennessee veterinarians and physicians engaged in clinical practice. A survey was mailed in January 2010 to 454 licensed veterinarians and 1,737 licensed physicians. 181 of 419 (43.20%) eligible veterinarians and 201 of 1,376 (14.61%) eligible physicians responded to the survey. A majority of both veterinarians (131\/179 [73.18%]) and physicians (97\/192 [50.52%]) indicated that veterinarians should always or almost always be involved in advising clients with HIV infection or AIDS. The majority of veterinarians (120\/173 [69.36%]) indicated they always or almost always discussed with clients the potential risk to immune-compromised persons after diagnosing a zoonosis. A high proportion (88\/94 [93.62%]) of physicians indicated they never or rarely initiated discussions about zoonoses with patients with HIV infection or AIDS. All physicians (94\/94 [100%]) indicated they never or rarely contacted veterinarians for advice on zoonoses. Similarly, 174 of 180 (96.76%) veterinarians had never or rarely contacted physicians for advice on zoonoses risks. Only 25.97% of veterinarians and 33.33% of physicians were correctly able to identify zoonotic pathogens of greatest concern to people with HIV infection or AIDS. We identified several implications for veterinary medical and medical practice that may reduce zoonoses transmission risks for people with HIV infection or AIDS, including increased communication between veterinarians and physicians, increased communication between people with HIV infection or AIDS and health-care providers, increased availability of client educational materials, and increased participation in zoonoses continuing education opportunities by health-care providers.","subset":"pubmed_abstract"} +{"meta":{"pmid":23083188,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Response behavior of diblock copolymer brushes in explicit solvent.\nThe understanding of phase behavior of copolymer brushes is of fundamental importance for the design of smart materials. In this paper, we have performed classical density functional theory calculations to study diblock copolymer brushes (A-B) in an explicit solvent which prefers the A block to B block. With increasing B-block length (N(B)), we find a structural transition of the copolymer brush from mixed to collapsed, partial-exposed, and exposed structure, which is qualitatively consistent with experiments. The phase transitions are attributed to the interplay between entropic cost of folding copolymer brushes and enthalpic effect of contact between unlike components. In addition, we examine the effect of different parameters, such as grafting density (\u03c1(g)), the bottom block length (N(A)), and the chain length of solvent (N(S)) on the solvent response of copolymer brushes. The transition chain length (N(B)) increases with decreasing \u03c1(g) and N(A), and a smaller solvent molecule makes the collapsed structure less stable due to its lower penetration cost. Our results provide the insight to phase behavior of copolymer brushes in selective solvents from a molecular view.","subset":"pubmed_abstract"} +{"meta":{"pmid":1481178,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations.\nCurrent treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods. Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification. The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80). The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.","subset":"pubmed_abstract"} +{"meta":{"pmid":31080237,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Assessment of Palatal Plane and Occlusal Plane for Determining Anteroposterior Jaw Relation.\nSagittal jaw relationship is an important parameter for orthodontic treatment planning. Angular and linear measurements both have been proposed and used in orthodontic cephalometrics to assess the sagittal jaw relationships. However, angular measurement has been questioned over the years for its reliability as a result of changes in facial height, jaw inclination and the variable positions of Nasion. So, the objective of our study was to assess the linear anteroposterior jaw relation in a sample of Nepali population using occlusal (Wits appraisal) and palatal planes as reference lines. A descriptive cross-sectional study was conducted using the lateral cephalogram of 101 individuals visiting the Department of Orthodontics, Kantipur Dental College, Kathmandu, Nepal. Individuals with Class I skeletal relation were selected using convenience sampling method. Radiographs were standardised and traced. Occlusal and palatal planes were drawn that were bisected by the perpendicular lines from Point A and Point B. The linear distances between the intersections were measured to determine sagittal jaw relations. In Nepali individuals with normal ANB angle (3.05\u00b0\u00b12.511\u00b0), the sagittal jaw relation with reference to occlusal (Wits appraisal) and palatal planes were found to be 0.203\u00b13.343mm and 3.574\u00b14.074mm respectively. Various methods has been proposed and used to assess the sagittal jaw relation and each method has its own strength and limitations. So, it is well advised to use additional cephalometric analysis whenever possible before arriving at any diagnosis and treatment plans.","subset":"pubmed_abstract"} +{"meta":{"pmid":22564070,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Dynamical genetic programming in XCSF.\nA number of representation schemes have been presented for use within learning classifier systems, ranging from binary encodings to artificial neural networks. This paper presents results from an investigation into using a temporally dynamic symbolic representation within the XCSF learning classifier system. In particular, dynamical arithmetic networks are used to represent the traditional condition-action production system rules to solve continuous-valued reinforcement learning problems and to perform symbolic regression, finding competitive performance with traditional genetic programming on a number of composite polynomial tasks. In addition, the network outputs are later repeatedly sampled at varying temporal intervals to perform multistep-ahead predictions of a financial time series.","subset":"pubmed_abstract"} +{"meta":{"pmid":24117693,"dup_signals":{"dup_doc_count":34,"dup_dump_count":31,"dup_details":{"curated_sources":3,"2023-06":1,"2022-27":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-13":1,"2018-09":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2023-40":1,"2017-13":1,"2024-30":1}}},"text":"Optimizing accu time-of-flight\/direct analysis in real time for explosive residue analysis.\nThe use of a direct analysis in real time (DART) mass spectrometer (MS) instrument was optimized for 22 compounds of organic explosive residues to provide a guide for DART-MS users in rapid screening of explosive compounds. Samples were introduced as neat solutions and sequential dilutions to determine optimal instrument conditions and lowest concentration detectable. Most compounds were optimized to 250\u00b0C in the negative ion mode, and several compounds benefited from the addition of a chloride dopant from methylene chloride (amino-dinitrotoluenes, RDX, EGDN, and PETN). Few compounds were more sensitive in the positive ion mode (TEGDN, DEGDN, HNS, and DMNB). Mixtures of compounds were detected using clean room wipes, directly from their surfaces and from subsequent extractions. Compounds from the mixtures were also successfully detected in soil and from swipes of spiked surfaces. The instrument showed merit in detection of pg\/\u03bcL solutions for most of the compounds and among the substrates tested.","subset":"pubmed_abstract"} +{"meta":{"pmid":2094004,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Ultrastructural investigations of the bone and fibrous connective tissue interface with endosteal dental implants.\nThe interface between the tissues of the oral cavity and ceramic and titanium cylindrical endosteal dental implants was investigated with correlated light microscopy, transmission electron microscopy and scanning electron microscopy. This study suggested that mandibular bone can directly interface and form an intimate association with one-stage endosteal dental implants. This potential attachment matrix is composed of a composite of calcified bone, and an osteoid unmineralized matrix in association with an apparent osteogenic connective tissue. Further, results from this study suggested that at a level inferior to the junctional epithelium, and superior to the level of crestal bone, fibrous connective tissue can attach to the dental implant. This non-loadbearing attachment of gingival connective tissue could, by contact inhibition, prevent apical epithelial migration. In association with previously documented epithelial attachment, such apical support and connective tissue attachment appears to suggest that endosteal dental implants can be adequately maintained in the oral cavity.","subset":"pubmed_abstract"} +{"meta":{"pmid":34737002,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"New telomere to telomere assembly of human chromosome 8 reveals a previous underestimation of G-quadruplex forming sequences and inverted repeats.\nTaking advantage of evolving and improving sequencing methods, human chromosome 8 is now available as a gapless, end-to-end assembly. Thanks to advances in long-read sequencing technologies, its centromere, telomeres, duplicated gene families and repeat-rich regions are now fully sequenced. We were interested to assess if the new assembly altered our understanding of the potential impact of non-B DNA structures within this completed chromosome sequence. It has been shown that non-B secondary structures, such as G-quadruplexes, hairpins and cruciforms, have important regulatory functions and potential as targeted therapeutics. Therefore, we analysed the presence of putative G-quadruplex forming sequences and inverted repeats in the current human reference genome (GRCh38) and in the new end-to-end assembly of chromosome 8. The comparison revealed that the new assembly contains significantly more inverted repeats and G-quadruplex forming sequences compared to the current reference sequence. This observation can be explained by improved accuracy of the new sequencing methods, particularly in regions that contain extensive repeats of bases, as is preferred by many non-B DNA structures. These results show a significant underestimation of the prevalence of non-B DNA secondary structure in previous assembly versions of the human genome and point to their importance being not fully appreciated. We anticipate that similar observations will occur as the improved sequencing technologies fill in gaps across the genomes of humans and other organisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":22461428,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5.\nIn rodent lungs, a major part of the myelinated vagal airway afferents selectively contacts pulmonary neuroepithelial bodies (NEBs). Because most myelinated vagal airway afferents concern physiologically characterized mechanoreceptors, the present study aimed at unraveling the potential involvement of NEB cells in transducing mechanosensory information from the airways to the central nervous system. Physiological studies were performed using confocal Ca(2+) imaging of airway epithelium in murine lung slices. Mechanical stimulation by short-term application of a mild hypoosmotic solution (230 mosmol) resulted in a selective, fast, reversible, and reproducible Ca(2+) rise in NEB cells. Other airway epithelial cells could only be activated using more severe hypoosmotic stimuli (< 200 mosmol). NEB cells selectively expressed the Ca(2+)-permeable osmo- and mechanosensitive transient receptor potential canonical channel 5 (TRPC5) in their apical membranes, whereas immunoreactivity for TRP vanilloid-4 and TRP melastatin-3 was abundant in virtually all other airway epithelial cells. Hypoosmotic activation of NEB cells was prevented by GsMTx-4, an inhibitor of mechanosensitive ion channels, and by SKF96365, an inhibitor of TRPC channels. Short application of gadolinium, reported to activate TRPC5 channels, evoked a transient Ca(2+) rise in NEB cells. Osmomechanical activation of NEB cells gave rise to a typical delayed activation of Clara-like cells due to the release of ATP from NEB cells. Because ATP may activate the NEB-associated P2X(2\/3) ATP receptor expressing myelinated vagal afferents, the current observations strongly suggest that pulmonary NEB cells are fully equipped to initiate mechanosensory signal transduction to the central nervous system via a purinergic signaling pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":29452110,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":2,"2024-22":2,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Exploring the impact of house screening intervention on entomological indices and incidence of malaria in Arba Minch town, southwest Ethiopia: A randomized control trial.\nHouse is the major site for malaria infection where most human-vector contact takes place. Hence, improving housing might reduce the risk of malaria infection by limiting house entry of vectors. This study aimed to explore the impact of screening doors and windows with wire meshes on density and entomological inoculation rate (EIR) of malaria vector, and malaria incidence, and assess the acceptability, durability, and cost of the intervention. The susceptibility status of malaria vector was also assessed. A two-arm randomized trial was done in Arba Minch Town, southwest Ethiopia. 92 houses were randomly included in the trial. The baseline entomological and malaria prevalence data were collected. The mosquito sampling was done twice per household per month by Centers for Diseases Control and Prevention (CDC) light traps for six months. The baseline prevalence of malaria was assessed by testing 396 (83% of the 447 study participants) household members in all the eligible houses. The 92 houses were then randomized into control and intervention groups using mosquito and malaria prevalence baseline data to make the two groups comparable except the intervention. Then, we put wire-mesh on doors and windows of 46 houses. Post-screening mosquito collection was done in each household twice per month for three months. Each household member was visited twice per month for six months to assess malaria episodes. The frequency of damage to different structure of screening was measured twice. In-depth interview was conducted with 24 purposely selected household heads from intervention group. Speciation of Anopheles mosquito was done by morphological key, and the circum-sporozoite proteins (CSPs) analysis was done using enzyme-linked immunosorbent assay. A generalized estimating equation with a negative binomial distribution was used to assess the impact of the intervention on the indoor density of vectors. Clinical malaria case data were analyzed using Poisson regression with generalized linear model. Screening doors and windows reduced the indoor density of An. arabiensis by 48% (mean ratio of intervention to control = 0.85\/1.65; 0.52) (P = .001). Plasmodium falciparum CSP rate was 1.6% (3\/190) in the intervention houses, while it was 2.7% (10\/372) in the control houses. The protective efficacy of screening intervention from CSP positive An. arabiensis was 41% (mean ratio of intervention to control = 1.6\/2.7; 0.59), but was not statistically significant (P = .6). The EIR of An. arabiensis was 1.91 in the intervention group, whereas it was 6.45 in the control group. 477 participants were followed for clinical malaria (50.1% from intervention and 49.9% from the control group). Of 49 RDT positive cases, 45 were confirmed to be positive with microscopy. 80% (n = 36) cases were due to P. falciparum and the rest 20% (n = 9) were due to P. vivax. The incidence of P. falciparum in the intervention group was lower (IRR: 0.39, 95% CI: 0.2-0.80; P = .01) than in the control group. Using incidence of P. falciparum infection, the protective efficacy of intervention was 61% (95% CI: 18-83; P = .007). 97.9% of screened windows and 63.8% of screened doors were intact after eleven months of installation. Malaria mosquito was resistance (mortality rate of 75%) to the insecticide used for bed nets treatment. Almost all participants of intervention arm were willing to continue using screened doors and windows. Screening doors and windows reduced the indoor exposure to malaria vectors. The intervention is effective, durable and well-accepted. Hence, the existing interventions can be supplemented with house screening intervention for further reduction and ultimately elimination of malaria by reducing insecticide pressure on malaria vectors. However, further research could be considered in broad setting on different housing improvement and in the way how to scale-up for wider community.","subset":"pubmed_abstract"} +{"meta":{"pmid":32734378,"dup_signals":{"dup_doc_count":11}},"text":"Cathodal Cerebellar tDCS Combined with Visual Feedback Improves Balance Control.\nBalance control is essential to maintain a stable body position and to prevent falls. The aim of this study was to determine whether balance control could be improved by using cerebellar transcranial direct current stimulation (tDCS) and visual feedback in a combined approach. A total of 90 healthy volunteers were randomly assigned to six groups defined by the delivery of tDCS (cathodal or anodal or sham) and the provision or not of visual feedback on balance during the acquisition phase. tDCS was delivered over the cerebellar hemisphere ipsilateral to the dominant leg for 20 min at 2 mA during a unipedal stance task. Body sway (i.e., ankle angle and hip position) was measured as an overall maximal unit in anteroposterior and mediolateral direction, together with participant rating of perception of stability, before (baseline), during (acquisition), and after (final) the intervention. We found a reduction in body sway during the acquisition session when visual feedback alone was provided. When the visual feedback was removed (final session), however, body sway increased above baseline. Differently, the reduction in overall maximal body sway was maintained during the final session when the delivery of cathodal tDCS and visual feedback was combined. These findings suggest that cathodal tDCS may support the short-term maintenance of the positive effects of visual feedback on balance and provide the basis for a new approach to optimize balance control, with potential translational implications for the elderly and patients with impaired posture control.","subset":"pubmed_abstract"} +{"meta":{"pmid":18627268,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions.\nHighly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.","subset":"pubmed_abstract"} +{"meta":{"pmid":29137609,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":2,"2021-49":1,"2020-40":1,"2019-51":1,"2018-51":1,"2018-43":3,"2018-34":1,"2018-30":1,"2018-17":1,"2023-40":1,"2024-26":1,"2024-30":1}}},"text":"A comparative content analysis of media reporting of sports betting in Australia: lessons for public health media advocacy approaches.\nHarmful gambling is a significant public health issue. There has been widespread discussion in the Australian media about the extent and impact of sports betting on the Australian community, particularly relating to young men and children. Given the role that the media plays in influencing policy change and political agendas, and the acknowledgement that media based advocacy is a fundamental component of successful advocacy campaigns, this research aimed to investigate how different stakeholder groups discuss sports betting within the Australian print media. The study uses this information to provide recommendations to guide public health media advocacy approaches. A quantitative content analysis of print media articles was conducted during two significant Parliamentary Inquiries about sports betting - (1) The Joint Select Committee Inquiry into the Advertising and Promotion of Gambling Services in Sport (2012\/2013), and (2) 'The Review of Illegal Offshore Wagering (2015\/2016). A total of 241 articles from 12 daily Australian newspapers were analysed. Statistical analysis was used to compare frequency of, and changes in, themes, voices and perspectives over time. Discussions about the marketing and communication of sports betting was a main theme in media reporting (n = 165, 68.5%), while discussions about gambling reform decreased significantly across the two time periods (p < 0.0001). The presence of sports betting industry (p < 0.0001), sporting code (p < 0.0001) and public health expert (p = 0.001) voices all increased significantly across the two time periods. There were very few (n = 11, 4.6%) voices from those who had experienced gambling harm. Finally, while there were significantly fewer articles taking the perspective that regulation changes were needed to protect vulnerable sub-populations (p < 0.0001), articles that had a neutral perspective about the need for regulation change increased significantly across the two time periods (p < 0.0001). Mapping the media reporting of sports betting is important in developing effective public health advocacy approaches. This study indicates that discussions about the marketing strategies utilised by the sports betting industry was still a main theme in media articles. However, discussions relating to sports betting reforms, in particular to protect individuals who may be vulnerable to the harm associated with these products and their promotional strategies (for example children and young men) decreased during the time periods. Public health advocates may seek to address the decrease in media reports about reform by developing clear evidence-based messages about why regulatory reform is needed, as well as the potential consequences of not implementing reforms. Working with organisations to build capacity for people who have experienced gambling harm may help ensure that individuals with a lived experience of harm have an increased voice in the media.","subset":"pubmed_abstract"} +{"meta":{"pmid":19478340,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":17}}},"text":"Effect of caffeine on quadriceps muscle pain during acute cycling exercise in low versus high caffeine consumers.\nThis experiment examined the effect of a moderate dose of caffeine on quadriceps muscle pain during a bout of high-intensity cycling in low- versus high-caffeine-consuming males. College-age men who were low (< or =100 mg\/day; n = 12) or high (> or =400 mg\/day; n = 13) habitual caffeine consumers ingested caffeine (5 mg\/kg body weight) or a placebo in a counterbalanced order and 1 hr later completed 30 min of cycle ergometry at 75-77% of peak oxygen consumption. Perceptions of quadriceps muscle pain, as well as oxygen consumption, heart rate, and work rate, were recorded during both bouts of exercise. Caffeine ingestion resulted in a statistically significant and moderate reduction in quadriceps muscle-pain-intensity ratings during the 30-min bout of high-intensity cycle ergometry compared with placebo ingestion in both low (d = -0.42) and high (d = -0.55) caffeine consumers. The results suggest that caffeine ingestion is associated with a moderate hypoalgesic effect during high-intensity cycling in college-age men who are low or high habitual caffeine consumers, but future work should consider better defining and differentiating pain and effort when examining the effects of caffeine during acute exercise.","subset":"pubmed_abstract"} +{"meta":{"pmid":19697418,"dup_signals":{"dup_doc_count":11}},"text":"Viral load and physical status of human papillomavirus (HPV) 18 in cervical samples from female sex workers infected with HPV 18 in Burkina Faso.\nViral DNA load and physical status might be predictive of either high-grade cervical lesions or disease progression among women infected by human papillomavirus (HPV) 16, but these virological markers have rarely been studied in HPV 18 infections. The relationships between HPV 18 DNA load, viral genome physical status and cervical squamous intraepithelial lesions were analyzed among female sex workers infected with HPV18 in Burkina Faso. HPV 18 E2 and E6 genes were quantitated by real-time PCR. Among 21 women infected with HPV 18, 67% of whom were HIV-1-seropositive, 11 (52.4%) had a normal cytology, 8 (38.1%) had low-grade squamous intraepithelial lesions, and 2 (9.5%) had high-grade squamous intraepithelial lesions. Total viral load and integrated viral load were higher in women with squamous intraepithelial lesions than in women with normal cytology (P = 0.01 for both parameters). Total viral load and integrated viral load were higher in HIV-1-seropositive women than in those who were not infected with HIV (P = 0.01, and P, 0.01, respectively). Total viral load or integrated viral load >1,000 copies\/ng of DNA were more frequent in women with squamous intraepithelial lesions than in women with normal cytology (7\/10 vs. 1\/11; P = 0.007) and in HIV-1-seropositive women (8\/14 vs. 0\/7 in HIV-uninfected women; P = 0.02). Both HPV 18 DNA and integrated DNA loads might represent markers of cervical lesions. Prospective evaluations are needed to establish the value of these parameters to predict high-grade lesion or lesion progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":15772317,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-18":1,"unknown":3}}},"text":"Spatio-temporal distribution of Plasmodium falciparum and p. Vivax malaria in Thailand.\nMalaria incidence data at the district level from 1997 to 2002 and total malaria case data from 1965 to 2002 in Thailand were analyzed to determine the spatial and temporal dynamics of Plasmodium falciparum and P. vivax malaria incidence. Over the 37-year period, there was a 35-fold reduction in the incidence rates of P. falciparum malaria (11.86% in 1965 versus 0.34% in 2002) and a 7-fold reduction in P. vivax malaria (2.89% in 1965 versus 0.40% in 2002). The incidence ratio of P. falciparum to P. vivax malaria was reduced from 4.1 to 0.8 during this period. Malaria incidence rate exhibited the most rapid reduction between 1975 and 1985, coinciding with the introduction of a combination of antifolate drugs (sulfadoxine-pyrimethamine). The distribution maps of P. falciparum and P. vivax malaria incidence rates indicated a high spatial heterogeneity. The Thailand-Myanmar and Thailand-Cambodia border areas, where migration of foreign workers was pronounced, had the highest incidence rates for P. falciparum, P. vivax, and mixed-species infections. Transition probability analysis based on the malaria incidence rate among Thai residents indicated that there was an overall trend of decrease in the number of malaria cases and the number of high incidence districts between 1997 and 2002. High spatial variation in malaria incidence and local human migration patterns suggest that malaria control measures need to be adjusted according to local environmental and demographic settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":14638564,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":7}}},"text":"The long-term effects of a self-management program for inner-city primary care patients with acute low back pain.\nWe evaluated the effect of a self-management program for low-income primary care patients with acute low back pain (ALBP) from inner-city neighborhood health centers. We conducted a randomized controlled trial of a self-management program compared with usual care at university-affiliated neighborhood health centers and an emergency department of an inner-city public teaching hospital. We enrolled 211 patients who visited a physician for ALBP (<90 days' duration). The self-management program consisted of 3 group sessions and telephone follow-up that focused on understanding back pain, increasing physical activity, and dealing with fears and frustrations. At baseline, 4 months, and 12 months, blinded interviewers assessed back pain physical function (Roland Disability Questionnaire), health status (Arthritis Impact Measurement Scales), self-efficacy, and time spent in physical activity. Compared with patients receiving usual care, intervention patients reported significantly better scores on the Roland Disability Questionnaire (P =.009), mental functioning (P =.009), self-efficacy to manage ALBP (P =.03), time spent in physical activity (P =.047), and reduced fears of movement\/reinjury (P =.005) after 12 months. A self-management program can improve and maintain functional status, mental functioning, and self-efficacy to manage future symptoms for 1 year among primary care patients with ALBP living in the urban, inner city.","subset":"pubmed_abstract"} +{"meta":{"pmid":26490442,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The Effects of Cell Phone and Text Message Conversations on Simulated Street Crossing.\nA fully immersive, high-fidelity street-crossing simulator was used to examine the effects of texting on pedestrian street-crossing performance. Research suggests that street-crossing performance is impaired when pedestrians engage in cell phone conversations. Less is known about the impact of texting on street-crossing performance. Thirty-two young adults completed three distraction conditions in a simulated street-crossing task: no distraction, phone conversation, and texting. A hands-free headset and a mounted tablet were used to conduct the phone and texting conversations, respectively. Participants moved through the virtual environment via a manual treadmill, allowing them to select crossing gaps and change their gait. During the phone conversation and texting conditions, participants had fewer successful crossings and took longer to initiate crossing. Furthermore, in the texting condition, smaller percentage of time with head orientation toward the tablet, fewer number of head orientations toward the tablet, and greater percentage of total characters typed before initiating crossing predicted greater crossing success. Our results suggest that (a) texting is as unsafe as phone conversations for street-crossing performance and (b) when subjects completed most of the texting task before initiating crossing, they were more likely to make it safely across the street. Sending and receiving text messages negatively impact a range of real-world behaviors. These results may inform personal and policy decisions.","subset":"pubmed_abstract"} +{"meta":{"pmid":21975641,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2021-21":1,"2020-24":1,"2020-10":1,"2019-51":3,"2019-47":3,"2019-39":1,"2021-49":1}}},"text":"Environmental influences on physical activity in rural adults: the relative contributions of home, church and work settings.\nThis study examines the relative contribution of social (eg, social support) and physical (eg, programs and facilities) aspects of worksite, church, and home settings to physical activity levels among adults in rural communities. Data are from a cross-sectional survey of 268 African American and Caucasian adults, ages 40-70, living in southwest Georgia. Separate regression models were developed for walking, moderate, vigorous, and total physical activity as measured in METs-minutes-per-week. Social support for physical activity was modest in all 3 settings (mean scores 1.5-1.9 on a 4-point scale). Participants reported limited (<1) programs and facilities for physical activity at their worksites and churches. An interaction of physical and social aspects of the home setting was observed for vigorous and moderate physical activity and total METs. There were also interactions between gender and social support at church for vigorous activity among women, and between race and the physical environment at church for moderate physical activity. A cross-over interaction was found between home and church settings for vigorous physical activity. Social support at church was associated with walking and total METs. Homes and churches may be important behavioral settings for physical activity among adults in rural communities.","subset":"pubmed_abstract"} +{"meta":{"pmid":15157127,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Speech recognition in fluctuating and continuous maskers: effects of hearing loss and presentation level.\nListeners with normal-hearing sensitivity recognize speech more accurately in the presence of fluctuating background sounds, such as a single competing voice, than in unmodulated noise at the same overall level. These performance differences are greatly reduced in listeners with hearing impairment, who generally receive little benefit from fluctuations in masker envelopes. If this lack of benefit is entirely due to elevated quiet thresholds and the resulting inaudibility of low-amplitude portions of signal + masker, then listeners with hearing impairment should derive increasing benefit from masker fluctuations as presentation levels increase. Listeners with normal-hearing (NH) sensitivity and listeners with hearing impairment (HI) were tested for sentence recognition at moderate and high presentation levels in competing speech-shaped noise, in competing speech by a single talker, and in competing time-reversed speech by the same talker. NH listeners showed more accurate recognition at moderate than at high presentation levels and better performance in fluctuating maskers than in unmodulated noise. For these listeners, modulated versus unmodulated performance differences tended to decrease at high presentation levels. Listeners with HI, as a group, showed performance that was more similar across maskers and presentation levels. Considered individually, only 2 out of 6 listeners with HI showed better overall performance and increasing benefit from masker fluctuations as presentation level increased. These results suggest that audibility alone does not completely account for the group differences in performance with fluctuating maskers; suprathreshold processing differences between groups also appear to play an important role. Competing speech frequently provided more effective masking than time-reversed speech containing temporal fluctuations of equal magnitude. This finding is consistent with \"informational\" masking resulting from competitive processing of words and phrases within the speech masker that would notoccur for time-reversed sentences.","subset":"pubmed_abstract"} +{"meta":{"pmid":23024441,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Learning to live on a Mars day: fatigue countermeasures during the Phoenix Mars Lander mission.\nTo interact with the robotic Phoenix Mars Lander (PML) spacecraft, mission personnel were required to work on a Mars day (24.65 h) for 78 days. This alien schedule presents a challenge to Earth-bound circadian physiology and a potential risk to workplace performance and safety. We evaluated the acceptability, feasibility, and effectiveness of a fatigue management program to facilitate synchronization with the Mars day and alleviate circadian misalignment, sleep loss, and fatigue. Operational field study. PML Science Operations Center. Scientific and technical personnel supporting PML mission. Sleep and fatigue education was offered to all support personnel. A subset (n = 19) were offered a short-wavelength (blue) light panel to aid alertness and mitigate\/reduce circadian desynchrony. They were assessed using a daily sleep\/work diary, continuous wrist actigraphy, and regular performance tests. Subjects also completed 48-h urine collections biweekly for assessment of the circadian 6-sulphatoxymelatonin rhythm. Most participants (87%) exhibited a circadian period consistent with adaptation to a Mars day. When synchronized, main sleep duration was 5.98 \u00b1 0.94 h, but fell to 4.91 \u00b1 1.22 h when misaligned (P < 0.001). Self-reported levels of fatigue and sleepiness also significantly increased when work was scheduled at an inappropriate circadian phase (P < 0.001). Prolonged wakefulness (\u2265 21 h) was associated with a decline in performance and alertness (P < 0.03 and P < 0.0001, respectively). The ability of the participants to adapt successfully to the Mars day suggests that future missions should utilize a similar circadian rhythm and fatigue management program to reduce the risk of sleepiness-related errors that jeopardize personnel safety and health during critical missions.","subset":"pubmed_abstract"} +{"meta":{"pmid":28274051,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Effectiveness of Two Topical Anaesthetic Agents used along with Audio Visual Aids in Paediatric Dental Patients.\nTopical anaesthetic agents enable pain free intraoral procedures, symptomatic pain relief for toothache, superficial mucosal lesions and pain related to post extraction time. Most common anxiety provoking and fearful experience for children in dental operatory is administration of local anaesthesia because on seeing the needle, children usually become uncooperative. One of recent trend of behaviour management technique is using non-aversive techniques out of which audiovisual distraction has emerged as a very successful technique for managing children in dental settings. Audio visual distraction could decrease the procedure related anxiety of patients undergoing dental treatment and can be very relaxing for highly anxious patients. The aim of the present study was to compare the efficacy of topical anaesthetics EMLA (Eutectic Mixture of Local Anaesthetics) cream and benzocaine (20%) gel in reducing the pain during the needle insertion with and without the use of Audio Visual (AV) aids. The study was conducted on 120 children, the age range of 3-14 years attending the outpatient department for their treatment. EMLA and benzocaine gel (20%) were assessed for their effectiveness in reducing the pain on needle insertion during local anaesthesia administration. Based on the inclusion and the exclusion criteria, children requiring local anaesthesia for the dental treatment were randomly divided into four equal groups of 30 children based upon whether AV aids were used or not. AV aids were given using Sony Vaio laptop with earphones with nursery rhymes and cartoon movies DVD. The pain assessment was done by using the Visual Analogue Scale (VAS) scale and measurement of the physiological responses of pulse rate and oxygen saturation were done by pulse oximeter. There was a statistically significant difference in the mean pain score, pulse rate and mean oxygen saturation rate when it was compared between the four groups. EMLA with AV aids was found to be a better topical anaesthestic agent as compared to other three groups. EMLA with AV aids was better when compared with EMLA without AV aids followed by benzocaine with AV aids. Benzocaine topical anaesthetic agent without AV aids was least effective in reducing the pain scores and improving the oxygen saturation rate.","subset":"pubmed_abstract"} +{"meta":{"pmid":33678178,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"unknown":7}}},"text":"The socio-economic transition and health professions education in Mongolia: a qualitative study.\nFormer socialist countries have undergone a socio-economic transition in recent decades. New challenges for the healthcare system have arisen in the transition economy, leading to demands for better management and development of the health professions. However, few studies have explored the effects of this transition on health professions education. Thus, we investigated the effects of the socio-economic transition on the health professions education system in Mongolia, a transition economy country, and to identify changes in requirements. We used a multi-level perspective to explore the effects of the transition, including the input, process, and output levels of the health professions education system. The input level refers to planning and management, the process level refers to the actual delivery of educational services, and the output level refers to issues related to the health professionals, produced by the system. This study utilized a qualitative research design, including document review and interviews with local representatives. Content analysis and the constant comparative method were used for data analysis. We explored tensions in the three levels of the health professions education system. First, medical schools attained academic authority for planning and management without proper regulation and financial support. The government sets tuition fees, which are the only financial resource of medical schools; thus, medical schools attempt to enroll more students in order to adapt to the market environment. Second, the quality of educational services varies across institutions due to the absence of a core curriculum and differences in the learning environment. After the transition, the number of private medical schools rapidly increased without quality control, while hospitals started their own specialized training programs. Third, health professionals are struggling to maintain their professional values and development in the market environment. Fixed salaries lead to a lack of motivation, and quality evaluation measures more likely reflect government control than quality improvement. Mongolia continues to face the consequences of the socio-economic transition. Medical schools' lack of financial authority, the varying quality of educational services, and poor professional development are the major adverse effects. Finding external financial support, developing a core curriculum, and reforming a payment system are recommended.","subset":"pubmed_abstract"} +{"meta":{"pmid":8546704,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Biosynthesis of vitamin B12: the preparative multi-enzyme synthesis of precorrin-3A and 20-methylsirohydrochlorin (a 2,7,20-trimethylisobacteriochlorin).\nThe Bacillus subtilis genes hemB, hemC and hemD, encoding respectively the enzymes porphobilinogen synthase, hydroxymethylbilane synthase and uroporphyrinogen III synthase, have been expressed in Escherichia coli using a single plasmid construct. An enzyme preparation from this source converts 5-aminolaevulinic acid (ALA) preparatively and in high yield into uroporphyrinogen III. The Pseudomonas denitrificans genes cobA and cobI, encoding respectively the enzymes S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) and S-adenosyl-L-methionine:precorrin-2 methyltransferase (SP2MT), were also expressed in E. coli. When SUMT was combined with the coupled-enzyme system that produces uroporphyrinogen III, precorrin-2 was synthesized from ALA, and when SP2MT was also added the product from the coupling of five enzymes was precorrin-3A. Both of these products are precursors of vitamin B12, and they can be used directly for biosynthetic experiments or isolated as their didehydro octamethyl esters in > 40% overall yield. The enzyme system which produces precorrin-3A is sufficiently stable to allow long incubations on a large scale, affording substantial quantities (15-20 mg) of product.","subset":"pubmed_abstract"} +{"meta":{"pmid":29162584,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Individualized Glycemic Goals and an Expanded Classification of Severe Hypoglycemia in Diabetes.\nThe view that a hemoglobin A1c (A1C) level <7% (55 mmol\/mol) is the accepted glycemic goal for most people with diabetes sometimes conflicts with the view that glycemic goals should be individualized and, thus, that somewhat higher A1C levels are appropriate for some, particularly many at risk for iatrogenic hypoglycemia because of treatment with insulin, a sulfonylurea, or a glinide. The relationship between A1C and chronic complications of diabetes is curvilinear, A1C is a relatively weak predictor of cardiovascular disease, and minor elevations of A1C above 7% have not been found to be associated with increased mortality. Iatrogenic hypoglycemia causes recurrent morbidity in diabetes and is sometimes fatal. In those at risk for hypoglycemia, a reasonable individualized glycemic goal is the lowest A1C that does not cause severe hypoglycemia and preserves awareness of hypoglycemia, preferably with little or no symptomatic or even asymptomatic hypoglycemia, at a given stage in the evolution of the individual's diabetes. A somewhat higher A1C level is appropriate in those who have previously experienced hypoglycemia or have potential high risk for hypoglycemia, have a long duration of diabetes, and have a short life expectancy, among other traits. Given the importance of severe hypoglycemia in selecting glycemic goals, it is proposed to expand the classification of severe hypoglycemia beyond a hypoglycemic event requiring assistance from another person to include a measured glucose concentration <50 mg\/dL (2.8 mmol\/L), a level associated with sudden death.","subset":"pubmed_abstract"} +{"meta":{"pmid":19884931,"dup_signals":{"dup_doc_count":41,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2022-33":1,"2022-05":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-09":2,"2017-47":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":2,"2016-44":2,"2016-36":3,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-35":1,"2015-32":2,"2015-27":1,"2015-22":3,"2022-40":1,"2017-13":2}}},"text":"Visual sensitivity and cortical response to the temporal envelope of amplitude-modulated flicker.\nTo investigate the perception of a temporal envelope of flickering light is important for understanding nonlinear temporal processing in the visual system. The influence of the frequency components of a flickering light on the perception of the envelope remains unclear, with few studies having investigated the cortical activities for the envelope. We investigated the detection thresholds, brightness, and magnetoencephalographic responses related to amplitude-modulated (AM) flickering lights. The results showed that the sensitivity to flicker at the envelope periodicity of the AM flickering light was lower for a high-frequency carrier (40 Hz) than for a lower-frequency one (10, 20, or 30 Hz). Also, the primary visual cortex responded at the frequency corresponding to the envelope periodicity of the AM flickering light, and the strength of the cortical response reflected the brightness of the flicker at the envelope periodicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":34939641,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"The fuzzy sphere morphology is responsible for the increase in light scattering during the shrinkage of thermoresponsive microgels.\nThermoresponsive microgels undergo a volume phase transition from a swollen state under good solvent conditions to a collapsed state under poor solvent conditions. The most prominent examples of such responsive systems are based on poly-(N-isopropylacrylamide). When cross-linked with N,N'-methylenebisacrylamide, such microgels typically possess a fuzzy-spherelike morphology with a higher cross-linked core and a loosely cross-linked fuzzy shell. Despite the efforts devoted to understanding the internal structure of microgels and their kinetics during collapse\/swelling, the origins of the accompanying changes in light scattering intensity have barely been addressed. In this work, we study core-shell microgels that contain small gold nanoparticle cores with microgel shells of different thicknesses and cross-linker densities. All microgels are small enough to fulfill the Rayleigh-Debye-Gans criterion at all stages of swelling. Due to the high X-ray contrast of the gold cores, we can use absolute intensity small-angle X-ray scattering to determine the number density in the dilute dispersions. This allows us to extract polymer volume fractions of the microgels at different stages of swelling from form factor analysis of small-angle neutron scattering data. We match our findings to results from temperature-dependent absorbance measurements. The increase in absorbance during the shrinkage of the microgels is related to the transition from fuzzy spheres to hard sphere-like scattering objects with a rather homogeneous density profile. We provide a first attempt to model experimental spectra using finite difference time domain simulations that take into account the structural changes during the volume phase transition. Our findings significantly contribute to the understanding of the optical properties of thermoresponsive microgels. Further, we provide polymer volume fractions and microgel refractive indices as a function of the swelling state.","subset":"pubmed_abstract"} +{"meta":{"pmid":21881833,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":9}}},"text":"Stable changes in mesenchymal stromal cells from multiple myeloma patients revealed through their responses to Toll-like receptor ligands and epidermal growth factor.\nIn human multiple myeloma (MM), the tumor cells exhibit strict dependence on bone marrow (BM) stromal elements. It has been suggested that, in turn, MM cells modify multipotent stromal cells (MSCs), diverting them to support the myeloma. We investigated MM-derived MSCs by comparing their toll-like receptor (TLR) responses to those of MSCs derived from healthy controls. We now report that MM-derived MSCs manifested intact proliferation responses and IL-6 secretion and their adipose and osteogenic differentiation responses to TLR ligands were also similar to those of healthy controls, ranging from augmentation to inhibition. However, MM-derived MSCs were found to be defective in IL-8 secretion and ERK1\/2 phosphorylation following TLR-2 activation. Moreover, MM-derived MSCs failed to respond to EGF by elevation of ERK1\/2 phosphorylation. The persistence of these changes in extensively cultured MM-derived MSCs, suggests that these cells are stably, if not irreversibly modified.","subset":"pubmed_abstract"} +{"meta":{"pmid":31637110,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Spatial Distribution of Noninvasive Break Up Times and Clinical Relevance in Healthy Participants and Mild Dry Eye.\nNoninvasive keratograph break up times (NIKBUTs) are preferred to dye-based methods to evaluate tear stability in translational medicine. We analyzed the NIKBUTs in different regions of the precorneal tear by using a common imaging technology and explored potential correlations with clinical parameters. We tested NIKBUTs of 120 participants (62.5% females, aged 61.0 \u00b1 13.8 years) with the Keratograph 5M, with standardized symptoms, ocular surface evaluation, and tear lipid layer interferometry. NIKBUTs were obtained from color maps in up to 165 spatial zones corresponding to 7 concentric rings. The lowest NIKBUT of tested zones averaged 7.8 \u00b1 7.4 seconds (median, 4.5; range, 1.5-24 seconds), with the lowest NIKBUT measuring <2 seconds in many inferior zones. A mean of 5 zones had broken up by 2 seconds compared to a mean of about 50 zones by 10 seconds. NIKBUTs in specific inferior peripheral zones were significantly directly correlated to tear lipid thicknesses. The receiver operating characteristics for detecting reduced tear lipid thickness were better than overall NIKBUTs for participants with readings in these zones. Weaker correlations of NIKBUTs with symptoms were observed in two other zones. Overall, the NIKBUT displayed by keratograph was not significantly associated with any clinical parameters. Decreased NIKBUTs in specific peripheral locations may be associated with lower lipid thicknesses. Future measurements of NIKBUTs should ideally be determined in smaller defined zones than current maps. An understanding of how to evaluate tear stability allows a more robust clinical evaluation of new drugs and medical devices for dry eye.","subset":"pubmed_abstract"} +{"meta":{"pmid":22056486,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2017-51":1,"2017-43":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies.\nTo assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. Patients scheduled for CRT in NYHA class II-IV, left ventricular ejection fraction <35%, QRS \u2265 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. 52 patients (age 60.3 \u00b1 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p=0.002), the percent of LGE was higher (7.7% [0-13.5%] vs. 19.0% (0-31.9%], p=0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 \u00b1 0.08 vs. 0.34 \u00b1 0.09, p=0.009) and uniformity of radial strain was higher (0.72 \u00b1 0.25 vs. 0.56 \u00b1 0.29, p=0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02-5.02, p=0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p=0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77-0.98, p=0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p=0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p=0.002) and uniformity of radial strain was lower (0.52 vs. 0.80, p=0.049) in non-responders vs. responders. Univariable logistic regression showed that RVV was a predictor of response to CRT (HR 1.50, 95% CI 1.06-2.13, p=0.022), providing the sensitivity of 94% and specificity of 85% at the cutoff point of 0.31. CMR derived parameters of dyssynchrony such as RVV may provide an additive value in prediction of response to CRT, especially in patients with non-ischaemic etiology of heart failure. In patients with ischaemic HF the transmurality of LGE is an important predictor of lack of response to CRT.","subset":"pubmed_abstract"} +{"meta":{"pmid":17601001,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Preventing mother-to-child transmission: factors affecting mothers' choice of feeding--a case study from Cameroon.\nThis paper reports on factors influencing the decision of mothers regarding the type of feeding method for their babies in a rural setting in Cameroon. The aim of the study was to ascertain the proportion of mothers choosing the different methods of feeding, to determine the various factors influencing their choices, and to ascertain the relationships of these factors to their respective choices. Questionnaires were used on 108 HIV-positive mothers who had delivered babies and who were administered nevirapine at least 3 months prior to the study. A focus group discussion with mothers also took place. Findings were that more mothers (84%) chose breastfeeding than artificial feeding (16%), while a minority (4%) selected mixed feeding. Factors found to militate against artificial feeding were cost (69%), stigma (64%), family pressure (44%), inconvenience in preparation\/administration (38%), prior education from health workers (23%), and loss of special attention from family (8%). On the other hand, advice of health worker (44%), ill health (19.5%), free milk (12.5%),job pressure (12.5%) and loss of beauty (12.5%) were found to militate against breastfeeding. A direct relationship was also found between age, educational level, income size, marital status and choice of feeding. Policies targeting stigma reduction and socio-cultural factors affecting the choice of feeding are needed to optimise uptake of the less risky methods of feeding which could in turn contribute to a reduction in transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":27493478,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":1,"2024-10":1,"unknown":12}}},"text":"The Perception and Estimation of Others' Pain according to Children.\nAccurate interpretation of pain expressed by others is important for socialization; however, the development of this skill in children is still poorly understood. Empathy for pain models propose two main components (affective and cognitive), which develop at different stages of life. The study's objective was to investigate the children's ability between 3 and 12 years of age to detect and assess the pain intensity in others using visual stimuli depicting either facial expressions of pain or hands in painful contexts. 40 preschool children and 62 school-aged children were recruited. Children observed series of stimuli and evaluated the pain intensity depicted. Results demonstrated that children as young as three years old were able to detect and assess pain in both types of stimuli and this ability continued to improve until the age of 12. Participants demonstrated better detection performance with hands than with faces. Results were coherent with the idea that the two types of stimuli presented recruit different processes. Pain detection in hands appears to rely mostly on affective sharing processes that are effective early in life, while older children's higher ability to perceive pain in facial expressions suggests that this ability is associated with the gradual development of cognitive processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22168277,"dup_signals":{"dup_doc_count":44,"dup_dump_count":36,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":1,"2022-05":1,"2021-43":2,"2020-50":1,"2019-51":1,"2019-43":1,"2019-18":1,"2018-22":2,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":4,"2014-41":1,"2023-23":1,"2015-18":1,"2015-11":1,"2015-06":1,"2017-13":1}}},"text":"Anti-influenza virus effect of aqueous extracts from dandelion.\nHuman influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM) has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza virus activity of an aqueous extract from dandelion, which was tested for in vitro antiviral activity against influenza virus type A, human A\/PR\/8\/34 and WSN (H1N1). Results obstained using antiviral assays, minigenome assay and real-time reverse transcription-PCR analysis showed that 0.625-5 mg\/ml of dandelion extracts inhibited infections in Madin-Darby canine kidney (MDCK) cells or Human lung adenocarcinoma cell line (A549) of PR8 or WSN viruses, as well as inhibited polymerase activity and reduced virus nucleoprotein (NP) RNA level. The plant extract did not exhibit any apparent negative effects on cell viability, metabolism or proliferation at the effective dose. This result is consistent with the added advantage of lacking any reported complications of the plant's utility in traditional medicine over several centuries. The antiviral activity of dandelion extracts indicates that a component or components of these extracts possess anti-influenza virus properties. Mechanisms of reduction of viral growth in MDCK or A549 cells by dandelion involve inhibition on virus replication.","subset":"pubmed_abstract"} +{"meta":{"pmid":36280785,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":3,"2024-26":2,"2024-10":2,"unknown":7}}},"text":"Dual ancestries and ecologies of the Late Glacial Palaeolithic in Britain.\nGenetic investigations of Upper Palaeolithic Europe have revealed a complex and transformative history of human population movements and ancestries, with evidence of several instances of genetic change across the European continent in the period following the Last Glacial Maximum (LGM). Concurrent with these genetic shifts, the post-LGM period is characterized by a series of significant climatic changes, population expansions and cultural diversification. Britain lies at the extreme northwest corner of post-LGM expansion and its earliest Late Glacial human occupation remains unclear. Here we present genetic data from Palaeolithic human individuals in the United Kingdom and the oldest human DNA thus far obtained from Britain or Ireland. We determine that a Late Upper Palaeolithic individual from Gough's Cave probably traced all its ancestry to Magdalenian-associated individuals closely related to those from sites such as El Mir\u00f3n Cave, Spain, and Troisi\u00e8me Caverne in Goyet, Belgium. However, an individual from Kendrick's Cave shows no evidence of having ancestry related to the Gough's Cave individual. Instead, the Kendrick's Cave individual traces its ancestry to groups who expanded across Europe during the Late Glacial and are represented at sites such as Villabruna, Italy. Furthermore, the individuals differ not only in their genetic ancestry profiles but also in their mortuary practices and their diets and ecologies, as evidenced through stable isotope analyses. This finding mirrors patterns of dual genetic ancestry and admixture previously detected in Iberia but may suggest a more drastic genetic turnover in northwestern Europe than in the southwest.","subset":"pubmed_abstract"} +{"meta":{"pmid":15339970,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":11}}},"text":"Burden of illness in cancer survivors: findings from a population-based national sample.\nPopulation trends in aging and improved cancer survival are likely to result in increased cancer prevalence in the United States, but few estimates of the burden of illness among cancer survivors are currently available. The purpose of this study was to estimate the burden of illness in cancer survivors in a national, population-based sample. A total of 1823 cancer survivors and 5469 age-, sex-, and educational attainment-matched control subjects were identified from the 2000 National Health Interview Survey. Multiple measures of burden, including utility, a summary measure of health, and days lost from work, were compared using two-sided tests of statistical significance for the two groups overall and for subgroups stratified by tumor site and time since diagnosis. Compared with matched control subjects, cancer survivors had poorer outcomes across all burden measures (P<.01). Cancer survivors had lower utility values (0.74 versus 0.80; P<.001) and higher levels of lost productivity and were more likely to report their health as fair or poor (31.0% versus 17.9%; P<.001) than matched control subjects. Cancer survivors reported statistically significantly higher burden than did control subjects across tumor sites and across time since diagnosis (i.e., within the past year, 2-5 years, 6-10 years, and > or =11 years for the majority of measures. Cancer survivors have poorer health outcomes than do similar individuals without cancer across multiple burden measures. These decrements are consistent across tumor sites and are found in patients many years following reported diagnosis. Improved measurement of long-term burden of illness will be important for future prospective research.","subset":"pubmed_abstract"} +{"meta":{"pmid":24992959,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effect of ion structure on nanoscale friction in protic ionic liquids.\nThe effect of ionic liquid (IL) molecular structure on nanoscale friction has been investigated using colloidal probe Friction Force Microscopy (FFM). The ILs studied were ethylammonium formate (EAF), ethylammonium nitrate (EAN), propylammonium formate (PAF), propylammonium nitrate (PAN), dimethylethylammonium formate (DMEAF), and ethanolammonium nitrate (EtAN). ILs were confined between a silica colloid probe and a mica surface, and the friction force was measured as a function of normal load for sliding velocities between 10 and 40 \u03bcm s(-1). At low normal forces, multiple IL layers are found between the probe and the surface, but at higher force, in the boundary layer regime, a single ion layer separates the probe and the surface. In the boundary layer regime energy is dissipated by two main pathways. Firstly, the ionic liquid near the surface, with the exception of the boundary layer, is expelled from the advancing contact made by the probe on the surface. This disruption in the interactions between the boundary layer and the near surface multilayers, leads to energy dissipation and depends on the strength of the attraction between the boundary and near surface layers. The second pathway is via rotations and twists of ions in the boundary layer, primarily associated with the cation terminal methyl group. The friction coefficient did not vary over the limited range of sliding speeds investigated.","subset":"pubmed_abstract"} +{"meta":{"pmid":35013427,"dup_signals":{"dup_doc_count":63,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":5,"2023-23":9,"2023-14":7,"2023-06":5,"2022-49":2,"2022-40":4,"2022-21":7,"2024-30":5,"2024-26":4,"2024-22":4,"2024-18":2,"2024-10":3}}},"text":"Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound.\nAlthough certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.","subset":"pubmed_abstract"} +{"meta":{"pmid":27460923,"dup_signals":{"dup_doc_count":25,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-10":1,"2017-13":1,"2024-30":1,"unknown":18}}},"text":"Modeling, Simulation, and Implementation of Solar-Driven Water-Splitting Devices.\nAn integrated cell for the solar-driven splitting of water consists of multiple functional components and couples various photoelectrochemical (PEC) processes at different length and time scales. The overall solar-to-hydrogen (STH) conversion efficiency of such a system depends on the performance and materials properties of the individual components as well as on the component integration, overall device architecture, and system operating conditions. This Review focuses on the modeling- and simulation-guided development and implementation of solar-driven water-splitting prototypes from a holistic viewpoint that explores the various interplays between the components. The underlying physics and interactions at the cell level is are reviewed and discussed, followed by an overview of the use of the cell model to provide target properties of materials and guide the design of a range of traditional and unique device architectures.","subset":"pubmed_abstract"} +{"meta":{"pmid":31308836,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Calcium channel blocker monotherapy versus combination with renin-angiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients.\nIn real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose \u2265 126 mg\/dL or hemoglobin A1c \u2265 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). After propensity score-matched (PSM) analysis, two propensity-matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700-1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544-1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.","subset":"pubmed_abstract"} +{"meta":{"pmid":17673654,"dup_signals":{"dup_doc_count":69,"dup_dump_count":42,"dup_details":{"curated_sources":3,"2023-50":3,"2023-40":3,"2023-14":3,"2022-49":2,"2022-40":2,"2022-27":1,"2022-21":2,"2022-05":2,"2021-43":1,"2021-39":2,"2021-31":1,"2021-25":1,"2021-21":2,"2021-17":1,"2021-10":3,"2021-04":3,"2020-50":2,"2020-40":3,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":1,"2024-18":3,"2017-13":2,"2024-30":1}}},"text":"Emerging challenges in regulatory T cell function and biology.\nMuch progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses.","subset":"pubmed_abstract"} +{"meta":{"pmid":23449122,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":15}}},"text":"Epigenetic regulation of the Wnt signaling inhibitor DACT2 in human hepatocellular carcinoma.\nDACT2 (Dapper, Dishevelled-associated antagonist of \u03b2-catenin homolog 2) is a member of the DACT family involved in the regulation of embryonic development. Human DACT2 is localized on 6q27, a region of frequent loss of heterozygosity in human cancers. However, the regulation of DACT2 expression and function in hepatocellular carcinoma (HCC) remains unclear. In this study, genetic and epigenetic changes of DACT2 were analyzed in HCC cell lines and primary cancer. We found no single-nucleotide polymorphism (SNP) associated with HCC. Promoter region methylation was correlated with loss or reduction of DACT2 expression, and restoration of DACT2 expression was induced by 5-aza-2'-deoxycytidine (5-AZA) in HCC cell lines. Promoter region methylation was found in 54.84% of primary HCC. Reduction of DACT2 expression was associated with promoter hypermethylation, and expression of DACT2 was inversely related to \u03b2-catenin expression in primary HCC. DACT2 suppressed cell proliferation, induced G 2-M arrest in cell lines and inhibited tumor growth in xenograft nude mice. The transcriptional activity of TCF-4 and the expression of Wnt signaling downstream genes were suppressed by DACT2 re-expression and reactivated by depletion of DACT2. In conclusion, DACT2 is frequently methylated in HCC and its expression is regulated by promoter hypermethylation. DACT2 suppresses HCC by inhibiting Wnt signaling in human HCC.","subset":"pubmed_abstract"} +{"meta":{"pmid":25986730,"dup_signals":{"dup_doc_count":13}},"text":"Are associations between electronic media use and BMI different across levels of physical activity?\nThe use of electronic media has been found to be a risk factor for higher BMI and for being overweight. Physical activity has been found to be associated with lower BMI and lower risk for being overweight. Little is known about whether the associations between physical activity and electronic media use are additive or interactive in predicting BMI and risk for overweight among adolescents. The data used in this study stem from the 2009\/2010 survey of \"Health Behaviour in School-aged Children (HBSC) study: A WHO Cross-National Survey. The sample consisted of 107184 13 and 15 year students from 30 different countries. Multilevel regression models were used to produce the presented estimates. Overall, 18% of boys and 11% of girls were classified as overweight. EM use was found to be associated with increased BMI z-scores and odds for overweight among both boys and girls who did not comply with physical activity guidelines. Among physically active adolescents, EM was found to be significantly associated with BMI or odds for overweight among girls, but not among boys. While the usage of EM appear to be inconsequential for BMI and the risk of overweight among physically active boys, we find evidence indicating that EM use is associated with BMI and risk for overweight among girls, including those who report complying with MVPA guidelines.","subset":"pubmed_abstract"} +{"meta":{"pmid":18188236,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Excitation of self-transparency Bragg solitons in quadratic media.\nWe show that self-transparent or gap solitons with leading-order components at fundamental frequency can be generated in a singly resonant Bragg grating by second-harmonic generation. We discuss the conditions required for exciting these localized waves.","subset":"pubmed_abstract"} +{"meta":{"pmid":17676945,"dup_signals":{"dup_doc_count":30,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2021-49":2,"2021-43":1,"2021-10":1,"2021-04":2,"2020-50":1,"2020-24":1,"2020-05":1,"2018-43":1,"2018-17":1,"2018-13":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-40":1,"2024-26":1,"2024-18":1,"2017-13":1,"2024-30":1}}},"text":"Patient adherence to tuberculosis treatment: a systematic review of qualitative research.\nTuberculosis (TB) is a major contributor to the global burden of disease and has received considerable attention in recent years, particularly in low- and middle-income countries where it is closely associated with HIV\/AIDS. Poor adherence to treatment is common despite various interventions aimed at improving treatment completion. Lack of a comprehensive and holistic understanding of barriers to and facilitators of, treatment adherence is currently a major obstacle to finding effective solutions. The aim of this systematic review of qualitative studies was to understand the factors considered important by patients, caregivers and health care providers in contributing to TB medication adherence. We searched 19 electronic databases (1966-February 2005) for qualitative studies on patients', caregivers', or health care providers' perceptions of adherence to preventive or curative TB treatment with the free text terms \"Tuberculosis AND (adherence OR compliance OR concordance)\". We supplemented our search with citation searches and by consulting experts. For included studies, study quality was assessed using a predetermined checklist and data were extracted independently onto a standard form. We then followed Noblit and Hare's method of meta-ethnography to synthesize the findings, using both reciprocal translation and line-of-argument synthesis. We screened 7,814 citations and selected 44 articles that met the prespecified inclusion criteria. The synthesis offers an overview of qualitative evidence derived from these multiple international studies. We identified eight major themes across the studies: organisation of treatment and care; interpretations of illness and wellness; the financial burden of treatment; knowledge, attitudes, and beliefs about treatment; law and immigration; personal characteristics and adherence behaviour; side effects; and family, community, and household support. Our interpretation of the themes across all studies produced a line-of-argument synthesis describing how four major factors interact to affect adherence to TB treatment: structural factors, including poverty and gender discrimination; the social context; health service factors; and personal factors. The findings of this study are limited by the quality and foci of the included studies. Adherence to the long course of TB treatment is a complex, dynamic phenomenon with a wide range of factors impacting on treatment-taking behaviour. Patients' adherence to their medication regimens was influenced by the interaction of a number of these factors. The findings of our review could help inform the development of patient-centred interventions and of interventions to address structural barriers to treatment adherence.","subset":"pubmed_abstract"} +{"meta":{"pmid":31918439,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"The Limited Utility of Ranking Hospitals Based on Their Colon Surgery Infection Rates.\nThe Centers for Medicare and Medicaid Services (CMS) use colon surgical site infection (SSI) rates to rank hospitals and apply financial penalties. The CMS' risk-adjustment model omits potentially impactful variables that might disadvantage hospitals with complex surgical populations. We analyzed adult patients who underwent colon surgery within facilities associated with HCA Healthcare from 2014 to 2016. SSIs were identified from National Health Safety Network (NHSN) reporting. We trained and validated 3 SSI prediction models, using (1) current CMS model variables, including hospital-specific random effects (HCA-adapted CMS model); (2) demographics and claims-based comorbidities (expanded-claims model); and (3) demographics, claims-based comorbidities, and NHSN variables (claims-plus-electronic health record [EHR] model). Discrimination, calibration, and resulting rankings were compared among all models and the current CMS model with published coefficient values. We identified 39 468 colon surgeries in 149 hospitals, resulting in 1216 (3.1%) SSIs. Compared to the HCA-adapted CMS model, the expanded-claims model had similar performance (c-statistic, 0.65 vs 0.67, respectively), while the claims-plus-EHR model was more accurate (c-statistic, 0.70; 95% confidence interval, .67-.73; P = .004). The sampling variation, due to the low surgical volume and small number of infections, contributed 74% of the total variation in observed SSI rates between hospitals. When CMS model rankings were compared to those from the expanded-claims and claims-plus-EHR models, 18 (15%) and 26 (22%) hospitals changed quartiles, respectively, and 10 (8.3%) and 12 (10%) hospitals changed into or out of the lowest-performing quartile, respectively. An expanded set of variables improved colon SSI risk predictions and quartile assignments, but low procedure volumes and SSI events remain a barrier to effectively comparing hospitals.","subset":"pubmed_abstract"} +{"meta":{"pmid":30565630,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Bi2SiO5@g-SiO2 upconverting nanoparticles: a bismuth-driven core-shell self-assembly mechanism.\nCore-shell systems have attracted increasing interest among the research community in recent years due to their unique properties and structural features, and the development of new synthetic strategies is still a challenge. In this work, we have investigated lanthanide-doped Bi2SiO5 nanocrystal formation inside mesoporous silica nanoparticles (MSNs). The role of both synthesis temperature and concentration of the bismuth precursor impregnated into the MSNs is discussed, showing an unprecedented strategy for the simultaneous stabilization of a crystalline core and a glassy shell. Temperature dependent synchrotron radiation X-ray powder diffraction (SR-XRPD) and high resolution transmission electron microscopy (HR-TEM) analyses allow one to follow the crystalline core growth. A mechanism for the formation of a Bi2SiO5@g-SiO2 core-shell nanosystem is proposed. In addition, the easy tunability of the color output of the upconverting system is demonstrated by means of suitable doping lanthanide ions with potential applications in several fields.","subset":"pubmed_abstract"} +{"meta":{"pmid":21574139,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"Ala-9Val polymorphism of Mn-SOD gene in sickle cell anemia.\nOxidative stress may be contributory to the pathophysiology of the abnormalities that underlie the clinical course of sickle cell anemia. We looked for a possible genetic association between the functional polymorphism Ala-9Val in the human Mn-SOD gene and sickle cell anemia. One hundred and twenty-seven patients with sickle cell anemia and 127 healthy controls were recruited into the study. Alanine versus valine polymorphism in the signal peptide of the Mn-SOD gene was evaluated using a primer pair to amplify a 107-bp fragment followed by digestion with the restriction enzyme NgoMIV. In the sickle cell anemia patients, the frequency of Val\/Val genotype was approximately 1.4-fold lower and that of Ala\/Val was 1.3-fold higher compared to the controls. No significant difference in genotype frequencies was found between patients and controls (\u03c7(2) = 4.561, d.f. = 2, P = 0.101). The Val-9 was the most common allele in patient and healthy subjects. No significant difference in allele frequencies was found between patients and controls (\u03c7(2) = 1.496, d.f. = 1, P = 0.221). We conclude that the Mn-SOD gene polymorphism is not associated with sickle cell anemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":34259196,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update.\nInfertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and\/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and\/or retrieve spermatozoa; (3) time - to consider the available \"treatment window\", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic.","subset":"pubmed_abstract"} +{"meta":{"pmid":21506925,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The role of eosinophils in non-parasitic infections.\nEosinophils are a subset of leukocytes traditionally associated with Th2-related diseases and helminth infections. However, accumulating evidence suggests eosinophils play a more prominent role in the immune response to bacterial and viral pathogens than previously realized. Specifically, eosinophils possess antimicrobial properties against a broad range of pathogens, and release specific and secondary granules as a result of pathogen recognition. Pathogen recognition is accomplished through expression of Toll-like receptors, as well as other surface and intracellular receptors expressed by the eosinophil. Interestingly, specific killing mechanisms employed by each granule protein differ based on pathogen recognition, but ultimately release of eosinophil granules leads to direct killing of many different pathogens. The precise mechanisms of killing by granule proteins and the circumstances in which specific proteins are secreted are only now being determined. Future efforts to understand these mechanisms may lead toward clinical use of granule proteins as antimicrobial agents in humans, in addition to revealing implications regarding the use of eosinophil-depleting therapies for allergic disorders. This review will summarize the literature to date regarding the role of eosinophils in non-parasitic infections.","subset":"pubmed_abstract"} +{"meta":{"pmid":31876914,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer.\nConcurrent chemoradiotherapy is the standard-of-care curative treatment for many cancers but is associated with substantial morbidity. Concurrent chemoradiotherapy administered with proton therapy might reduce toxicity and achieve comparable cancer control outcomes compared with conventional photon radiotherapy by reducing the radiation dose to normal tissues. To assess whether proton therapy in the setting of concurrent chemoradiotherapy is associated with fewer 90-day unplanned hospitalizations (Common Terminology Criteria for Adverse Events, version 4 [CTCAEv4], grade \u22653) or other adverse events and similar disease-free and overall survival compared with concurrent photon therapy and chemoradiotherapy. This retrospective, nonrandomized comparative effectiveness study included 1483 adult patients with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy with curative intent from January 1, 2011, through December 31, 2016, at a large academic health system. Three hundred ninety-one patients received proton therapy and 1092, photon therapy. Data were analyzed from October 15, 2018, through February 1, 2019. Proton vs photon chemoradiotherapy. The primary end point was 90-day adverse events associated with unplanned hospitalizations (CTCAEv4 grade \u22653). Secondary end points included Eastern Cooperative Oncology Group (ECOG) performance status decline during treatment, 90-day adverse events of at least CTCAEv4 grade 2 that limit instrumental activities of daily living, and disease-free and overall survival. Data on adverse events and survival were gathered prospectively. Modified Poisson regression models with inverse propensity score weighting were used to model adverse event outcomes, and Cox proportional hazards regression models with weighting were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach. Among the 1483 patients included in the analysis (935 men [63.0%]; median age, 62 [range, 18-93] years), those receiving proton therapy were significantly older (median age, 66 [range, 18-93] vs 61 [range, 19-91] years; P < .01), had less favorable Charlson-Deyo comorbidity scores (median, 3.0 vs 2.0; P < .01), and had lower integral radiation dose to tissues outside the target (mean [SD] volume, 14.1 [6.4] vs 19.1 [10.6] cGy\/cc \u00d7 107; P < .01). Baseline grade \u22652 toxicity (22% vs 24%; P = .37) and ECOG performance status (mean [SD], 0.62 [0.74] vs 0.68 [0.80]; P = .16) were similar between the 2 cohorts. In propensity score weighted-analyses, proton chemoradiotherapy was associated with a significantly lower relative risk of 90-day adverse events of at least grade 3 (0.31; 95% CI, 0.15-0.66; P = .002), 90-day adverse events of at least grade 2 (0.78; 95% CI, 0.65-0.93; P = .006), and decline in performance status during treatment (0.51; 95% CI, 0.37-0.71; P < .001). There was no difference in disease-free or overall survival. In this analysis, proton chemoradiotherapy was associated with significantly reduced acute adverse events that caused unplanned hospitalizations, with similar disease-free and overall survival. Prospective trials are warranted to validate these results.","subset":"pubmed_abstract"} +{"meta":{"pmid":24200211,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Functional connectivity and cannabis use in high-risk adolescents.\nAdolescence is a unique neurodevelopmental period when regions of the brain most able to assess risk and reward are still in development. Cannabis use during adolescence has been associated with persistent negative outcomes. Although measures of resting brain activity are useful in assessing functional connectivity, such measures have not been broadly applied in adolescent cannabis-users. The goal of the present study was to analyze the associations between cannabis use and resting brain activity in a sample of high-risk adolescents. Eighty-two high-risk youth between 14-18 years old were recruited from a juvenile justice day program. Youth completed a brief neurocognitive battery including assessments of cannabis use and a 5-minute resting functional magnetic resonance imaging (fMRI) scan. Intrinsic connectivity networks were extracted using the GIFT toolbox. Brain activity in a fronto-temporal network was compared in youth with high cannabis use vs. low cannabis use using an independent-samples t-test with alcohol use entered as a covariate. Analysis revealed two elements within the fronto-temporal network related to cannabis use: one in middle frontal gyrus related to high cannabis use, and one in middle temporal gyrus related to low cannabis use. Only the frontal source survived application of a cluster size threshold and was significant at p < 0.005. These results are consistent with patterns of activity in adult cannabis-users. The observed effect may reflect either pre-existing risk factors or near-term consequences of cannabis use. Prevention and intervention strategies that address fronto-temporal functioning may be particularly helpful in this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":25256039,"dup_signals":{"dup_doc_count":54,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":2,"2023-14":2,"2023-06":1,"2022-49":2,"2022-27":2,"2022-05":3,"2021-49":1,"2021-39":1,"2021-31":3,"2021-21":2,"2021-17":2,"2021-04":1,"2020-45":1,"2020-40":1,"2020-24":1,"2020-16":1,"2020-10":1,"2019-43":1,"2019-39":2,"2019-26":2,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":2,"2018-22":1,"2018-13":2,"2017-51":2,"2017-43":2,"2017-34":2,"2024-18":2,"2024-30":1}}},"text":"Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.\nNeurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2\/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLC\u03b3 docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment.","subset":"pubmed_abstract"} +{"meta":{"pmid":16455230,"dup_signals":{"dup_doc_count":26,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-23":2,"2022-21":1,"2022-05":1,"2021-49":2,"2021-21":2,"2021-10":1,"2020-50":2,"2020-40":4,"2020-29":2,"2020-10":1,"2020-05":2,"2023-50":1,"2024-10":2,"2024-26":1}}},"text":"Assessment of the human epidermis model SkinEthic RHE for in vitro skin corrosion testing of chemicals according to new OECD TG 431.\nBased on two successfully completed ECVAM validation studies for in vitro skin corrosion testing of chemicals, the National Co-ordinators of OECD Test Guideline Programme endorsed in 2002 two new test guidelines: TG 430 'Transcutaneous Electrical Resistance assay' and TG 431 'Human Skin Model Test'. To allow all suitable in vitro human reconstructed (dermal or epidermal) models to be used for skin corrosion testing, the OECD TG 431 defines general and functional conditions that the model must meet before it will be routinely used for skin corrosion testing. In addition, the guideline requires correct prediction of 12 reference chemicals and assessment of intra- and inter-laboratory variability. To show that the OECD TG 431 concept works, in 2003 ZEBET tested several chemicals from the ECVAM validation trials on the SkinEthic reconstituted human epidermal (RHE) model. Based on knowledge that reconstructed human skin models perform similarly in toxicological studies, it was decided to adopt the validated EpiDerm skin corrosion test protocol and prediction model to the SkinEthic model. After minor technical changes, classifications were obtained in concordance with those reported for the validated human skin models EPISKIN and EpiDerm. To allow adequate determination of inter-laboratory reproducibility, a blind trial was conducted in three laboratories -- ZEBET (D), Safepharm (UK) and BASF (D), in which the 12 endorsed reference chemicals were tested. Results obtained with the SkinEthic epidermal model were reproducible, both within and between laboratories, and over time. Concordance between the in vitro predictions of skin corrosivity potential obtained with the SkinEthic model and the predictions obtained with the accepted tests of OECD TG 430 and TG 431 was very good. The new test was able to distinguish between corrosive and non-corrosive reference chemicals with an accuracy of 93%.","subset":"pubmed_abstract"} +{"meta":{"pmid":15450183,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2022-49":2,"2022-21":1,"2021-43":1,"2021-21":1,"2021-04":1,"2020-45":1,"2020-34":2,"2020-05":2,"2023-23":1,"2024-10":1}}},"text":"Cryptococcus neoformans capsule biosynthesis and regulation.\nThe capsule is certainly the most prominent virulence factor in Cryptococcus neoformans: acapsular strains are avirulent, and capsular polysaccharides have a deleterious effect on the immune system. Until very recently, very few genes involved in capsule biosynthesis had been identified - and this despite the existence of a detailed body of work concerning the capsule's composition, structure and their regulation by environmental factors. The tremendous development of experimental tools and techniques suited to the study of C. neoformans biology together with the sequencing of three complete genomes have, over the last three years, enabled the identification of a number of proteins which participate directly in biosynthesis of the capsule or which regulate its size. Even though this knowledge is still preliminary, it gives us a clearer picture of the various events needed for biosynthesis of this fascinating structure.","subset":"pubmed_abstract"} +{"meta":{"pmid":28414036,"dup_signals":{"dup_doc_count":11}},"text":"Blunted cortisol response to acute pre-learning stress prevents misinformation effect in a forced confabulation paradigm.\nResearch examining the effects of stress on false memory formation has been equivocal, partly because of the complex nature of stress-memory interactions. A major factor influencing stress effects on learning is the timing of stress relative to encoding. Previous work has shown that brief stressors administered immediately before learning enhance long-term memory. Thus, we predicted that brief stress immediately before learning would decrease participants' susceptibility to subsequent misinformation and reduce false memory formation. Eighty-four male and female participants submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they viewed an 8-min excerpt from the Disney movie Looking for Miracles. The next day, participants were interviewed and asked several questions about the video, some of which forced them to confabulate responses. Three days and three weeks later, respectively, participants completed a recognition test in the lab and a free recall test via email. Our results revealed a robust misinformation effect, overall, as participants falsely recognized a significant amount of information that they had confabulated during the interview as having occurred in the original video. Stress, overall, did not significantly influence this misinformation effect. However, the misinformation effect was completely absent in stressed participants who exhibited a blunted cortisol response to the stress, for both recognition and recall tests. The complete absence of a misinformation effect in non-responders may lend insight into the interactive roles of autonomic arousal and corticosteroid levels in false memory development.","subset":"pubmed_abstract"} +{"meta":{"pmid":22555303,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2017-13":1,"unknown":7}}},"text":"Interaction patterns of nurturant support exchanged in online health social networking.\nExpressing emotion in online support communities is an important aspect of enabling e-patients to connect with each other and expand their social resources. Indirectly it increases the amount of support for coping with health issues. Exploring the supportive interaction patterns in online health social networking would help us better understand how technology features impacts user behavior in this context. To build on previous research that identified different types of social support in online support communities by delving into patterns of supportive behavior across multiple computer-mediated communication formats. Each format combines different architectural elements, affecting the resulting social spaces. Our research question compared communication across different formats of text-based computer-mediated communication provided on the MedHelp.org health social networking environment. We identified messages with nurturant support (emotional, esteem, and network) across three different computer-mediated communication formats (forums, journals, and notes) of an online support community for alcoholism using content analysis. Our sample consisted of 493 forum messages, 423 journal messages, and 1180 notes. Nurturant support types occurred frequently among messages offering support (forum comments: 276\/412 messages, 67.0%; journal posts: 65\/88 messages, 74%; journal comments: 275\/335 messages, 82.1%; and notes: 1002\/1180 messages, 84.92%), but less often among messages requesting support. Of all the nurturing supports, emotional (ie, encouragement) appeared most frequently, with network and esteem support appearing in patterns of varying combinations. Members of the Alcoholism Community appeared to adapt some traditional face-to-face forms of support to their needs in becoming sober, such as provision of encouragement, understanding, and empathy to one another. The computer-mediated communication format may have the greatest influence on the supportive interactions because of characteristics such as audience reach and access. Other factors include perception of community versus personal space or purpose of communication. These results lead to a need for further research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22466190,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Optical readout method based on a narrow-strip filter for microcantilever array sensing.\nAn effective optical readout approach based on a narrow-strip filter is presented to detect bends of a bimaterial microcantilever focal plane array, by which light intensity of the image plane (CCD image sensor plane) can be increased and its uniformity on the image plane effectively enhanced. It reduces the noise equivalent temperature difference of the microcantilever focal plane array IR imaging system and improves uniformity of the IR images. A comparative experiment is designed to verify effectiveness. The experimental results show that the proposed method has advantages of preferable effect.","subset":"pubmed_abstract"} +{"meta":{"pmid":7924986,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The fates of the blastomeres of the 16-cell zebrafish embryo.\nWe present a fate map for the 16-cell-stage blastomeres of the zebrafish embryo Brachydanio rerio. We injected high molecular weight fluorescent dextran into cleavage-stage cells to observe the contributions of the descendants of the first 16 cells to the adult. The patterns derived from these early cells are similar, but not identical among different embryos. Furthermore, two-color injections showed that sister blastomeres at the 16-cell stage regularly contribute to different sets of adult structures. A few of the scored tissues could not be mapped in a manner consistent with the predicted axes. Other tissues were mapped to several of the 16 blastomeres. Many of the tissues map with high probability to a few 16-cell-stage blastomeres. Thus, based on 112 injections in 56 different embryos, we have constructed a fate map by assigning probabilities for the contribution of each blastomere to each of 31 tissues in the 26-hour embryo.","subset":"pubmed_abstract"} +{"meta":{"pmid":35166335,"dup_signals":{"dup_doc_count":45,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":26,"2024-26":10,"2024-22":2,"unknown":5}}},"text":"Pupil dilation and constriction in the skate Leucoraja erinacea in a simulated natural light field.\nThe skate Leucoraja erinacea has an elaborately shaped pupil, whose characteristics and functions have received little attention. The goal of our study was to investigate the pupil response in relation to natural ambient light intensities. First, we took a recently developed sensory-ecological approach, which gave us a tool for creating a controlled light environment for behavioural work: during a field survey, we collected a series of calibrated natural habitat images from the perspective of the skates' eyes. From these images, we derived a vertical illumination profile using custom-written software for quantification of the environmental light field (ELF). After collecting and analysing these natural light field data, we created an illumination set-up in the laboratory, which closely simulated the natural vertical light gradient that skates experience in the wild and tested the light responsiveness - in particular the extent of dilation - of the skate pupil to controlled changes in this simulated light field. Additionally, we measured pupillary dilation and constriction speeds. Our results confirm that the skate pupil changes from nearly circular under low light to a series of small triangular apertures under bright light. A linear regression analysis showed a trend towards smaller skates having a smaller dynamic range of pupil area (dilation versus constriction ratio around 4-fold), and larger skates showing larger ranges (around 10- to 20-fold). Dilation took longer than constriction (between 30 and 45 min for dilation; less than 20 min for constriction), and there was considerable individual variation in dilation\/constriction time. We discuss our findings in terms of the visual ecology of L. erinacea and consider the importance of accurately simulating natural light fields in the laboratory.","subset":"pubmed_abstract"} +{"meta":{"pmid":22064258,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Maternal and fetal outcome in patients with eclampsia at Murtala Muhammad specialist Hospital Kano, Nigeria.\nEclampsia is a major contributor to maternal and perinatal mortality worldwide. It is much more common in developing countries like Nigeria where presentation is usually late and resources are scarce. The staggering figures of maternal death (46%) reported by the Society of Obstetricians and Gynaecologists of Nigeria (SOGON) in 2004 moved the Kano State government to initiate programs that will reduce maternal mortality in the state. The objectives of this report were; 1) to determine the prevalence of eclampsia at Murtala Muhammad Specialist hospital (MMSH) Kano between April 2008 and May 2009; 2) to determine maternal and fetal outcome in eclamptic patients admitted to MMSH Kano between April 2008 and May 2009. Case records of all patients admitted to MMSH between April 2008 and May 2009 were retrieved and analyzed using Epi-info version 3.2.2 April 2004 (CDC Atlanta, USA). Information extracted includes demographic data, maternal and fetal outcome. A P value of less than 0.05 was considered significant. There were 688 eclamptic patients admitted and 13 943 women delivered during the study period giving a prevalence of 5% of total deliveries. One hundred and twenty six women died giving a maternal mortality ratio (MMR) of 904\/100 000, among them 36 were eclamptics. The perinatal mortality rate for the eclamptics was 132\/1 000. 81.4% of the women were primigravidas and majority (82.2%) were at term. Almost 83.3% presented within 12 hours of the onset of the fits and nearly half (44.9%) had their convulsion before the onset of labor. The incidence of eclampsia is 5% of total deliveries. Delay in presentation is associated with poor outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":25888865,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":15}}},"text":"Spatial variation in hyperthermia emergency department visits among those with employer-based insurance in the United States - a case-crossover analysis.\nPredictions of intense heat waves across the United States will lead to localized health impacts, most of which are preventable. There is a need to better understand the spatial variation in the morbidity impacts associated with extreme heat across the country to prevent such adverse health outcomes. Hyperthermia-related emergency department (ED) visits were obtained from the Truven Health MarketScan(\u00ae) Research dataset for 2000-2010. Three measures of daily ambient heat were constructed using meteorological observations from the National Climatic Data Center (maximum temperature, heat index) and the Spatial Synoptic Classification. Using a time-stratified case crossover approach, odds ratio of hyperthermia-related ED visit were estimated for the three different heat measures. Random effects meta-analysis was used to combine the odds ratios for 94 Metropolitan Statistical Areas (MSA) to examine the spatial variation by eight latitude categories and nine U.S. climate regions. Examination of lags for all three temperature measures showed that the odds ratio of ED visit was statistically significant and highest on the day of the ED visit. For heat waves lasting two or more days, additional statistically significant association was observed when heat index and synoptic classification was used as the temperature measure. These results were insensitive to the inclusion of air pollution measures. On average, the maximum temperature on the day of an ED visit was 93.4\u00b0F in 'South' and 81.9\u00b0F in the 'Northwest' climatic regions of United States. The meta-analysis showed higher odds ratios of hyperthermia ED visit in the central and the northern parts of the country compared to the south and southwest. The results showed spatial variation in average temperature on days of ED visit and odds ratio for hyperthermia ED visits associated with extreme heat across United States. This suggests that heat response plans need to be customized for different regions and the potential role of hyperthermia ED visits in syndromic surveillance for extreme heat.","subset":"pubmed_abstract"} +{"meta":{"pmid":10931462,"dup_signals":{"dup_doc_count":11}},"text":"Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma.\nThe aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma. The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression. Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome. Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":22170711,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Relation of vascular growth factors with CT-derived measures of body fat distribution: the Framingham Heart Study.\nVisceral adiposity is associated with metabolic risk. Given that angiogenesis is a key feature of adipogenesis, variation in the association of levels of circulating vascular growth factors (and their soluble receptors) with distinct body fat compartments may explain differences in the systemic pathogenicity of regional fat depots. Four body fat compartments [visceral adipose tissue (VAT), sc adipose tissue (SAT), thoracic periaortic fat, and pericardial fat] derived from computed tomography were related to serum concentrations of vascular endothelial growth factor (VEGF), the soluble VEGF receptor (fms-like tyrosine kinase-1), hepatocyte growth factor (HGF), and angiopoietin-2 and its soluble receptor (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2 sTie-2) in 1806 Framingham Heart Study participants (mean age 44.9 yr, 44.5% women). In multivariable models, we observed positive associations between several fat compartments and VEGF and HGF levels. The magnitude of the associations were similar for VAT, SAT, and periaortic fat. We observed effect modification by sex. A stronger association was observed between VAT and HGF levels in women; higher VAT and periaortic fat were jointly associated with higher HGF concentrations (P=0.02 and P=0.051, respectively). In women within the highest tertile of VAT, HGF levels significantly increased with higher periaortic fat (P=0.0005). In our large community-based sample, greater adiposity was associated with higher circulating growth factor levels in general. Additional studies are warranted to confirm the stronger association of VAT and periaortic fat with HGF in women and to examine its potential contribution to the sex-related differences in cardiometabolic risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":10898958,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Too much interference: injection of double-stranded RNA has nonspecific effects in the zebrafish embryo.\nWe have investigated the ability of double-stranded RNA (dsRNA) to inhibit gene expression in a vertebrate, the zebrafish, Danio rerio. Injection of dsRNA corresponding to the T-box gene tbx16\/spadetail (spt) into early wild-type embryos caused a rapid and dramatic loss of tbx16\/spt mRNA in the blastula. mRNAs from the papc, tbx6, and gata1 genes, which depend on tbx16\/spt function for their expression, were reduced, apparently mimicking the spt mutant phenotype. However, mRNAs from a number of genes that are unaffected by the spt mutation, such as beta catenin, stat3, and no tail, were also lost, indicating that the \"interference\" effect of tbx16\/spt dsRNA was not restricted to the endogenous tbx16\/spt mRNA. We compared the effects of injecting dsRNA from the zebrafish tbx16\/spadetail, nieuwkoid\/bozozok, and Brachyury\/no tail genes with dsRNA from the bacterial lacZ gene. In each case the embryos displayed a variable syndrome of abnormalities at 12 and 24 h postfertilization. In blind studies, we could not distinguish between the effects of the various dsRNAs. Consistent with a common effect of dsRNA, regardless of sequence, injection of dsRNA from the lacZ gene was likewise effective in strongly reducing tbx16\/spt and beta catenin mRNA in the blastula. These findings indicate that, despite published reports, the current methodology of double-stranded RNA interference is not a practical technique for investigating zygotic gene function during early zebrafish development.","subset":"pubmed_abstract"} +{"meta":{"pmid":2828076,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2023-23":1,"2024-10":1}}},"text":"Monoclonal anti-HBs antibodies radioimmunoassay and serum HBV-DNA hybridization as diagnostic tools of HBV infection: relative prevalence among HBsAg-negative alcoholics, patients with chronic hepatitis or hepatocellular carcinomas and blood donors.\nAnti-HBs monoclonal antibodies radioimmunoassay (m-RIA) and HBV-DNA hybridization techniques were used to detect HBs antigen (HBsAg)--associated determinants (evidence of HBV on-going infection) and HBV-DNA sequences (evidence of viral multiplication) in the serum samples of 479 patients who were HBsAg negative by standard solid-phase radioimmunoassay. They included 128 alcoholics, 104 patients with chronic hepatitis, fifty-four with an hepatocellular carcinoma, 100 with coagulation disorders and ninety-three blood donors. The aim of this study was the comparison in these populations of the prevalence of the various HBV markers. m-RIA detected HBsAg-associated determinants in 1% of blood donors, 3% of coagulation disorders, 3.1% of the alcoholics, 21.1% of chronic hepatitis and 16.6% of hepatocellular carcinoma; hybridization identified HBV-DNA sequences in 0.9%, 2.2%, 10.9%, 9.6% and 5.5% of these cases, respectively. The combined prevalence of both markers of an on-going HBV infection (with or without viral multiplication) was 14.16%, 26.9% and 22.2% in the latter groups, respectively, as compared with only 3% in patients with coagulation disorders and 2.1% of blood donors. These results confirm the frequency of HBV or HBV-related virus infection in alcoholics, in chronic hepatitis and hepatocellular carcinomas, despite the absence of HBsAg by standard RIA (or even of any other usual marker); this gives further evidence for variations in the expression of HBV infection. A high and quite similar prevalence of usual serum markers and hybridization results was observed in the alcoholics and in the patients with chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":27269966,"dup_signals":{"dup_doc_count":33,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-06":2,"2022-40":2,"2022-21":2,"2021-49":2,"2021-43":2,"2021-31":2,"2021-21":2,"2021-17":1,"2021-10":3,"2021-04":1,"2020-50":1,"2020-40":2,"2024-26":2,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Genetic risk of Parkinson's disease in the general population.\nWe investigated whether a risk score based on genetic risk variants for Parkinson's disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals. Within the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL. During follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], \u0394C = 0.011 [-0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23]). Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction.","subset":"pubmed_abstract"} +{"meta":{"pmid":10525763,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2021-25":1,"2021-04":1,"2020-50":1,"2020-29":2,"2020-10":1,"2020-05":2,"2019-51":1,"2019-43":2,"2019-30":1,"2022-33":1}}},"text":"Accuracy of MRI-guided stereotactic thalamic functional neurosurgery.\nOur goal was to evaluate the accuracy of stereotactic technique using MRI in thalamic functional neurosurgery. A phantom study was designed to estimate errors due to MRI distortion. Stereotactic mechanical accuracy was assessed with the Suetens-Gybels-Vandermeulen (SGV) angiographic localiser. Three-dimensional MRI reconstructions of 86 therapeutic lesions were performed. Their co-ordinates were corrected from adjustments based on peroperative electrophysiological data and compared to those planned. MR image distortion (maximum: 1 mm) and chemical shift of petroleum oil-filled localiser rods (2.2 mm) induced an anterior target displacement of 2.6 mm (at a field strength of 1.5 T, frequency encoding bandwidth of 187.7 kHz, on T1-weighted images). The average absolute error of the stereotactic material was 0.7 mm for anteroposterior (AP), 0.5 mm for mediolateral (ML) and 0.8 mm for dorsoventral (DV) co-ordinates (maximal absolute errors: 1.6 mm, 2.2 mm and 1.7 mm, respectively; mean euclidean error: 1 mm). Three-dimensional MRI reconstructions showed an average absolute error of 0.8 mm, 0.9 mm and 1.9 mm in AP, ML and DV co-ordinates, respectively (maximal absolute errors: 2.4 mm, 2.7 mm and 5.7 mm, respectively; mean euclidean error: 2.3 mm). MRI distortion and chemical-shift errors must be determined by a phantom study and then compensated for. The most likely explanation for an average absolute error of 1.9 mm in the DV plane is displacement of the brain under the pressure of the penetrating electrode. When this displacement is corrected for by microelectrode recordings and stimulation data, MRI offers a high degree of accuracy and reliability for thalamic stereotaxy.","subset":"pubmed_abstract"} +{"meta":{"pmid":9738811,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Erythema after cutaneous laser resurfacing using a porcine model.\nTo measure and compare postoperative erythema after laser cutaneous resurfacing using 2 carbon dioxide laser systems and varying postoperative treatment methods. Carbon dioxide laser systems are used as cutaneous resurfacing tools. The continuous-wave lasers have been associated with postoperative erythema, but the short-pulsed lasers reportedly result in less postoperative erythema because of shorter pulse durations. Although subjective evaluations of results have been published, a side-by-side comparison with digital photography has not been performed. Furthermore, postoperative treatment varies among physicians, and objective data about this treatment are scarce. To compare postoperative erythema, we created 240 resurfacing wounds on 8 piglets with continuous-wave and short-pulsed lasers, using the manufacturers' suggested settings. By using photography and computed color analysis, we measured the resultant erythema after 1, 3, and 5 laser passes at days 0, 1, 3, 5, 7, and 14. Tissue samples were obtained for histological analysis on days 0, 3, 7, and 14. We compared the resolution of erythema after postoperative treatment with petroleum jelly (Vaseline), a wound dressing (Vigilon), partially hydrogenated vegetable oil (Crisco), or a combination drug, bacitracin zinc-neomycin sulfate-polymyxin B sulfate on the wounds. The short-pulsed carbon dioxide laser resulted in an average of 22% less erythema compared with the continuous-wave laser (P<.001). No statistically significant difference in erythema was found among the postoperative treatment methods (P>.10). Compared with the continuous-wave laser, the short-pulsed carbon dioxide laser results in less postoperative erythema. However, the type of postoperative treatment has little, if any, beneficial effect for reducing erythema.","subset":"pubmed_abstract"} +{"meta":{"pmid":19220343,"dup_signals":{"dup_doc_count":14,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2018-26":1,"2018-09":1,"2018-05":1,"2017-47":2,"2017-43":1,"2017-39":1,"2017-30":2,"2018-30":1}}},"text":"Everything depends on everything else.\nIn physics the concept of entanglement is well established and it has become increasingly apparent that all levels of biological organization (communities, organisms, cells, metabolism) consist of mosaics of interactive networks. There is a universe of bioactive microbial chemicals that have so far only been considered for their therapeutic applications; for example, the environmental roles of antibiotics have been little investigated. At sub-inhibitory concentrations, so-called antibiotics have been shown to modulate bacterial functions in subtle ways; they behave more like signals than toxins. It is proposed that networks of microbial cell signalling are primarily based on the interactions of low molecular weight compounds with macromolecular receptors; studies of the nature of these signals will reveal important information on the functions of microbial communities.","subset":"pubmed_abstract"} +{"meta":{"pmid":18196282,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities.\nWe have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 degrees C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients' lower limbs were calculated. Following LTSB, the patients' deep body temperature increased significantly by 1 degrees C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":26508517,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis.\nThe prevalence of plaque rupture at the culprit lesion identified by optical coherence tomography (OCT) in different clinical subset of patients undergoing coronary angiography and its clinical predictors remain to be defined. All studies including patients with OCT evaluation of the culprit coronary plaque were included. The prevalence of culprit plaque rupture (CPR) and thin-cap fibro-atheroma (TCFA) were the primary endpoints. The factors associated with these findings were studied in a subset of patients with different clinical presentations [ST-elevation myocardial (STEMI) vs. nonST-elevation myocardial infarction (NSTEMI) vs. unstable angina (UA) vs. stable angina pectoris (SAP)]. One hundred and fifty citations were initially appraised at the abstract level and 23 full-text studies were assessed. The mean prevalence of CPR and TCFA was 48.1% (40.5-55.8) and 48.7% (37.4-60.1), respectively. The prevalence of CPR and TCFA were higher in STEMI (70.4 and 76.6%) than in NSTEMI (55.6 and 56.3%) and UA (39.1 and 52.9%) or SAP (6.2 and 22.8%). In the overall population at meta-regression analysis, TCFA and current smoking were the only predictors of CPR (B 3.6:2.0-5.1, P < 0.001 and 0.06:0.02-0.1, P = 0.002, respectively). The factors associated with CPR were different depending on clinical presentation. Hypertension was the only clinical predictor for STEMI (B 3.3: 1.2.-5.3 P = 0.001), while advanced age (B 0.12: 0.02-0.22, P = 0.021), diabetes mellitus (B 0.04: 0.01-0.08, P = 0.012), and hyperlipidaemia (B 0.07:0.02-0.11, P = 0.005) were the predictors in NSTEMI and UA. No clinical predictor was found in SA. Our analysis showed high rates of CPR and TCFA detected by OCT in CAD patients, especially in those with ACS, although their prevalence is not negligible in stable patients. TCFA seems to be a strong predictor of CPR in all the ACS scenarios.","subset":"pubmed_abstract"} +{"meta":{"pmid":8643078,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":7}}},"text":"Epidermal growth factor-mediated inhibition of neurotransmitter glutamate release from rat forebrain synaptosomes.\nWe investigated the possibility that receptor tyrosine kinases are involved in modulating neurotransmitter release from isolated nerve terminals. We examined the effects of epidermal growth factor on the release of neurotransmitter glutamate evoked from rat forebrain synaptosomes by KCI and 4-aminopyridine. We detected a significant inhibition of the Ca2+-dependent component of release. This effect appears to be mediated by a reduction in the depolarization-evoked increase in cytosolic free calcium levels, in the absence of significant effects on the plasma membrane potential. On depolarization, a Ca2+-dependent increase was observed in the phosphotyrosine content of bands at molecular masses of approximately 107 and approximately 40 kDa. The addition of epidermal growth factor before depolarization induced a significant phosphorylation of the growth factor receptor in the absence of detectable changes in the phosphotyrosine pattern of total synaptosomal proteins, suggesting that phosphorylation of a minor protein is responsible for the epidermal growth factor-mediated inhibition of glutamate release.","subset":"pubmed_abstract"} +{"meta":{"pmid":26913148,"dup_signals":{"dup_doc_count":36,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-06":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-10":1,"2019-47":1,"2019-43":2,"2019-35":3,"2019-30":2,"2019-26":2,"2019-22":1,"2019-18":2,"2019-09":2,"2019-04":1,"2018-51":2,"2018-47":2,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-14":1}}},"text":"Persistent Muscle Fiber Regeneration in Long Term Denervation. Past, Present, Future.\nDespite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI) patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES). Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb). Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest that the MHCemb positive muscle fibers we observe result from the activation, proliferation and fusion of satellite cells, the myogenic precursors present under the basal lamina of the muscle fibers. Using morphological features and molecular biomarkers, we show that severely atrophic muscle fibers, with a peculiar cluster reorganization of myonuclei, are present in rodent muscle seven-months after neurectomy and in human muscles 30-months after complete Conus-Cauda Equina Syndrome and that these are structurally distinct from early myotubes. Beyond reviewing evidence from rodent and human studies, we add some ultrastructural evidence of muscle fiber regeneration in long-term denervated human muscles and discuss the options to substantially increase the regenerative potential of severely denervated human muscles not having been treated with h-bFES. Some of the mandatory procedures, are ready to be translated from animal experiments to clinical studies to meet the needs of persons with long-term irreversible muscle denervation. An European Project, the trial Rise4EU (Rise for You, a personalized treatment for recovery of function of denervated muscle in long-term stable SCI) will hopefully follow.","subset":"pubmed_abstract"} +{"meta":{"pmid":33197716,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":3,"2024-18":1,"2024-30":1,"unknown":4}}},"text":"Accurate brain age prediction with lightweight deep neural networks.\nDeep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.","subset":"pubmed_abstract"} +{"meta":{"pmid":26806667,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation.\nThere are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and\/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":30145171,"dup_signals":{"dup_doc_count":16}},"text":"Advancing Research on Care Needs and Supportive Approaches for Persons With Dementia: Recommendations and Rationale.\nThe first National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers was held on October 16-17, 2017, at the National Institutes of Health. In this paper, participants from the Summit Session on Research on Care Needs and Supportive Approaches for Persons with Dementia summarize the state of the science, identify gaps in knowledge, and offer recommendations to improve science and practice in long-term care. Recommendations cover 4 areas focused on persons living with dementia: (1) symptoms (behavioral and psychological symptoms of dementia, function, cognition, and sleep); (2) dementia care settings (physical and social environments, home, and residential care); (3) living with dementia (living well with dementia, living alone with dementia, and living with dementia and intellectual and developmental disabilities); and (4) technology as a cross-cutting theme. The participants identify 10 of the most pressing research issues based on the findings from their collective papers. Final Summit recommendations included those presented by session participants and will be used to advise federal agencies and other organizations that fund research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22687168,"dup_signals":{"dup_doc_count":21,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2017-13":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"unknown":7}}},"text":"Venous angioplasty in multiple sclerosis: neurological outcome at two years in a cohort of relapsing-remitting patients.\nAn open study was conducted with the aim of reporting long-term clinical outcome of endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). Twenty-nine patients with clinically definite relapsing-remitting MS underwent percutaneous transluminal angioplasty for CCSVI, outside a clinical relapse. All the patients were regularly observed over at least two years before the first endovascular treatment and for at least two years after it (mean post-procedure follow up 30.6\u00b16.1 months). The following clinical outcome measures were used: annual relapse rate and Expanded Disability Status Scale (EDSS) score. All the patients were observed intensively (mean 6 hours) on the day of the endovascular treatment to monitor for possible complications (bleeding, shock, heart attack, death). We compared the annual relapse rate before and after treatment (in the two years before and the two years after the first endovascular treatment) and the EDSS score recorded two years before versus two years after the treatment. Overall, 44 endovascular procedures were performed in the 29 patients, without complications. Thirteen of the 29 patients (45%) underwent more than one treatment session because of venous re-stenosis: 11 and two patients underwent two and three endovascular treatments respectively. The annual relapse rate of MS was significantly lower post-procedure (0.45\u00b10.62 vs 0.76\u00b10.99; p=0.021), although it increased in four patients. The EDSS score two years after treatment was significantly lower compared to the EDSS score recorded at the examination two years before treatment (1.98\u00b10.92 vs 2.27\u00b10.93; p=0.037), although it was higher in four patients. Endovascular treatment of concurrent CCSVI seems to be safe and repeatable and may reduce annual relapse rates and cumulative disability in patients with relapsing-remitting MS. Randomized controlled studies are needed to further assess the clinical effects of endovascular treatment of CCSVI in MS.","subset":"pubmed_abstract"} +{"meta":{"pmid":10993949,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Neuronal density in the human retinal ganglion cell layer from 16-77 years.\nLiterature assessing whether or not neurons (retinal ganglion cells and displaced amacrine cells) are lost from the retinal ganglion cell layer in mammals with age is still controversial, some studies finding a decrease in cell density and others not. To date there have been no studies estimating the total number of neurons in the retinal ganglion cell layer of humans throughout life. Recent studies have concentrated on the macular region and examined cell densities, which are reported to decrease during aging. In a study of the human retinal pigment epithelium (RPE), we showed that, while RPE cell number does not change, cell density increases significantly in central temporal retina (macular region) as the retina ages. We speculated that the increase in density represents a \"drawing together\" of the retinal sheet to maintain high cell densities, in this region of the neural retina, in the face of presumed cell loss from the ganglion cell layer due to aging. Here, therefore, we have sampled the entire ganglion cell layer of the human retina and estimated total neuron numbers in 12 retinae aged from 16 to 77 years. Human retinae, fixed in formalin, were obtained from the Queensland Eye Bank and whole-mounted, ganglion cell layer uppermost. The total number of neurons was lower in the older than younger retinae and neuronal density was lower in most retinal regions in older retinae. Retinal area increased with age and neuronal density fell throughout the retina with a mean reduction of 0.53% per year. However, the percentage reduction in density was much lower for the macular region, with a value of 0.29% per year. It is possible that this lesser reduction in cell density in the macula is a result of the drawing together of the retinal sheet in this region as we speculated from RPE data.","subset":"pubmed_abstract"} +{"meta":{"pmid":32311293,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Neurodevelopmental Outcome of Extremely Low Birth Weight Infants Fed an Exclusive Human Milk Diet Is Not Affected by Growth Velocity.\nBackground: An exclusive human milk (EHM) diet in extremely low birth weight (ELBW) infants (birth weight \u22641,000 g) is linked to an increased likelihood of extrauterine growth restriction (EUGR, weight <10% at discharge). Past studies associated EUGR with worse neurodevelopmental (ND) outcomes; however, its impact when an EHM diet is used is unknown. Objective: Determine whether EUGR adversely affects 2-year ND outcomes of ELBW infants fed an EHM diet. Secondary aims were to compare short-term morbidities and growth through 2 years corrected age (CA). Materials and Methods: Prospective cohort study of ELBW infants fed an EHM diet until 34 weeks corrected gestational age and assessed at 2 years CA. ND outcomes between EUGR and non-EUGR infants were compared using the Bayley Scales of Infant Development 3rd Ed (BSID-III). Results: Eighty-one ELBW infants survived, 44 were seen for follow-up, and 16 (36%) were EUGR. Baseline characteristics and Neonatal Intensive Care Unit (NICU) morbidities were similar. There were no statistically significant differences (median [25-75%]) between EUGR and non-EUGR groups in cognition, (90 [80-99] versus 95 [90-104]), language (84 [68-105] versus 89 [75-100]), or motor composite scores (87 [74-96] versus 91 [88-96]). Weight z-scores during NICU stay dropped in both groups, more pronounced for the EUGR infants. There was no difference in linear or head growth. Conclusion: In our institution, ND outcomes at 2 years CA for ELBW infants fed an EHM diet were similar regardless of EUGR status. This suggests a neuroprotective effect of EHM diet in the ELBW population, despite weight gain velocity during NICU stay.","subset":"pubmed_abstract"} +{"meta":{"pmid":16984714,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":15}}},"text":"'They're not racist ...' prejudice denial, mitigation and suppression in dialogue.\nSocial scientific work on the suppression, mitigation or denial of prejudiced attitudes has tended to focus on the strategic self-presentation and self-monitoring undertaken by individual social actors on their own behalf. In this paper, we argue that existing perspectives might usefully be extended to incorporate three additional considerations. First, that social actors may, on some occasions, act to defend not only themselves, but also others from charges of prejudice. Second, that over the course of any social encounter, interactants may take joint responsibility for policing conversation and for correcting and suppressing the articulation of prejudiced talk. Third, that a focus on the dialogic character of conversation affords an appreciation of the ways in which the status of any particular utterance, action or event as 'racist' or 'prejudiced' may constitute a social accomplishment. Finally, we note the logical corollary of these observations - that in everyday life, the occurrence of 'racist discourse' is likely to represent a collaborative accomplishment, the responsibility for which is shared jointly between the person of the speaker and those other co-present individuals who occasion, reinforce or simply fail to suppress it.","subset":"pubmed_abstract"} +{"meta":{"pmid":21220404,"dup_signals":{"dup_doc_count":21,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-33":1,"2019-26":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-05":2,"2017-22":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2022-40":1}}},"text":"A prospective study of the effects of optimism on adolescent health risks.\nThe promotion of optimism has been widely advocated for children and adolescents, but epidemiologic data to support this approach are scant. This was a 3-wave longitudinal study of health and social development in younger adolescents from 3 Australian states. The 5634 student participants, initially aged 12 to 14 years, were assessed for optimistic thinking style, emotional problems, substance use, and antisocial behaviors. Cross-sectional associations between optimism and each of the study outcomes were strongly protective but tended to differ according to gender in extent. In prospective analyses of the onset of new cases of each study outcome, protective associations were weaker. Those in the highest optimism quartile had risks for depressive symptoms that were reduced by almost half (odds ratio: 0.54 [95% confidence interval: 0.42-0.70]) compared with those in the lowest category. No effect was seen in prevention of anxiety symptoms after adjustment for other aspects of psychological style. In predicting the onset of heavy substance use and antisocial behavior, high optimism had modest protective effects. Optimistic thinking style is somewhat protective against adolescent health risks; the clearest effects are seen against depressive symptoms. Promoting optimism along with other aspects of psychological and emotional style has a role in mental health promotion that is likely to be enhanced if an intervention also addresses risk and protective factors in an adolescent's social context.","subset":"pubmed_abstract"} +{"meta":{"pmid":27517891,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Phytoestrogen Metabolism by Adult Human Gut Microbiota.\nPhytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic\/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI\/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.","subset":"pubmed_abstract"} +{"meta":{"pmid":29753019,"dup_signals":{"dup_doc_count":19}},"text":"Psychophysical and neuroimaging responses to moving stimuli in a patient with the Riddoch phenomenon due to bilateral visual cortex lesions.\nPatients with injury to early visual cortex or its inputs can display the Riddoch phenomenon: preserved awareness for moving but not stationary stimuli. We provide a detailed case report of a patient with the Riddoch phenomenon, MC. MC has extensive bilateral lesions to occipitotemporal cortex that include most early visual cortex and complete blindness in visual field perimetry testing with static targets. Nevertheless, she shows a remarkably robust preserved ability to perceive motion, enabling her to navigate through cluttered environments and perform actions like catching moving balls. Comparisons of MC's structural magnetic resonance imaging (MRI) data to a probabilistic atlas based on controls reveals that MC's lesions encompass the posterior, lateral, and ventral early visual cortex bilaterally (V1, V2, V3A\/B, LO1\/2, TO1\/2, hV4 and VO1 in both hemispheres) as well as more extensive damage to right parietal (inferior parietal lobule) and left ventral occipitotemporal cortex (VO1, PHC1\/2). She shows some sparing of anterior occipital cortex, which may account for her ability to see moving targets beyond ~15 degrees eccentricity during perimetry. Most strikingly, functional and structural MRI revealed robust and reliable spared functionality of the middle temporal motion complex (MT+) bilaterally. Moreover, consistent with her preserved ability to discriminate motion direction in psychophysical testing, MC also shows direction-selective adaptation in MT+. A variety of tests did not enable us to discern whether input to MT+ was driven by her spared anterior occipital cortex or subcortical inputs. Nevertheless, MC shows rich motion perception despite profoundly impaired static and form vision, combined with clear preservation of activation in MT+, thus supporting the role of MT+ in the Riddoch phenomenon.","subset":"pubmed_abstract"} +{"meta":{"pmid":3494809,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Aging in man. Linear increase of a novel T cell subset defined by antiganglioside monoclonal antibody 3G5.\nA new human T cell subset defined by antineuronal ganglioside mAb 3G5 increases linearly with advancing age in man. The percentage of circulating 3G5+ T cells in 21 normal individuals, quantitated by cytofluorograph analysis, increases linearly from age 7 (23-30%) to age 84 (58%) (r = 0.85, p less than 0.001). The antigen on T cells has the biochemical properties of a ganglioside that migrates between GM1 and GM2 ganglioside markers on TLC. The 3G5 subset represents the first T cell subset that reflects aging in man.","subset":"pubmed_abstract"} +{"meta":{"pmid":8167132,"dup_signals":{"dup_doc_count":65,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2023-50":2,"2023-40":6,"2023-23":3,"2023-14":3,"2023-06":3,"2022-49":1,"2022-40":3,"2022-27":1,"2022-21":3,"2022-05":1,"2021-49":5,"2021-43":2,"2021-39":1,"2021-31":4,"2021-21":2,"2021-17":2,"2021-10":2,"2021-04":3,"2020-50":3,"2020-45":1,"2020-40":3,"2024-22":3,"2024-18":4,"2024-30":1}}},"text":"Preoperative predictors of survival in patients with Thoratec ventricular assist devices as a bridge to heart transplantation. Thoratec Ventricular Assist Device Principal Investigators.\nApproximately two-thirds of patients implanted with ventricular assist devices recover sufficiently to requalify for heart transplantation, and the other one-third die of complications that are often secondary to delayed ventricular assist device implantation and subsequent end-organ failure. To determine whether any preoperative predictors of survival exist, univariate statistics and multivariate stepwise logistic regression analysis were performed on pre-ventricular assist device demographics, hemodynamics, and blood chemistry in 186 patients receiving Thoratec ventricular assist devices (Thoratec Laboratories Corp., Berkeley, Calif.) while awaiting transplantation. The duration of circulatory support averaged 19.6 days (maximum, 226 days). One hundred thirty-seven patients (74%) received biventricular support, 47 received isolated left ventricular assist devices, and two received right ventricular assist devices. The average blood flow was 5.0 +\/- 0.9 L\/min. One hundred eighteen patients (63%) ultimately received heart transplants, of whom 96 patients were discharged. Age, gender, weight, and diagnosis were not related to survival, nor were preoperative cardiac index, pulmonary capillary wedge pressure, intraaortic balloon pumps, or cardiac arrests. Pre-ventricular assist device creatinine levels (p = 0.24) and total bilirubin levels (p = 0.09) were not significant, but blood urea nitrogen level (p = 0.02) and previous operations (p = 0.05) were related to survival, using univariate techniques. Patients with cardiac operations more than 30 days previously had the lowest survival-to-transplantation (39%) compared with patients with no previous operations (67%) or operations within the previous 30 days (61%). Blood urea nitrogen level was the only parameter found to be significant (p = 0.016) in a multivariate model.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":15821118,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":2,"2023-14":1,"2022-27":2,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2024-10":1,"2024-26":1}}},"text":"Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell-type-specific manner.\nMIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Glucocorticoids (GC) have been reported to induce secretion of MIF in rodent cells, and as MIF counteracts the anti-inflammatory effects of GC, this has implications for human inflammatory disease. Transient transfection studies showed that the MIF promoter was repressed by dexamethasone (Dex) (10 nM) in CEM C7A cells, with up to 50% suppression by 100 nM. However, there was no regulation of the promoter by GC in A549 cells. We also found that subnanomolar concentrations of Dex suppressed MIF secretion, measured by ELISA, by 80% in both human T lymphoblasts (CEM C7A) and human lung epithelial cells (A549). Endogenous MIF mRNA was also repressed by GC in CEM C7A cells, measured both by Northern blot and quantitative RT-PCR assays, but there was no such regulation in A549 cells. This suggests that GC affects translation rather than transcription of MIF in A549 cells. These results contradict earlier results with the rat cell line RAW 264.7. Therefore, we analysed MIF secretion from RAW 264.7 cells but found no GC effect on secretion. Understanding how GC regulates MIF in a cell-type-dependent manner may give insights into GC-refractory human inflammatory diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":18357316,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":15}}},"text":"Ozone and water-vapor measurements by Raman lidar in the planetary boundary layer: error sources and field measurements.\nA new lidar instrument has been developed to measure tropospheric ozone and water vapor at low altitude. The lidar uses Raman scattering of an UV beam from atmospheric nitrogen, oxygen, and water vapor to retrieve ozone and water-vapor vertical profiles. By numerical simulation we investigate the sensitivity of the method to both atmospheric and device perturbations. The aerosol optical effect in the planetary boundary layer, ozone interference in water-vapor retrieval, statistical error, optical cross talk between Raman-shifted channels, and optical cross talk between an elastically backscattered signal in Raman-shifted signals and an afterpulse effect are studied in detail. In support of the main conclusions of this model study, time series of ozone and water vapor obtained at the Swiss Federal Institute of Technology in Lausanne and during a field campaign in Crete are presented. They are compared with point monitor and balloon sounding measurements for daytime and nighttime conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":32173657,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis.\nScleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC. ARA-positive patients (n = 99) with at least 5 years' follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort. Analysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 \u00d7 10-5), CTNND2 (rs1859082; P = 5.58 \u00d7 10-5), HECW2 (rs16849716; P = 1.2 \u00d7 10-4), and GPATCH2L (rs935332; P = 4.92 \u00d7 10-5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP. Increased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.","subset":"pubmed_abstract"} +{"meta":{"pmid":23861542,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":14}}},"text":"Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression.\nTumor necrosis factor-\u03b1 (TNF-\u03b1) elicits its biological activities through activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as p75). The activities of both receptors are required for the TNF-\u03b1-induced proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is critical for either p55- or p75-mediated activation of nuclear factor \u03baB (NF-\u03baB) and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression. We identified nonmuscle myosin II (myosin) as a binding partner of p75. TNF-\u03b1-dependent signaling by p75 and induction of target gene expression persisted substantially longer in cells deficient in myosin regulatory light chain (MRLC; a component of myosin) than in cells replete in myosin. In resting endothelial cells, myosin was bound constitutively to the intracellular region of p75, a region that overlaps with the TRAF2-binding domain, and TNF-\u03b1 caused the rapid dissociation of myosin from p75. At early time points after exposure to TNF-\u03b1, p75 activated Rho-associated kinase 1 (ROCK1). Inhibition of ROCK1 activity blocked TNF-\u03b1-dependent phosphorylation of MRLC and the dissociation of myosin from p75. ROCK1-dependent release of myosin was necessary for the TNF-\u03b1-dependent recruitment of TRAF2 to p75 and for p75-specific activation of NF-\u03baB and MAPK signaling. Thus, our findings have revealed a previously uncharacterized, noncanonical regulatory function of myosin in cytokine signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":22201207,"dup_signals":{"dup_doc_count":43,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-23":2,"2023-06":2,"2022-40":2,"2022-21":2,"2021-49":3,"2021-43":1,"2021-31":2,"2021-17":2,"2021-04":1,"2020-50":1,"2020-45":1,"2019-26":1,"2019-04":1,"2018-43":1,"2018-26":1,"2018-17":2,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2023-40":1,"2024-18":4,"2024-10":1,"2024-30":1}}},"text":"Cluster randomised trials.\nAlthough randomised controlled trials are the reference methodology to assess the effects of therapeutic interventions, for interventions that naturally occur in groups of individuals random allocation of participants may be inappropriate. In these cases, the unit of random allocation may be the group or cluster, rather than the individual. Clinical trials that randomly allocate groups or clusters of individuals are called cluster randomised trials. This article briefly presents the main implications of cluster randomisation with respect to the following methodological aspects: generalisability, concealment of allocation, comparability at baseline, blindness, loss of clusters and intra-class correlation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21529718,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":19}}},"text":"A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue.\nHigh-content screening for gene profiling has generally been limited to single cells. Here, we explore an alternative approach-profiling gene function by analyzing effects of gene knockdowns on the architecture of a complex tissue in a multicellular organism. We profile 554 essential C. elegans genes by imaging gonad architecture and scoring 94 phenotypic features. To generate a reference for evaluating methods for network construction, genes were manually partitioned into 102 phenotypic classes, predicting functions for uncharacterized genes across diverse cellular processes. Using this classification as a benchmark, we developed a robust computational method for constructing gene networks from high-content profiles based on a network context-dependent measure that ranks the significance of links between genes. Our analysis reveals that multi-parametric profiling in a complex tissue yields functional maps with a resolution similar to genetic interaction-based profiling in unicellular eukaryotes-pinpointing subunits of macromolecular complexes and components functioning in common cellular processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27270106,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Selfish drive can trump function when animal mitochondrial genomes compete.\nMitochondrial genomes compete for transmission from mother to progeny. We explored this competition by introducing a second genome into Drosophila melanogaster to follow transmission. Competitions between closely related genomes favored those functional in electron transport, resulting in a host-beneficial purifying selection. In contrast, matchups between distantly related genomes often favored those with negligible, negative or lethal consequences, indicating selfish selection. Exhibiting powerful selfish selection, a genome carrying a detrimental mutation displaced a complementing genome, leading to population death after several generations. In a different pairing, opposing selfish and purifying selection counterbalanced to give stable transmission of two genomes. Sequencing of recombinant mitochondrial genomes showed that the noncoding region, containing origins of replication, governs selfish transmission. Uniparental inheritance prevents encounters between distantly related genomes. Nonetheless, in each maternal lineage, constant competition among sibling genomes selects for super-replicators. We suggest that this relentless competition drives positive selection, promoting change in the sequences influencing transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":11961969,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-30":1,"unknown":14}}},"text":"[Incidental finding of inguinal hernia sac cancer].\nThe presence of cancer in a hernia sac is uncommon. The tumor can involve the hernia sac, the herniated mass or be external to the hernia sac. We report two cases with this condition. A 68 years old male was operated of a right inguinal hernia. During surgery, several white nodules were noted in the internal side of hernia sac. The same lesions were present in the mesentery. Pathological study revealed an adenocarcinoma. The primary tumor was not located and the patient died one and a half years after the procedure. A 62 years old male was operated due to an irreducible inguinal mass, seven months after a subtotal gastrectomy for gastric cancer. During the resection of the mass, metastasis implants in the mesenteric adipose tissue were noted. A mini laparotomy was performed and an extensive peritoneal tumor dissemination was found. The patient died two months after surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":7900593,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Transcranial Doppler ultrasound in the evaluation of collateral blood flow in patients with internal carotid artery occlusion: correlation with cerebral angiography.\nTo determine the accuracy of transcranial Doppler (TCD) ultrasound for evaluation of collateral supply through the circle of Willis in patients with internal carotid artery (ICA) occlusion. The evaluation of the collateral pathways through the circle of Willis with TCD ultrasound and with cerebral angiography was compared in 40 patients (30 men, 10 women; mean age, 55 +\/- 9 years) in a total of 44 ICA occlusions of which 43 had a suitable ipsilateral temporal bone window for TCD examination. By TCD, a patent anterior communicating artery is indicated by a reversal blood flow in the A1-segment of the anterior cerebral artery or by a prompt fall of blood velocity in the middle cerebral artery after compression of the nonoccluded contralateral carotid artery. In 42 of 43 instances of ICA occlusion, TCD and angiography agreed in the evaluation of a present or absent anterior communicating artery collateral supply. TCD's sensitivity was 95%, its specificity 100%. A collateral supply through the basilar artery was assumed with TCD when there was: (a) a basilar artery blood velocity of more than 70 cm\/s; (b) a marked increase of basilar artery blood velocity after compression of the nonoccluded carotid artery; (c) an evident side-to-side asymmetry of the blood velocity of the posterior cerebral arteries with high blood velocity ipsilateral to the ICA occlusion. For evaluating the collateralization via the basilar artery, TCD and angiography agreed in 37 of 40 ICA occlusions. TCD's sensitivity was 87%, its specificity 95%. TCD is a reliable tool for the evaluation of the collateral supply in patients with ICA occlusions.","subset":"pubmed_abstract"} +{"meta":{"pmid":32405459,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-30":1,"unknown":19}}},"text":"Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study.\nWhile the COVID-19 pandemic will increase mortality due to the virus, it is also likely to increase mortality indirectly. In this study, we estimate the additional maternal and under-5 child deaths resulting from the potential disruption of health systems and decreased access to food. We modelled three scenarios in which the coverage of essential maternal and child health interventions is reduced by 9\u00b78-51\u00b79% and the prevalence of wasting is increased by 10-50%. Although our scenarios are hypothetical, we sought to reflect real-world possibilities, given emerging reports of the supply-side and demand-side effects of the pandemic. We used the Lives Saved Tool to estimate the additional maternal and under-5 child deaths under each scenario, in 118 low-income and middle-income countries. We estimated additional deaths for a single month and extrapolated for 3 months, 6 months, and 12 months. Our least severe scenario (coverage reductions of 9\u00b78-18\u00b75% and wasting increase of 10%) over 6 months would result in 253 500 additional child deaths and 12 200 additional maternal deaths. Our most severe scenario (coverage reductions of 39\u00b73-51\u00b79% and wasting increase of 50%) over 6 months would result in 1 157 000 additional child deaths and 56 700 additional maternal deaths. These additional deaths would represent an increase of 9\u00b78-44\u00b77% in under-5 child deaths per month, and an 8\u00b73-38\u00b76% increase in maternal deaths per month, across the 118 countries. Across our three scenarios, the reduced coverage of four childbirth interventions (parenteral administration of uterotonics, antibiotics, and anticonvulsants, and clean birth environments) would account for approximately 60% of additional maternal deaths. The increase in wasting prevalence would account for 18-23% of additional child deaths and reduced coverage of antibiotics for pneumonia and neonatal sepsis and of oral rehydration solution for diarrhoea would together account for around 41% of additional child deaths. Our estimates are based on tentative assumptions and represent a wide range of outcomes. Nonetheless, they show that, if routine health care is disrupted and access to food is decreased (as a result of unavoidable shocks, health system collapse, or intentional choices made in responding to the pandemic), the increase in child and maternal deaths will be devastating. We hope these numbers add context as policy makers establish guidelines and allocate resources in the days and months to come. Bill & Melinda Gates Foundation, Global Affairs Canada.","subset":"pubmed_abstract"} +{"meta":{"pmid":6360757,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Preparation of high-potency, non-aggregating insulins using a novel sulfation procedure.\nThe marked propensity of insulin to self-associate into large aggregates causes significant mechanical problems in insulin delivery devices and may also stimulate production of a tissue-amyloid A precursor in some patients. Although conventionally prepared sulfated insulin (SI) resists aggregation, clinical application has been limited by major insulin bioactivity losses that occur during synthesis. To eliminate this problem, insulin sulfation was carried out in the organic solvent dimethylformamide in the presence of condensing agents such as N,N'-dicyclohexyl carbodiimide (DCC) and a sulfate donor. With this new procedure, the degree of sulfation could be controlled over an eightfold range by varying the amount of condensing agent. The bioactivity of these new SI derivatives varied between 78% and 87% of unmodified insulin. Insulin aggregation, induced by passage through a syringe and needle, did not occur with derivatives having two or more sulfate moieties per insulin molecule. Diffusion velocity studies using \"non-aggregated\" insulin solutions demonstrated that aggregates were present in crystalline zinc and sodium porcine insulin. In contrast, SI having more than 0.5 mole sulfate per mole of insulin dialyzed as it were predominantly in the monomeric form. Results from the studies described in this report now provide the means for selectively designing and preparing specific high-potency, non-aggregating insulins, which may be necessary for optimal use of current and future insulin delivery devices.","subset":"pubmed_abstract"} +{"meta":{"pmid":14972980,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2021-21":1,"2021-10":1,"2020-10":1,"2019-39":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2021-49":1,"2024-10":1,"2024-26":1}}},"text":"Turbulent transfer in a deciduous forest.\nCarbon dioxide, water vapor and other passive scalars are physically transferred between a plant canopy and the atmosphere by turbulence. Intense and intermittent sweep and ejection events transfer most of the mass. Although the capacity for turbulence to transfer material is high, mass transfer is coupled to the diffusive source or sink strength of the foliage and soil and is ultimately limited to a minimum level set by the supply of material, or the demand for it. The diffusive source\/sink strength of material leaving or entering leaves and the soil is a function of many physical, biological and chemical attributes and processes. These attributes and processes include the amount and distribution of foliage, the leaf boundary layer and surface resistances, the turbulence and radiative regimes in the canopy, biochemical and photochemical reactions and the scalar concentration field within and above the canopy and inside leaves and the soil. Here we discuss how these factors contribute to turbulent transfer in a deciduous forest.","subset":"pubmed_abstract"} +{"meta":{"pmid":21898601,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Sleep fears, sleep disturbance, and PTSD symptoms in minority youth exposed to Hurricane Katrina.\nPosttraumatic stress disorder (PTSD) is common following the experience of a natural disaster and sleep disturbance is an important influence on its course in adults, but little research is available examining sleep and PTSD in youths. This study's objective was to evaluate the role of sleep disturbance and the developmentally influenced factor of fear of sleeping alone in the maintenance of posttraumatic stress (PTS) symptoms in youths. Deidentified data of 191 Hurricane Katrina survivors ages 8 to 15 were used in this study. We found cross-sectional relationships of sleep disturbance and fear of sleeping alone with PTS symptom severity. Longitudinal analysis also indicated that general sleep disturbance at 24 months (T1) was predictive of PTS symptoms severity at 30 months (T2) even after adjusting for PTS symptom severity at T1, age, sex, and continued disrepair to the home. These results have implications for intervention strategies among youth exposed to traumatic events.","subset":"pubmed_abstract"} +{"meta":{"pmid":24743344,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Highly differentiated ZW sex microchromosomes in the Australian Varanus species evolved through rapid amplification of repetitive sequences.\nTransitions between sex determination systems have occurred in many lineages of squamates and it follows that novel sex chromosomes will also have arisen multiple times. The formation of sex chromosomes may be reinforced by inhibition of recombination and the accumulation of repetitive DNA sequences. The karyotypes of monitor lizards are known to be highly conserved yet the sex chromosomes in this family have not been fully investigated. Here, we compare male and female karyotypes of three Australian monitor lizards, Varanus acanthurus, V. gouldii and V. rosenbergi, from two different clades. V. acanthurus belongs to the acanthurus clade and the other two belong to the gouldii clade. We applied C-banding and comparative genomic hybridization to reveal that these species have ZZ\/ZW sex micro-chromosomes in which the W chromosome is highly differentiated from the Z chromosome. In combination with previous reports, all six Varanus species in which sex chromosomes have been identified have ZZ\/ZW sex chromosomes, spanning several clades on the varanid phylogeny, making it likely that the ZZ\/ZW sex chromosome is ancestral for this family. However, repetitive sequences of these ZW chromosome pairs differed among species. In particular, an (AAT)n microsatellite repeat motif mapped by fluorescence in situ hybridization on part of W chromosome in V. acanthurus only, whereas a (CGG)n motif mapped onto the W chromosomes of V. gouldii and V. rosenbergi. Furthermore, the W chromosome probe for V. acanthurus produced hybridization signals only on the centromeric regions of W chromosomes of the other two species. These results suggest that the W chromosome sequences were not conserved between gouldii and acanthurus clades and that these repetitive sequences have been amplified rapidly and independently on the W chromosome of the two clades after their divergence.","subset":"pubmed_abstract"} +{"meta":{"pmid":20973697,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Children and youth with fetal alcohol spectrum disorders: summary of intervention recommendations after clinical diagnosis.\nChildren with fetal alcohol spectrum disorders (FASDs) present with a wide range of developmental disabilities; however, clinical standards of care after a diagnosis are not well established. This retrospective review summarizes the types of intervention recommendations generated by an interdisciplinary FASD diagnostic team for 120 children ages 0.2 to 16.5 years receiving an FASD diagnosis at the University of Washington FAS Diagnostic & Prevention Network Clinic. Intervention recommendations documented in a FASD diagnostic summary report and submitted to each patient's medical record were subject to masked review and content analysis. Intervention recommendations were compared across 3 FASD diagnostic groups and selected demographic variables. The results show the type and frequency of services, supports, and resources recommended to a clinical sample of children with FASD.","subset":"pubmed_abstract"} +{"meta":{"pmid":12218732,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Possible mechanism of quadriceps femoris weakness in patients with ruptured anterior cruciate ligament.\nThe purpose of this study was to test the hypothesis that loss of afferent feedback due to rupture of anterior cruciate ligament (ACL) is the cause of quadriceps femoris (QF) weakness through gamma loop. Two experiments were designed to prove our hypothesis. In experiment 1, the maximal voluntary contraction (MVC) of knee extension and integrated electromyogram (I-EMG) of vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) were measured in 13 patients with ruptured ACL and 7 healthy volunteers before and after injection of anesthetic agent into the knee. In experiment 2, MVC of knee extension and I-EMG of the VM, VL, and RF were measured in 13 patients with ruptured ACL, 7 knee-anesthetized healthy subjects, and 12 normal subjects, before and after 20-min vibration stimulation applied to the infrapatellar tendon. The results of experiment 1 revealed that injection of anesthetic agent into the knee capsule resulted in significant decrease of MVC and I-EMGs. In experiment 2, the mean percentage change of MVC in the control group was significantly lower than that in the other two groups. There was no significant difference between knee-anesthetized group and patients with ruptured ACL. The mean percentage change of I-EMG showed a pattern similar to that of MVC. Our results suggest that loss of feedback from mechanoreceptors in ACL is the underlying mechanism of weakness of QF in patients with ACL lesion. This conclusion is based on chronic suppression of recruitment of high-threshold motor units during voluntary contraction because ACL lesion leads to chronic reduction in Ia-feedback to muscles around the knee due to a lack of feedback from ACL to gamma motor neurons.","subset":"pubmed_abstract"} +{"meta":{"pmid":26066564,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Multiple factors, including non-motor impairments, influence decision making with regard to exercise participation in Parkinson's disease: a qualitative enquiry.\nTo explore how the meaning of exercise and other factors interact and influence the exercise behaviour of individuals with Parkinson's disease (PD) enrolled in a 6-month minimally supervised exercise program to prevent falls, regardless of whether they completed the prescribed exercise or not. This qualitative study utilised in-depth semi-structured interviews analysed using grounded theory methodology. Four main themes were constructed from the data: adapting to change and loss, the influence of others, making sense of the exercise experience and hope for a more active future. Participation in the PD-specific physiotherapy program involving group exercise provided an opportunity for participants to reframe their identity of their \"active\" self. Three new influences on exercise participation were identified and explored: non-motor impairments of apathy and fatigue, the belief in a finite energy quota, and the importance of feedback. A model was developed incorporating the themes and influences to explain decision-making for exercise participation in this group. Complex and interacting issues, including non-motor impairments, need to be considered in order to enhance the development and ongoing implementation of effective exercise programmes for people with PD. Exercise participation can assist individuals to reframe their identity as they are faced with losses associated with Parkinson's disease and ageing. Non-motor impairments of apathy and fatigue may influence exercise participation in people with Parkinson's disease. Particular attention needs to be paid to the provision of feedback in exercise programs for people with Parkinson's disease as it important for their decision-making about continuing exercise.","subset":"pubmed_abstract"} +{"meta":{"pmid":11238972,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-26":1,"unknown":9}}},"text":"Characterization of a copper-transport operon, copYAZ, from Streptococcus mutans.\nA copper-transport (copYAZ) operon was cloned from the oral bacterium Streptococcus mutans JH1005. DNA sequencing showed that the operon contained three genes (copY, copA and copZ), which were flanked by a single promoter and a factor-independent terminator. copY encoded a small protein of 147 aa with a heavy-metal-binding motif (CXCX(4)CXC) at the C-terminus. CopY shared extensive homology with other bacterial negative transcriptional regulators. copA encoded a 742 aa protein that shared extensive homology with P-type ATPases. copZ encoded a 67 aa protein that also contained a heavy-metal-binding motif (CXXC) at the N-terminus. Northern blotting showed that a 3.2 kb transcript was produced by Cu2+-induced Strep. mutans cells, suggesting that the genes were synthesized as a polycistronic message. The transcriptional start site of the cop operon was mapped and shown to lie within the inverted repeats of the promoter-operator region. Strep. mutans wild-type cells were resistant to 800 microM Cu2+, whereas cells of a cop knock-out mutant were killed by 200 microM Cu2+. Complementation of the cop knock-out mutant with the cop operon restored Cu2+ resistance to wild-type level. The wild-type and the mutant did not show any differences in susceptibility to other heavy metals, suggesting that the operon was specific for copper. By using a chloramphenicol acetyltransferase reporter gene fusion, the cop operon was shown to be negatively regulated by CopY and could be derepressed by Cu2+.","subset":"pubmed_abstract"} +{"meta":{"pmid":23798000,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-48":1,"unknown":9}}},"text":"Recent advances in Parkinson's disease genetics.\nThe last 5 years have seen rapid progress in Parkinson's disease (PD) genetics, with the publication of a series of large-scale genome wide association studies for PD, and evaluation of the roles of the LRRK2 and GBA genes in the aetiology of PD. We are beginning to develop a coherent picture of the interplay of Mendelian and non-Mendelian factors in PD. Pathways involved in mitochondrial quality control (mitophagy), lysosomal function and immune function are emerging as important in the pathogenesis of PD. These pathways represent a target for therapeutic intervention and a way in which the heterogeneity of disease cause, as well as disease mechanism, can be established. In the future, there is likely to be an individualised basis for the treatment of PD, linked to the identification of specific genetic factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":30699568,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Quick and Accurate Detection and Quantification of Magnaporthe oryzae in Rice Using Real-Time Quantitative Polymerase Chain Reaction.\nRice blast, caused by Magnaporthe oryzae, is one of the most severe fungal diseases in rice worldwide. In this study, we developed methods to quickly and accurately detect and quantify M. oryzae in the pure cultures of the fungus, rice plants, and rice seed by using SYBR Green I of the real-time quantitative polymerase chain reaction (qPCR). Results of absolute qPCR show that Magnaporthe oryzae can be detected at as low as 6.9 \u00d7 10-5 ng of genomic DNA. Results also show that all 10 varieties of rice seed examined in this study contain this fungus, indicating that M. oryzae is generally widespread in rice seed. We report the quantification of DNA of M. oryzae in rice leaves collected in the field, instead of in the lab, using relative qPCR by using rice actin gene as a housekeeping gene. Our results show great practical significance because we would know the potential fungal infection even before planting.","subset":"pubmed_abstract"} +{"meta":{"pmid":23046183,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Large-scale field study on thin-layer capping of marine PCDD\/F-contaminated sediments in Grenlandfjords, Norway: physicochemical effects.\nA large-scale field experiment on in situ thin-layer capping was carried out in the polychlorinated dibenzodioxin and dibenzofuran (PCDD\/F) contaminated Grenlandsfjords, Norway. The main focus of the trial was to test the effectiveness of active caps (targeted thickness of 2.5 cm) consisting of powdered activated carbon (AC) mixed into locally dredged clean clay. Nonactive caps (targed thickness of 5 cm) consisting of clay without AC as well as crushed limestone were also tested. Fields with areas of 10,000 to 40,000 m(2) were established at 30 to 100 m water depth. Auxiliary shaken laboratory batch experiments showed that 2% of the applied powdered AC substantially reduced PCDD\/F porewater concentrations, by >90% for tetra-, penta- and hexa-clorinated congeners to 60-70% for octachlorinated ones. In-situ AC profiles revealed that the AC was mixed into the sediment to 3 to 5 cm depth in 20 months. Only around 25% of the AC was found inside the pilot fields. Sediment-to-water PCDD\/F fluxes measured by in situ diffusion chambers were significantly lower at the capped fields than at reference fields in the same fjord, reductions being largest for the limestone (50-90%) followed by clay (50-70%), and the AC + clay (60%). Also reductions in overlying aqueous PCDD\/F concentrations measured by passive samplers were significant in most cases (20-40% reduction), probably because of the large size of the trial fields. The AC was less effective in the field than in the laboratory, probably due to prolonged sediment-to-AC mass transfer times for PCDD\/Fs and field factors such as integrity of the cap, new deposition of contaminated sediment particles, and bioturbation. The present field data indicate that slightly thicker layers of limestone and dredged clay can show as good physicochemical effectiveness as thin caps of AC mixed with clay, at least for PCDD\/Fs during the first two years after cap placement.","subset":"pubmed_abstract"} +{"meta":{"pmid":22659350,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":7}}},"text":"Coping with chronic complex regional pain syndrome: advice from patients for patients.\nTo explore what advice people currently living with chronic complex regional pain syndrome would offer to another person coming to terms with a diagnosis of chronic complex regional pain syndrome. Semi-structured interviews with 21 adults (5 male) living with chronic complex regional pain syndrome who had completed a complex regional pain syndrome rehabilitation programme were conducted. Effectively self-managing complex regional pain syndrome required individuals to play an active role. This could only be achieved if they felt they had sufficient control. Means of attaining control involved attaining a level of acceptance, becoming well-informed and accessing the right kind of support. The advice offered by patients for patients largely reflected that offered by healthcare professionals. One area where there was a conflict concerned sleep hygiene. Our study provides support both for the argument put forward by Redman that without appropriate preparation and support, self-management is ineffective, and that by Skuladottir and Hallsdottir that the main challenge of the chronic pain trajectory is that of retaining a sense of control. The clinical implications of this are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":8025163,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"In vitro development of in vitro-matured porcine oocytes following chemical activation or in vitro fertilization.\nPorcine cumulus-oocyte complexes were cultured in BSA-free Whitten's medium or modified Medium 199, each supplemented with porcine follicular fluid (PFF) and hormonal supplements (OMWM and OMM199, respectively) for 20 h; they then were cultured without hormonal supplements for an additional 20 (experiments 1 and 3) or 24 h (experiment 2). At the end of culture (experiment 1), the intracellular glutathione concentration was higher (p < 0.05) in oocytes matured in OMWM vs. OMM199. After activation by Ca2+ ionophore (experiment 2), the incidence of activation in the OMWM group was lower (p < 0.01) than in the OMM199 group. However, the incidence of pronuclear formation was higher (p < 0.01) in the OMWM group than in the OMM199 group at 8 h after activation. The percentage of embryos that developed to the morula stage was higher (p < 0.01) in the group matured in OMWM vs. OMM199 after 5 days of culture. After in vitro fertilization (experiment 3), the incidence of male pronuclear formation and the percentage of monospermic oocytes that formed one male and one female pronuclei were higher (p < 0.05) after maturation in OMWM vs. OMM199. The percentage of cleaved embryos that developed to the 8-cell and morula stages was higher (p < 0.05) in the OMWM group as compared to the OMM199 group. These results indicate that culture in modified Whitten's medium as compared with a standard medium (modified Medium 199) improves cytoplasmic maturation of porcine oocytes as evaluated by intracellular glutathione content, pronuclear formation, and development in vitro after artificial activation or fertilization in vitro.","subset":"pubmed_abstract"} +{"meta":{"pmid":17307799,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"KLRG1 binds cadherins and preferentially associates with SHIP-1.\nThe killer cell lectin-like receptor G1 (KLRG1) is a unique inhibitory receptor expressed on a phenotypically mature subset of resting NK cells as well as subsets of T cells in naive mice. In vivo, pathogenic immune system activation induces dramatic changes in the expression patterns of KLRG1 among the different cell subsets. In order to enhance our understanding of KLRG1 signaling properties and to clarify the functions of KLRG1 on these cells, we identified the broadly expressed N-cadherin molecule as a ligand for KLRG1. We further demonstrate that a second member of this superfamily of adhesion molecules, E-cadherin, binds to KLRG1. Additionally, we show that upon phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) tyrosine, KLRG1 recruits both SHIP-1 and SHP-2 but not SHP-1. We also delineate the key KLRG1 ITIM amino acid residues required for optimal association with these phosphatases. Finally, we demonstrate that KLRG1 engagement can inhibit sub-optimal TCR signaling. Taken together, our results indicate that KLRG1 may differentially regulate NK cell and T cell functions through the association with different ligands as well as the recruitment of distinct phosphatases.","subset":"pubmed_abstract"} +{"meta":{"pmid":11717410,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy.\nMuscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":21429740,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-33":1,"2022-21":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2023-50":1,"2024-22":1}}},"text":"Acclimation of Nannochloropsis gaditana to different illumination regimes: effects on lipids accumulation.\nAlgae are interesting potential sources of biodiesel, although research is still needed to develop efficient large scale productions. One major factor affecting productivity is light use efficiency. The effect of different light regimes on the seawater alga Nannochloropsis gaditana was accessed monitoring growth rate and photosynthetic performances. N. gaditana showed the capacity of acclimating to different light intensities, optimizing its photosynthetic apparatus to illumination. Thanks to this response, N. gaditana maintained similar growth rates under a wide range of irradiances, suggesting that this organism is a valuable candidate for outdoor productions in variable conditions. In the conditions tested here, without external CO(2) supply, light intensity alone was not found to be a major signal affecting lipids accumulation showing the absence of a direct regulatory link between the light stress and lipids accumulation. Strong illumination can nevertheless indirectly influences lipid accumulation if combined with other stresses or in the presence of excess CO(2).","subset":"pubmed_abstract"} +{"meta":{"pmid":27226695,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Twelve-Minute Daily Yoga Regimen Reverses Osteoporotic Bone Loss.\nAssess the effectiveness of selected yoga postures in raising bone mineral density (BMD). Ten-year study of 741 Internet-recruited volunteers comparing preyoga BMD changes with postyoga BMD changes. Dual-energy x-ray absorptiometric scans. Optional radiographs of hips and spine and bone quality study (7 Tesla). Bone mineral density improved in spine, hips, and femur of the 227 moderately and fully compliant patients. Monthly gain in BMD was significant in spine (0.0029 g\/cm2, P = .005) and femur (0.00022 g\/cm2, P = .053), but in 1 cohort, although mean gain in hip BMD was 50%, large individual differences raised the confidence interval and the gain was not significant for total hip (0.000357 g\/cm2). No yoga-related serious injuries were imaged or reported. Bone quality appeared qualitatively improved in yoga practitioners. Yoga appears to raise BMD in the spine and the femur safely.","subset":"pubmed_abstract"} +{"meta":{"pmid":27449128,"dup_signals":{"dup_doc_count":39,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":2,"2024-18":1,"2024-10":2,"unknown":31}}},"text":"Participatory approaches involving community and healthcare providers in family planning\/contraceptive information and service provision: a scoping review.\nAs efforts to address unmet need for family planning and contraception (FP\/C) accelerate, voluntary use, informed choice and quality must remain at the fore. Active involvement of affected populations has been recognized as one of the key principles in ensuring human rights in the provision of FP\/C and in improving quality of care. However, community participation continues to be inadequately addressed in large-scale FP\/C programmes. Community and healthcare providers' unequal relationship can be a barrier to successful participation. This scoping review identifies participatory approaches involving both community and healthcare providers for FP\/C services and analyzes relevant evidence. The detailed analysis of 25 articles provided information on 28 specific programmes and identified three types of approaches for community and healthcare provider participation in FP\/C programmes. The three approaches were: (i) establishment of new groups either health committees to link the health service providers and users or implementation teams to conduct specific activities to improve or extend available health services, (ii) identification of and collaboration with existing community structures to optimise use of health services and (iii) operationalization of tools to facilitate community and healthcare provider collaboration for quality improvement. Integration of community and healthcare provider participation in FP\/C provision were conducted through FP\/C-only programmes, FP\/C-focused programmes and\/or as part of a health service package. The rationales behind the interventions varied and may be multiple. Examples include researcher-, NGO- or health service-initiated programmes with clear objectives of improving FP\/C service provision or increasing demand for services; facilitating the involvement of community members or service users and, in some cases, may combine socio-economic development and increasing self-reliance or control over sexual and reproductive health. Although a number of studies reported increase in FP\/C knowledge and uptake, the lack of robust monitoring and evaluation mechanisms and quantitative and comparable data resulted in difficulties in generating clear recommendations. It is imperative that programmes are systematically designed, evaluated and reported.","subset":"pubmed_abstract"} +{"meta":{"pmid":2995175,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Long term cultivation of Namalva cells for interferon production: stable cytogenetic markers for identification of cells in spite of drastic chromosomal variation.\nNamalva cells were propagated continuously over a period of up to 18 months. During this period the chromosomal status of the cell populations were investigated cytogenetically. The ability of the cells to produce interferons after induction with Sendai virus was monitored. In contrast to the drastic chromosomal variation observed, interferon production was remarkably stable. Comparison of the various cytogenetic data revealed the presence of marker chromosomes and chromosomal constellations which were excluded from the drift. Some of these are useful for unequivocal identification of Namalva cells during long term cultivation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22240014,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2014-10":1,"unknown":11}}},"text":"Functional characteristics of mesenchymal stem cells derived from bone marrow of patients with myelodysplastic syndromes.\nMesenchymal stem cells (MSCs) have emerged as excellent candidates for clinical application because of their capabilities of immunomodulatory and supporting hematopoiesis. Nevertheless, it is unclear whether the characteristics of MSCs are altered in diseased states. In this study, we obtained and expanded MSCs from bone marrow of patients with myelodysplastic syndromes (MDS). Our results showed that MSCs derived from MDS (MDS-MSCs) were similar to normal adult bone marrow derived MSCs in morphology, growth property, surface epitopes, and differentiation ability in vitro. In addition, MDS-MSCs had normal karyotype and ultrastructure. However, MDS-MSCs appeared to be impaired in immunomodulatory and supporting hematopoiesis function. Although, MDS-MSCs could express hematopoietic cytokines and support hematopoiesis in long term culture, Real time quantitative polymerase chain reaction showed that the expression of hematopoietic cytokines in MDS-MSCs was much lower than that of normal adult derived MSCs. Moreover, MDS-MSCs showed reduced hematopoiesis support function, as compared to their normal counterparts. Lastly, the capacity of MDS-MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. These results indicate that MDS-MSCs have impaired immunomodulatory and hematopoiesis support functions, suggesting their critical role in the pathogenesis of MDS.","subset":"pubmed_abstract"} +{"meta":{"pmid":18636461,"dup_signals":{"dup_doc_count":35,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":1,"2023-06":3,"2022-49":1,"2022-33":1,"2022-27":1,"2021-43":1,"2021-31":1,"2021-25":2,"2021-21":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-10":1,"2019-22":1,"2018-26":1,"2018-05":1,"2017-43":1,"2017-30":1,"2017-17":1,"2017-09":1,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":3,"2024-30":1}}},"text":"Adipose-derived stem cell: a better stem cell than BMSC.\nTo further study the proliferation and multi-differentiation potentials of adipose-derived stem cells (ADSCs), the cells were isolated with improved methods and their growth curves were achieved with cck-8. Surface protein expression was analyzed by flow cytometry to characterize the cell phenotype. The multi-lineage potential of ADSCs was testified by differentiating cells with adipogenic, chondrogenic, osteogenic, and myogenic inducers. The results showed that about 5 x 10(5) stem cells could be obtained from 400 to 600 mg adipose tissue. The ADSCs can be continuously cultured in vitro for up to 1 month without passage and they have several logarithmic growth phases during the culture period. Also, the flow cytometry analysis showed that ADSCs expressed high levels of stem cell-related antigens (CD13, CD29, CD44, CD105, and CD166), while did not express hematopoiesis-related antigens CD34 and CD45, and human leukocyte antigen HLA-DR was also negative. Moreover, stem cell-related transcription factors, Nanog, Oct-4, Sox-2, and Rex-1 were positively expressed in ADSCs. The expression of alkaline phosphatase (ALP) was detected in the early osteogenic induction and the calcified nodules were observed by von Kossa staining. Intracellular lipid droplets could be observed by Oil Red staining. Differentiated cardiomyocytes were observed by connexin43 fluorescent staining. In order to obtain more stem cells, we can subculture ADSCs every 14 days instead of the normal 5 days. ADSCs still keep strong proliferation ability, maintain their phenotypes, and have stronger multi-differentiation potential after 25 passages.","subset":"pubmed_abstract"} +{"meta":{"pmid":27136457,"dup_signals":{"dup_doc_count":13}},"text":"Potentially inappropriate prescribing according to STOPP and START and adverse outcomes in community-dwelling older people: a prospective cohort study.\nThis study aims to determine if potentially inappropriate prescribing (PIP) is associated with increased healthcare utilization, functional decline and reduced quality of life (QoL) in a community-dwelling older cohort. This prospective cohort study included participants aged \u226565 years from The Irish Longitudinal Study on Ageing (TILDA) with linked administrative pharmacy claims data who were followed up after 2 years. PIP was defined by the Screening Tool for Older Persons Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START). The association with number of emergency department (ED) visits and GP visits reported over 12 months was analyzed using multivariate negative binomial regression adjusting for confounders. Marginal structural models investigated the presence of time-dependent confounding. Of participants followed up (n = 1753), PIP was detected in 57% by STOPP and 41.8% by START, 21.7% reported an ED visit and 96.1% visited a GP (median 4, IQR 2.5-6). Those with any STOPP criterion had higher rates of ED visits (adjusted incident rate ratio (IRR) 1.30, 95% confidence interval (CI) 1.02, 1.66) and GP visits (IRR 1.15, 95%CI 1.06, 1.24). Patients with two or more START criteria had significantly more ED visits (IRR 1.45, 95%CI 1.03, 2.04) and GP visits (IRR 1.13, 95%CI 1.01, 1.27) than people with no criteria. Adjusting for time-dependent confounding did not affect the findings. Both STOPP and START were independently associated with increased healthcare utilization and START was also related to functional decline and QoL. Optimizing prescribing to reduce PIP may provide an improvement in patient outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":30334795,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"CPU Isosurface Ray Tracing of Adaptive Mesh Refinement Data.\nAdaptive mesh refinement (AMR) is a key technology for large-scale simulations that allows for adaptively changing the simulation mesh resolution, resulting in significant computational and storage savings. However, visualizing such AMR data poses a significant challenge due to the difficulties introduced by the hierarchical representation when reconstructing continuous field values. In this paper, we detail a comprehensive solution for interactive isosurface rendering of block-structured AMR data. We contribute a novel reconstruction strategy-the octant method-which is continuous, adaptive and simple to implement. Furthermore, we present a generally applicable hybrid implicit isosurface ray-tracing method, which provides better rendering quality and performance than the built-in sampling-based approach in OSPRay. Finally, we integrate our octant method and hybrid isosurface geometry into OSPRay as a module, providing the ability to create high-quality interactive visualizations combining volume and isosurface representations of BS-AMR data. We evaluate the rendering performance, memory consumption and quality of our method on two gigascale block-structured AMR datasets.","subset":"pubmed_abstract"} +{"meta":{"pmid":3418284,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Cigarette smoking and male lung cancer in an area of very high incidence. I. Report of a case-control study in the West of Scotland.\nAltogether 656 male lung cancer cases and 1312 age and sex matched controls were interviewed between 1976 and 1981 in a case-control study of cigarette smoking habits and lung cancer in Glasgow and the West of Scotland, an area with the highest recorded incidence in the world. The relative risk of lung cancer increased significantly for smokers whose consumption was below 20 cigarettes per day but did not rise significantly in those who smoked more than 20 cigarettes per day. Other smoking characteristics such as inhalation and tar yields of brands smoked did not explain this finding. Additionally, the relative risks observed at all levels of cigarette consumption were low in comparison with those in the published literature. By constructing an index of cigarette exposure which included the tar yields of brands smoked, an assessment of the risk of lung cancer in relation to tar exposure independent of amount smoked was derived. Only in smokers of less than 15 cigarettes per day was there a statistically significant reduction in risk of lung cancer associated with lower levels of tar yield.","subset":"pubmed_abstract"} +{"meta":{"pmid":22203799,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Synaptic scaling in combination with many generic plasticity mechanisms stabilizes circuit connectivity.\nSynaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, synaptic scaling changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable, and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models that reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially enables robust dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. Synaptic scaling combined with plasticity could thus be the basis for learning structured behavior even in initially random networks.","subset":"pubmed_abstract"} +{"meta":{"pmid":16842007,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Polyamide platinum anticancer complexes designed to target specific DNA sequences.\nTwo new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence: d(CATTGTCAGAC)(2), than toward either d(GTCTGTCAATG)(2,) which contains different flanking sequences, or d(CATTGAGAGAC)(2), which contains a double base pair mismatch sequence. DJ1953-2 unwinds the DNA helix by around 13 degrees , but neither metal complex significantly affects the DNA melting temperature. Unlike simple DNA minor groove binders, DJ1953-2 is able to inhibit, in vitro, RNA synthesis. The cytotoxicity of both metal complexes in the L1210 murine leukaemia cell line was also determined, with DJ1953-6 (34 microM) more active than DJ1953-2 (>50 microM). These results demonstrate the potential of polyamide platinum complexes and provide the structural basis for designer agents that are able to recognize biologically relevant sequences and prevent DNA transcription and replication.","subset":"pubmed_abstract"} +{"meta":{"pmid":10542475,"dup_signals":{"dup_doc_count":13,"dup_dump_count":6,"dup_details":{"curated_sources":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":4}}},"text":"[Assessment of a health program for the non-insured population].\nPresent the results of the evaluation of a program for the non-insured population of the four poorest states of the country implemented by the Ministry of Health of Mexico between 1991 and 1995. The effects of the program were evaluated in three areas: i) increase in health services coverage; ii) delivery of personal health services, and iii) changes in health conditions of the target population. The extension of coverage was measured by the increase in potential access due to the construction of health infrastructure projects and the use of additional health manpower, mainly primary health care workers. For the evaluation of the impact of the program on the delivery of services, three surveys were developed: one for service utilization, another one for accessibility, and a third for quality of care. The impact on health conditions was evaluated by changes in health indicators of children under five and women of reproductive age. The Program had a positive impact on coverage, accessibility and quality of services. Its impact on health conditions was also positive. However, these last changes cannot be attributed only to the program, but to the sum of several concurrent activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":17657103,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Nephronophthisis-medullary cystic kidney disease: from bedside to bench and back again.\nMedullary cystic kidney disease (MCKD) belongs with nephronophthisis (NPH) to the NPH-MCKD complex, a group of inherited tubulointerstitial nephritis which share some morphological and clinical features. Juvenile NPH, the most frequent variant of the complex, is a recessive disease with onset in childhood leading to end stage renal disease (ESRD) within the 2nd decade of life. The most frequent extrarenal involvement is tapeto-retinal degeneration. MCKD is a less frequent disease with dominant inheritance; it is recognized later in life, leading to ESRD at the age of 50 years, and may be associated with hyperuricemia and gout. In an early phase, both NPH and MCKD are pauci-symptomatic, major signs being confined to polyuria. Later in the course, clinical findings are related to the progressive renal insufficiency, such as anemia, uremic symptoms and, in NPH, growth retardation. On renal ultrasound, the kidneys present an increased medullary echogenicity with diminished cortico-medullary differentiation. Renal cysts may be present, usually at corticomedullary boundary. Due to the clinico-pathological identity, the two diseases were considered to be a single disorder, and the compromise appellation of NPH-MCKD complex was suggested. This unifying conception was subsequently refuted following the identification of MCKD dominant families. The recent advances of the molecular genetics changed the traditional classification of NPH-MCKD complex. The majority of cases of juvenile NPH are due to deletion of the NPHP1 gene on chromosome 2q13. Genes for infantile and adolescent NPH have been localized to chromosome 9q22-q31 and 3q22, respectively. A new locus, NPHP4, has been recently mapped on chromosome 1p36. Two genes predisposing to dominant MCKD, MCKD1 and MCKD2, have been localized to chromosome 1q21 and to chromosome 16p12. Moreover, a gene for familial juvenile hyperuricemic nephropathy (FJHN), a phenotype very similar to MCKD, was mapped to 16p12 in a region overlapping with the MCKD2 locus. The proof of the allelism between MCKD2 and FJHN has been recently provided by the identification of four novel uromodulin (UMOD) gene mutations, segregating with the disease phenotype in three families with FJHN and one with family with MCKD2. These data provide the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":24748717,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Neural Encoding of Speech and Music: Implications for Hearing Speech in Noise.\nUnderstanding speech in a background of competing noise is challenging, especially for individuals with hearing loss or deficits in auditory processing ability. The ability to hear in background noise cannot be predicted from the audiogram, an assessment of peripheral hearing ability; therefore, it is important to consider the impact of central and cognitive factors on speech-in-noise perception. Auditory processing in complex environments is reflected in neural encoding of pitch, timing, and timbre, the crucial elements of speech and music. Musical expertise in processing pitch, timing, and timbre may transfer to enhancements in speech-in-noise perception due to shared neural pathways for speech and music. Through cognitive-sensory interactions, musicians develop skills enabling them to selectively listen to relevant signals embedded in a network of melodies and harmonies, and this experience leads in turn to enhanced ability to focus on one voice in a background of other voices. Here we review recent work examining the biological mechanisms of speech and music perception and the potential for musical experience to ameliorate speech-in-noise listening difficulties.","subset":"pubmed_abstract"} +{"meta":{"pmid":11996044,"dup_signals":{"dup_doc_count":12}},"text":"Usefulness as guided bone regeneration membrane of the alginate membrane.\nAlginate membrane is a new bioabsorbable, guided bone regeneration (GBR) membrane, which is placed directly on the surface of the bone defect. It is designed to drop a calcium chloride aqueous solution into the bone defect, which is filled with sodium alginate aqueous solution. Alginate membrane is an excellent agent for this procedure due to its close assimilation to the surface of the bone. In this study, we evaluated the short-term biocompatibility of alginate membrane in the bone defects of rat tibiae. GBR membrane availability was also examined. Consequently, we found that the healing process in bone defects covered with an alginate membrane was delayed in comparison with that of controls, however, the defect was restored to nearly original condition. In contrast, in the controls, bone defect repairs exhibited partitioning as a result of connective tissue involvement. Furthermore, we observed a relation between the sodium alginate concentration and the rate of absorption of the sodium alginate membrane. Absorption of a 1.5% sodium alginate membrane was slow. As a result, the compound was not absorbed completely and bone repairs resembled an hourglass. Moreover, the inflammatory response was absent surrounding the alginate membrane. The present findings suggested that the alginate membrane functions effectively as a GBR membrane. In addition, the alginate membrane derived from 3% calcium chloride and 1% sodium alginate was most suitable as a GBR membrane.","subset":"pubmed_abstract"} +{"meta":{"pmid":32675902,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Review of Episiotomy and the Effect of its Risk Factors on Postepisiotomy Complications at the University of Port Harcourt Teaching Hospital.\nThis study aimed to determine the prevalence of episiotomy and postepisiotomy complications and to assess the relationship between the risk factors and postepisiotomy complications in the University of Port Harcourt Teaching Hospital. This was a descriptive longitudinal study, in which 403 consecutive women who had episiotomy in the labor ward were recruited for the study. They were followed up and reviewed at the postnatal clinic on the 1st and 6th weeks postdelivery. Data regarding age, marital status, occupation, educational status, address, parity, booking status, postepisiotomy complications, and the associated risk factors were entered adequately into a prestructured pro forma, and statistical analysis was done using statistical software (SPSS for Windows\u00ae version 19.0). t-test was used to explore the association of risk factors to postepisiotomy complications. The episiotomy rate was 22.1%. The prevalence of postepisiotomy complications was 52.1%. The mean age of the women was 23.8 (standard deviation \u00b1 3.2) years. Seventy-two (34.3%) patients had perineal pain, which lasted for 72 h or more; 61 (29.1%) had difficulty in walking, while 37 (17.6%) had perineal discomfort. Four (1.9%) had wound infection and only one (0.4%) had wound dehiscence. The development of postepisiotomy complications was not statistically significantly associated with risk factors such as gestational age (T = 1.4, P = 0.1), packed cell volume on admission (T = 1.0, P = 0.2), duration of first stage of labor (T = 0.5, P = 0.1), duration of second stage of labor (T = 0.7, P = 0.3), duration of rupture of fetal membranes (T = 0.8, P = 0.4), delivery repair interval (T = 0.6, P = 0.2), estimated blood loss (T = 0.9, P = 0.2), duration of Sitz bath (T = 1.0, P = 0.2), duration of analgesic (T = 1.2, P = 0.1), duration of antibiotics (T = 1.3, P = 0.1), or the operator who performed or repaired the episiotomy (P = 0.2). The prevalence of episiotomy and postepisiotomy complications in this study was high. Necessary attention should be given to ensure adequate pain relief for all parturients who had episiotomy, and the policy of restrictive use of episiotomy should be fully implemented in the department in line with the best practices and evidence-based recommendations. This will further reduce the incidence of episiotomy rate as well complications that may arise from it and ensure a positive pregnancy experience for pregnant women.","subset":"pubmed_abstract"} +{"meta":{"pmid":22688927,"dup_signals":{"dup_doc_count":42,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2018-26":2,"2018-22":1,"2018-17":2,"2018-13":1,"2018-09":3,"2018-05":1,"2017-51":2,"2017-47":3,"2017-43":2,"2017-39":3,"2017-34":2,"2017-30":3,"2017-26":2,"2017-22":3,"2017-17":2,"2017-09":3,"2018-30":1,"2017-13":2}}},"text":"Lyme disease following a dog bite--was there a tick?\nLyme disease is the most common tick borne infection in temperate zones and the reported incidence of the condition is increasing. Erythema migrans is one of the few clinical signs of Lyme disease and is usually indicative of recently acquired infection. A case is presented of Lyme disease with erythema migrans which followed shortly after a dog bite. The author is not aware of any previously reported similar case. The author considers that the development of Lyme disease in the case was most likely due to a coincidental tick bite which was not noticed by the patient but an alternative possibility is that the disease was activated from a latent form. Patients with Lyme disease may not give a history of tick bite and clinicians should be aware of this.","subset":"pubmed_abstract"} +{"meta":{"pmid":27443955,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective.\nIn most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.","subset":"pubmed_abstract"} +{"meta":{"pmid":26604095,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":2,"2024-18":1,"unknown":9}}},"text":"Generalisation, decision making, and embodiment effects in mental rotation: A neurorobotic architecture tested with a humanoid robot.\nMental rotation, a classic experimental paradigm of cognitive psychology, tests the capacity of humans to mentally rotate a seen object to decide if it matches a target object. In recent years, mental rotation has been investigated with brain imaging techniques to identify the brain areas involved. Mental rotation has also been investigated through the development of neural-network models, used to identify the specific mechanisms that underlie its process, and with neurorobotics models to investigate its embodied nature. Current models, however, have limited capacities to relate to neuro-scientific evidence, to generalise mental rotation to new objects, to suitably represent decision making mechanisms, and to allow the study of the effects of overt gestures on mental rotation. The work presented in this study overcomes these limitations by proposing a novel neurorobotic model that has a macro-architecture constrained by knowledge held on brain, encompasses a rather general mental rotation mechanism, and incorporates a biologically plausible decision making mechanism. The model was tested using the humanoid robot iCub in tasks requiring the robot to mentally rotate 2D geometrical images appearing on a computer screen. The results show that the robot gained an enhanced capacity to generalise mental rotation to new objects and to express the possible effects of overt movements of the wrist on mental rotation. The model also represents a further step in the identification of the embodied neural mechanisms that may underlie mental rotation in humans and might also give hints to enhance robots' planning capabilities.","subset":"pubmed_abstract"} +{"meta":{"pmid":24731565,"dup_signals":{"dup_doc_count":13,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-26":1,"2024-22":1,"2024-18":2,"2024-10":2,"2024-30":1,"unknown":5}}},"text":"Time to unravel the conceptual confusion of authenticity and fidelity and their contribution to learning within simulation-based nurse education. A discussion paper.\nHigh-fidelity patient simulation is a method of education increasingly utilised by educators of nursing to provide authentic learning experiences. Fidelity and authenticity, however, are not conceptually equivalent. Whilst fidelity is important when striving to replicate a life experience such as clinical practice, authenticity can be produced with low fidelity. A challenge for educators of undergraduate nursing is to ensure authentic representation of the clinical situation which is a core component for potential success. What is less clear is the relationship between fidelity and authenticity in the context of simulation based learning. Authenticity does not automatically follow fidelity and as a result, educators of nursing cannot assume that embracing the latest technology-based educational tools will in isolation provide a learning environment perceived authentic by the learner. As nursing education programmes increasingly adopt simulators that offer the possibility of representing authentic real world situations, there is an urgency to better articulate and understand the terms fidelity and authenticity. Without such understanding there is a real danger that simulation as a teaching and learning resource in nurse education will never reach its potential and be misunderstood, creating a potential barrier to learning. This paper examines current literature to promote discussion within nurse education, concluding that authenticity in the context of simulation-based learning is complex, relying on far more than engineered fidelity.","subset":"pubmed_abstract"} +{"meta":{"pmid":31381332,"dup_signals":{"dup_doc_count":18,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2022-21":1,"2021-43":2,"2021-25":2,"2021-10":2,"2020-50":2,"2020-40":2,"2022-27":1,"2024-10":1,"2024-26":1}}},"text":"Cytotoxic and Antibacterial Cervinomycins B1-4 from a Streptomyces Species.\nAntiSMASH analysis of genome DNA of Streptomyces CPCC 204980, a soil isolate with potent antibacterial activity, revealed a gene cluster for polycyclic xanthones. A subsequent chemical study confirmed that the microorganism produced polycyclic xanthone cervinomycin A2 (1) and the new congeners cervinomycins B1-4 (2-5). The structures of 1-5 were determined by comprehensive analyses of MS and NMR data, which indicated that 2-5 featured a common dihydro-D ring in the polycyclic xanthone core moiety of their molecules. 2-5 are toxic to human cancer cells and active against Gram-positive bacteria.","subset":"pubmed_abstract"} +{"meta":{"pmid":32185305,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"Patient with ankylosing spondylitis and scleroderma renal crisis.\nWe report a 56-year-old man with a history of ankylosing spondylitis and systemic scleroderma. The patient had been diagnosed with ankylosing spondylitis 20 years ago and had been receiving treatment with NSAIDs and anti TNF\u03b1 drugs. He referred to our rheumatology department for Raynaud's phenomenon, arthralgias and weight loss. Physical examination revealed stiffness of the skin with difficulty in pinching (mainly at lower extremities, from knee to ankle). Soon after his first visit to our department, he developed renal scleroderma crisis with abrupt increase in blood pressure, decline in renal function, and microangiopathic haemolytic anaemia in accordance with positive antinuclear autoantibodies and positive anti-topoisomerase I antibody (anti-Scl70). This is one of the few reports in the literature of coexistence of ankylosing spondylitis and systemic scleroderma. A genetic correlation seems to be an explanation in some patients who carry one or two susceptibility alleles to both diseases. Thus, this might be the case of a 'genetic trap' in which distinct genes are cooperating to favour the susceptibility to two different HLA-associated systemic autoimmune diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":30747191,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Heterogeneous hydrosilylation reaction catalysed by platinum complexes immobilized on bipyridine-periodic mesoporous organosilicas.\nThe utility of a bipyridine periodic mesoporous organosilica, BPy-PMO, as a support material of a hydrosilylation catalyst was investigated in the hydrosilylation of phenylacetylene with trimethoxysilane. [PtMe2(BPy-PMO)] (1) exhibited a moderate catalytic activity, whereas the reaction was successfully catalysed by [PtMe2(BPy-PMO-TMS)] (2) bearing end-capped TMS groups on the surface. Spectroscopic analyses of 2 revealed that the porous structure of BPy-PMO-TMS remained almost unchanged through the reaction. The hot filtration test supported the nonleaching property of 2, thereby exhibiting good reusability without the loss of the product yields.","subset":"pubmed_abstract"} +{"meta":{"pmid":31640988,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":3,"unknown":12}}},"text":"A disease-associated mutation in fibrillin-1 differentially regulates integrin-mediated cell adhesion.\nFibrillins serve as scaffolds for the assembly of elastic fibers that contribute to the maintenance of tissue homeostasis and regulate growth factor signaling in the extracellular space. Fibrillin-1 is a modular glycoprotein that includes 7 latent transforming growth factor \u03b2 (TGF\u03b2)-binding protein-like (TB) domains and mediates cell adhesion through integrin binding to the RGD motif in its 4th TB domain. A subset of missense mutations within TB4 cause stiff skin syndrome (SSS), a rare autosomal dominant form of scleroderma. The fibrotic phenotype is thought to be regulated by changes in the ability of fibrillin-1 to mediate integrin binding. We characterized the ability of each RGD-binding integrin to mediate cell adhesion to fibrillin-1 or a disease-causing variant. Our data show that 7 of the 8 RGD-binding integrins can mediate adhesion to fibrillin-1. A single amino acid substitution responsible for SSS (W1570C) markedly inhibited adhesion mediated by integrins \u03b15\u03b21, \u03b1v\u03b25, and \u03b1v\u03b26, partially inhibited adhesion mediated by \u03b1v\u03b21, and did not inhibit adhesion mediated by \u03b18\u03b21 or \u03b1IIb\u03b23. Adhesion mediated by integrin \u03b1v\u03b23 depended on the cell surface expression level. In the SSS mutant background, the presence of a cysteine residue in place of highly conserved tryptophan 1570 alters the conformation of the region containing the exposed RGD sequence within the same domain to differentially affect fibrillin's interactions with distinct RGD-binding integrins.","subset":"pubmed_abstract"} +{"meta":{"pmid":19292649,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Combining feature- and correspondence-based methods for visual object recognition.\nWe present an object recognition system built on a combination of feature- and correspondence-based pattern recognizers. The feature-based part, called preselection network, is a single-layer feedforward network weighted with the amount of information contributed by each feature to the decision at hand. For processing arbitrary objects, we employ small, regular graphs whose nodes are attributed with Gabor amplitudes, termed parquet graphs. The preselection network can quickly rule out most irrelevant matches and leaves only the ambiguous cases, so-called model candidates, to be verified by a rudimentary version of elastic graph matching, a standard correspondence-based technique for face and object recognition. According to the model, graphs are constructed that describe the object in the input image well. We report the results of experiments on standard databases for object recognition. The method achieved high recognition rates on identity and pose. Unlike many other models, it can also cope with varying background, multiple objects, and partial occlusion.","subset":"pubmed_abstract"} +{"meta":{"pmid":31243390,"dup_signals":{"dup_doc_count":35,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-40":4,"2023-23":1,"2023-14":1,"2023-06":3,"2022-49":1,"2022-40":1,"2022-27":2,"2022-21":2,"2021-49":2,"2021-31":2,"2021-21":2,"2021-10":3,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2024-26":1,"2024-22":1,"2024-18":2,"2024-30":1}}},"text":"Role of aspirin in primary prevention of cardiovascular disease.\nThe benefits of aspirin therapy for the secondary prevention of cardiovascular disease clearly outweigh the risks of bleeding, and low-dose aspirin is uniformly recommended in this setting. However, no clear consensus exists about whether, and if so in whom, aspirin therapy is appropriate for the primary prevention of cardiovascular disease. Three trials of low-dose aspirin versus placebo in three populations at increased risk of myocardial infarction or ischaemic stroke in the absence of established cardiovascular disease were reported in 2018. The ASPREE trial in elderly people was terminated early for futility because aspirin had no effect on disability-free survival but significantly increased the risk of major haemorrhage and, unexpectedly, all-cause mortality. In the ASCEND trial in patients with diabetes mellitus and no evidence of vascular disease, aspirin significantly reduced serious vascular events but increased major bleeding. In the ARRIVE trial in people with multiple risk factors for cardiovascular disease, aspirin had no effect on major cardiovascular events but increased gastrointestinal bleeding. The aim of this Review is to place these new results in the context of previous evidence on aspirin for the primary prevention of cardiovascular disease and to appraise whether the new evidence is likely to enable the more targeted use of aspirin in particular individuals for whom the net benefit is both clinically worthwhile and statistically definite.","subset":"pubmed_abstract"} +{"meta":{"pmid":20172953,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":1,"2013-20":1,"2015-06":1,"unknown":8}}},"text":"Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice.\nVitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 mo of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":32599710,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Genetic Basis of Maize Resistance to Multiple Insect Pests: Integrated Genome-Wide Comparative Mapping and Candidate Gene Prioritization.\nSeveral species of herbivores feed on maize in field and storage setups, making the development of multiple insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to fall armyworm (FAW), whilst bulked grains were subjected to a maize weevil (MW) bioassay and genotyped with Diversity Array Technology's single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance levels of 0.05 and 0.01, respectively, and located within or close to multiple insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple traits, of which, six were associated with resistance to both FAW and MW, suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30 kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of the five of the six combined resistance QTNs, thus reinforcing the pleiotropy hypothesis. In addition, through in silico co-functional network inferences, an additional 107 network-based CGs (NbCGs), biologically connected to the 64 GbCGs, and differentially expressed under biotic or abiotic stress, were revealed within MIRGRs. The provided multiple insect resistance physical map should contribute to the development of combined insect resistance in maize.","subset":"pubmed_abstract"} +{"meta":{"pmid":12370695,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-18":1,"unknown":7}}},"text":"NTP Technical Report on the metabolism, toxicity and predicted carcinogenicity of diazoaminobenzene (CAS No. 136-35-6).\nDiazoaminobenzene is used as an intermediate, complexing agent, and polymer additive. It is also an impurity in certain color additives used in cosmetics, food products, and pharmaceuticals. Diazoaminobenzene was selected for metabolism and toxicity studies based on the potential for worker exposure from its use in laboratories, positive Salmonella typhimurium gene mutation data, its presence as an impurity in foods and cosmetics, and the lack of adequate toxicity data. Several structural analogues and presumed metabolites of diazoaminobenzene are carcinogenic, providing evidence for the possible carcinogenicity of diazoaminobenzene. The chemical structure of diazoaminobenzene suggested that it would be metabolized into aniline and benzene; therefore, metabolism and disposition studies were performed in male and female F344\/N rats and male B6C3F1 mice administered a single oral, dermal, or intravenous dose of diazoaminobenzene. Electron spin resonance (ESR) studies were conducted to assess the possible formation of a phenyl radical from the reduction of diazoaminobenzene by components of the cytochrome P450 mixed-function oxidase (P450) system in microsomes or by gut microflora in anaerobic cecal incubations. Bile duct-cannulated male F344\/N rats were administered diazoaminobenzene and 5,5-dimethyl-1- pyrroline-N-oxide (DMPO) for in vivo determination of the DMPO-phenyl radical. 16-Day toxicity studies were performed to identify target organs of diazoaminobenzene following dermal application to male and female F344\/N rats and B6C3F1 mice. In the disposition and metabolism studies, oral doses of 20 mg\/kg to male and female rats and male mice were readily absorbed and excreted mainly in the urine, with exhalation of volatile organics accounting for about 1% of the dose. The only volatile metabolite detected in the breath was benzene, and all the metabolites in the urine were those previously shown to result from the metabolism of benzene and aniline in rats and mice. While dermal doses to rats and mice (2 and 20 mg\/cm2) were only slightly absorbed, benzene and aniline metabolites were nonetheless detected in the urine. High circulating levels of benzene, aniline, and their metabolites were detected in the blood of rats administered 20 mg\/kg diazoaminobenzene as early as 15 minutes after exposure. At 24 hours after dosing, diazoaminobenzene was detected at low levels (<1%) in the adipose tissue, blood, kidney, liver, muscle, skin, and spleen. Metabolites of benzene and aniline were also formed in an in vitro study using human liver slices. In the ESR spin-trapping experiments, the ESR spectrum of the DMPO-phenyl radical was detected when diazoaminobenzene was incubated with microsomes or P450 reductase, DMPO, and NADPH, or when incubated with cecal contents and DMPO. The DMPO-phenyl radical spectrum was not attenuated by the P450 inhibitor, 1-aminobenzotriazole, or carbon monoxide suggesting that P450s were not required. In in vivo experiments in which rats were administered diazoaminobenzene and DMPO, the DMPO-phenyl radical adduct was detected in bile within 1 hour after treatment. In the 16-day toxicity studies, groups of five male and five female F344\/N rats and B6C3F1 mice received dermal applications of 0, 12.5, 25, 50, 100, or 200 mg diazoaminobenzene\/kg body weight. Animals were evaluated for absolute and relative organ weights, for hematological effects, and for gross and microscopic lesions. No mortality occurred in rats. However, most male mice exposed to concentrations of 50 mg\/kg or greater and female mice exposed to 200 mg\/kg died. Body weights of male and female rats and female mice were less than those of the vehicle controls. Similar chemical-related toxicities were observed in both species. Clinical pathology data indicated a chemical-related methemoglobinemia and Heinz body formation in male and female rats and mice. Analysis of organ weights indicated possible chemical-related effects in the thymus, heart, spleen, kidney, and liver of rats and\/or mice. Increases in the incidences of several skin lesionseral skin lesions, including hyperplasia of the epidermis and hair follicles, and inflammation in rats and mice and ulceration in female mice were observed. Other nonneoplastic lesions that were considered to be related to diazoaminobenzene administration were atrophy of the thymus, mandibular and\/or mesenteric lymph nodes, and white pulp of the spleen, as well as splenic hematopoietic cell proliferation in rats and mice. In mice, there were increased incidences of atrial thrombosis, and necrosis was observed in the renal tubules and liver. Diazoaminobenzene was mutagenic in S. typhimurium strains TA98, TA100, and TA1537 with induced rat or hamster liver S9 enzymes; no activity was noted in strain TA1535, with or without S9. In vivo, two gavage administrations of either diazoaminobenzene or benzene induced highly significant increases in micronucleated polychromatic erythrocytes in bone marrow of male B6C3F1 mice at all doses tested. Diazoaminobenzene is metabolized to the known carcinogens benzene and aniline. Further evidence of this metabolism is that some toxic effects associated with aniline (methemoglobinemia) and benzene (atrophy of the lymphoid tissue) were identified. Based on these results, it is predicted that diazoaminobenzene is a carcinogen.","subset":"pubmed_abstract"} +{"meta":{"pmid":23286094,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":16}}},"text":"Data-driven visual tracking in retinal microsurgery.\nIn the context of retinal microsurgery, visual tracking of instruments is a key component of robotics assistance. The difficulty of the task and major reason why most existing strategies fail on in-vivo image sequences lies in the fact that complex and severe changes in instrument appearance are challenging to model. This paper introduces a novel approach, that is both data-driven and complementary to existing tracking techniques. In particular, we show how to learn and integrate an accurate detector with a simple gradient-based tracker within a robust pipeline which runs at framerate. In addition, we present a fully annotated dataset of retinal instruments in in-vivo surgeries, which we use to quantitatively validate our approach. We also demonstrate an application of our method in a laparascopy image sequence.","subset":"pubmed_abstract"} +{"meta":{"pmid":11026729,"dup_signals":{"dup_doc_count":50,"dup_dump_count":40,"dup_details":{"curated_sources":1,"2022-49":1,"2022-05":1,"2021-31":1,"2021-17":1,"2021-10":1,"2020-40":1,"2020-24":1,"2020-05":1,"2019-39":1,"2019-35":1,"2018-22":2,"2018-09":1,"2017-51":2,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":2,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-50":1}}},"text":"Vision of the hand and environmental context in human prehension.\nPrevious findings on the role of visual contact with the hand in the control of reaching and grasping have been contradictory. Some studies have shown that such contact is largely irrelevant, while more recent ones have emphasised its importance. In contrast, information arising from the surrounding environment has received relatively little attention in the study of prehensile actions. In order to identify the roles of both sources of information, we made kinematic comparisons between three conditions. In the first, reaching was performed in a dimly lit room and compared with a second condition in which reaches in the dark, but with the thumb and first finger illuminated, were made to a luminous object. This contrast allows the effects of environmental context to be identified. A comparison between the second and a third condition, in which both vision of the hand and the environment was removed, but the object was still visually available, enabled the assessment of how and when vision of the hand plays a role. Removing environmental cues had effects both early and late in the reach, while vision of the hand was only crucial in the period after peak deceleration. In addition, removal of both sources of information resulted in larger grip apertures. Differences and similarities between our findings and those of other studies are discussed, as is the ongoing debate about the relative importance of visual feedback of the hand in the control and co-ordination of prehensile actions. We conclude with suggestions for further research based on the set-up used in the present study.","subset":"pubmed_abstract"} +{"meta":{"pmid":32017050,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-30":1,"unknown":15}}},"text":"Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real-world patients.\nNon-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M\/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM\/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission\/unconfirmed, the two-year relapse risk was 6% but diminished to 0\u00b76% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0\u00b74 (95% CI: -0\u00b77 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.","subset":"pubmed_abstract"} +{"meta":{"pmid":22479156,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":2,"2024-18":1,"unknown":7}}},"text":"No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial.\nThe objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1\u22361\u22361 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1\u22361 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells\/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies\/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies\/ml in the 24- and 60-wk treatment arms (between groups: p < 0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk treatment arms (log rank test, p < 0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART. In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":29445619,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Incidence and biochemical parameters of dermatophilosis in Nigerian cattle breeds from livestock markets, Oyo state, Nigeria.\nDermatophilosis is one of the major economically important diseases of cattle in Nigeria. Managing the condition has been very challenging and re-occurrence has been reported with moderate to high morbidity and mortality. The incidence and biochemical features of cattle with dermatophilosis was conducted in June to December 2016 across the four geopolitical zones of Oyo state, Nigeria. Clinical diagnosis were made based on appearance of dermatophilosis lesion, breeds morphologically characterized, ageing were based on rostral dentition and severity based on the extent and nature of the lesion. Biochemical analysis was based on standard procedure as prescribed by Fortress International. Fifty cattle were found to be infected with clinical dermatophilosis during the period of the study. Twenty four (48%) in Ibadan zone, 14 (28%) in Oyo\/Ogbomosho, 8 (16%) in Oke-ogun and 4 (8%) in Ibarapa zone. Breeds distribution across the zones showed 28 (56%) White Fulani, 5 (10%) Sokoto Gudali, 3 (6%) Adamawa Gudali, 7 (14%) Red Bororo, 5 (10%) Cross breeds while the Kuri was 2 (4%). Regarding animal ages, less than 2 years old were 2 animals (4%) while the adults were 48 animals (96%) and they fall under the categories of 2-2\u00bd years of age, 3-3\u00bd years of age and those which are over 3\u00bd years of age. The different levels of severity were categorized into mild (20 (40%)), moderate (23 (46%)) and severe (7 (14%)) .The best parameters were seen in White Fulani, while the least were seen in Adamawa Gudali. The age group in the category of 3 - 3\u00bd years had most of the best serum values while the least values were seen in animals less than 2 years of age. Cattle exhibiting mild lesions had most of the best serum values and the least values were observed in cattle with severe lesions. No significant difference (p > 0.05) was observed in the mean values for the various parameters studied among the breeds, age, and severity of condition.","subset":"pubmed_abstract"} +{"meta":{"pmid":26854925,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-10":1,"unknown":10}}},"text":"ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions.\nThe recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM\/liver\/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS.","subset":"pubmed_abstract"} +{"meta":{"pmid":11099627,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2022-27":1,"2022-05":1,"2021-39":1,"2021-31":1,"2021-17":1,"2021-10":1,"2020-34":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-35":1,"2023-06":1}}},"text":"The role of the pediatrician in the oral health of children: A national survey.\nTo assess pediatricians' knowledge, attitudes, and professional experience regarding oral health, and to determine willingness to incorporate fluoride varnish into their practices. Poor and minority children suffer disproportionately from dental caries and have limited access to dental care. In a recent analysis of national survey data, the General Accounting Office reported that poor children had 5 times more untreated decay than did children from higher income families. Untreated decay can lead to problems with eating, speaking, and attending to learning. Children who are poor suffer 12 times the number of restricted activity days because of dental problems, compared with more affluent children. Despite higher rates of dental decay, poor children had one half the number of dental visits compared with higher income children in 1996. Medicaid's Early Periodic Screening Diagnosis and Treatment (EPSDT) program is intended to provide regular dental screenings and appropriate treatment but has apparently played a limited role in improving access to dental care for poor children. According to a report by the Office of the Inspector General of the Department of Health and Human Services, only 20% of children under 21 years of age, who were enrolled in Medicaid and eligible for EPSDT, actually received preventive dental services. By increasing their involvement in oral health prevention during well-child care visits, pediatricians may be able to play an important role in improving the dental health of their patients who have difficulty obtaining access to professional dental care. However, it is unclear to what degree pediatricians are knowledgeable about preventive oral health and the extent to which they may already be participating in prevention and assessment. Also, little is known about the incidence of dental problems in pediatric practice, and whether pediatricians perceive barriers to their patients' receiving professional dental care. Finally, it is important to know how pediatricians value the promotion of oral health and whether they would be willing to take on additional activities aimed at its improvement. We addressed these questions in a national survey of pediatricians. We surveyed a national sample of 1600 pediatricians randomly selected from the American Medical Association Master File to assess their knowledge, current practice, and opinion on their role in the promotion of oral health; experience with dental decay among patients and in referring patients for professional dental care; and willingness to apply fluoride varnish. Of 1386 eligible survey recipients, 862 returned surveys for a response rate of 62%. Respondents reported seeing dental problems regularly. Two thirds of respondents observed caries in their school-aged patients at least once a month. Of the respondents, 55% reported difficulty achieving successful dental referrals for their uninsured patients and 38% reported difficulty referring their Medicaid patients. More than 90% of the respondents agreed that they had an important role in identifying dental problems and counseling families on the prevention of caries. Moreover, respondents were interested in increasing their involvement: 74% expressed a willingness to apply fluoride varnish in their practices. One half of the respondents, however, reported no previous training in dental health issues during medical school or residency, and only 9% correctly answered all 4 knowledge questions. Access to dental care and unmet dental health needs are serious, under addressed problems for poor and minority children in the United States. In promoting preventive oral health, pediatricians benefit all children and particularly the underserved. We know of 2 states, Washington and North Carolina, that have acknowledged, through the provision of reimbursement, that pediatricians have a unique opportunity at well-child care visits to provide caries prevention c","subset":"pubmed_abstract"} +{"meta":{"pmid":27063852,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"The development of a single-use, capsule-free multi-breath tobramycin dry powder inhaler for the treatment of cystic fibrosis.\nThe aerosol performance and delivery characteristics of tobramycin for the treatment of respiratory infection were evaluated using the Orbital\u2122, a multi-breath, high dose, dry powder inhaler (DPI). Micronised tobramycin was prepared and tested in the Orbital and in the commercially available TOBI Podhaler (Novartis AG). Furthermore, the TOBI Podhaler formulation containing tobramycin as Pulmospheres was tested in both the commercial Podhaler device (T-326) and Orbital for comparison. By varying the puck geometry of the Orbital, it was possible to deliver equivalent doses of micronised tobramycin (114.09\u00b15.86mg) to that of the Podhaler Pulmosphere product (116.01\u00b12.59mg) over 4 sequential simulated breaths (60Lmin-1 for 4s) without the need for multiple capsules. In general, the aerosol performance of the micronised tobramycin from the Orbital was higher than the T-326 Podhaler device, with fine particle fraction (FPF) of 44.99%\u00b11.09% and 37.03%\u00b10.86%, respectively. When testing the Pulmosphere powder in the two devices, the T-326 had marginally better performance with a FPF of 68.77%\u00b12.10% compared to 61.30%\u00b13.45%. This is to be expected since the TOBI Podhaler and Pulmosphere are an optimised powder and device combination. The Orbital was shown to be capable of delivering high efficiency, high dose antibiotic therapy for inhalation without the need for the use of multiple capsules as used in current devices. This approach may pave the way for a number of antibiotic therapies and medicaments where high dose respiratory deposition is required.","subset":"pubmed_abstract"} +{"meta":{"pmid":19646366,"dup_signals":{"dup_doc_count":67,"dup_dump_count":26,"dup_details":{"curated_sources":3,"2018-22":1,"2018-13":1,"2018-05":2,"2017-51":1,"2017-47":2,"2017-43":1,"2017-39":3,"2016-36":3,"2016-30":3,"2016-26":1,"2016-22":2,"2016-18":2,"2016-07":3,"2015-48":2,"2015-40":2,"2015-35":3,"2015-32":3,"2015-27":2,"2015-22":2,"2015-14":3,"2014-52":2,"2014-49":5,"2014-42":5,"2014-41":6,"2014-35":3,"2021-10":1}}},"text":"Psychiatric diagnoses in patients previously overdiagnosed with bipolar disorder.\nIn a previous article from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we reported that bipolar disorder is often overdiagnosed in psychiatric outpatients. An important question not examined in that article was what diagnoses were given to the patients who had been overdiagnosed with bipolar disorder. In the present report from the MIDAS project, we examined whether there was a particular diagnostic profile associated with bipolar disorder overdiagnosis. Eighty-two psychiatric outpatients reported having been previously diagnosed with bipolar disorder that was not confirmed when they were interviewed with the Structured Clinical Interview for DSM-IV (SCID). Psychiatric diagnoses were compared in these 82 patients and in 528 patients who were not previously diagnosed with bipolar disorder. Patients were interviewed by a highly trained diagnostic rater who administered a modified version of the SCID for DSM-IV Axis I disorders and the Structured Interview for DSM-IV Personality for DSM-IV Axis II disorders. This study was conducted from May 2001 to March 2005. The most frequent lifetime diagnosis in the 82 patients previously diagnosed with bipolar disorder was major depressive disorder (82.9%, n = 68). The patients overdiagnosed with bipolar disorder were significantly more likely to be diagnosed with borderline personality disorder compared to patients who were not diagnosed with bipolar disorder (24.4% vs 6.1%; P < .001). A previous diagnosis of bipolar disorder was also associated with significantly higher lifetime rates of major depressive disorder (P < .01), posttraumatic stress disorder (P < .05), impulse control disorders (P < .05), and eating disorders (P < .05), although only the association with impulse control disorders remained significant after controlling for the presence of borderline personality disorder. Psychiatric outpatients overdiagnosed with bipolar disorder were characterized by more Axis I and Axis II diagnostic comorbidity in general, and borderline personality disorder in particular.","subset":"pubmed_abstract"} +{"meta":{"pmid":34000257,"dup_signals":{"dup_doc_count":55,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-30":7,"2024-26":10,"2024-22":4,"2024-18":4,"2024-10":12,"unknown":17}}},"text":"Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial.\nMany patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1\u00b700, 95% CI 0\u00b793-1\u00b707; p=0\u00b795). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0\u00b799, 95% CI 0\u00b794-1\u00b703; p=0\u00b757). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0\u00b799, 95% CI 0\u00b793-1\u00b705; p=0\u00b779). In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. UK Research and Innovation (Medical Research Council) and National Institute of Health Research.","subset":"pubmed_abstract"} +{"meta":{"pmid":24963652,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Preparation, characterization, in vitro release and degradation of cathelicidin-BF-30-PLGA microspheres.\nCathelicidin-BF-30 (BF-30), a water-soluble peptide isolated from the snake venom of Bungarus fasciatus containing 30 amino acid residues, was incorporated in poly(D,L-lactide-co-glycolide) (PLGA) 75\u223625 microspheres (MS) prepared by a water in oil in water W\/O\/W emulsification solvent extraction method. The aim of this work was to investigate the stability of BF-30 after encapsulation. D-trehalose was used as an excipient to stabilize the peptide. The MS obtained were mostly under 2 \u00b5m in size and the encapsulation efficiency was 88.50\u00b11.29%. The secondary structure of the peptide released in vitro was determined to be nearly the same as the native peptide using Circular Dichroism (CD). The ability of BF-30 to inhibit the growth of Escherichia coli was also maintained. The cellular relative growth and hemolysis rates were 92.16\u00b13.55% and 3.52\u00b10.45% respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":10934223,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2.\nTuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4(+) T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4(+) T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4(+) T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4(+) T cells are believed to be a major source of interferon (IFN)-gamma, expression of the gene for IFN-gamma in the lungs of CD4(+) T cell-depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4(+) T cell depletion, indicating that macrophage activation was present even during CD4(+) T cell deficiency. These data indicate that CD4(+) T cells are necessary to prevent reactivation but may have roles in addition to IFN-gamma production and macrophage activation in controlling a persistent tuberculous infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":29147648,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer.\nOver the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.","subset":"pubmed_abstract"} +{"meta":{"pmid":17331211,"dup_signals":{"dup_doc_count":44,"dup_dump_count":28,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2022-05":2,"2021-49":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-40":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":2,"2017-51":2,"2017-43":2,"2017-34":2,"2023-50":1,"2024-26":6,"2024-22":2}}},"text":"A numerical study of red-green colour opponent properties in the primate retina.\nIt remains an important question whether neural function is mediated entirely by its tailored circuitry. A persistent debate in retinal colour vision is whether the centre and the surround of a ganglion cell receptive field receive dominant inputs either from L or M cones in an antagonistic manner (the selective wiring model) or mixed inputs (the mixed wiring model). Despite many anatomical, physiological and psychophysical experiments, a decisive conclusion has not been reached. An in-depth examination of what the pure mixed wiring mechanisms predicts is therefore important. These two models make different predictions both for the fovea and for the peripheral retina. Recently, a dynamic cellular model of the primate fovea was developed [Momiji et al. (2006) Vis. Res., 46, 365-381]. Unlike earlier models, it explicitly incorporates spatial non-uniformities, such as the random arrangement of L and M cones. Here, a related model is developed for the peripheral retina by incorporating anatomically reasonable degrees of convergence between cones, bipolar cells and ganglion cells. These two models, in which selective wiring mechanisms are absent, are applied to describe both foveal and peripheral colour vision. In numerical simulations, peripheral ganglion cells are less colour sensitive than foveal counterparts, but none-the-less display comparative sensitivities. Furthermore, peripheral colour sensitivity increases with temporal frequency, relative to foveal sensitivity. These results are congruent with recent physiological experiments.","subset":"pubmed_abstract"} +{"meta":{"pmid":37399189,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2024-26":2,"unknown":5}}},"text":"Overexpression of REDUCED WALL ACETYLATION C increases xylan acetylation and biomass recalcitrance in Populus.\nPlant lignocellulosic biomass, i.e., secondary cell walls of plants, is a vital alternative source for bioenergy. However, the acetylation of xylan in secondary cell walls impedes the conversion of biomass to biofuels. Previous studies have shown that REDUCED WALL ACETYLATION (RWA) proteins are directly involved in the acetylation of xylan, but the regulatory mechanism of RWAs is not fully understood. In this study, we demonstrate that overexpression of a Populus trichocarpa PtRWA-C gene increases the level of xylan acetylation, increases lignin content and S\/G ratio, ultimately yielding poplar woody biomass with reduced saccharification efficiency. Furthermore, through gene co-expression network and expression quantitative trait loci (eQTL) analysis, we found that PtRWA-C was not only regulated by the secondary cell wall hierarchical regulatory network, but also by an AP2 family transcription factor HARDY (HRD). Specifically, HRD activates PtRWA-C expression by directly binding to the PtRWA-C promoter, which is also the cis-eQTL for PtRWA-C. Taken together, our findings provide insights into the functional roles of PtRWA-C in xylan acetylation and consequently saccharification, and shed light on synthetic biology approaches to manipulate this gene and alter cell wall properties. These findings have substantial implications for genetic engineering of woody species, which could be used as a sustainable source of biofuels, valuable biochemicals, and biomaterials.","subset":"pubmed_abstract"} +{"meta":{"pmid":11091774,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Combination antiretroviral therapy: health care providers confront emerging dilemmas.\nRecent editorials, conferences and clinical practice articles have discussed providers' concerns and practices regarding prescribing antiretroviral combination therapy for HIV. We aimed to deepen our understanding of these largely anecdotal reports and of the challenges facing experienced HIV clinicians today using qualitative methodology. Eight focus groups using a structured discussion guide were conducted. Data were analyzed by constant comparative analysis and open codes. Participants were a diverse group of 23 physicians, eight nurse practitioners and four physician assistants with significant experience providing care to HIV-seropositive patients in various San Francisco Bay Area health care settings. The following major themes emerged from the data: (1) providers expressed new optimism about helping HIV-seropositive patients live; (2) the main factors affecting providers' decisions about when to start combination therapy were the risks versus benefits of delaying therapy, and patients' health status, readiness to adhere and treatment preferences; (3) providers lacked resources to prepare patients to begin therapy and enhance adherence; (4) providers varied regarding assessment of adherence; and (5) providers were anxious about making decisions under conditions of uncertainty and were concerned about patient health outcomes. We concluded that experienced HIV clinicians were hopeful and excited about their increasing ability to help patients. This hope, however, was tempered by scepticism about the future and by their daily struggles to make treatment decisions under conditions of great uncertainty. Without access to adjunct supports or a multidisciplinary team, providers may not be able to optimally assess and enhance antiretroviral medication adherence.","subset":"pubmed_abstract"} +{"meta":{"pmid":22239941,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":14}}},"text":"A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians.\nThere is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.","subset":"pubmed_abstract"} +{"meta":{"pmid":30975912,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-22":1,"2024-18":2,"unknown":10}}},"text":"Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1\/TET1\/5hmC.\nHomoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth\/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1\/TET1 axis, and TET1 depletion mimics homoharringtonine's therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of homoharringtonine\/SP1\/TET1\/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of homoharringtonine, which involves suppression of the SP1\/TET1\/5hmC\/FLT3\/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.","subset":"pubmed_abstract"} +{"meta":{"pmid":3358643,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Cellular and genetic properties of two melanoma cell lines established from the same tumor.\nWe report here the detailed cellular and genetic analysis of two new human melanoma cell lines established from the same tumor biopsy. Although derived from the same tumor biopsy, the two lines differed in their method of in vitro culture establishment with one line (HA-A) grown first in agar culture and then transferred to liquid culture, while the second cell line (HA-L) was established directly from cells grown in liquid culture. Detailed characterization of both cell lines was performed using techniques to analyze their cytogenetic, surface marker, morphology (light and electron microscopy), growth (in agar and in nude mice), and drug sensitivity profiles in comparison to the original tumor biopsy. Our results revealed no significant biologic or genetic difference between the two cell lines established by different culture techniques. Our results suggest that in some cases agar culture prior to liquid culture may be useful in establishment of human tumor cell lines.","subset":"pubmed_abstract"} +{"meta":{"pmid":19913825,"dup_signals":{"dup_doc_count":46,"dup_dump_count":37,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2023-06":1,"2022-49":2,"2022-27":2,"2022-05":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2020-29":1,"2020-16":1,"2020-10":2,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":1,"2019-35":1,"2019-30":1,"2019-22":2,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2024-26":1,"2024-10":1,"2024-30":1}}},"text":"Retrospective descriptive analysis of 1,176 patients with failed hypospadias repair.\nTo our knowledge epidemiological data on the incidence of failed hypospadias repair and the number of patients seeking further surgical treatment remain unknown. We report an observational, descriptive survey of patients who were evaluated and treated for urethral stricture disease and\/or penile defects after primary hypospadias repair. We performed a retrospective observational chart analysis of patients evaluated and treated for urethral stricture disease and\/or penile defects at 2 tertiary European centers from January 1998 to December 2007. In each case we investigated the primary abnormal meatal site, the number of operations needed to repair primary hypospadias and complications of this primary repair. Patients were offered surgical repair for previous failed hypospadias treatment. After surgery evaluation was scheduled at 3, 6 and 9 months. Success was defined as a functional urethra without fistula, stricture or residual chordee and a cosmetically acceptable glanular meatus after the completion of all secondary procedures. A total of 1,176 patients with a mean age of 31 years were evaluated and treated. To treat failed hypospadias repair 760 (64.6%) and 416 patients (35.4%) underwent 1-stage and staged repair, respectively. Mean followup was 60.4 months. Of 1,176 cases 1,036 (88.1%) were classified as successful and 140 (11.9%) were considered failures. Failed hypospadias repair may be corrected by multiple and complex surgeries. Its effects are experienced during the lifetime of the patient and parents.","subset":"pubmed_abstract"} +{"meta":{"pmid":6296865,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2013-20":1,"2024-30":1,"unknown":8}}},"text":"31P NMR study of erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency.\nThe composition of phosphate metabolites and the intracellular pH in erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency were examined using 31P NMR spectroscopy. Several resonances were identified in spectra from intact cells and from extracts. The 2,3-bisphosphoglycerate line intensities were normal but the NTP resonances were about twice normal due to the presence of millimolar quantities of pyrimidine phosphates. Several intense resonances were also observed in the diphosphodiester region of the spectrum. One compound contributing to these lines has been identified as cytidine diphosphocholine. The resonances of NTPs were in a position indicating that the additional triphosphates were also bound by Mg2+. Direct measurement shows that there is a nearly proportional increase in total cell Mg2+ in the patient's cells, in agreement with the interpretation of the spectra. The intracellular pH was about 0.2 unit lower in the patient's erythrocytes. This lower pH is due to the elevation in intracellular fixed negative charges and the shift in permeable anions consequent to the Donnan equilibrium. We suggest that the lower intracellular pH may explain the lower oxygen affinity of these cells in the presence of otherwise normal 2,3-bisphosphoglycerate levels and the increased Mg2+ triphosphates level, because the Mg2+ form of NTPs is known not to alter the oxygen affinity of hemoglobin under physiologic conditions. Furthermore, the lower intracellular pH can also explain the abnormalities in glycolytic intermediates observed for these cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23447480,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Tranexamic acid-induced toxic epidermal necrolysis.\nTo report a case of toxic epidermal necrolysis (TEN) induced by orally administered tranexamic acid in a patient with liver cirrhosis and acute rectal bleeding. A 67-year-old male with a history of liver cirrhosis due to alcohol consumption with ascitic decompensation, esophageal varices, and multifactorial renal insufficiency presented with rectal bleeding. The patient was prescribed oral tranexamic acid (1000 mg every 8 hours), with partial resolution of symptoms. Ten days after treatment with tranexamic acid began, a purplish macular rash appeared over the patient's trunk. The dose of tranexamic acid was reduced to 1000 mg every 12 hours, adjusting for renal function. In the following days the lesions extended and became confluent with blisters and epidermal necrosis. Multiple mucosal surfaces were also affected. He denied allergies to any medications and had no history of tranexamic acid exposure. Treatment with tranexamic acid was suspended and fluid replacement therapy, oral prednisone therapy (0.4 mg\/kg per day), and N-acetylcysteine 2 g every 6 hours was started, with the empiric diagnosis of TEN. Results of a skin biopsy were compatible with TEN. Resolution of the skin lesions was favorable, but after 2 weeks the patient died secondary to acute renal failure, respiratory infection, and multiorgan failure. TEN is a rare, severe mucocutaneous adverse reaction. Although infrequent, TEN has a significant impact on public health because of its high mortality. Its pathogenesis is unclear, but it seems to be a form of delayed hypersensitivity. To our knowledge, a well-documented case of TEN following tranexamic acid use has not been reported (MEDLINE search to June 2012). There have been recent reports of skin hypersensitivity reactions through different mechanisms (immunologic and nonimmunologic). The Naranjo probability scale indicates a probable relationship between the development of TEN and tranexamic acid use in our patient. This appears to be the first report of a case of TEN that occurred in a patient being treated with oral tranexamic acid. Clinicians should be made aware of this potential severe cutaneous adverse reaction that may be caused by tranexamic acid administration.","subset":"pubmed_abstract"} +{"meta":{"pmid":35351049,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"The impact of new government childcare accreditation standards on children's in-care physical activity and sedentary time.\nA new physical activity and sedentary behaviour accreditation standard criterion for childcare settings was introduced by the provincial government in Alberta, Canada. The primary objective of this study was to examine if changes for in-care physical activity and sedentary time (ST) differed between centres in and around Edmonton, Alberta after implementing the new accreditation standards and non-accredited control centres in and around Ottawa, Ontario. Secondary objectives were to examine whether baseline age group (toddler, preschooler) or the childcare environment moderated any group differences in change of the primary outcomes. Furthermore, accreditation and control group differences in change of children's body mass index (BMI) Z-scores or cognitive development as well as educators' perceptions of the primary outcomes were explored. Participants were 252 toddlers (19-35 months) and preschoolers (36-60 months) in childcare centres from Alberta (n = 11) and Ontario (n = 8) in the supporting Healthy physical AcTive CHildcare setting (HATCH) study. In-care ST, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were accelerometer-derived before and 6 months after the implementation of the new standards. At both time points, cognitive development (working memory, expressive vocabulary), heights, and weights were measured, and BMI Z-scores were calculated. Additionally, the childcare environment was observed using the Environment and Policy Assessment and Observation (EPAO) and Movement Environment Rating Scale (MOVERS) tools. Demographic characteristics were parent-reported and weather variables were derived from Environment Canada data. Mixed models were conducted. In adjusted models (n = 241), change in children's in-care ST (B = -0.07, 95%CI: - 1.43,1.29), LPA (B = 0.08, 95%CI: - 0.89,1.05), and log-transformed MVPA (B = 0.01, 95%CI: - 0.09,0.11) were not significantly different between accreditation and control groups. Age group and the childcare environment were not moderators. Significant increases in BMI Z-score (B = 0.19, 95%CI: 0.03,0.35) and high working memory (OR = 3.24, 95%CI: 1.32,7.97) were observed in the accreditation group and significant increases in expressive vocabulary (B = 3.18, 95%CI: 0.05,6.30) were observed in the control group. The new accreditation criterion may not significantly change physical activity or ST in childcare settings and therefore may not explain findings for BMI Z-scores and cognitive development. Additional training and resources may be needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":3011949,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-10":1,"unknown":12}}},"text":"Recognition of cloned vesicular stomatitis virus internal and external gene products by cytotoxic T lymphocytes.\nIt has generally been assumed that most if not all CTL specific for vesicular stomatitis virus (VSV)-infected cells recognize the viral glycoprotein (G), an integral membrane protein abundantly expressed on infected cell surfaces. Using recombinant vaccinia viruses containing copies of cloned VSV genes to examine CTL recognition of VSV, we have confirmed that G is recognized by VSV-specific CTL. More interestingly, however, we have also found that nucleocapsid protein (N), an internal virion protein, can be detected on infected cell surfaces using mAb, and serves as a major target antigen for VSV-specific CTL. In contrast to the highly serotype-specific recognition of G, N is recognized by a major population of CTL able to lyse cells infected with either the Indiana or New Jersey VSV serotypes. Using target cells expressing a cloned MHC class I gene, we could directly show that CTL recognition of N occurs in the context of the MHC Ld molecule.","subset":"pubmed_abstract"} +{"meta":{"pmid":23404247,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy.\nKRAS mutations are the most common oncogenic event in colorectal cancer (CRC) progression and their occurrence is associated with lack of response to anti epidermal growth factor receptor (EGFR) targeted therapies. Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1,039 CRC samples to assess the prevalence of KRAS amplification in this tumor type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7\/1,039 (0.67%) and 1\/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumors or cell lines harboring this genetic lesion are not responsive to anti-EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti-EGFR treatment in a small proportion of patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":22940095,"dup_signals":{"dup_doc_count":19,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2018-26":2,"2018-22":2,"2018-17":2,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":2,"2017-43":3,"2017-34":2,"2017-26":2}}},"text":"Ras and Rap1 govern spatiotemporal dynamic of activated ERK in pituitary living cells.\nThe Ras\/Raf\/MEK\/ERK is a conserved signalling pathway involved in the control of fundamental cellular processes. Despite extensive research, how this pathway can process a myriad of diverse extracellular inputs into substrate specificity to determine biological outcomes is not fully understood. It has been established that the ERK1\/2 pathway is an integrative point in the control of the pituitary function exerted by various extracellular signals. In addition we previously established that the GTPases Ras and Rap1 play a key role in the regulation of ERK1\/2-dependent prolactin transcription by EGF or the cAMP-dependent neuropeptide VIP. In this report, using the FRET-based biosensor of ERK activity (EKAR) in the pituitary GH4C1 cell line, we show that both EGF and VIP tightly control the spatiotemporal dynamic of activated ERK with different magnitude and duration. Importantly, we provide the first evidence of a differential control of cytoplasmic and nuclear pools of activated ERK by the GTPases Ras and Rap1. Ras is required for nuclear magnitude and duration of EGF-dependent ERK activation, whereas it is required for both VIP-activated cytoplasmic and nuclear ERK pools. Rap1 is exclusively involved in VIP-activated ERK nuclear pool. Moreover, consistent with the control of the nuclear pool of activated ERK by the GTPases, we observe the same differential role of Ras and Rap1 on ERK nuclear translocation triggered by EGF or VIP. Together these findings identify Ras and Rap1 as determinant partners in shaping nuclear and cytoplasmic ERK kinetics in response to EGF and VIP, which in turn should control pituitary secretion.","subset":"pubmed_abstract"} +{"meta":{"pmid":25898205,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The influence of artificially introduced N-glycosylation sites on the in vitro activity of Xenopus laevis erythropoietin.\nErythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity. Seven xlEPO muteins, containing 1-3 additional N-linked carbohydrates at positions 24, 38, and\/or 83, were expressed in COS-1 cells. The muteins exhibited lower secretion efficiency, higher hydrophilicity, and stronger acidic properties than the wild type. All muteins stimulated the proliferation of both cell lines, xlEPO receptor-expressing xlEPOR-FDC\/P2 cells and huEPO receptor-expressing UT-7\/EPO cells, in a dose-dependent manner. Thus, the muteins retained their in vitro biological activities. The maximum effect on xlEPOR-FDC\/P2 proliferation was decreased by the addition of N-linked carbohydrates, but that on UT-7\/EPO proliferation was not changed, indicating that the muteins act as partial agonists to the xlEPO receptor, and near-full agonists to the huEPO receptor. Hence, the EPO-EPOR binding site in X. laevis locates the distal region of artificially introduced three N-glycosylation sites, demonstrating that the vital conformation to exert biological activity is conserved between humans and X. laevis, despite the low similarity in primary structures of EPO and EPOR.","subset":"pubmed_abstract"} +{"meta":{"pmid":29195639,"dup_signals":{"dup_doc_count":65,"dup_dump_count":39,"dup_details":{"curated_sources":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":5,"2020-50":1,"2020-45":2,"2020-40":2,"2020-34":2,"2020-24":4,"2020-10":2,"2020-05":3,"2019-51":2,"2019-47":1,"2019-43":2,"2019-39":2,"2019-35":3,"2019-30":2,"2019-26":2,"2019-22":2,"2019-18":2,"2019-13":1,"2019-09":2,"2019-04":1,"2018-51":1,"2018-47":1,"2018-43":2,"2018-39":2,"2018-34":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-05":1,"2017-51":1,"2023-23":1}}},"text":"Married women's negotiation for safer sexual intercourse in Kenya: Does experience of female genital mutilation matter?\nMarried women's ability to negotiate for safer sex is important for HIV prevention in sub-Saharan Africa, including Kenya. Yet, its relationship to female genital mutilation is rarely explored, although female genital mutilation has been described as a social norm and marker of womanhood that can control women's sexuality. Drawing on the social normative influence theory, this study addressed this void in the literature. We analysed data from the 2014 Kenya Demographic and Health Survey using logistic regression. Our sample included 8,602 married women. Two indicators of safer sex, namely the ability to refuse sex and the ability to ask for condom use, were explored. We found that women who had undergone genital mutilation were significantly less likely to report that they can refuse sex (OR=0.87; p<.05) and that they can ask for condom use during sexual intercourse (OR=0.62; p<.001) than their counterparts who had not undergone genital mutilation, while controlling for theoretically relevant variables. Our findings indicate that the experience of female genital mutilation may influence married women's ability to negotiate for safer sex through gendered socialization and expectations. Based on these findings, several policy implications are suggested. For instance, culturally sensitive programmes are needed that target both married women who have undergone genital mutilation and their husbands to understand the importance of safer sexual practices within marriage.","subset":"pubmed_abstract"} +{"meta":{"pmid":2155289,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Interaction of bluetongue virus with bovine lymphocytes.\nFreshly isolated, and established, cultures of bovine peripheral blood mononuclear leukocytes (PBMLs) were exposed to bluetongue virus (BTV) for the purpose of defining potential lymphotropism. PBML cultures were established in the presence of interleukin 2 (IL-2) and mitogen and maintained either as bulk culture or were cloned prior to infectivity studies. All cultures appeared to be of the T cell phenotype based on the following characteristics: binding of T lymphocyte-specific lectins (i.e. peanut agglutinin and Helix pomatia), rosetting of sheep erythrocytes, binding of a putative pan-T monoclonal antibody, and absence of surface immunoglobulin (Ig). T lymphocyte cultures were further characterized by their ability to elicit lectin-dependent cellular cytotoxicity (LDCC). Exposure of established lymphocyte cultures to BTV resulted in productive cytopathic and non-cytopathic infections. Non-cytopathic productive infections were observed in LDCC-negative cultures whereas cytopathic and non-cytopathic infections were observed in LDCC-positive cultures. Exposure of freshly isolated PBMLs to BTV resulted in minimal virus replication; addition of mitogen and IL-2 to such cultures did not augment virus replication. Addition of mitogen and IL-2 induced negligible blast transformation, whereas PBML viability was minimally affected. These studies establish a tropism of BTV for bovine T lymphocytes with virus replication being limited to those cells undergoing blastogenesis. Establishment of infected lymphocyte cultures, without loss of culture viability, suggest such an interaction may contribute to the long term viraemias associated with BTV infection of cattle.","subset":"pubmed_abstract"} +{"meta":{"pmid":33088454,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"How Healthy are Children at the Beginning of Primary School in Iran?\nChildhood is the most important life stages where personality is built and formed. Since children are as a treasured capital for each society, assessment of their health status is so vital. This study assessed the health indices of children starting the primary school and considered parental factors influencing kid's health. An analytical descriptive cross-sectional study applied to measure the health status of children at the beginning primary school. The data extracted from 7768 primary school children with an average value of age 7 years and their parents, who were referred to Children Health Testing centers in the school year of 2016, in all provinces of Iran. From 7768 kids, 52.3% were boys and 47.7% were girls. The mean of weight and height of children was 20.65 kg, and 115.84 cm, respectively. The mean body mass index (BMI, kg\/m2) for age ratio of children in the country was 16.26. In addition, 4.9% of boys and 3.7% of girls were short stature, 0.5% of boys and 1.8% of girls were tall and 94.5% of kids had normal growth. About 5.3% of boys and 6.8% of girls were underweight, 9.2% of boys and 7.7% of girls were overweight, and 4.7% of boys and 3.4% of girls were obese. The overweight and severe short stature problems in children were more dominant than underweight and severe tall. Although underweight is more common in girls than boys, it is reversed in the case of overweight and obesity. In addition, the ratio of health problems among children in different provinces was dissimilar, thus considering the health status of children in each province to find a solution was crucial.","subset":"pubmed_abstract"} +{"meta":{"pmid":23723032,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Role of ion transport in control of apoptotic cell death.\nCell shrinkage is a hallmark and contributes to signaling of apoptosis. Apoptotic cell shrinkage requires ion transport across the cell membrane involving K(+) channels, Cl(-) or anion channels, Na(+)\/H(+) exchange, Na(+),K(+),Cl(-) cotransport, and Na(+)\/K(+)ATPase. Activation of K(+) channels fosters K(+) exit with decrease of cytosolic K(+) concentration, activation of anion channels triggers exit of Cl(-), organic osmolytes, and HCO3(-). Cellular loss of K(+) and organic osmolytes as well as cytosolic acidification favor apoptosis. Ca(2+) entry through Ca(2+)-permeable cation channels may result in apoptosis by affecting mitochondrial integrity, stimulating proteinases, inducing cell shrinkage due to activation of Ca(2+)-sensitive K(+) channels, and triggering cell-membrane scrambling. Signaling involved in the modification of cell-volume regulatory ion transport during apoptosis include mitogen-activated kinases p38, JNK, ERK1\/2, MEKK1, MKK4, the small G proteins Cdc42, and\/or Rac and the transcription factor p53. Osmosensing involves integrin receptors, focal adhesion kinases, and tyrosine kinase receptors. Hyperosmotic shock leads to vesicular acidification followed by activation of acid sphingomyelinase, ceramide formation, release of reactive oxygen species, activation of the tyrosine kinase Yes with subsequent stimulation of CD95 trafficking to the cell membrane. Apoptosis is counteracted by mechanisms involved in regulatory volume increase (RVI), by organic osmolytes, by focal adhesion kinase, and by heat-shock proteins. Clearly, our knowledge on the interplay between cell-volume regulatory mechanisms and suicidal cell death is still far from complete and substantial additional experimental effort is needed to elucidate the role of cell-volume regulatory mechanisms in suicidal cell death.","subset":"pubmed_abstract"} +{"meta":{"pmid":8626128,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-33":1,"2022-27":1,"2021-49":1,"2021-39":1,"2021-21":2,"2020-50":2,"2020-29":1,"2020-24":1,"2023-23":1,"2024-26":1}}},"text":"p53 overexpression and bcl-2 persistence in endometrial carcinoma: comparison of papillary serous and endometrioid subtypes.\nForty-two cases, including 21 uterine papillary serous carcinomas (UPSC) and 21 age-, nuclear-grade-, and clinical-stage-matched uterine endometrioid carcinomas (UEC), were studied immunohistochemically for p53 and bcl-2 in archival paraffin-embedded tissue. Compared to UEC (28.6% positive), UPSC (71.4% positive) had a significantly higher frequency of p53 overexpression (P = 0.005); furthermore, in a clinical-stage-matched fashion, a higher frequency of p53 overexpression was found in early-stage cases (P = 0.032), but not in late-stage cases. In a nuclear-grade-matched comparison, no statistical difference in p53 overexpression was identified between the two subtypes, although UPSC had stronger p53 immunoreactivity than UEC. Of UPSC, no difference in p53 overexpression was detected between tumors of early and late stages; additionally, in 5 cases, there was an abrupt transition from nonstaining morphologically benign glands to uniformly positive p53 nuclear staining in regions of intraepithelial carcinoma. Conversely, in UEC, there was a significant difference in p53 immunostaining between tumors of early and late stages (P = 0.01); no case had an abrupt transition for p53 immunostaining. For bcl-2 immunostaining, UEC had a significantly higher immunohistochemical staining score than did UPSC (P = 0.0002). In general, the staining intensity of bcl-2 diminished progressively from proliferative phase and hyperplastic endometrium to UEC and then to UPSC, with 3 of 21 (14.3%) UPSC being negative. These results suggest that p53 alteration may be an early event in the development of UPSC and may be related to its clinical aggressiveness, while it is a late event in UEC. Early detection of p53 nuclear accumulation may help to identify precursor lesions of UPSC. bcl-2 persistence is frequently associated with endometrial carcinoma, and failure to inactivate bcl-2 expression probably is related to the development of endometrial carcinoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":30319567,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Comparative Genomics of Degradative Novosphingobium Strains With Special Reference to Microcystin-Degrading Novosphingobium sp. THN1.\nBacteria in genus Novosphingobium associated with biodegradation of substrates are prevalent in environments such as lakes, soil, sea, wood and sediments. To better understand the characteristics linked to their wide distribution and metabolic versatility, we report the whole genome sequence of Novosphingobium sp. THN1, a microcystin-degrading strain previously isolated by Jiang et al. (2011) from cyanobacteria-blooming water samples from Lake Taihu, China. We performed a genomic comparison analysis of Novosphingobium sp. THN1 with 21 other degradative Novosphingobium strains downloaded from GenBank. Phylogenetic trees were constructed using 16S rRNA genes, core genes, protein-coding sequences, and average nucleotide identity of whole genomes. Orthologous protein analysis showed that the 22 genomes contained 674 core genes and each strain contained a high proportion of distributed genes that are shared by a subset of strains. Inspection of their genomic plasticity revealed a high number of insertion sequence elements and genomic islands that were distributed on both chromosomes and plasmids. We also compared the predicted functional profiles of the Novosphingobium protein-coding genes. The flexible genes and all protein-coding genes produced the same heatmap clusters. The COG annotations were used to generate a dendrogram correlated with the compounds degraded. Furthermore, the metabolic profiles predicted from KEGG pathways showed that the majority of genes involved in central carbon metabolism, nitrogen, phosphate, sulfate metabolism, energy metabolism and cell mobility (above 62.5%) are located on chromosomes. Whereas, a great many of genes involved in degradation pathways (21-50%) are located on plasmids. The abundance and distribution of aromatics-degradative mono- and dioxygenases varied among 22 Novosphingoibum strains. Comparative analysis of the microcystin-degrading mlr gene cluster provided evidence for horizontal acquisition of this cluster. The Novosphingobium sp. THN1 genome sequence contained all the functional genes crucial for microcystin degradation and the mlr gene cluster shared high sequence similarity (\u226585%) with the sequences of other microcystin-degrading genera isolated from cyanobacteria-blooming water. Our results indicate that Novosphingobium species have high genomic and functional plasticity, rearranging their genomes according to environment variations and shaping their metabolic profiles by the substrates they are exposed to, to better adapt to their environments.","subset":"pubmed_abstract"} +{"meta":{"pmid":15916615,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Deletion of GEL2 encoding for a beta(1-3)glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus.\nThe first fungal glycosylphosphatidylinositol anchored beta(1-3)glucanosyltranferase (Gel1p) has been described in Aspergillus fumigatus and its encoding gene GEL1 identified. Glycosylphosphatidylinositol-anchored glucanosyltransferases play an active role in the biosynthesis of the fungal cell wall. We characterize here GEL2, a homologue of GEL1. Both homologues share common characteristics: (i) GEL1 and GEL2 are constitutively expressed during over a range of growth conditions; (ii) Gel2p is also a putative GPI-anchored protein and shares the same beta(1-3)glucanosyltransferase activity as Gel1p and (iii) GEL2, like GEL1, is able to complement the Deltagas1 deletion in Saccharomyces cerevisiae confirming that Gelp and Gasp have the same enzymatic activity. However, disruption of GEL1 did not result in a phenotype whereas a Deltagel2 mutant and the double mutant Deltagel1Deltagel2 exhibit slower growth, abnormal conidiogenesis, and an altered cell wall composition. In addition, the Deltagel2 and the Deltagel1Deltagel2 mutant have reduced virulence in a murine model of invasive aspergillosis. These data suggest for the first time that beta(1-3)glucanosyltransferase activity is required for both morphogenesis and virulence in A. fumigatus.","subset":"pubmed_abstract"} +{"meta":{"pmid":26811510,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"Republished review: Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms.\nElective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":22272953,"dup_signals":{"dup_doc_count":25,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2017-13":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"unknown":14}}},"text":"The Consumer Protection Act: no-fault liability of health care providers.\nThe introduction of no-fault or strict liability by the Consumer Protection Act 68 of 2008 (CPA) poses serious problems in the health care context. With a patient as a 'consumer' in terms of the CPA, health care practitioners may find themselves as 'suppliers' or 'retailers' as part of a supply chain, and potentially liable for harm and loss suffered by a patient in terms of the new no-fault liability provision. The claimant (patient) can sue anyone in the supply chain in terms of this provision, which places the health care practitioner who delivered the care in a very difficult position, as he or she is the most easily and often only identifiable person in the supply chain. Although the causal link between the harm suffered by the complainant will still need to be established on a balance of probabilities, the traditional common law obstacle requiring proof of negligence no longer applies. The article argues that this situation is unsatisfactory, as it places an increasingly onerous burden on certain health care practitioners.","subset":"pubmed_abstract"} +{"meta":{"pmid":28817782,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Cost-effectiveness of a patient navigation program to improve cervical cancer screening.\nTo assess the cost-effectiveness of a community-based patient navigation program to improve cervical cancer screening among Hispanic women 18 or older in San Antonio, Texas. We used a microsimulation model of cervical cancer to project the long-term cost-effectiveness of a community-based patient navigation program compared with current practice. We used program data from 2012 to 2015 and published data from the existing literature as model input. Taking a societal perspective, we estimated the lifetime costs, life expectancy, and quality-adjusted life-years and conducted 2-way sensitivity analyses to account for parameter uncertainty. The patient navigation program resulted in a per-capita gain of 0.2 years of life expectancy. The program was highly cost-effective relative to no intervention (incremental cost-effectiveness ratio of $748). The program costs would have to increase up to 10 times from $311 for it not to be cost-effective. The 3-year community-based patient navigation program effectively increased cervical cancer screening uptake and adherence and improved the cost-effectiveness of the screening program for Hispanic women 18 years or older in San Antonio, Texas. Future research is needed to translate and disseminate the patient navigation program to other socioeconomic and demographic groups to test its robustness and design.","subset":"pubmed_abstract"} +{"meta":{"pmid":32726989,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Cotton Terry Textiles with Photo- and Bio-Activity in a Model Study and Real Conditions.\nThe aim of the study was to assess the photocatalytic (decompose staining particles, K\/S values, the color differences, CIE L*a*b* color) and antimicrobial properties of textiles modified with TiO2 and ZnO nanoparticles (NPs) confirmed by X-ray diffraction, dynamic light scattering, SEM-EDX) in visible light conditions. The antimicrobial effectiveness of modified textiles under model conditions has been reported against 5 microorganisms: Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Candida albicans, Aspergillus niger (AATCC Test Method 100-2004). In real conditions in bathrooms, significant biostatic activity was shown on the surface of the modified towels. The number of microorganisms decreased by 1-5 log to the level of 0-5 CFU\/cm2 in the case of bacteria: Enterobacteriaceae, Enterococcus, the coli group and E. coli, Pseudomonas. Statistically significant reduction of the total number of bacteria and fungi (by 1 log), and the concentration of gases (NO2, CO2, CO) in the air of bathrooms was determined. The removal or reduction of volatile organic compounds (VOCs) concentration (SPME-GC-MS analysis) in the air above the modified towels has also been determined. It was found that the lighting type (natural, artificial), time (1.5 and 7 h\/day), air humidity (RH = 36-67%) and light intensity (81-167 lux) are important for the efficiency of photocatalysis. Textile materials modified with TiO2 and ZnO NPs can be used as self-cleaning towels. They can also help purify air from microorganisms, VOCs and undesirable gases.","subset":"pubmed_abstract"} +{"meta":{"pmid":11177402,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Virologic and CD4 cell response to zidovudine or zidovudine and lamivudine following didanosine treatment of human immunodeficiency virus infection.\nTo optimize nucleoside reverse transcriptase inhibitor (nRTI) antiretroviral therapy, 137 subjects who had been treated with didanosine monotherapy for more than 3 years in the AIDS Clinical Trials Group (ACTG) 175 study were randomized to zidovudine and didanosine (dual therapy) or zidovudine, didanosine, and lamivudine (triple therapy). Evaluation of early (8 week) change in HIV plasma RNA demonstrated that addition of lamivudine and zidovudine provided significantly greater virologic suppression compared to the addition of zidovudine alone (mean decrease of 1.27 vs. 0.74 log(10) copies\/ml, n = 108, p = 0.007). Both dual and triple therapy provided significant long-term decreases (from study entry to mean at Weeks 40 and 48) in HIV plasma RNA: 0.62 and 0.86 log(10) copies\/ml, respectively (n = 110). However, the difference between treatments was not significant (p = 0.16). At 48 weeks, 26% of subjects starting study treatment had <500 copies\/ml of plasma HIV RNA. The CD4 count response was greater at 4 weeks for triple versus dual therapy: a mean increase of 51 vs. 12 CD4 cells\/ml(3) (n = 126, p = 0.039). The difference at Weeks 40 and 48 was not significant (a 22 cell increase vs. a 1 cell decrease, n = 129, p = 0.41). Zidovudine and didanosine treatment, with or without lamivudine, was well tolerated and only 2 of 137 (1.5%) of study participants developed an AIDS-defining event over 48 weeks.","subset":"pubmed_abstract"} +{"meta":{"pmid":26509415,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Optimization of the method for assessment of brain perfusion in humans using contrast-enhanced reflectometry: multidistance time-resolved measurements.\nThe aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.","subset":"pubmed_abstract"} +{"meta":{"pmid":16967806,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2017-13":1,"2015-11":1,"2014-10":1,"2024-10":1,"unknown":5}}},"text":"Retinal vessel segmentation using the 2-D Gabor wavelet and supervised classification.\nWe present a method for automated segmentation of the vasculature in retinal images. The method produces segmentations by classifying each image pixel as vessel or nonvessel, based on the pixel's feature vector. Feature vectors are composed of the pixel's intensity and two-dimensional Gabor wavelet transform responses taken at multiple scales. The Gabor wavelet is capable of tuning to specific frequencies, thus allowing noise filtering and vessel enhancement in a single step. We use a Bayesian classifier with class-conditional probability density functions (likelihoods) described as Gaussian mixtures, yielding a fast classification, while being able to model complex decision surfaces. The probability distributions are estimated based on a training set of labeled pixels obtained from manual segmentations. The method's performance is evaluated on publicly available DRIVE (Staal et al., 2004) and STARE (Hoover et al., 2000) databases of manually labeled images. On the DRIVE database, it achieves an area under the receiver operating characteristic curve of 0.9614, being slightly superior than that presented by state-of-the-art approaches. We are making our implementation available as open source MATLAB scripts for researchers interested in implementation details, evaluation, or development of methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":27262172,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"A Novel Chemotherapeutic Agent to Treat Tumors with DNA Mismatch Repair Deficiencies.\nImpairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutS\u03b1-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a MMR-dependent manner. In MutS\u03b1-proficient cells, baicalein binds to MutS\u03b1 to dissociate CHK2 from MutS\u03b1 leading to S-phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutS\u03b1-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutS\u03b1-deficient xenograft tumors and inhibits the growth of AOM-DSS-induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency. Cancer Res; 76(14); 4183-91. \u00a92016 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":27489022,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Premedication with Clarithromycin Is Effective against Secondary Bacterial Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.\nSecondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A\/PR8\/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-\u03b3 levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-\u03b3 production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited.","subset":"pubmed_abstract"} +{"meta":{"pmid":18473886,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"New therapies for sepsis.\nSepsis is a common clinical problem that is responsible for an increasing number of deaths. Many new therapies for severe sepsis have been developed but few have shown benefit in rigorous clinical trials. To date the most successful therapies are relatively simple clinical interventions: appropriate broad spectrum antibiotics; early goal directed therapies to restore tissue oxygen delivery; physiological dose hydrocortisone in patients with relative adrenal insufficiency; intensive insulin therapy to maintain normoglycemia; and lung-protective ventilation strategies. The only adjunctive therapy supported by strong evidence of benefit is Activated Protein C. Experimental therapies are being developed with improved in vitro and animal models and better understanding of the pathophysiology of sepsis in humans. Neutralization of the triggers of inflammation, such as endotoxin, and inhibition of the signal transduction mechanisms are promising new strategies. Statins may be beneficial in prevention of sepsis and as adjunctive treatments. Reconstitution of the immune response with interferon-gamma or granulocyte-macrophage colony stimulating factor may reverse immunoparesis in severe sepsis. Many other molecular targets have been identified for possible therapeutic intervention, but there are still fundamental difficulties to be overcome in demonstrating efficacy in clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":32573343,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Descriptive epidemiology and correlates of children's swimming competence.\nThis study examined the swimming competence of primary school children, and how it was related to swimming activity, non-fatal aquatic events, and demographic factors. Primary school students (N = 4959; female = 2705, male = 2241; age range = 5 to 14 years) across 28 schools in the 15 districts of Hong Kong completed the Swimming Competence Questionnaire, and questions about their swimming experience, non-fatal aquatic events, and demographic variables. Descriptive statistics showed that over 60% of children could swim more than 5m, but less than 50% could swim over 25m. Over 50% of children were able to perform some basic swimming skills (e.g., holding breath underwater, floating, poolside\/kickboard kicking, and treading water). Swimming competence was positively predicted by the demographic factors (i.e., age, sex, family income, and parents' highest education level), swimming experience, learning experience, and swimming location. Treading water was the only factor of swimming competence that established asignificant negative association with non-fatal aquatic events. Current results can be used to target key groups to improve children's swimming competence and reduce non-fatal aquatic events; children from lower socio-economic backgrounds and with less swimming experience should be encouraged to participate in more formal learn to swim lessons.","subset":"pubmed_abstract"} +{"meta":{"pmid":28255923,"dup_signals":{"dup_doc_count":16}},"text":"Transmission differentials for multiple pathogens as inferred from their prevalence in larva, nymph and adult of Ixodes ricinus (Acari: Ixodidae).\nIxodes ricinus serves as vector for a range of microorganisms capable of causing clinical illness in humans. The microorganisms occur in the same vector populations and are generally affected by the same tick-host interactions. Still, the instars have different host preferences which should manifest in different transmission patterns for various microorganisms in the tick populations, i.e., most microorganisms increase in prevalence rate from larvae to nymphs because their reservoirs are among small mammals and birds that serve as blood hosts for larvae. Other microorganisms, like Anaplasma phagocytophilum, mainly increase in prevalence rates from nymphs to adults, because their reservoirs are larger ungulates that serve as primary blood hosts for nymphs and adults. We sampled a representative sample of ticks from 12 locations on Zealand and Funen, Denmark, and investigated the differences in prevalence rate of infection in larvae, nymphs and adults for multiple pathogens. Prevalence of infection for larvae, nymphs and adults, respectively, was: 0, 1.5 and 4.5% for Borrelia burgdorferi; 0, 4.2 and 3.9% for Borrelia garinii; 0, 6.6 and 6.1% for Borrelia afzelii; 0, 0 and 0.6% for Borrelia valaisiana; 0, 3.7 and 0.6% for Borrelia spielmanii; 0, 0.7 and 1.2% for Babesia divergens; 0, 0, 0.6% for Babesia venatorum; 0, 1.5 and 6.1% for A. phagocytophilum. The results were in general compatible with the hypothesis i.e., that differences in blood host for larvae and nymphs define differences in transmission of infectious agents, but other factors than differences in blood hosts between larvae and nymphs may also be important to consider.","subset":"pubmed_abstract"} +{"meta":{"pmid":32733044,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"The role of aspartic acid in reducing coral calcification under ocean acidification conditions.\nBiomolecules play key roles in regulating the precipitation of CaCO3 biominerals but their response to ocean acidification is poorly understood. We analysed the skeletal intracrystalline amino acids of massive, tropical Porites spp. corals cultured over different seawater pCO2. We find that concentrations of total amino acids, aspartic acid\/asparagine (Asx), glutamic acid\/glutamine and alanine are positively correlated with seawater pCO2 and inversely correlated with seawater pH. Almost all variance in calcification rates between corals can be explained by changes in the skeletal total amino acid, Asx, serine and alanine concentrations combined with the calcification media pH (a likely indicator of the dissolved inorganic carbon available to support calcification). We show that aspartic acid inhibits aragonite precipitation from seawater in vitro, at the pH, saturation state and approximate aspartic acid concentrations inferred to occur at the coral calcification site. Reducing seawater saturation state and increasing [aspartic acid], as occurs in some corals at high pCO2, both serve to increase the degree of inhibition, indicating that biomolecules may contribute to reduced coral calcification rates under ocean acidification.","subset":"pubmed_abstract"} +{"meta":{"pmid":18215650,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":1,"2024-30":1,"unknown":11}}},"text":"A miniature cytometry platform for capture and characterization of T-lymphocytes from human blood.\nGiven the clinical and diagnostic importance of blood analysis, there is considerable interest in developing novel miniature devices for rapid characterization of blood constituents. The present paper describes development of a miniature cytometry platform aimed at analysis of T-lymphocytes from peripheral human blood. Microarrays of T-cell-specific antibodies (Abs), including anti-CD3, -CD4, -CD8 and mouse IgG (negative control) were robotically printed onto glass slides coated with a non-fouling poly(ethylene glycol) (PEG) hydrogel. The glass substrates containing Ab arrays were incubated with 100 microL of red blood cell (RBC)-depleted whole human blood for 15 min and then exposed to a controlled shear of approximately 2 dyncm(-2) for additional 10 min. This process led to the removal of non-specific leukocytes and \"development\" of patterns of T-cells captured on the Ab spots. The immunofluorescent staining of the surface-bound cells revealed the presence of purified CD4(+) and CD8(+) T-cells (purity >94%) on their respective Ab spots. Importantly, the proportions of CD4(+) and CD8(+) T-cells captured on the Ab spots correlated closely (R(2) -0.9) with flow cytometry analysis of T-cell subsets in blood. Overall, this cytometry platform allowed to rapidly (under 30 min) capture pure T-cell subsets from minimally processed human blood. Significantly, our device provided quantitative information about subset abundance solely based on the location of cells within the microarray. This cytometry platform is envisioned as a miniature immunology tool for determination of T-cell phenotype and will have immediate applications in HIV diagnostics and research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22240259,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"MiR-200a is involved in rat epididymal development by targeting \u03b2-catenin mRNA.\nThe expression of 350 microRNAs (miRNAs) in epididymis of rat from postnatal development to adult (from postnatal days 7-70) was profiled with home-made miRNA microarray. Among them, 48 miRNAs changed significantly, in which the expression of miR-200a increased obviously with time, in a good agreement with that obtained from northern blot analysis. The real-time quantitative-polymerase chain reaction result indicated that temporal expression of rat \u03b2-catenin was exactly inversed to that of miR-200a during rat epididymal development, implying that miR-200a might also target \u03b2-catenin mRNA in rat epididymis as reported by Saydam et al. in humans. The bioinformatic analysis indicated that 3' untranslated region of rat \u03b2-catenin mRNA did contain a putative binding site for miR-200a. Meanwhile, it was found that the sequence of this binding site was different from that of human \u03b2-catenin mRNA with a deletion of two adjacent nucleotides (U and C). But the results of luciferase targeting assay in HEK 293T cells and the overexpression of miR-200a in rat NRK cells demonstrated that miR-200a did target rat \u03b2-catenin mRNA and cause the suppression of its expression. All these results show that miR-200a should be involved in rat epididymal development by targeting \u03b2-catenin mRNA of rat and suppressing its expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":22555187,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-39":1,"2021-17":1,"2020-45":1,"2020-34":1,"2020-05":1,"2019-51":1,"2018-30":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2022-33":1}}},"text":"Introducing solid foods to preterm infants in developed countries.\nThe addition of solid foods to an infant's diet is required to provide adequate nutrition, as eventually an infant will be unable to consume a sufficient volume of breast milk to meet their nutritional needs. The timing of this important dietary change for infants born preterm (<37 weeks of gestation) should take into consideration their delayed early gross motor developmental progress, increased nutritional requirements, organ immaturity, increased gut permeability and increased risk of hospitalization from infections. Good head control is important for safe eating of solid foods: this developmental milestone may be delayed in preterm infants up to 3 months of corrected age. One randomized controlled trial has demonstrated improved nutritional intakes with the introduction of nutrient-dense solid foods from 13 weeks of uncorrected age, resulting in improved nutritional iron status and greater rate of growth during infancy. There is neither current evidence for an increased infection rate with an early introduction of solid foods in developed countries, nor is there evidence that in preterm infants maturation of renal function is reduced. However, one observational study has determined that preterm infants who had 4 or more solid foods introduced prior to 17 weeks of corrected age, or who had any solid foods introduced prior to 10 weeks of corrected age, had an increased risk of eczema development. A compromise is needed to balance the nutritional benefits of commencing solid foods from 13 weeks of uncorrected age with the risks of increased eczema development, along with ensuring developmental readiness. Based on the current evidence, 3 months (13 weeks) of corrected age seems to be an appropriate age to commence nutrient-dense solid foods for most preterm infants. Further research, with an emphasis on immediate as well as longer-term consequences, would be valuable to provide more specific evidence-based guidelines regarding the introduction of solid food for preterm infants.","subset":"pubmed_abstract"} +{"meta":{"pmid":19002211,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2017-13":1,"2014-10":1,"2024-22":1,"unknown":15}}},"text":"Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21.\nDown syndrome (DS) is one of the most frequent congenital birth defects, and the most common genetic cause of mental retardation. In most cases, DS results from the presence of an extra copy of chromosome 21. DS has a complex phenotype, and a major goal of DS research is to identify genotype-phenotype correlations. Cases of partial trisomy 21 and other HSA21 rearrangements associated with DS features could identify genomic regions associated with specific phenotypes. We have developed a BAC array spanning HSA21q and used array comparative genome hybridization (aCGH) to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA21. We report the identification and mapping of 30 pathogenic chromosomal aberrations of HSA21 consisting of 19 partial trisomies and 11 partial monosomies for different segments of HSA21. The breakpoints have been mapped to within approximately 85 kb. The majority of the breakpoints (26 of 30) for the partial aneuploidies map within a 10-Mb region. Our data argue against a single DS critical region. We identify susceptibility regions for 25 phenotypes for DS and 27 regions for monosomy 21. However, most of these regions are still broad, and more cases are needed to narrow down the phenotypic maps to a reasonable number of candidate genomic elements per phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":10413473,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":2,"2021-39":1,"2021-10":1,"2020-45":1,"2023-50":1,"2024-26":1,"2024-30":1}}},"text":"Models for molybdenum coordination during the catalytic cycle of periplasmic nitrate reductase from Paracoccus denitrificans derived from EPR and EXAFS spectroscopy.\nThe periplasmic nitrate reductase from Paracoccus denitrificans is a soluble two-subunit enzyme which binds two hemes (c-type), a [4Fe-4S] center, and a bis molybdopterin guanine dinucleotide cofactor (bis-MGD). A catalytic cycle for this enzyme is presented based on a study of these redox centers using electron paramagnetic resonance (EPR) and extended X-ray absorption fine structure (EXAFS) spectroscopies. The Mo(V) EPR signal of resting NAP (High g [resting]) has g(av) = 1.9898 is rhombic, exhibits low anisotropy, and is split by two weakly interacting protons which are not solvent-exchangeable. Addition of exogenous ligands to this resting state (e.g., nitrate, nitrite, azide) did not change the form of the signal. A distinct form of the High g Mo(V) signal, which has slightly lower anisotropy and higher rhombicity, was trapped during turnover of nitrate and may represent a catalytically relevant Mo(V) intermediate (High g [nitrate]). Mo K-edge EXAFS analysis was undertaken on the ferricyanide oxidized enzyme, a reduced sample frozen within 10 min of dithionite addition, and a nitrate-reoxidized form of the enzyme. The oxidized enzyme was fitted best as a di-oxo Mo(VI) species with 5 sulfur ligands (4 at 2. 43 A and 1 at 2.82 A), and the reduced form was fitted best as a mono-oxo Mo(IV) species with 3 sulfur ligands at 2.35 A. The addition of nitrate to the reduced enzyme resulted in reoxidation to a di-oxo Mo(VI) species similar to the resting enzyme. Prolonged incubation of NAP with dithionite in the absence of nitrate (i.e., nonturnover conditions) resulted in the formation of a species with a Mo(V) EPR signal that is quite distinct from the High g family and which has a g(av) = 1.973 (Low g [unsplit]). This signal resembles those of the mono-MGD xanthine oxidase family and is proposed to arise from an inactive form of the nitrate reductase in which the Mo(V) form is only coordinated by the dithiolene of one MGD. In samples of NAP that had been reduced with dithionite, treated with azide or cyanide, and then reoxidized with ferricyanide, two Mo(V) signals were detected with g(av) elevated compared to the High g signals. Kinetic analysis demonstrated that azide and cyanide displayed competitive and noncompetitive inhibition, respectively. EXAFS analysis of azide-treated samples show improvement to the fit when two nitrogens are included in the molybdenum coordination sphere at 2.52 A, suggesting that azide binds directly to Mo(IV). Based on these spectroscopic and kinetic data, models for Mo coordination during turnover have been proposed.","subset":"pubmed_abstract"} +{"meta":{"pmid":22475005,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":2,"2013-20":1,"2015-18":1,"unknown":7}}},"text":"Sex-specific mouse liver gene expression: genome-wide analysis of developmental changes from pre-pubertal period to young adulthood.\nEarly liver development and the transcriptional transitions during hepatogenesis are well characterized. However, gene expression changes during the late postnatal\/pre-pubertal to young adulthood period are less well understood, especially with regards to sex-specific gene expression. Microarray analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the late postnatal\/pre-pubertal period to young adulthood. A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p < E-76) in the set of genes positively regulated by the liver transcription factor HNF4\u03b1, as determined in a liver-specific HNF4\u03b1 knockout mouse model, while genes down regulated during this developmental period showed significant enrichment (p < E-65) for negative regulation by HNF4\u03b1. Significant enrichment of the developmentally regulated genes in the set of genes subject to positive and negative regulation by pituitary hormone was also observed. Five sex-specific transcriptional regulators showed sex-specific expression at 4 wk (male-specific Ihh; female-specific Cdx4, Cux2, Tox, and Trim24) and may contribute to the developmental changes that lead to global acquisition of liver sex-specificity by 8 wk of age. Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver.","subset":"pubmed_abstract"} +{"meta":{"pmid":26121492,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Single Exposure to near Roadway Particulate Matter Leads to Confined Inflammatory and Defense Responses: Possible Role of Metals.\nInhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single (\"subclinical response\") exposure to water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-\u03b1), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":29152569,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":9}}},"text":"Vocalizing in chimpanzees is influenced by social-cognitive processes.\nAdjusting communication to take into account information available to one's audience is routine in humans but is assumed absent in other animals, representing a recent development on the lineage leading to humans. This assumption may be premature. Recent studies show changes in primate alarm signaling to threats according to the receivers' risk. However, a classic problem in these and other perspective-taking studies is discerning whether signalers understand the receivers' mental states or simply are responding to their behavior. We designed experiments to exclude concurrent reading of the receivers' behavior by simulating receivers using prerecorded calls of other group members. Specifically, we tested whether wild chimpanzees emitted differing signals in response to a snake model when simulated receivers previously emitted either snake-related calls (indicating knowledge) or acoustically similar non-snake-related calls (indicating ignorance). Signalers showed more vocal and nonvocal signaling and receiver-directed monitoring when simulated receivers had emitted non-snake-related calls. Results were not explained by signaler arousal nor by receiver identity. We conclude that chimpanzees are aware enough of another's perspective to target information toward ignorant group members, suggesting that the integration of signaling and social cognition systems was already emerging in early hominoid lineages before the advent of more language-specific features, such as syntax.","subset":"pubmed_abstract"} +{"meta":{"pmid":30758283,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"Profundibacter amoris gen. nov., sp. nov., a new member of the Roseobacter clade isolated from Loki's Castle Vent Field on the Arctic Mid-Ocean Ridge.\nA bacterial strain, designated BAR1T, was isolated from a microbial mat growing on the surface of a barite chimney at the Loki's Castle Vent Field, at a depth of 2216 m. Cells of strain BAR1T were rod-shaped, Gram-reaction-negative and grew on marine broth 2216 at 10-37 \u00b0C (optimum 27-35 \u00b0C), pH 5.5-8.0 (optimum pH 6.5-7.5) and 0.5-5.0 % NaCl (optimum 2 %). The DNA G+C content was 57.38 mol%. The membrane-associated major ubiquinone was Q-10, the fatty acid profile was dominated by C18 : 1\u03c97c (91 %), and the polar lipids detected were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminolipid, one unidentified lipid and one unidentified phospholipid. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain BAR1T clustered together with Rhodobacterales bacterium PRT1, as well as the genera Halocynthiibacter and Pseudohalocynthiibacter in a polyphyletic clade within the Roseobacter clade. Several characteristics differentiate strain BAR1T from the aforementioned genera, including its motility, its piezophilic behaviour and its ability to grow at 35 \u00b0C and under anaerobic conditions. Accordingly, strain BAR1T is considered to represent a novel genus and species within the Roseobacter clade, for which the name Profundibacter amoris gen. nov., sp. nov. is proposed. The type strain is Profundibacter amoris BAR1T (=JCM 31874T=DSM 104147T).","subset":"pubmed_abstract"} +{"meta":{"pmid":22560020,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":2,"2020-05":1,"2019-51":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2021-17":1}}},"text":"Effects of X-ray treatments on pathogenic bacteria, inherent microflora, color, and firmness on whole cantaloupe.\nInactivation of inoculated Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica and Shigella flexneri on whole cantaloupes using X-ray at different doses (0.1, 0.5, 1.0, 1.5, and 2.0 kGy) was studied. The effect of X-ray on quality parameters (color and texture) of untreated and treated whole cantaloupes was instrumentally determined. The effect of X-ray on microflora counts (mesophilic counts, psychrotrophic counts and yeast and mold counts) of untreated and treated whole cantaloupes was also determined during storage at 22\u00b0C for 20 days. A mixture of three strains of each tested organism was spot inoculated (100 \u03bcl), separately, onto the surface (5 cm(2)) of cantaloupe rinds (approximately 8-9 log CFU ml(-1)) separately, air dried (60 min), and then treated with X-ray at 22\u00b0C and 55% relative humidity. Surviving bacterial populations on cantaloupe surfaces were evaluated using a nonselective medium (tryptic soy agar) with a selective medium overlay for each bacterium; E. coli O157:H7 (CT-SMAC agar), L. monocytogenes (MOA), and S. enterica and S. flexneri (XLD). More than a 5 log CFU reduction was achieved after treatment with 2.0 kGy X-ray, for all tested pathogens. No significant effect of X-ray treatment on cantaloupe color or firmness was detected. Furthermore, treatment with X-ray significantly reduced the initial inherent microflora on whole cantaloupes and inherent levels were significantly (p<0.05) lower than the control sample throughout storage for 20 days.","subset":"pubmed_abstract"} +{"meta":{"pmid":21533132,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.\nMethamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis\/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":7054292,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"New immunoglobulin IgG allotypes and haplotypes found in wild mice with monoclonal anti-allotope antibodies.\nSera from 156 wild mice (Mus musculus L.) collected from parts of Eurasia, Northern Africa, and the Americas were tested in solid-phase radioimmunoassays for reactivity with 20 monoclonal anti-allotope antibodies directed against gene products of the Igh-1, Igh-3, and Igh-4 loci. Most of the wild mice have Igh phenotypes similar to those of inbred strains or heterozygotes thereof, but frequently the wild mice showed unique combinations of allotypes on a given chromosome (haplotypes) not seen in inbred strains. We found new allotypes of the Igh-1 and Igh-4 loci. Mice from three regions (Poland, Taiwan, and Japan) possess combinations of allotypes indicating that recombination, gene conversion, or other gene duplication events have occurred in portions of the Igh constant region gene complex. Most interestingly, sera of three mice from Egypt possess immunoglobulin molecules appearing to result from an intragenic recombination event involving either Igh-1d or Igh-3d with Igh-1b. Two mice from Pakistan and one from Seychelles Island in the Indian Ocean also showed similar unusual phenotypes. These mice possess two CH2 IgH-1b and two CH2 Igh-1a\/CH2 Igh-1d determinants, suggesting that these variant immunoglobulin arose from recombinations within the CH2 domain.","subset":"pubmed_abstract"} +{"meta":{"pmid":8530441,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":4,"unknown":8}}},"text":"Requirement of calmodulin-dependent protein kinase II in cyclic ADP-ribose-mediated intracellular Ca2+ mobilization.\nCyclic ADP-ribose (cADPR) is generated in pancreatic islets by glucose stimulation, serving as a second messenger for Ca2+ mobilization from the endoplasmic reticulum for insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, we observed that the addition of calmodulin (CaM) to rat islet microsomes sensitized and activated the cADPR-mediated Ca2+ release. Inhibitors for CaM-dependent protein kinase II (CaM kinase II) completely abolished the glucose-induced insulin secretion as well as the cADPR-mediated and CaM-activated Ca2+ mobilization. Western blot analysis revealed that the microsomes contain the alpha isoform of CaM kinase II but do not contain CaM. When the active 30-kDa chymotryptic fragment of CaM kinase II was added to the microsomes, fully activated cADPR-mediated Ca2+ release was observed in the absence of CaM. These results along with available evidence strongly suggest that CaM kinase II is required to phosphorylate and activate the ryanodine-like receptor, a Ca2+ channel for cADPR as an endogenous activator, for the cADPR-mediated Ca2+ release.","subset":"pubmed_abstract"} +{"meta":{"pmid":9463361,"dup_signals":{"dup_doc_count":23,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2021-04":1,"2020-10":1,"2019-51":1,"2019-43":1,"2019-39":1,"2019-26":1,"2019-04":1,"2018-22":1,"2017-51":1,"2017-39":1,"2017-22":1,"2017-09":1,"2016-44":2,"2016-36":1,"2016-30":1,"2016-22":1,"2016-07":1,"2021-10":1}}},"text":"Strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila.\nPolarity in the Drosophila eye is manifested as a dorsoventral reflection of two chiral forms of the individual unit eyes, or ommatidia. These forms fall on opposite sides of a dorsoventral midline of mirror symmetry known as the equator. Polarity is established in the eye imaginal disc as cells adopt their fates and as the ommatidial precursors undergo coordinated rotation within the epithelium; the mechanisms that coordinate these early patterning events remain poorly understood. We have identified a novel gene, strabismus (stbm), which is required to establish polarity in the eye, legs and bristles of Drosophila. Many stbm ommatidia are reversed anteroposteriorly and\/or dorsoventrally. In stbm eye discs, ommatidial rotation is delayed and some ommatidial precursors initiate rotation in the wrong direction. Mosaic analysis indicates that stbm is ommatidium autonomous and required in most, if not all, photoreceptors within an ommatidium to establish normal polarity. stbm also appears to play an instructive role during the establishment of the fates of photoreceptors R3 and R4. stbm encodes a novel protein with a potential PDZ domain-binding motif and two possible transmembrane domains. Sequence analysis of both vertebrate and invertebrate homologs indicates that stbm has been highly conserved throughout evolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":21208598,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Massage therapy for children with autism spectrum disorders: a systematic review.\nWe aimed to assess the effectiveness of massage as a treatment option for autism. We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was \"(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder).\" The references in all located articles were also searched. No language restrictions were imposed. Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":16556051,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Clinical activity of pemetrexed: a multitargeted antifolate anticancer agent.\nPemetrexed is a new generation antifolate anticancer agent that inhibits several folate-dependent enzymes required for production of DNA and RNA intermediates. Early studies showed significant hematologic and nonhematologic toxicities with this agent. However it was found that many of these toxicities related to functional folate status and could be markedly reduced through routine supplementation with folic acid and vitamin B(12), without adversely affecting efficacy. Phase III studies with pemetrexed have established a clinical role for this drug as a single agent in the second-line treatment of non-small cell lung cancer and in combination with cisplatin for the frontline treatment of unresectable malignant pleural mesothelioma. Clinical trials of pemetrexed alone or in combination with other chemotherapeutic agents have shown considerable activity in many tumor types including colorectal, pancreatic and breast cancer, and urothelial tumors.","subset":"pubmed_abstract"} +{"meta":{"pmid":20208936,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2017-22":1,"2017-09":2,"2016-44":1,"2016-30":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":2,"2015-27":1,"2015-22":1,"2017-34":1,"2015-18":1}}},"text":"Distortion-tolerant 3D recognition of underwater objects using neural networks.\nA method for distortion-tolerant recognition of objects in water using three-dimensional (3D) integral imaging with a neural network classification architecture is presented. Recognition algorithms are developed and experimental results are presented with rotation-variable 3D objects. To test the robustness of the system, objects are placed under a variety of water conditions, including variable Maalox-induced scattering levels and occlusion using pine needles. Neural networks have long been used for two-dimensional recognition and have recently been used for 3D digital holographic recognition. To the best of our knowledge, this is the first use of neural networks for passive 3D integral imaging and recognition of underwater objects.","subset":"pubmed_abstract"} +{"meta":{"pmid":24759174,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Immunogenicity of a West Nile virus DIII-cholera toxin A2\/B chimera after intranasal delivery.\nWest Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA2\/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB\/c mice were immunized intranasally with DIII-CTA2\/B, DIII, DIII mixed with CTA2\/B, or CTA2\/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA2\/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA2\/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA2\/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA2\/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate.","subset":"pubmed_abstract"} +{"meta":{"pmid":8336669,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Biology of Frankia strains, actinomycete symbionts of actinorhizal plants.\nFrankia strains are N2-fixing actinomycetes whose isolation and cultivation were first reported in 1978. They induce N2-fixing root nodules on diverse nonleguminous (actinorhizal) plants that are important in ecological successions and in land reclamation and remediation. The genus Frankia encompasses a diverse group of soil actinomycetes that have in common the formation of multilocular sporangia, filamentous growth, and nitrogenase-containing vesicles enveloped in multilaminated lipid envelopes. The relatively constant morphology of vesicles in culture is modified by plant interactions in symbiosis to give a diverse array of vesicles shapes. Recent studies of the genetics and molecular genetics of these organisms have begun to provide new insights into higher-plant-bacterium interactions that lead to productive N2-fixing symbioses. Sufficient information about the relationship of Frankia strains to other bacteria, and to each other, is now available to warrant the creation of some species based on phenotypic and genetic criteria.","subset":"pubmed_abstract"} +{"meta":{"pmid":12667760,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Effects of acidic deposition on forest and aquatic ecosystems in New York State.\nAcidic deposition is comprised of sulfuric and nitric acids and ammonium derived from atmospheric emissions of sulfur dioxide, nitrogen oxides, and ammonia, respectively. Acidic deposition has altered soil through depletion of labile pools of nutrient cations (i.e. calcium, magnesium), accumulation of sulfur and nitrogen, and the mobilization of elevated concentrations of inorganic monomeric aluminum to soil solutions in acid-sensitive areas. Acidic deposition leaches essential calcium from needles of red spruce, making this species more susceptible to freezing injury. Mortality among sugar maples appears to result from deficiencies of nutrient cations, coupled with other stresses such as insect defoliation or drought. Acidic deposition has impaired surface water quality in the Adirondack and Catskill regions of New York by lowering pH levels, decreasing acid-neutralizing capacity, and increasing aluminum concentrations. Acidification has reduced the diversity and abundance of aquatic species in lakes and streams. There are also linkages between acidic deposition and fish mercury contamination and eutrophication of estuaries.","subset":"pubmed_abstract"} +{"meta":{"pmid":21896654,"dup_signals":{"dup_doc_count":25,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2023-14":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-26":3,"2024-22":1}}},"text":"Ending the message: poly(A) signals then and now.\nPolyadenylation [poly(A)] signals (PAS) are a defining feature of eukaryotic protein-coding genes. The central sequence motif AAUAAA was identified in the mid-1970s and subsequently shown to require flanking, auxiliary elements for both 3'-end cleavage and polyadenylation of premessenger RNA (pre-mRNA) as well as to promote downstream transcriptional termination. More recent genomic analysis has established the generality of the PAS for eukaryotic mRNA. Evidence for the mechanism of mRNA 3'-end formation is outlined, as is the way this RNA processing reaction communicates with RNA polymerase II to terminate transcription. The widespread phenomenon of alternative poly(A) site usage and how this interrelates with pre-mRNA splicing is then reviewed. This shows that gene expression can be drastically affected by how the message is ended. A central theme of this review is that while genomic analysis provides generality for the importance of PAS selection, detailed mechanistic understanding still requires the direct analysis of specific genes by genetic and biochemical approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":26333303,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Fetal anterior abdominal wall thickness may be an early ultrasonographic sign of gestational diabetes mellitus.\nThe aim of the study was to investigate standard biometric measurements, such as biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), estimated fetal weight (EFW) and anterior abdomen wall thickness (AAWT) in fetuses complicated by gestational diabetes mellitus (GDM) at the time of GDM screening, and to compare the results with healthy pregnant controls. A total of 124 pregnant women between 26 and 28 weeks' gestation were included in the study. These patients were divided into two groups based on their 75-g oral glucose tolerance test results. The study group consisted of 55 pregnant women with GDM, and 69 healthy pregnant women constituted our control group. The study groups did not differ with respect to the mean BPD, FL, AC and EFW; however, the mean AAWT was significantly higher in the GDM group, 4.07 \u00b1 0.46 mm versus 3.28 \u00b1 0.37 mm in the control group (p < 0.001). The only fetal sonographic measurement found to significantly differ between the study groups was the AAWT in 26 weeks at the time of gestational diabetes screening, suggesting that measuring the AAWT may have a role in the evaluation of fetal growth in pregnancies complicated by gestational diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":15558585,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.\nThe efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.","subset":"pubmed_abstract"} +{"meta":{"pmid":28984470,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":16}}},"text":"Advances in systemic therapy for malignant mesothelioma: future perspectives.\nMalignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":24950976,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Proteome-scale identification of outer membrane proteins in Mycobacterium avium subspecies paratuberculosis using a structure based combined hierarchical approach.\nOuter membrane proteins (OMPs) in eubacteria have several important roles, which range from membrane transport to the host-pathogen interactions. These are directly involved in pathogen attachment, entry and activation of several pathogen-induced signaling cascades in the cell. The cardinal structural features of OMPs include the presence of a \u03b2-barrel, a signal peptide and the absence of the transmembrane helix. This is the first report on proteome-wide identification of OMPs of ruminant pathogen, Mycobacterium avium subsp. paratuberculosis (MAP). The complete proteome of MAP was analyzed using a pipeline of algorithms, which screens the amino acid sequences and structural features shared by OMPs in other bacteria. Secondary structure of these proteins is also analyzed and scores are calculated for amphiphilic \u03b2-strands. From the set of 588 exported proteins, 264 proteins are predicted to be inner membrane proteins while 83 proteins are identified as potential OMPs in MAP. Finally, this study identified 57 proteins as top candidates, on the basis of computed isoelectric points, as the core set of OMPs. Significantly, the resulting data for OMPs are not only useful in designing novel vaccines but may also open avenues for the development of early serodiagnostic tools for MAP.","subset":"pubmed_abstract"} +{"meta":{"pmid":11802537,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Linkage and mutation analysis in two Taiwanese families with long QT syndrome.\nLong QT syndrome (LQT) is a cardiovascular disorder causing syncope and sudden death from arrhythmias. Mutations in KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A genes encoding cardiac potassium and sodium ion channels cause LQT. Two Taiwanese LQT families were screened for mutations in these ion channel genes. In family H87, the diagnosis was made in the 25-year-old female proband and six family members based on recurrent syncope and\/or a prolonged QT interval. Genotyping revealed a novel nonsense mutation, R744X (C to T transition in codon 744), in the KCNH2 potassium channel gene, resulting in truncation of the putative cyclic nucleotide-binding domain and C-terminal region of the HERG K(+)-channel in all affected family members. The mutation was confirmed by DdeI endonuclease digestion of the DNA from each family member. The 26-year-old female proband in family L89 developed repeated syncope with QTc of 0.61 seconds. After linkage and mutation analysis, the syndrome in this family was associated with a novel KCNQ1 missense mutation, T309I, causing the substitution of a threonine residue at position 309, in the pore region of the KvLQT1 K(+)-channel, with an isoleucine. By Tsp45I restriction analysis, the mutation was noted in the proband and the proband's asymptomatic brother, but was not detected in 100 unrelated normal individuals. Identification of a mutation has clinical implications for presymptomatic diagnosis and therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":28339249,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-27":1,"2020-34":1,"2020-29":1,"2019-47":1,"2018-47":1,"2018-34":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-14":1,"2024-26":1}}},"text":"Electric Control of Dirac Quasiparticles by Spin-Orbit Torque in an Antiferromagnet.\nSpin orbitronics and Dirac quasiparticles are two fields of condensed matter physics initiated independently about a decade ago. Here we predict that Dirac quasiparticles can be controlled by the spin-orbit torque reorientation of the N\u00e9el vector in an antiferromagnet. Using CuMnAs as an example, we formulate symmetry criteria allowing for the coexistence of topological Dirac quasiparticles and N\u00e9el spin-orbit torques. We identify the nonsymmorphic crystal symmetry protection of Dirac band crossings whose on and off switching is mediated by the N\u00e9el vector reorientation. We predict that this concept verified by minimal model and density functional calculations in the CuMnAs semimetal antiferromagnet can lead to a topological metal-insulator transition driven by the N\u00e9el vector and to the topological anisotropic magnetoresistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":23401472,"dup_signals":{"dup_doc_count":22,"dup_details":{"curated_sources":5,"unknown":17}}},"text":"Epigenetic regulation is a crucial factor in the repression of UGT1A1 expression in the human kidney.\nHuman uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds, such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter (-85 to +40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver. A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of hepatocyte nuclear factor (HNF) 1\u03b1 to the promoter. The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but this promoter was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells. The transfection of an HNF1\u03b1 expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-aza-dC. In summary, we found that DNA hypermethylation, along with histone hypoacetylation, interferes with the binding of HNF1\u03b1, resulting in the defective expression of UGT1A1 in the human kidney. Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1.","subset":"pubmed_abstract"} +{"meta":{"pmid":12270816,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":3,"2023-14":2,"2023-06":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":2,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-22":1}}},"text":"Tactic responses to oxygen in the phototrophic bacterium Rhodobacter sphaeroides WS8N.\nThe temporal and spatial behavior of a number of mutants of the photosynthetic, facultative anaerobe Rhodobacter sphaeroides to both step changes and to gradients of oxygen was analyzed. Wild-type cells, grown under a range of conditions, showed microaerophilic behavior, accumulating in a 1.3-mm band about 1.3 mm from the meniscus of capillaries. Evidence suggests this is the result of two signaling pathways. The strength of any response depended on the growth and incubation conditions. Deletion of either the complete chemosensory operons 1 and 2 plus the response regulator genes cheY(4) and cheY(5) or cheA(2) alone led to the loss of all aerotactic responses, although the cells still swam normally. The Prr system of R. sphaeroides responds to electron flow through the alternative high-affinity cytochrome oxidase, cbb(3), controlling expression of a wide range of metabolic pathways. Mutants with deletions of either the complete Prr operon or the histidine kinase, PrrB, accumulated up to the meniscus but still formed a thick band 1.3 mm from the aerobic interface. This indicates that the negative aerotactic response to high oxygen levels depends on PrrB, but the mutant cells still retain the positive response. Tethered PrrB(-) cells also showed no response to a step-down in oxygen concentration, although those with deletions of the whole operon showed some response. In gradients of oxygen where the concentration was reduced at 0.4 micro M\/s, tethered wild-type cells showed two different phases of response, with an increase in stopping frequency when the oxygen concentration fell from 80 to 50% dissolved oxygen and a decrease in stopping at 50 to 20% dissolved oxygen, with cells returning to their normal stopping frequency in 0% oxygen. PrrB and CheA(2) mutants showed no response, while PrrCBA mutants still showed some response.","subset":"pubmed_abstract"} +{"meta":{"pmid":221977,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.\nThe effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into reticulocyte ghosts increased the number of beta-adrenergic receptor sites. The appearance of beta-adrenergic binding sites was dependent on the formation of phosphatidylcholine by the enzyme that converts phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. Both the synthesis of phosphatidylcholine and the unmasking of cryptic receptors were time and temperature dependent and did not occur in the presence of the methyl transferase inhibitor, S-adenosyl-L-homocysteine.","subset":"pubmed_abstract"} +{"meta":{"pmid":19487683,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist.\nBreast cancer patients have benefited from the use of targeted therapies directed at specific molecular alterations. To identify additional opportunities for targeted therapy, we searched for genes with marked overexpression in subsets of tumors across a panel of breast cancer profiling studies comprising 3,200 microarray experiments. In addition to prioritizing ERBB2, we found AGTR1, the angiotensin II receptor type I, to be markedly overexpressed in 10-20% of breast cancer cases across multiple independent patient cohorts. Validation experiments confirmed that AGTR1 is highly overexpressed, in several cases more than 100-fold. AGTR1 overexpression was restricted to estrogen receptor-positive tumors and was mutually exclusive with ERBB2 overexpression across all samples. Ectopic overexpression of AGTR1 in primary mammary epithelial cells, combined with angiotensin II stimulation, led to a highly invasive phenotype that was attenuated by the AGTR1 antagonist losartan. Similarly, losartan reduced tumor growth by 30% in AGTR1-positive breast cancer xenografts. Taken together, these observations indicate that marked AGTR1 overexpression defines a subpopulation of ER-positive, ERBB2-negative breast cancer that may benefit from targeted therapy with AGTR1 antagonists, such as losartan.","subset":"pubmed_abstract"} +{"meta":{"pmid":26914831,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Association Study of a Functional Variant on ABCG2 Gene with Sunitinib-Induced Severe Adverse Drug Reaction.\nSunitinib is a tyrosine kinase inhibitor and used as the first-line treatment for advanced renal cell carcinoma (RCC). Nevertheless, inter-individual variability of drug's toxicity was often observed among patients who received sunitinib treatment. This study is to investigate the association of a functional germline variant on ABCG2 that affects the pharmacokinetics of sunitinib with sunitinib-induced toxicity of RCC patients in the Japanese population. A total of 219 RCC patients were recruited to this pharmacogenetic study. ABCG2 421C>A (Q141K) was genotyped by using PCR-Invader assay. The associations of both clinical and genetic variables were evaluated with logistic regression analysis and subsequently receiver operating characteristic (ROC) curve was plotted. About 43% (92\/216) of RCC patients that received sunitinib treatment developed severe grade 3 or grade 4 thrombocytopenia according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 3.0, the most common sunitinib-induced adverse reaction in this study. In the univariate analysis, both age (P = 7.77x10(-3), odds ratio (OR) = 1.04, 95%CI = 1.01-1.07) and ABCG2 421C>A (P = 1.87x10(-2), OR = 1.71, 95%CI = 1.09-2.68) showed association with sunitinib-induced severe thrombocytopenia. Multivariate analysis indicated that the variant ABCG2 421C>A is suggestively associated with severe thrombocytopenia (P = 8.41x10(-3), OR = 1.86, 95% CI = 1.17-2.94) after adjustment of age as a confounding factor. The area under curve (AUC) of the risk prediction model that utilized age and ABCG2 421C>A was 0.648 with sensitivity of 0.859 and specificity of 0.415. Severe thrombocytopenia is the most common adverse reaction of sunitinib treatment in Japanese RCC patients. ABCG2 421C>A could explain part of the inter-individual variability of sunitinib-induced severe thrombocytopenia.","subset":"pubmed_abstract"} +{"meta":{"pmid":19017851,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Biomechanical risk factors in the development of medial tibial stress syndrome in distance runners.\nWe investigated the relationship between functional and static foot posture and medial tibial stress syndrome in distance runners. Twenty-eight runners with a clinical diagnosis of medial tibial stress syndrome and 12 asymptomatic runners were assessed with the Foot Posture Index to measure static overpronation. Range of motion was measured at the talocrural joint, with the knee extended and flexed as was range of motion at the first metatarsophalangeal joint and the angular difference between the neutral and relaxed calcaneal stance positions. Each participant was then videotaped while running on a treadmill shod and unshod. This videotape was analyzed using freeze frame to identify abnormal or mistimed pronation at each phase of gait. The results were analyzed using logistic regression to give the probability that a runner is likely to experience medial tibial stress syndrome, predicted from the static measurements and dynamic observations. Variables identified as being significant predictors of medial tibial stress syndrome were the difference between the neutral and relaxed calcaneal stance positions, range of motion of the talocrural joint with the knee extended, early heel lift and abductory twist during gait, and apropulsive gait. Runners with suspected symptoms of medial tibial stress syndrome should be assessed dynamically and statically for abnormal or mistimed pronation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28621422,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"A new role of the membrane-type matrix metalloproteinase 16 (MMP16\/MT3-MMP) in neural crest cell migration.\nNeural crest cells (NCCs) are a transient population of neuroectodermal-originated cells that populate the dorsal neural tube (dNT), before migrating and giving rise to multiple cell lineages in the developing embryo. Prior to their migration, NCCs undergo epithelial-to-mesenchymal-transition (EMT) through which they lose cell contacts and detach from the dNT to invade their surrounding environment. Multiple signals and transcription factors have been identified to regulate these events. Yet, less is known regarding effectors that act downstream to execute the actual NCC separation and migration. Matrix metalloproteinases (MMPs) are a family of proteases that degrade the extracellular matrix as well as other pericellular proteins during processes of tissue remodeling, angiogenesis and metastasis. Previously, we and others have demonstrated the role of the gelatinases MMP2 and MMP9 during the onset of NCC migration. Several evidences link the cleavage and activation of these secreted gelatinases to the activity of membrane-type MMPs (MT-MMP), such as MMP14 and MMP16, which are tethered to plasma membrane and affect various cellular behaviors. The aim of this study was to investigate whether MMP16 acts in NCCs. Here we demonstrate the expression of MMP16 mRNA and protein in cranial NCCs in avian embryos. Knockdown of MMP16 inhibited NCC migration. This inhibition was rescued by the addition of recombinant MMP16, which was also sufficient to increase proper NCC migration. Furthermore, excess MMP16 caused enhanced NCC EMT, concomitant with degradation of dNT-related proteins, laminin and N-cadherin. Altogether, these results uncover MMP16 as a new effector participating in EMT and in the migration of NCCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":19218827,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":10}}},"text":"Reliability and validity of the Massachusetts general hospital cognitive and physical functioning questionnaire.\nWe have recently developed the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and we here report on its reliability and validity. The internal consistency of the CPFQ was assessed by computing Cronbach's coefficient alpha based upon the average intercorrelation of the 7 items of the CPFQ in a sample of depressed outpatients and by factor analyzing data from the same sample to confirm that the scale is unifactorial and measuring a single construct. Test-retest reliability of the CPFQ was assessed in a different sample of depressed outpatients by computing Pearson's correlation coefficient between pretreatment screening scores and pretreatment baseline scores. Sensitivity to change of the CPFQ was assessed by computing the dependent t test for the subjects in the active treatment condition in the second sample of depressed outpatients. Finally, convergent validity for the CPFQ was assessed in two different ways. We found that the CPFQ is a unifactorial scale, with strong internal consistency. It has good temporal stability as indicated by high test-retest reliability. The CPFQ was also found to be sensitive to change with treatment and displayed convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy and neuropsychological functioning. Although, as expected, the CPFQ was significantly correlated with a measure of depression, the moderate correlation (r approximately 0.30) indicates that the CPFQ is measuring a different construct. In summary, the CPFQ is a unifactorial scale, with strong internal consistency, good temporal stability and sensitivity to change with treatment. Further studies will be needed to assess the validity and reliability of this instrument in other psychiatric and neuropsychiatric conditions associated with cognitive dysfunction.","subset":"pubmed_abstract"} +{"meta":{"pmid":31601890,"dup_signals":{"dup_doc_count":36,"dup_dump_count":21,"dup_details":{"curated_sources":1,"2023-50":2,"2023-40":1,"2023-23":1,"2023-14":2,"2023-06":1,"2022-40":1,"2022-33":1,"2022-27":2,"2022-21":2,"2022-05":4,"2021-43":1,"2021-39":2,"2021-25":3,"2021-21":3,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":2,"2020-29":2}}},"text":"Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.\nAdult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer's Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":3514754,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Selective phagocytosis of gram-positive bacteria and interleukin 1-like factor production by a subpopulation of large granular lymphocytes.\nThere has been a consensus that a large granular lymphocyte (LGL) population with natural killer (NK) function is nonadherent and nonphagocytic. However, a significant proportion of the nonadherent cells purified by the two-step depletion of adherent cells with a plastic surface and nylon wool columns engulfed Sta. aureus into their cytoplasm. These cells were morphologically identified as LGL in light and electron microscopies. Two-color immunofluorescence tests, furthermore, demonstrated that Leu-11+ LGL, Leu-11+7-, and Leu-11+7+, but not Leu-11-7+, phagocytosed Sta. aureus. Among the particles tested here, only Gram(+) bacteria were preferentially phagocytosed, whereas Gram(-) bacteria, other large-sized microbes (e.g., baker's yeast and Candida albicans), latex, silica, and carbonyl iron were not. LGL exhibited a substantial level of bactericidal activity against Sta. aureus, although the level was one third of that mediated by monocytes. When Gram(+) bacteria were incubated with nonadherent cells for 18 hr, significant amounts of interleukin 1 (IL 1)-like factors (or IL 1 itself) as well as interferon were detected in the supernatants. On the other hand, this incubation did not induce interleukin 2 (IL 2). The IL 1-like factor producer cells were demonstrated to be the low-density lymphocytes on Percoll separation and to have the Leu-11+ phenotype. The phagocytosis was suggested to be an important stimulus in producing IL 1-like factors from LGL. Thus, the treatment of cells with cytochalasin B, a microfilament disrupting agent, completely abrogated both phagocytosis and IL 1-like factor production. Some cell wall components of Gram(+) bacteria might be important to a recognition process of the phagocytosis, since the protoplasts of Sta. aureus, when prepared by the treatment of bacteria with lysostaphin, were no longer phagocytosed by LGL. The present results therefore identify an additional unique characteristic similar to, but not identical with, the myelomonocytic nature of Leu-11+ LGL.","subset":"pubmed_abstract"} +{"meta":{"pmid":30699898,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":15}}},"text":"The Influence of Physical Fitness on Reasons for Academy Separation in Law Enforcement Recruits.\nThis study analyzed the effects physical fitness may have on reasons for academy separation in law enforcement recruits. A retrospective analysis was conducted on 401 recruits; 330 recruits graduated (GRAD), and 71 recruits separated at various times during academy. Twenty-eight recruits separated for personal reasons (SEPPR); 18 due to physical training failures (i.e., poor fitness) or injury (SEPFI); and 25 due to academic or scenario failures (SEPAS). Fitness testing occurred prior to academy, and included: Push-ups and sit-ups in 60s; a 75-yard pursuit run (75PR); vertical jump; medicine ball throw; and multistage fitness test (MSFT). A one-way ANOVA with Bonferroni post hoc compared between-group fitness test performance. A multiple stepwise regression calculated whether recruit characteristics or fitness could predict separation. The GRAD group was younger than the SEPAS group (p < 0.01), faster in the 75PR than the SEPFI group (p = 0.02), and completed more MSFT shuttles than the SEPPR and SEPFI groups (p = 0.01). Age predicted GRAD and SEPAS group inclusion; MSFT predicted GRAD, SEPPR, and SEPFI group inclusion. Recruits who had superior high-intensity running capacity (75PR) and aerobic fitness (MSFT) should have a better chance of completing academy. However, this could be influenced by training practices adopted during academy.","subset":"pubmed_abstract"} +{"meta":{"pmid":18445925,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":5}}},"text":"Knowledge and attitudes of pharmacists regarding oral health care and oral hygiene products in Chennai city.\nThis study was done to find out the knowledge and attitudes of pharmacists regarding oral health care and oral hygiene products in Chennai city. A cross-sectional survey among a sample of the pharmacists in Chennai city was done and data regarding their knowledge and attitudes towards oral health care and oral hygiene products were obtained using a closed-ended questionnaire. Among the 60 pharmacies approached, 50 pharmacists participated in the study and completed the questionnaire. Though 48% of the participants gave a positive answer when asked whether they had met the dentist practicing close to their pharmacies, the frequency with which they met the dentist ranged from once a week (24%) to once a month (28%). Most of the pharmacists stocked oral health-related products, which comprised 15-25% of their total stock. Of these products toothpaste was the most common (62%), followed by mouth rinses (12%). Toothache or painful teeth was the most common dental problem (78%) for which patients approached the pharmacists for advice. With regard to the advice given, 38.5% of the pharmacists asked the patient to consult a nearby dentist after dispensing medications, while 22.4% of the pharmacists dispensed antibiotics and painkillers without any referral. Seventy percent of the pharmacists expressed interest in giving oral health care advice to patients. However, many of them (38%) felt that lack of proper knowledge is a barrier to providing oral health care advice. It is clear from the present study that pharmacists are presently an underutilized resource, and there is a definitive need to improve their training and access to information on available dental services.","subset":"pubmed_abstract"} +{"meta":{"pmid":22765934,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":4,"unknown":11}}},"text":"Innovative primary care delivery in rural Alaska: a review of patient encounters seen by community health aides.\nFor more than 50 years, Community Health Aides and Community Health Practitioners (CHA\/Ps) have resided in and provided care for the residents of their villages. This study is a systematic description of the clinical practice of primary care health workers in rural Alaska communities. This is the first evaluation of the scope of health problems seen by these lay health workers in their remote communities. Retrospective observational review of administrative records for outpatient visits seen by CHA\/Ps in 150 rural Alaska villages (approximate population 47,370). Analysis of electronic records for outpatient visits to CHA\/Ps in village clinics from October 2004 through September 2006. Data included all outpatient visits from the Indian Health Service National Patient Information Reporting System. Descriptive analysis included comparisons by region, age, sex, clinical assessment and treatment. In total 272,242 visits were reviewed. CHA\/Ps provided care for acute, chronic, preventive, and emergency problems at 176,957 (65%) visits. The remaining 95,285 (35%) of records did not include a diagnostic code, most of which were for administrative or medication-related encounters. The most common diagnostic codes were: pharyngitis (11%), respiratory infections (10%), otitis media (8%), hypertension (6%), skin infections (4%), and chronic lung disease (4%). Respiratory distress and chest pain accounted for 75% (n=10,552) of all emergency visits. CHA\/Ps provide a broad range of primary care in remote Alaskan communities whose residents would otherwise be without consistent medical care. Alaska's CHA\/P program could serve as a health-care delivery model for other remote communities with health care access challenges.","subset":"pubmed_abstract"} +{"meta":{"pmid":21541254,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2019-09":1,"2018-51":1,"2018-39":1,"2018-34":1,"2018-17":1,"2018-13":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-22":1,"2017-17":1,"2019-22":1}}},"text":"Morbidity, including fatal morbidity, throughout life in men entering adult life as obese.\nThe association between obesity in adults and excess morbidity and mortality is well established, but the health impact throughout adult life of being obese in early adulthood needs elucidation. We investigated somatic morbidity, including fatal morbidity, throughout adulthood in men starting adult life as obese. Among 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (defined as BMI\u226531.0 kg\/m(2)), and, as controls, a random 1% sample of the others was identified. In the age range of 18-25 years, there were 1,862 obese, which encompass the men above the 99.5 percentile, and 3,476 controls. Information on morbidity was obtained via national registers. Cox regression models were used to estimate the relative morbidity assessed as first incidence of disease, occurrence of disease in the year preceding death and prevalent disease at time of death. From age 18 through 80 years the obese had an increased risk of becoming diseased by or die from a broad range of diseases. Generally, the incidence of first event, occurrence in the year prior to death, and prevalence at time of death showed the same pattern. As an example, the relative hazard of type 2 diabetes was constant throughout life at 4.9 (95% confidence intervals [CI]: 4.1-5.9), 5.2 (95% CI: 3.6-7.5), and 6.8 (95% CI: 4.6-10.1), respectively. Our findings strongly support the continued need to avoid beginning adult life as obese, as obese young men experience an increased morbidity, including fatal morbidity, from many diseases throughout life.","subset":"pubmed_abstract"} +{"meta":{"pmid":18194533,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2015-18":1,"2014-10":3,"2024-10":1,"unknown":5}}},"text":"Evaluation of a joint Bioinformatics and Medical Informatics international course in Peru.\nNew technologies that emerge at the interface of computational and biomedical science could drive new advances in global health, therefore more training in technology is needed among health care workers. To assess the potential for informatics training using an approach designed to foster interaction at this interface, the University of Washington and the Universidad Peruana Cayetano Heredia developed and assessed a one-week course that included a new Bioinformatics (BIO) track along with an established Medical\/Public Health Informatics track (MI) for participants in Peru. We assessed the background of the participants, and measured the knowledge gained by track-specific (MI or BIO) 30-minute pre- and post-tests. Participants' attitudes were evaluated both by daily evaluations and by an end-course evaluation. Forty-three participants enrolled in the course - 20 in the MI track and 23 in the BIO track. Of 20 questions, the mean % score for the MI track increased from 49.7 pre-test (standard deviation or SD = 17.0) to 59.7 (SD = 15.2) for the post-test (P = 0.002, n = 18). The BIO track mean score increased from 33.6 pre-test to 51.2 post-test (P < 0.001, n = 21). Most comments (76%) about any aspect of the course were positive. The main perceived strength of the course was the quality of the speakers, and the main perceived weakness was the short duration of the course. Overall, the course acceptability was very good to excellent with a rating of 4.1 (scale 1-5), and the usefulness of the course was rated as very good. Most participants (62.9%) expressed a positive opinion about having had the BIO and MI tracks come together for some of the lectures. Pre- and post-test results and the positive evaluations by the participants indicate that this first joint Bioinformatics and Medical\/Public Health Informatics (MI and BIO) course was a success.","subset":"pubmed_abstract"} +{"meta":{"pmid":25576333,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2021-04":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-09":1,"2018-51":1,"2018-43":1,"2023-06":1,"2024-18":1}}},"text":"Length and weight of newborns in Croatia from 1985 to 2009.\nConstitutional characteristics of humans are changing. People are becoming taller and they weigh more. These changes influence birth weight and birth length as well. A study was conducted on 2414 mothers and their newborns from 1985 to 2009 in Zagreb, Croatia, to establish a secular change in the weight and length of infants and the factors that are most related to these changes. Birth weight has increased significantly in the past 25 years, and it is higher in male newborns. Taller mothers, with higher weight and body mass index, deliver newborns with higher birth weight. Weight gain in pregnancy has positive impact on birth weight. Multiparas and older and more educated women deliver newborns with higher weight. Birth weight does not depend on father's education. The number of newborns with birth weight more than 4000 g is increasing, but not significantly. Birth length was not significantly higher. Birth length is higher in male newborns, in newborns with higher birth weight and newborns of older and more educated mothers. Better life conditions and better health care improves population constitutional characteristics that have implications in higher birth weight and birth length. This could be an important change that influences delivery modalities.","subset":"pubmed_abstract"} +{"meta":{"pmid":23954609,"dup_signals":{"dup_doc_count":32,"dup_dump_count":26,"dup_details":{"curated_sources":2,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":2,"2014-49":1,"2014-42":2,"2014-41":2,"2014-23":2,"2017-04":1,"2015-11":1,"2015-06":1,"2014-10":1,"2015-18":1}}},"text":"Safety of protocol violations in acute stroke tPA administration.\nIntravenous (IV) tissue plasminogen activator remains the only approved therapy for acute ischemic stroke (AIS) in the United States; however, less than 10% of patients receive treatment. This is partially because of the large number of contraindications, narrow treatment window, and physician reluctance to deviate from these criteria. We retrospectively analyzed consecutive patients who received IV thrombolysis at our stroke center for National Institute of Neurological Disorders and Stroke (NINDS) protocol violations and rates of symptomatic intracerebral hemorrhage (sICH). Other outcome variables included systemic hemorrhage, modified Rankin Scale at discharge, and discharge disposition. A total of 212 patients were identified in our stroke registry between 2009 and 2011 and included in the analysis. Protocol violations occurred in 76 patients (36%). The most common violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure management (15%), elevated prothrombin time (PT) or partial thromboplastin time (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%), and stroke within 3 months (3%). There were no significant differences in any of the safety outcomes or discharge disposition between patients with or without protocol violations. Controlling for age, National Institutes of Health Stroke Scale on admission, and glucose on admission, there was no significant increase in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who had protocol violations. Despite more than one third of patients receiving thrombolysis with protocol violations, overall rates of hemorrhage remained low and did not differ from those who did not have violations. Our data support the need to expand access to thrombolysis in AIS patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":2112327,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Fast multiphase MR imaging of aqueductal CSF flow: 2. Study in patients with hydrocephalus.\nThe signal intensity in the region corresponding to the cerebral aqueduct was evaluated in three patients with noncommunicating tension hydrocephalus (caused by aqueductal obstruction in two and type I Arnold-Chiari malformation in the other), seven patients with suspected normal-pressure hydrocephalus (three of whom subsequently underwent successful shunting), and 10 patients with ex vacuo (atrophic) hydrocephalus. A gradient-echo MR sequence, called fast multiphase imaging, was used. Serial images corresponding to different phases of the cardiac cycle were acquired. No flow-related enhancement was observed over the entire cardiac cycle in the patients with noncommunicating hydrocephalus. Patients with normal-pressure hydrocephalus showed a higher aqueductal CSF signal intensity, consistent with increased systolic flow rates, than patients with ex vacuo hydrocephalus. When comparing the above two groups of patients with a control group of healthy volunteers, significantly higher and lower values of the (mean) maximum aqueductal signal intensity were found in the normal-pressure hydrocephalus patients and the ex vacuo hydrocephalus patients, respectively. Fast multiphase MR evaluation of aqueductal CSF flow may help to differentiate patients with different types of hydrocephalus.","subset":"pubmed_abstract"} +{"meta":{"pmid":19881893,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":1,"2023-06":2,"2022-40":2,"2021-21":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-24":1,"2019-39":1,"2019-30":1,"2019-18":1,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Cost disparities in lung cancer treatment by disability status, sex, and race.\nThe recent literature contains numerous reports of disparities in the diagnosis, treatment, and outcomes of lung cancer across a growing list of population subgroups, including disability status. A common assumption is that disparities stem mainly from variations in the level and type of treatment resources available to specific subgroups. Few studies, however, have directly measured resource differentials. Since policy makers identify reducing health disparities as a critical priority, this study examined whether cumulative Medicare costs (resource consumption) for lung cancer treatment differ across eight patient subgroups defined by disability status, sex, and race. Treatment disparities across the eight subgroups will be reflected in variations in the cumulative cost profiles of those subgroups, controlling for other plausible cost drivers. Failure to detect statistically significant differentials in these cost profiles implies that treatment disparities stem from factors other than access to, and utilization of, health care services. Linked SEER-Medicare data were used to construct cost profiles by service type and treatment phase for roughly 80,000 incident lung cancer cases in patients aged 45 to 85 years at diagnosis. Multiple regression models then tested for cost differentials across the eight subgroups, controlling for various patient and disease characteristics. Significant cost differentials were detected, some unanticipated. Women tended to have higher treatment costs than men; they also had more favorable survivals. Nonwhites also tended to have higher treatment costs than whites, although they had significantly shorter survivals. On average, men with disabilities consumed the fewest treatment resources and had the shortest survivals. Mixed results were obtained for women with disabilities. Among others, the findings suggest that reducing disparities will take more than just improving access to health care. Special attention must be paid to lung cancer patients with disabilities by both policy makers and clinicians.","subset":"pubmed_abstract"} +{"meta":{"pmid":23316942,"dup_signals":{"dup_doc_count":17,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2018-17":1,"2017-47":1,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2018-26":1}}},"text":"Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report.\nAnti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet's syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet's syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently commenced on immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present with a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titres of anti-myeloperoxidase-anti-neutrophil cytoplasmic antibody with multi-antigenicity, positive anti-histone antibodies and the lack of immunoglobulin and complement deposition histopathogically. A rash that is characteristic of Sweet's syndrome has also been described as an association. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed for definite treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":23036998,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Pupillometric evaluation of the dynamics of the pupillary response to a brief light stimulus in healthy subjects.\nTo investigate the correlation between measurements of amplitude (A) and peak velocity (V) of constriction in the pupil light reflex of normal subjects, and to determine the effects of stimulus intensity, pupil size, and age on this relationship. The pupil response to a variable intensity 1.0 second light stimulus presented under open-loop conditions (Maxwellian optics) was measured using infrared video techniques in 43 healthy subjects aged 20 to 75 years old. In response to the \"standard-intensity\" light stimulus, mean measurements of A and V were 1.92 mm (SD 0.39) and 5.65 mm\/s (SD 1.17), respectively. Over a 4.0 log unit range of stimulus intensities measurements of A and V were seen to co-vary with the data being best fit by the equation V=0.86+2.65A (linear regression coefficient, R = 0.919, P < 0.001). In each subject the regression plot was used to normalize the velocity estimates for A = 1.0 mm; these normalized velocity estimates showed no significant correlation with the starting size of the pupil or the age of the subject. There is a strong linear correlation between amplitude and peak velocity of constriction for the pupil light reflex in normal subjects. This relationship is unaffected by the stimulus intensity, size of the pupil, or age of the subject. Clinicians and researchers must keep this interdependence in mind when drawing inferences from the observed (or measured) speed of the pupillary constriction to light.","subset":"pubmed_abstract"} +{"meta":{"pmid":23416607,"dup_signals":{"dup_doc_count":54,"dup_dump_count":42,"dup_details":{"curated_sources":4,"2018-51":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":2,"2016-36":2,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":2,"2014-41":3,"2014-35":2,"2014-23":2,"2014-15":2,"2022-33":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2017-13":1}}},"text":"Adsorption of methylene blue and methyl red dyes from aqueous solutions onto modified zeolites.\nZeolite, hematite, modified zeolite and commercial activated charcoal were examined for their ability to remove methylene blue (MB) and methyl red (MR) from their aqueous solutions. Modified zeolite and hematite were produced according to the Schwertmann and Cornell method while zeolite and commercial activated charcoal were obtained from S&B and Fluka AG companies, respectively. Adsorption experiments were conducted at three different adsorbent-to-solution ratios, namely 8, 16 and 24 g\/L under environmental conditions and continuous stirring. Equilibrium isotherms of MB and MR were studied at different initial concentrations (from 5 \u00d7 10(-4) to 5 \u00d7 10(-3) g\/L). MB adsorption kinetics were also studied. The maximum adsorption of MB and MR from their aqueous solutions was achieved at 24 g\/L (adsorbent-to-dye solution ratio) after 1 h and was equal to 100% (MB) on modified zeolite and 99% (MR) on commercial activated charcoal, respectively. All the other materials achieved intermediate values of dye adsorption. From the applied kinetic models, the pseudo-second-order equation best described the adsorption of MB and MR. Consequently, modified zeolite showed the highest adsorption capacity for MB, while commercial activated charcoal showed the highest adsorption capacity of MR. The studied adsorbents can be used as filters to remove dyes from wastewaters.","subset":"pubmed_abstract"} +{"meta":{"pmid":27458840,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"2024-18":1,"2024-10":2,"unknown":5}}},"text":"Differential enrichment of TTF-I and Tip5 in the T-like promoter structures of the rDNA contribute to the epigenetic response of Cyprinus carpio during environmental adaptation.\nTo ensure homeostasis, ectothermic organisms adapt to environmental variations through molecular mechanisms. We previously reported that during the seasonal acclimatization of the common carp Cyprinus carpio, molecular and cellular functions are reprogrammed, resulting in distinctive traits. Importantly, the carp undergoes a drastic rearrangement of nucleolar components during adaptation. This ultrastructural feature reflects a fine modulation of rRNA gene transcription. Specifically, we identified the involvement of the transcription termination factor I (TTF-I) and Tip-5 (member of nucleolar remodeling complex, NoRC) in the control of rRNA transcription. Our results suggest that differential Tip5 enrichment is essential for silencing carp ribosomal genes and that the T0 element is key for regulating the ribosomal gene during the acclimatization process. Interestingly, the expression and content of Tip5 were significantly higher in winter than in summer. Since carp ribosomal gene expression is lower in the winter than in summer, and considering that expression concomitantly occurs with nucleolar ultrastructural changes of the acclimatization process, these results indicate that Tip5 importantly contributes to silencing the ribosomal genes. In conclusion, the current study provides novel evidence on the contributions of TTF-I and NoRC in the environmental reprogramming of ribosomal genes during the seasonal adaptation process in carp.","subset":"pubmed_abstract"} +{"meta":{"pmid":15875860,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":16}}},"text":"Silver halide colloid precursors for the synthesis of monolayer-protected clusters.\nA new method for the synthesis of monolayer-protected silver clusters (MPCs) based on the two-phase reduction of a stable negatively charged silver bromide sol is described. Phase transfer of the colloid to toluene is accomplished using tetra-n-octylammonium bromide as the phase transfer reagent. The advantage of this synthesis is to uncouple the formation of the silver halide colloid from its transfer and reduction in the organic phase, thus allowing control over each reaction step. The silver colloid in toluene was reduced with aqueous borohydride in the presence of 4-bromobenzenethiol as the passivating agent. The UV-visible absorption spectra indicate the intermediate formation of Ag(core)AgBr(shell) clusters during reduction. The resulting MPCs have been characterized by optical and transmission electron microscopy, energy-dispersive X-ray analysis, thermogravimetry, and UV-vis absorption spectroscopy. The formation of spiral cracks in the nanoparticulate agglomerates on solvent evaporation was observed. The spectra of thin films obtained by solvent evaporation have been analyzed using an effective medium theory.","subset":"pubmed_abstract"} +{"meta":{"pmid":26061590,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Morphological Control of Anisotropic Self-Assemblies from Alternating Poly(p-dioxanone)-poly(ethylene glycol) Multiblock Copolymer Depending on the Combination Effect of Crystallization and Micellization.\nA novel and facile method was developed for morphological controlling of self-assemblies prepared by crystallization induced self-assembly of crystalline-coil copolymer depending on the combination effect of crystallization and micellization. The morphological evolution of the self-assemblies of alternating poly(p-dioxanone)-block-poly(ethylene glycol) (PPDO-PEG) multiblock copolymer prepared by different solvent mixing methods in aqueous solution were investigated. \"Chrysanthemum\"-like and \"star anise\"-like self-assemblies were obtained at different rates of solvent mixing. The results suggested gradually change in solvent quality (slowly dropping water into DMF solution) leaded to a hierarchical micellization-crystallization process of core-forming PPDO blocks, and flake-like particles were formed at the initial stage of crystallization. Meanwhile, crystallization induced micellization process occurred when solvent quality changed drastically. Shuttle-like particles, which have much smaller size than those of flake-like particles, were formed at the initial stage of crystallization when quickly injecting water into DMF solution of the copolymer. Therefore, owing to the different changing rate of solvent quality, which may result in different combination effect of crystallization and micellization during self-assembly of the copolymer, PPDO-PEG self-assemblies with different hierarchical morphology in nano scale could be obtained.","subset":"pubmed_abstract"} +{"meta":{"pmid":22642807,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Recurrent phosphaturic mesenchymal tumour of the temporal bone causing deafness and facial nerve palsy.\nWe describe the first reported case of a phosphaturic mesenchymal tumour, mixed connective tissue variant, invading the temporal bone. A female patient presented with increasing deafness. On examination there appeared to be a mass behind an intact tympanic membrane. Further radiological investigation showed a vascular mass occupying the middle ear, mastoid and internal auditory meatus. This was surgically resected and revealed to be a benign phosphaturic mesenchymal tumour, mixed connective tissue variant. The tumour recurred a year later, presenting as facial nerve palsy. A revision procedure was carried out; the tumour was excised with the sacrifice of a segment of the facial nerve, and a facial-hypoglossal nerve anastomosis was performed. This case report highlights the occurrence of this benign but sometimes aggressive tumour, of which both clinicians and pathologists should be aware. Early recognition of the condition remains of utmost importance to minimise the debilitating consequences of long-term osteomalacia in affected patients, and to prevent extracranial and intracranial complications caused by the tumour.","subset":"pubmed_abstract"} +{"meta":{"pmid":19715269,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-26":1,"unknown":17}}},"text":"Implementation of high resolution 43Ca solid state NMR spectroscopy: toward the elucidation of calcium sites in biological materials.\nCalcium is one of the most abundant cations in living organisms. It is found in the mineral phase of bone and in proteins like calmodulin. However, its exact environment beyond the first coordination sphere is often unknown, thus hampering the understanding of many biological processes. Here, calcium benzoate trihydrate (Ca(C(6)H(5)COO)(2) x 3 H(2)O) was used as a model for the NMR analysis of calcium sites in biological materials, because of the similarity of its calcium coordination, to water and carboxylate ligands, to that in several calcium-proteins. First, calcium-43 magic angle spinning (MAS) and static NMR spectra of a (43)Ca enriched sample were recorded at different magnetic fields, to investigate the electronic environment of calcium. Complex static lineshapes were obtained because of the presence of anisotropic NMR interactions of similar magnitude (chemical shift anisotropy and quadrupolar interaction), and the full interpretation of the spectra required simulations and gauge-including projector augmented wave (GIPAW) DFT calculations. An NMR investigation of the coordination environment of Ca(2+) was carried out, using high resolution (13)C-(43)Ca MAS NMR experiments such as TRAPDOR (transfer of population double resonance) and heteronuclear J-spin-echoes. It was shown that despite the weakness of (13)C-(43)Ca interactions, it is possible to discriminate carbon atoms according to their calcium environment. Long-range calcium-carbon correlations were even evidenced by TRAPDOR, reaching distances >5.6 A. This work demonstrates that by combining solid state NMR experiments, DFT calculations, and simulations, it will be possible to elucidate the electronic and coordination environment of calcium in many important and complex materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":24013175,"dup_signals":{"dup_doc_count":11}},"text":"Evaluation of cardiac functions of patients with benign joint hypermobility syndrome.\nWe sought to investigate whether echocardiography with tissue Doppler imaging identifies myocardial dysfunction in children with benign joint hypermobility syndrome (BJHS). This cross-sectional study enrolled 75 children with BJHS and 70 healthy children. We performed detailed echocardiography in individuals with BJHS without inherited connective tissue disorders. Any congenital or acquired cardiac disease was excluded by clinical and echocardiographic examination. Both groups were similar in terms of age, sex, and body mass index. The diameter of the aortic annulus and sinus valsalva were wider in patients with BJHS. There was no significant differences in ejection fraction or mitral and tricuspid annular plane systolic excursion between the two groups. Pulsed-wave Doppler-derived E\/A ratios in mitral and tricuspid valves were similar in both groups. Deceleration time of early mitral inflow was prolonged in patients with BJHS. Mitral and tricuspid annulus Ea velocity were significantly lower in children with BJHS. Ea, Aa, and Ea\/Aa ratios in the interventricular septum, left ventricle posterior wall, and right ventricle free wall were lower in patients with BJHS than in the control group. The E\/Ea ratio was greater in patients with BJHS than in the control group. Isovolumic relaxation time and right-ventricular (RV) and left-ventricular (LV) myocardial performance indices (MPIs) were greater in patients with BJHS. This study showed the diastolic dysfunction in patients with BJHS. In addition, we detected increased LV and RV MPI. We believe that BJHS may affect proteins of the myocardial cytoskeleton and extracellular matrix.","subset":"pubmed_abstract"} +{"meta":{"pmid":12786630,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":10}}},"text":"Mycophenolate mofetil in refractory inflammatory bowel disease.\nMycophenolate mofetil has been claimed to be effective and well tolerated in refractory inflammatory bowel disease although there is little information regarding its use in clinical practice. To review our experience in achieving and maintaining remission in refractory inflammatory bowel disease and to document tolerability, major toxicity and efficacy. A retrospective audit was performed of the records of all patients with inflammatory bowel disease treated with mycophenolate mofetil (1-2 g\/day) over a 3-year period. Thirty-nine patients were identified. Almost all had been intolerant of, or had not responded to azathioprine, and 38 were steroid-dependent. mycophenolate mofetil was discontinued in 22 patients, 11 due to intolerance and 10 because of lack of efficacy. Of the 17 on treatment at the end of the study period 16 were in remission and off all steroid therapy, but one needed infliximab to maintain remission. No major toxicity was noted and there was no major sepsis. Approximately 40% of patients with severe refractory inflammatory bowel disease achieved remission and complete steroid withdrawal on mycophenolate mofetil therapy, almost 30% could not tolerate the drug, and a further 30% did not respond. Mycophenolate mofetil therapy may have a role for steroid-dependent patients refractory to azathioprine.","subset":"pubmed_abstract"} +{"meta":{"pmid":18171187,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Predictive factors for the development of central line-associated bloodstream infection due to gram-negative bacteria in intensive care unit patients after surgery.\nTo examine the relative proportions of central line-associated bloodstream infection (BSI) due to gram-negative bacteria and due to gram-positive bacteria among patients who had undergone surgery and patients who had not. The study also evaluated clinical predictive factors and unadjusted outcomes associated with central line-associated BSI caused by gram-negative bacteria in the postoperative period. Observational, case-control study based on a retrospective review of medical records. University of Chicago Medical Center, a 500-bed tertiary care center located on Chicago's south side. Adult intensive care unit (ICU) patients who developed central line-associated BSI. There were a total of 142 adult patients who met the Centers for Disease Control and Prevention National Nosocomial Infection Surveillance System definition for central line-associated BSI. Of those, 66 patients (46.5%) had infections due to gram-positive bacteria, 49 patients (34.5%) had infections due to gram-negative bacteria, 23 patients (16.2%) had infections due to yeast, and 4 patients (2.8%) had mixed infections. Patients who underwent surgery were more likely to develop central line-associated BSI due to gram-negative bacteria within 28 days of the surgery, compared with patients who had not had surgery recently (57.6% vs 27.3%; P= .002). On multivariable logistic regression analysis, diabetes mellitus (adjusted odds ratio [OR], 4.6 [95% CI, 1.2-18.1]; P= .03) and the presence of hypotension at the time of the first blood culture positive for a pathogen (adjusted OR, 9.8 [95% CI, 2.5-39.1]; P= .001) were found to be independently predictive of central line-associated BSI caused by gram-negative bacteria. Unadjusted outcomes were not different in the group with BSI due to gram-negative pathogens, compared to the group with BSI due to gram-positive pathogens. Clinicians caring for critically ill patients after surgery should be especially concerned about the possibility of central line-associated BSI caused by gram-negative pathogens. The presence of diabetes and hypotension appear to be significant associated factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":27035955,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":2,"2024-30":1,"unknown":11}}},"text":"Structures of E. coli \u03c3S-transcription initiation complexes provide new insights into polymerase mechanism.\nIn bacteria, multiple \u03c3 factors compete to associate with the RNA polymerase (RNAP) core enzyme to form a holoenzyme that is required for promoter recognition. During transcription initiation RNAP remains associated with the upstream promoter DNA via sequence-specific interactions between the \u03c3 factor and the promoter DNA while moving downstream for RNA synthesis. As RNA polymerase repetitively adds nucleotides to the 3'-end of the RNA, a pyrophosphate ion is generated after each nucleotide incorporation. It is currently unknown how the release of pyrophosphate affects transcription. Here we report the crystal structures of E coli transcription initiation complexes (TICs) containing the stress-responsive \u03c3(S) factor, a de novo synthesized RNA oligonucleotide, and a complete transcription bubble (\u03c3(S)-TIC) at about 3.9-\u00c5 resolution. The structures show the 3D topology of the \u03c3(S) factor and how it recognizes the promoter DNA, including likely specific interactions with the template-strand residues of the -10 element. In addition, \u03c3(S)-TIC structures display a highly stressed pretranslocated initiation complex that traps a pyrophosphate at the active site that remains closed. The position of the pyrophosphate and the unusual phosphodiester linkage between the two terminal RNA residues suggest an unfinished nucleotide-addition reaction that is likely at equilibrium between nucleotide addition and pyrophosphorolysis. Although these \u03c3(S)-TIC crystals are enzymatically active, they are slow in nucleotide addition, as suggested by an NTP soaking experiment. Pyrophosphate release completes the nucleotide addition reaction and is associated with extensive conformational changes around the secondary channel but causes neither active site opening nor transcript translocation.","subset":"pubmed_abstract"} +{"meta":{"pmid":32566039,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Strong-LAMP Assay Based on a Strongyloides spp.-Derived Partial Sequence in the 18S rRNA as Potential Biomarker for Strongyloidiasis Diagnosis in Human Urine Samples.\nHuman strongyloidiasis a soil-transmitted infection caused by Strongyloides stercoralis is one of the most neglected amongst the so-called Neglected Tropical Diseases (NTDs). S. stercoralis is a nematode, which is distributed worldwide; it has been estimated that it could affect millions of people, mainly in tropical and subtropical endemic regions. The difficulties of diagnosis lead to infection rates being underreported. Asymptomatic patients have chronic infections that can lead to severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. Strongyloidiasis can easily be misdiagnosed because conventional faecal-based techniques lack of sensitivity for the morphological identification of infective larvae in faeces. None of the currently used molecular methods have used urine samples as an alternative to faecal samples for diagnosing strongyloidiasis. This study was thus aimed at comparing, for the first time, the use of a new loop-mediated isothermal amplification (LAMP) molecular assay (Strong-LAMP) to traditional methods on patients' urine samples. Twenty-four urine samples were taken from patients included in a study involving two Spanish hospitals for strongyloidiasis screening using parasitological and serological tests. Strongyloides larvae were found in 11 patients' faecal samples, thereby ascertaining that they had the disease. Other patients had high antibody titres but no larvae were found in their faeces. All urine samples were analysed by PCR and Strong-LAMP assay. No amplification occurred when using PCR. Strong-LAMP led to detecting S. stercoralis DNA in urine samples from patients having previously confirmed strongyloidiasis by parasitological tests and\/or a suspicion of being infected by serological ones. The Strong-LAMP assay is a useful molecular tool for research regarding strongyloidiasis in human urine samples. After further validation, the Strong-LAMP assay could also be used for complementary and effective diagnosis of strongyloidiasis in a clinical setting.","subset":"pubmed_abstract"} +{"meta":{"pmid":10721933,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Advances in the development of retinoids as chemopreventive agents.\nWith the inclusion of brief discussions of retinoid drug development in animal carcinogenesis models (e.g., skin, breast, oral cavity, lung, prostate or bladder) and clinical trials (e.g., head and neck or cervix), this review will focus on recent advances in retinoid molecular targeting studies designed primarily to develop retinoids with reduced toxicity, while maintaining or enhancing activity in the context of chemoprevention. Major current retinoid molecular targets include the six known nuclear retinoid receptors (RAR and RXR). Receptor numbers, distinct functions, tissue-expression patterns, ligand specificities, functional redundancy and regulation of multiple pathways make retinoid signaling highly complex. Development of receptor-selective synthetic retinoids is a major focus of molecular retinoid development. RAR heterodimerize with RXR and mediate classic retinoid activity\/toxicity. RXR are more promiscuous, heterodimerizing with several other members of the steroid receptor superfamily [e.g., peroxisome proliferator-activated receptors (PPAR) or vitamin D receptors]. RXR-selective ligands are less toxic and more active in animal breast cancer prevention studies and less toxic than RAR ligands in clinical trials. Other new avenues of retinoid molecular drug development include newly identified retinoid-regulated genes, orphan-receptor ligands\/functions, novel retinoid mechanisms involving potent receptor-independent apoptosis-inducing activity (e.g., 4-HPR or anhydroretinol), synergistic combinations [e.g., RXR agonists plus selective estrogen receptor modulators (SERM)], activity in other diseases and novel delivery systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":36150279,"dup_signals":{"dup_doc_count":22,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-30":3,"2024-26":3,"2024-22":1,"2024-18":2,"2024-10":5,"unknown":7}}},"text":"Triangulating Amsterdam's illicit stimulant use trends by wastewater analysis and recreational drug use monitoring.\nDrug consumption estimates are of relevance because of public health effects as well as associated criminal activities. Wastewater analysis of drug residues enables the estimation of drug consumption and drug markets. Short-term and long-term trends of cocaine, MDMA (ecstasy), amphetamine (speed) and methamphetamine (crystal meth), were studied for the city of Amsterdam. MDMA (+41%) and cocaine (+26%) showed significantly higher weekend vs. week consumption, while no differences were observed for the other drugs. The consumption of MDMA, cocaine, amphetamine and methamphetamine significantly increased between 2011 and 2019. Weekly trends emerging from wastewater analyses were supported by qualitative and quantitative data from a recreational drug use monitoring scheme. However, information collected in panel interviews within nightlife networks and surveys among visitors of pubs, clubs and festivals only partially reflected the long term increase in consumption as registered from wastewater analysis. Furthermore, methamphetamine use was not well presented in survey data, panel studies and test service samples, but could be monitored trough wastewater analysis. This illustrates that wastewater analysis can function as an early warning if use and user groups are small or difficult to reach trough other forms of research. All in all, this study illustrates that wastewater-based epidemiology is complementary to research among user groups, and vice versa. These different types of information enable to connect observed trends in total drug consumption to behaviour of users and the social context in which the use takes place as well as validate qualitative signals about (increased) consumption of psychoactive substances. Such a multi angular approach to map the illicit drug situation on local or regional scale can provide valuable information for public health.","subset":"pubmed_abstract"} +{"meta":{"pmid":2926320,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Kappa-bungarotoxin blocks nicotinic transmission at an identified invertebrate central synapse.\nA comparison was made between the effects of kappa-bungarotoxin and alpha-bungarotoxin upon nicotinic cholinergic transmission at an identified synapse (the cereal afferent, giant interneurone 2 synapse) in the central nervous system of the cockroach (Periplaneta americana). kappa-Bungarotoxin, a snake venom kappa-neurotoxin, completely blocked nicotinic unitary excitatory postsynaptic potentials (EPSPs) and evoked composite EPSPs when applied at a concentration of 1.0 x 10(-7) moll-1. No recovery was observed after a 2h wash in normal saline. kappa-Bungarotoxin produced a decrease in acetylcholine-induced nicotinic responses which paralleled decreases in nicotinic synaptic potentials and currents, indicating that kappa-bungarotoxin blocked postsynaptic nicotinic receptors. This blockade appeared to be specific as resting membrane potential, input resistance and the ability to elicit an action potential in response to direct stimulation of giant interneurone 2 were unchanged following prolonged toxin exposures. Samples of alpha-bungarotoxin which were free from kappa-neurotoxin contamination were also found to be potent antagonists of cockroach neuronal nicotinic receptors. It is concluded that the cockroach receptor is the first reported example of a neuronal nicotinic receptor which is sensitive to blockade by both kappa-neurotoxins and alpha-neurotoxins.","subset":"pubmed_abstract"} +{"meta":{"pmid":15827794,"dup_signals":{"dup_doc_count":11}},"text":"Isolated hepatic perfusion for the treatment of patients with colorectal cancer liver metastases after irinotecan-based therapy.\nIrinotecan given with 5-fluorouracil and leucovorin is currently used as first-line therapy for patients with metastatic colorectal cancer (CRC). However, the response duration is <1 year, and second-line systemic chemotherapy has limited efficacy. We analyzed the efficacy of isolated hepatic perfusion (IHP) for patients with progressive CRC liver metastases after irinotecan. Between March 1993 and February 2003, 124 patients with CRC liver metastases underwent IHP on institutional review board-approved protocols. The overall treatment mortality was 4% (5 of 124). Twenty-five patients (10 women and 15 men; mean age, 53 years) were identified who had progressive liver metastases by carcinoembryonic antigen, imaging studies, or both after irinotecan. A 1-hour hyperthermic IHP (mean hepatic temperature, 40.0 degrees C) with melphalan 1.5 mg\/kg (mean total dose, 100 mg) was administered via laparotomy. Perfusion with an oxygenated extracorporeal circuit was established with inflow via a cannula in the gastroduodenal artery and common hepatic artery inflow occlusion. Outflow was via a cannula in an isolated segment of the inferior vena cava. During IHP, portal and inferior vena caval flow were shunted to the axillary vein. Patients were assessed for radiographical response, recurrence pattern, and survival. The mean number of prior irinotecan cycles in 25 patients was 6 (range, 2-14), and it was given primarily as second-line therapy. The median number of liver metastases before IHP was 10 (range, 1-50), and the median percentage of hepatic replacement by tumor was 25%. The mean operative time was 9 hours (range, 6-12 hours), and the median hospital stay was 11 days (range, 8-76 days). There was 1 complete response and there were 14 partial responses in 25 patients (60%), with a median duration of 12 months (range, 5-35 months). Disease progressed systemically in 13 of 25 patients at a median of 5 months (range, 3-16 months). The median overall survival was 12 months (range, 1-47 months), and the 2-year survival was 28%. For patients with progressive CRC liver metastases after irinotecan, IHP has good efficacy in terms of response rate and duration. Continued evaluation of IHP with melphalan as second-line therapy in this clinical setting is justified.","subset":"pubmed_abstract"} +{"meta":{"pmid":11828592,"dup_signals":{"dup_doc_count":23,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2,"2017-13":1,"unknown":8}}},"text":"Sources of health insurance and characteristics of the uninsured: analysis of the March 2001 Current Population Survey.\nThis Issue Brief provides summary data on the insured and uninsured populations in the nation and in each state. It discusses the characteristics most closely related to an individual's health insurance status. Based on EBRI estimates from the March 2001 Current Population Survey (CPS), it represents 2000 data--the most recent available. Between 1999 and 2000, the percentage of Americans with health insurance increased: 84.1 percent of nonelderly Americans were covered by some form of health insurance in 2000, up from 83.8 percent in 1999. The percentage of nonelderly Americans without health insurance coverage declined from 16.2 percent in 1999 to 15.9 percent in 2000, continuing a trend that started between 1998 and 1999. The main reason for the decline in the number of uninsured Americans was the strong economy and low unemployment. Between 1999 and 2000, the percentage of nonelderly Americans covered by employment-based health insurance increased from 66.6 percent to 67.3 percent, continuing a longer-term trend that started between 1993 and 1994. In 2000, 34.3 million Americans received health insurance from public programs, and an additional 16.1 million purchased it directly from an insurer. More than 25 million Americans participated in Medicaid or the State Children's Health Insurance Program, and 6.1 million received their health insurance through the Tricare and CHAMPVA programs and other government programs designed to provide coverage for retired military members and their families. Even though the number and percentage of uninsured declined substantially between 1998 and 2000, more than 38 million Americans remain uninsured. While an increasing percentage of Americans were being covered by employment-based health plans, this trend may not continue because of the combined re-emergence of health care cost inflation and the weak economy. As long as the economy is strong and unemployment is low, employment-based health insurance coverage will expand and the uninsured will decline gradually. However, the combination of the current weak economy and the rising cost of providing health benefits will likely result in more Americans without health insurance coverage. Should the uninsured remain unchanged and continue to represent 15.9 percent of the nonelderly population, 40 million would be uninsured by 2005. If the uninsured represented 25 percent of the population, 63 million would be uninsured in 2005 and 65 million nonelderly Americans would be uninsured by 2010.","subset":"pubmed_abstract"} +{"meta":{"pmid":28423147,"dup_signals":{"dup_doc_count":16}},"text":"Adherence to High-Intensity Statins Following a Myocardial Infarction Hospitalization Among Medicare Beneficiaries.\nHigh-intensity statins are recommended following myocardial infarction. However, patients may not continue taking this medication with high adherence. To estimate the proportion of patients filling high-intensity statin prescriptions following myocardial infarction who continue taking this medication with high adherence and to analyze factors associated with continuing a high-intensity statin with high adherence after myocardial infarction. Retrospective cohort study of Medicare patients following hospitalization for myocardial infarction. Medicare beneficiaries aged 66 to 75 years (n = 29 932) and older than 75 years (n = 27 956) hospitalized for myocardial infarction between 2007 and 2012 who filled a high-intensity statin prescription (atorvastatin, 40-80 mg, and rosuvastatin, 20-40 mg) within 30 days of discharge. Beneficiaries had Medicare fee-for-service coverage including pharmacy benefits. Sociodemographic, dual Medicare\/Medicaid coverage, comorbidities, not filling high-intensity statin prescriptions before their myocardial infarction (ie, new users), and cardiac rehabilitation and outpatient cardiologist visits after discharge. High adherence to high-intensity statins at 6 months and 2 years after discharge was defined by a proportion of days covered of at least 80%, down-titration was defined by switching to a low\/moderate-intensity statin with a proportion of days covered of at least 80%, and low adherence was defined by a proportion of days covered less than 80% for any statin intensity without discontinuation. Discontinuation was defined by not having a statin available to take in the last 60 days of each follow-up period. Approximately half of the beneficiaries were women and fourth-fifths were white. At 6 months and 2 years after discharge among beneficiaries 66 to 75 years of age, 17 633 (58.9%) and 10 308 (41.6%) were taking high-intensity statins with high adherence, 2605 (8.7%) and 3315 (13.4%) down-titrated, 5182 (17.3%) and 4727 (19.1%) had low adherence, and 3705 (12.4%) and 4648 (18.8%) discontinued their statin, respectively. The proportion taking high-intensity statins with high adherence increased between 2007 and 2012. African American patients, Hispanic patients, and new high-intensity statin users were less likely to take high-intensity statins with high adherence, and those with dual Medicare\/Medicaid coverage and more cardiologist visits after discharge and who participated in cardiac rehabilitation were more likely to take high-intensity statins with high adherence. Results were similar among beneficiaries older than 75 years of age. Many patients filling high-intensity statins following a myocardial infarction do not continue taking this medication with high adherence for 2 years postdischarge. Interventions are needed to increase high-intensity statin use and adherence after myocardial infarction.","subset":"pubmed_abstract"} +{"meta":{"pmid":16661554,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Efficiency of hydrogen photoproduction by chloroplast-bacterial hydrogenase systems.\nA comparative study of H(2) photoproduction by chloroplasts and solubilized chlorophyll was performed in the presence of hydrogenase preparations of Clostridium butyricum. The photoproduction of H(2) by chloroplasts in the absence of exogenous electron donors, and with irreversibly oxidized dithiothreitol and cysteine, is thought to be limited by a cyclic transport of electrons wherein methylviologen short-circuits the electron transport in photosystem I. The efficiency of H(2) photoproduction by chloroplasts with ascorbate and NADPH is limited by a back reaction between light-reduced methylviologen and the oxidized electron donors. The use of a combination of electron donors (dithiothreitol and ascorbate), providing anaerobiosis without damage to chloroplasts, makes it possible to avoid consumption of reduced methylviologen for the reduction of oxidized electron donors and to exclude the short-circuiting of electron transfer. Under these conditions, photoproduction of H(2) was observed to occur with a rate of 350 to 400 micromoles H(2) per milligram chlorophyll per hour. In this case, the full electron-transferring capability of photosystem I (measured by irreversible photoreduction of methyl red or O(2)) is used to produce H(2).","subset":"pubmed_abstract"} +{"meta":{"pmid":35101861,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":3,"2024-10":3,"unknown":10}}},"text":"The cost of illness for childhood clinical pneumonia and invasive pneumococcal disease in Nigeria.\nPneumococcal disease contributes significantly to childhood morbidity and mortality and treatment is costly. Nigeria recently introduced the pneumococcal conjugate vaccine (PCV) to prevent pneumococcal disease. The aim of this study is to estimate health provider and household costs for the treatment of pneumococcal disease in children aged <5 years (U5s), and to assess the impact of these costs on household income. We recruited U5s with clinical pneumonia, pneumococcal meningitis or pneumococcal septicaemia from a tertiary level hospital and a secondary level hospital in Kano, Nigeria. We obtained resource utilisation data from medical records to estimate costs of treatment to provider, and household expenses and income loss data from caregiver interviews to estimate costs of treatment to households. We defined catastrophic health expenditure (CHE) as household costs exceeding 25% of monthly household income and estimated the proportion of households that experienced it. We compared CHE across tertiles of household income (from the poorest to least poor). Of 480 participants recruited, 244 had outpatient pneumonia, and 236 were hospitalised with pneumonia (117), septicaemia (66) and meningitis (53). Median (IQR) provider costs were US$17 (US$14-22) for outpatients and US$272 (US$271-360) for inpatients. Median household cost was US$51 (US$40-69). Overall, 33% of households experienced CHE, while 53% and 4% of the poorest and least poor households, experienced CHE, respectively. The odds of CHE increased with admission at the secondary hospital, a diagnosis of meningitis or septicaemia, higher provider costs and caregiver having a non-salaried job. Provider costs are substantial, and households incur treatment expenses that considerably impact on their income and this is particularly so for the poorest households. Sustaining the PCV programme and ensuring high and equitable coverage to lower disease burden will reduce the economic burden of pneumococcal disease to the healthcare provider and households.","subset":"pubmed_abstract"} +{"meta":{"pmid":22732312,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":10}}},"text":"Recruiting and retaining low-income, multi-ethnic women into randomized controlled trials: successful strategies and staffing.\nDeveloping effective recruitment and retention strategies in populations with traditionally high attrition rates is critical to the success of Randomized Controlled Trials (RCTs). Data on successful participation of women from low-income, minority populations in RCTs of behavioral interventions are limited. This is problematic given the multiplicity of Healthy People 2020 goals that target health disparities in these populations. This paper reports successful recruitment and retention methods from two separately funded NIH clinical trials of primary care-based prenatal interventions to increase breastfeeding among ethnically diverse, low-income women in urban medical centers in the Bronx, NY. It also presents the required staff effort necessary to conduct such a successful RCT, in terms of full-time equivalents (FTEs). Results include timely recruitment of 941 participants over 29 months, with 98.1% completing >\u00af\u00af1 follow-up interview. A recruitment and retention plan that maximized study staff access and availability to the participant, as well as strong study staff rapport with participants, addressed previously reported barriers in this population, optimizing follow-up rates. A qualitative assessment of the participants' study experience suggesting that high retention was due to strong rapport with participants, short interviews requiring little time commitment, and participants' perception of the study as informative, provides further evidence of our approach's effectiveness. Logistical protocol procedures and staff management strategies relating to successful recruitment\/retention are provided to propose a practical, cost-effective and translational recruitment-retention plan for other researchers to adopt.","subset":"pubmed_abstract"} +{"meta":{"pmid":24008558,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium.\nLiver tumors are rare in children, and their diagnoses may be challenging particularly because of the lack of a current consensus classification system. Systematic central histopathological review of these tumors performed as part of the pediatric collaborative therapeutic protocols has allowed the identification of histologic subtypes with distinct clinical associations. As a result, histopathology has been incorporated within the Children's Oncology Group (COG) protocols, and only in the United States, as a risk-stratification parameter and for patient management. Therefore, the COG Liver Tumor Committee sponsored an International Pathology Symposium in March 2011 to discuss the histopathology and classification of pediatric liver tumors, and hepatoblastoma in particular, and work towards an International Pediatric Liver Tumors Consensus Classification that would be required for international collaborative projects. Twenty-two pathologists and experts in pediatric liver tumors, including those serving as central reviewers for the COG, European Soci\u00e9t\u00e9 Internationale d'Oncologie P\u00e9diatrique, Gesellschaft f\u00fcr P\u00e4diatrische Onkologie und H\u00e4matologie, and Japanese Study Group for Pediatric Liver Tumors protocols, as well as pediatric oncologists and surgeons specialized in this field, reviewed more than 50 pediatric liver tumor cases and discussed classic and newly reported entities, as well as criteria for their classification. This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology. A standardized, clinically meaningful classification will also be necessary to allow the integration of new biological parameters and to move towards clinical algorithms based on patient characteristics and tumor genetics, which should improve future patient management and outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":7004743,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Long-term regulation of arterial pressure, glomerular filtration and renal sodium reabsorption by angiotensin II in dogs.\n1. This study was designed to quantify the role of angiotensin II in determining the chronic relationships between arterial pressure, renal haemodynamics and sodium excretion. 2. In six control dogs sodium balance was achieved during chronic increases in sodium intake from 5 to 495 mmol\/day with small increases in arterial pressure (7mmHg), moderate increases in glomerular filtration rate (19%) and decreases in filtration fraction. Similar increases in sodium intake in dogs whose circulating levels of angiotensin II were fixed, due to a constant intravenous infusion of 4.85 pmol of angiotensin II min-1 kg-1, caused large increases in arterial pressure (42%), glomerular filtration rate (31%), filtration fraction and calculated renal sodium reabsorption above control. In six dogs whose angiotensin II formation was blocked by SQ 14 225, sodium balance at intakes of 5-80 mmol\/day occurred at reduced arterial pressure, glomerular filtration rate, filtration fraction and sodium reabsorption although plasma aldosterone concentration was not substantially different from that in control dogs. At sodium intakes above 240 mmoL\/day arterial pressure was not altered by SQ 14 225. 3. These data indicate that during chronic variations in sodium intake angiotensin II plays a major role, independently of changes in plasma aldosterone concentration, in allowing sodium balance without large fluctuations in glomerular filtration rate or arterial pressure. The mechanism whereby angiotensin II conserves sodium chronically is through increased sodium reabsorption, since steady-state sodium reabsorption was increased by angiotensin II and decreased by SQ 14 225.","subset":"pubmed_abstract"} +{"meta":{"pmid":32673110,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":8}}},"text":"Funding and Service Delivery in Rural and Urban Local US Health Departments in 2010 and 2016.\nObjectives. To investigate differences in funding and service delivery between rural and urban local health departments (LHDs) in the United States.Methods. In this repeated cross-sectional study, we examined rural-urban differences in funding and service provision among LHDs over time using 2010 and 2016 National Association of County and City Health Officials data.Results. Local revenue among urban LHDs (41.2%) was higher than that in large rural (31.3%) and small rural LHDs (31.2%; P < .05). Small (20.9%) and large rural LHDs (19.8%) reported greater reliance on revenue from Center for Medicare and Medicaid Services than urban LHDs (11.5%; P < .05). All experienced decreases in clinical revenue between 2010 and 2016. Urban LHDs provided less primary care services in 2016; rural LHDs provided more mental health and substance abuse services (P < .05).Conclusions. Urban LHDs generated more revenues from local sources, and rural LHDs generated more from the Center for Medicare and Medicaid Services and clinical services. Rural LHDs tended to provide more clinical services. Given rural LHDs' reliance on clinical revenue, decreases in clinical services could have disproportionate effects on them.Public Health Implications. Differences in financing and service delivery by rurality have an impact on the communities. Rural LHDs rely more heavily on state and federal dollars, which are vulnerable to changes in state and national health policy.","subset":"pubmed_abstract"} +{"meta":{"pmid":8419165,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":13}}},"text":"Correlation between cell-mediated immunity and degree of infection in subjects living in an endemic area of schistosomiasis.\nCell-mediated immunity to Schistosoma mansoni antigens, unrelated antigens and mitogens was evaluated in 50 subjects with the same degree of exposure to infection living in an endemic area of schistosomiasis. The degree of infection, assessed by the number of eggs\/g of stool, was variable in this population (0-5604), suggesting differences in susceptibility to infection. Absence of lymphoproliferative response was observed in 56% of this group, despite having a response to purified protein derivative of tuberculin (PPD) and tetanus toxoid (TT) antigens and to pokeweed mitogen. The 50 subjects were divided into two groups, according to their degree of infection. The lymphoproliferative responses to schistosomula and adult worm antigens in the group with a low degree of infection (< 400 eggs\/g of stool) were higher than the ones documented in patients with a high degree of infection (> 400 eggs\/g of stool), and these differences were statistically significant (p < 0.001). An inverse correlation between the lymphocyte proliferation in response to S. mansoni antigens and the degree of infection was also observed (p = 0.02), indicating that subjects with a lower degree of infection have a higher lymphoproliferative response to schistosomula and adult worm antigens. No differences in the lymphocyte reactivity to other antigens (PPD and TT) were detected in these groups. An impairment of interferon-gamma in vitro production was observed when the lymphocytes from these subjects were stimulated with S. mansoni adult worm antigen, although they produced gamma interferon in response to phytohemagglutinin.","subset":"pubmed_abstract"} +{"meta":{"pmid":24992093,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.\nDelivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-\u03baB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":21782652,"dup_signals":{"dup_doc_count":12,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-22":1,"2024-18":1,"2024-10":1,"2017-13":1,"2024-30":1,"unknown":6}}},"text":"Heavy metals in soil, vegetables and fruits in the endemic upper gastrointestinal cancer region of Turkey.\nThe environmental exposure to heavy metals is a well-known risk factor for cancer. We investigated levels of seven different heavy metals, (Co, Cd, Pb, Zn, Mn, Ni and Cu) in soil, fruit and vegetable samples of Van region in Eastern Turkey where upper gastrointestinal (GI) cancers are endemic. Heavy metal contents of the samples were determined by flame atomic absorption spectrometer. Four heavy metals (Cd, Pb, Cu and Co) were present in 2- to 50-fold higher concentrations whereas zinc levels were present in 40-fold lower concentrations in soil. The fruit and vegetable samples were found to contain 3.5- to 340-fold higher amounts of the six heavy metals (Co, Cd, Pb, Mn, Ni and Cu) tested. The volcanic soil, fruit and vegetable samples contain potentially carcinogenic heavy metals in such a high levels that these elements could be related to the high prevalence of upper GI cancer rates in Van region.","subset":"pubmed_abstract"} +{"meta":{"pmid":28009109,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Computational models of the neural control of breathing.\nThe ongoing process of breathing underlies the gas exchange essential for mammalian life. Each respiratory cycle ensues from the activity of rhythmic neural circuits in the brainstem, shaped by various modulatory signals, including mechanoreceptor feedback sensitive to lung inflation and chemoreceptor feedback dependent on gas composition in blood and tissues. This paper reviews a variety of computational models designed to reproduce experimental findings related to the neural control of breathing and generate predictions for future experimental testing. The review starts from the description of the core respiratory network in the brainstem, representing the central pattern generator (CPG) responsible for producing rhythmic respiratory activity, and progresses to encompass additional complexities needed to simulate different metabolic challenges, closed-loop feedback control including the lungs, and interactions between the respiratory and autonomic nervous systems. The integrated models considered in this review share a common framework including a distributed CPG core network responsible for generating the baseline three-phase pattern of rhythmic neural activity underlying normal breathing. WIREs Syst Biol Med 2017, 9:e1371. doi: 10.1002\/wsbm.1371 For further resources related to this article, please visit the WIREs website.","subset":"pubmed_abstract"} +{"meta":{"pmid":37614308,"dup_signals":{"dup_doc_count":40,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":3,"2024-18":32,"2024-10":4}}},"text":"Dynamics of Skeletal Status under Optimized Management during Subsequent Pregnancy in Three Women with a History of Pregnancy- and Lactation-Associated Osteoporosis Carrying pathogenic Variants in WNT1 and LRP5.\nPregnancy- and lactation-associated osteoporosis (PLO) is a rare but clinically highly relevant condition, characterized by reduced bone mineral density (BMD) and acute onset of severe pain due to symptomatic bone marrow edema of the hip or vertebral and\/or insufficiency fractures, among others. Previous reports showed a high frequency of hereditary bone disorders unmasked by PLO, predisposing for more severe forms. To date, no data on the risk for additional fractures during subsequent pregnancy in women with PLO and genetic bone disorder have been available. To address this question, we retrospectively analyzed the clinical, biochemical, and densitometric course of three women with a history of PLO and detected variants in WNT1 or LRP5 and subsequent pregnancies. Calcium homeostasis and bone turnover were optimized by basic treatment, and timely initiation of weaning was recommended. Teriparatide treatment for 12 months under strict contraception was initiated in one woman after the diagnosis of PLO. In none of the women did additional fractures or symptomatic bone marrow edemas occur, and BMD by dual-energy X-ray absorptiometry as bone microarchitecture by high-resolution peripheral quantitative computed tomography remained stable. In conclusion, this report expands the understanding of this rare but severe condition and helps to improve clinical counseling and management. \u00a9 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.","subset":"pubmed_abstract"} +{"meta":{"pmid":29230958,"dup_signals":{"dup_doc_count":11}},"text":"Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia.\nTreatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes. Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.","subset":"pubmed_abstract"} +{"meta":{"pmid":29315160,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Preventive Effects of Vitamin D on Seasonal Influenza A in Infants: A Multicenter, Randomized, Open, Controlled Clinical Trial.\nThis study aimed to evaluate the clinical efficacy and safety of vitamin D for preventing influenza A in 400 infants in a multicenter, randomized, open, controlled clinical trial. The infants were randomized into low-dose and high-dose vitamin D groups, and serum calcium, inorganic phosphorus and 25-hydroxyvitamin D levels were detected thrice in 4 months. Infants infected with influenza A were monitored for symptoms including fever, cough and wheezing. Pathogen levels and safety of vitamin D treatment were also evaluated. Of 121 cases in total, 78 and 43 cases of influenza A infection occurred in the low-dose and high-dose vitamin D groups, respectively. There was a significant difference between the groups (\u03c7 = 14.6324, P = 0.0001). Among the cases of influenza infection, the median durations for fever, cough and wheezing were shorter in the high-dose vitamin D group than in the low-dose vitamin D group. The viral loads showed a downward trend in both groups and were significantly different between the groups at the second and third detections. Additionally, the incidences of adverse events and severe adverse events were very low and not significantly different between the 2 groups. High-dose vitamin D (1200 IU) is suitable for the prevention of seasonal influenza as evidenced by rapid relief from symptoms, rapid decrease in viral loads and disease recovery. In addition, high-dose vitamin D is probably safe for infants.","subset":"pubmed_abstract"} +{"meta":{"pmid":27996035,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2019-13":1}}},"text":"Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity.\nTumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells. The mechanism by which CNT-induced CAF-like cells promote tumor growth involved the acquisition of cancer stem cells (CSCs) in cancer population. Gene knockdown experiments showed that an expression of podoplanin on CAF-like cells is essential for their effects, indicating the functional role of CAF-like cells and podoplanin in CNT tumorigenic process. Our findings unveil a novel mechanism of CNT-induced carcinogenesis through the induction of CAF-like cells that support CSCs and drive tumor formation. Our results also suggest the potential utility of podoplanin as a mechanism-based biomarker for rapid screening of carcinogenicity of CNTs and related nanomaterials for their safer design.","subset":"pubmed_abstract"} +{"meta":{"pmid":1782104,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-22":1}}},"text":"Appendicular skeletal status and hip fracture in the elderly: 14-year prospective data.\nFourteen-year follow-up of 535 elderly people included in a British survey in 1973 revealed 23 incident hip fractures. The relationship between appendicular bone mass, assessed in the initial survey by metacarpal morphometry, and fracture risk was analyzed. There was an increased risk of hip fracture with declining metacarpal cortical index at baseline. The risk increase, however, was not statistically significant. It remained similar after adjustment was made for the reported prevalence of falls. These prospective data suggest that osteoporosis may contribute less to the risk of hip fracture in the very elderly than in younger individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":19892869,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":7}}},"text":"Automated assessment of keratocyte density in stromal images from the ConfoScan 4 confocal microscope.\nPurpose. To develop a program to determine cell densities in images from the ConfoScan 4 (Nidek, Inc., Freemont, CA) confocal microscope and compare the densities with those determined in images obtained by the Tandem Scanning confocal microscope (Tandem Scanning Corp., Reston, VA). Methods. A program was developed that used image-processing routines to identify stromal cell nuclei in images from the ConfoScan 4 confocal microscope. Cell selection parameters were set to match cell densities from the program with those determined manually in 15 normal corneas of 15 volunteers. The program was tested on scans from 16 other normal volunteers and 17 volunteers 3 years after LASIK. Cell densities were compared to densities determined by manual assessment and to those in scans by the Tandem Scanning confocal microscope in the same corneas. Results. The difference in cell density between the automatic and manual assessment was -539 +\/- 3005 cells\/mm(3) (mean +\/- SD, P = 0.11) in the 16 test corneas. Densities estimated from the ConfoScan 4 agreed with those from the Tandem Scanning confocal microscope in all regions of the stroma except in the anterior 10%, where the ConfoScan 4 indicated a 30% lower density. Conclusions. Differences in anterior stromal cell density between the ConfoScan 4 and the Tandem Scanning confocal microscope can be explained by the different optical designs. The lower spatial resolution of the ConfoScan 4 limits its ability to resolve thin layers. The adaptation of our earlier cell-counting program to the ConfoScan 4 provides a timesaving, objective, and reproducible means of determining stromal cell densities in images from the ConfoScan 4.","subset":"pubmed_abstract"} +{"meta":{"pmid":10722779,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":14}}},"text":"Do regular high protein diets have potential health risks on kidney function in athletes?\nExcess protein and amino acid intake have been recognized as hazardous potential implications for kidney function, leading to progressive impairment of this organ. It has been suggested in the literature, without clear evidence, that high protein intake by athletes has no harmful consequences on renal function. This study investigated body-builders (BB) and other well-trained athletes (OA) with high and medium protein intake, respectively, in order to shed light on this issue. The athletes underwent a 7-day nutrition record analysis as well as blood sample and urine collection to determine the potential renal consequences of a high protein intake. The data revealed that despite higher plasma concentration of uric acid and calcium, Group BB had renal clearances of creatinine, urea, and albumin that were within the normal range. The nitrogen balance for both groups became positive when daily protein intake exceeded 1.26 g.kg but there were no correlations between protein intake and creatinine clearance, albumin excretion rate, and calcium excretion rate. To conclude, it appears that protein intake under 2. 8 g.kg does not impair renal function in well-trained athletes as indicated by the measures of renal function used in this study","subset":"pubmed_abstract"} +{"meta":{"pmid":26751411,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2021-25":1,"2021-21":1,"2019-35":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-22":1,"2018-13":1,"2017-51":1,"2023-23":1,"2024-18":1}}},"text":"Spontaneous cleavage of proteins at serine and threonine is facilitated by zinc.\nOld proteins are widely distributed in the body. Over time, they deteriorate and many spontaneous reactions, for example isomerisation of Asp and Asn, can be replicated by incubation of peptides under physiological conditions. One of the signatures of long-lived proteins that has proven to be difficult to replicate in vitro is cleavage on the N-terminal side of Ser residues, and this is important since cleavage at Ser, and also Thr, has been observed in a number of human proteins. In this study, the autolysis of Ser- and Thr-containing peptides was investigated with particular reference to discovering factors that promote cleavage adjacent to Ser\/Thr at neutral pH. It was found that zinc catalyses cleavage of the peptide bond on the N-terminal side of Ser residues and further that this process is markedly accelerated if a His residue is adjacent to the Ser. NMR analysis indicated that the imidazole group co-ordinates zinc and that once zinc is co-ordinated, it can polarize the carbonyl group of the peptide bond in a manner analogous to that observed in the active site of the metalloexopeptidase, carboxypeptidase A. The hydroxyl side chain of Ser\/Thr is then able to cleave the adjacent peptide bond. These observations enable an understanding of the origin of common truncations observed in long-lived proteins, for example truncation on the N-terminal side of Ser 8 in Abeta, Ser 19 in alpha B crystallin and Ser 66 in alpha A crystallin. The presence of zinc may therefore significantly affect the long-term stability of cellular proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":22355008,"dup_signals":{"dup_doc_count":12}},"text":"Working memory capacity and its relation to stroop interference and facilitation effects in individuals with mild cognitive impairment.\nThe purposes of the study were to investigate (a) the task-specific differences in short-term memory (STM) and working memory capacity (WMC) in individuals with mild cognitive impairment (MCI) and normal elderly adults (NEAs), (b) the Stroop interference and facilitation effects, and (c) the relationship of STM and WMC to the Stroop effects. Thirty-two individuals participated in the study (n = 16 for each group). WMC demands were increased using a computerized Stroop-like token task to add more linguistic units. Six STM and WMC measures were administered overall. Digit-related tasks and an alphabet span task sensitively differentiated individuals with MCI from the NEA group. The group with MCI exhibited greater Stroop interference effects than the NEA group, but the 2 groups did not exhibit different Stroop facilitation effects. WMC significantly predicted performance on the response time analyses but not on the error rate analyses. Task-specific differences emerged in the group with MCI, and a reduced WMC accounts for the impaired inhibitory and goal maintenance processes. It is critical that WMC demands be systematically manipulated to tax individuals' WMC in a way that can clearly demonstrate their deficits, especially in individuals who are at risk for clinically demented states.","subset":"pubmed_abstract"} +{"meta":{"pmid":25579380,"dup_signals":{"dup_doc_count":31,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2021-43":1,"2018-30":2,"2018-22":1,"2018-17":2,"2018-13":1,"2018-09":1,"2018-05":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2022-05":1,"2024-30":2,"2024-22":1,"2017-13":1}}},"text":"Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.\nThe protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg\/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-\u03b3, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-\u03b1), and IL-1\u03b2], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1\u03b1], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-\u03baB (p65 and phospho-I\u03baB\u03b1) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)\/IFN-\u03b3(+), and CD4(+)\/IL-17(+) T cells, but increased the number of CD4(+)\/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.","subset":"pubmed_abstract"} +{"meta":{"pmid":27004417,"dup_signals":{"dup_doc_count":35,"dup_dump_count":31,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-40":1,"2024-30":2,"2024-26":1,"2024-10":2,"2017-13":1}}},"text":"Protist metabarcoding and environmental biomonitoring: Time for change.\nHigh-throughput amplicon sequencing of environmental DNA and\/or RNA proved to be a powerful tool to describe protist diversity. This new approach called also the metabarcoding has totally transformed our view of protist diversity, revealing a large number of novel lineages and expanding the range of protist phylogenetic diversity at almost every taxonomic level. However, until now the objectives of the vast majority of metabarcoding studies were purely academic. Practical applications of protist metabarcoding are surprisingly scarce, despite the fact that several groups of protists are commonly used as bioindicators of environmental impacts in freshwater or marine ecosystems. Here, we are reviewing studies that examine the ecological applications of metabarcoding for two groups of well-known protist bioindicators: diatoms and foraminifera. The results of these studies show that despite some biological and technical biases, molecular data quite faithfully reflect the morphology-based biotic indices and provide a similar assessment of ecosystem status. In view of these results, protist metabarcoding appears as a rapid and accurate tool for the evaluation of the quality of aquatic ecosystems. Hence, we plead for integration of protist metabarcoding in future biomonitoring projects as a complement of traditional methods and a source of new biosensors for environmental impact assessment.","subset":"pubmed_abstract"} +{"meta":{"pmid":18927056,"dup_signals":{"dup_doc_count":11}},"text":"Social working memory: Memory for another rat's spatial choices can increase or decrease choice tendencies.\nIn two experiments using a radial-arm maze, pairs of rats made choices among eight maze locations, each containing a large quantity of one of two food types. The choices made by 1 rat affected the choices made by the other rat. Under most conditions, visits by 1 rat increased the tendency of the other rat to subsequently choose that maze location. However, the effect depended on the quality of the food available in a particular location. When it was possible for the rats to observe each other on the maze arms and a rat had experienced that a location contained the less preferred food type, a previous visit to that location by the foraging partner decreased the tendency to visit that location. These effects are attributed to working memory for the spatial choices of another rat, and they indicate that memory produced by a rat's own visit to a maze location is integrated with memory for the behavior of another rat to determine spatial choice.","subset":"pubmed_abstract"} +{"meta":{"pmid":22470237,"dup_signals":{"dup_doc_count":51,"dup_dump_count":32,"dup_details":{"curated_sources":8,"2023-40":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-27":1,"2021-17":1,"2021-10":2,"2020-50":2,"2020-45":2,"2020-34":2,"2020-10":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":2,"2019-26":1,"2019-18":1,"2019-09":2,"2018-51":1,"2018-34":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":2,"2024-26":2,"2024-18":1,"2024-10":2,"2024-30":1}}},"text":"Ozone therapy: A clinical review.\nOzone (O(3)) gas discovered in the mid-nineteenth century is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Although O(3) has dangerous effects, yet researchers believe it has many therapeutic effects. Ozone therapy has been utilized and heavily studied for more than a century. Its effects are proven, consistent, safe and with minimal and preventable side effects. Medical O(3) is used to disinfect and treat disease. Mechanism of actions is by inactivation of bacteria, viruses, fungi, yeast and protozoa, stimulation of oxygen metabolism, activation of the immune system. Medication forms in a gaseous state are somewhat unusual, and it is for this reason that special application techniques have had to be developed for the safe use of O(3). In local applications as in the treatment of external wounds, its application in the form of a transcutaneous O(3) gas bath has established itself as being the most practical and useful method, for example at low (sub-atmospheric) pressure in a closed system guaranteeing no escape of O(3) into the surrounding air. Ozonized water, whose use is particularly known in dental medicine, is optimally applied as a spray or compress. Diseases treated are infected wounds, circulatory disorders, geriatric conditions, macular degeneration, viral diseases, rheumatism\/arthritis, cancer, SARS and AIDS.","subset":"pubmed_abstract"} +{"meta":{"pmid":20203828,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":11}}},"text":"Carbon dioxide spectral line frequencies for the 4.3-microm region.\nThe frequencies of CO(2) lines in the 3.77-4.26-microm region, which were obtained experimentally, have been compared with those listed on two tapes of the AFCRL Atmospheric Absorption Line Parameters Compilation. The experimental line frequencies were obtained in absorption using a high-resolution Michelson interferometer. Discrepancies between the present experimental values and the frequencies listed on the AFCRL tapes are tabulated. Consistency checks were also made by comparing calculated line frequencies with those on the tapes, and these findings are also reported.","subset":"pubmed_abstract"} +{"meta":{"pmid":12894611,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":3,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2023-40":1,"2024-18":1,"2017-13":1,"2024-22":1}}},"text":"Old and homeless: a review and survey of older adults who use shelters in an urban setting.\nResearch on the mental health and service needs of homeless seniors has been scant. This paper reviews the available literature and presents findings of a Toronto survey in an effort to describe the demographics of homeless seniors, their level of impairment, and their mental and physical health needs. We searched the Medline, AgeLine, and PsycINFO databases, using the following key words: elderly homeless, elderly hostel users, and urban geriatrics. To better describe the service needs of the elderly homeless, we obtained demographic data from the Community and Neighbourhood Services Department and distributed a survey questionnaire to 11 Toronto hostel directors. The questionnaire elicited data relating to reasons for shelter use, problem behaviours, and mental health needs of those over age 65 years. Although seniors represent a small percentage of the homeless population, their numbers are growing. The available literature suggests a high prevalence of psychiatric disorders and cognitive impairment in this population, with a greater proportion of older women than men having severe mental illness. Further, our survey suggests that the service needs of elderly hostel users in Toronto differ from those of their younger counterparts. The homeless elderly are the most vulnerable of this impoverished population. Although more research is needed to define their mental and physical health needs and ways of meeting them, their characteristics appear to be unique. Geriatric psychiatrists could play a significant role in evaluating and treating this population more comprehensively.","subset":"pubmed_abstract"} +{"meta":{"pmid":28677123,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"The influence of Chinese culture on family caregivers of stroke survivors: A qualitative study.\nTo explore and describe the caregiving experiences of Chinese stroke caregivers. Previous research has indicated that culture can have a significant impact on the stroke caregiving experience. Moreover, scant research exists on stroke caregivers' experience within the Chinese culture. A qualitative descriptive design was used. In-depth, semistructured interviews were conducted with 25 family caregivers of stroke survivors. The interviews were audiotaped, transcribed and analysed. Content analysis was also performed. Twenty-five family caregivers of stroke survivors were recruited for the study. On average, respondents were 66 years old (range 45-82 years). Of 25 interviewees, 76% were female, 64% were spouse-caregivers and 36% were children-caregivers. Three themes reflecting the influence of Chinese culture on stroke caregiving emerged from the interviews. (i) Caregiving role perception. Informants accepted caregiving for the sick family member as an expected part of life, a culturally prescribed obligation and an expression of reciprocal love. (ii) Coping strategies. Connecting with family resources and connecting with inner strength were frequently reported coping strategies. (iii) Self-sacrifice. Informants identified self-reliance and feeling of restraint in their utilisation or access of formal caregiving service. Chinese caregivers sacrifice themselves for the care recipients regardless of the hardships and the neglect of their own health. Our findings provide a comprehensive and culturally sensitive perspective in understanding the experience of stroke caregivers in Chinese communities. Cultural and religious backgrounds were found to influence Chinese stroke caregivers' experience, coping strategies and self-sacrifice behaviour in idiosyncratic ways. Research on the practice of culture can serve as a basis for the formulation of specific policies and effective interventions for supporting stroke caregivers of different cultural backgrounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":16044093,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Hepatocellular damage following therapeutic intravenous iron sucrose infusion in a child.\nThe maximum tolerated single dose of intravenous iron infusion and iron pharmacokinetics are not known in children and not clear in adults. The case reported here is of a child given a large dose of intravenous iron sucrose (16 mg\/kg) over 3 hours, who subsequently developed features of systemic iron toxicity. A TDM consultant discusses the case in the context of toxicokinetic analysis. Because the maximum tolerated dose and pharmacokinetics of intravenous iron preparations are not known, their use in both adults and children should still be undertaken with caution.","subset":"pubmed_abstract"} +{"meta":{"pmid":30344806,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":11}}},"text":"Efficacy of Gastric Electrical Stimulation for Gastroparesis: US\/European Comparison.\nGastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location. We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female. European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023). Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.","subset":"pubmed_abstract"} +{"meta":{"pmid":27775375,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases.\nWhile chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":9020322,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Laparoscopic assisted live donor nephrectomy--a comparison with the open approach.\nLive donor renal transplantation provides significant advantages when compared with cadaveric donor renal transplantation in terms of improved patient and graft survival, a lower incidence of delayed function, and a shorter waiting time. Yet despite these advantages, live donors continue to be an under utilized source of kidneys for transplantation. Disincentives to live donation include the length of hospitalization, postoperative pain, cosmetic concerns, and the prolonged convalescence associated with the donor operation. In many instances minimally invasive video-assisted techniques have proven more efficacious than standard open procedures in terms of patient discomfort, length of hospital stay, cost, and length of time until the patient can return to full activity. Laparoscopic live donor nephrectomies are being performed at our institution in an attempt to make live donation more attractive to the potential donor. The purpose of this study was to retrospectively review the results of laparoscopic live donor nephrectomy (LapNx) and to compare them with those obtained using the standard open approach (OpenNx). Ten consecutive LapNx were performed from February 1995 through April 1996. The control group consisted of the 20 consecutive OpenNx performed at the same institution from January 1991 through January 1995 immediately before the initiation of the LapNx program. Live donors were considered candidates for LapNx if they possessed at least one kidney with normal renal anatomy with single renal vessels and a single ureter. LapNx was safely performed in all cases. No patients required open conversion or blood transfusions. The allograft warm ischemic time for the laparoscopic cases was 4.2+\/-1.3 min. All kidneys harvested laparoscopically produced urine on the table immediately upon revascularization. Presently nine of the ten recipients have functioning allografts. At three months posttransplant the calculated recipient creatinine clearances were 67.0+\/-11.5 ml\/min and 64.8+\/-21.4 ml\/min for the LapNx and OpenNx groups, respectively (P=NS). The LapNx donors had a significantly decreased estimated blood loss, shorter time until resumption of oral intake, decreased postoperative pain (in terms of decreased analgesic requirements), shorter hospitalization, and a shorter interval until the resumption of full activities (P<0.05 for all). In addition, the LapNx group donors returned to work sooner than the OpenNx group (3.9+\/-1.6 wk vs. 6.4+\/-3.1 wk, respectively) (P=0.024). Four individuals agreed to donate a kidney only after learning of the availability of the laparoscopic approach. We conclude that laparoscopic live donor nephrectomy is technically feasible. In addition, it may offer significant advantages over the standard open approach in terms of patient comfort and convenience. These advantages may make live donor renal transplantation more attractive to prospective donors. The potential decrease in hospitalization and convalescence may also prove to be financially advantageous. We believe that further careful study of this procedure is warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":20220096,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections.\nIL-22 is a member of the IL-10 cytokine family and signals through a heterodimeric receptor composed of the common IL-10R2 subunit and the IL-22R subunit. IL-10 and IL-22 both activate the STAT3 signaling pathway; however, in contrast to IL-10, relatively little is known about IL-22 in the host response to infection. In this study, using IL-22(-\/-) mice, neutralizing Abs to IL-22, or both, we show that IL-22 is dispensable for the development of immunity to the opportunistic pathogens Toxoplasma gondii and Mycobacterium avium when administered via the i.p. or i.v. route, respectively. IL-22 also played little to no role in aerosol infections with Mycobacterium tuberculosis and in granuloma formation and hepatic fibrosis following chronic percutaneous infections with the helminth parasite Schistosoma mansoni. A marked pathogenic role for IL-22 was, however, identified in toxoplasmosis when infections were established by the natural oral route. Anti-IL-22 Ab-treated mice developed significantly less intestinal pathology than control Ab-treated mice even though both groups displayed similar parasite burdens. The decreased gut pathology was associated with reduced IL-17A, IL-17F, TNF-alpha, and IFN-gamma expression. In contrast to the prior observations of IL-22 protective effects in the gut, these distinct findings with oral T. gondii infection demonstrate that IL-22 also has the potential to contribute to pathogenic inflammation in the intestine. The IL-22 pathway has emerged as a possible target for control of inflammation in certain autoimmune diseases. Our findings suggest that few if any infectious complications would be expected with the suppression of IL-22 signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":34009523,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":1,"unknown":7}}},"text":"How to Cost the Implementation of Major System Change for Economic Evaluations: Case Study Using Reconfigurations of Specialist Cancer Surgery in Part of London, England.\nStudies have been published regarding the impact of major system change (MSC) on care quality and outcomes, but few evaluate implementation costs or include them in cost-effectiveness analysis (CEA). This is despite large potential costs of MSC: change planning, purchasing or repurposing assets, and staff time. Implementation costs can influence implementation decisions. We describe our framework and principles for costing MSC implementation and illustrate them using a case study. We outlined MSC implementation stages and identified components, using a framework conceived during our work on MSC in stroke services. We present a case study of MSC of specialist surgery services for prostate, bladder, renal and oesophagogastric cancers, focusing on North Central and North East London and West Essex. Health economists collaborated with qualitative researchers, clinicians and managers, identifying key reconfiguration stages and expenditures. Data sources (n = approximately 100) included meeting minutes, interviews, and business cases. National Health Service (NHS) finance and service managers and clinicians were consulted. Using bottom-up costing, items were identified, and unit costs based on salaries, asset costs and consultancy fees assigned. Itemised costs were adjusted and summed. Cost components included options appraisal, bidding process, external review; stakeholder engagement events; planning\/monitoring boards\/meetings; and making the change: new assets, facilities, posts. Other considerations included hospital tariff changes; costs to patients; patient population; and lifetime of changes. Using the framework facilitated data identification and collection. The total adjusted implementation cost was estimated at \u00a37.2 million, broken down as replacing robots (\u00a34.0 million), consultancy fees (\u00a31.9 million), staff time costs (\u00a31.1 million) and other costs (\u00a30.2 million). These principles can be used by funders, service providers and commissioners planning MSC and researchers evaluating MSC. Health economists should be involved early, alongside qualitative and health-service colleagues, as retrospective capture risks information loss. These analyses are challenging; many cost factors are difficult to identify, access and measure, and assumptions regarding lifetime of the changes are important. Including implementation costs in CEA might make MSC appear less cost effective, influencing future decisions. Future work will incorporate this implementation cost into the full CEAs of the London Cancer MSC. Not applicable.","subset":"pubmed_abstract"} +{"meta":{"pmid":31080134,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":13}}},"text":"Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration.\nThe liver can substantially regenerate after injury, with both main epithelial cell types, hepatocytes and biliary epithelial cells (BECs), playing important roles in parenchymal regeneration. Beyond metabolic functions, BECs exhibit substantial plasticity and in some contexts can drive hepatic repopulation. Here, we performed single-cell RNA sequencing to examine BEC and hepatocyte heterogeneity during homeostasis and after injury. Instead of evidence for a transcriptionally defined progenitor-like BEC cell, we found significant homeostatic BEC heterogeneity that reflects fluctuating activation of a YAP-dependent program. This transcriptional signature defines a dynamic cellular state during homeostasis and is highly responsive to injury. YAP signaling is induced by physiological bile acids (BAs), required for BEC survival in response to BA exposure, and is necessary for hepatocyte reprogramming into biliary progenitors upon injury. Together, these findings uncover molecular heterogeneity within the ductal epithelium and reveal YAP as a protective rheostat and regenerative regulator in the mammalian liver.","subset":"pubmed_abstract"} +{"meta":{"pmid":19019422,"dup_signals":{"dup_doc_count":57,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-06":2,"2022-49":2,"2022-40":1,"2022-21":3,"2021-49":2,"2021-43":2,"2021-31":3,"2021-21":1,"2021-17":3,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":3,"2020-40":2,"2019-13":2,"2018-51":2,"2018-39":2,"2018-30":3,"2018-22":1,"2018-17":1,"2018-13":2,"2017-51":2,"2017-43":2,"2017-34":2,"2024-22":2,"2013-48":1,"2024-26":1}}},"text":"Insecticide-treated net coverage in Africa: mapping progress in 2000-07.\nInsecticide-treated bednets (ITNs) provide a means to improve child survival across Africa. Sales figures of these nets and survey coverage data presented nationally mask inequities in populations at biological and economic risk, and do not allow for precision in the estimation of unmet commodity needs. We gathered subnational ITN coverage sample survey data from 40 malaria-endemic countries in Africa between 2000 and 2007. We computed the projected ITN coverage among children aged less than 5 years for age-adjusted population data that were stratified according to malaria transmission risks, proximate determinants of poverty, and methods of ITN delivery. In 2000, only 1.7 million (1.8%) African children living in stable malaria-endemic conditions were protected by an ITN and the number increased to 20.3 million (18.5%) by 2007 leaving 89.6 million children unprotected. Of these, 30 million were living in some of the poorest areas of Africa: 54% were living in only seven countries and 25% in Nigeria alone. Overall, 33 (83%) countries were estimated to have ITN coverage of less than 40% in 2007. On average, we noted a greater increase in ITN coverage in areas where free distribution had operated between survey periods. By mapping the distribution of populations in relation to malaria risk and intervention coverage, we provide a means to track the future requirements for scaling up essential disease-prevention strategies. The present coverage of ITN in Africa remains inadequate and a focused effort to improve distribution in selected areas would have a substantial effect on the continent's malaria burden.","subset":"pubmed_abstract"} +{"meta":{"pmid":24795620,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Efficient generation of connectivity in neuronal networks from simulator-independent descriptions.\nSimulator-independent descriptions of connectivity in neuronal networks promise greater ease of model sharing, improved reproducibility of simulation results, and reduced programming effort for computational neuroscientists. However, until now, enabling the use of such descriptions in a given simulator in a computationally efficient way has entailed considerable work for simulator developers, which must be repeated for each new connectivity-generating library that is developed. We have developed a generic connection generator interface that provides a standard way to connect a connectivity-generating library to a simulator, such that one library can easily be replaced by another, according to the modeler's needs. We have used the connection generator interface to connect C++ and Python implementations of the previously described connection-set algebra to the NEST simulator. We also demonstrate how the simulator-independent modeling framework PyNN can transparently take advantage of this, passing a connection description through to the simulator layer for rapid processing in C++ where a simulator supports the connection generator interface and falling-back to slower iteration in Python otherwise. A set of benchmarks demonstrates the good performance of the interface.","subset":"pubmed_abstract"} +{"meta":{"pmid":27779290,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":8}}},"text":"[Child psychiatry: limited research, evidence for cost-effectiveness of treatment].\nResearch into cost-effectiveness of treatment of child psychiatric disorders is extremely limited. There are two main reasons for this: it's a new field and the type of research required is intrinsically complicated. AIM: To review selected articles that reveal the prevalence of child psychiatric disorders, demonstrate the complexity of cost-efficiency research in child psychiatry and point to the possible benefits of appropriate treatment. METHOD: We provide an overview of a selected number of articles dealing with the prevalence of child psychiatric disorders and the costs involved, we stress the diffulty of assessing whether current treatment is cost-effective and we describe the possible benefits of treatment. RESULTS: However, the limited number of articles that we located do indicate that the treatment of children with psychiatric disorders is cost-effective. Not only does it benefit the child, it also eases the burden on the parents and on society as a whole. Findings need to be interpreted in the light of the limited scope and shortcomings of the research done so far. CONCLUSION: Although current research seems to be cost-effective, we stress the need for further investigations, particularly in the form of longer-term studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":24191947,"dup_signals":{"dup_doc_count":22,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-25":1,"2021-10":1,"2021-04":1,"2020-34":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2023-50":1,"2024-22":1}}},"text":"CRIMALDDI: a prioritized research agenda to expedite the discovery of new anti-malarial drugs.\nThe CRIMALDDI Consortium has been a three-year project funded by the EU Framework Seven Programme. It aimed to develop a prioritized set of recommendations to speed up anti-malarial drug discovery research and contribute to the setting of the global research agenda. It has attempted to align thinking on the high priority issues and then to develop action plans and strategies to address these issues. Through a series of facilitated and interactive workshops, it has concluded that these priorities can be grouped under five key themes: attacking artemisinin resistance; creating and sharing community resources; delivering enabling technologies; exploiting high throughput screening hits quickly; and, identifying novel targets. Recommendations have been prioritized into one of four levels: quick wins; removing key roadblocks to future progress; speeding-up drug discovery; and, nice to have (but not essential). Use of this prioritization allows efforts and resources to be focused on the lines of work that will contribute most to expediting anti-malarial drug discovery. Estimates of the time and finances required to implement the recommendations have also been made, along with indications of when recommendations within each theme will make an impact. All of this has been collected into an indicative roadmap that, it is hoped, will guide decisions about the direction and focus of European anti-malarial drug discovery research and contribute to the setting of the global research agenda.","subset":"pubmed_abstract"} +{"meta":{"pmid":10208360,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":9}}},"text":"Competence in the context of adversity: pathways to resilience and maladaptation from childhood to late adolescence.\nCompetent outcomes in late adolescence were examined in relation to adversity over time, antecedent competence and psychosocial resources, in order to investigate the phenomenon of resilience. An urban community sample of 205 (114 females, 90 males; 27% minority) children were recruited in elementary school and followed over 10 years. Multiple methods and informants were utilized to assess three major domains of competence from childhood through adolescence (academic achievement, conduct, and peer social competence), multiple aspects of adversity, and major psychosocial resources. Both variable-centered and person-centered analyses were conducted to test the hypothesized significance of resources for resilience. Better intellectual functioning and parenting resources were associated with good outcomes across competence domains, even in the context of severe, chronic adversity. IQ and parenting appeared to have a specific protective role with respect to antisocial behavior. Resilient adolescents (high adversity, adequate competence across three domains) had much in common with their low-adversity competent peers, including average or better IQ, parenting, and psychological well-being. Resilient individuals differed markedly from their high adversity, maladaptive peers who had few resources and high negative emotionality. Results suggest that IQ and parenting scores are markers of fundamental adaptational systems that protect child development in the context of severe adversity.","subset":"pubmed_abstract"} +{"meta":{"pmid":26030991,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2021-43":1,"2021-39":1,"2021-21":2,"2021-17":1,"2021-10":1,"2020-40":1,"2020-05":1,"2019-43":1,"2019-09":1,"2018-39":1,"2018-34":1,"2022-05":1}}},"text":"Differential effects of single and double parental death on child emotional functioning and daily life in South Africa.\nThere is a high level of orphaning in Africa due to war, violence, and more recently HIV and AIDS. This study examines parental death in South African children and examines the differential impact on child functioning of double, single and non-orphanhoods. Bereavement, depression, behavior problems, and violence were examined in a consecutive sample of 381 children\/adolescents (51.2% girls) between 8 and 19 years of age (M = 12.8). Parental death experience was high; 70 (17.5%) reported the death of one parent, and a further 24 (6%) reported the death of both. Group comparisons showed double orphans had elevated depression, worse psychosocial functioning, were more likely to be kept home from school for household chores, and were more likely to be slapped. Single orphans were more similar to the non-orphans than the double orphans on most scores. Our study reveals that parental loss should be studied with more fine-grained definitions and that emotional sequelae should be addressed.","subset":"pubmed_abstract"} +{"meta":{"pmid":31219523,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":15}}},"text":"Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.\nBirth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":128820,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro.\nRabbit aortic medial cells were grown on purified elastin membranes, which were then subjected to repeated elongation and relaxation or to agitation without stretching. Cells remained attached to the membranes, and cyclic stretching resulted in a two- to fourfold increase in rates of collagen, hyaluronate, and chondroitin 6-sulfate synthesis over those in agitated or stationary preparations. Synthesis of types I and III collagen was increased to the same degree. Stretching did not increase rates of chondroitin 4-sulfate or dermatan sulfate synthesis. Differences were not attributable to differences in cell number, for DNA synthetic rates were not increased by stretching. The model system devised to demonstrate these effects provides a means for relating various modes of mechanical stimulation to cell metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":30566452,"dup_signals":{"dup_doc_count":16}},"text":"Evaluation of habitat protection under the European Natura 2000 conservation network - The example for Germany.\nThe world\u00b4s largest network of protected areas-Natura 2000 (N2000)-has been implemented to protect Europe\u00b4s biodiversity. N2000 is built upon two cornerstones, the Birds Directive, which lists 691 bird species (plus one additional bird genus with no further classification) and the Habitats Directive, which lists next to a variety of species, 233 habitat types to be protected. There is evidence of the positive impact of the Directives on the EU\u00b4s biodiversity, although the overall improvement reported for species in favourable condition in the last assessment was low. However, most of the assessments are species focused, while habitats have received very little attention. Here we developed a generic workflow, which we exemplified for Germany, to assess the status of habitat coverage within the N2000 network combining information from publicly available data sources. Applying the workflow allows identification of gaps in habitat protection, followed by the prioritization of potential areas of high protection value using the conservation planning software Marxan. We found that, in Germany, N2000 covers all target habitats. However, common habitats were proportionally underrepresented relative to rare ones, which contrasts with studies focussing on the representation of species. Moreover, the German case study suggests that especially highly protected areas (i.e. covered by more than 90% with N2000 sites) build an excellent basis towards a cost-effective and efficient conservation network. Our workflow provides a generic approach to deal with the common problem of missing habitat distribution data outside of N2000 sites, information which is however crucial for managers to plan conservation actions appropriately across Europe. To avoid a biased representation of habitat types within N2000, our results underpin the importance of defining qualitative and quantitative conservation targets which will allow assesment of the trajectory of habitat protection in Europe as well as adjustment of the network accordingly-a future necessity in the light of climate change.","subset":"pubmed_abstract"} +{"meta":{"pmid":18943801,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Spatial pattern analysis of hop powdery mildew in the pacific northwest: implications for sampling.\nABSTRACT The spatial pattern of hop powdery mildew was characterized using 3 years of disease incidence data collected in commercial hop yards in the Pacific Northwest. Yards were selected randomly from yards with a history of powdery mildew, and two to five rows were selected for sampling within each yard. The proportion of symptomatic leaves out of 10 was determined from each of N sampling units in a row. The binomial and the beta-binomial frequency distributions were fit to the N sampling units observed in each row and to SigmaN sampling units observed in each yard. Distributional analyses indicated that disease incidence was better characterized by the beta-binomial than the binomial distribution in 25 and 47% of the data sets at the row and yard scales, respectively, according to a log-likelihood ratio test. Median values of the beta-binomial parameter theta, a measure of small-scale aggregation, were near 0 at both sampling scales, indicating that disease incidence was close to being randomly distributed. The variability in disease incidence among rows sampled in the same yard generally increased with mean incidence at the yard scale. Spatial autocorrelation analysis, used to measure large-scale patterns of aggregation, indicated that disease incidence was not correlated between sampling units over several lag distances. Results of a covariance analysis showed that heterogeneity of disease incidence was not dependent upon cultivar, region, or time of year when sampling was conducted. A hierarchical analysis showed that disease incidence at the sampling unit scale (proportion of sampling units with one or more diseased leaves) increased as a saturation-type curve with respect to incidence at the leaf level and could be described by a binomial function modified to account for the effects of heterogeneity through an effective sample size. Use of these models permits sampling at the sampling unit scale while allowing inferences to be made at the leaf scale. Taken together, hop powdery mildew was nearly randomly distributed with no discernable foci, suggesting epidemics are initiated from a well-distributed or readily dispersible overwintering population. Implications for sampling are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":22764294,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2020-05":1,"2019-47":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-47":2,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2020-34":1}}},"text":"Assessment of interferon-\u03b3 levels and leishmanin skin test results in persons recovered for leishmaniasis.\nPatients who recover from leishmaniasis usually show development of strong immunity and induction of interferon-\u03b3 (IFN-\u03b3) and delayed type hypersensitivity. In a randomized trial, we analyzed the IFN-\u03b3 response by using a Quantiferon-Leishmania assay against three Leishmania peptide antigens and compared it with results of the leishmanin skin test (LST) in persons residing in areas in Iran to which zoonotic cutaneous leishmaniasis (ZCL, 181 persons), anthroponotic cutaneous leishmaniasis (ACL, 104 persons), and zoonotic visceral leishmaniasis (ZVL, 67 persons) are endemic. The percentage of persons with an IFN-\u03b3-positive response (> 0.2 IU\/mL) to three antigens and the mean concentration of IFN-\u03b3 induced by the antigens were higher for persons from areas endemic for ZVL than for persons from areas endemic for ZCL and ACL. The percentage of persons with LST-positive results (\u2265 5 mm indurations) was 99%, 94%, and 70% for areas with ZCL, ACL, and ZVL, respectively. Our data indicate that the LST is significantly more sensitive than IFN-\u03b3 levels in persons who have been cured of cutaneous leishmaniasis than in persons who have been cured of ZVL.","subset":"pubmed_abstract"} +{"meta":{"pmid":34061193,"dup_signals":{"dup_doc_count":16,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2023-06":1,"2022-33":1,"2021-49":1,"2021-43":1,"2021-31":2,"2021-25":3,"2023-50":1,"2024-30":2}}},"text":"Readiness Assessment for Extubation Planning in the Intensive Care Unit: A Quality Improvement Initiative.\nExtubation failure is the reintubation of patients meeting criteria for weaning from mechanical ventilation. Extubation failure is correlated with mortality, prolonged mechanical ventilation, and longer hospital stays. Noninvasive ventilation or high-flow nasal cannula oxygen therapy after extubation is recommended to prevent extubation failure in high-risk patients. The extubation failure rate is unknown. Prophylactic measures (noninvasive ventilation or high-flow nasal cannula) after extubation are not commonly used and vary among clinicians. The objective was to assess extubation planning readiness by determining extubation failure rate, identifying high-risk patients, and determining prophylactic measure compliance. A quality improvement initiative included an evidence-based extubation failure risk assessment that identified high-risk patients and determined prophylactic measure compliance. A 2-year retrospective medical record review was used to determine baseline patient characteristics and extubation failure rate. Results Extubation failure rate within the retrospective cohort was 13 of 146 patients (8.9%). Extubation failure did not correlate with previously identified risk factors; however, 150 identified patients were excluded from analysis. During risk assessment integration, the extubation failure rate was 3 of 37 patients (8.1%) despite identifying 24 high-risk patients (65%). Few high-risk patients received prophylactic measures (noninvasive ventilation, 17%; high-flow nasal cannula, 12%). Extubation failure should be routinely measured because of its effects on patient outcomes. This project reveals the multifactorial nature of extubation failure. Further research is needed to assess patients' risk and account for acute conditions. This project used best practice guidelines for routine patient care and added transparency to a previously unmeasured event.","subset":"pubmed_abstract"} +{"meta":{"pmid":27616206,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":1,"2019-39":1,"2019-30":2,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":1,"2017-39":1,"2017-34":1,"2021-04":1}}},"text":"Endomyocardial proteomic signature corresponding to the response of patients with dilated cardiomyopathy to immunoadsorption therapy.\nDilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA\/IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential biomarker is available to predict improvement of cardiac function after therapy accurately. This shotgun proteome study aims to disclose the differences in the endomyocardial proteome between patients with improved LVEF after IA\/IgG (responders) and those without improvement (non-responders) before therapy start. Comparative analysis revealed 54 differentially abundant proteins that were mostly confined to carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these proteins revealed highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA\/IgG therapy. We evaluated the differences in the myocardial proteome of responder and non-responder DCM patients before immunoadsorption therapy and identified a number of differentially abundant proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results. Proteins S100-A8, perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption therapy treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":17307305,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-04":1,"2017-13":1}}},"text":"Human binucleate hepatocytes: are they a defence during chronic liver diseases?\nBinucleate cells are commonly found in various human organs including liver, salivary glands and endometrium, but their functional advantage remains unknown. The increased occurrence of binucleate hepatocytes during the necro-inflammation stage of progressive chronic hepatitis and its end-stage of cirrhosis, but their absence in hepatocellular carcinoma (HCC), has led us to hypothesise that they may be an index of the severity of hepatic illness rather than the result of errors occurring during the course of the cell cycle. This hypothesis is supported by the immunohistochemical analysis of retinol-binding protein expression, and the different life cycles of hepatitis B virus in mononucleate and binucleate hepatocytes. If founded, this hypothesis would add to our understanding of the relationship between binucleate hepatocytes and the evolution of chronic liver disease, and promises the ideation of new criteria for identifying potential HCC patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":12498461,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The use of computerized tomography for diagnosis and treatment planning in implant dentistry.\nPreoperative radiographic imaging of recipient sites for implant placement is imperative to obtain a functional and aesthetic implant-supported prosthesis. Although conventional radiographic techniques have inherent problems that restrict accurate imaging, the main drawback of panoramic and periapical radiography is the two-dimensional image. Computerized tomography provides cross-sectional radiographic images that facilitate proper assessment of potential recipient sites for implant placement. This paper reviews the role of computerized tomography in implant dentistry.","subset":"pubmed_abstract"} +{"meta":{"pmid":27007278,"dup_signals":{"dup_doc_count":15}},"text":"Altered primary chromatin structures and their implications in cancer development.\nCancer development is a complex process involving both genetic and epigenetic changes. Genetic changes in oncogenes and tumor-suppressor genes are generally considered as primary causes, since these genes may directly regulate cellular growth. In addition, it has been found that changes in epigenetic factors, through mutation or altered gene expression, may contribute to cancer development. In the nucleus of eukaryotic cells DNA and histone proteins form a structure called chromatin which consists of nucleosomes that, like beads on a string, are aligned along the DNA strand. Modifications in chromatin structure are essential for cell type-specific activation or repression of gene transcription, as well as other processes such as DNA repair, DNA replication and chromosome segregation. Alterations in epigenetic factors involved in chromatin dynamics may accelerate cell cycle progression and, ultimately, result in malignant transformation. Abnormal expression of remodeler and modifier enzymes, as well as histone variants, may confer to cancer cells the ability to reprogram their genomes and to yield, maintain or exacerbate malignant hallmarks. At the end, genetic and epigenetic alterations that are encountered in cancer cells may culminate in chromatin changes that may, by altering the quantity and quality of gene expression, promote cancer development. During the last decade a vast number of studies has uncovered epigenetic abnormalities that are associated with the (anomalous) packaging and remodeling of chromatin in cancer genomes. In this review I will focus on recently published work dealing with alterations in the primary structure of chromatin resulting from imprecise arrangements of nucleosomes along DNA, and its functional implications for cancer development. The primary chromatin structure is regulated by a variety of epigenetic mechanisms that may be deregulated through gene mutations and\/or gene expression alterations. In recent years, it has become evident that changes in chromatin structure may coincide with the occurrence of cancer hallmarks. The functional interrelationships between such epigenetic alterations and cancer development are just becoming manifest and, therefore, the oncology community should continue to explore the molecular mechanisms governing the primary chromatin structure, both in normal and in cancer cells, in order to improve future approaches for cancer detection, prevention and therapy, as also for circumventing drug resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":19810584,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-49":2,"2022-40":1,"2022-21":1,"2022-05":1,"2021-31":1,"2021-25":1,"2021-17":1,"2019-51":1,"2023-06":1,"2024-10":1}}},"text":"Effect of yoga-nidra on blood glucose level in diabetic patients.\nDiabetes is a metabolic disorder, which has become a major health challenge worldwide. South East Asian countries have a highest burden of diabetes. In India the prevalence of diabetes is rising rapidly especially in the urban population because of increasing obesity and reduced physical activity. An objective of this study is to evaluate the effect of Yoga-Nidra on blood glucose level in diabetic patients. This study was conducted on 41, middle aged, type-2 diabetic patients, who were on oral hypoglycaemic. These patients were divided in to two groups: (a) 20 patients on oral hypoglycaemic with yoga-nidra, and (b) 21 were on oral hypoglycaemic alone. Yoga-nidra practiced for 30 minutes daily up to 90 days, parameters were recorded every. 30th day. Results of this study showed that most of the symptoms were subsided (P < 0.004, significant), and fall of mean blood glucose level was significant after 3-month of Yoga-nidra. This fall was 21.3 mg\/dl, P < 0.0007, (from 159 +\/- 12.27 to 137.7 +\/- 23.15,) in fasting and 17.95 mg\/dl, P = 0.02, (from 255.45 +\/- 16.85 to 237.5 +\/- 30.54) in post prandial glucose level. Results of this study suggest that subjects on Yoga-nidra with drug regimen had better control in their fluctuating blood glucose and symptoms associated with diabetes, compared to those were on oral hypoglycaemics alone.","subset":"pubmed_abstract"} +{"meta":{"pmid":31266095,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"The impact of home-delivered meal services on the nutritional intake of community living older adults: a systematic literature review.\nThere is a global increase in populations aged over 65 years. Physiological changes that occur during ageing may increase the nutritional risk for older adults. To avoid malnutrition and address some of the barriers to obtain an adequate food supply, home-delivered meals services provide meals in the home or in congregate settings for older adults who require nutritional support. This systematic literature review explored whether nutritional intake is improved in community-living older adults when receiving meal services compared to when meal services are not received. Four electronic databases were searched up to 31 January 2019. In total, 13 original studies were included in this analysis with the components: intervention of home-delivered meal or congregate meal services to older adults; comparison with groups not receiving meal services or days not receiving the meal service; and nutritional intake as an outcome measured by food history, dietary recall and\/or food frequency questionnaire. The results supported a beneficial effect of home-delivered meals on dietary intake of energy, protein and\/or certain micronutrients in older adults. The increased total energy intake is a positive influence on malnutrition risk in frail older adults and the increased protein intake supports good health, promotes recovery from illness and assists in maintaining functionality in older adults. Additionally, there was a particular increase in calcium intake, which is relevant in ageing, especially for bone health.","subset":"pubmed_abstract"} +{"meta":{"pmid":27565902,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Long-term Consequences of Finasteride vs Placebo in the Prostate Cancer Prevention Trial.\nFinasteride has been found to reduce the risk of low-grade prostate cancer but to have no impact on overall survival. The long-term adverse and beneficial consequences of finasteride have not been examined. We used a linkage between data from the Prostate Cancer Prevention Trial (PCPT) and Medicare claims. Patients were examined by randomized study arm (finasteride vs placebo for 7 years) for long-term consequences of the intervention, including cardiac, endocrine, and sexual dysfunction, depression, diabetes, and benign prostatic hyperplasia (BPH)-related events. To examine time to events, we used cumulative incidence and Cox regression, adjusting for covariates. All statistical tests were two-sided. A total of 13 935 of 18 880 participants (73.8%) in the PCPT were linked to Medicare claims, with median Medicare follow-up assessment time of 16 years from trial registration. There were no differences between finasteride and placebo participants with respect to important baseline factors or amount of Medicare follow-up assessment time. Finasteride patients had a 10% higher risk of new claims for depression (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.01 to 1.19, P = .04) and a 6% lower risk of procedures for BPH-related events (primarily lower urinary tract symptoms; HR = 0.94, 95% CI = 0.89 to 1.00, P = .03). No other differences were found in rates of long-term consequences of intervention in the two study arms. Finasteride use is associated with reduced need for procedures for relief of BPH-related events and a modest increase in depression. Overall, there is little need to worry about long-term noncancer consequences of finasteride use in those who use it for treatment of symptomatic BPH, hair growth, or prevention of cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":20671565,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-45":1,"2018-47":1,"2018-30":1,"2018-26":1,"2018-05":1,"2017-51":1,"2017-34":1,"2016-44":1,"2015-48":1,"2021-04":1}}},"text":"Determinants of global perceived health in community-dwelling elderly screened for heart failure and sleep-disordered breathing.\nThe relationships between heart failure (HF), sleep-disordered breathing (SDB), insomnia, depressive symptoms, and excessive daytime sleepiness (EDS), as well as their relationship to Global Perceived Health (GPH) in an elderly community-dwelling population, have not been explored. Data from 331 community-dwelling elderly (71-87 years old) were collected by echocardiography, polygraphy, and specific questionnaires. Factor analyses and structural equation modeling were used to explore the relationships between HF, SDB, sleep, psychosocial factors, and GPH. Exploratory and confirmatory factor analyses derived a 5-factor model representing SDB, insomnia, systolic function, breathlessness\/physical function, and psychosocial function. Structural equation modeling analyses were used to explore the relationships between the 5 factors and to GPH. Sleep-disordered breathing had a weak effect on systolic function, but no effects on any of the other factors or GPH were found. Psychosocial function and breathlessness\/physical function directly affected GPH. Indirect effects on GPH, mediated by psychosocial function, were found for breathlessness\/physical function and insomnia. Systolic function also had an indirect effect on GPH. The fact that SDB in the elderly has no obvious negative associations to sleep complaints or GPH does not exclude them from being adequately treated for SDB. However, the present study has shown that SDB, by means of self-rated sleep complaints and health-related quality of life, can be problematic to detect. Psychosocial function was the most important factor for perceived GPH as it had a direct effect, as well as mediated the factors breathlessness\/physical function and insomnia effects, on GPH. This study indicates that interventions in clinical practice targeting psychosocial dysfunction, such as depressive symptoms, could help to improve GPH in the elderly with or without HF.","subset":"pubmed_abstract"} +{"meta":{"pmid":8200553,"dup_signals":{"dup_doc_count":17,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":2,"2022-27":1,"2022-21":1,"2021-31":1,"2021-04":1,"2020-50":1,"2020-34":1,"2019-47":1,"2018-30":1,"2018-05":1,"2017-34":1,"2023-06":1}}},"text":"Smoking, alcohol, and analgesics in dyspepsia and among dyspepsia subgroups: lack of an association in a community.\nDyspepsia is common in the general population, and despite a paucity of data, smoking, alcohol, and analgesics are believed to be important risk factors. The role of these environmental factors in subjects with uninvestigated dyspepsia was evaluated in a representative population sample. An age and gender stratified random sample of residents of Olmsted County, Minnesota, aged 20 to 64 years was mailed a valid self report questionnaire; 77% responded (n = 1644). Age and gender adjusted (1990 US white population) prevalence rates for dyspepsia (defined as frequent pain located in the upper abdomen, or nausea in the absence of a history of peptic ulcer disease) were calculated. Logistic regression analysis was used to estimate the association between dyspepsia and potential risk factors. The age and gender adjusted prevalence (per 100) of dyspepsia in the community was 21.8 (95% confidence interval 19.6, 23.9). Dyspepsia was significantly more common in younger subjects and females. Adjusting for age and gender, paracetamol (odds ratio (OR) = 2.2), aspirin (OR = 1.8), and smoking (OR = 1.5), but not alcohol (OR = 0.9), were associated with dyspepsia (all p < 0.05). When non-gastrointestinal somatic complaints were included in the logistic models, however, these environmental factors were no longer significant (OR = 1.3, 1.1, 1.2 and 0.9, respectively). Similar results were obtained when ulcer-like, dysmotility-like, and reflux-like dyspepsia were considered separately. The results were not significantly changed when subjects with a history of ulcer disease were included in the analyses. Smoking, alcohol, and analgesics may not therefore be important risk factors for dyspepsia in the community.","subset":"pubmed_abstract"} +{"meta":{"pmid":11844942,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":9}}},"text":"A randomised controlled clinical trial on the additional effect of hypnosis in a comprehensive treatment programme for in-patients with conversion disorder of the motor type.\nThe primary aim of this study was threefold: (1) to examine the additional effects of hypnosis aimed at symptom reduction, using symptom-oriented and expression- and insight-oriented techniques in a comprehensive clinical treatment programme for in-patients with a persistent conversion disorder of the motor type; (2) to assess whether the level of hypnotisability was predictive of treatment outcome, and (3) to explore the efficacy of the total clinical treatment programme. The study population consisted of 45 in-patients between 18 and 65 years of age meeting the DSM-III-R criteria for conversion disorder of the motor type or somatisation disorder with motor conversion symptoms. A randomised controlled clinical trial was undertaken. The primary outcome measures were the Video Rating Scale for Motor Conversion Symptoms, the D(isabilities) code items from the International Classification of Impairments, Disabilities and Handicaps and the Symptom Checklist-90. Measures of the credibility of treatment and patient expectations of treatment outcome were used as manipulation checks. Hypnotisability was measured using the Stanford Hypnotic Clinical Scale. Significant treatment results for all outcome measures were found for the total sample. These effects proved to be clinically significant. The use of hypnosis had no additional effect on treatment outcome. Hypnotisability was not predictive of treatment outcome. A comprehensive treatment programme, either with or without hypnosis, can be worthwhile for patients with long-standing conversion symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":17004272,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":13}}},"text":"Sulfidogenic fluidized-bed treatment of metal-containing wastewater at low and high temperatures.\nThe applicability of a fluidized-bed reactor (FBR)-based sulfate reducing bioprocess was investigated for the treatment of iron-containing (40-90 mg\/L) acidic wastewater at low (8 degrees C) and high (65 degrees C) temperatures. The FBRs operated at low and high temperatures were inoculated with cultures of sulfate-reducing bacteria (SRB) originally enriched from arctic and hot mining environments, respectively. Ethanol was supplemented as carbon and electron source for SRB. At 8 degrees C, ethanol oxidation and sulfate reduction rates increased steadily and reached 320 and 265 mg\/L.day, respectively, after 1 month of operation. After this point, the rates did not change significantly during 130 days of operation. Despite the complete ethanol oxidation and iron precipitation, the average sulfate reduction efficiency was 35 +\/- 4% between days 30 and 130 due to the accumulation of acetate. At 65 degrees C, a rapid startup was observed as 99.9, 46, and 29% ethanol, sulfate, acetate removals, in respective order, were observed after 6 days. The feed pH was decreased gradually from its initial value of 6 to around 3.7 during 100 days of operation. The wastewater pH of 4.3-4.4 was neutralized by the alkalinity produced in acetate oxidation and the average effluent pH was 7.8 +\/- 0.8. As in the low temperature FBR, acetate accumulated. Hence, the oxidation of acetate is the rate-limiting step in the sulfidogenic ethanol oxidation by thermophilic and psychrotrophic SRB. The sulfate reduction rate is three times and acetate oxidation rate is four times higher at 65 degrees C than at 8 degrees C.","subset":"pubmed_abstract"} +{"meta":{"pmid":9575495,"dup_signals":{"dup_doc_count":59,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-50":4,"2023-23":6,"2023-14":1,"2022-49":4,"2022-27":4,"2022-21":3,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":3,"2021-21":3,"2021-17":2,"2021-10":2,"2021-04":2,"2020-50":2,"2020-40":5,"2020-16":1,"2024-22":5,"2024-18":1,"2024-10":2,"2024-26":1}}},"text":"Hypoxia and the regulation of gene expression.\nThe optimal delivery of oxygen to tissues is essential both to ensure adequate energy provision and to avoid the toxic effects of higher oxygen concentrations. For this to occur, organisms must be able to sense oxygen and respond to changes in oxygen tension by altering gene expression. The analysis of the regulation of erythropoiesis has provided important insights into the mechanisms of oxygen-regulated gene expression. These mechanisms have a role in the regulation of many genes, in many cell types and appear to be of relevance to many common pathologies in which disturbances of oxygen supply are central.","subset":"pubmed_abstract"} +{"meta":{"pmid":30306986,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Engineering more stable proteins.\nProtein function requires the folded protein form, but this form is unstable mainly because it readily unfolds into a flexible, unstructured form. Protein folding is favored by burying of hydrophobic side chains and hydrogen bonding between the amino acids. Protein unfolding is favored by the increase in conformational freedom of the main chain of amino acids upon unfolding. Protein stability is usually measured by the reversible unfolding of the protein with either heat or chemical additives like urea. Engineering mores stable proteins involves making substitutions that shift the folding-unfolding balance toward the folded form. Stabilizing substitutions can either stabilize the folded conformation or destabilize the unfolded ensemble. This tutorial emphasizes web-based tools to identify substitutions that stabilize proteins. Besides unfolding, other sources of protein instability are chemical modifications like oxidations or cleavage by proteases and aggregation of partly unfolded proteins into insoluble particles.","subset":"pubmed_abstract"} +{"meta":{"pmid":27511791,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"The initial break-up of Pang\u00e6a elicited by Late Pal\u00e6ozoic deglaciation.\nThe break-up of Pang\u00e6a was principally facilitated by tensional plate stress acting on pre-existing suture zones. The rifting of Pang\u00e6a began during the Early Permian along the southern Tethys margin and produced the lenticular-shaped continent known as Cimmeria. A mantle-plume model is ascribed to explain the rift-related volcanism but the NW-SE oriented Cimmerian rifts do not correlate well with pre-existing suture zones or 'structural heterogeneities' but appear to have a pertinent spatial and temporal association with Late Pal\u00e6ozoic glacial-interglacial cycles. Mantle potential temperature estimates of Cimmerian rift-related basalts (1410 \u00b0C \u00b1 50 \u00b0C) are similar to ambient mantle conditions rather than an active mantle-plume rift as previously suggested. Moreover, we find that the distribution of glacial deposits shows significant temporal and spatial concurrence between the glacial retreat margins and rifting sites. We conclude that the location and timing of Cimmerian rifting resulted from the exploitation of structural heterogeneities within the crust that formed due to repeated glacial-interglacial cycles during the Late Pal\u00e6ozoic. Such effects of continental deglaciation helped to create the lenticular shape of Cimmeria and Neotethys Ocean suggesting that, in some instances, climate change may directly influence the location of rifting.","subset":"pubmed_abstract"} +{"meta":{"pmid":23576902,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Current concepts and management approaches in nonalcoholic fatty liver disease.\nNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction worldwide. NAFLD may progress to nonalcoholic steatohepatitis (NASH) and in turn cirrhosis. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols and diacylglycerols in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA) flux creating an environment appropriate for the development of NAFLD. The generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation will ultimately lead to the initiation and progression of fibrosis. Lifestyle modifications specifically weight loss, physical exercise, and cognitive behavior therapy have been recommended as treatments for NASH. Dietary fructose is an independent risk factor for the development of NAFLD. Pioglitazone can be used to treat biopsy-proven NASH; however, its safety risks should be considered carefully. Greater consumption for coffee, independent of its caffeine component, has been associated with a significant reduced risk of advanced fibrosis in NASH. Additional data are needed before recommending bariatric surgery as an established option for the specific treatment of NASH.","subset":"pubmed_abstract"} +{"meta":{"pmid":23976946,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"In-lake processes offset increased terrestrial inputs of dissolved organic carbon and color to lakes.\nIncreased color in surface waters, or browning, can alter lake ecological function, lake thermal stratification and pose difficulties for drinking water treatment. Mechanisms suggested to cause browning include increased dissolved organic carbon (DOC) and iron concentrations, as well as a shift to more colored DOC. While browning of surface waters is widespread and well documented, little is known about why some lakes resist it. Here, we present a comprehensive study of M\u00e4laren, the third largest lake in Sweden. In M\u00e4laren, the vast majority of water and DOC enters a western lake basin, and after approximately 2.8 years, drains from an eastern basin. Despite 40 years of increased terrestrial inputs of colored substances to western lake basins, the eastern basin has resisted browning over this time period. Here we find the half-life of iron was far shorter (0.6 years) than colored organic matter (A\u2084\u2082\u2080; 1.7 years) and DOC as a whole (6.1 years). We found changes in filtered iron concentrations relate strongly to the observed loss of color in the western basins. In addition, we observed a substantial shift from colored DOC of terrestrial origin, to less colored autochthonous sources, with a substantial decrease in aromaticity (-17%) across the lake. We suggest that rapid losses of iron and colored DOC caused the limited browning observed in eastern lake basins. Across a wider dataset of 69 Swedish lakes, we observed greatest browning in acidic lakes with shorter retention times (< 1.5 years). These findings suggest that water residence time, along with iron, pH and colored DOC may be of central importance when modeling and projecting changes in brownification on broader spatial scales.","subset":"pubmed_abstract"} +{"meta":{"pmid":7966307,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Refined X-ray structure of Dictyostelium discoideum nucleoside diphosphate kinase at 1.8 A resolution.\nThe X-ray structure of the nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been refined at 1.8 A resolution from a hexagonal crystal form with a 17 kDa monomer in its asymmetric unit. The atomic model was derived from the previously determined structure of a point mutant of the protein. It contains 150 amino acid residues out of 155, and 95 solvent molecules. The R-factor is 0.196 and the estimated accuracy of the average atomic position, 0.25 A. The Dictyostelium structure is described in detail and compared to those of Drosophila and Myxococcus xanthus NDP kinases. The protein is a hexamer with D3 symmetry. Residues 8 to 138 of each subunit form a globular alpha\/beta domain. The four-stranded beta-sheet is antiparallel; its topology is different from other phosphate transfer enzymes, and also from the HPr protein which, like NDP kinase, carries a phosphorylated histidine. The same topology is nevertheless found in several other proteins that bind mononucleotides, RNA or DNA. Strand connections in NDP kinase involve alpha-helices and a 20-residue segment called the Kpn loop. The beta-sheet is regular except for a beta-bulge in edge strand beta 2 and a gamma-turn at residue Ile120 just preceding strand beta 4. The latter may induce strain in the main chain near the active site His122. The alpha 1 beta 2 motif participates in forming dimers within the hexamer, helices alpha 1 and alpha 3, the Kpn loop and C terminus, in forming trimers. The subunit fold and dimer interactions found in Dictyostelium are conserved in other NDP kinases. Trimer interactions probably occur in all eukaryotic enzymes. They are absent in the bacterial Myxococcus xanthus enzyme which is a tetramer, even though the subunit structure is very similar. In Dictyostelium, contacts between Kpn loops near the 3-fold axis block access to a central cavity lined with polar residues and filled with well-defined solvent molecules. Biochemical data on point mutants highlight the contribution of the Kpn loop to protein stability. In Myxococcus, the Kpn loops are on the tetramer surface and their sequence is poorly conserved. Yet, their conformation is maintained and they make a similar contribution to the substrate binding site.","subset":"pubmed_abstract"} +{"meta":{"pmid":27001548,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2021-25":1,"2021-21":1,"2020-24":1,"2019-30":1,"2019-09":1,"2018-34":1,"2018-09":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2022-33":1,"2017-13":1,"2024-10":1}}},"text":"Validation of PRISM (Pictorial Representation of Illness and Self Measure) as a novel visual assessment tool for the burden of suffering in tinnitus patients.\nChronic subjective tinnitus is a frequent condition that affects the subject's quality of life. The lack of objective measures of tinnitus necessitates the use of self-reporting and often time-consuming questionnaires for evaluating tinnitus severity. The Pictorial Representation of Illness and Self Measure (PRISM) is a two dimensional pictorial method to assess the burden of suffering. Patients illustrate their burden of suffering by the distance from a \"self\" to an illness circle, whereby a shorter distance indicates a higher burden of suffering. The aim of this prospective observational study was to validate the burden of suffering measured with PRISM in tinnitus patients by comparing it with different standardized questionnaires currently used in tinnitus evaluation. A total of 188 patients filled out an online-based survey including sociodemographic variables and the following questionnaires: Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), WHO Quality of Life-Questionnaire (WHOQOL-BREF), and the Beck Depression Inventory (BDI). The subtle differences in the burden of suffering were accessed by using PRISM as an iPad version. Based on PRISM performance patients could easily be assigned in three groups, these being mildly, moderately, or severely affected akin to the standard questionnaires. The burden of suffering measured with PRISM correlated with the tinnitus severity (THI and TQ), depressive symptoms (BDI), and health related quality of life (WHOQOL-BREF) (all p \u2264 0.001). In the three PRISM groups tinnitus severity (THI and TQ), and depressive symptoms (BDI) differed significantly (all p \u2264 0.01). PRISM is an easily understood and time saving method for the assessment of burden of suffering in tinnitus patients. In daily clinical practice PRISM can help to identify patients with decompensated tinnitus that require more intensive treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":33019510,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"The Cutaneous Physiological Redox: Essential to Maintain but Difficult to Define.\nSkin is a unique tissue, possessing extremely efficient protective and regulative mechanisms, similar only to the gut and lungs. These tissues serve as an interface with the environment and are exposed to stressors from both endogenous and exogenous sources. Interestingly, all these stressors lead downstream to a cellular production of reactive oxygen species (ROS) and other electrophiles, which, in turn could have deleterious outcomes for the living organism. Hence, such tissues should always maintain a \"high-alert\" condition in order to cope with these various insults. Nevertheless, a moderate production of ROS induced by stressors could actually be beneficial, although it is impossible to predict if and which exposure would lead to which outcome. Consequently, a parameter which would indicate the skin's readiness to cope with continuously fluctuating conditions is required. It has been proposed that the redox status may serve as a suitable indicator. In this opinion manuscript, we argue that the redox status is a vague parameter that is difficult to characterized and quantify due to its extremely dynamic nature. The common convention that the redox status is composed solely of the balance between oxidants and reductants (ROS and antioxidants) is also thought-provoking. Since this parameter in vivo behaves in a dynamic and complex manner, it better fits the description of a process, rather than an individual parameter. We suggest that the homeostatic modulation of the physiological redox (PR) should be in focus, rather than the redox status parameter itself. It is further suggested that low molecular weight antioxidants (LMWA) are, in fact, rather insignificant concerning the PR maintenance, and that the major contributors to this delicate modulation are regulative, protein-based systems such as the protective phase II antioxidant enzymes. Moreover, we show that skin microbiome and cutaneous advanced lipid peroxidation end-products (ALEs) take part in sustaining the cutaneous PR homoeostasis via activation of the Nrf2-Keap1 protective pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":8182727,"dup_signals":{"dup_doc_count":53,"dup_dump_count":39,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-49":2,"2021-43":1,"2021-39":1,"2021-31":2,"2021-25":1,"2021-21":2,"2021-17":1,"2021-10":3,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2020-34":1,"2020-24":1,"2019-51":1,"2019-47":1,"2019-43":3,"2019-39":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-47":1,"2017-26":1,"2024-26":2,"2024-22":1,"2024-18":1,"2024-10":2,"2015-18":1,"2024-30":1}}},"text":"The molecular basis of genetic dominance.\nStudies of mutagenesis in many organisms indicate that the majority (over 90%) of mutations are recessive to wild type. If recessiveness represents the 'default' state, what are the distinguishing features that make a minority of mutations give rise to dominant or semidominant characters? This review draws on the rapid expansion in knowledge of molecular and cellular biology to classify the molecular mechanisms of dominant mutation. The categories discussed include (1) reduced gene dosage, expression, or protein activity (haploinsufficiency); (2) increased gene dosage; (3) ectopic or temporally altered mRNA expression; (4) increased or constitutive protein activity; (5) dominant negative effects; (6) altered structural proteins; (7) toxic protein alterations; and (8) new protein functions. This provides a framework for understanding the basis of dominant genetic phenomena in humans and other organisms.","subset":"pubmed_abstract"} +{"meta":{"pmid":11014533,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":16}}},"text":"Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system.\nThe long-term durability of Guglielmi detachable coil (GDC) embolization of cerebral aneurysms is still unknown. The purpose of this study was to evaluate the anatomical evolution of neck remnants in aneurysms treated with GDCs. Of 455 aneurysms treated with GDCs from 1990 to 1998 at the University of California at Los Angeles Medical Center, 178 aneurysms (39%) had residual necks postembolization. Long-term follow-up angiograms were obtained in 73 of these aneurysms in 71 patients. The mean duration of angiographic follow up was 17.3 months. Twenty-four of the aneurysms were small with small necks, 24 were small with wide necks, 15 were large, and 10 were giant aneurysms. In small aneurysms with small necks, postembolization angiography revealed 12 aneurysms (50%) with progressive thrombosis, eight (33%) unchanged, and four (17%) with recanalization. In small aneurysms with wide necks, six (25%) had progressive thrombosis, eight (33%) remained unchanged, and 10 (42%) had recanalization. In large aneurysms, two (13%) were unchanged and 13 (87%) had recanalization. Of the giant aneurysms only one (10%) remained unchanged and nine (90%) had recanalization. Overall, 18 aneurysms (25%) exhibited progressive thrombosis, 19 (26%) remained unchanged, and 36 (49%) displayed recanalization on follow-up angiography. During the last 2 years of the study, the recanalization rate decreased and a higher rate of progressive thrombosis was noted in aneurysms with small necks. These positive changes are related to important new technical developments. Treatment with GDCs appears to be effective and the results permanent in most small aneurysms with small necks. However, there are important technical limitations in the current GDC technology that prevent recanalization in wide-necked or large or giant aneurysms.","subset":"pubmed_abstract"} +{"meta":{"pmid":22471343,"dup_signals":{"dup_doc_count":19,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2020-40":2,"2020-34":1,"2020-05":1,"2019-47":4,"2019-43":5,"2013-48":2,"2013-20":1,"2014-10":1}}},"text":"Validation of activity questionnaires in patients with cystic fibrosis by accelerometry and cycle ergometry.\nThe objective of this study was to validate physical activity questionnaires for cystic fibrosis (CF) against accelerometry and cycle ergometry. 41 patients with CF (12-42 years) completed the Habitual Activity Estimation Scale (HAES), the 7-Day Physical Activity Recall questionnaire (7D-PAR) and the Lipid Research Clinics questionnaire (LRC) and performed an incremental exercise test according to the Godfrey protocol up to volitional fatigue. Time spent in moderate and vigorous physical activity (MVPA) assessed objectively by accelerometry was related to the time spent in the respective activity categories by correlation analyses and calculating intraclass correlation coefficients (ICC). Furthermore, the results of the exercise test were correlated with the results of the questionnaires. Time spent in the categories 'hard','very hard' and 'hard & very hard' of the 7D-PAR (0.41 < r < 0.56) and 'active' (r = 0.33) of the HAES correlated significantly with MVPA. The activity levels of the LRC were not related to objectively determined physical activity. Significant ICCs were only observed between the 7D-PAR activitiy categories and MVPA (ICC = 0.40-0.44). Only the LRC showed moderate correlations with the exercise test (Wmax: r = 0.46, p = 0.002; VO2peak: r = 0.32, p = 0.041). In conclusion, the activity categories 'hard' and 'very hard' of the 7D-PAR best reflected objectively measured MVPA. Since the association was at most moderate, the 7D-PAR may be selected to describe physical activity within a population. None of the evaluated questionnaires was able to generate valid physical activity data exercise performance data at the individual level. Neither did any of the questionnaires provide a valid assessment of aerobic fitness on an invidual level.","subset":"pubmed_abstract"} +{"meta":{"pmid":21871600,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"The impact of contact lens wear and visual display terminal work on ocular surface and tear functions in office workers.\nTo evaluate the effect of contact lens (CL) wear and visual display terminal (VDT) work on the ocular surface and tear functions. Prospective case-control study. Sixty-nine CL wearers (45 women and 24 men; mean age, 35.2 \u00b1 7.3 years), and 102 age- and sex-matched non-CL wearers were enrolled in the study (66 women and 36 men; mean age, 36.7 \u00b1 7.3 years). Ocular surface and tear function tests, including vital stainings (fluorescein and rose bengal), Schirmer test, tear meniscus height measurement, and tear film break-up time were performed. The subjective symptoms of dry eyes were evaluated using a dry eye symptom questionnaire. The participants were divided into 4 subgroups according to the total time of VDT work in 1 day (VDT work time in 1 day \u2265 4 hours or < 4 hours) and presence of CL wear. Main outcome measures included ocular surface vital staining scores, Schirmer test results, tear film break-up time, tear meniscus height measurement, and symptom questionnaire score. CL users and long-term VDT workers showed significantly worse tear meniscus height values than non-CL users and short-term VDT workers (P < .001). The mean visual symptom scores in CL wearers and long-term VDT workers were significantly higher than the other groups (P < .001). Office workers who wore CLs and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume with significant dry eye and visual symptoms triggered by environmental factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":19723985,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2014-10":4,"2013-48":4,"2013-20":2,"unknown":7}}},"text":"Geographic mapping of meniscus and cartilage lesions associated with anterior cruciate ligament injuries.\nDetailed descriptions of meniscus and articular cartilage lesions associated with anterior cruciate ligament injury have not been presented in the literature. Our goal was to determine the associations between patient sex, age, and surgical delay and the frequency and location of meniscus and articular cartilage lesions seen at the time of the anterior cruciate ligament reconstruction. Data were obtained retrospectively from a database of 1209 consecutive patients undergoing anterior cruciate ligament reconstruction between 1988 and 2002. All knee cartilage, meniscus, and ligament injuries were documented on anatomic maps at the time of surgery, and the data were analyzed. Meniscus injuries were identified in 722 (65%) of the 1104 patients who met the criteria for inclusion in the study. Female patients were less likely to have a meniscus injury than male patients were (56% compared with 71%), and male patients were more likely to have combined medial and lateral meniscus injuries than female patients were (20% compared with 11%). Patients with a surgical delay of less than three months were less likely to have a medial meniscus injury (8% compared with 19%). Femoral articular cartilage injuries were identified in 472 patients (43%). Patients who were twenty-five years of age or older were more likely to have multiple cartilage lesions throughout the knee (7.7% compared with 1.3%) and to have more isolated medial femoral condyle lesions (24.2% compared with 13.3%). Patients with a surgical delay of more than one year were more likely to have a lesion (60% compared with 47% for all others), and a surgical delay of more than one year resulted in a greater proportion of large and grade-3 lesions of the lateral femoral condyle. Female patients had a greater proportion of grade-1 lesions of the medial femoral condyle (29% compared with 16%), whereas male patients had a greater proportion of grade-3 and 4 lesions of the medial femoral condyle (49% compared with 35%). In patients who were thirty-five years of age or older, meniscus injuries were more frequent and were located more frequently on the medial side; femoral articular cartilage lesions were also located more frequently on the medial side. Increased age, male sex, and increased surgical delay all increase the frequency and severity of injuries of the meniscus and\/or articular cartilage after an anterior cruciate ligament tear.","subset":"pubmed_abstract"} +{"meta":{"pmid":22720904,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-23":2,"2014-15":2,"2015-48":1}}},"text":"Observations on Neotricula aperta (Gastropoda: Pomatiopsidae) population densities in Thailand and central Laos: implications for the spread of Mekong schistosomiasis.\nThe snail Neotricula aperta transmits Mekong schistosomiasis in southern Laos and Cambodia, with about 1.5 million people at risk of infection. Plans are under consideration for at least 12 hydroelectric power dams on the lower Mekong river and much controversy surrounds predictions of their environmental impacts. Unfortunately, there are almost no ecological data (such as long-term population trend studies) available for N. aperta which could be used in impact assessment. Predictions currently assume that the impacts will be the same as those observed in Africa (i.e., a worsening of the schistosomiasis problem); however, marked ecological differences between the snails involved suggest that region specific models are required. The present study was performed as an initial step in providing data, which could be useful in the planning of water resource development in the Mekong. Snail population density records were analyzed for populations close to, and far downstream of, the Nam Theun 2 (NT2) project in Laos in order to detect any changes that might be attributable to impoundment. The population immediately downstream of NT2 and that sampled 400 km downstream in Thailand both showed a long-term trend of slow growth from 1992 to 2005; however, both populations showed a marked decline in density between 2005 and 2011. The decline in Thailand was to a value significantly lower than that predicted by a linear mixed model for the data, whilst the population density close to NT2 fell to undetectable levels in 2011 from densities of over 5000 m(-2) in 2005. The NT2 dam began operation in 2010. The impact of the NT2 dam on N. aperta population density could be more complex than first thought and may reflect the strict ecological requirements of this snail. There was no indication that responses of N. aperta populations to dam construction are similar to those observed with Bulinus and Schistosoma haematobium in Africa, for example. In view of the present findings, more ecological data (in particular population density monitoring and surveillance for new habitats) are urgently required in order to understand properly the likely impacts of water resource development on Mekong schistosomiasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":8540697,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.\nPegylated amphotericin B (AmB) liposomes (PEG-AmB-LIP) were compared with laboratory-prepared nonpegylated AmB liposomes (AmB-LIP), a formulation with a lipid composition the same as that in AmBisome, as well as with industrially prepared AmBisome regarding their in vitro antifungal activities, toxicities, blood residence times, and therapeutic efficacies. Killing of Candida albicans (> 99.9%) during short-term (6-h) incubation was observed at 0.2 mg of AmB per liter for AmB desoxycholate, 0.4 mg of AmB per liter for PEG-AmB-LIP, 0.8 mg of AmB per liter for AmB-LIP, and 12.8 mg of AmB per liter for AmBisome. The maximum tolerated doses of PEG-AmB-LIP, AmB-LIP, and AmBisome were 15, 19, and > 31 mg of AmB per kg of body weight, respectively. In contrast to AmB-LIP, the blood residence time of PEG-AmB-LIP was prolonged and dose independent. In a model of systemic candidiasis in leukopenic mice at a dose of 5 mg of AmB per kg, PEG-AmB-LIP was completely effective and AmB-LIP was partially effective, whereas AmBisome was not effective. AmB-LIP at 11 mg of AmB per kg was partially effective. AmBisome at 29 mg of AmB per kg was completely effective. In conclusion, the therapeutic efficacies of AmB liposomes can be improved by preparing AmB liposomes in which a substantial reduction in toxicity is achieved while antifungal activity is retained. In addition, therapeutic efficacy is favored by a prolonged residence time of AmB liposomes in blood.","subset":"pubmed_abstract"} +{"meta":{"pmid":21324965,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study.\nDuring OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 \u00b1 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.","subset":"pubmed_abstract"} +{"meta":{"pmid":15352540,"dup_signals":{"dup_doc_count":53,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2016-26":2,"2016-22":2,"2016-18":1,"2016-07":2,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":1,"2015-22":2,"2015-14":2,"2014-52":2,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":3,"2014-23":3,"2014-15":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":3}}},"text":"Bulk tank milk urea nitrogen: seasonal patterns and relationship to individual cow milk urea nitrogen values.\nThe objectives of this study were: 1) to determine if bulk tank milk urea nitrogen (BTMUN) and whole herd weighted average of the individual cow MUN levels (WHMUN) were equivalent measurements of herd MUN status; and 2) to determine the seasonal variation in BTMUN concentrations in Prince Edward Island (PEI) dairy herds. For BTMUN-WHMUN correlation testing, bulk tank milk samples from 176 herds were tested for MUN once every 1 to 2 wk between September 1999 and August 2002, as part of routine BTM testing for milk components. During this 3-year period, all herds had all milking cows tested for MUN once a month at the same lab. The WHMUN levels (weighted for milk production) were calculated for each month, and were compared to BTMUN levels using a concordance correlation coefficient (CCC) and a graphic procedure. Tests were only compared if they occurred on the same date, producing a final dataset of 669 comparisons. The BTMUN had good (but not perfect) correlation with WHMUN (CCC = 0.91). This high reliability extended to both the pasture and non-pasture seasons, various milk sampling protocols, and all herd sizes seen in PEI. For evaluating the seasonal variation of BTMUN, the 3 y worth of data (24 803 observations) were divided into 15 seasonal categories, 5 seasons per year (early, mid, and late pasture, and early and late stable). Using linear mixed modelling, significantly (P < 0.05) higher BTMUN values were found during the mid and late pasture seasons of 2000, likely because the precipitation was unusually high during this period, enhancing pasture growth.","subset":"pubmed_abstract"} +{"meta":{"pmid":2990044,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"A large deletion within the T-cell receptor beta-chain gene complex in New Zealand white mice.\nThe T-cell receptor beta-chain gene complex contains a duplication of D beta, J beta, and C beta gene segments in mice and man. When DNA from many inbred strains of mice was screened an unusual allele of the beta locus was identified in New Zealand White (NZW) mice. This allele is distinguished by the deletion of an 8.8-kilobase segment of DNA containing C beta 1, D beta 2 and the J beta 2 cluster. Despite the fact that all NZW T-cell receptors must be derived from a single set of beta-chain gene segments, this strain has functional T cells and is phenotypically normal. This deletion of T-cell receptor beta-chain segments occurs in a strain known to contribute to lupus-like autoimmune disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":7658531,"dup_signals":{"dup_doc_count":17}},"text":"Indications for lower urinary tract reconstruction in women after cystectomy for bladder cancer: a pathological review of female cystectomy specimens.\nIn an attempt to identify women who may be appropriate candidates for orthotopic lower urinary tract reconstruction, archival cystectomy specimens from female patients undergoing cystectomy for primary bladder cancer were reviewed. These pathological findings should provide a better understanding of tumor involvement at the bladder neck (vesicourethral junction) and urethra in women with transitional cell carcinoma of the bladder. Cystectomy specimens of 67 consecutive women undergoing surgery for biopsy proved transitional cell carcinoma of the bladder between July 1982 and July 1990 were pathologically reviewed. Histological evidence of tumor (carcinoma in situ or gross carcinoma) involving the urethra was present in 9 patients (13%). Tumor was confined to the proximal and mid urethra, and the distal urethra was not involved. All patients with carcinoma involving the urethra had concomitant evidence of carcinoma involving the bladder neck. A total of 17 patients (25%) had tumor involvement of the bladder neck and those with an uninvolved bladder neck also had an uninvolved urethra. The association between the presence of tumor in the bladder neck and urethra was highly significant (p < or = 0.00012). Tumor involving the bladder neck and urethra tended to be more commonly associated with high grade and stage tumors, and node-positive disease. Although the fate of the retained urethra following cystectomy for bladder cancer in women is unknown, these results show that women with transitional cell carcinoma of the bladder without evidence of tumor involving the bladder neck are at low risk for urethral malignancy. These patients may be offered lower urinary tract reconstruction that includes preservation of and diversion through the urethra (orthotopic diversion). Urethral surveillance will be necessary, as it is in men after orthotopic urinary diversion.","subset":"pubmed_abstract"} +{"meta":{"pmid":29780911,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-21":1,"2021-39":1,"2021-17":1,"2021-04":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-26":1,"2018-13":1,"2023-50":1,"2024-26":1,"2024-18":1,"2024-30":1}}},"text":"Long-term visual outcomes of laser anterior ciliary excision.\nTo determine the long-term visual outcomes of six eyes of 3 patients up to 13 years following the Laser Anterior Ciliary Excision (LaserACE) procedure. Three male patients of ages 59, 59, and 60 presented for evaluation at Storm Eye Institute, Medical University of South Carolina at 8, 10, and 13 years after the LaserACE procedure for presbyopia, respectively. All 3 patients had a history of laser vision correction (LVC) prior to LaserACE treatment. Visual performance was evaluated using ray-tracing aberrometry, specifically higher-order aberrations, visual Strehl of the optical transfer function (VSOTF), depth of focus (DoF), and effective range of focus (EROF). VSOTF was computed as a function of defocus using a through-focus curve. Subjective DoF was overlaid on the VSOTF through-focus curve to establish the best image quality metric threshold value for correlation between subjective and objective DoF. EROF was determined by measuring the difference in diopters between the near and distance DoF curves, at 50% of VSOTF. Distance-corrected visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity for all patients remained at 20\/20 or better up to 13 years postoperatively. EROF averaged 1.56 \u00b1 0.36 (D) for all eyes. LaserACE provided improvement in near vision functionality in these LVC patients with long-term stability. The LaserACE procedure is not on the visual axis, therefore these patients could still receive correction to their hyperopic regression.","subset":"pubmed_abstract"} +{"meta":{"pmid":26346215,"dup_signals":{"dup_doc_count":24,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2023-23":3,"2023-06":1,"2022-49":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-39":1,"2019-18":1,"2018-51":1,"2018-30":1,"2018-09":1,"2017-34":1,"2017-26":1,"2024-18":1}}},"text":"The effects of teacher read-alouds and student silent reading on predominantly bilingual high school seniors' learning and retention of social studies content.\nTeacher read-alouds (TRA) are common in middle and high school content area classes. Because the practice of reading the textbook out loud to students is often used out of concern about students' ability to understand and learn from text when reading silently (SR), this randomized controlled trial was designed to experimentally manipulate text reading while blocking on all other instructional elements to determine the relative effects on learning content. Predominantly Spanish-English bilingual twelfth-graders (n = 123) were randomly assigned to either a TRA or SR condition and provided 1 week of high quality instruction in US history. Daily lessons included teaching key terms in the passage, previewing text headings, and conducting comprehension checks. Results of immediate, 1-week delayed, and 1-month delayed assessments of content learning revealed no significant differences between the two groups. Students were also asked to rate the method of reading they believed best helped them understand and remember information. Students in the SR condition more consistently agreed that reading silently was beneficial. Findings suggest low performing adolescents of different linguistic backgrounds can learn content as well when reading appropriately challenging text silently as when the teacher reads the text aloud to them.","subset":"pubmed_abstract"} +{"meta":{"pmid":15615717,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":6,"2020-29":1,"2019-35":1,"2018-39":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2021-31":1,"2017-13":1}}},"text":"A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein.\nSeveral proteins linked to neurodegenerative diseases, such as the beta-amyloid precursor protein, amyloid beta-peptide, beta-secretase, and tau, undergo selective polarized sorting. We investigated polarized sorting of the mammalian prion protein (PrP(C)) and its homologue doppel (Dpl). In contrast to Dpl, which accumulates on the apical surface, PrP(C) is targeted selectively to the basolateral side in Madin-Darby canine kidney cells. An extensive deletion and domain swapping analysis revealed that the internal hydrophobic domain (HD) of PrP (amino acids 113-133) confers basolateral sorting in a dominant manner. PrP mutants lacking the HD are sorted apically, while Dpl chimeras containing the HD of PrP are directed to the basolateral membrane. Furthermore, a pathogenic PrP missense mutation within the HD leads to aberrant apical sorting of PrP as well.","subset":"pubmed_abstract"} +{"meta":{"pmid":27618527,"dup_signals":{"dup_doc_count":24,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-43":4,"2021-39":2,"2021-31":4,"2021-25":1,"2021-10":1,"2020-29":1,"2020-16":2,"2023-06":1}}},"text":"The Relationship Between Maximal Strength and Reactive Strength.\nMaximum- and reactive-strength qualities both have important roles in athletic movements and sporting performance. Very little research has investigated the relationship between maximum strength and reactive strength. The aim of this study was to investigate the relationship between maximum-strength (isometric midthigh-pull peak force [IMTP PF]) and reactive-strength (drop-jump reactive-strength index [DJ-RSI]) variables at 0.3-m, 0.4-m, 0.5-m, and 0.6-m box heights. A secondary aim was to investigate the between- and within-group differences in reactive-strength characteristics between relatively stronger athletes (n = 11) and weaker athletes (n = 11). Forty-five college athletes across various sports were recruited to participate in the study (age, 23.7 \u00b1 4.0 y; mass, 87.5 \u00b1 16.1 kg; height, 1.80 \u00b1 0.08 m). Pearson correlation results showed that there was a moderate association (r = .302-.431) between maximum-strength variables (absolute, relative, and allometric scaled PF) and RSI at 0.3, 0.4, 0.5 and 0.6 m (P \u2264 .05). In addition, 2-tailed independent-samples t tests showed that the RSIs for relatively stronger athletes (49.59 \u00b1 2.57 N\/kg) were significantly larger than those of weaker athletes (33.06 \u00b1 2.76 N\/kg) at 0.4 m (Cohen d = 1.02), 0.5 m (d = 1.21), and 0.6 m (d = 1.39) (P \u2264 .05). Weaker athletes also demonstrated significant decrements in RSI as eccentric stretch loads increased at 0.3-m through 0.6-m box heights, whereas stronger athletes were able to maintain their reactive-strength ability. This research highlights that in specific sporting scenarios, when there are high eccentric stretch loads and fast stretch-shortening-cycle demands, athletes' reactive-strength ability may be dictated by their relative maximal strength, specifically eccentric strength.","subset":"pubmed_abstract"} +{"meta":{"pmid":29309528,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-40":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-24":1,"2020-16":1,"2020-10":1,"2019-13":1,"2019-04":1,"2018-51":1,"2023-40":1,"2024-10":1}}},"text":"Modeling the cumulative incidence function of multivariate competing risks data allowing for within-cluster dependence of risk and timing.\nWe propose to model the cause-specific cumulative incidence function of multivariate competing risks data using a random effects model that allows for within-cluster dependence of both risk and timing. The model contains parameters that makes it possible to assess how the two are connected, e.g. if high-risk is related to early onset. Under the proposed model, the cumulative incidences of all failure causes are modeled and all cause-specific and cross-cause associations specified. Consequently, left-truncation and right-censoring are easily dealt with. The proposed model is assessed using simulation studies and applied in analysis of Danish register-based family data on breast cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":29487214,"dup_signals":{"dup_doc_count":24,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":1,"2021-04":1,"2020-40":1,"2020-29":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella.\nSalmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only \u223c1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.","subset":"pubmed_abstract"} +{"meta":{"pmid":9364466,"dup_signals":{"dup_doc_count":97,"dup_dump_count":70,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-14":4,"2023-06":2,"2022-49":3,"2022-40":1,"2022-27":1,"2022-21":3,"2022-05":2,"2021-43":1,"2021-39":3,"2021-31":2,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":3,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":2,"2020-24":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":2,"2018-17":2,"2018-09":1,"2018-05":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":2,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-50":1,"2024-30":3,"2024-26":1,"2024-18":1,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1}}},"text":"Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke.\nMultiple sclerosis (MS) and stroke pathology are characterized blood-brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A, gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia\/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood-brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28304323,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Diabetic ketoacidosis complicating pregnancy.\nAlthough diabetic ketoacidosis (DKA) in pregnancy can result in significant adverse consequences for both mother and fetus, the response to treatment, time course of recovery, and perinatal outcomes have not been well studied in pregnancy. We examined the precipitating factors, laboratory abnormalities, treatment strategies, and clinical recovery in pregnancies complicated by DKA. This is a retrospective cohort study of pregnancies complicated by DKA between October 1999 and June 2015. The diagnosis was verified by hyperglycemia; anion gap >12 mEq\/L, pH <7.3, HCO3 <15 mEq\/L; and the presence of ketones. Each episode of DKA was reviewed and subsequent perinatal outcomes analyzed. During this period, we identified 33 women with 40 admissions (incidence: 0.2%). The majority of women had type 1 diabetes (67%), and almost all presented with nausea and vomiting (97%). Over half had poor compliance with prescribed insulin. The initial mean blood glucose was 380 mg\/dL, within 6 hours, it was <200 mg\/dL. By 12 hours, the acidosis had resolved in 90% of patients. Nausea and vomiting is a prominent presenting feature of DKA in pregnancy. With aggressive insulin and resuscitation, hyperglycemia and acidosis improve rapidly. With current treatment, good perinatal outcomes can be expected.","subset":"pubmed_abstract"} +{"meta":{"pmid":458425,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Modulation by centrifugation of cell susceptibility to chlamydial infection.\nEnhancement of chlamydial infection of cell monolayers by centrifugation was shown to depend on induced cell surface changes. Evidence for this came from analysis of two forms of organism attachment which take place during centrifugation. In 'productive binding', organisms attached to cells and then entered and infected them. In 'unproductive binding', organisms became attached to cells but were not ingested. These organisms could be stripped from the cells by treatment with trypsin and could then infect fresh monolayers. Measurement of attachment kinetics during centrifugation showed that cells passed through three different susceptibility states. Only productive binding occurred in the first 20 min; cells then entered a refractory state during which no attachment took place At about 45 min, attachment recommenced but this allowed only unproductive binding. Induced movement of cell surface structures may enhance infection by promoting specific or non-specific interactions. Failure of ingestion may result from insufficient cell 'receptors' for circumferential binding of the whole chlamydial surface so that engulfment cannot take place.","subset":"pubmed_abstract"} +{"meta":{"pmid":26962158,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":13}}},"text":"Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment.\nThe vast majority of ovarian cancer-related deaths are caused by metastatic dissemination of tumor cells, resulting in subsequent organ failure. However, despite our increased understanding of the physiological processes involved in tumor metastasis, there are no clinically approved drugs that have made a major impact in increasing the overall survival of patients with advanced, metastatic ovarian cancer. We identified prosaposin (psap) as a potent inhibitor of tumor metastasis, which acts via stimulation of p53 and the antitumorigenic protein thrombospondin-1 (TSP-1) in bone marrow-derived cells that are recruited to metastatic sites. We report that more than 97% of human serous ovarian tumors tested express CD36, the receptor that mediates the proapoptotic activity of TSP-1. Accordingly, we sought to determine whether a peptide derived from psap would be effective in treating this form of ovarian cancer. To that end, we developed a cyclic peptide with drug-like properties derived from the active sequence in psap. The cyclic psap peptide promoted tumor regression in a patient-derived tumor xenograft model of metastatic ovarian cancer. Thus, we hypothesize that a therapeutic agent based on this psap peptide would have efficacy in treating patients with metastatic ovarian cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":32358459,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Effect of Athletic Chest Protectors on the Performance of Manual and Mechanical CPR: A Simulation Study.\nSudden cardiac arrest is a leading cause of death in athletes. Although athletes wear various athletic chest protectors (ACPs) to prevent commotio cordis (CC), cardiac arrest cases still occur. Although it is established that cardiopulmonary resuscitation (CPR) quality affects outcome, little research has evaluated the effect of ACPs on CPR compressions quality. This study aimed to observe whether: (1) ACPs impact depth, rate, and hand positioning of both bystander and LUCAS CPR. (2) LUCAS devices affect CPR performance compared with traditional compressions. An observational, prospective, convenient sample of 26 emergency medicine residents performed CPR on a high-fidelity Laerdal mannequin, which recorded real-time performance data. Baseline CPR for 1- and 2-minute cycles, CPR on a mannequin wearing the ACP, and ACP removal time was recorded. LUCAS CPR performance was measured at baseline and over the ACP. Bystander CPR had a statistically significant difference in both hand placement and compression rate for baseline versus ACP compressions (85% vs 57%, P < 0.05; 138 vs 142, P < 0.05, respectively), but not in compression depth (51.08 vs 50.05 mm, P = 0.39). LUCAS CPR had no significant difference in CPR performance. Bystander versus LUCAS CPR had a significant difference in compression rate (138 vs 101, P < 0.01), but not in depth or hand placement. Athletic chest protectors significantly impacted hand placement during bystander CPR, which may diminish CPR quality. Considering ACP removal required only 5.4 seconds, removing the ACP before standard CPR may improve quality.","subset":"pubmed_abstract"} +{"meta":{"pmid":32788572,"dup_signals":{"dup_doc_count":61,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":4,"2023-23":1,"2023-14":7,"2023-06":4,"2022-49":1,"2022-40":2,"2022-27":2,"2022-21":3,"2022-05":4,"2021-49":3,"2021-43":2,"2021-39":2,"2021-31":4,"2021-21":2,"2021-17":2,"2021-10":2,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":1,"2024-18":4,"2024-10":1,"2024-30":1}}},"text":"Reduced axonal caliber and structural changes in a rat model of Fragile X syndrome with a deletion of a K-Homology domain of Fmr1.\nFragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.","subset":"pubmed_abstract"} +{"meta":{"pmid":3652978,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-04":2,"2018-17":1,"2017-47":1,"2017-43":1,"2017-22":1,"2017-09":1,"2016-44":1,"2016-40":2,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1}}},"text":"The formation of the area centralis of the retinal ganglion cell layer in the chick.\nIn adult domestic chickens, the neurones in the retinal ganglion cell layer are very unevenly disposed such that there is a sixfold increase in neurone density from the retinal edge to the retinal centre. The formation of the high ganglion-cell-density area centralis was studied on chick retinal wholemounts from the 8th day of incubation (E8) to 4 weeks after hatching (4WAH). The density of viable neurones and the number and the distribution of pyknotic neurones in the ganglion cell layer were estimated across the whole retina. Between E8 and E10, the distribution of neurones in the ganglion cell layer was anisodensitic with 53,000 mm-2 in the centre compared to 34,000 mm-2 in the periphery of the retina. Thereafter, a progressively steeper gradient of neurone density developed, which decreased from 24,000 mm-2 in the retinal centre to 6000 mm-2 at the retinal periphery by 4WAH. Neuronal pyknosis in the ganglion cell layer was observed between E9 and E17. From E11 onwards, consistently more pyknotic neurones were found in the peripheral than in the central retina. It was estimated that over the period of cell death approximately twice as many neurones died per unit area in the retinal periphery than in the centre. Retinal area measurements and estimation of neurone densities in the ganglion cell layer after the period of neurone generation and neurone death indicated differential retinal expansion, with more expansion in the peripheral than in the central retina. These observations allow us to conclude that the formation of the area centralis of the chick retina involves (1) slightly higher cell generation in the retinal centre, (2) higher rate of cell loss in the retinal periphery and (3) differential retinal expansion.","subset":"pubmed_abstract"} +{"meta":{"pmid":31235969,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Post-traumatic Articular Cartilage Lesions Increase at Second-look Arthroscopy Following Primary Anterior Cruciate Ligament Reconstruction.\nAnterior cruciate ligament (ACL) reconstruction (ACLR) after ACL rupture improves the instability of the knee joint and decreases mechanical stress to the meniscus and articular cartilage. However, there are reports that post-traumatic osteoarthritis (PTOA) is observed over time following ACLR. In this study, we assessed changes in cartilage lesions by arthroscopic findings following anatomical double-bundle ACLR and at post-operative second-look arthroscopy about 14 months later. We retrospectively evaluated 37 knees in cases with patients <40 years of age who had undergone an anatomical double-bundle ACL reconstruction <1 year after ACL rupture injury from March 2012 to December 2016. Clinical results and arthroscopic cartilage\/meniscal lesion were evaluated and compared between a cartilage lesion-detected group and intact-cartilage group. Surgery improved anteroposterior laxity and other clinical measures; however, cartilage lesions were detected at 11 sites during ACLR and at 54 sites at second-look arthroscopy. The periods from injury to second-look arthroscopy and from ACLR to second-look arthroscopy were significantly longer in the cartilage-lesion group (n=23) than in the intact-cartilage group (n=14). Conversely, 96% of meniscal damage observed during ACLR was cured at the time of second-look arthroscopy. Knee articular cartilage lesions after ACL rupture cannot be completely suppressed, even using the anatomical ACL reconstruction technique. This study suggested that articular cartilage lesions can progress to a level that can be confirmed arthroscopically at approximately 17 months after ACL injury. Therefore, in ACLR patients, the possibility of developing knee articular cartilage lesions and PTOA should be considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":30568629,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":2,"2021-43":1,"2021-39":1,"2021-25":1,"2020-29":1,"2019-22":1,"2019-09":1,"2023-50":1,"2024-22":2,"2024-18":1}}},"text":"Postural Dynamics Are Associated With Cognitive Decline in Parkinson's Disease.\nEarly features of Parkinson's disease (PD) include both motor and cognitive changes, suggesting shared common pathways. A common motor dysfunction is postural instability, a known predictor of falls, which have a major impact on quality of life. Understanding mechanisms of postural dynamics in PD and specifically how they relate to cognitive changes is essential for developing effective interventions. The aims of this study were to examine the changes that occur in postural metrics over time and explore the relationship between postural and cognitive dysfunction. The study group consisted of 35 people (66 \u00b1 8years, 12 female, UPDRS III: 22.5 \u00b1 9.6) diagnosed with PD who were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation-PD Gait (ICICLE-GAIT) study. Postural and cognitive assessments were performed at 18, 36, and 54 months after enrolment. Participants stood still for 120 s, eyes open and arms by their side. Postural dynamics were measured using metrics derived from a single tri-axial accelerometer (Axivity AX3, York, UK) on the lower back. Accelerometry metrics included jerk (derivative of acceleration), root mean square, frequency, and ellipsis (acceleration area). Cognition was evaluated by neuropsychological tests including the Montreal Cognitive Assessment (MoCA) and digit span. There was a significant decrease in accelerometry parameters, greater in the anteroposterior direction, and a decline in cognitive function over time. Accelerometry metrics were positively correlated with lower cognitive function and increased geriatric depression score and negatively associated with a qualitative measure of balance confidence. In conclusion, people with PD showed reduced postural dynamics that may represent a postural safety strategy. Associations with cognitive function and depression, both symptoms that may pre-empt motor symptoms, suggest shared neural pathways. Further studies, involving neuroimaging, may determine how these postural parameters relate to underlying neural and clinical correlates.","subset":"pubmed_abstract"} +{"meta":{"pmid":22962460,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":2,"2013-48":1,"unknown":10}}},"text":"Inferring duplications, losses, transfers and incomplete lineage sorting with nonbinary species trees.\nGene duplication (D), transfer (T), loss (L) and incomplete lineage sorting (I) are crucial to the evolution of gene families and the emergence of novel functions. The history of these events can be inferred via comparison of gene and species trees, a process called reconciliation, yet current reconciliation algorithms model only a subset of these evolutionary processes. We present an algorithm to reconcile a binary gene tree with a nonbinary species tree under a DTLI parsimony criterion. This is the first reconciliation algorithm to capture all four evolutionary processes driving tree incongruence and the first to reconcile non-binary species trees with a transfer model. Our algorithm infers all optimal solutions and reports complete, temporally feasible event histories, giving the gene and species lineages in which each event occurred. It is fixed-parameter tractable, with polytime complexity when the maximum species outdegree is fixed. Application of our algorithms to prokaryotic and eukaryotic data show that use of an incomplete event model has substantial impact on the events inferred and resulting biological conclusions. Our algorithms have been implemented in Notung, a freely available phylogenetic reconciliation software package, available at http:\/\/www.cs.cmu.edu\/~durand\/Notung. firstname.lastname@example.com.","subset":"pubmed_abstract"} +{"meta":{"pmid":15800937,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease.\nWe completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg\/day) and 12 weeks (200 mg\/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":23588937,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Race, ethnicity, and disease outcomes in juvenile idiopathic arthritis: a cross-sectional analysis of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.\nTo measure the associations between self-reported race and ethnicity and disease outcomes, including joint damage, pain, and functional ability, in children with juvenile idiopathic arthritis (JIA). A cross-sectional analysis of children with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between May 2010 and March 2012. Mann-Whitney U test and chi-square testing were used to compare patient characteristics between race (white, African American, or Asian) and ethnicity (Non-Hispanic and Non-Latino; Hispanic or Latino) categories. Logistic regression was used to measure the associations between each race or ethnicity category and the outcome of interest. Race category was available for 4292 of 4682 children (93% white, 5% African American, Asian 3%). Ethnicity data were available for 4644 (11% Hispanic or Latino). African American children with polyarticular-course JIA had an elevated OR for joint damage on radiographic imaging compared to white children (OR 1.9, 95% CI 1.0-3.1; p = 0.04). Hispanic\/Latino children had increased odds of having disability scores > 75th percentile (OR 1.5, 95% CI 1.1-2.1; p < 0.01) compared to non-Hispanic\/Latino children; however, these odds were no longer significant when the cohort was limited to children with polyarticular-course JIA. Asian children had decreased odds of higher pain and functional disability compared to white children (p < 0.05). Race and ethnicity were variably associated with joint damage, pain, and functional ability. Understanding outcome variation between different race and ethnicity groups may help to optimize care for children with JIA.","subset":"pubmed_abstract"} +{"meta":{"pmid":26752394,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"\"She Just Doesn't Know Him Like We Do\": Illuminating Complexities in Surrogate Decision Making.\nWhen patients are not able to speak for themselves, surrogate decision makers are asked to guide treatment decisions and formulate a plan of care in accordance with what the patients would have wanted. This necessitates an exploration into the patients' views about life and how it should be lived, how the patients constructed their identity or life story, and their attitudes towards sickness and suffering. When an individual appoints a surrogate, such as a healthcare power of attorney, a common presumption is that this designation evinces merit. This obscures the possibility of multiple other considerations that influence individual choice. This article presents a clinical case in which the claim to know someone best created a controversy that brought treatment decisions to a standstill. Further, it illuminates how the question, \"Given the current medical condition, what would this person want?\" risks presuming that a singular, unambiguous preference exists and that one person can provide the answer. Clinical ethicists can play a vital role in situations when there is a dispute among a designated surrogate and family members over a patient's preference. By embracing the complexity of the desire to synthesize seemingly irreconcilable perspectives about identity, uncovering the reasons that underlie disagreement, and guiding inquiry in such a way that allows stakeholders to move beyond the conflict, clinical ethicists can facilitate decision making that honors the patient and may mitigate moral distress.","subset":"pubmed_abstract"} +{"meta":{"pmid":23020030,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"A model to account for variations in holm-oak (Quercus ilex subsp. ballota) acorn production in southern Spain.\nOne of the characteristics of holm-oak acorn production is its high variability among individuals and years. To examine the main causes of this fact, a study was conducted from 1998-2010 in a natural area of holm-oak in southern Spain, where floral phenology, fruit production, fruit size, airborne pollen emission and meteorology factors were analyzed with the ultimate aim of developing a model for forecasting holm-oak yield. Pollen emission during flowering season was the main factor determining the final acorn harvest, but also some meteorological variables played an important role in explaining acorn crop variations, especially humidity and temperature during the months of April and September. The reliability of the proposed model was externally validated using data not included in its construction; validation yielded acceptable results, with a minimum error of estimation. Our results appear to be very useful for planning cropping and pig feeding strategies. Further research could extend the use of airborne pollen counts in forest studies relating to anemophilous species, in order to optimize agricultural policies.","subset":"pubmed_abstract"} +{"meta":{"pmid":18304487,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Dynamic ensemble odor coding in the mammalian olfactory bulb: sensory information at different timescales.\nNeural firing discharges are often temporally patterned, but it is often ambiguous as to whether the temporal features of these patterns constitute a useful code. Here we show in the mouse olfactory bulb that ensembles of projection neurons respond with complex odor- and concentration-specific dynamic activity sequences developing below and above sniffing frequency. Based on this activity, almost optimal discrimination of presented odors was possible during single sniffs, consistent with reported behavioral data. Within a sniff cycle, slower features of the dynamics alone (>100 ms resolution, including mean firing rate) were sufficient for maximal discrimination. A smaller amount of information was also observed in faster features down to 20-40 ms resolution. Therefore, mitral cell ensemble activity contains information at different timescales that could be separately or complementarily exploited by downstream brain centers to make odor discriminations. Our results also support suggestive analogies in the dynamics of odor representations between insects and mammals.","subset":"pubmed_abstract"} +{"meta":{"pmid":32815251,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"ZnO\/Nanocarbons-Modified Fibrous Scaffolds for Stem Cell-Based Osteogenic Differentiation.\nCurrently, mesenchymal stem cells (MSCs)-based therapies for bone regeneration and treatments have gained significant attention in clinical research. Though many chemical and physical cues which influence the osteogenic differentiation of MSCs have been explored, scaffolds combining the benefits of Zn2+ ions and unique nanostructures may become an ideal interface to enhance osteogenic and anti-infective capabilities simultaneously. In this work, motivated by the enormous advantages of Zn-based metal-organic framework-derived nanocarbons, C-ZnO nanocarbons-modified fibrous scaffolds for stem cell-based osteogenic differentiation are constructed. The modified scaffolds show enhanced expression of alkaline phosphatase, bone sialoprotein, vinculin, and a larger cell spreading area. Meanwhile, the caging of ZnO nanoparticles can allow the slow release of Zn2+ ions, which not only activate various signaling pathways to guide osteogenic differentiation but also prevent the potential bacterial infection of implantable scaffolds. Overall, this study may provide new insight for designing stem cell-based nanostructured fibrous scaffolds with simultaneously enhanced osteogenic and anti-infective capabilities.","subset":"pubmed_abstract"} +{"meta":{"pmid":9512461,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Evolution of alanine:glyoxylate aminotransferase intracellular targeting: structural and functional analysis of the guinea pig gene.\nThe distribution of alanine:glyoxylate aminotransferase 1 (AGT) within liver cells has changed many times during mammalian evolution. Depending on the particular species, AGT can be found in mitochondria or peroxisomes, or mitochondria and peroxisomes. In some cases significant cytosolic AGT is also present. In the livers of most rodents, AGT has what is thought to be the more 'ancestral' distribution (i.e. mitochondrial and peroxisomal). However, AGT is distributed very differently in the guinea pig, being peroxisomal and cytosolic. In this study, we have attempted to determine the molecular basis for the loss of mitochondrial AGT targeting and the apparent inefficiency of peroxisomal targeting of AGT in the guinea pig. Our results show that the former is owing to the evolutionary loss of the more 5' of two potential transcription and translation initiation sites, resulting in the loss of the ancestral N-terminal mitochondrial targeting sequence from the open reading frame. Guinea pig AGT is targeted to peroxisomes via the peroxisomal targeting sequence type 1 (PTS1) peroxisomal import machinery, even though its C-terminal tripeptide, HRL, deviates from the standard consensus PTS1 motif. Although HRL appears to target AGT to peroxisomes less efficiently than the classical PTS1 SKL, the main reason for the low efficiency of AGT peroxisomal targeting in guinea pig cells (compared with cells from other species) lies not with guinea pig AGT but with some other, as yet undefined, part of the guinea pig peroxisomal import machinery.","subset":"pubmed_abstract"} +{"meta":{"pmid":24474278,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2022-27":1,"2021-43":1,"2021-25":1,"2020-24":1,"2020-16":2,"2019-43":1,"2019-26":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2023-50":1}}},"text":"Knockdown of both p120 catenin and Kaiso promotes expansion of human corneal endothelial monolayers via RhoA-ROCK-noncanonical BMP-NF\u03baB pathway.\nTo determine the signaling pathway involved in expanding contact-inhibited human corneal endothelial cells (HCECs) using p120 and Kaiso small interfering RNAs (siRNAs). Expansion of HCEC monolayers on collagen IV in SHEM using p120 siRNA was optimized regarding various dosage, frequency, and starting date before being added Kaiso siRNA or various inhibitors of Rho, ROCK, NF\u03baB, and TAK1. Phase contrast micrographs were used for monitoring cell shape, monolayer size, and cell density. Immunostaining was used to determine cytolocalization of BrdU, p120, pNFkB, F-actin, \u03b1-catenin, \u03b2-catenin, LEF1, Na+\/K+-ATPase, N-cadherin, ZO-1, and S100A4. Western blotting was used to determine the protein level of RhoA and RhoA-guanosine-5'-triphosphate (GTP). The HCEC monolayer size in diameter was expanded from 2.1 \u00b1 0.4 mm to 4.3 \u00b1 0.3 mm (P < 0.05) by increasing p120 siRNA from 40 nM to 100 nM starting at day 7, to 5.0 \u00b1 0.4 mm (P < 0.05) by adding 100 nM Kaiso siRNA, to 6.8 \u00b1 0.3 mm by using one-fourth corneoscleral rim (P < 0.05), and to 8.1 \u00b1 0.5 mm by using one-half corneoscleral rim (P < 0.05). Such proliferative effect required activation of RhoA-ROCK-noncanonical bone morphogenic protein (BMP) signaling and nuclear translocation of phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (pNF\u03baB). After withdrawal of siRNAs for 1 week, the resultant HCEC monolayer maintained a hexagonal shape, the average cell density of 2254 \u00b1 87 mm(2) (n = 3), and normal expression patterns of F-actin, \u03b1-catenin, \u03b2-catenin, N-cadherin, ZO-1, and Na+\/K+-ATPase without S100A4 and alpha-smooth muscle actin (\u03b1-SMA). The optimized knockdown with p120 and Kaiso siRNAs further expands the size of HCEC monolayers without endothelial mesenchymal transition (EMT) via selective activation of p120\/Kaiso signaling that requires the RhoA-ROCK-noncanonical BMP-NFkB signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":35118196,"dup_signals":{"dup_doc_count":21,"dup_dump_count":9,"dup_details":{"curated_sources":5,"2023-40":2,"2023-14":2,"2022-49":2,"2022-27":4,"2022-21":2,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Host Directed Therapies for Tuberculous Meningitis.\nA dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.","subset":"pubmed_abstract"} +{"meta":{"pmid":30583288,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Density-dependent enhanced replication of a densovirus in Wolbachia-infected Aedes cells is associated with production of piRNAs and higher virus-derived siRNAs.\nThe endosymbiotic bacterium Wolbachia pipientis has been shown to restrict a range of RNA viruses in Drosophila melanogaster and transinfected dengue mosquito, Aedes aegypti. Here, we show that Wolbachia infection enhances replication of Aedes albopictus densovirus (AalDNV-1), a single stranded DNA virus, in Aedes cell lines in a density-dependent manner. Analysis of previously produced small RNAs of Aag2 cells showed that Wolbachia-infected cells produced greater absolute abundance of virus-derived short interfering RNAs compared to uninfected cells. Additionally, we found production of virus-derived PIWI-like RNAs (vpiRNA) produced in response to AalDNV-1 infection. Nuclear fractions of Aag2 cells produced a primary vpiRNA signature U1 bias whereas the typical \"ping-pong\" signature (U1 - A10) was evident in vpiRNAs from the cytoplasmic fractions. This is the first report of the density-dependent enhancement of DNA viruses by Wolbachia. Further, we report the generation of vpiRNAs in a DNA virus-host interaction for the first time.","subset":"pubmed_abstract"} +{"meta":{"pmid":19496943,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":3,"2021-43":1,"2020-45":1,"2020-05":1,"2019-22":1,"2019-13":1,"2018-39":1,"2018-17":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2023-06":1,"2017-13":1}}},"text":"Effects of postgastric 13C-acetate processing on measurement of gastric emptying: a systematic investigation in health.\nUniform postgastric processing of the gastric emptying (GE) marker 13C-acetate (Ac) is an unverified assumption behind its widespread application to measure GE. This study assessed the postgastric processing of Ac administered by intraduodenal (i.d.) infusion simulating different physiological conditions. 13CO2 in breath was assessed in three groups of six volunteers after i.d. administration of A: Different caloric densities (0.75\/1.5\/3 kcal min(-1) in a 200 mL meal at constant 1 mg Ac min(-1) simulating a physiological range of nutrient delivery rates; B: different tracer delivery rates (0.5\/1.0\/2.5 mg Ac min(-1) simulating delayed, normal and increased GE; C1: a 500 mL meal resulting in same marker and caloric delivery compared to protocol A; C2: 50 mL water bolus injections of 12.5\/25\/50\/100 mg Ac and C3 bolus injections of 50 mg Ac in 50\/100\/200 mL water in randomized order. A: 13CO2 excretion was independent of caloric load (P = 0.59). B: The dynamic of 13CO2 excretion was modulated by tracer elimination which was in turn dependent on the speed of tracer delivery, i.e. with faster deliveries resulting in lower 13CO2 recovery during infusion (P < 0.001). C: Increasing Ac doses resulted in decreased 13CO2 recovery (P < 0.001) over the first hour. 13CO2 recovery kinetics was independent of the volume delivered. This study shows 13C-acetate absorption and metabolism is independent of the volume and caloric delivery of test meals. The 'lag' in estimates of GE derived from 13CO2 breath tests is due to a postgastric, dose-dependent delay to 13CO2 elimination. This can be corrected for in analytical derivations of GE parameters based on 13C-acetate breath test measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":12788880,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mutation of IVS2 -12A\/C>G in combination with 707-714delGAGACTAC in the CYP21 gene is caused by deletion of the C4-CYP21 repeat module with steroid 21-hydroxylase deficiency.\nMore than 90% of the cases of congenital adrenal hyperplasia are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed apparent gene conversion, from the neighboring CYP21P pseudogene. Among them, mutation of the aberrant splicing donor site of IVS2 -12A\/C>G at nucleotide (nt) 655 is believed to be a result derived from this mechanism and is the most prevalent case among all ethnic groups. However, mutation of 707-714delGAGACTAC rarely exists alone, although this locus is a distance of 53 nt away from IVS2 -12A\/C>G. From the molecular characterization of the mutation of IVS2 -12A\/C>G combined with 707-714delGAGACTAC in patients with congenital adrenal hyperplasia, we found that it appeared to be in a 3.2-rather than a 3.7-kb fragment generated by Taq I digestion in a PCR product of the CYP21 gene. Interestingly, the 5' end region of such a CYP21 haplotype had CYP21P-specific sequences. Our results indicate that the coexistence of these two mutations is caused by deletion of the CYP21P, XA, RP2, and C4B genes and intergenic recombination in the C4-CYP21 repeat module. Surprisingly, this kind of the haplotype of the mutated CYP21 gene has not been reported as a gene deletion.","subset":"pubmed_abstract"} +{"meta":{"pmid":16968563,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A nutrition odyssey: knowledge discovery, translation, and outreach. 2006 Ryley-Jeffs Memorial Lecture.\nThe 21st-century model of health research is founded on a broad base of multidisciplinary research that is expeditiously and effectively translated into evidence-based practice, education, policy, and advocacy. The key objective is to improve the health of populations. DIETITIANS' ROLES: Dietitians, whether they are working in clinical or public health nutrition or food science, have a vital role to play in this paradigm of health research. As dietitians' roles have evolved beyond the traditional ones into subspecialties including epidemiology, nutrigenomics, functional foods, nutraceuticals, toxicology, natural health products, and multidisciplinary research, the need for advanced training in subspecialty fields has become essential. A dietetics background is an excellent foundation upon which to develop a research career in one of these new areas of nutrition. Opportunities for personnel awards and research funding targeted at nutrition clinician-scientists and other nutrition subspecialists have grown tremendously in recent years. The information in this paper is intended to inspire dietitians seeking advanced academic training in one of the new exciting avenues for a career in nutrition. These avenues will permit dietitians to contribute to knowledge discovery, translation, and outreach to improve the nutritional status and health of populations in Canada and globally.","subset":"pubmed_abstract"} +{"meta":{"pmid":32257576,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Clipping versus coiling in unruptured anterior cerebral circulation aneurysms.\nUnruptured intracranial aneurysms (UIAs) are not uncommon, especially in Japan. Treatment strategy for UIAs has evolved in the past decades in Western countries with the increased use of endovascular treatment as the primary option, but in Japan, clipping still has the upper hand. This study retrospectively included 200 patients treated by clipping or coiling for UIAs located in the anterior cerebral circulation. Postoperative angiographic and clinical outcomes were evaluated. Of 200 UIAs, 147 and 53 were treated by surgery and coiling, respectively. The average follow-up duration was 30.2 \u00b1 18.8 months for clipping and 29.3 \u00b1 17.6 months for coiling. Complete occlusion was greater in the surgery group (78.9%) than the endovascular group (18.8%). Regrowth occurred in 1.4% of the clipping group and 13.2% of the coiling group. Ischemic events were encountered in both groups; asymptomatic ones were higher in the coiling group (24.5%) than in the clipping group (2%), while symptomatic ischemic complications were equal (7.5%) in both groups. The deterioration of modified Rankin scale was detected totally in 13 UIAs (6.5%) with no statistical difference between groups. Postoperative hospital period was longer in clipping (P = 0.01). Clipping and coiling were both safe and feasible in the treatment of unruptured aneurysms. The clipping was advantageous in durability, while the rate of morbidity was lower, and hospitalization period was shorter in the coiling group. The clipping and coiling should coexist while complementing each other by understanding the advantages and disadvantages of both.","subset":"pubmed_abstract"} +{"meta":{"pmid":24992851,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"A comparative evaluation of linear dimensional accuracy of the dies obtained using three conceptually different die systems in the fabrication of implant prosthesis: an in vitro study.\nGiven that meticulous implant prosthodontic procedures are recommended to obtain the best possible intraoral fit, the die systems used for multi implant casts warrant further investigation. Die stone expansion and errors introduced by removable die casts may exceed the accuracy required for the passive fit of implant prosthesis. The purpose of the study was to evaluate the linear dimensional accuracy between the implant master die and three conceptually different die systems such as Pindex system, Accu-trac precision die system, and Conventional brass dowel pin system. Thirty impressions of implant master die were made with polyether impression material. Ten experimental implant casts were fabricated for each of the three different die systems tested: Accu-trac precision die tray system, Pindex system, and conventional brass dowel pin system. The solid experimental casts were sectioned and then removed from the die system 30 times. Linear distances between all six possible distances were measured from one centre of the transfer coping to the other, using a co-ordinate measuring machine in millimeters up to accuracy of 0.5 microns. Data were tabulated and statistically analyzed by Binomial non parametric test using SPSS version 15. Significant differences were found for distance A-B (P = 0.002), A-C ( P = 0.002), A-D (P value = 0.002), and B-D ( P = 0.021) in Conventional Dowel pin system however for Accu-trac precision die tray system, it was significant only for distance A-D (P = 0.002) but for Pindex system it was non-significant for all the distances measured. Within the limitations of this study, use of Pindex system is recommended when sectioned dies are needed for a multi implant retained prosthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":33203120,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Injectable Gel Form of a Decellularized Bladder Induces Adipose-Derived Stem Cell Differentiation into Smooth Muscle Cells In Vitro.\nBiologic scaffolds composed of extracellular matrix components have been proposed to repair and reconstruct a variety of tissues in clinical and pre-clinical studies. Injectable gels can fill and conform any three-dimensional shape and can be delivered to sites of interest by minimally invasive techniques. In this study, a biological gel was produced from a decellularized porcine urinary bladder by enzymatic digestion with pepsin. The enzymatic digestion was confirmed by visual inspection after dissolution in phosphate-buffered saline solution and Fourier-transform infrared spectroscopy. The rheological and biological properties of the gel were characterized and compared to those of the MatrigelTM chosen as a reference material. The storage modulus G' reached 19.4 \u00b1 3.7 Pa for the 30 mg\/mL digested decellularized bladder gels after ca. 3 h at 37 \u00b0C. The results show that the gel formed of the porcine urinary bladder favored the spontaneous differentiation of human and rabbit adipose-derived stem cells in vitro into smooth muscle cells to the detriment of cell proliferation. The results support the potential of the developed injectable gel for tissue engineering applications to reconstruct for instance the detrusor muscle part of the human urinary bladder.","subset":"pubmed_abstract"} +{"meta":{"pmid":29249501,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":13}}},"text":"Predictors of survival in octogenarians after mitral valve surgery for degenerative disease: The Mitral Surgery in Octogenarians study.\nAn increasing number of octogenarians are referred to undergo mitral valve surgery for degenerative disease, and percutaneous approaches are being increasingly used in this subgroup of patients. We sought to determine the survival and its predictors after Mitral Valve Surgery in Octogenarians (MiSO) in a multicenter UK study of high-volume specialized centers. Pooled data from 3 centers were collected retrospectively. To identify the predictors of short-term composite outcome of 30 days mortality, acute kidney injury, and cerebrovascular accident, a multivariable logistic regression model was developed. Multiple Cox regression analysis was performed for late mortality. Kaplan-Meier curves were generated for long-term survival in various subsets of patients. Receiver operating characteristic analysis was done to determine the predictive power of the logistic European System for Cardiac Operative Risk Evaluation. A total of 247 patients were included in the study. The median follow-up was 2.9 years (minimum 0, maximum 14 years). A total of 150 patients (60.7%) underwent mitral valve repair, and 97 patients (39.3%) underwent mitral valve replacement. Apart from redo cardiac surgery (mitral valve repair 6 [4%] vs mitral valve replacement 11 [11.3%], P = .04) and preoperative atrial fibrillation (mitral valve repair 79 [52.6%] vs mitral valve replacement 34 [35.1%], P < .01), there was no significant difference in terms of any other preoperative characteristics between the 2 groups. Patient operative risk, as estimated by logistic European System for Cardiac Operative Risk Evaluation, was lower in the mitral valve repair group (10.2 \u00b1 11.8 vs 13.7 \u00b1 15.2 in mitral valve replacement; P = .07). No difference was found between groups for duration of cardiopulmonary bypass and aortic crossclamp times. The 30-day mortality for the whole cohort was 13.8% (mitral valve repair 4.7% vs mitral valve replacement 18.6%; P < .01). No differences were found in terms of postoperative cerebrovascular accident (2% vs 3.1%; P = .9), acute kidney injury requiring dialysis (6.7% vs 13.4%; P = .12), and superficial or deep sternal wound infection (10% vs 16.5%, P = .17; 2% vs 3.1%, P = .67, respectively). The final multiple regression model for short-term composite outcome included previous cardiac surgery (odds ratio [OR], 4.47; 95% confidence interval [CI], 1.37-17.46; P = .02), intra-aortic balloon pump use (OR, 4.77; 95% CI, 1.67-15.79; P < .01), and mitral valve replacement (OR, 7.7; 95% CI, 4.04-14.9; P < .01). Overall survival for the entire cohort at 1, 5, and 10 years was 82.4%, 63.7%, and 45.5% (mitral valve repair vs mitral valve replacement: 89.9% vs 70.7% at 1 year, 69.6% vs 54% at 5 years, and 51.8% vs 35.5% at 10 years; P = .0005). Cox proportional hazard model results showed mitral valve replacement (hazard ratio, 1.88; 95% CI, 1.22-2.89; P < .01) and intra-aortic balloon pump use (hazard ratio, 2.54; 95% CI, 1.26-5.13; P < .01) to be independent predictor factors affecting long-term survival. Logistic European System for Cardiac Operative Risk Evaluation did not perform well in predicting early mortality (area under the curve, 0.57%). In octogenarians, mitral valve repair for degenerative disease is associated with good survival and remains the gold standard, whereas mitral valve replacement is still associated with significant mortality. Logistic European System for Cardiac Operative Risk Evaluation was unable to predict early mortality in our cohort of patients. Larger international multicenter registries are required to optimize the decision-making process in such a high-risk subgroup.","subset":"pubmed_abstract"} +{"meta":{"pmid":30939346,"dup_signals":{"dup_doc_count":16,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2020-24":6,"2020-16":2,"2020-10":1,"2019-43":2,"2019-39":1,"2022-05":1,"2024-26":1}}},"text":"Gemini surfactants as efficient dispersants of multiwalled carbon nanotubes: Interplay of molecular parameters on nanotube dispersibility and debundling.\nSurfactants have been widely employed to debundle, disperse and stabilize carbon nanotubes in aqueous solvents. Yet, a thorough understanding of the dispersing mechanisms at molecular level is still warranted. Herein, we investigated the influence of the molecular structure of gemini surfactants on the dispersibility of multiwalled carbon nanotubes (MWNTs). We used dicationic n-s-n gemini surfactants, varying n and s, the number of alkyl tail and alkyl spacer carbons, respectively; for comparisons, single-tailed surfactant homologues were also studied. Detailed curves of dispersed MWNT concentration vs. surfactant concentration were obtained through a stringently controlled experimental procedure, allowing for molecular insight. The gemini are found to be much more efficient dispersants than their single-tailed homologues, i.e. lower surfactant concentration is needed to attain the maximum dispersed MWNT concentration. In general, the spacer length has a comparatively higher influence on the dispersing efficiency than the tail length. Further, scanning electron microscopy imaging shows a sizeable degree of MWNT debundling by the gemini surfactants in the obtained dispersions. Our observations also point to an adsorption process that does not entail the formation of micelle-like aggregates on the nanotube surface, but rather coverage by individual molecules, among which the ones that seem to be able to adapt best to the nanotube surface provide the highest efficiency. These studies are relevant for the rational design and choice of optimal dispersants for carbon nanomaterials and other similarly water-insoluble materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":31064329,"dup_signals":{"dup_doc_count":15}},"text":"\"If we miss this chance, it's futile later on\" - late antenatal booking and its determinants in Bhutan: a mixed-methods study.\nTo achieve the Sustainable Development Goal related to maternal and neonatal outcomes, the World Health Organization advocates for a first antenatal care (ANC) contact before 12 weeks of gestation. In order to guide interventions to achieve early ANC in the lower middle-income setting of Bhutan, we conducted an assessment of the magnitude and determinants of late ANC in this context. This was a mixed-methods study with quantitative (cross-sectional study) and qualitative (in-depth interviews with pregnant women and ANC providers) component in a concurrent triangulation design. The quantitative component retrospectively analysed the socio-demographic and clinical characteristics, and the gestational age at booking of women who were provided care for delivery or miscarriages at the three tertiary hospitals in Bhutan from May-August 2018. The qualitative component involved thematic analysis of in-depth interviews with ten women attending ANC visits and four healthcare workers involved in ANC provision. Among 868 women studied, 67% (n = 584) had a late booking (after 12 weeks), and 1% (n = 13) had no booking. Women with only primary education and those residing in rural areas were more likely to have a late first ANC booking. While many women achieved the recommended eight ANC visits, this did not necessarily reflect early booking. Late booking was common among multigravida women. The interviews illustrated a general understanding and recognition of the importance of early ANC. Support from peers, family and co-workers, and male participation in accessing ANC were seen as enablers. The outreach clinics (ORCs) at the primary healthcare level were an important means of reaching the ANC services to women in rural areas where geographical accessibility was a barrier. Specific barriers to early ANC were gender insensitivity in providing care through male health workers, cost\/time in ANC visits, and the inability to produce the documents of the father for booking ANC. Late ANC booking was common in Bhutan, and appeared to be associated with educational, geographic, socio-cultural and administrative characteristics. A comprehensive information package on ANC needs to be developed for pregnant mothers, and the quality of ANC coverage needs to be measured in terms of early ANC booking.","subset":"pubmed_abstract"} +{"meta":{"pmid":10794718,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"JNK (c-Jun N-terminal kinase) and p38 activation in receptor-mediated and chemically-induced apoptosis of T-cells: differential requirements for caspase activation.\nActivation of the stress-activated mitogen-activated protein kinases (MAP kinases), c-Jun N-terminal kinase (JNK) and p38, is necessary for the induction of apoptosis in neuronal cells; however, in other cell types their involvement may be stimulus-dependent. In the present study we investigate the activation of JNK and p38 in a single non-neuronal cell type, undergoing receptor-mediated (tumour necrosis factor-related apoptosis-inducing ligand and CD95) or chemically-induced (lactacystin) apoptosis. In Jurkat T-cells, receptor-mediated and chemically-induced apoptosis resulted in a time-dependent activation of the initiator caspases-8 and -9, respectively. Both types of stimuli resulted in a significant activation of JNK and p38, which closely paralleled the time-dependent induction of apoptosis. The caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (z-VAD.FMK) inhibited receptor-mediated apoptosis and suppressed JNK and p38 activation. In contrast, inhibition of lactacystin-induced apoptosis with z-VAD.FMK, as assessed by phosphatidylserine exposure and poly(ADP-ribose) polymerase cleavage, did not inhibit activation of JNK or p38, demonstrating that during chemically-induced apoptosis, activation of JNK and p38 is independent of effector caspases. The role of p38 in apoptosis was assessed using the specific p38 inhibitor, SB203580. No effect on the induction of apoptosis or caspase activation was observed, although activation of mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK-2), an immediate downstream target of p38, was inhibited. Therefore neither p38 activation nor activation of MAPKAPK-2 is critical for induction of either receptor- or chemically-induced apoptosis. Thus, within a single cell type, (1) the mechanism of p38 and JNK activation during apoptosis is stimulus-dependent and (2) activation of the p38 pathway is not required for caspase activation or apoptosis, assessed by phosphatidylserine exposure, but may still be required to elicit other features of the apoptotic phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":29136014,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Treatment guidelines and early loss from care for people living with HIV in Cape Town, South Africa: A retrospective cohort study.\nSouth Africa has undergone multiple expansions in antiretroviral therapy (ART) eligibility from an initial CD4+ threshold of \u2264200 cells\/\u03bcl to providing ART for all people living with HIV (PLWH) as of September 2016. We evaluated the association of programmatic changes in ART eligibility with loss from care, both prior to ART initiation and within the first 16 weeks of starting treatment, during a period of programmatic expansion to ART treatment at CD4+ \u2264 350 cells\/\u03bcl. We performed a retrospective cohort study of 4,025 treatment-eligible, non-pregnant PLWH accessing care in a community health center in Gugulethu Township affiliated with the Desmond Tutu HIV Centre in Cape Town. The median age of participants was 34 years (IQR 28-41 years), almost 62% were female, and the median CD4+ count was 173 cells\/\u03bcl (IQR 92-254 cells\/\u03bcl). Participants were stratified into 2 cohorts: an early cohort, enrolled into care at the health center from 1 January 2009 to 31 August 2011, when guidelines mandated that ART initiation required CD4+ \u2264 200 cells\/\u03bcl, pregnancy, advanced clinical symptoms (World Health Organization [WHO] stage 4), or comorbidity (active tuberculosis); and a later cohort, enrolled into care from 1 September 2011 to 31 December 2013, when the treatment threshold had been expanded to CD4+ \u2264 350 cells\/\u03bcl. Demographic and clinical factors were compared before and after the policy change using chi-squared tests to identify potentially confounding covariates, and logistic regression models were used to estimate the risk of pre-treatment (pre-ART) loss from care and early loss within the first 16 weeks on treatment, adjusting for age, baseline CD4+, and WHO stage. Compared with participants in the later cohort, participants in the earlier cohort had significantly more advanced disease: median CD4+ 146 cells\/\u03bcl versus 214 cells\/\u03bcl (p < 0.001), 61.1% WHO stage 3\/4 disease versus 42.8% (p < 0.001), and pre-ART mortality of 34.2% versus 16.7% (p < 0.001). In total, 385 ART-eligible PLWH (9.6%) failed to initiate ART, of whom 25.7% died before ever starting treatment. Of the 3,640 people who started treatment, 58 (1.6%) died within the first 16 weeks in care, and an additional 644 (17.7%) were lost from care within 16 weeks of starting ART. PLWH who did start treatment in the later cohort were significantly more likely to discontinue care in <16 weeks (19.8% versus 15.8%, p = 0.002). After controlling for baseline CD4+, WHO stage, and age, this effect remained significant (adjusted odds ratio [aOR] = 1.30, 95% CI 1.09-1.55). As such, it remains unclear if early attrition from care was due to a \"healthy cohort\" effect or to overcrowding as programs expanded to accommodate the broader guidelines for treatment. Our findings were limited by a lack of generalizability (given that these data were from a single high-volume site where testing and treatment were available) and an inability to formally investigate the effect of crowding on the main outcome. Over one-quarter of this ART-eligible cohort did not achieve the long-term benefits of treatment due to early mortality, ART non-initiation, or early ART discontinuation. Those who started treatment in the later cohort appeared to be more likely to discontinue care early, and this outcome appeared to be independent of CD4+ count or WHO stage. Future interventions should focus on those most at risk for early loss from care as programs continue to expand in South Africa.","subset":"pubmed_abstract"} +{"meta":{"pmid":22179651,"dup_signals":{"dup_doc_count":23,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2020-45":1,"2018-22":1,"2018-17":1,"2018-09":1,"2017-51":2,"2017-43":1,"2017-34":1,"2017-30":2,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-43":1,"2017-13":2}}},"text":"An integrated approach for urban water quality assessment.\nThis paper introduces an integrated approach for the assessment of receiving water quality and the relative contribution of the urban drainage system to perceived receiving water quality problems. The approach combines mass balances with relatively simple receiving water impact models. The research project has learned that the urban drainage system is only one of the determining factors with respect to receiving urban water quality problems. The morphology of the receiving waters and the non-sewer sources of pollution, such as waterbirds, dogs, or inflow of external surface water might be equally important. This conclusion underlines the necessity to changes today's emission based approach and adopt an integral and immission based approach. The integrated approach is illustrated on a case study in Arnhem, where the receiving water quality remained unsatisfactory even after retrofitting a combined sewer system into a separated sewer system.","subset":"pubmed_abstract"} +{"meta":{"pmid":17671843,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":12}}},"text":"Cross-species chromosome painting among camel, cattle, pig and human: further insights into the putative Cetartiodactyla ancestral karyotype.\nThe great karyotypic differences between camel, cattle and pig, three important domestic animals, have been a challenge for comparative cytogenetic studies based on conventional cytogenetic approaches. To construct a genome-wide comparative chromosome map among these artiodactyls, we made a set of chromosome painting probes from the dromedary camel (Camelus dromedarius) by flow sorting and degenerate oligonucleotide primed-PCR. The painting probes were first used to characterize the karyotypes of the dromedary camel (C. dromedarius), the Bactrian camel (C. bactrianus), the guanaco (Lama guanicoe), the alpaca (L. pacos) and dromedary x guanaco hybrid karyotypes (all with 2n = 74). These FISH experiments enabled the establishment of a high-resolution GTG-banded karyotype, together with chromosome nomenclature and idiogram for C. dromedarius, and revealed that these camelid species have almost identical karyotypes, with only slight variations in the amount and distribution patterns of heterochromatin. Further cross-species chromosome painting between camel, cattle, pig and human with painting probes from the camel and human led to the establishment of genome-wide comparative maps. Between human and camel, pig and camel, and cattle and camel 47, 53 and 53 autosomal conserved segments were detected, respectively. Integrated analysis with previously published comparative maps of human\/pig\/cattle enabled us to propose a Cetartiodactyla ancestral karyotype and to discuss the early karyotype evolution of Cetartiodactyla. Furthermore, these maps will facilitate the positional cloning of genes by aiding the cross-species transfer of mapping information.","subset":"pubmed_abstract"} +{"meta":{"pmid":9334919,"dup_signals":{"dup_doc_count":31,"dup_details":{"curated_sources":2,"unknown":29}}},"text":"The limits of social learning: translating analysis into action.\nIn what respects does public-policy making reflect social learning, drawing lessons from previous experiences and from the experiences of governments in other settings? Starting with an examination of the effect of policy legacies on current policy making, I present a process model of social learning embedded within the larger policy-making process resting at the intersection of the nation's constitutional context, technological change, and political influences exogenous to social learning. The model first distinguishes between the structural and the social learning effects of policy legacies. I then conceptually divide social learning into separate streams of substantive learning and situational learning. The effect that each of these has on policy making depends on the relative position of three categories of participants in the policy-making process (experts, organized interests, and politicians), as well as on the scope of the policy issue being considered (ranging from routine change to major reform). This analysis, with reference to recent health care policy making, reveals the full extent to which social learning is often a decidedly political struggle over ideas and information in which advocates promote lessons that severe their specific interests within a given institutional context and political setting. I consider the implications of social learning for understanding likely policy responses to the rise of market forces in health care.","subset":"pubmed_abstract"} +{"meta":{"pmid":37815076,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"Effects of Genes, Lifestyles, and Noise Kurtosis on Noise-Induced Hearing Loss.\nTo explore the association of lifestyles, caspase gene (CASP), and noise kurtosis with noise-induced hearing loss (NIHL). Three hundred seven NIHL individuals and 307 matched controls from factories in Chinese factories participated in this case-control study. Age, sex, noise exposure, exfoliated oral mucosa cells, and lifestyles of participants were gathered by the authors. The single nucleotide polymorphisms (SNPs) were genotyped using the Kompetitive Allele Specific polymerase chain reaction (KASP) method. The risk of NIHL was higher for people who worked in the complex noise environment than for people exposed to steady noise environment (adjusted: OR = 1.806, P = 0.002). Smoking and regular earphone use increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038). The GG genotype of the recessive model and G allele in rs1049216, together with the TT genotype of the recessive model in rs6948 decreased the NIHL risk (adjusted: OR = 0.659, P = 0.017). Oppositely, the AA genotype of additive model in rs12415607 had a higher NIHL risk (adjusted: OR = 1.804, P = 0.024). In the additive models, there was a positive interaction between noise kurtosis and CASP3 polymorphisms (RERI = 1.294, P = 0.013; RERI = 1.198, P = 0.031). Noise kurtosis, three SNPs (rs1049216, rs6948, and rs12415607), smoking and earphone use were found to be related to NIHL, and there was a positive interaction between noise kurtosis and CASP3. Results from this study can be used to prevent and detect NIHL and for genetic testing.","subset":"pubmed_abstract"} +{"meta":{"pmid":9258567,"dup_signals":{"dup_doc_count":12}},"text":"The association of respiratory problems in a community sample with self-reported chemical intolerance.\nThis epidemiological study evaluated respiratory histories in those individuals reporting chemical intolerance (CI) in a community population sample. The subsample of 181 completed standard Respiratory Health Questionnaires. CI was determined from self-ratings of feeling 'moderately' to 'severely' ill from exposure to at least three of five common chemicals (paint, pesticides, car exhaust, new carpet, and perfume); the prevalence rate was 22.7%. The comparison group (CN) (31.5% of the sample) were selected from their reports of 'never' feeling ill from the same chemicals. The prevalence rate of CI in females was over twice that in males (28% vs 12.9%), a significant difference. There were no significant differences in smoking, age, or education between CI and CN. Prevalence rates for symptoms and Relative Risk Ratios (RR) indicated that the CI were significantly more likely to report chronic cough, phlegm, wheeze, chest tightness, exertional dyspnea, acute respiratory illnesses, hay fever, child respiratory trouble, and physician confirmed asthma. Several of these respiratory symptoms were significantly, though differentially, related to 'current' asthma and hay fever reports. Results suggest a potential vulnerability to and greater interference from respiratory illness for the CI, which have implications for women's health and quality of life.","subset":"pubmed_abstract"} +{"meta":{"pmid":29217962,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Spectrophotometric Evaluation of Crown Fragment a Year After Reattachment Using Fiber-Reinforced Post: A Case Report.\nCrown fracture is the most common type of fracture and frequently affects the anterior teeth. Crown fractures have been treated in several ways depending on the location and kind of fracture. This case emphasizes reattachment of fractured fragments using fiber-reinforced post. Also this case report underlines the related aesthetic concerns of reattaching of the fractured fragment. Intraorally, examination revealed a complicated crown-root fracture of the left maxillary central (#21) and lateral incisor (#22). Moreover, the incisal one-third of the right maxillary central incisor (#11) was fractured. Baseline color of the tooth was recorded with a spectrophotometer to compare final color of tooth treated with fiber post. The root canal of 21 and 22 was filled with a sealer and gutta-percha. Then, the fiber-reinforced post was placed into the canals, and fractured segments were bonded with self-adhesive resin cement. Direct composite resin restoration was applied to 11. A year later, a second color measurement was recorded, and color differences (\u0394E) were calculated. In 12 months' follow-up, 11, 21 and 22 were asymptomatic with satisfying aesthetics, maxillar right incisor was vital. When crown discoloration was examined, there was clinically perceptible but acceptable discoloration without periapical pathology. Fiber reinforced post empowers not only the protection and reinforcement of tooth structure but also provides esthetic restoration.","subset":"pubmed_abstract"} +{"meta":{"pmid":27912012,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Coast-wide recruitment dynamics of Olympia oysters reveal limited synchrony and multiple predictors of failure.\nRecruitment of new propagules into a population can be a critical determinant of adult density. We examined recruitment dynamics in the Olympia oyster (Ostrea lurida), a species occurring almost entirely in estuaries. We investigated spatial scales of interannual synchrony across 37 sites in eight estuaries along 2,500 km of Pacific North American coastline, predicting that high vs. low recruitment years would coincide among neighboring estuaries due to shared exposure to regional oceanographic factors. Such synchrony in recruitment has been found for many marine species and some migratory estuarine species, but has never been examined across estuaries in a species that can complete its entire life cycle within the same estuary. To inform ongoing restoration efforts for Olympia oysters, which have declined in abundance in many estuaries, we also investigated predictors of recruitment failure. We found striking contrasts in absolute recruitment rate and frequency of recruitment failure among sites, estuaries, and years. Although we found a positive relationship between upwelling and recruitment, there was little evidence of synchrony in recruitment among estuaries along the coast, and only limited synchrony of sites within estuaries, suggesting recruitment rates are affected more strongly by local dynamics within estuaries than by regional oceanographic factors operating at scales encompassing multiple estuaries. This highlights the importance of local wetland and watershed management for the demography of oysters, and perhaps other species that can complete their entire life cycle within estuaries. Estuaries with more homogeneous environmental conditions had greater synchrony among sites, and this led to the potential for estuary-wide failure when all sites had no recruitment in the same year. Environmental heterogeneity within estuaries may thus buffer against estuary-wide recruitment failure, analogous to the portfolio effect for diversity. Recruitment failure was correlated with lower summer water temperature, higher winter salinity, and shorter residence time: all indicators of stronger marine influence on estuaries. Recruitment failure was also more common in estuaries with limited networks of nearby adult oysters. Large existing oyster networks are thus of high conservation value, while estuaries that lack them would benefit from restoration efforts to increase the extent and connectivity of sites supporting oysters.","subset":"pubmed_abstract"} +{"meta":{"pmid":17661589,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":16}}},"text":"Severity of mastitis symptoms as a predictor of C-reactive protein in milk and blood during lactation.\nTo investigate the presence of C-reactive protein (CRP) in breast milk and any relationship between changes in CRP in breast milk and blood, and the severity of systemic and breast symptoms experienced during mastitis. Mothers (n = 26) were followed prospectively from day 5 postpartum to the end of their lactation. Milk from each breast, blood, 24-hour urine samples and data on breast and systemic pathologies were collected at reference intervals during the first 3 months postpartum, daily during the occurrence of any breast inflammation and at 7 days after resolution of symptoms. CRP in blood was significantly increased during mastitis (p < 0.001, df:1,81; F = 31) and severity of systemic symptoms was a significant predictor for changes of CRP in blood (p < 0.01; df:3,42; F = 9.6). During mastitis both the symptomatic breast (p < 0.001; df:1,79; F = 19) and the contralateral asymptomatic breast (p < 0.004; df:1,75; F = 8.7) had a significantly higher milk CRP when compared with women with no mastitis. Although an increasing severity of breast and systemic symptoms in mastitis was predictive of an increasing CRP in milk and blood, respectively, the presence of CRP in similar concentrations in the mastitis and asymptomatic breast suggests it is of little use in making a differential diagnosis between infective verses noninfective forms of mastitis.","subset":"pubmed_abstract"} +{"meta":{"pmid":30249004,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation?\nEpidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate additional approaches to move beyond the associations that are reported in traditional epidemiological analyses and incorporate information on molecular pathologic signatures as a requirement to posit causal inferences. In particular, we point to the efforts of the transdisciplinary field of molecular pathological epidemiology (MPE) to evaluate possible causal relationships, if any, of alcohol consumption and breast cancer. A wider application of the principles of MPE to this field would constitute a giant step that could enhance our understanding of breast cancer and multiple modifiable risk factors, a step that would be particularly suited to the era of \"personalized medicine\".","subset":"pubmed_abstract"} +{"meta":{"pmid":30823194,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Occurrence and Pathogenicity of Puccinia hordei on Barley in South Africa.\nAlthough leaf rust, caused by Puccinia hordei, is considered an important disease of barley (Hordeum vulgare) and regularly reaches epidemic proportions, pathogenic variability has never been studied in South Africa. From 1994 to 1997, only one pathotype (SAPh 3231) was identified with virulence to resistance genes Rph1, Rph4, Rph5, Rph10, and Rph11. During 1998, a second pathotype (SAPh 7321) was identified, differing from pathotype SAPh 3231 only in virulence to Rph12. Pathotype SAPh 7321 increased rapidly in the area where it was first detected, resulting in localized epidemic outbreaks in 1999. The reactions of various South African cultivars and breeding lines toward these pathotypes were determined, and the presence of Rph12 was postulated for B93\/4, Krona, Optic, Prisma, and SSG 532. Rph genes showed varying degrees of temperature sensitivity, with none of the known genes displaying major changes in their phenotypes except Rph8, which was less effective at higher temperatures. Eight accessions of two wild Hordeum spp. occurring abundantly in the barley growing regions were found to be either weak or nonhosts for P. hordei.","subset":"pubmed_abstract"} +{"meta":{"pmid":16506909,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2014-10":1,"unknown":6}}},"text":"Use of helical computed tomography for measurement of thyroid glands in clinically normal cats.\nTo determine the dimensions and volume of thyroid tissue in clinically normal cats by use of computed tomography. 8 cats. Helical computed tomography images (2-mm collimation) were acquired from the cranial aspect of the second cervical vertebra through the caudal aspect of the fourth cervical vertebra. Data were acquired before contrast medium administration (n = 7 cats) and immediately after contrast medium enhancement (1 cat). Length, width, and height measurements of each thyroid lobe were made by use of transverse, dorsal, and sagittal plane images. Thyroid lobe volume was estimated by use of 3 methods. All thyroid lobes were histologically normal. Mean dimensions for a thyroid lobe were 16.5 x 2.00 x 4.31 mm (length x width x height) using only data from transverse images. Mean thyroid lobar volume was 113.75 mm(3) using the sum of areas method. Mean total volume of thyroid tissue was 215.25 mm(3) using the sum of areas method. Results may be useful for computed tomography evaluation of abnormal thyroid glands in cats, which warrants investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22549005,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2015-27":1,"2015-22":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-35":1,"2014-23":2,"2014-15":2,"2015-40":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Reconciling taxonomy and phylogenetic inference: formalism and algorithms for describing discord and inferring taxonomic roots.\nAlthough taxonomy is often used informally to evaluate the results of phylogenetic inference and the root of phylogenetic trees, algorithmic methods to do so are lacking. In this paper we formalize these procedures and develop algorithms to solve the relevant problems. In particular, we introduce a new algorithm that solves a \"subcoloring\" problem to express the difference between a taxonomy and a phylogeny at a given rank. This algorithm improves upon the current best algorithm in terms of asymptotic complexity for the parameter regime of interest; we also describe a branch-and-bound algorithm that saves orders of magnitude in computation on real data sets. We also develop a formalism and an algorithm for rooting phylogenetic trees according to a taxonomy. The algorithms in this paper, and the associated freely-available software, will help biologists better use and understand taxonomically labeled phylogenetic trees.","subset":"pubmed_abstract"} +{"meta":{"pmid":33406647,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Simplicity Out of Complexity: Band Structure for W20O58 Superconductor.\nThe band structure, density of states, and the Fermi surface of a recently discovered superconductor, oxygen-deficient tungsten oxide WO2.9 that is equivalent to W20O58, is studied within the density functional theory (DFT) in the generalized gradient approximation (GGA). Here we show that despite the extremely complicated structure containing 78 atoms in the unit cell, the low-energy band structure is quite feasible. Fermi level is crossed by no more than 10 bands per one spin projection (and even 9 bands per pseudospin projection when the spin-orbit coupling is considered) originating from the t2g 5d-orbitals of tungsten atoms forming zigzag chains. These bands become occupied because of the specific zigzag octahedra distortions. To demonstrate the role of distortions, we compare band structures of W20O58 with the real crystal structure and with the idealized one. We also propose a basis for a minimal low-energy tight-binding model for W20O58.","subset":"pubmed_abstract"} +{"meta":{"pmid":11185513,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Powering the nanoworld.\nDevens Gust, a chemist at Arizona State University in Tempe, and a handful of colleagues have built tiny refineries that convert the energy in sunlight to chemical fuel to power nanomachines. The fuel in this case is adenosine triphosphate, the same energy-rich molecule that powers chemical reactions inside cells. At last August's meeting of the American Chemical Society in Washington, D.C., Gust reported that he and his colleagues had collaborated with other groups to run their protein-based molecular machines on little more than sunlight.","subset":"pubmed_abstract"} +{"meta":{"pmid":19034105,"dup_signals":{"dup_doc_count":11}},"text":"Phase 2, double-blind, placebo-controlled, dose-response trial of intravenous adenosine for perioperative analgesia.\nAdenosine regulates pain transmission by actions at spinal, supraspinal, and peripheral sites. A few studies have suggested that administration of adenosine might be associated with anesthetic- and analgesic-sparing effects. The primary aim of this multicenter study was to determine the dose-response profile of adenosine with respect to perioperative analgesia. Women undergoing major gynecologic surgery were enrolled. Subjects were randomly assigned to receive one of four doses of adenosine (25, 50, 100, or 200 microg x kg x min) or matching placebo. A dose-escalation cohort approach was followed. Study drug administration was started in the operating room at the time of skin incision and discontinued at the end of surgery. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia system. Data were collected in the hospital and after discharge daily through postoperative day 7. A total of 166 subjects received treatment with study drug: 125 received adenosine and 41 received placebo. Except for height, there were no differences between treatment groups with respect to demographic or baseline characteristics. Cumulative opioid use during the initial 24-h period after extubation was not significantly different between treatment groups. There were also no differences between treatment groups with respect to cumulative anesthetic use, intraoperative opioid requirements, pain scores, sedation, time to readiness for discharge from the postanesthesia care unit, time to readiness for discharge from the hospital, opioid-related symptom distress scores, patient satisfaction with pain control, and occurrence of adverse events. There were no differences between placebo and adenosine with respect to efficacy and safety for perioperative analgesia.","subset":"pubmed_abstract"} +{"meta":{"pmid":2306217,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2022-49":1,"2022-05":1,"2019-43":1,"2019-22":1,"2019-13":1,"2018-22":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-40":1}}},"text":"Topography of the combining region of a Thomsen-Friedenreich-antigen-specific lectin jacalin (Artocarpus integrifolia agglutinin). A thermodynamic and circular-dichroism spectroscopic study.\nThermodynamic analysis of carbohydrate binding by Artocarpus integrifolia (jackfruit) agglutinin (jacalin) shows that, among monosaccharides, Me alpha GalNAc (methyl-alpha-N-acetylgalactosamine) is the strongest binding ligand. Despite its strong affinity for Me alpha GalNAc and Me alpha Gal, the lectin binds very poorly when Gal and GalNAc are in alpha-linkage with other sugars such as in A- and B-blood-group trisaccharides, Gal alpha 1-3Gal and Gal alpha 1-4Gal. These binding properties are explained by considering the thermodynamic parameters in conjunction with the minimum energy conformations of these sugars. It binds to Gal beta 1-3GalNAc alpha Me with 2800-fold stronger affinity over Gal beta 1-3GalNAc beta Me. It does not bind to asialo-GM1 (monosialoganglioside) oligosaccharide. Moreover, it binds to Gal beta 1-3GalNAc alpha Ser, the authentic T (Thomsen-Friedenreich)-antigen, with about 2.5-fold greater affinity as compared with Gal beta 1-3GalNAc. Asialoglycophorin A was found to be about 169,333 times stronger an inhibitor than Gal beta 1-3GalNAc. The present study thus reveals the exquisite specificity of A. integrifolia lectin for the T-antigen. Appreciable binding of disaccharides Glc beta 1-3GalNAc and GlcNAc beta 1-3Gal and the very poor binding of beta-linked disaccharides, which instead of Gal and GalNAc contain other sugars at the reducing end, underscore the important contribution made by Gal and GalNAc at the reducing end for recognition by the lectin. The ligand-structure-dependent alterations of the c.d. spectrum in the tertiary structural region of the protein allows the placement of various sugar units in the combining region of the lectin. These studies suggest that the primary subsite (subsite A) can accommodate only Gal or GalNAc or alpha-linked Gal or GalNAc, whereas the secondary subsite (subsite B) can associate either with GalNAc beta Me or Gal beta Me. Considering these factors a likely arrangement for various disaccharides in the binding site of the lectin is proposed. Its exquisite specificity for the authentic T-antigen, Gal beta 1-3GalNAc alpha Ser, together with its virtual non-binding to A- and B-blood-group antigens, Gal beta 1-3GalNAc beta Me and asialo-GM1 should make A. integrifolia lectin a valuable probe for monitoring the expression of T-antigen on cell surfaces.","subset":"pubmed_abstract"} +{"meta":{"pmid":26973608,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Biological Phosphorus Removal During High-Rate, Low-Temperature, Anaerobic Digestion of Wastewater.\nWe report, for the first time, extensive biologically mediated phosphate removal from wastewater during high-rate anaerobic digestion (AD). A hybrid sludge bed\/fixed-film (packed pumice stone) reactor was employed for low-temperature (12\u00b0C) anaerobic treatment of synthetic sewage wastewater. Successful phosphate removal from the wastewater (up to 78% of influent phosphate) was observed, mediated by biofilms in the reactor. Scanning electron microscopy and energy dispersive X-ray analysis revealed the accumulation of elemental phosphorus (\u223c2%) within the sludge bed and fixed-film biofilms. 4', 6-diamidino-2-phenylindole (DAPI) staining indicated phosphorus accumulation was biological in nature and mediated through the formation of intracellular inorganic polyphosphate (polyP) granules within these biofilms. DAPI staining further indicated that polyP accumulation was rarely associated with free cells. Efficient and consistent chemical oxygen demand (COD) removal was recorded, throughout the 732-day trial, at applied organic loading rates between 0.4 and 1.5 kg COD m(-3) d(-1) and hydraulic retention times of 8-24 h, while phosphate removal efficiency ranged from 28 to 78% on average per phase. Analysis of protein hydrolysis kinetics and the methanogenic activity profiles of the biomass revealed the development, at 12\u00b0C, of active hydrolytic and methanogenic populations. Temporal microbial changes were monitored using Illumina MiSeq analysis of bacterial and archaeal 16S rRNA gene sequences. The dominant bacterial phyla present in the biomass at the conclusion of the trial were the Proteobacteria and Firmicutes and the dominant archaeal genus was Methanosaeta. Trichococcus and Flavobacterium populations, previously associated with low temperature protein degradation, developed in the reactor biomass. The presence of previously characterized polyphosphate accumulating organisms (PAOs) such as Rhodocyclus, Chromatiales, Actinobacter, and Acinetobacter was recorded at low numbers. However, it is unknown as yet if these were responsible for the luxury polyP uptake observed in this system. The possibility of efficient phosphate removal and recovery from wastewater during AD would represent a major advance in the scope for widespread application of anaerobic wastewater treatment technologies.","subset":"pubmed_abstract"} +{"meta":{"pmid":37066381,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":7,"unknown":7}}},"text":"Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate.\nTelomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay (\"Telo-CISH\") produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.","subset":"pubmed_abstract"} +{"meta":{"pmid":17321544,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2021-31":1,"2021-21":2,"2020-40":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-18":1,"2023-06":1,"2024-30":1}}},"text":"A novel two-domain architecture within the amino acid kinase enzyme family revealed by the crystal structure of Escherichia coli glutamate 5-kinase.\nGlutamate 5-kinase (G5K) makes the highly unstable product glutamyl 5-phosphate (G5P) in the initial, controlling step of proline\/ornithine synthesis, being feedback-inhibited by proline or ornithine, and causing, when defective, clinical hyperammonaemia. We determined two crystal structures of G5K from Escherichia coli, at 2.9 A and 2.5 A resolution, complexed with glutamate and sulphate, or with G5P, sulphate and the proline analogue 5-oxoproline. E. coli G5K presents a novel tetrameric (dimer of dimers) architecture. Each subunit contains a 257 residue AAK domain, typical of acylphosphate-forming enzymes, with characteristic alpha(3)beta(8)alpha(4) sandwich topology. This domain is responsible for catalysis and proline inhibition, and has a crater on the beta sheet C-edge that hosts the active centre and bound 5-oxoproline. Each subunit contains a 93 residue C-terminal PUA domain, typical of RNA-modifying enzymes, which presents the characteristic beta(5)beta(4) sandwich fold and three alpha helices. The AAK and PUA domains of one subunit associate non-canonically in the dimer with the same domains of the other subunit, leaving a negatively charged hole between them that hosts two Mg ions in one crystal, in line with the G5K requirement for free Mg. The tetramer, formed by two dimers interacting exclusively through their AAK domains, is flat and elongated, and has in each face, pericentrically, two exposed active centres in alternate subunits. This would permit the close apposition of two active centres of bacterial glutamate-5-phosphate reductase (the next enzyme in the proline\/ornithine-synthesising route), supporting the postulated channelling of G5P. The structures clarify substrate binding and catalysis, justify the high glutamate specificity, explain the effects of known point mutations, and support the binding of proline near glutamate. Proline binding may trigger the movement of a loop that encircles glutamate, and which participates in a hydrogen bond network connecting active centres, which is possibly involved in the cooperativity for glutamate.","subset":"pubmed_abstract"} +{"meta":{"pmid":23817542,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A clinical protocol for intraoral digital impression of screw-retained CAD\/CAM framework on multiple implants based on wavefront sampling technology.\nTo obtain an accurate CAD\/CAM metal framework over 6 implants using a Chairside Intraoral Scanner based on the principle of active (optical) wavefront sampling. Six prototype cylindrical scan bodies screwed in the implants were used to obtain an intraoral digital impression. A conventional resin tooth try-in was fabricated and digitized with an extraoral scanner, and this dataset was merged to the digital data obtained from the intraoral impression to calculate the best framework design with advanced CAD software. The framework was fabricated with a 5-axis computer numerical control milling unit. Three clinical tests (saliva intrusion, Sheffield test, and screw resistance test) were performed to assess the fit of the framework. Under 3 clinical tests, an accurate fit was observed. The case presented in this report proposes a new clinical protocol for obtaining accurate digital impressions of multiple implants.","subset":"pubmed_abstract"} +{"meta":{"pmid":17297116,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Effects of dietary protein and starch on intake, milk production, and milk fatty acid profiles of dairy cows fed corn silage-based diets.\nFeed intake, milk production, and milk fatty acid profiles of dairy cows fed corn silage-based diets with different protein and starch concentrations were measured in a 3-period experiment in a changeover design using 12 Holstein cows. Each experimental period lasted for 3 wk. The diet fed as a total mixed ration consisted of 45% corn silage, 5% coarsely chopped wheat straw, and 50% concentrate, on a dry matter (DM) basis. The 4 treatments, formulated to be isoenergetic and to differ in concentrations of dietary crude protein (CP) and starch (DM basis), were as follows: low CP and low starch (LPLS; 14% CP and 15% starch), low CP and high starch (LPHS; 14% CP and 25% starch), high CP and low starch (HPLS; 16% CP and 15% starch), and high CP and high starch (HPHS; 16% CP and 25% starch). The LPLS treatment led to lower DM intake, milk yield, milk protein concentration, and milk lactose yield, probably due to a shortage of both rumen-degradable protein supply to rumen microbes and glucogenic nutrients to the animal. There were no differences between protein-rich diets and LPHS, suggesting that this diet satisfied the rumen-degradable protein requirements of rumen microbes and did not limit feed intake, and the increased supply of glucogenic nutrients spared AA so that the nutrient requirements of mid lactation dairy cows were met. Further increases in CP concentration increased plasma urea concentration and resulted in decreased efficiency of conversion of dietary N into milk N. Milk fatty acid profiles were affected by starch and protein supply, with starch having the largest effect. Additionally, increasing dietary starch concentration decreased the apparent transfer of dietary polyunsaturated fatty acids to milk, suggesting an increased channeling of fatty acids to adipose tissue. The results further suggest that C(15:0) and C(17:0) are synthesized de novo in animal tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":17631513,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2018-05":1,"2017-43":1,"2017-34":2,"2014-15":1,"2019-04":1,"2013-20":1,"2013-48":1}}},"text":"Use of intensive case management to reduce time in hospital in people with severe mental illness: systematic review and meta-regression.\nTo explain why clinical trials of intensive case management for people with severe mental illness show such inconsistent effects on the use of hospital care. Systematic review with meta-regression techniques applied to data from randomised controlled trials. Cochrane central register of controlled trials, CINAHL, Embase, Medline, and PsychINFO databases from inception to January 2007. Additional anonymised data on patients were obtained for multicentre trials. Included trials examined intensive case management compared with standard care or low intensity case management for people with severe mental illness living in the community. We used a fidelity scale to rate adherence to the model of assertive community treatment. Multicentre trials were disaggregated into individual centres with fidelity data specific for each centre. A multivariate meta-regression used mean days per month in hospital as the dependent variable. We identified 1335 abstracts with a total of 5961 participants. Of these, 49 were eligible and 29 provided appropriate data. Trials with high hospital use at baseline (before the trial) or in the control group were more likely to find that intensive case management reduced the use of hospital care (coefficient -0.23, 95% confidence interval -0.36 to -0.09, for hospital use at baseline; -0.44, -0.57 to -0.31, for hospital use in control groups). Case management teams organised according to the model of assertive community treatment were more likely to reduce the use of hospital care (coefficient -0.31, -0.59 to -0.03), but this finding was less robust in sensitivity analyses and was not found for staffing levels recommended for assertive community treatment. Intensive case management works best when participants tend to use a lot of hospital care and less well when they do not. When hospital use is high, intensive case management can reduce it, but it is less successful when hospital use is already low. The benefits of intensive case management might be marginal in settings that have already achieved low rates of bed use, and team organisation is more important than the details of staffing. It might not be necessary to apply the full model of assertive community treatment to achieve reductions in inpatient care.","subset":"pubmed_abstract"} +{"meta":{"pmid":2528207,"dup_signals":{"dup_doc_count":18,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2020-45":2,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":2,"2019-30":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-39":1,"2017-09":1,"2024-30":1}}},"text":"Osteoclastic bone resorption by a polarized vacuolar proton pump.\nBone resorption depends on the formation, by osteoclasts, of an acidic extracellular compartment wherein matrix is degraded. The mechanism by which osteoclasts transport protons into that resorptive microenvironment was identified by means of adenosine triphosphate-dependent weak base accumulation in isolated osteoclast membrane vesicles, which exhibited substrate and inhibition properties characteristic of the vacuolar, electrogenic H+-transporting adenosine triphosphatase (H+-ATPase). Identify of the proton pump was confirmed by immunoblot of osteoclast membrane proteins probed with antibody to vacuolar H+-ATPase isolated from bovine kidney. The osteoclast's H+-ATPase was immunocytochemically localized to the cell-bone attachment site. Immunoelectron microscopy showed that the H+-ATPase was present in the ruffled membrane, the resorptive organ of the cell.","subset":"pubmed_abstract"} +{"meta":{"pmid":536928,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The effects of post-ganglionic axotomy on selective synaptic connexions in the superior cervical ganglion of the guinea-pig.\nStimulation of preganglionic axons arising from different levels of the thoracic spinal cord causes different effects on end-organs supplied by the superior cervical ganglion (Langley, 1892; Nja & Purves, 1977a; Lichtman, Purves & Yip, 1979). For example, stimulation of the first thoracic ventral root (T1) causes pupillary dilatation and widening of the palpebral fissure; stimulation of T4, on the other hand, has little effect on the eye, even though axons arising from this level innervate about as many superior cervical ganglion cells as those from T1. Thus ganglion cell innervation is selective. (1) Three months after crushing the major post-ganglionic branches of the superior cervical ganglion this differential effectiveness is lost: T1 and T4 stimulation have approximately equal effects on the end-organs of the eye. (2) In normal animals, the cellular counterpart of selective end-organ effects is the innervation of each ganglion cell by a contiguous subset of the spinal segments that innervate the ganglion as a whole. One of these segments is usually dominant, the strength of innervation from adjacent segments falling off as a function of distance from the dominant one (Nja & Purves, 1977a). Intracellular recordings from ganglion cells 3 months after post-ganglionic axotomy showed that this selective pattern is re-established. (3) Since the innervation of ganglion cells appears normal, the abnormal end-organ responses after post-ganglionic axotomy suggest that ganglion cell axons are not limited to their original targets during peripheral re-innervation. This suggestion is supported by the finding that ganglion cells sending axons to different peripheral destinations via the second and third cervical spinal nerves were no longer distinguishable on the basis of their segmented inputs 3 months after post-ganglionic axotomy. (4) Similar results were obtained when the preganglionic cervical trunk was cut at the same time as the post-ganglionic axons were crushed; the pattern of end-organ responses was abnormal, whereas individual ganglion cells were re-innervated according to the rules of contiguity and segmental dominance. (5) These results indicate that ganglion cells do not undergo a compensatory change in the segmental innervation they receive when their axons regenerate to targets different from, or in addition to those they originally innervated, even when an entirely new set of ganglionic connexions is formed. This suggests that ganglion cells, or some aspect of their immediate environment, possess a permanent label that determines the segmental innervation they receive.","subset":"pubmed_abstract"} +{"meta":{"pmid":21991321,"dup_signals":{"dup_doc_count":19,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2017-13":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":13}}},"text":"The breadth, but not the magnitude, of circulating memory B cell responses to P. falciparum increases with age\/exposure in an area of low transmission.\nMalaria caused by Plasmodium falciparum remains a major cause of death in sub-Saharan Africa. Immunity against symptoms of malaria requires repeated exposure, suggesting either that the parasite is poorly immunogenic or that the development of effective immune responses to malaria may be impaired. We carried out two age-stratified cross-sectional surveys of anti-malarial humoral immune responses in a Gambian village where P. falciparum malaria transmission is low and sporadic. Circulating antibodies and memory B cells (MBC) to four malarial antigens were measured using ELISA and cultured B cell ELISpot. The proportion of individuals with malaria-specific MBC and antibodies, and the average number of antigens recognised by each individual, increased with age but the magnitude of these responses did not. Malaria-specific antibody levels did not correlate with either the prevalence or median number of MBC, indicating that these two assays are measuring different aspects of the humoral immune response. Among those with immunological evidence of malaria exposure (defined as a positive response to at least one malarial antigen either by ELISA or ELISPOT), the median number of malaria-specific MBC was similar to median numbers of diphtheria-specific MBC, suggesting that the circulating memory cell pool for malaria antigens is of similar size to that for other antigens.","subset":"pubmed_abstract"} +{"meta":{"pmid":23024971,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2013-48":1,"unknown":10}}},"text":"Psychiatric problems in fibromyalgia: clinical and neurobiological links between mood disorders and fibromyalgia.\nTo review the literature addressing the relationship between mood disorders and fibromyalgia\/chronic pain and our current understanding of overlapping pathophysiological processes and pain and depression circuitry. We selectively reviewed articles on the co-occurrence of mood disorders and fibromyalgia\/chronic pain published between 1990 and July 2012 in PubMed. Bibliographies and cross references were considered and included when appropriate. Forty-nine out of 138 publications were retained for review. The vast majority of the studies found an association between depression and fibromyalgia. There is evidence that depression is often accompanied by symptoms of opposite polarity characterised by heights of mood, thinking and behaviour that have a considerable impact on pharmacological treatment. Recent developments support the view that the high rates of fibromyalgia and mood disorder comorbidity is generated by largely overlapping pathophysiological processes in the brain, that provide a neurobiological basis for the bidirectional, mutually exacerbating and disabling relationship between pain and depression. The finding of comparable pathophysiological characteristics of pain and depression provides a framework for understanding the relationship between the two conditions and sheds some light on neurobiological and therapeutic aspects.","subset":"pubmed_abstract"} +{"meta":{"pmid":15845506,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Efficient Ex vivo stimulation of Mycobacterium tuberculosis-specific T cells by genetically detoxified Bordetella pertussis adenylate cyclase antigen toxoids.\nMycobacterium tuberculosis is a significant threat to global health. Mycobacterium bovis BCG vaccine provides only partial protection, and the skin test reagent used to aid diagnosis of both active and latent tuberculosis, purified protein derivative (PPD), lacks specificity and sensitivity. The use of genetically detoxified Bordetella pertussis adenylate cyclase toxin (CyaA) as a delivery system for two immunodominant proteins of M. tuberculosis that are of greater specificity than PPD, early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), was therefore investigated. CyaA toxoids incorporating these antigens were able to restimulate T cells from more than 91% tuberculosis patients and healthy sensitized donors. Delivery of antigen by CyaA decreased by 10-fold the amount of ESAT-6 and CFP-10 required to restimulate T cells, and in low responders, the overall frequency of gamma interferon-producing cells detected by enzyme-linked immunospot assay was increased (P < 0.01 for both antigens). Delivery of ESAT-6 and CFP-10 by CyaA enabled the detection of both CD4(+) and CD8(+) T cells: these responses could be blocked by inhibition of major histocompatibility complex class II or class I, respectively. Covalent linkage of antigen to the CyaA vector was required for enhancement to occur, as a mixture of mock CyaA toxoid plus recombinant ESAT-6 did not lead to enhancement. In a simplified whole-blood model to detect tuberculosis infection, the frequency of positive responses to CFP-10 was increased by CyaA delivery, a potentially important attribute that could facilitate the identification of latent infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":8571432,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mitochondrial generation of reactive oxygen species after brain ischemia in the rat.\nBrain mitochondria have a substantial capacity to generate reactive oxygen species after ischemia when the components of the respiratory chain are reduced and molecular oxygen is present. We tested the hypothesis that brain mitochondria in vivo produce reactive oxygen species after ischemia\/reperfusion (IR) in rats at a rate sufficient to escape endogenous antioxidant defenses. Ischemia-dependent production of hydroxyl radical in the hippocampus of the anesthetized rat was monitored with the use of intracerebral microdialysis. Transient global ischemia was produced by bilateral carotid artery occlusion and hemorrhagic hypotension to a mean arterial pressure of 35 mm Hg for 15 minutes followed by reperfusion for 60 minutes. Salicylic acid was infused into the hippocampus during the experiments, and changes in the recovery of its hydroxylated product, 2,3-dihydroxybenzoic acid (2,3-DHBA), were used to assess the effects of inhibitors of mitochondrial complex I on formation of hydroxyl radical during IR. Hydroxylation data from control groups of animals were compared with data from animals undergoing IR during treatment with either a mitochondrial complex I inhibitor alone or the inhibitor plus succinic acid. Transient ischemia led to a fivefold increase in the recovery of 2,3-DHBA by microdialysis after 1 hour relative to control animals (P < .05). Inhibition of mitochondrial complex I prevented 2,3-DHBA formation after IR; this effect could be reversed by infusion of succinic acid by microdialysis during IR. The data indicate that reactive oxygen species generated by mitochondrial electron transport escape cellular antioxidant defenses and promote highly damaging hydroxyl radical activity after transient brain ischemia in the rat.","subset":"pubmed_abstract"} +{"meta":{"pmid":22266796,"dup_signals":{"dup_doc_count":26,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2021-21":1,"2021-17":2,"2021-10":2,"2021-04":2,"2020-45":5,"2020-34":3,"2020-29":1,"2020-24":1,"2020-10":1,"2020-05":1,"2019-43":1,"2019-39":1,"2019-30":1,"2017-51":1,"2017-43":1,"2021-25":1}}},"text":"Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence.\nThe t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence.","subset":"pubmed_abstract"} +{"meta":{"pmid":21307304,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Disclosing individual CDKN2A research results to melanoma survivors: interest, impact, and demands on researchers.\nWhether to return individual research results from cancer genetics studies is widely debated, but little is known about how participants respond to results disclosure or about its time and cost burdens on investigators. We recontacted participants at one site of a multicenter genetic epidemiologic study regarding their CDKN2A gene test results and implications for melanoma risk. Interested participants were disclosed their results by telephone and followed for 3 months. Among 39 patients approached, 27 were successfully contacted, and 19 (70% uptake) sought results, including three with mutations. Prior to disclosure, participants endorsed numerous benefits of receiving results (mean=7.7 of 9 posed), including gaining information relevant to their children's disease risk. Mean psychological well-being scores did not change from baseline, and no decreases to melanoma prevention behaviors were noted. Fifty-nine percent of participants reported that disclosure made participation in future research more likely. Preparation for disclosure required 40 minutes and $611 per recontact attempt. An additional 78 minutes and $68 was needed to disclose results. Cancer epidemiology research participants who received their individual genetic research results showed no evidence of psychological harm or false reassurance from disclosure and expressed strong trust in the accuracy of results. Burdens to our investigators were high, but protocols may differ in their demands and disclosure may increase participants' willingness to enroll in future studies. Providing individual study results to cancer genetics research participants poses potential challenges for investigators, but many participants desire and respond positively to this information.","subset":"pubmed_abstract"} +{"meta":{"pmid":28807981,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Delineation of the timing of second-line therapy post-autologous stem cell transplant in patients with AL amyloidosis.\nAmong patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur. We conducted a retrospective study to evaluate the patterns of relapse or progression (R\/P) and the timing of reinitiating therapy among 235 patients initially treated with autologous stem cell transplant (ASCT) at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median difference of free light chain (dFLC) was 9.9 mg\/dL (42% of diagnosis value), 32% had a dFLC <5 mg\/dL, and 63% met criteria for organ R\/P. The indications for retreatment were (1) clinical suspicion of R\/P, 10%; 92) hematologic R\/P only, 23%; (3) organ R\/P only, 32%; (4) both hematologic and organ R\/P, 31%; and (5) suboptimal response to ASCT and second-line therapy as consolidation, 4%. Patients with organ progression at the time of second-line therapy had inferior survival. Although a dFLC of >5 mg\/dL at the time of reinstituting therapy was associated with risk, patients relapsing from very good partial response (VGPR) or better had a longer time to develop organ progression after hematologic R\/P (24.2 vs 3.2 months, P = .007). These data suggest that the best candidates for clinical trials testing novel plasma cell-directed chemotherapy beyond first line may be those patients who are either relapsing from VGPR or better (dFLC at diagnosis was >5 mg\/dL) or having inadequate response to prior therapy. This strategy should allow for hematologic response assessment while avoiding the risk of deleterious organ progression. Implementation of more stringent progression criteria may also be warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":17297802,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"An in vitro setup to test the relevance and the accuracy of low-order vocal folds models.\nAn experimental setup and human vocal folds replica able to produce self-sustained oscillations are presented. The aim of the setup is to assess the relevance and the accuracy of theoretical vocal folds models. The applied reduced mechanical models are a variation of the classical two-mass model, and a simplification inspired on the delayed mass model for which the coupling between the masses is expressed as a fixed time delay. The airflow is described as a laminar flow with flow separation. The influence of a downstream resonator is taken into account. The oscillation pressure threshold and fundamental frequency are predicted by applying a stability analysis to the mechanical models. The measured frequency response of the mechanical replica together with the initial (rest) area allows us to determine the model parameters (spring stiffness, damping, geometry, masses). Validation of theoretical model predictions to experimental data shows the relevance of low-order models in gaining a qualitative understanding of phonation. However, quantitative discrepancies remain large due to an inaccurate estimation of the model parameters and the crudeness in either flow or mechanical model description. As an illustration it is shown that significant improvements can be made by accounting for viscous flow effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":25769109,"dup_signals":{"dup_doc_count":13}},"text":"Correlates of depressive symptoms among North Korean refugees adapting to South Korean society: the moderating role of perceived discrimination.\nAlthough the prevalence of depressive disorders among North Korean (NK) refugees living in South Korea has been reported to be twice the rate of their South Korean counterparts, little is known about the correlates of depressive symptoms among this population. Despite their escape from a politically and economically repressive setting, NK refugees continue to face multidimensional hardships during their adaptation process in South Korea, which can adversely affect their mental health. However, to our knowledge, no empirical research exists to date on depressive symptoms in the context of adaptation or perceived discrimination among NK refugees. To fill this gap, this study used a sample of 261 NK refugees in South Korea from the 2010 National Survey on Family Violence to examine associations between sociocultural adaptation, perceived discrimination, and depressive symptoms, as well as the moderation effect of discrimination on adaptation to depressive symptoms. We found that poor sociocultural adaptation and perception of discrimination were associated with increased levels of depressive symptoms. Perception of discrimination attenuated the association between better adaptation and fewer depressive symptoms, when compared to no perception of discrimination. These findings highlight the need to improve NK refugees' adaptation and integration as well as their psychological well-being in a culturally sensitive and comprehensive manner. They also underscore the importance of educating South Koreans to become accepting hosts who value diversity, yet in a homogeneous society.","subset":"pubmed_abstract"} +{"meta":{"pmid":7476571,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2017-13":1,"unknown":8}}},"text":"Dog model for cerebrovascular studies of the proximal-to-distal distribution of sequentially injected emboli.\nThis study was undertaken to determine whether microemboli injected in a predetermined sequence would maintain that sequence once they came to rest in brain microvessels. If so, the injection of different-colored microspheres at different times could be used to bracket-in-time emboli that are known to be released into the circulation during cardiopulmonary bypass. We injected different-colored microspheres into the arterial circulation of anesthetized dogs before and after the injection of fat emboli and before and after cardiopulmonary bypass. Coronal slices of the dog brains were embedded in celloidin, sectioned at 100 microns, and stained for alkaline phosphatase. The afferent cerebrovasculature stained dark brown against a light background, and the proximal\/distal orientation of many of the arterioles could be determined by following their course within the thick sections. When different types of emboli were found in a single arteriole, they appeared in the order injected or the order of occurrence in the bypass protocol in 99.3% of the 867 such arterioles counted. Therefore, the microemboli maintained their ordered sequence with only a very small degree of mixing. Once they came to rest, there was not sufficient collateral blood flow in the brain microvessels to move them into disordered positions. This dog model should facilitate studies of the time of release of microemboli within narrower windows of time during cardiopulmonary bypass.","subset":"pubmed_abstract"} +{"meta":{"pmid":17238437,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"CARE+ user study: usability and attitudes towards a tablet pc computer counseling tool for HIV+ men and women.\nCARE+ is a tablet PC-based computer counseling tool designed to support medication adherence and secondary HIV prevention for people living with HIV. Thirty HIV+ men and women participated in our user study to assess usability and attitudes towards CARE+. We observed them using CARE+ for the first time and conducted a semi-structured interview afterwards. Our findings suggest computer counseling may reduce social bias and encourage participants to answer questions honestly. Participants felt that discussing sensitive subjects with a computer instead of a person reduced feelings of embarrassment and being judged, and promoted privacy. Results also confirm that potential users think computers can provide helpful counseling, and that many also want human counseling interaction. Our study also revealed that tablet PC-based applications are usable by our population of mixed experience computer users. Computer counseling holds great potential for providing assessment and health promotion to individuals with chronic conditions such as HIV.","subset":"pubmed_abstract"} +{"meta":{"pmid":30305562,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Nephroprotective Effect of Essential Oils from Ginger (Zingiber officinale) and Turmeric (Curcuma longa) Rhizomes against Cadmium-induced Nephrotoxicity in Rats.\nSeveral studies have shown that cadmium (Cd) induces nephrotoxicity and many plant foods phytochemicals have been found useful but their possible mechanism of action still remains unexplored. Hence, this study aimed to investigate the nephroprotective effect of essential oils from Nigeria ginger and turmeric rhizomes in cadmium-treated rats by examining their effect on renal function biomarkers (creatinine, urea and BUN), inflammatory cytokines (IL-6, IL-10 and TNF-Alpha) and renal adenosine deaminase (ADA) activity. The result revealed that essential oils from ginger and turmeric rhizomes exert anti-inflammatory effect by preventing alterations of renal function markers and cytokines (IL-6, IL-10 and TNF-Alpha) levels in Cd-treated rats. In addition, the essential oils inhibited renal ADA activity in Cdtreated rats. In conclusion, inhibition of ADA activity and modulation of inflammatory cytokines could be suggested as the possible mechanism of action by which essential oils from ginger and turmeric rhizomes exert their nephroprotective activities.","subset":"pubmed_abstract"} +{"meta":{"pmid":9131825,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"The determinants of trust and credibility in environmental risk communication: an empirical study.\nThis study examines a key component of environmental risk communication; trust and credibility. The study was conducted in two parts. In the first part, six hypotheses regarding the perceptions and determinants of trust and credibility were tested against survey data. The hypotheses were supported by the data. The most important hypothesis was that perceptions of trust and credibility are dependent on three factors: perceptions of knowledge and expertise; perceptions of openness and honesty; and perceptions of concern and care. In the second part, models were constructed with perceptions of trust and credibility as the dependent variable. The goal was to examine the data for findings with direct policy implications. One such finding was that defying a negative stereotype is key to improving perceptions of trust and credibility.","subset":"pubmed_abstract"} +{"meta":{"pmid":27260007,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Comorbidity of Alcohol and Gambling Problems in Emerging Adults: A Bifactor Model Conceptualization.\nAddictive disorders, such as pathological gambling and alcohol use disorders, frequently co-occur at greater than chance levels. Substantive questions stem from this comorbidity regarding the extent to which shared variance between gambling and alcohol use reflects a psychological core of addictive tendencies, and whether this differs as a function of gender. The aims of this study were to differentiate both common and unique variance in alcohol and gambling problems in a bifactor model, examine measurement invariance of this model by gender, and identify substantive correlates of the final bifactor model. Undergraduates (N = 4475) from a large northwestern university completed an online screening questionnaire which included demographics, quantity of money lost and won when gambling, the South Oaks Gambling Screen, the AUDIT, gambling motives, drinking motives, personality, and the Brief Symptom Inventory. Results suggest that the bifactor model fit the data well in the full sample. Although the data suggest configural invariance across gender, factor loadings could not be constrained to be equal between men and women. As such, general and specific factors were examined separately by gender with a more intensive subsample of females and males (n = 264). Correlations with motivational tendencies, personality traits, and mental health symptoms indicated support for the validity of the bifactor model, as well as gender-specific patterns of association. Results suggest informative distinctions between shared and unique attributes related to problematic drinking and gambling.","subset":"pubmed_abstract"} +{"meta":{"pmid":28734631,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2019-51":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-09":1,"2017-47":1,"2020-05":1}}},"text":"Sexting and the Definition Issue.\nSexting among youths has become a necessary topic of interest in research because of the negative consequences that this activity could create, especially when content is shared with others. Indeed, this loss of control could lead to humiliation, (cyber)bullying, or harassment. The development of new technologies, press coverage, and increase of prevalence rates could also explain the growth of interest in sexting. However, its definition is still a gray area. This review examines the different definitions of sexting used in the literature and its correlates. Several elements of the definition of sexting were assessed: actions (sending, receiving, and forwarding); media types (text, images, and videos); sexual characteristics; and transmission modes. Nine databases were searched for studies on sexting among youths up to 18 years of age. Eighteen studies published between 2012 and 2015 were included. Prevalence rates of sexting ranged between .9% and 60% partly depending on the definition. Most studies assessed sending, but when sending and receiving were measured, prevalence rates were higher for receiving. Some articles found associations with age, gender, race, sexual behavior, romantic relationships, risky behaviors, online activity, psychological difficulties, and social pressure. Finding a consensus regarding the definition is essential to assess accurately the activity and adapt prevention. Adolescents' interpretations of the activity are important as sexting could be used as a sexual behavior between two consenting persons. Prevention strategies should focus on sexting that goes wrong when it is forwarded to a third party and when it occurs in a context of pressure or harassment.","subset":"pubmed_abstract"} +{"meta":{"pmid":3004107,"dup_signals":{"dup_doc_count":24,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":1,"2023-14":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2024-22":1}}},"text":"Cyclic AMP potentiates glucose-induced insulin release from mouse pancreatic islets without increasing cytosolic free Ca2+.\nThe effects of various stimulants of insulin release on cytosolic free Ca2+, [Ca2+]i, in dispersed and cultured pancreatic beta-cells from ob\/ob-mice were studied using the indicator quin-2, which in itself has only slight effects on the glucose-induced insulin release and the metabolism of the sugar. The resting [Ca2+]i was 158 +\/- 7 nM. After increasing glucose to 20 mM there was a lag-period of 1-2 min before [Ca2+]i gradually rose, reaching a new plateau 60% higher after 5-6 min. Increasing intracellular cyclic AMP by adding forskolin did not further increase [Ca2+]i; on the contrary there was a slight temporary reduction despite a doubling of insulin secretion. The maintenance of the beta-cell function was evident from a marked increase of cytosolic [Ca2+]i after depolarization evoked by high extracellular K+. Also dibutyryl cyclic AMP and theophylline lacked the ability to raise [Ca2+]i beyond that obtained by glucose. The results suggest that cyclic AMP potentiates glucose-induced insulin release by sensitizing the secretory machinery to changes of [Ca2+]i rather than by increasing the cytosolic concentration of the ion.","subset":"pubmed_abstract"} +{"meta":{"pmid":26334534,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Using genome-wide associations to identify metabolic pathways involved in maize aflatoxin accumulation resistance.\nAflatoxin is a potent carcinogen that can contaminate grain infected with the fungus Aspergillus flavus. However, resistance to aflatoxin accumulation in maize is a complex trait with low heritability. Here, two complementary analyses were performed to better understand the mechanisms involved. The first coupled results of a genome-wide association study (GWAS) that accounted for linkage disequilibrium among single nucleotide polymorphisms (SNPs) with gene-set enrichment for a pathway-based approach. The rationale was that the cumulative effects of genes in a pathway would give insight into genetic differences that distinguish resistant from susceptible lines of maize. The second involved finding non-pathway genes close to the most significant SNP-trait associations with the greatest effect on reducing aflatoxin in multiple environments. Unlike conventional GWAS, the latter analysis emphasized multiple aspects of SNP-trait associations rather than just significance and was performed because of the high genotype x environment variability exhibited by this trait. The most significant metabolic pathway identified was jasmonic acid (JA) biosynthesis. Specifically, there was at least one allelic variant for each step in the JA biosynthesis pathway that conferred an incremental decrease to the level of aflatoxin observed among the inbred lines in the GWAS panel. Several non-pathway genes were also consistently associated with lowered aflatoxin levels. Those with predicted functions related to defense were: leucine-rich repeat protein kinase, expansin B3, reversion-to-ethylene sensitivity1, adaptor protein complex2, and a multidrug and toxic compound extrusion protein. Our genetic analysis provided strong evidence for several genes that were associated with aflatoxin resistance. Inbred lines that exhibited lower levels of aflatoxin accumulation tended to share similar haplotypes for genes specifically in the pathway of JA biosynthesis, along with several non-pathway genes with putative defense-related functions. Knowledge gained from these two complementary analyses has improved our understanding of population differences in aflatoxin resistance.","subset":"pubmed_abstract"} +{"meta":{"pmid":7585534,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Combined vaccination with major histocompatibility class I and interleukin 2 gene-transduced melanoma cells synergizes the cure of postsurgical established lung metastases.\nWe have analyzed and compared in detail the malignant phenotypes of, the immune mechanisms induced by, and the immunotherapeutic potentials of B16-F10.9 melanoma cells manipulated by gene transfer to express syngeneic H-2Kb molecules or to secrete the cytokines interleukin 2 (IL-2) or IL-6. Local tumor growth in the footpad of transduced cells is mainly retarded by expression of H-2Kb and IL-2 genes and less by expression of IL-6. Mice given injections intrafootpad of tumorigenic doses of transduced clones manifested significantly reduced postsurgical spontaneous metastasis. After i.v. inoculation, mice given injections of F10.9-Kb expressors did not develop experimental lung metastases; mice given injections of F10.9-IL-6 secretors developed reduced metastatic loads; whereas mice given injections of F10.9-IL-2 secretors developed high loads of lung metastases. On the basis of injections into nude mice, in vivo depletions of CD4+, CD8+, and NK1.1+ cells, and in vitro CTL and natural killer (NK) assays, we show that all F10.9-modified cells induce CD8+ tumor-specific CTL activity and that F10.9-IL-2 secretors also induce nonspecific NK\/lymphokine-activated killer cell activity. Vaccinations with F10.9-modified cells were capable of significantly reducing metastatic spread from small established F10.9 footpad tumors. However, in mice carrying preestablished lung metastases, a highly therapeutic effect was achieved only when H-2Kb expressors and IL-2 secretors were combined in vaccination, whereas individual vaccines or other combinations had marginal effects. This higher efficiency of the combined vaccine is due to the combined effect of efficient CTL induction and NK\/lymphokine-activated killer cell activity as concluded from depletion of CD8+ and NK1.1 cells during immunotherapy. Thus, the cure of established metastasis can be achieved by the synergistic effects of vaccination with class I and IL-2-transduced tumor cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":9521677,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"DNA minor groove binding-directed poisoning of human DNA topoisomerase I by terbenzimidazoles.\nWe have employed a broad range of spectroscopic, calorimetric, DNA cleavage, and DNA winding\/unwinding measurements to characterize the DNA binding and topoisomerase I (TOP1) poisoning properties of three terbenzimidazole analogues, 5-phenylterbenzimidazole (5PTB), terbenzimidazole (TB), and 5-(naphthyl[2,3-d]imidazo-2-yl)bibenzimidazole (5NIBB), which differ with respect to the substitutions at their C5 and\/or C6 positions. Our results reveal the following significant features. (i) The overall extent to which the three terbenzimidazole analogues poison human TOP1 follows the hierarchy 5PTB > TB >> 5NIBB. (ii) The impact of the three terbenzimidazole analogues on the superhelical state of plasmid DNA depends on the [total ligand] to [base pair] ratio (rbp), having no effect on DNA superhelicity at rbp ratios < or = 0.1, while weakly unwinding DNA at rbp ratios > 0.1. This weak DNA unwinding activity exhibited by the three terbenzimidazoles does not appear to be correlated with the abilities of these compounds to poison TOP1. (iii) Upon complexation with both poly(dA).poly(dT) and salmon testes DNA, the three terbenzimidazole analogues exhibit flow linear dichroism properties characteristic of a minor groove-directed mode of binding to these host DNA duplexes. (iv) The apparent minor groove binding affinities of the three terbenzimidazole analogues for the d(GA4T4C)2 duplex follow a qualitatively similar hierarchy to that noted above for ligand-induced poisoning of human TOP1-namely, 5PTB > TB > 5NIBB. In the aggregate, our results suggest that DNA minor groove binding, but not DNA unwinding, is important in the poisoning of TOP1 by terbenzimidazoles.","subset":"pubmed_abstract"} +{"meta":{"pmid":23436917,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Childhood weight gain and thyroid autoimmunity at age 60-64 years: the 1946 British birth cohort study.\nComplex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, including thyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and other thyroid disorders at age 60-64 years in a large population-based birth cohort study. In the UK Medical Research Council 1946 British Birth Cohort study, at age 60-64 years, 1277 women and 1185 men (78% of the target sample) responded to a postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood. At age 60-64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU\/mL), consistent with thyroid autoimmunity. Among women, both T4 use and positive anti-TPO antibodies at age 60-64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03-1.42) and positive anti-TPO antibodies (1.21, 1.00-1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12-3.76). In men and women without any thyroid disorders, serum free T4 concentrations were inversely associated with concurrent body mass index (P = .002). Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women.","subset":"pubmed_abstract"} +{"meta":{"pmid":22744497,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-18":2,"2024-10":1,"unknown":4}}},"text":"An improved kinematic model of the spine for three-dimensional motion analysis in the Vicon system.\nThe mechanism of creation and pathomechanics of lateral spinal deformation is still not fully explained. Modern medical imaging techniques give scientists possibility to understand some aspects, but vast majority of those techniques is based on static trials. A motion capture system belongs to techniques which enable visualization of a spine during dynamic trials; however, due to lack of appropriate computational model, it is unsuitable for scoliosis imaging. A few years ago our group has proposed a kinematic model of the spine to be used with Vicon Motion Capture System, which was based on B\u00e9zier curves. That model allowed for much more precise investigation of spinal kinematics during dynamic trials as compared with other computational models. However, it did not allowed to restrict only selected movements for particular segments of the spine (e.g. axial rotation for lumbar spine). The aim of the current work is to improve the proposed model in order to be able to restrict selected movements according to the knowledge concerning spinal anatomy and spinal range of motion. The new kinematic model of the spine was written in BodyBuilder for Biomechanics Language. For the purpose of visualization also an accurate graphical representation of each vertebra (polygon mesh) was computed and adapted to be compatible with the kinematic model. Using a new version of the model it is possible to perform precise analysis of movement of all vertebrae during such dynamic activities as e.g. gait and forward or lateral bending, as well as to present the results not only on the charts, but also as a 3D animation of movements of a realistically looking spine. The paper describes the new kinematic model and the process of creating graphical representation of the vertebrae. Also sample results obtained using that model are presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":27244564,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-21":2,"2021-17":1,"2020-40":1,"2020-29":1,"2019-18":1,"2019-04":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-26":1,"2017-17":1,"2023-50":1,"2017-13":1,"2024-10":1}}},"text":"Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart.\nStudies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electrotonic conduction occurs across non-myocyte gaps in the heart and is partly mediated by Connexin43 (Cx43). We investigated whether non-myocytes in ventricular scar tissue are electrically connected to surrounding myocardial tissue in wild type and fibroblast-specific protein-1 driven conditional Cx43 knock-out mice (Cx43fsp1KO). Electrical coupling between the scar and uninjured myocardium was demonstrated by injecting current into the myocardium and recording depolarization in the scar through optical mapping. Coupling was significantly reduced in Cx43fsp1KO hearts. Voltage signals were recorded using microelectrodes from control scars but no signals were obtained from Cx43fsp1KO hearts. Recordings showed significantly decreased amplitude, depolarized resting membrane potential, increased duration and reduced upstroke velocity compared to surrounding myocytes, suggesting that the non-excitable cells in the scar closely follow myocyte action potentials. These results were further validated by mathematical simulations. Optical mapping demonstrated that current delivered within the scar could induce activation of the surrounding myocardium. These data demonstrate non-myocytes in the scar are electrically coupled to myocytes, and coupling depends on Cx43 expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":24834208,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"History of upper gastrointestinal cancers in relatives: a community-based estimate.\nThe present study aimed to evaluate the prevalence of positive family history of these cancers in a large population-based sample of Tehran province, capital of Iran. Upper gastrointestinal (UGI) cancers (gastric and esophagus cancer) constitute a major health problem worldwide. A family history of cancer can increase the risk for developing cancer and recognized as one of the most important risk factors in predicting personal cancer risk. This study designed as a cross-sectional survey in general population (2006-2007) of Tehran province. Totally 7,300 persons (age > = 20 years) sampled by random sampling on the basis of the list of postal, of whom 6,700 persons agreed to participate (response rate 92%). Respondents were asked if any first-degree (FDR) or second-degree (SDR) relatives had gastric or esophageal cancer. Totally, 6,453 respondents (48% male) entered to the study. The mean age of responders with positive FH was significantly higher than those with negative FH (P < 0.05). In total, 341 respondents (5.3%) reporting a history of UGI cancers in their relatives, 134(2.1%) in FDRs, and 207(3.2%) in SDRs. Our findings showed that the reported prevalence of FH of UGI cancers was relatively low and varied by specific respondent characteristics such as age and sex. However, the estimates of prevalence presented here are likely to be conservative compared with actual prevalence because of self-reported data gathering.","subset":"pubmed_abstract"} +{"meta":{"pmid":28785410,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Can images of pain enhance patient-clinician rapport in pain consultations?\nA variety of treatment outcomes in chronic pain are influenced by patient-clinician rapport. Patients often report finding it difficult to explain their pain, and this potential obstacle to mutual understanding may impede patient-clinician rapport. Previous research has argued that the communication of both patients and clinicians is facilitated by the use of pain-related images in pain assessments. This study investigated whether introducing pain-related images into pain assessments would strengthen various components of patient-clinician rapport, including relative levels of affiliation and dominance, and interpersonal coordination between patient and clinician behaviour. Videos of 35 pain assessments in which pain images were present or absent were used to code behavioural displays of patient and clinician rapport at fixed intervals across the course of the assessment. Mixed modelling was used to examine patterns of patient and clinician affiliation and dominance with consultation type (Image vs Control) as a moderator. When pain images were present, clinicians showed more affiliation behaviour over the course of the consultation and there was greater correspondence between the affiliation behaviour of patient and clinician. However, relative levels of patient and clinician dominance were unaffected by the presence of pain images in consultations. Additional analyses revealed that clinicians responded directly to patients' use of pain images with displays of affiliation. Based on the results of this study, we recommend further investigation into the utility and feasibility of incorporating pain images into pain assessments to enhance patient-clinician communication.","subset":"pubmed_abstract"} +{"meta":{"pmid":23666128,"dup_signals":{"dup_doc_count":20,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":1,"2014-10":2,"2013-48":2,"unknown":9}}},"text":"Current trends in wireless mesh sensor networks: a review of competing approaches.\nFinding a complete mesh-based solution for low-rate wireless personal area networks (LR-WPANs) is still an open issue. To cope with this concern, different competing approaches have emerged in the Wireless Mesh Sensor Networks (WMSNs) field in the last few years. They are usually supported by the IEEE 802.15.4 standard, the most commonly adopted LR-WPAN recommendation for point-to-point topologies. In this work, we review the most relevant and up-to-date WMSN solutions that extend the IEEE 802.15.4 standard to multi-hop mesh networks. To conduct this review, we start by identifying the most significant WMSN requirements (i.e., interoperability, robustness, scalability, mobility or energy-efficiency) that reveal the benefits and shortcomings of each proposal. Then, we re-examine thoroughly the group of proposals following different design guidelines which are usually considered by end-users and developers. Among all of the approaches reviewed, we highlight the IEEE 802.15.5 standard, a recent recommendation that, in its LR-WPAN version, fully satisfies the greatest number of WMSN requirements. As a result, IEEE 802.15.5 can be an appropriate solution for a wide-range of applications, unlike the majority of the remaining solutions reviewed, which are usually designed to solve particular problems, for instance in the home, building and industrial sectors. In this sense, a description of IEEE 802.15.5 is also included, paying special attention to its efficient energy-saving mechanisms. Finally, possible improvements of this recommendation are pointed out in order to offer hints for future research.","subset":"pubmed_abstract"} +{"meta":{"pmid":6954540,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Identification of the stereospecific hexose transporter from starved and fed chicken embryo fibroblasts.\nWhen deprived of D-glucose for 24 hr, chicken embryo fibroblasts exhibit a marked increase in hexose transport activity compared with that of control cells. Scatchard analysis of [3H]cytochalasin B binding to starved cell plasma membranes (46 pmol\/mg) indicated a six-fold increase compared with fed cell plasma membranes (7.5 pmol\/mg). Irradiation of starved cell plasma membranes with high-intensity UV light in the presence of 0.5 microM [3H]cytochalasin B resulted in covalent labeling of polypeptides of Mr 52,000 and 46,000. In fed cell plasma membranes irradiated under the same conditions, both polypeptides were labeled but at greatly decreased levels. In fact, labeling of the Mr 52,000 polypeptide was barely detectable. The amount of D-glucose-sensitive [3H]cytochalasin B covalent insertion into these membrane components was increased 11 +\/- 2 (n = 4)-fold in starved versus fed cell plasma membranes. Photoaffinity labeling of both polypeptides in starved cell plasma membranes was inhibited by D-glucose, 3-O-methylglucose, 2-deoxyglucose, cytochalasin B, and cytochalasin A but not by D-sorbitol, L-glucose, or cytochalasin E. Half-maximal inhibition of labeling of the Mr 52,000 polypeptide occurred at 8 mM D-glucose whereas, for the Mr 46,000 polypeptide, half-maximal inhibition occurred at 40 mM D-glucose. It is concluded that (i) two hexose transport proteins, one of Mr 46,000 and one of Mr 52,000, have been identified in chicken embryo fibroblasts and (ii) the increased affinity labeling of these transporter components after cell starvation may reflect increased numbers of transporters in the plasma membrane.","subset":"pubmed_abstract"} +{"meta":{"pmid":32845044,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Intramolecular Coupling of Terminal Alkynes by Atom Manipulation.\nGlaser-like coupling of terminal alkynes by thermal activation is extensively used in on-surface chemistry. Here we demonstrate an intramolecular version of this reaction performed by atom manipulation. We used voltage pulses from the tip to trigger a Glaser-like coupling between terminal alkyne carbons within a custom-synthesized precursor molecule adsorbed on bilayer NaCl on Cu(111). Different conformations of the precursor molecule and the product were characterized by molecular structure elucidation with atomic force microscopy and orbital density mapping with scanning tunneling microscopy, accompanied by density functional theory calculations. We revealed partially dehydrogenated intermediates, providing insight into the reaction pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":21308171,"dup_signals":{"dup_doc_count":46,"dup_dump_count":36,"dup_details":{"curated_sources":4,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2017-43":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-20":1,"2024-18":1}}},"text":"[Local governance in the decentralized health care system in Brazil].\nTo analyze the changes in local health care governance resulting from the decentralization process associated with the Unified Health System (SUS) in Brazil between 1996 and 2006. A questionnaire was answered in 1996 and again in 2006 by all city officials involved in health care management in Brazil. Information was collected on the innovative characteristics of administrative practices in terms of three dimensions: social, management, and care. The present article analyzes the results relating to the social dimension (relationship between municipal officials and the various community actors) according to four attributes: preparing the budget (degree of influence of various actors), establishing priorities, accountability, and flow of information to the community. The influence of municipal secretaries of health and health councils on budget preparation has increased, with a decrease of local politician influence. In prioritizing health issues, local politicians and spontaneous demands have also become less influential, with strengthening of the influence of technical opinions and proposals by health councils and conferences. Public disclosure of results has become institutionalized as a result of the diversification of stakeholders (especially municipal secretaries and health councils) and of the methods available for disclosure, even though balance sheets are still the most common type of information disclosed (which imply technical knowledge for interpretation of results). Finally, the information conveyed to the community still mainly refers to health actions and campaigns and functioning of health services, even though a larger amount of innovative information is being communicated. This was observed in all regions and in cities of all sizes, with a more progressive trend in the South of Brazil. The relationship between government and society has changed toward a more democratic standard of local governance, despite the maintenance of centralized government decision-making practices. The process of decentralization still faces important obstacles to the establishment of a more participative model, with enhanced social control, accountability and interaction between government and society.","subset":"pubmed_abstract"} +{"meta":{"pmid":30640653,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Interfascial block at the serratus muscle plane versus conventional analgesia in breast surgery: a randomized controlled trial.\nIn the context of opioid-sparing perioperative management, there is still little evidence from randomized controlled trials regarding the effectiveness of interfascial thoracic blocks. This study hypothesizes that receiving a serratus plane block reduces opioid requirements, pain scores, and rescue medication needs. This double-blind, randomized controlled study was conducted on 60 adult females undergoing oncologic breast surgery. After general anesthesia, patients were randomly allocated to either conventional analgesia (control group, n=30) or single-injection serratus block with L-bupivacaine 0.25% 30mL (study group, n=30). First 24-hour total morphine consumption (primary outcome), pain scores at 1, 3, 6, 12, and 24 hours, time-to-first opioid rescue analgesia, and adverse effects were recorded. Median 24 hours' opioid dose was greater in the control group (median difference 9 mg (95% CI 4 to 14.5 mg); p<0.001). Proportional odds model showed that the study group has a lower probability of receiving opioid drugs (OR=0.26 (95% CI 0.10 to 0.68); p<0.001), while mastectomies have a higher probability of receiving them (OR=4.11 (95% CI 1.25 to 13.58); p=0.002). Pain scores in the study group were significantly lower throughout the follow-up period (p<0.001). Control group subjects needed earlier morphine rescue and had a higher risk of rescue dose requirement (p=0.002). Interfascial serratus plane block reduces opioid requirements and is associated with better pain scores and lower and later rescue analgesia needs in the first 24 hours, compared with conventional intravenous analgesia, in breast surgery. NCT02905149.","subset":"pubmed_abstract"} +{"meta":{"pmid":15356063,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Analysis of immune regulatory genes in familial and sporadic Graves' disease.\nGraves' disease (GD) is seen in apparently sporadic and familial forms. At least two immune regulatory genes are associated with GD, human leukocyte antigen (HLA) and cytotoxic T lymphocyte antigen-4 (CTLA-4). The aim of our study was to examine the contributions of HLA and CTLA-4 to the familial clustering of GD by analyzing them for association with familial and sporadic GD. We analyzed 160 Caucasian GD patients (69 familial and 91 sporadic), and 150 matched controls. Analysis of all GD patients demonstrated significant associations between GD and HLA-DR3 [P = 9.0 x 10(-7); relative risk (RR) = 3.8] and two CTLA-4 single nucleotide polymorphisms (SNPs), A\/G(49) SNP (P = 0.03; RR = 1.5), and CT60 SNP (P = 0.03; RR = 1.4). Moreover, there was evidence for joint susceptibility to risk between HLA-DR3 and CTLA-4, giving a combined RR of 5.9. Subset analysis demonstrated no significant difference between the frequencies of HLA-DR3 and the susceptibility alleles of CTLA-4 A\/G(49) and CT60 SNPs in the familial and sporadic GD subsets (P > 0.05). These results suggested that HLA-DR3 and CTLA-4 conferred a general increased risk for GD in both the sporadic and familial forms, and that the risk conferred by them was additive. However, HLA-DR3 and CTLA-4 did not have a stronger effect in the familial GD patients, suggesting that additional genes must contribute to the aggregation of GD within families.","subset":"pubmed_abstract"} +{"meta":{"pmid":12231840,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Further Characterization of Expression of Auxin-Induced Genes in Tobacco (Nicotiana tabacum) Cell-Suspension Cultures.\nWe have described the modulation of four auxin-regulated genes during the growth cycle of suspension-cultured tobacco (Nicotiana tabacum [L.] var White Burley) cells. The genes were transiently expressed 2 to 8 h after transfer of stationary phase cells to fresh medium, during the transition from the quiescent phase of cells leaving the mitotic cycle to the synthesis phase of the cell cycle. After this transient induction, the cells showed a decreased sensitivity to auxin. Although the expression pattern suggests that induction of these genes might be important for cell division, over-production of antisense mRNA for one of these genes (pCNT103) did not influence cell division in transgenic tobacco cells. Furthermore, stimuli such as salicylic acid were capable of inducing gene expression but were unable to restore cell division. Although these data do not conclusively exclude a role for these genes in cell division, their significance in this process is discussed in view of their homology with other auxin-induced genes and in view of the specificity of hormone-induced early responses.","subset":"pubmed_abstract"} +{"meta":{"pmid":11359645,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":12}}},"text":"Stochastic organization of output codes in multiclass learning problems.\nThe best-known decomposition schemes of multiclass learning problems are one per class coding (OPC) and error-correcting output coding (ECOC). Both methods perform a prior decomposition, that is, before training of the classifier takes place. The impact of output codes on the inferred decision rules can be experienced only after learning. Therefore, we present a novel algorithm for the code design of multiclass learning problems. This algorithm applies a maximum-likelihood objective function in conjunction with the expectation-maximization (EM) algorithm. Minimizing the augmented objective function yields the optimal decomposition of the multiclass learning problem in two-class problems. Experimental results show the potential gain of the optimized output codes over OPC or ECOC methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":34835180,"dup_signals":{"dup_doc_count":24,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":4,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":15}}},"text":"Stability of Chimpanzee Adenovirus Vectored Vaccines (ChAdOx1 and ChAdOx2) in Liquid and Lyophilised Formulations.\nAdenovirus vectored vaccines have entered global use during the COVID-19 pandemic, and are in development for multiple other human and veterinary applications. An attraction of the technology is the suitability of the vaccines for storage at 2-8 \u00b0C for months. Widely used COVID-19 vaccine ChAdOx1 nCoV-19 (University of Oxford\/AstraZeneca) is based on a species E simian adenovirus. Species E simian serotypes have been used in a wide range of other development programs, but the stability of such vectors has not been extensively described in the peer-reviewed literature. Here, we explore the stability of two candidate vaccines based on two species E serotypes: a Rift Valley fever vaccine based upon the ChAdOx1 vector (Y25 serotype) used in ChAdOx1 nCoV-19, and a rabies vaccine based upon a ChAdOx2 vector (AdC68 serotype). We describe each vector's stability in liquid and lyophilised formulations using in vitro and in vivo potency measurements. Our data support the suitability of liquid formulations of these vectors for storage at 2-8 \u00b0C for up to 1 year, and potentially for nonrefrigerated storage for a brief period during last-leg distribution (perhaps 1-3 days at 20 \u00b0C-the precise definition of acceptable last-leg storage conditions would require further product-specific data). Depending upon the level of inprocess potency loss that is economically acceptable, and the level of instorage loss that is compatible with maintenance of acceptable end-of-storage potency, a previously reported lyophilised formulation may enable longer term storage at 20 \u00b0C or storage for a number of days at 30 \u00b0C.","subset":"pubmed_abstract"} +{"meta":{"pmid":31507507,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"MRI Atlas of the Human Deep Brain.\nMastering detailed anatomy of the human deep brain in clinical neurosciences is challenging. Although numerous pioneering works have gathered a large dataset of structural and topographic information, it is still difficult to transfer this knowledge into practice, even with advanced magnetic resonance imaging techniques. Thus, classical histological atlases continue to be used to identify structures for stereotactic targeting in functional neurosurgery. Physicians mainly use these atlases as a template co-registered with the patient's brain. However, it is possible to directly identify stereotactic targets on MRI scans, enabling personalized targeting. In order to help clinicians directly identify deep brain structures relevant to present and future medical applications, we built a volumetric MRI atlas of the deep brain (MDBA) on a large scale (infra millimetric). Twelve hypothalamic, 39 subthalamic, 36 telencephalic, and 32 thalamic structures were identified, contoured, and labeled. Nineteen coronal, 18 axial, and 15 sagittal MRI plates were created. Although primarily designed for direct labeling, the anatomic space was also subdivided in twelfths of AC-PC distance, leading to proportional scaling in the coronal, axial, and sagittal planes. This extensive work is now available to clinicians and neuroscientists, offering another representation of the human deep brain ([https:\/\/hal.archives-ouvertes.fr\/] [hal-02116633]). The atlas may also be used by computer scientists who are interested in deciphering the topography of this complex region.","subset":"pubmed_abstract"} +{"meta":{"pmid":30756315,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":12}}},"text":"Patient-Derived Xenografts Can Be Reliably Generated from Patient Clinical Biopsy Specimens.\nPatient-derived xenografts (PDX) are clinically relevant human cancer models that can be used to guide individualized medicine. We aimed to generate PDX models from clinically obtained biopsy specimens (surgical or image-guided) hypothesizing that low volume biopsy specimens could provide sufficient viable tissue to successfully engraft PDX models from patients with unresectable or metastatic disease. We maintain a prospective high volume gastrointestinal malignancy PDX program. With informed consent and institutional approval, biopsy specimens (surgical or image-guided) were obtained from patients with unresectable or metastatic tumors: pancreatic adenocarcinoma (PDAC), cholangiocarcinoma, gastric and gallbladder carcinoma. Biopsies were implanted into immunodeficient mice. Tumor growth was monitored, viable tumor was passed into subsequent generations, and histopathology was confirmed. In this study, biopsy specimens from 29 patients were used for PDX engraftment. Successful PDX engraftment was variable with highest engraftment rates in gastric and gallbladder carcinoma specimens (100%) compared to engraftment rates of 33% and 29% in PDAC and cholangiocarcinoma respectively. PDX models created from metastasis biopsies compared to unresectable primary tumor tissue demonstrated higher engraftment rates (69% versus 15.4%, p = 0.001). PDX models demonstrated higher engraftment rates when biopsies were obtained during surgical operations (n = 15) compared to image-guided (n = 14) (73% versus 14%, p = 0.003). Patient age, pretreatment status, or ischemic time was not different between biopsy methods. PDX models can be successfully created from clinical biopsy specimens in patients with metastatic or unresectable GI cancers. The use of clinical biopsy specimens for PDX engraftment can expand the repertoire of stage-specific PDX models for downstream basic\/translational research.","subset":"pubmed_abstract"} +{"meta":{"pmid":33202060,"dup_signals":{"dup_doc_count":20,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":2,"2024-22":5,"2024-18":2,"2024-10":1,"unknown":5}}},"text":"Can psychological characteristics, football experience, and player status predict state anxiety before important matches in Danish elite-level female football players?\nElite football can make players feel nervous, and personality characteristics, as well as experience, affect how well pressure is handled before important games. Studying the psychological characteristics of female football players can provide information on how well psychological pressure is handled and generate knowledge on how to support players in order to improve performance. Based on a sample of 128 female elite football players from 8 top-level teams, the present study investigates whether psychological characteristics and football experience\/player stus in elite female football players can predict state anxiety before important matches. Our results outline that high age and national team experience negatively predicted most of the trait anxiety subscales. In line with previous research, no psychological differences were found between goalkeepers, defenders, midfielders, and strikers while starting players revealed to have significantly lower trait anxiety. When measuring before important matches, we found that somatic state anxiety was negatively associated with senior national team experience and positively associated with worry trait anxiety and fear of failure. Cognitive state anxiety was negatively associated with hope for success and positively associated with somatic and worry trait anxiety. Self-confidence was positively associated with youth national team experience and negatively associated with worry trait anxiety. It can be concluded that psychological characteristics and national team experience are both important for optimal state anxiety before important matches in elite-level women's football. Implications for practice and future research are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":17111071,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A horse chestnut extract, which induces contraction forces in fibroblasts, is a potent anti-aging ingredient.\nContraction forces generated by non-muscle cells, such as fibroblasts, play important roles in determining cell morphology, vasoconstriction, and\/or wound healing. We have searched among various plant extracts for ingredients that generate cell contraction forces using fibroblast-populated collagen gels. Using that model, we found that an extract of horse chestnuts (Aesculus hippocastanum) is able to generate such contraction forces in fibroblasts. The involvement of stress fiber formation in that response is suggested by the inhibition of such force generation by cytochalasin D and rhodamine phalloidin stain. Clinical testing of the extract was carried out using 40 healthy female volunteers. A gel formulation that included 3% of the extract was applied topically to the skin around the eye three times daily for nine weeks. The efficacy of the extract to diminish wrinkles was evaluated by visual scoring based on photo scales. After six weeks, significant decreases in the wrinkle scores at the corners of the eye or in the lower eyelid skin were observed compared with controls. After nine weeks, similar results were obtained. Taken together, our results suggest that an extract of horse chestnuts can generate contraction forces in fibroblasts and is a potent anti-aging ingredient.","subset":"pubmed_abstract"} +{"meta":{"pmid":24838986,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Carbon tips for all-carbon single-molecule electronics.\nWe present here an exhaustive ab initio study of the use of carbon-based tips as electrodes in single-molecule junctions. Motivated by recent experiments, we show that carbon tips can be combined with other carbon nanostructures, such as graphene, to form all-carbon molecular junctions with molecules like benzene or C60. Our results show that the use of carbon tips can lead to relatively conductive molecular junctions. However, contrary to junctions formed with standard metals, the conductance traces recorded during the formation of the all-carbon single-molecule junctions do not exhibit clear conductance plateaus, which can be attributed to the inability of the hydrogenated carbon tips to form chemical bonds with the organic molecules. Additionally, we explore here the use of carbon tips for scanning tunneling microscopy and show that they are well suited for obtaining sample images with atomic resolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":28300519,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":2,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2023-50":1,"2024-22":1}}},"text":"On Suggestibility and Placebo: A Follow-Up Study.\nIdentifying what makes some people respond well to placebos remains a major challenge. Here, we attempt to replicate an earlier study in which we found a relationship between hypnotic suggestibility and subjective ratings of relaxation following the ingestion of a placebo sedative (Sheiner, Lifshitz, & Raz, 2016). To assess the reliability of this effect, we tested 34 participants using a similar design. Participants ingested a placebo capsule in one of two conditions: (1) relaxation, wherein we described the capsule as a herbal sedative, or (2) control, wherein we described the capsule as inert. To index placebo response, we collected measures of blood pressure and heart rate, as well as self-report ratings of relaxation and drowsiness. Despite using a similar experimental design as in our earlier study, we were unable to replicate the correlation between hypnotic suggestibility and placebo response. Furthermore, whereas in our former experiment we observed a change in subjective ratings of relaxation but no change in physiological measures, here we found that heart rate dropped in the relaxation condition while subjective ratings remained unchanged. Even within a consistent context of relaxation, therefore, our present results indicate that placebos may induce effects that are fickle, tenuous, and unreliable. Although we had low statistical power, our findings tentatively accord with the notion that placebo response likely involves a complex, multifaceted interaction between traits, expectancies, and contexts.","subset":"pubmed_abstract"} +{"meta":{"pmid":3605497,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2020-45":1,"2020-29":1,"2020-10":1,"2019-51":1,"2019-39":1,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2022-27":1}}},"text":"Comparative sensitivity and specificity of ELISA and IHA for serodiagnosis of strongyloidiasis with larval antigens.\nSera from 68 patients with parasitologically proven strongyloidiasis were tested by the ELISA and IHA tests using larval antigens prepared from Strongyloides stercoralis and Strongyloides ratti. The ELISA using the S. stercoralis antigen detected the greatest number of sero-reactors (83.8%), whereas the IHA using the S. ratti antigen detected the fewest (55.9%). In addition, the S. stercoralis antigen had higher geometric mean titers than the S. ratti antigen in both the ELISA and the IHA tests. Sera from 37 presumed normal individuals also were tested by IHA and ELISA and nonspecific reactions were seen only with the IHA test. When sera from patients with parasitic infections other than strongyloidiasis were tested, the only consistent cross-reactions were with those sera from patients who had occult filariasis and acute schistosomiasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":37873687,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":5,"2024-10":1,"unknown":5}}},"text":"Diet composition, adherence to calorie restriction, and cardiometabolic disease risk modification.\nCalorie restriction (CR) is a promising approach for attenuating the risk of age-related disease. However, the role of diet composition on adherence to CR and the effects of CR on cardiometabolic markers of healthspan remains unknown. We used the Geometric Framework for Nutrition approach to examine the association between macronutrient composition and CR adherence during the 2-year CALERIE trial. Adult participants without obesity were randomized to a 25% CR intervention or an ad libitum intake control. Correlations of cardiometabolic risk factors with macronutrient composition and standard dietary pattern indices [Alternate Mediterranean Diet Index (aMED), Dietary Inflammatory Index (DII), and Healthy Eating Index (HEI)] were also evaluated by Spearman's correlation at each time point. The mean age was 38.1 \u00b1 7.2 years at baseline and the mean BMI was 25.1 \u00b1 1.7. The study population was 70% female. The CR group, but not the control, consumed a higher percentage reported energy intake from protein and carbohydrate and lower fat at 12 months compared to baseline; comparable results were observed at 24 months. Protein in the background of higher carbohydrate intake was associated with greater adherence at 24 months. There was no correlation between macronutrient composition and cardiometabolic risk factors in the CR group. However, statistically significant correlations were observed for the DII and HEI. These findings suggest that individual self-selected macronutrients have an interactive but not independent role in CR adherence. Additional research is required to examine the impact of varying macronutrient compositions on adherence to CR and resultant modification to cardiometabolic risk factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":7625622,"dup_signals":{"dup_doc_count":18}},"text":"Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens.\nTo compare the effectiveness and tolerability of three misoprostol dosing regimens for the prevention of gastric and duodenal ulcers associated with long-term nonsteroidal anti-inflammatory drug (NSAID) therapy. A multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel, four-limb study. Eligibility criteria included upper gastrointestinal symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession and regimen-compliance criteria and completed the trial. These 1197 patients composed the evaluable group. Patients were randomly assigned to one of four regimens: placebo four times daily; 200 micrograms of misoprostol twice daily and placebo twice daily; 200 micrograms of misoprostol three times daily and placebo once daily; and 200 micrograms of misoprostol four times daily. Upper gastrointestinal endoscopic examinations for ulcers were done after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were assessed by adverse-event monitoring. In the placebo group, the incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was 7.5%. The incidence of gastric ulcers was significantly lower in the groups receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to 12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to 16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to 16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was significantly higher in patients receiving misoprostol twice daily compared with those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to 7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was significantly lower in the groups receiving misoprostol twice daily (2.6%; difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%; difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%; difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No significant difference was detected between patients receiving misoprostol twice daily and those receiving misoprostol three times daily, and no dose-response effect was noted with duodenal ulcers. The incidence of withdrawals for adverse events was significantly lower in the groups receiving misoprostol twice daily (12%) and three times daily (12%) than in the group receiving it four times daily (20%). The incidence of gastrointestinal adverse events was significantly higher in the group receiving misoprostol four times daily (74%) than in the placebo group (62%). Misoprostol, 200 micrograms twice or three times daily, offers substantial protection against gastric and duodenal ulcers in patients receiving long-term NSAID therapy. These dosages were better tolerated than the currently approved regimen of 200 micrograms four times daily.","subset":"pubmed_abstract"} +{"meta":{"pmid":16039027,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":1,"2024-30":1,"unknown":10}}},"text":"The voices of older women in a disadvantaged community: issues of health and social capital.\nThe voices of older women are rarely heard in debates about the health of disadvantaged groups. Despite growing interest in health in old age, the health experiences of older women as gendered social beings have yet to be fully explored. Their potential to contribute positively to family and community health is seldom acknowledged. The aim of this article is to present findings from a qualitative British Health Development Agency funded project on the relationship between social capital, health and gender, focusing on the health and social networks of older women in a socially disadvantaged community in the north of England. Seventy-seven community members were interviewed, of these 19 were older women aged 55-78 years. Their accounts of ill health in the context of ageing were analysed to explore the intricate ways in which social capital was created, maintained and linked to health. Findings suggest that social constructions of motherhood and caring underpinned responsibility for their own and others' health. Their experiences of dealing with health matters, together with frequent health talk, gave the women confidence as lay health experts, enabling them to contest medical advice. Drawing on personal experiences of trust and reciprocity, they recognised the importance of social networking in alleviating the problems of loneliness and isolation. At stressful times in their lives they were able to draw on existing support networks and, in spite of occasional personal conflicts, some benefited from the empowering and health-enhancing role of formal and informal participation in community life. These findings indicate that older women can operate autonomously in health matters and can substantially influence the development of healthy communities, although this can sometimes be at a personal cost.","subset":"pubmed_abstract"} +{"meta":{"pmid":22747910,"dup_signals":{"dup_doc_count":17,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-18":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":12}}},"text":"Shape engineering vs organic modification of inorganic nanoparticles as a tool for enhancing cellular internalization.\nIn nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmacokinetics and biodistribution, which are also decisive for the passive targeting and nonspecific cellular uptake of nanoparticles. Size and surface charge are, consequently, two main determining factors in nanomedicine applications. Another important parameter which has received much less attention is the morphology (shape) of the nanocarrier. In order to investigate the morphology effect on the extent of cellular internalization, two similarly sized but differently shaped rod-like and spherical mesoporous silica nanoparticles were synthesized, characterized and functionalized to yield different surface charges. The uptake in two different cancer cell lines was investigated as a function of particle shape, coating (organic modification), surface charge and dose. According to the presented results, particle morphology is a decisive property regardless of both the different surface charges and doses tested, whereby rod-like particles internalized more efficiently in both cell lines. At lower doses whereby the shape-induced advantage is less dominant, charge-induced effects can, however, be used to fine-tune the cellular uptake as a prospective 'secondary' uptake regulator for tight dose control in nanoparticle-based drug formulations.","subset":"pubmed_abstract"} +{"meta":{"pmid":16660559,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Nickel in plants: I. Uptake kinetics using intact soybean seedlings.\nThe absorption of Ni(2+) by 21-day-old soybean plants (Glycine max cv. Williams) was investigated with respect to its concentration dependence, transport kinetics, and interactions with various nutrient cations. Nickel absorption, measured as a function of concentration (0.02 to 100 mum), demonstrated the presence of multiple absorption isotherms. Each of the three isotherms conforms to Michaelis-Menten kinetics; kinetic constants are reported for uptake by the intact plant and for transfer from root to shoot tissues. The absorption of Ni(2+) by the intact plant and its transfer from root to shoot were inhibited by the presence of Cu(2+), Zn(2+), Fe(2+), and Co(2+). Competition kinetic studies showed Cu(2+) and Zn(2+) to inhibit Ni(2+) absorption competitively, suggesting that Ni(2+), Cu(2+), and Zn(2+) are absorbed using the same carrier site. Calculated K(m) and K(i) constants for Ni(2+) in the presence and absence of Cu(2+) were 6.1 and 9.2 mum, respectively, whereas K(m) and K(i) constants were calculated to be 6.7 and 24.4 mum, respectively, for Ni(2+) in the presence and absence of Zn(2+). The mechanism of inhibition of Ni(2+) in the presence of Fe(2+) and Co(2+) was not resolved by classical kinetic relationships.","subset":"pubmed_abstract"} +{"meta":{"pmid":11226301,"dup_signals":{"dup_doc_count":84,"dup_dump_count":41,"dup_details":{"curated_sources":3,"2023-50":2,"2023-40":3,"2023-23":4,"2023-06":2,"2022-49":2,"2022-40":2,"2022-33":2,"2022-27":3,"2022-21":4,"2022-05":1,"2021-49":3,"2021-43":2,"2021-39":1,"2021-31":3,"2021-25":1,"2021-21":1,"2021-17":3,"2021-10":1,"2021-04":3,"2020-50":1,"2020-45":2,"2020-40":2,"2020-34":1,"2020-05":1,"2019-51":1,"2019-13":2,"2019-09":1,"2018-51":2,"2018-47":1,"2018-43":2,"2018-39":1,"2018-34":2,"2018-30":1,"2018-26":2,"2018-17":2,"2018-09":2,"2017-47":2,"2017-39":2,"2017-30":1,"2024-22":6,"2024-18":1}}},"text":"Alkaline-mediated differential interaction (AMDI): a simple automatable single-nucleotide polymorphism assay.\nThe key requirements for high-throughput single-nucleotide polymorphism (SNP) typing of DNA samples in large-scale disease case-control studies are automatability, simplicity, and robustness, coupled with minimal cost. In this paper we describe a fluorescence technique for the detection of SNPs that have been amplified by using the amplification refractory mutation system (ARMS)-PCR procedure. Its performance was evaluated using 32 sequence-specific primer mixes to assign the HLA-DRB alleles to 80 lymphoblastoid cell line DNAs chosen from our database for their diversity. All had been typed previously by alternative methods, either direct sequencing or gel electrophoresis. We believe the detection system that we call AMDI (alkaline-mediated differential interaction) satisfies the above criteria and is suitable for general high-throughput SNP typing.","subset":"pubmed_abstract"} +{"meta":{"pmid":30151508,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":14}}},"text":"Effect of cobalt content on the electrochemical properties and structural stability of NCA type cathode materials.\nAt present, the most common type of cathode materials, NCA (Li1-xNi0.80Co0.15Al0.05O2, x = 0 to 1), have a very high concentration of cobalt. Since cobalt is toxic and expensive, the existing design of cathode materials is neither cost-effective nor environmentally benign. We have performed density functional theory (DFT) calculations to investigate electrochemical, electronic, and structural properties of four types of NCA cathode materials with the simultaneous decrease in Co content along with the increase in Ni content. Our results show that even if the cobalt concentration is significantly decreased from 16.70% (NCA_I) to 4.20% (NCA_IV), variation in intercalation potential and specific capacity is not significant. For example, in the case of 50% Li concentration, the voltage drop is only \u223c17% while the change in specific capacity is negligible. Moreover, we have also explored the influence of sodium doping in the intercalation site on the electrochemical, electronic, and structural properties. By considering two extreme cases of NCAs (i.e., with highest and lowest Co content: NCA_I and NCA_IV, respectively), we have demonstrated the importance of Na doping from the structural and electronic point of view. Our results provide insight into the design of environmentally benign, low-cost cathode materials with reduced cobalt concentration.","subset":"pubmed_abstract"} +{"meta":{"pmid":30647183,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Position Statement: A Pragmatic Approach for Medical Cannabis and Patients with Rheumatic Diseases.\nPain is one reason some rheumatology patients may consider use of medical cannabis, a product increasingly perceived as a safe and neglected natural treatment option for many conditions. Legalization of recreational cannabis in Canada will promote access to cannabis. Physicians must therefore provide patients with the best evidence-based information regarding the medicinal effects and harm of cannabis. The Canadian Rheumatology Association (CRA) mandated the development of a position statement for medical cannabis and the rheumatology patient. The current literature regarding the effects of medical cannabis for rheumatology patients was assessed, and a pragmatic position statement to facilitate patient care was developed by the Therapeutics Committee of the CRA and approved by the CRA board. There are no clinical trials of medical cannabis in rheumatology patients. Evidence is insufficient about the benefit of pharmaceutical cannabinoids in fibromyalgia, osteoarthritis, rheumatoid arthritis, and back pain, but there is evidence of a high risk of harm. Extrapolating from other conditions, medical cannabis may provide some symptom relief for some patients. Short-term risks of psychomotor effects can be anticipated, but longterm risks have not been determined and are of concern. Despite lack of evidence for use of medical cannabis in rheumatology patients, we acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually respectful manner to ensure harm reduction for patients and society.","subset":"pubmed_abstract"} +{"meta":{"pmid":18946929,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":7}}},"text":"The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity.\nThe non-classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)-E is the least polymorphic of all the MHC class I molecules and acts as a ligand for receptors of both the innate and the adaptive immune systems. The recognition of self-peptides complexed to HLA-E by the CD94-NKG2A receptor expressed by natural killer (NK) cells represents a crucial checkpoint for immune surveillance by NK cells. However, HLA-E can also be recognised by the T-cell receptor expressed by alphabeta CD8 T cells and therefore can play a role in the adaptive immune response to invading pathogens. The recent resolution of HLA-E in complex with both innate and adaptive ligands has provided insight into the dual role of this molecule in immunity.","subset":"pubmed_abstract"} +{"meta":{"pmid":28547620,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":12}}},"text":"Cycles and synchrony in the Collared Lemming (Dicrostonyx groenlandicus) in Arctic North America.\nLemming populations are generally characterised by their cyclic nature, yet empirical data to support this are lacking for most species, largely because of the time and expense necessary to collect long-term population data. In this study we use the relative frequency of yearly willow scarring by lemmings as an index of lemming abundance, allowing us to plot population changes over a 34-year period. Scars were collected from 18 sites in Arctic North America separated by 2-1,647 km to investigate local synchrony among separate populations. Over the period studied, populations at all 18 sites showed large fluctuations but there was no regular periodicity to the patterns of population change. Over all possible combinations of pairs of sites, only sites that were geographically connected and close (<6 km) showed significant synchrony in fluctuations. The populations studied may not even be cyclic, at least for the time period 1960 to 1994, and although fluctuating, randomisation tests could not reject the null hypothesis of random fluctuations. These data have implications for the testing of hypotheses regarding lemming cycles and highlight the need for long-term trapping data to characterise the lemming cycle.","subset":"pubmed_abstract"} +{"meta":{"pmid":22300804,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Control of HBV replication by antiviral microRNAs transferred by lentiviral vectors for potential cell and gene therapy approaches.\nBecause molecular mechanisms regulating host cell and virus interactions are not fully understood, we further defined roles of antiviral microRNAs (miRNAs) in HBV replication. We studied small interfering RNA sequences inserted into the miR-30 backbone in cell systems. Antiviral sequences were cloned into lentiviral vectors upstream of a green fluorescent protein reporter. Transduced cells included HepG2 or HepG2 2.2.15 cell lines and hTERT-FH-B fetal human liver cells. HBV replication was analysed by several assays. In 2.2.15 cells treated with constructs primarily targeting HBV polymerase and surface antigen or HBV polymerase and X open reading frames, HBV core protein, HBV DNA and HBV RNA expression decreased. This antiviral effect was more pronounced when the two constructs were expressed together. Similarly, antiviral constructs decreased HBV replication in HepG2 cells transduced with adenoviral vector to express HBV. Although antiviral sequences were expressed in hTERT-FH-B cells, these cells were non-permissive for HBV, possibly owing to expression of miRNAs reported to inhibit HBV replication, whereas these miRNAs were absent in HepG2 cells. Expression of antiviral miRNAs did not affect cell viability or proliferation and no deleterious changes were observed in expression of native cellular miRNAs. Moreover, expression of antiviral miRNA did not affect engraftment and survival of transplanted cells in mice. Identification of effective antiviral miRNAs and transfer of suitable constructs by lentiviral vectors will be helpful for pathophysiological studies of host cell-virus interactions. Simultaneously, this will advance potential mechanisms for cell\/gene therapy in those afflicted with chronic hepatitis and refractory liver disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":28964836,"dup_signals":{"dup_doc_count":48,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":2,"2023-14":1,"2023-06":1,"2022-49":2,"2022-27":4,"2022-21":1,"2022-05":1,"2021-39":2,"2021-25":2,"2021-21":2,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":2,"2020-45":1,"2020-40":1,"2020-29":1,"2019-47":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2023-50":1,"2024-30":3,"2024-26":1,"2024-22":1,"2024-18":3,"2024-10":1}}},"text":"Update on forebrain evolution: From neurogenesis to thermogenesis.\nComparative developmental studies provide growing understanding of vertebrate forebrain evolution. This short review directs the spotlight to some newly emerging aspects, including the evolutionary origin of the proliferative region known as the subventricular zone (SVZ) and of intermediate progenitor cells (IPCs) that populate the SVZ, neural circuits that originated within homologous regions across all amniotes, and the role of thermogenesis in the acquisition of an increased brain size. These data were presented at the 8th European Conference on Comparative Neurobiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":27493557,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Physical aspects of sensory transduction on seeing, hearing and smelling.\nWhat is the general principle of sensory transduction? Sensory transduction is defined as energy transformation from the external world to the internal world. The energy of the external world, such as thermal energy (heat), electro-magnetic energy (light), mechanical energy (sound) and the energy from molecules (chemicals), is converted into electrochemical events in the animal nervous system. The following five classes of special sense receptors are utilized for energy conversion: vision (photo); audition (sound); taste and smell (chemo); and tactile (mechano). There are also other special sense receptors, including thermo and noxious receptors. The focus of this study is on photoreceptors, sound-receptors and odorant-receptors because the transduction mechanisms of these receptors are explained biochemically and understood by a common physical principle; these biochemical models are well known in neuroscience. The following notable problems are inherent in these biochemical models: the cGMP ionophore model of the vertebrate photoreceptor cannot explain the fast photo-response (\u223cmsec); the tip links connection model of stereocilia in the basilar membrane for opening the K(+) channel on the tip of a hair has difficulty explaining the high frequency vibration of hair cells without a damping of the oscillation, and the odorant shape-specific receptor model for olfactory transduction has difficulty in discriminating the minute differences among similar fragrant smells of essential oils with different molecular shapes. These difficulties might arise from a lack of the physical sense when the transduction models were proposed. This article will reconsider these problems and propose rational models for visual, olfactory and auditory transduction.","subset":"pubmed_abstract"} +{"meta":{"pmid":30856834,"dup_signals":{"dup_doc_count":25,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":21}}},"text":"Changes in the Racial Composition of Phytophthora sojae in Australia Between 1979 and 1996.\nSurveys of commercial soybean fields, disease nurseries, and trial plots of soybean were conducted throughout eastern Australia between 1979 and 1996, and 694 isolates of Phytophthora sojae were collected and classified into races. Fourteen races, 1, 2, 4, 10, 15, and 25, and eight new races, 46 to 53, were identified, but only races 1, 4, 15, 25, 46, and 53 were found in commercial fields. Races 1 and 15 were the only races found in commercial fields in the soybean-growing areas of Australia up until 1989, with race 1 being the dominant race. Race 4 was found in central New South Wales in 1989 on cultivars with the Rps1a gene, and it is now the dominant race in central and southern New South Wales. Races 46 and 53 have only been found once, in southern New South Wales, and race 25 was identified in the same region in 1994 on a cultivar with the Rps1k gene. Only races 1 and 15 have been found in the northern soybean-growing regions, with the latter dominating, which coincides with the widespread use of cultivars with the Rps2 gene. Changes in the race structure of the P. sojae population from commercial fields in Australia follow the deployment of specific resistance genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":21307935,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-48":1,"unknown":9}}},"text":"Functional identification of an aggression locus in the mouse hypothalamus.\nElectrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.","subset":"pubmed_abstract"} +{"meta":{"pmid":37728040,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"An examination of willingness to participate and willingness to pay for a universal school food program in the Canadian context.\nTo examine parents'\/caregivers' willingness to participate and willingness to pay (WTP) for a cost-shared school food program (SFP) and its associated factors. A quantitative survey design was used where WTP for a hypothetical SFP was elicited using a double-bounded dichotomous choice elicitation method. We used a double hurdle (logistic and truncated regression) model to examine WTP and positively or negatively associated factors. Saskatoon Public School Division elementary schools situated in high-, mid- or low-median-income neighbourhoods. Parents or caregivers of children attending grades 1 to grade 8 in the Saskatoon Public School Division elementary schools. 94 % respondents were willing to participate in a SFP while less than two-thirds of participants were willing to pay for such a program. Over 90 % respondents from all the socio-economic groups were willing to participate. Multiple household income earners, higher household income, higher number of children, household food security status and higher academic attainment of parents'\/caregivers predicted greater willingness to pay. Mean willingness to pay was $4\u00b768 (CAN), and households reporting moderate or severe food insecurity were likely to be willing to pay significantly less for a SFP. A cost-shared program might be financially sustainable in Canada if community characteristics such as household food insecurity status, economic participation of women and average household size are kept in mind while determining the price of the program.","subset":"pubmed_abstract"} +{"meta":{"pmid":10806251,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Regulation of carbonic anhydrase expression by zinc, cobalt, and carbon dioxide in the marine diatom Thalassiosira weissflogii.\nTWCA1 is the major Zn-requiring isoform of carbonic anhydrase (CA) in the marine diatom Thalassiosira weissflogii. We have examined the roles that trace metals and CO(2) play in the regulation of TWCA1 expression over ranges of concentrations that bracket those encountered in the marine environment. Both steady-state levels of TWCA1 and the kinetics of induction were measured by western analysis. TWCA1 levels correlated well with cellular CA activity levels. TWCA1 was induced at a low CO(2) concentration but the level of induction, as determined by western analysis, was dependent on the availability of Zn. Co effectively substituted for Zn in regulating TWCA1 expression and promoting TWCA1 activity. Upon shift from low to high CO(2), the concentration of TWCA1 decreased. The expression of TWCA1 is diel cycle regulated, and cellular TWCA1 decreased during the dark phase. These results provide the basis for studying the expression of CA in field populations and, taken together with previous radiolabeling studies, provide strong evidence of in vivo metal substitution of Co for Zn in a CA. Our data also support the conclusion that TWCA1 plays a central role in carbon acquisition in T. weissflogii.","subset":"pubmed_abstract"} +{"meta":{"pmid":10589750,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors.\nStandard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.","subset":"pubmed_abstract"} +{"meta":{"pmid":7904156,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Lipoamide influences substrate selection in post-ischaemic perfused rat hearts.\nWe investigated whether lipoamide and diacetyl-lipoamide are able to change the substrate selection in post-ischaemic myocardium. This can be important, because shifting heart metabolism from fatty acid to carbohydrate oxidation can decrease ischaemic injury. Studying the metabolism of [1,2-13C]diacetyl-lipoamide in situ in perfused rat heart by 13C n.m.r., we found intense 13C labelling in glutamate and aspartate, showing that acetyl groups from diacetyl-lipoamide are effectively transferred to CoA and metabolized in heart tissue. From analysis of glutamate C-3 and C-4 isotopomers, we determined the [1,2-13C]acetate\/[3-13C]lactate utilization ratio in normoxic and post-ischaemic hearts, where under our experimental conditions the acetate\/lactate utilization ratios were 1.2 +\/- 0.2 and 2.4 +\/- 0.3 in normoxic and post-ischaemic hearts respectively. When 0.25 mM lipoamide was added to the perfusate the acetate\/lactate utilization ratio decreased to 1.4 +\/- 0.1, which is almost equal to that found for normoxic hearts, showing that lipoamide increased the lactate utilization. In accordance with these data, we found that lipoamide activated pyruvate dehydrogenase by 50% in post-ischaemic myocardium. Competition between [3-13C]lactate and unlabelled octanoate was also studied in post-ischaemic hearts, and we found that lipoamide increased lactate utilization by 100% and increased the rate of the tricarboxylic acid cycle by 64%. Under the same experimental conditions, lipoamide significantly promoted the recovery of post-ischaemic unpaced hearts, showing the positive effect of increased lactate oxidation in post-ischaemic myocardium.","subset":"pubmed_abstract"} +{"meta":{"pmid":28980724,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":14}}},"text":"Minimal mechanical load and tissue culture conditions preserve native cell phenotype and morphology in tendon-a novel ex vivo mouse explant model.\nAppropriate mechanical load is essential for tendon homeostasis and optimal tissue function. Due to technical challenges in achieving physiological mechanical loads in experimental tendon model systems, the research community still lacks well-characterized models of tissue homeostasis and physiological relevance. Toward this urgent goal, we present and characterize a novel ex vivo murine tail tendon explant model. Mouse tail tendon fascicles were extracted and cultured for 6 days in a load-deprived environment or in a custom-designed bioreactor applying low magnitude mechanical load (intermittent cycles to 1% strain, at 1 Hz) in serum-free tissue culture. Cells remained viable, as did collagen structure and mechanical properties in all tested conditions. Cell morphology in mechanically loaded tendon explants approximated native tendon, whereas load-deprived tendons lost their native cell morphology. These losses were reflected in altered gene expression, with mechanical loading tending to maintain tendon specific and matrix remodeling genes phenotypic of native tissue. We conclude from this study that ex vivo load deprivation of murine tendon in minimal culture medium results in a degenerative-like phenotype. We further conclude that onset of tissue degeneration can be suppressed by low-magnitude mechanical loading. Thus a minimal explant culture model featuring serum-free medium with low mechanical loads seems to provide a useful foundation for further investigations. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1383-1390, 2018.","subset":"pubmed_abstract"} +{"meta":{"pmid":7050288,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Identification of a T cell hybridoma that produces large quantities of macrophage-activating factor.\nA murine T cell hybridoma, constructed by fusion of alloantigen-activated T cells with the BW5147 T cell lymphoma, which produces a lymphokine capable of inducing tumoricidal activity in macrophages, has been identified. Lymphokine release could be detected only after mitogen stimulation of the T cell hybridoma culture. Upon cloning of the parental hybridoma, 24 out of 27 clones produced tumoricidal-inducing activity. Seven clones produced more cytocidal-inducing activity than did conventional supernatants, generated by concanavalin A stimulation of normal murine spleen cell cultures, which contained macrophage-activating factor (MAF). The supernatant of hybridoma clone 24\/G1 was 25 times more active than conventional MAF preparations. Using supernatants from a variety of clones, the levels of macrophage-activating activity and interleukin 2 were found to vary independently of one another. The lymphokine produced by hybridoma clone 24\/G1 appeared to be identical to conventional MAF by a variety of criteria including: (a) a requirement for a second signal for induction of tumoricidal activity in macrophages, (b) inactivation after incubation for 1 h at 65 degrees C, and (c) loss of activity after treatment at pH 4.0 but not at pH 5.0. Like conventional MAF, the hybridoma MAF eluted as a single peak after molecular sieve chromatography on Sephadex G100 and exhibited an apparent molecular weight of 55,000. Although somewhat heterogeneous, the majority of hybridoma 24\/G1 MAF displayed an isoelectric point of 5.4 as determined using the chromatofocusing technique. These results thus illustrate the usefulness of T cell hybridomas in distinguishing between various lymphokine activities and indicate that the T cell hybridoma clone 24\/G1 will be of particular usefulness in achieving the biochemical purification of substantial quantities of murine MAF.","subset":"pubmed_abstract"} +{"meta":{"pmid":21320597,"dup_signals":{"dup_doc_count":12,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2023-06":1,"2022-33":2,"2022-05":1,"2021-39":1,"2021-17":1,"2020-40":1,"2020-24":1,"2018-39":1,"2018-17":1,"2023-14":1}}},"text":"Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications.\nGlucocorticoid (GC) is an adrenal steroid hormone that controls a variety of physiological processes such as metabolism, immune response, cardiovascular activity, and brain function. In addition to GC induction in response to stress, even in relatively undisturbed states its circulating level is subjected to a robust daily variation with a peak around the onset of the active period of the day. It has long been believed that the synthesis and secretion of GC are primarily regulated by the hypothalamus-pituitary-adrenal (HPA) neuroendocrine axis. However, recent chronobiological research strongly supports the idea that multiple regulatory mechanisms along with the classical HPA neuroendocrine axis underlie the diurnal rhythm of circulating GC. Most notably, recent studies demonstrate that the molecular circadian clockwork is heavily involved in the daily GC rhythm at multiple levels. The daily GC rhythm is implicated in various human diseases accompanied by abnormal GC levels. Patients with such diseases frequently show a blunted GC rhythmicity and, more importantly, circadian rhythm-related symptoms. In this review, we focus on recent advances in the understanding of the circadian regulation of adrenal GC and its implications in human health and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":18620564,"dup_signals":{"dup_doc_count":27,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2014-52":1,"2014-49":2,"2014-42":2,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2018-05":1,"2015-18":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":3,"2013-20":1}}},"text":"The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response.\nFUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA\/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":8410609,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-24":2,"2020-10":1,"2019-47":2,"2019-43":1,"2019-09":1,"2018-34":1,"2018-13":1,"2017-39":1,"2017-22":1,"2017-04":1}}},"text":"The rate of periodontal attachment loss in subjects with established periodontitis.\nA stepwise approach to determine attachment level changes was utilized to assess the nature of progression of periodontal disease. Following initial screening, 51 subjects with established periodontitis were monitored quarterly for 9 more months. Probing depth (PD) and relative attachment level (RAL) were recorded using an automated, pressure sensitive probe system. To establish intra-examiner error, repeated measurements were performed for all sites at the final visit. An overall standard deviation (SD) for RAL repeated measurements was initially calculated (0.76 mm) using all 6,935 double measurements. Sites were sorted by factors which contribute to the error of attachment level measurements; i.e., pocket depth (shallow, moderate, deep), tooth type (molar, non-molar) and location (buccal, lingual). Data were sorted by the above 12 groups, and SD for repeated measurements was calculated separately for them. The ratio between these SD and the overall SD served as the corrective factor. Each patient's initial threshold (2 SD) was multiplied by these corrective factors thus resulting in 12 thresholds for each subject. Next, linear, exponential and logarithmic regression models were tested for each site, and the regression model showing the highest R value was chosen for that site. AL changes were tested against the patient's threshold for that site. Sites with attachment loss exceeding the threshold were deemed active. Five hundred eighty-one sites (8.3%) exhibited attachment loss exceeding the various thresholds. Of these, linear progression occurred in 195, logarithmic in 224, and exponential in 162 sites. Individual patient's attachment loss ranged from 0.6 to 19.4% of all sites.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":28981154,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":12}}},"text":"Variation in SWI\/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations.\nTesting for direct gene or single nucleotide polymorphism replication of association across studies may not capture the true importance of a candidate locus; rather, we suggest that relevant replication across studies may be found at the level of a biological process. We previously observed that variation in 2 members of the switching defective\/sucrose nonfermenting (SWI\/SNF) chromatin remodeling complex is associated with alcohol dependence (AD) in the Irish Affected Sib Pair Study for Alcohol Dependence. Here, we tested for association with alcohol-related outcomes using a set of genes functioning in the SWI\/SNF complex in 2 independent samples. We used a set-based analysis to examine the 29 genes of the SWI\/SNF complex for evidence of association with (i) AD in the adult Collaborative Study on the Genetics of Alcoholism (COGA) case-control sample and (ii) antisocial behavior, hypothesized to be a genetically related developmental precursor, in a younger population sample (Spit for Science [S4S]). We found evidence for association of the SWI\/SNF complex with AD in COGA (p = 0.0435) and more general antisocial behavior in S4S (p = 0.00026). The genes that contributed most strongly to the signal in COGA were SS18L1, SMARCD1, BRD7, BCL7B, SMARCB1, and BCL11A. In the S4S sample, ACTB, ARID2, BCL11A, BCL11B, BCL7B, BCL7C, DPF2, and DPF3 all contributed strongly to the signal. We detected associations between the SWI\/SNF complex and AD in an adult population selected from treatment-seeking probands and antisocial behavior in an adolescent population sample. This provides strong support for a role for SWI\/SNF in the development of alcohol-related problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":30822525,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"A Chromosome-Scale Genome Assembly of Paper Mulberry (Broussonetia papyrifera) Provides New Insights into Its Forage and Papermaking Usage.\nPaper mulberry (Broussonetia papyrifera) is a well-known woody tree historically used for Cai Lun papermaking, one of the four great inventions of ancient China. More recently, Paper mulberry has also been used as forage to address the shortage of feedstuff because of its digestible crude fiber and high protein contents. In this study, we obtained a chromosome-scale genome assembly for Paper mulberry using integrated approaches, including Illumina and PacBio sequencing platform as well as Hi-C, optical, and genetic maps. The assembled Paper mulberry genome consists of 386.83 Mb, which is close to the estimated size, and 99.25% (383.93 Mb) of the assembly was assigned to 13 pseudochromosomes. Comparative genomic analysis revealed the expansion and contraction in the flavonoid and lignin biosynthetic gene families, respectively, accounting for the enhanced flavonoid and decreased lignin biosynthesis in Paper mulberry. Moreover, the increased ratio of syringyl-lignin to guaiacyl-lignin in Paper mulberry underscores its suitability for use in medicine, forage, papermaking, and barkcloth making. We also identified the root-associated microbiota of Paper mulberry and found that Pseudomonas and Rhizobia were enriched in its roots and may provide the source of nitrogen for its stems and leaves via symbiotic nitrogen fixation. Collectively, these results suggest that Paper mulberry might have undergone adaptive evolution and recruited nitrogen-fixing microbes to promote growth by enhancing flavonoid production and altering lignin monomer composition. Our study provides significant insights into genetic basis of the usefulness of Paper mulberry in papermaking and barkcloth making, and as forage. These insights will facilitate further domestication and selection as well as industrial utilization of Paper mulberry worldwide.","subset":"pubmed_abstract"} +{"meta":{"pmid":22967181,"dup_signals":{"dup_doc_count":50,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-30":2,"2024-10":1,"2015-06":1,"2013-48":1,"2013-20":1,"unknown":43}}},"text":"Dietary vegetable oils do not alter the intestine transcriptome of gilthead sea bream (Sparus aurata), but modulate the transcriptomic response to infection with Enteromyxum leei.\nStudies conducted with gilthead sea bream (Sparus aurata L.) have determined the maximum dietary replacement of fish meal and oil without compromising growth or product quality. The present study aimed to analyze the effect of the nutritional background on fish health and fish fed plant protein-based diets with fish oil (FO diet) or a blend of vegetable oils (66VO diet) were exposed for 102 days to the intestinal myxosporean parasite Enteromyxum leei, and the intestine transcriptome was analyzed with a customized oligo-microarray of 7,500 annotated genes. Infection prevalence was high and similar in the two diet groups, but the outcome of the disease was more pronounced in fish fed the 66VO diet. No differences were found in the transcriptome of both diet control groups, whereas the number of differentially expressed genes in infected groups was considerable. K-means clustering of these differentially expressed genes identified four expression patterns that reflected the progression of the disease with the magnitude of the fold-change being higher in infected 66VO fish. A positive correlation was found between the time of infection and the magnitude of the transcriptional change within the 66VO group, being higher in early infected animals. Within this diet group, a strong up-regulation of many components of the immune specific response was evidenced, whereas other genes related to complement response and xenobiotic metabolism were down-regulated. The high replacement of fish oil by vegetable oils in practical fish feeds did not modify the intestine transcriptome of gilthead sea bream, but important changes were apparent when fish were exposed to the myxosporean E. leei. The detected changes were mostly a consequence rather than a cause of the different disease progression in the two diet groups. Hence, the developed microarray constitutes an excellent diagnostic tool to address changes associated with the action of intestinal pathogens, but lacks a prognostic value to predict in advance the different susceptibility of growing fish to the current pathogen.","subset":"pubmed_abstract"} +{"meta":{"pmid":32552276,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.\nRecently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion. EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 \u2265 0.7. Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":20975775,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Model-Independent 3D Descriptors of Vertebral Cancellous Bone Architecture.\nHigh-resolution micro computed tomography has enabled measurement of bone architecture derived from 3D representations of cancellous bone. Twenty-eight vertebral bodies were obtained from four embalmed male cadavers. From 3D anaglyphs, trabecular rod thickness and length were measured and the trabecular rod Buckling index was calculated. From 3D voxel-based datasets, bone volume density, trabecular thickness, and trabecular separation were measured. Also, trabecular bone pattern factor, structural model index, connectivity density, and degree of anisotropy were calculated. Bone volume density alone explains 59% of the variability in trabecular rod Buckling index. The addition of connectivity density, trabecular separation, and structural model index, in a multiple regression statistical model, improves the explanatory power to 77%. The relationships between measures of cancellous bone architecture and a derived measure of trabecular rod strength were investigated. Morphological descriptors of cancellous bone provide a composite explanatory model of trabecular rod strength.","subset":"pubmed_abstract"} +{"meta":{"pmid":18758462,"dup_signals":{"dup_doc_count":16,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1,"unknown":10}}},"text":"Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12.\nWe carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.","subset":"pubmed_abstract"} +{"meta":{"pmid":19728793,"dup_signals":{"dup_doc_count":14,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":4}}},"text":"Fibroblast growth factor receptors in in vitro and in vivo chondrogenesis: relating tissue engineering using adult mesenchymal stem cells to embryonic development.\nAdult mesenchymal stem cells (MSCs) are considered promising candidate cells for therapeutic cartilage and bone regeneration. Because tissue regeneration and embryonic development may involve similar pathways, understanding common pathways may lead to advances in regenerative medicine. In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation. The aim of this study was to investigate and compare FGFR expression in in vivo embryonic limb development and in vitro chondrogenesis of MSCs. Our study showed that in in vitro chondrogenesis of MSCs three sequential stages can be found, as in embryonic limb development. A mesenchymal condensation (indicated by N-cadherin) is followed by chondrogenic differentiation (indicated by collagen II), and hypertrophy (indicated by collagen X). FGFR1-3 are expressed in a stage-dependent pattern during in vitro differentiation and in vivo embryonic limb development. In both models FGFR2 is clearly expressed by cells in the condensation phase. No FGFR expression was observed in differentiating and mature hyaline chondrocytes, whereas hypertrophic chondrocytes stained strongly for all FGFRs. To evaluate whether stage-specific modulation of chondrogenic differentiation in MSCs is possible with different subtypes of FGF, FGF2 and FGF9 were added to the chondrogenic medium during different stages in the culture process (early or late). FGF2 and FGF9 differentially affected the amount of cartilage formed by MSCs depending on the stage in which they were added. These results will help us understand the role of FGF signaling in chondrogenesis and find new tools to monitor and control chondrogenic differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":15771598,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Thyroid volume measurement by ultrasound in schoolchildren from mildly iodine-deficient area.\nThyroid size was estimated by ultrasound and physical examination in 480 schoolchildren (238 boys and 242 girls), 7-14 years old, living in Tuzla Canton. By physical examination goiter was found in 13.5% (n=65) of subjects. When compared with the upper limits of the reference thyroid volumes reported by WHO and ICCIDD, goiter by ultrasonography was found in 12.9% (n=62) of all subjects. All goitrous children had a diffuse goiter. The differences in mean thyroid volumes between groups with and without goiter detected by physical examination were significant in all age groups (p<0.05). The results of ultrasound examinations correlate well with palpatory findings and show higher values for the thyroid volume in children with goiter. It generally confirms the values of the findings by palpation, even in areas with mild iodine deficiency.","subset":"pubmed_abstract"} +{"meta":{"pmid":8723413,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":2,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2023-40":1,"2024-18":1,"2024-30":1}}},"text":"Absence of antineutrophil cytoplasmic antibodies in relatives of UK patients with primary sclerosing cholangitis and ulcerative colitis.\nPerinuclear antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients and relatives of patients with ulcerative colitis and primary sclerosing cholangitis, suggesting that ANCA may be a genetic marker of disease susceptibility. The reported frequency of ANCA in relatives has varied greatly, between 0 and 30%. We therefore studied the prevalence of ANCA in unaffected first-degree relatives of British patients with primary sclerosing cholangitis and ulcerative colitis. Thirty-six patients with ulcerative colitis, 33 with primary sclerosing cholangitis and 187 relatives were studied. Ninety-seven relatives were from the primary sclerosing cholangitis proband and 90 were from the ulcerative colitis proband. As an environmental control, 32 spouses were included: 14 from the primary sclerosing cholangitis group and 18 from the ulcerative colitis group. Eighteen healthy volunteers were additional controls. ANCA was detected using immunoalkaline phosphatase method. Only 3 of 97 (3%) of the primary sclerosing cholangitis proband relatives had ANCA. One of these had ulcerative colitis, one had rheumatoid arthritis and the third systemic lupus erythematosus. Both rheumatoid arthritis and system lupus erythematosus are known to exhibit ANCA. All other sera were negative. ANCA was found only in patients with primary cholangitis and ulcerative colitis and not in their healthy first-degree relatives. ANCA is therefore not a genetic marker for increased disease susceptibility to primary sclerosing cholangitis or ulcerative colitis in the British population.","subset":"pubmed_abstract"} +{"meta":{"pmid":23993196,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2021-43":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2021-49":1,"2017-13":1}}},"text":"Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep.\nThe persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (-13910(\u2217)T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (-13907(\u2217)G, rs41525747; -13915(\u2217)G, rs41380347; -14010(\u2217)C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, -14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the -14009(\u2217)G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.","subset":"pubmed_abstract"} +{"meta":{"pmid":28977716,"dup_signals":{"dup_doc_count":12}},"text":"Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT.\nThe efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.","subset":"pubmed_abstract"} +{"meta":{"pmid":19905409,"dup_signals":{"dup_doc_count":69,"dup_dump_count":62,"dup_details":{"curated_sources":3,"2022-33":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":2,"2014-15":1,"2022-49":1,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1}}},"text":"Rotating bouncing disks, tossing pizza dough, and the behavior of ultrasonic motors.\nPizza tossing and certain forms of standing-wave ultrasonic motors (SWUMs) share a similar process for converting reciprocating input into continuous rotary motion. We show that the key features of this motion conversion process such as collision, separation and friction coupling are captured by the dynamics of a disk bouncing on a vibrating platform. The model shows that the linear or helical hand motions commonly used by pizza chefs and dough-toss performers for single tosses maximize energy efficiency and the dough's airborne rotational speed; on the other hand, the semielliptical hand motions used for multiple tosses make it easier to maintain dough rotation at the maximum speed. The system's bifurcation diagram and basins of attraction also provide a physical basis for understanding the peculiar behavior of SWUMs and provide a means to design them. The model is able to explain the apparently chaotic oscillations that occur in SWUMs and predict the observed trends in steady-state speed and stall torque as preload is increased.","subset":"pubmed_abstract"} +{"meta":{"pmid":10895802,"dup_signals":{"dup_doc_count":27,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":2,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2023-50":1,"2024-26":3,"2024-22":1}}},"text":"TENS: a treatment option for bladder dysfunction.\nTo ascertain the mode of action and benefits of transcutaneous electrical nerve stimulation (TENS) in detrusor overactivity, stress incontinence and interstitial cystitis, an English-language literature search using Medline (1984-1995) was undertaken with detrusor instability, incontinence, interstitial cystitis, neuromodulation, transcutaneous electrical nerve stimulation and urodynamics as keywords and the material so identified was reviewed. The mode of action of TENS and optimal stimulation parameters in bladder dysfunction remain unclear. Lack of strict selection criteria and deficient reporting of subjective and objective outcomes precluded full assessment of therapeutic efficacy. A beneficial effect was evident in some studies of detrusor overactivity and interstitial cystitis. A trial of TENS in detrusor overactivity and interstitial cystitis refractory to conventional therapy would seem justified. Continued experimental research and further clinical studies will lead to refinement of the treatment modality.","subset":"pubmed_abstract"} +{"meta":{"pmid":15866969,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":12}}},"text":"Function of skin grafts in children following acquired amputation of the lower extremity.\nInvestigators have recommended aggressive use of skin-grafting in order to preserve length and proximal joint function following an acquired amputation in children. However, there is little objective evidence to either support or refute that recommendation. We performed a retrospective review of the cases of all children for whom a skin graft had been applied to the residual limb following an acquired lower-extremity amputation at our Limb Deficiency Clinic between 1984 and 2002. Skin graft dysfunction, defined as breakdown, contracture, and\/or pain, was considered to be clinically relevant if it required the child to discontinue use of the prosthesis for any period of time or if it required revision surgery to facilitate continued prosthetic fitting. Twenty-three children (mean age at amputation, 4.4 years) with a total of thirty-one acquired lower-extremity amputations had been treated with skin-grafting. At a mean of 6.3 years after the operation, sixteen (52%) of the thirty-one extremities had had no episodes of skin graft dysfunction. The remaining fifteen extremities (48%) had had clinically relevant skin graft dysfunction (breakdown in thirteen and contracture and pain in one extremity each). Nine of the ten extensive skin grafts underwent clinically relevant breakdown, as did thirteen of the twenty-four grafts that were located distally on the residual limb. Subsequent surgical revision of the residual limb because of inadequate function of the skin graft was performed on seven extremities (23%), with revision to a more proximal limb-segment level required in five. Focal skin-grafting (involving < or = 25% of the surface area) of partial-thickness soft-tissue defects in order to optimize the length of the residual limb at the time of an amputation is an effective option for children with an acquired lower-extremity amputation. Limited skin-grafting (involving 26% to 50% of the surface area) is more likely to result in skin graft breakdown, particularly when it is done distally. Extensive skin-grafting, while technically possible, frequently requires revision and rarely results in an optimally functioning limb. Alternative treatment strategies should be considered for extremities that would require extensive, distal skin-grafting.","subset":"pubmed_abstract"} +{"meta":{"pmid":17261178,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-18":1,"2013-48":2,"2013-20":1,"2024-30":1,"unknown":6}}},"text":"The small FNR regulon of Neisseria gonorrhoeae: comparison with the larger Escherichia coli FNR regulon and interaction with the NarQ-NarP regulon.\nNeisseria gonorrhoeae can survive during oxygen starvation by reducing nitrite to nitrous oxide catalysed by the nitrite and nitric oxide reductases, AniA and NorB. The oxygen-sensing transcription factor, FNR, is essential for transcription activation at the aniA promoter, and full activation also requires the two-component regulatory system, NarQ-NarP, and the presence of nitrite. The only other gene known to be activated by the gonococcal FNR is ccp encoding a cytochrome c peroxidase, and no FNR-repressed genes have been reported in the gonococcus. In contrast, FNR acts as both an activator and repressor involved in the control of more than 100 operons in E. coli regulating major changes in the adaptation from aerobic to anaerobic conditions. In this study we have performed a microarray-led investigation of the FNR-mediated responses in N. gonorrhoeae to determine the physiological similarities and differences in the role of FNR in cellular regulation in this species. Microarray experiments show that N. gonorrhoeae FNR controls a much smaller regulon than its E. coli counterpart; it activates transcription of aniA and thirteen other genes, and represses transcription of six genes that include dnrN and norB. Having previously shown that a single amino acid substitution is sufficient to enable the gonococcal FNR to complement an E. coli fnr mutation, we investigated whether the gonococcal NarQ-NarP can substitute for E. coli NarX-NarL or NarQ-NarP. A plasmid expressing gonococcal narQ-narP was unable to complement E. coli narQP or narXL mutants, and was insensitive to nitrate or nitrite. Mutations that progressively changed the periplasmic nitrate sensing region, the P box, of E. coli NarQ to the sequence of the corresponding region of gonococcal NarQ resulted in loss of transcription activation in response to the availability of either nitrate or nitrite. However, the previously reported ligand-insensitive ability of gonococcal NarQ, the \"locked on\" phenotype, to activate either E. coli NarL or NarP was confirmed. Despite the sequence similarities between transcription activators of E. coli and N. gonorrhoeae, these results emphasise the fundamental differences in transcription regulation between these two types of pathogenic bacteria.","subset":"pubmed_abstract"} +{"meta":{"pmid":9109754,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Syphilitic uveitis in human immunodeficiency virus-infected patients.\nTo document the incidence and clinical features of syphilitic uveitis in patients coinfected with human immunodeficiency virus (HIV). Retrospective chart review. Single tertiary uveitis referral center. The charts of HIV-infected patients with uveitis and a reactive fluorescent treponemal antibody absorption test seen between November 1983 and June 1995 were reviewed. Syphilis was the most common bacterial cause of uveitis in this group. Thirteen patients (0.6% of the 2085 HIV-positive patients seen in the clinic during the study period) were dually infected. Twelve patients were male. Six patients (46%) had previously been treated for syphilis, 4 with intramuscular penicillin G benzathine only. Four patients (31%) had isolated anterior uveitis, 3 patients (23%) had anterior and intermediate uveitis, and 5 patients (38%) had panuveitis. One patient (8%) presented with optic nerve and retinal atrophy. Eight patients were treated with intravenous penicillin, 3 with intravenous and intramuscular penicillin, and 1 with intravenous ceftriaxone sodium. Of the 12 patients for whom follow-up examinations were available after treatment, ocular inflammation decreased in 11 (92%) and visual acuity improved in 8 (67%). Rapid plasma reagin titers decreased a median of 64-fold compared with pretreatment levels, and all patients with reactive cerebrospinal fluid who underwent pretreatment and posttreatment lumbar punctures normalized following therapy with intravenous antibiotics. Syphilis is an uncommon cause of uveitis in HIV-infected patients. Anterior uveitis is the most common ocular manifestation, but panuveitis is more common than isolated anterior uveitis. Intravenous penicillin is effective therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23580160,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":1,"2024-30":1,"unknown":11}}},"text":"Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet.\nHigh fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague-Dawley rats, weighing 170-200 g, were divided into six groups: control, control with vitamin E (100 mg\/kg\/day, i.p.), control with simvastatin (SIM) (10 mg\/kg of body weight\/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30711711,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"High voltage atmospheric cold air plasma control of bacterial biofilms on fresh produce.\nAtmospheric cold plasma (ACP) offers great potential for decontamination of food borne pathogens. This study examined the antimicrobial efficacy of ACP against a range of pathogens of concern to fresh produce comparing planktonic cultures, monoculture biofilms (Escherichia coli, Salmonella enterica, Listeria monocytogenes, Pseudomonas fluorescens) and mixed culture biofilms (Listeria monocytogenes and Pseudomonas fluorescens). Biotic and abiotic surfaces commonly occurring in the fresh food industry were investigated. Microorganisms showed varying susceptibility to ACP treatment depending on target and process factors. Bacterial biofilm populations treated with high voltage (80 kV) ACP were reduced significantly (p < 0.05) in both mono- and mixed species biofilms after 60 s of treatment and yielded non-detectable levels after extending treatment time to 120 s. However, an extended time was required to reduce the challenge mixed culture biofilm of L. monocytogenes and P. fluorescens inoculated on lettuce, which was dependent on biofilm formation conditions and substrate. Contained treatment for 120 s reduced L. monocytogenes and P. fluorescens inoculated as mixed cultures on lettuce (p < 0.05) by 2.2 and 4.2 Log10 CFU\/ml respectively. When biofilms were grown at 4 \u00b0C on lettuce, there was an increased resistance to ACP treatment by comparison with biofilm grown at temperature abuse conditions of 15 \u00b0C. Similarly, L. monocytogenes and P. fluorescens exposed to cold stress (4 \u00b0C) for 1 h demonstrated increased tolerance to ACP treatment compared to non-stressed cells. These finding demonstrates that bacterial form, mono versus mixed challenges as well as environmental stress conditions play an important role in ACP inactivation efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":33672229,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":2,"unknown":6}}},"text":"Feasibility of a Digital Intervention to Promote Healthy Weight Management among Postpartum African American\/Black Women.\nThe study aim was to implement and evaluate the feasibility of a culturally informed (\"BeFAB\") app for African American\/Black women to address postpartum weight. Women (n = 136; mean age = 27.8 \u00b1 5.4; mean BMI = 32.5 \u00b1 4.3) were recruited from postpartum units, and randomly assigned to receive BeFAB (n = 65) or usual care (n = 71) for 12 weeks. App content included didactic lessons delivered via a virtual coach, app-based messages, goal setting and tracking, and edutainment videos. Feasibility outcomes included recruitment, retention and engagement, and self-reported acceptability. Behavioral (i.e., diet, physical activity), psychosocial (i.e., stress, coping, support, self-efficacy) and weight outcomes were also examined. Recruitment goals were met, but attrition was high, with 56% retention at 12 weeks. Approximately half of participants accessed the app and set a goal \u2265one time, but <10% reported achieving a nutrition or activity goal. Among study completers, \u226560% found the app content at least somewhat helpful. Within-group changes for BeFAB among completers were found for increased moderate-to-vigorous physical activity and decreased fruit\/vegetable intake and weight. Findings indicate initial feasibility of recruiting postpartum women to participate in a digital healthy body weight program but limited use, reflecting low acceptability and challenges in engagement and retention. Future research is needed on strategies to engage and retain participants in postpartum interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":10798652,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":2,"unknown":21}}},"text":"Experimental glaucoma and cell size, density, and number in the primate lateral geniculate nucleus.\nTo examine the effects that elevated intraocular pressure (IOP), a glaucoma risk factor, has on the size, density, and number of neurons in the primate lateral geniculate nucleus (LGN). The monkey model of experimental glaucoma was combined with standard histologic staining and analysis techniques. Fourteen animals were examined. Mean IOPs higher than 40 mm Hg for 2.5, 4, 8, and 24 weeks resulted in reductions of 10% to 58% in the cross-sectional areas of LGN neurons receiving input from the glaucomatous eye. Reductions for animals with lower mean IOPs (37 and 28 mm Hg) for 16 and 27 weeks were 16% and 30%, respectively. Neurons receiving input from the normal eye also were reduced in size (4 -26%). No differential effect in cell size was seen for magnocellular versus parvocellular neurons. Elevation of IOP resulted in an increase in cell density in all layers of the LGN. The increase was approximately two times greater in parvocellular (59%) than magnocellular (31%) layers. When corrected for volumetric shrinkage of the LGN, the estimated loss of neurons was approximately four times greater in the magnocellular than parvocellular layers (38% versus 10%). Elevation of IOP affects the size, density, and number of neurons in the LGN, and the volume of the nucleus itself. Although higher mean pressures (more than 40 mm Hg) reduce the period during which these changes occur, comparable damage can be achieved by even moderate (28 -37 mm Hg) levels of elevated IOP. On the basis of cell loss, elevation of IOP appears to have a more profound degenerative effect on the magnocellular than on the parvocellular regions of the LGN.","subset":"pubmed_abstract"} +{"meta":{"pmid":29176452,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations.\nTo describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-\u03bcm thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 \u03bcm hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3\/10) cases. An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":22366162,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2021-10":1,"2020-16":1,"2018-39":1,"2018-13":1,"2017-43":2,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-27":1,"2017-13":1,"2024-26":1}}},"text":"STAY-GREEN and chlorophyll catabolic enzymes interact at light-harvesting complex II for chlorophyll detoxification during leaf senescence in Arabidopsis.\nDuring leaf senescence, plants degrade chlorophyll to colorless linear tetrapyrroles that are stored in the vacuole of senescing cells. The early steps of chlorophyll breakdown occur in plastids. To date, five chlorophyll catabolic enzymes (CCEs), NONYELLOW COLORING1 (NYC1), NYC1-LIKE, pheophytinase, pheophorbide a oxygenase (PAO), and red chlorophyll catabolite reductase, have been identified; these enzymes catalyze the stepwise degradation of chlorophyll to a fluorescent intermediate, pFCC, which is then exported from the plastid. In addition, STAY-GREEN (SGR), Mendel's green cotyledon gene encoding a chloroplast protein, is required for the initiation of chlorophyll breakdown in plastids. Senescence-induced SGR binds to light-harvesting complex II (LHCII), but its exact role remains elusive. Here, we show that all five CCEs also specifically interact with LHCII. In addition, SGR and CCEs interact directly or indirectly with each other at LHCII, and SGR is essential for recruiting CCEs in senescing chloroplasts. PAO, which had been attributed to the inner envelope, is found to localize in the thylakoid membrane. These data indicate a predominant role for the SGR-CCE-LHCII protein interaction in the breakdown of LHCII-located chlorophyll, likely to allow metabolic channeling of phototoxic chlorophyll breakdown intermediates upstream of nontoxic pFCC.","subset":"pubmed_abstract"} +{"meta":{"pmid":18045500,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2015-06":1,"2013-48":1,"2015-18":1,"unknown":7}}},"text":"Assessment of higher order cognitive skills in undergraduate education: modified essay or multiple choice questions? Research paper.\nReliable and valid written tests of higher cognitive function are difficult to produce, particularly for the assessment of clinical problem solving. Modified Essay Questions (MEQs) are often used to assess these higher order abilities in preference to other forms of assessment, including multiple-choice questions (MCQs). MEQs often form a vital component of end-of-course assessments in higher education. It is not clear how effectively these questions assess higher order cognitive skills. This study was designed to assess the effectiveness of the MEQ to measure higher-order cognitive skills in an undergraduate institution. An analysis of multiple-choice questions and modified essay questions (MEQs) used for summative assessment in a clinical undergraduate curriculum was undertaken. A total of 50 MCQs and 139 stages of MEQs were examined, which came from three exams run over two years. The effectiveness of the questions was determined by two assessors and was defined by the questions ability to measure higher cognitive skills, as determined by a modification of Bloom's taxonomy, and its quality as determined by the presence of item writing flaws. Over 50% of all of the MEQs tested factual recall. This was similar to the percentage of MCQs testing factual recall. The modified essay question failed in its role of consistently assessing higher cognitive skills whereas the MCQ frequently tested more than mere recall of knowledge. Construction of MEQs, which will assess higher order cognitive skills cannot be assumed to be a simple task. Well-constructed MCQs should be considered a satisfactory replacement for MEQs if the MEQs cannot be designed to adequately test higher order skills. Such MCQs are capable of withstanding the intellectual and statistical scrutiny imposed by a high stakes exit examination.","subset":"pubmed_abstract"} +{"meta":{"pmid":9241071,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to lifetime filter cigarette smoking.\nOver the past few decades, the incidence of adenocarcinoma (AC) of the lung increased much more rapidly than that of squamous cell carcinoma (SCC) in men and women. During this time period, filter cigarettes with substantially reduced \"tar\" and nicotine yields in the smoke came to dominate the market. The risk of SCC and AC in lifelong smokers of filter cigarettes relative to lifelong nonfilter cigarette smokers was assessed in a case-control study performed between 1977 and 1995 with 2292 lung carcinoma patients and 1343 hospital controls who were current smokers. Odds ratios (OR) for SCC in male and female subjects who had smoked filter cigarettes exclusively during their lives were slightly reduced relative to lifetime nonfilter cigarette smokers in men (OR = 0.8; 95% confidence interval [CI], 0.5-1.2), and significantly reduced in women (OR = 0.4; 95% CI, 0.2-0.8). No reduction in risk was observed for AC of the lung in men or women. Evidence that the increasing predominance of AC over SCC may be due in part to the reduced risk of SCC (but not AC) associated with lifelong filter cigarette smoking is strongest in women; for men, further studies that include larger numbers of lifetime filter smokers are needed to confirm this finding. A lack of protection against AC from low yield filter cigarettes may result from smokers' \"compensating\" with deeper and more frequent inhalation, thereby increasing delivery of carcinogens to the peripheral lung. The smoke of modern cigarettes also contains higher concentrations of nitrosamines that primarily produce AC.","subset":"pubmed_abstract"} +{"meta":{"pmid":22975990,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2022-49":1,"2022-33":1,"2022-05":1,"2020-29":1,"2020-10":1,"2019-18":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-26":1,"2018-22":1,"2023-06":1,"2024-30":1}}},"text":"Adjusting for confounding by neighborhood using generalized linear mixed models and complex survey data.\nWhen investigating health disparities, it can be of interest to explore whether adjustment for socioeconomic factors at the neighborhood level can account for, or even reverse, an unadjusted difference. Recently, we proposed new methods to adjust the effect of an individual-level covariate for confounding by unmeasured neighborhood-level covariates using complex survey data and a generalization of conditional likelihood methods. Generalized linear mixed models (GLMMs) are a popular alternative to conditional likelihood methods in many circumstances. Therefore, in the present article, we propose and investigate a new adaptation of GLMMs for complex survey data that achieves the same goal of adjusting for confounding by unmeasured neighborhood-level covariates. With the new GLMM approach, one must correctly model the expectation of the unmeasured neighborhood-level effect as a function of the individual-level covariates. We demonstrate using simulations that even if that model is correct, census data on the individual-level covariates are sometimes required for consistent estimation of the effect of the individual-level covariate. We apply the new methods to investigate disparities in recency of dental cleaning, treated as an ordinal outcome, using data from the 2008 Florida Behavioral Risk Factor Surveillance System (BRFSS) survey. We operationalize neighborhood as zip code and merge the BRFSS data with census data on ZIP Code Tabulated Areas to incorporate census data on the individual-level covariates. We compare the new results to our previous analysis, which used conditional likelihood methods. We find that the results are qualitatively similar.","subset":"pubmed_abstract"} +{"meta":{"pmid":27803058,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2021-04":1,"2020-40":1,"2020-29":1,"2019-47":1,"2023-40":1,"2024-22":3,"2024-18":1}}},"text":"Development of the neurons controlling fertility in humans: new insights from 3D imaging and transparent fetal brains.\nFertility in mammals is controlled by hypothalamic neurons that secrete gonadotropin-releasing hormone (GnRH). These neurons differentiate in the olfactory placodes during embryogenesis and migrate from the nose to the hypothalamus before birth. Information regarding this process in humans is sparse. Here, we adapted new tissue-clearing and whole-mount immunohistochemical techniques to entire human embryos\/fetuses to meticulously study this system during the first trimester of gestation in the largest series of human fetuses examined to date. Combining these cutting-edge techniques with conventional immunohistochemistry, we provide the first chronological and quantitative analysis of GnRH neuron origins, differentiation and migration, as well as a 3D atlas of their distribution in the fetal brain. We reveal not only that the number of GnRH-immunoreactive neurons in humans is significantly higher than previously thought, but that GnRH cells migrate into several extrahypothalamic brain regions in addition to the hypothalamus. Their presence in these areas raises the possibility that GnRH has non-reproductive roles, creating new avenues for research on GnRH functions in cognitive, behavioral and physiological processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27618961,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Autosomal dominant cortical tremor, myoclonus and epilepsy.\nThe term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.","subset":"pubmed_abstract"} +{"meta":{"pmid":30699315,"dup_signals":{"dup_doc_count":24,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":4,"2024-22":1,"2024-18":2,"2024-10":2,"unknown":10}}},"text":"Oral versus Intravenous Antibiotics for Bone and Joint Infection.\nThe management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).","subset":"pubmed_abstract"} +{"meta":{"pmid":25992608,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2021-17":1,"2020-16":2,"2019-51":2,"2019-43":1,"2019-39":1,"2018-26":1,"2018-09":1,"2017-47":1,"2017-39":1,"2021-25":1}}},"text":"Enhanced mitochondrial superoxide scavenging does not improve muscle insulin action in the high fat-fed mouse.\nImproving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and\/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(\u02d9-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(\u02d9-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(\u02d9-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging.","subset":"pubmed_abstract"} +{"meta":{"pmid":11086004,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":2,"2024-18":1,"unknown":6}}},"text":"Dissection of autophagosome biogenesis into distinct nucleation and expansion steps.\nRapamycin, an antifungal macrolide antibiotic, mimics starvation conditions in Saccharomyces cerevisiae through activation of a general G(0) program that includes widespread effects on translation and transcription. Macroautophagy, a catabolic membrane trafficking phenomenon, is a prominent part of this response. Two views of the induction of autophagy may be considered. In one, up-regulation of proteins involved in autophagy causes its induction, implying that autophagy is the result of a signal transduction mechanism leading from Tor to the transcriptional and translational machinery. An alternative hypothesis postulates the existence of a dedicated signal transduction mechanism that induces autophagy directly. We tested these possibilities by assaying the effects of cycloheximide and specific mutations on the induction of autophagy. We find that induction of autophagy takes place in the absence of de novo protein synthesis, including that of specific autophagy-related proteins that are up-regulated in response to rapamycin. We also find that dephosphorylation of Apg13p, a signal transduction event that correlates with the onset of autophagy, is also independent of new protein synthesis. Finally, our data indicate that autophagosomes that form in the absence of protein synthesis are significantly smaller than normal, indicating a role for de novo protein synthesis in the regulation of autophagosome expansion. Our results define the existence of a signal transduction-dependent nucleation step and a separate autophagosome expansion step that together coordinate autophagosome biogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":35682132,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"A Rapid Review of Environmental Health Gaps in Antimicrobial Resistance and Water-Related Research from 1990-2020.\nAntimicrobial resistance (AMR) is a pervasive global health threat linked to human antimicrobial misuse and abuse, food production, and broader environmental contamination. While global agencies promote a multi-sectoral One Health system approach to equitably combat human, animal, and environmental health AMR risks, it is widely acknowledged that the human and animal sectors dominate discussions. Given this disproportionate focus, identification of critical research gaps is needed to develop stewardship plans that equitably address One Health AMR threats. This review used natural language processing and term frequency algorithms to classify 12,638 records from 1990-2020 thematically in order to highlight sectoral prioritization and gaps. It also specifically assessed water-related gaps as water is recognized as both a primary environmental dissemination pathway and key means of intervention. Drawing from systemic health and integrated water management lenses, this review found that themes related to plant, wildlife, and environmental-related AMR threats-in particular, the role that environmental (ambient) waters play in AMR development, transmission, and spread-are under-prioritized as compared to human and food animal health concerns regardless of geographic region or income level. Further prioritization of these themes is needed to strengthen the environmental dimension of One Health AMR responses and systemically protect global health.","subset":"pubmed_abstract"} +{"meta":{"pmid":1297049,"dup_signals":{"dup_doc_count":19,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-06":1,"2022-40":1,"2022-27":1,"2021-43":1,"2021-31":2,"2021-17":2,"2021-04":2,"2020-40":2,"2020-24":1,"2023-40":1,"2024-22":1}}},"text":"Respiratory disorders in aluminium potroom workers.\nEpidemiological studies of aluminum potroom workers have been in progress in Norway since 1986. The occurrence of work-related asthmatic symptoms and their determinants were studied. Work-related asthmatic symptoms and airflow limitation were closely associated with duration of potroom employment. A significant relationship between current fluoride exposure and work-related asthmatic symptoms was observed in a smaller, cross-sectional population where a detailed exposure classification was carried out. A similar association and also a dose-response gradient was found in a longitudinal study of new employees. The existence of occupational asthma in aluminium potroom workers was confirmed by characteristic patterns of repeated peak flow measurements supported by changes in methacholine responsiveness in workers with suspected work-related asthma. Current smoking as a risk factor for work-related asthmatic symptoms was observed both in cross-sectional and in longitudinal investigations. Similarly to current fluoride exposure, a dose-response gradient was demonstrated in the association between work-related asthmatic symptoms and current amount of tobacco smoked. Allergy was not shown to be a determinant of work-related asthmatic symptoms in any part of the investigation. A family history of asthma and previous occupational exposure may have had some influence on the risk of developing symptoms but the findings were inconsistent and probably of minor importance. Methacholine challenge seemed inappropriate for the screening of aluminium potroom workers in order to detect work-related asthmatic symptoms, but was closely correlated to the severity of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":22541878,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2020-45":1,"2019-43":1,"2019-13":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2016-50":1,"2020-50":1,"2014-10":1,"2013-20":3,"2015-06":1}}},"text":"Comparison of neurological outcome between tracheal intubation and supraglottic airway device insertion of out-of-hospital cardiac arrest patients: a nationwide, population-based, observational study.\nThe effect of prehospital use of supraglottic airway devices as an alternative to tracheal intubation on long-term outcomes of patients with out-of-hospital cardiac arrest is unclear. We compared the neurological outcomes of patients who underwent supraglottic airway device insertion with those who underwent tracheal intubation. We conducted a nationwide population-based observational study using a national database containing all out-of-hospital cardiac arrest cases in Japan over a 3-year period (2005-2007). The rates of neurologically favorable 1-month survival (primary outcome) and of 1-month survival and return of spontaneous circulation before hospital arrival (secondary outcomes) were examined. Multiple logistic regression analyses were performed to adjust for potential confounders. Advanced airway devices were used in 138,248 of 318,141 patients, including an endotracheal tube (ETT) in 16,054 patients (12%), a laryngeal mask airway (LMA) in 34,125 patients (25%), and an esophageal obturator airway (EOA) in 88,069 patients (63%). The overall rate of neurologically favorable 1-month survival was 1.03% (1426\/137,880). The rates of neurologically favorable 1-month survival were 1.14% (183\/16,028) in the ETT group, 0.98% (333\/34,059) in the LMA group, and 1.04% (910\/87,793) in the EOA group. Compared with the ETT group, the rates were significantly lower in the LMA group (adjusted odds ratio 0.77, 95% confidence interval [CI] 0.64-0.94) and EOA group (adjusted odds ratio 0.81, 95% CI 0.68-0.96). Prehospital use of supraglottic airway devices was associated with slightly, but significantly, poorer neurological outcomes compared with tracheal intubation, but neurological outcomes remained poor overall.","subset":"pubmed_abstract"} +{"meta":{"pmid":15864341,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-10":2,"2014-10":1,"2013-48":1,"2013-20":1,"unknown":11}}},"text":"Chemokine-mediated angiogenesis: an essential link in the evolution of airway fibrosis?\nAngiogenesis may be an important factor in the development of fibrotic lung disease. Prior studies have strongly suggested a role for angiogenic vascular remodeling in pulmonary fibrosis, and emerging evidence indicates that new vessel formation is critical in airway fibrosis. Bronchiolitis obliterans syndrome is a fibrotic occlusion of distal airways that is largely responsible for the morbidity and mortality of patients after lung transplantation. In this issue, Belperio et al. demonstrate a role for CXC chemokine receptor 2 in the regulation of angiogenesis-mediated airway fibroproliferation. By integrating an understanding of neovascularization into the study of events that occur between inflammation and fibrosis, it becomes increasingly possible to rationally design therapies that can halt conditions of maladaptive fibrosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":23510582,"dup_signals":{"dup_doc_count":52,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":2,"2023-14":5,"2023-06":2,"2022-40":1,"2022-33":1,"2022-21":3,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-10":1,"2019-47":1,"2019-26":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":2,"2017-51":2,"2017-43":2,"2017-34":2,"2024-26":2,"2024-22":2,"2024-18":1,"2024-10":2,"2024-30":1}}},"text":"Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder.\nCognitive behavioral therapy (CBT) is an effective treatment for emotional disorders such as anxiety or depression, but the mechanisms underlying successful intervention are far from understood. Although it has been a long-held view that psychopharmacological approaches work by directly targeting automatic emotional information processing in the brain, it is usually postulated that psychological treatments affect these processes only over time, through changes in more conscious thought cycles. This study explored the role of early changes in emotional information processing in CBT action. Twenty-eight untreated patients with panic disorder were randomized to a single session of exposure-based CBT or waiting group. Emotional information processing was measured on the day after intervention with an attentional visual probe task, and clinical symptoms were assessed on the day after intervention and at 4-week follow-up. Vigilance for threat information was decreased in the treated group, compared with the waiting group, the day after intervention, before reductions in clinical symptoms. The magnitude of this early effect on threat vigilance predicted therapeutic response after 4 weeks. Cognitive behavioral therapy rapidly affects automatic processing, and these early effects are predictive of later therapeutic change. Such results suggest very fast action on automatic processes mediating threat sensitivity, and they provide an early marker of treatment response. Furthermore, these findings challenge the notion that psychological treatments work directly on conscious thought processes before automatic information processing and imply a greater similarity between early effects of pharmacological and psychological treatments for anxiety than previously thought.","subset":"pubmed_abstract"} +{"meta":{"pmid":16499544,"dup_signals":{"dup_doc_count":27,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":23}}},"text":"Measuring resident physicians' performance of preventive care. Comparing chart review with patient survey.\nThe Accreditation Council for Graduate Medical Education has suggested various methods for evaluation of practice-based learning and improvement competency, but data on implementation of these methods are limited. To compare medical record review and patient surveys on evaluating physician performance in preventive services in an outpatient resident clinic. Within an ongoing quality improvement project, we collected baseline performance data on preventive services provided for patients at the University of Alabama at Birmingham (UAB) Internal Medicine Residents' ambulatory clinic. Seventy internal medicine and medicine-pediatrics residents from the UAB Internal Medicine Residency program. Resident- and clinic-level comparisons of aggregated patient survey and chart documentation rates of (1) screening for smoking status, (2) advising smokers to quit, (3) cholesterol screening, (4) mammography screening, and (5) pneumonia vaccination. Six hundred and fifty-nine patient surveys and 761 charts were abstracted. At the clinic level, rates for screening of smoking status, recommending mammogram, and for cholesterol screening were similar (difference <5%) between the 2 methods. Higher rates for pneumonia vaccination (76% vs 67%) and advice to quit smoking (66% vs 52%) were seen on medical record review versus patient surveys. However, within-resident (N=70) comparison of 2 methods of estimating screening rates contained significant variability. The cost of medical record review was substantially higher ($107 vs $17\/physician). Medical record review and patient surveys provided similar rates for selected preventive health measures at the clinic level, with the exception of pneumonia vaccination and advising to quit smoking. A large variation among individual resident providers was noted.","subset":"pubmed_abstract"} +{"meta":{"pmid":15465489,"dup_signals":{"dup_doc_count":11}},"text":"Hox\/Pbx and Brn binding sites mediate Pax3 expression in vitro and in vivo.\nPax3 is a paired-homeodomain class transcription factor that serves a role in dorsal-ventral and medial-lateral patterning during vertebrate embryogenesis. Its expression is localized to dorsal domains within the developing neural tube and lateral domains within the developing somite. Additionally, modulation of its expression occurs along the rostral-caudal axis. Previous studies [Development 124 (1997) 617] have localized sequence elements required for expression of Pax3 in the neural tube and neural crest to a 1.6 kbp promoter fragment. In the present study, four discrete DNA elements within the 1.6 kbp promoter fragment are shown by electrophoretic mobility shift assays (EMSA) to exhibit sequence specific interactions with proteins present in nuclear extracts from P19 EC cells induced to express Pax3 by treatment with retinoic acid (RA). Proteins interacting at each of these elements are identified based on biochemical purification using DNA affinity chromatography or a candidate approach. These identifications were confirmed by the ability of specific antibodies to super-shift DNA-protein complexes in EMSA. Two of the four DNA sequence elements are shown to interact with the neural specific Pou-domain class III transcription factors Brn1 and Brn2. The remaining sites contain either consensus binding elements for heterodimers of Pbx and an anterior set of Hox family members, from paralogous groups 1-5, or monomeric Meis and are shown to interact with members of the Pbx and Meis families. Ectopic expression of Brn2 plus HoxA1 but not either factor alone, is sufficient to induce efficient expression from the endogenous Pax3 promoter in P19 EC stem cells under conditions where they would not otherwise express Pax3. Finally, in transgenic mice, mutation of either of the Pou-domain protein binding sites results in reduced expression throughout the neural tube while mutation of the Pbx\/Hox binding site results in loss of expression in the anterior domain in which Hox family members from paralogous groups 1-5 are expressed. These observations demonstrate that binding elements for both neural and anterior-posterior position specific transcription factors mediate domains of Pax3 expression.","subset":"pubmed_abstract"} +{"meta":{"pmid":19034530,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-40":3,"2023-23":1,"2023-06":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2024-26":1}}},"text":"Calcium effects on life-history traits in a wild population of the great tit (Parus major): analysis of long-term data at several spatial scales.\nCalcium is an essential micronutrient for birds during egg formation and for skeletal development in nestlings. Habitat level studies suggest that birds breeding in low-calcium areas may be limited in the size or number of eggs they lay and in the quality of their nestlings. However, as birds forage non-randomly and may travel considerable distances to acquire calcium, describing different breeding environments in terms of their calcium availability is problematic. Here we explore the spatial relationships between 300-fold variation in soil calcium and the life-history traits of ca. 6,000 pairs of great tits breeding in a single continuous woodland over 41 years. Controlling for other habitat differences, we found strong positive associations between soil calcium, clutch size and recruitment at spatial scales of over 300 m from each nestbox, suggesting that females may have been travelling inter-territorially to acquire calcium during egg formation. Soil calcium near each nestbox (mean distance = 58 m) was a strong positive predictor of mean fledgling mass, suggesting that local calcium was more important during nestling stages. We found no effect of soil calcium on lay-date or egg mass. This study is the first to provide evidence that small woodland passerines are limited by calcium availability at several different spatial scales. However, experimental work is necessary to test the causality of these spatial patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":30608098,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-10":1,"2020-40":1,"2019-30":1,"2019-26":1,"2019-18":2,"2019-13":1,"2019-09":2,"2019-04":2,"2021-25":1,"2024-10":1,"2024-26":1}}},"text":"Fiber plucking by molecular motors yields large emergent contractility in stiff biopolymer networks.\nThe mechanical properties of the cell depend crucially on the tension of its cytoskeleton, a biopolymer network that is put under stress by active motor proteins. While the fibrous nature of the network is known to strongly affect the transmission of these forces to the cellular scale, our understanding of this process remains incomplete. Here we investigate the transmission of forces through the network at the individual filament level, and show that active forces can be geometrically amplified as a transverse motor-generated force \"plucks\" the fiber and induces a nonlinear tension. In stiff and densely connected networks, this tension results in large network-wide tensile stresses that far exceed the expectation drawn from a linear elastic theory. This amplification mechanism competes with a recently characterized network-level amplification due to fiber buckling, suggesting that that fiber networks provide several distinct pathways for living systems to amplify their molecular forces.","subset":"pubmed_abstract"} +{"meta":{"pmid":10799999,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-22":1,"unknown":9}}},"text":"Comparison of transvaginal sonography, saline infusion sonography, and hysteroscopy in premenopausal women with abnormal uterine bleeding.\nSaline infusion sonography (SIS) is a relatively new technique in the evaluation of abnormal uterine bleeding. We compared the diagnostic accuracy of SIS with that of transvaginal sonography (TVS) in the detection of intracavitary abnormalities in premenopausal women with abnormal uterine bleeding. In this prospective study, consecutive premenopausal women who underwent a hysteroscopy for abnormal uterine bleeding also underwent TVS and SIS. The findings at TVS and SIS were compared with the hysteroscopic and histologic findings. Sensitivity, specificity, and likelihood ratios were calculated. Receiver operating characteristic curves were constructed to assess the performance of endometrial thickness measured using TVS. Sixty-two patients were included in the study. TVS demonstrated 60% sensitivity in directly visualizing intracavitary abnormalities and 93% specificity. The likelihood ratio of the presence of an intracavitary abnormality was 8, and the likelihood ratio of the absence of an intracavitary abnormality was 0.43. Defining an abnormality at TVS as direct visualization of an intracavitary abnormality or an endometrial thickness greater than 5 mm, TVS had an 85% sensitivity and a 21% specificity, with corresponding likelihood ratios of 1.1 and 0.71, respectively. For SIS, the sensitivity, specificity, and likelihood ratios of the presence and absence of intracavitary abnormalities were 88%, 95%, 10, and 0.13, respectively. SIS is more accurate in the diagnosis of intracavitary abnormalities in premenopausal women than is TVS. An approach using endometrial thickness measurement by TVS and reserving SIS for patients who have an endometrial thickness greater than 5 mm or an intracavitary abnormality visualized by TVS would be the most effective method to reduce the number of hysteroscopies.","subset":"pubmed_abstract"} +{"meta":{"pmid":10740507,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Physical-property comparison of a chairside- or laboratory-polymerized permanent soft-liner during 1 year.\nThis investigation examined the influence of polymerization mode and water storage duration on the Shore A hardness, water sorption, resin solubility, and glass transition temperature of Permasoft, a commercial soft denture liner that is polymerized either chairside or in the laboratory. Specimen disks (31-mm diameter x 10 mm thick) and bars (44 x 8.5 x 1.2 mm) were polymerized following manufacturer's recommendations. The chairside polymerization process was simulated by pouring the mixed components into a mold and processing at 70 degrees C for 15 minutes under 2-psi pressure. Laboratory-polymerized specimens of the same dimensions were fabricated by processing under 500-psi pressure at 100 degrees C for 45 minutes. Specimens were stored in distilled water at 37 degrees C for 1, 7, and 30 days, and 6 and 12 months. Specimens were tested for Shore A hardness, water sorption, resin solubility, and glass transition temperature after the prescribed interval. To determine the effects of polymerization mode and storage time on material properties, a repeated-measures ANOVA (hardness data) and a two-way ANOVA (sorption and solubility data) with appropriate post-hoc tests were used. Shore A hardness values increased from a low of 9.4 (+\/- 0.5) units immediately after fabrication to a maximum of 15.9 (+\/- 1.1) units after 1 year. Mode of polymerization did not influence hardness (p = .9851). Water-sorption values ranged from 4.2 (+\/- 0.2%) of dry weight to 14.7 (+\/- 2.5%) after 1 year. Resin solubility varied from 10.3 (+\/- 0.6%) of preimmersion weight to 15.4 (+\/- 1.1%), and immersion duration had no effect on solubility. In addition, after 1 year of storage, no difference in resin solubility or water sorption was found with respect to cure mode. The glass transition temperature for chairside-polymerized samples approximated -10 degrees C, while that for labpolymerized samples approximated -15 degrees C. With regard to the material properties evaluated in this study, clinically processed Permasoft liner was equivalent to the laboratory-processed material.","subset":"pubmed_abstract"} +{"meta":{"pmid":27025445,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2017-47":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2019-04":1,"2017-13":1}}},"text":"Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease.\nLevodopa does not improve dysarthria in patients with Parkinson Disease (PD), although vocal exercise therapy, such as \"LSVT\/LOUD(\u00ae)\", does improve vocal communication. Most patients receive vocal exercise therapy while concurrently being treated with levodopa, although the interaction between levodopa and vocal exercise therapy on communication in PD is relatively unknown. Further, carryover of vocal exercise therapy to novel situations is critical for successful outcomes, but the influence of novel situations on rehabilitated vocal communication is not well understood. To address the influence of exercise, medications, and environment on vocal communication with precise experimental control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion to the medial forebrain bundle), and assessed ultrasonic vocalizations after: vocal exercise, vocal exercise with levodopa, levodopa alone, and control conditions. We tested USVs in the familiar training environment of the home cage and a novel cage. We hypothesized that parkinsonian rats that undergo vocal exercise would demonstrate significant improvement of ultrasonic vocalization (USV) acoustic parameters as compared to the control exercise and levodopa-only treatment groups. We further hypothesized that vocal exercise in combination with levodopa administration, similar to what is common in humans, would lead to improvement in USV outcomes, particularly when tested in a familiar versus a novel environment. We found that the combination of exercise and levodopa lead to some improvement in USV acoustic parameters and these effects were stronger in a familiar vs. a novel environment. Our results suggest that although treatment can improve aspects of communication, environment can influence the benefits of these effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":32595413,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Two new species of Plectranthias (Teleostei, Serranidae, Anthiadinae) from mesophotic coral ecosystems in the tropical Central Pacific.\nTwo new species of Plectranthias perchlets are described, collected from mesophotic coral ecosystems in French Polynesia and the Republic of the Marshall Islands, in the tropical Central Pacific. Plectranthias polygonius sp. nov. was collected at a depth of 105 m in Tahiti, French Polynesia, and 120 m in Maloelap Atoll, Republic of the Marshall Islands. It was also observed in Moorea and Rangiroa (French Polynesia), and at Majuro and Erikub Atolls, Republic of the Marshall Islands. Plectranthias hinano sp. nov. was collected at a depth of 90-98 m in Tahiti, French Polynesia, and observed in Moorea. The barcode fragment of the cytochrome oxidase I gene of Plectranthias polygonius sp. nov. does not closely match any published sequence of Plectranthias, with approximately 15% uncorrected divergence from several species. Plectranthias polygonius sp. nov. can be distinguished from all of its congeners by coloration and morphology. The barcode fragment of the COI gene of Plectranthias hinano sp. nov. is closest to Plectranthias bennetti, with 5.4% uncorrected divergence. Plectranthias hinano sp. nov. is also distinguished from all of its congeners by morphology, and a coloration that includes two indistinct black spots along the base of the dorsal-fin, and transparent yellow dorsal and anal fin membranes. With this publication, the genus Plectranthias now comprises 58 valid species, with representatives from tropical to temperate waters of the Atlantic, Pacific, and Indian oceans. These two new discoveries add to the growing body of research highlighting the rich biodiversity of mesophotic ecosystems.","subset":"pubmed_abstract"} +{"meta":{"pmid":26811505,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-27":1,"2021-49":1,"2020-34":1,"2020-29":1,"2020-24":1,"2018-13":1,"2018-05":1,"2017-39":1,"2017-34":1,"2023-23":1}}},"text":"Role of UTS2 gene in the genetic susceptibility to atrial fibrillation in the Chinese population.\nAtrial fibrosis plays a key role in the inducibility and persistence of atrial fibrillation. Urotensin II (U-II\/UTS2) induces cardiac fibrosis by increasing fibroblast collagen synthesis and increased U-II plasma levels have been reported in patients with atrial fibrosis. Our objective was therefore to evaluate the possible role of the UTS2 gene polymorphisms Thr21Met and Ser89Asn in the genetic susceptibility to atrial fibrillation in a Chinese population. A case-control study was designed to compare the distribution of alleles and genotypes between controls (n=197) and patients with AF (n=197). The detection of UTS2 gene polymorphisms was undertaken using the PCR-restriction fragment length polymorphism technique. We identified statistically significant differences between the atrial fibrillation and control groups with regard to the frequency of genotype variant GA at the Ser89Asn locus (OR 1.955, 95% CI 1.071 to 3.566, p=0.029). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn was only seen in men in the additive tested inheritance model (OR 2.843, 95% CI 1.273 to 6.348, p=0.011). There was a statistical difference in Met21Met, implying a potential beneficial role for atrial fibrillation in the recessive tested inheritance model among men (OR 0.260, 95% CI 0.075 to 0.89, p=0.033; AA vs GA-GG). For subjects with atrial fibrillation, the Met21Met genotype was associated with a larger anteroposterior left atrial diameter (AA vs GG, 4.12\u00b10.62 vs 3.86\u00b10.51, p=0.028) and a smaller left ventricular end-diastolic diameter (AA vs GG, 4.50\u00b10.48 vs 4.78\u00b10.49, p=0.039). Ser89Asn polymorphisms of the UTS2 gene are significantly associated with atrial fibrillation in the Chinese population. Additionally, we demonstrated that genotype Met21Met may have a potential beneficial role in atrial fibrillation.","subset":"pubmed_abstract"} +{"meta":{"pmid":18204388,"dup_signals":{"dup_doc_count":26,"dup_dump_count":4,"dup_details":{"curated_sources":3,"2024-18":2,"2024-10":2,"2014-10":4,"2013-48":4,"unknown":11}}},"text":"Treatment of neck pain: injections and surgical interventions: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders.\nBest evidence synthesis. To identify, critically appraise, and synthesize literature from 1980 through 2006 on surgical interventions for neck pain alone or with radicular pain in the absence of serious pathologic disease. There have been no comprehensive systematic literature or evidence-based reviews published on this topic. We systematically searched Medline for literature published from 1980 to 2006 on percutaneous and open surgical interventions for neck pain. Publications on the topic were also solicited from experts in the field. Consensus decisions were made about the scientific merit of each article; those judged to have adequate internal validity were included in our Best Evidence Synthesis. Of the 31,878 articles screened, 1203 studies were relevant to the Neck Pain Task Force mandate and of these, 31 regarding treatment by surgery or injections were accepted as scientifically admissible. Radiofrequency neurotomy, cervical facet injections, cervical fusion and cervical arthroplasty for neck pain without radiculopathy are not supported by current evidence. We found there is support for short-term symptomatic improvement of radicular symptoms with epidural corticosteroids. It is not clear from the evidence that long-term outcomes are improved with the surgical treatment of cervical radiculopathy compared to nonoperative measures. However, relatively rapid and substantial symptomatic relief after surgical treatment seems to be reliably achieved. It is not evident that one open surgical technique is clearly superior to others for radiculopathy. Cervical foramenal or epidural injections are associated with relatively frequent minor adverse events (5%-20%); however, serious adverse events are very uncommon (<1%). After open surgical procedures on the cervical spine, potentially serious acute complications are seen in approximately 4% of patients. Surgical treatment and limited injection procedures for cervical radicular symptoms may be reasonably considered in patients with severe impairments. Percutaneous and open surgical treatment for neck pain alone, without radicular symptoms or clear serious pathology, seems to lack scientific support.","subset":"pubmed_abstract"} +{"meta":{"pmid":21454752,"dup_signals":{"dup_doc_count":32,"dup_dump_count":25,"dup_details":{"curated_sources":3,"2021-43":1,"2020-45":1,"2020-05":1,"2019-26":1,"2018-51":1,"2018-47":2,"2018-30":1,"2018-26":1,"2018-05":1,"2017-51":1,"2017-43":2,"2017-39":2,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":1,"2016-30":1,"2016-18":1,"2016-07":1,"2022-21":1,"2024-18":1,"2017-13":1,"2024-26":1}}},"text":"Topological phase transition and texture inversion in a tunable topological insulator.\nThe recently discovered three-dimensional or bulk topological insulators are expected to exhibit exotic quantum phenomena. It is believed that a trivial insulator can be twisted into a topological state by modulating the spin-orbit interaction or the crystal lattice, driving the system through a topological quantum phase transition. By directly measuring the topological quantum numbers and invariants, we report the observation of a phase transition in a tunable spin-orbit system, BiTl(S(1-\u03b4)Se(\u03b4))(2), in which the topological state formation is visualized. In the topological state, vortex-like polarization states are observed to exhibit three-dimensional vectorial textures, which collectively feature a chirality transition as the spin momentum-locked electrons on the surface go through the zero carrier density point. Such phase transition and texture inversion can be the physical basis for observing fractional charge (\u00b1e\/2) and other fractional topological phenomena.","subset":"pubmed_abstract"} +{"meta":{"pmid":29464163,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Innovative Use of Thighplasty to Improve Prosthesis Fit and Function in a Transfemoral Amputee.\nExcess residual limb fat is a common problem that can impair prosthesis control and negatively impact gait. In the general population, thighplasty and liposuction are commonly performed for cosmetic reasons but not specifically to improve function in amputees. The objective of this study was to determine if these procedures could enhance prosthesis fit and function in an overweight above-knee amputee. We evaluated the use of these techniques on a 50-year-old transfemoral amputee who was overweight. The patient underwent presurgical imaging and tests to measure her residual limb tissue distribution, socket-limb interface stiffness, residual femur orientation, lower-extremity function, and prosthesis satisfaction. A medial thighplasty procedure with circumferential liposuction was performed, during which 2,812 g (6.2 lbs.) of subcutaneous fat and skin was removed from her residual limb. Imaging was repeated 5 months postsurgery; functional assessments were repeated 9 months postsurgery. The patient demonstrated notable improvements in socket fit and in performing most functional and walking tests. Her comfortable walking speed increased 13.3%, and her scores for the Sit-to-Stand and Four Square Step tests improved over 20%. Femur alignment in her socket changed from 8.13 to 4.14 degrees, and analysis showed a marked increase in the socket-limb interface stiffness. This study demonstrates the potential of using a routine plastic surgery procedure to modify the intrinsic properties of the limb and to improve functional outcomes in overweight or obese transfemoral amputees. This technique is a potentially attractive option compared with multiple reiterations of sockets, which can be time-consuming and costly.","subset":"pubmed_abstract"} +{"meta":{"pmid":23322764,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Automated detection of instantaneous gait events using time frequency analysis and manifold embedding.\nAccelerometry is a widely used sensing modality in human biomechanics due to its portability, non-invasiveness, and accuracy. However, difficulties lie in signal variability and interpretation in relation to biomechanical events. In walking, heel strike and toe off are primary gait events where robust and accurate detection is essential for gait-related applications. This paper describes a novel and generic event detection algorithm applicable to signals from tri-axial accelerometers placed on the foot, ankle, shank or waist. Data from healthy subjects undergoing multiple walking trials on flat and inclined, as well as smooth and tactile paving surfaces is acquired for experimentation. The benchmark timings at which heel strike and toe off occur, are determined using kinematic data recorded from a motion capture system. The algorithm extracts features from each of the acceleration signals using a continuous wavelet transform over a wide range of scales. A locality preserving embedding method is then applied to reduce the high dimensionality caused by the multiple scales while preserving salient features for classification. A simple Gaussian mixture model is then trained to classify each of the time samples into heel strike, toe off or no event categories. Results show good detection and temporal accuracies for different sensor locations and different walking terrains.","subset":"pubmed_abstract"} +{"meta":{"pmid":35023657,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Clinical follow-up of children with high vitamin B12 values: should we worry?\nRequests of Vitamin B12 test increased with the widespread use of autoanalysers. Although the cause of requests was deficiency suspicions, an important ratio of high levels of Vitamin B12 were reported to physicians by laboratory. Ratios of values of high Vitamin B12 among test request in adults are reported as 14- 20% in present three monocentre studies and one multicentre study. There is no report on children with high vitamin B12 for both ratio in lab requests or clinical follow up. We evaluated the records of 40 children (23 male \/17 female) with high B12 values ( > 1000 pg\/ ml) retrospectively. Children were otherwise healthy children and were seen at outpatient pediatric clinics. Additionally, vitamin B12 values of 13 acute lymphoblastic leukemia patients at diagnosis time were retrieved to enlighten possible role of lymphocytes. Children did not have any malign or chronic diseases causing the high Vitamin B12 values. Holotranscobalamin levels were normal or slightly above. Two patients did develop leukemia later. Our follow up showed that high vitamin B12 values slightly decreased at 3 months and then remained unchanged later. The high numbers of T and B cells are not the source of vitamin B12 elevation. Our study suggests that high-vitamin B12 values are usually benign in children but some patients may develop leukemia later. We suggest that patients should be followed up for some time after testing for severe hematological diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":24854055,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":3,"unknown":11}}},"text":"Virtual sensors for on-line wheel wear and part roughness measurement in the grinding process.\nGrinding is an advanced machining process for the manufacturing of valuable complex and accurate parts for high added value sectors such as aerospace, wind generation, etc. Due to the extremely severe conditions inside grinding machines, critical process variables such as part surface finish or grinding wheel wear cannot be easily and cheaply measured on-line. In this paper a virtual sensor for on-line monitoring of those variables is presented. The sensor is based on the modelling ability of Artificial Neural Networks (ANNs) for stochastic and non-linear processes such as grinding; the selected architecture is the Layer-Recurrent neural network. The sensor makes use of the relation between the variables to be measured and power consumption in the wheel spindle, which can be easily measured. A sensor calibration methodology is presented, and the levels of error that can be expected are discussed. Validation of the new sensor is carried out by comparing the sensor's results with actual measurements carried out in an industrial grinding machine. Results show excellent estimation performance for both wheel wear and surface roughness. In the case of wheel wear, the absolute error is within the range of microns (average value 32 \u03bcm). In the case of surface finish, the absolute error is well below Ra 1 \u03bcm (average value 0.32 \u03bcm). The present approach can be easily generalized to other grinding operations.","subset":"pubmed_abstract"} +{"meta":{"pmid":22218658,"dup_signals":{"dup_doc_count":18,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":3,"2017-13":1,"unknown":2}}},"text":"[Relationship between health care insurance and Papanicolaou exam: a propensity score application using a complex sample inquiry].\nCervical uterine cancer is the second most common malignancy affecting women worldwide. Papanicolaou smear is a simple screening test that can detect the disease at an early and curable stage. Although indicated to every adult woman, Pap smear screening covers less than 70% of Brazilian women. This study aimed to evaluate if private health care insurance coverage was associated with Papanicolaou smear screening. We analyzed data from 6,299 women aged 35 years or older, resident in Rio de Janeiro state, who had been interviewed in the National Household Sample Survey (PNAD) in 2003. In order to minimize the occurrence of biases, we utilized the propensity score matching method, considering all information from sample design in the scores estimation (sample weights, strata and primary sampling units). A sub-sample of 2,348 women was then obtained, with socioeconomic and biological covariates equally distributed between the groups with and without private health insurance coverage (1,174 pairs). Logistic regression model was then used and the results showed that the chance of Papanicolaou smear screening is 26.1% higher (OR=1.261; p=0,096; CI 95%= [0.96;1.66]) for women with health insurance coverage when compared to women without health insurance coverage at 10% of significance. The results indicate the need of extending periodic cervical cancer screening for all women, reducing the inequalities still present nowadays.","subset":"pubmed_abstract"} +{"meta":{"pmid":22275473,"dup_signals":{"dup_doc_count":20,"dup_dump_count":8,"dup_details":{"curated_sources":3,"2023-23":3,"2023-14":3,"2022-21":2,"2022-05":3,"2021-49":3,"2021-43":1,"2021-17":1,"2021-04":1}}},"text":"Vitamin D and fertility: a systematic review.\nVitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men. The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals. We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011. The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":29160324,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Atomic layer MoS2-graphene van der Waals heterostructure nanomechanical resonators.\nHeterostructures play significant roles in modern semiconductor devices and micro\/nanosystems in a plethora of applications in electronics, optoelectronics, and transducers. While state-of-the-art heterostructures often involve stacks of crystalline epi-layers each down to a few nanometers thick, the intriguing limit would be hetero-atomic-layer structures. Here we report the first experimental demonstration of freestanding van der Waals heterostructures and their functional nanomechanical devices. By stacking single-layer (1L) MoS2 on top of suspended single-, bi-, tri- and four-layer (1L to 4L) graphene sheets, we realize an array of MoS2-graphene heterostructures with varying thickness and size. These heterostructures all exhibit robust nanomechanical resonances in the very high frequency (VHF) band (up to \u223c100 MHz). We observe that fundamental-mode resonance frequencies of the heterostructure devices fall between the values of graphene and MoS2 devices. Quality (Q) factors of heterostructure resonators are lower than those of graphene but comparable to those of MoS2 devices, suggesting interface damping related to interlayer interactions in the van der Waals heterostructures. This study validates suspended atomic layer heterostructures as an effective device platform and provides opportunities for exploiting mechanically coupled effects and interlayer interactions in such devices.","subset":"pubmed_abstract"} +{"meta":{"pmid":19709328,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"A prospective comparative study of gentamicin- and amikacin-induced nephrotoxicity in patients with normal baseline renal function.\nThe aim of this study was to compare the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in patients with normal baseline renal function. This study was a 1-year, non-interventional prospective study of patients administered either GM or AK. The study was carried out at the internal medicine department of Al-Watani governmental study. Nephrotoxicity was defined as a serum creatinine (SCr) increase of >or=0.5 mg\/dL from the basal (normal) SCr level. The two groups (GM, n = 45 and AK, n = 49) were similar in population composition, and underlying pathological and infectious processes requiring antimicrobials. No significant difference in age was found between patients in the GM and AK groups, P = 0.83. Patients in the GM group received comparatively lower doses than those in the AK group (mean = 2.5 mg\/kg\/day and 14.4 mg\/kg\/day, respectively) but the duration of treatment was similar. Sixteen of 45 patients receiving GM (35.6%) and eight of 49 patients receiving AK (16.3%) developed nephrotoxicity, P = 0.033. Single daily dosing with GM, regardless of the total daily dose, produced less nephrotoxicity than multiple dosing. In contrast, AK given at a total dose of 1 g daily, showed no benefit of single dosing compared with multiple dosing. In patients with initial normal renal function, GM was significantly more nephrotoxic than AK. Multiple dosing of GM was more nephrotoxic than single dosing. AK-induced nephrotoxicity was not significantly dependent on dosing frequency.","subset":"pubmed_abstract"} +{"meta":{"pmid":22258996,"dup_signals":{"dup_doc_count":76,"dup_dump_count":43,"dup_details":{"curated_sources":4,"2023-40":2,"2023-23":5,"2023-14":1,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":1,"2021-43":3,"2021-39":3,"2021-31":2,"2021-25":1,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":1,"2019-09":1,"2018-30":1,"2018-26":2,"2018-17":1,"2018-09":3,"2017-51":1,"2017-47":3,"2017-43":1,"2017-39":3,"2017-34":1,"2017-30":3,"2017-26":1,"2017-22":2,"2017-17":2,"2023-50":1,"2024-22":3,"2024-18":1,"2024-10":2,"2017-13":1,"2024-26":1}}},"text":"Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children.\nPlanning for outbreaks of influenza is a high priority public health issue for national governments. Neuraminidase inhibitors (NIs) are thought to help reduce the symptoms of influenza with several possible mechanisms proposed. NIs have been stockpiled with a view to their widespread use in the event of a pandemic. However, the evidence base for this class of agents remains a source of debate. In a previous review we have documented substantial risks of publication bias of trials of NIs for influenza (60% of patient data from phase III treatment trials of oseltamivir have never been published) and reporting bias in the published trials. Our confidence in the conclusions of previous versions of this review has been subsequently undermined. Since we have become aware of a large number of unpublished trials of NIs in the management of influenza, this review updates and merges existing reviews in this area. To review clinical study reports of placebo-controlled randomised trials, regulatory comments and reviews ('regulatory information') of the effects of the NIs oseltamivir and zanamivir for influenza in all age groups and appraise trial programmes, rather than single studies.Clinical study reports are very detailed, unpublished clinical trial data containing in-depth descriptions of protocol rationale, methods analysis plans, trial results and organisational documents (such as contracts). A series of clinical studies designed and conducted by one sponsor represents a trial programme of a drug indication (for example treatment of influenza). We searched trial registries, cross-referencing published and unpublished sources and corresponded with manufacturers and regulators. We searched the archives of the US Food and Drug Administration (FDA) and European and Japanese regulators. The evidence in this review reflects searches to obtain relevant information up to 12 April 2011. We included regulatory information based on assessments of randomised controlled trials (RCTs) conducted in people of any age who had either confirmed or suspected influenza, or who had been exposed to influenza in the local community or place of residence. We included information which had been made available by our deadline. We indexed regulatory information in two purpose-built instruments and reconstructed trials using CONSORT statement-based templates. To progress to Stage 2 (full analysis) we sought manufacturer explanations of discrepancies in the data. GlaxoSmithKline (GSK) offered us individual patient data and responded to our queries, but Roche did not provide us with complete clinical study reports. In Stage 2 we intended to analyse trials with validated data (i.e. assuming our validation questions aimed at clarifying omissions and discrepancies were resolved). No studies progressed to Stage 2. We carried out analyses of the effects of oseltamivir on time to first alleviation of symptoms and hospitalisations using the intention-to-treat (ITT) population and tested five hypotheses generated post-protocol publication. We included and analysed data from 25 studies (15 oseltamivir and 10 zanamivir studies). We could not use data from a further 42 studies due to insufficient information or unresolved discrepancies in their data. The included trials were predominantly conducted in adults during influenza seasons in both hemispheres. A small number of studies were conducted in older people residing in care homes and in people with underlying respiratory diseases. The studies had adequate randomisation and blinding procedures, but imbalances in the analysis populations available (ITT influenza-infected) left many of the studies at risk of attrition bias. All the studies were sponsored by manufacturers of NIs. Time to first alleviation of symptoms in people with influenza-like illness symptoms (i.e. ITT population) was a median of 160 hours (range 125 to 192 hours) in the placebo groups and oseltamivir shortened this by around 21 hours (95% confidence interval (CI) -29.5 to -12.9 hours, P < 0.001; five studies) but there was no evidence of effect on hospitalisations based on seven studies with a median placebo group event rate of 0.84% (range 0% to 11%): odds ratio (OR) 0.95; 95% CI 0.57 to 1.61, P = 0.86). These results are based on the comprehensive ITT population data and are unlikely to be biased. A post-protocol analysis showed that participants randomised to oseltamivir in treatment trials had a reduced odds being diagnosed with influenza (OR 0.83; 95% CI 0.73 to 0.94, P = 0.003; eight studies), probably due to an altered antibody response. Zanamivir trials showed no evidence of this. Due to limitations in the design, conduct and reporting of the trial programme, the data available to us lacked sufficient detail to credibly assess a possible effect of oseltamivir on complications and viral transmission. We postponed analysis of zanamivir evidence because of the offer of individual patient data (IPD) from its manufacturer. The authors have been unable to obtain the full set of clinical study reports or obtain verification of data from the manufacturer of oseltamivir (Roche) despite five requests between June 2010 and February 2011. No substantial comments were made by Roche on the protocol of our Cochrane Review which has been publicly available since December 2010. We found a high risk of publication and reporting biases in the trial programme of oseltamivir. Sub-population analyses of the influenza infected population in the oseltamivir trial programme are not possible because the two arms are non-comparable due to oseltamivir's apparent interference with antibody production. The evidence supports a direct oseltamivir mechanism of action on symptoms but we are unable to draw conclusions about its effect on complications or transmission. We expect full clinical study reports containing study protocol, reporting analysis plan, statistical analysis plan and individual patient data to clarify outstanding issues. These full clinical study reports are at present unavailable to us.","subset":"pubmed_abstract"} +{"meta":{"pmid":27139621,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Myoepithelioma of Soft Tissues: A Single Institution Retrospective Case Series.\nMyoepithelioma of the soft tissues is a rare entity and little is known about how best to manage locally recurrent and high-grade disease. Here, we retrospectively examined outcomes of surgery, chemotherapy, and radiation therapy (RT) for treatment of low-grade and high-grade myoepithelioma of soft tissues. We reviewed 20 cases of myoepithelioma of soft tissues seen at Mayo Clinic between 1994 and 2014. The effect of histologic grade and therapies received on relapse and survival were assessed. We identified 13 patients with low-grade disease and 7 patients with high-grade disease. We found that low-grade disease was frequently effectively managed with surgical resection alone, whereas high-grade disease frequently metastasized and was often fatal. The 5-year event-free survival was 88% (confidence interval, 46%-98%) for low-grade disease versus 36% (confidence interval, 7%-75%; P=0.04) for high-grade disease. The relapse rate in low-grade disease was 29% at 5 years versus 64% (P=0.04) in high-grade disease. No significant responses to chemotherapy were noted, however, excellent responses to perioperative RT were seen. Surgery continues as the primary modality of treatment for myoepithelioma of soft tissues. Our study did not show a clear benefit of chemotherapy in the metastatic disease setting, but supports the use of perioperative RT in the management of high-grade disease; further investigation is warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":18535668,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":4,"2020-45":1,"2020-10":7,"2020-05":2,"2020-50":1}}},"text":"Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney.\nDiabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":19306176,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":3,"2024-22":1,"2024-30":1,"unknown":8}}},"text":"The Fisher grading correlated to outcome in patients with subarachnoid haemorrhage.\nCerebral vasospasm is the major cause of delayed ischemia in patients with subarachnoid haemorrhage (SAH). The Fisher grading scale has been used to predict patients in risk of developing vasospasm. Improved radiological techniques and treatment may have changed the relevance of the Fisher scale. We have now evaluated the Fisher scale, Hunt and Hess and age in relation to outcome in patients with SAH. Eighty- three patients were admitted with SAH during two years, and 84 aneurysms were treated in 78 patients. The Glasgow outcome score (GOS) within 3 months were as follows; GOS 1 (19%), GOS 2 (2%), GOS 3 (11%), GOS 4 (9%), GOS 5 (59%). There was a significant correlation between both the Fisher grading scale, Hunt and Hess scale and outcome. Age was not correlated to the Fisher grading scale or the Hunt and Hess scale. Age was also not correlated to outcome in our patients. Despite the correlation to outcome both Hunt and Hess and the Fisher grading scale had a limited predictive value of outcome due to a low specificity and\/or sensitivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":10743905,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"The role of formalin-induced pain in morphine tolerance, withdrawal, and reward.\nThe effect of a commonly used experimental pain-induction procedure (formalin injection into a hindpaw site) on morphine tolerance, withdrawal, and reward was examined in rats. Results suggest that the effects of morphine are different in the organism that is experiencing pain at the time it receives the drug than in the organism that is pain free. The presence of pain at the time of each morphine administration decreased analgesic tolerance, decreased naloxone-precipitated withdrawal, and enhanced the rewarding effect of the opiate. These findings, together with those of previous studies, suggest that theories of opiate tolerance, withdrawal, and reward should incorporate the effects of pain.","subset":"pubmed_abstract"} +{"meta":{"pmid":32286338,"dup_signals":{"dup_doc_count":11}},"text":"RNA-Seq of human whole blood: Evaluation of globin RNA depletion on Ribo-Zero library method.\nPeripheral blood is a highly accessible biofluid providing a rich source of information about human physiology and health status. However, for studies of the blood transcriptome with RNA sequencing (RNA-Seq) techniques, high levels of hemoglobin mRNAs (hgbRNA) present in blood can occupy valuable sequencing space, impacting detection and quantification of non-hgbRNAs. In this study, we evaluated two methods for preparing ribosomal RNA (rRNA)-depleted sequencing libraries for RNA-Seq of whole blood, one of which is also designed to deplete hgbRNAs. Two experiments were performed: one evaluating library performance across 6 human blood samples and the other examining library reproducibility and performance in a two-subject subset. We find that addition of hgbRNA depletion to the rRNA-depletion protocol for library preparation from blood RNA effectively reduces highly abundant hgbRNA reads; however, it does not result in a statistically significant increase in differentially expressed genes in our patient-control study. Bioinformatic removal of globin gene counts in non-hgbRNA depleted libraries provides improvement in overall performance of these libraries. We conclude that use of a standard ribosomal RNA depletion method for library preparation coupled with bioinformatic removal of globin gene counts is sufficient for reproducible and sensitive measurement of both coding and noncoding RNAs in the blood transcriptome.","subset":"pubmed_abstract"} +{"meta":{"pmid":21540516,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Boron and nitrogen impurities in SiC nanoribbons: an ab initio investigation.\nUsing ab initio calculations based on density-functional theory we have performed a theoretical investigation of substitutional boron and nitrogen impurities in silicon carbide (SiC) nanoribbons. We have considered hydrogen terminated SiC ribbons with zigzag and armchair edges. In both systems we verify that the boron and nitrogen atoms energetically prefer to be localized at the edges of the nanoribbons. However, while boron preferentially substitutes a silicon atom, nitrogen prefers to occupy a carbon site. In addition, our electronic-structure calculations indicate that (i) substitutional boron and nitrogen impurities do not affect the semiconducting character of the armchair SiC nanoribbons, and (ii) the half-metallic behavior of the zigzag nanoribbons is maintained in the presence of substitutional boron impurities. In contrast, nitrogen atoms occupying edge carbon sites transform half-metallic zigzag nanoribbons into metallic systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":17293719,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":3,"2024-26":1,"unknown":2}}},"text":"The effect of definitions of activities of daily living on estimates of changing ability among older people.\nPhysical functioning status is often assessed using scales of activities of daily living and instrumental activities of daily living. Different ways of defining change in adequacy of performance of both activities of daily living and instrumental activities of daily living tasks may be used, including increasing difficulty in performance, the need for assistance and inability to do tasks. In this prospective study, we investigated the effect of different definitions of decline on estimates of physical function, and explored the relationships between decline in each activity of daily living individually and potential predictors. The study was based on a sample of 999 individuals aged 65 years or more who participated in a national survey of quality of life, of whom 531 (68% of those eligible for follow up) responded 12-18 months later. Different definitions of decline were used and the prevalence of decline was, depending on the individual activities of daily living item, used as an outcome in logistic regression models. The results showed that the strength of association with chronic diseases, demographic, psychological and environmental factors varied by altering the activities of daily living item used. Decline in ability to walk 400 yards was strongly associated with respiratory problems (odds ratio 3.5 [95% confidence interval 1.3-9.0]) while decline in ability to get on a bus was associated with musculoskeletal problems (odds ratio 2.8 [95% confidence interval 1.4-5.6]). In conclusion, the prevalence of decline varies by definition, and summary measures which are customarily used to describe disability, may be inadequate for the assessment and identification of predictors of decline in functional ability.","subset":"pubmed_abstract"} +{"meta":{"pmid":19667173,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2015-18":1,"unknown":9}}},"text":"Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.\nWe provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by (1)H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":34077469,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Modelling future trajectories of obesity and body mass index in England.\nObesity is a leading risk for poor health outcomes in England. We examined best- and worst-case scenarios for the future trajectory of the obesity epidemic. Taking the last 27 years of Health Survey for England data, we determined both position and shape of the adult body mass index (BMI) distribution and projected these parameters 20 years forward in time. For the best-case scenario, we fitted linear models, allowing for a quadratic relationship between the outcome variable and time, to reflect a potential reversal in upwards trends. For the worst-case scenario, we fitted non-linear models that applied an exponential function to reflect a potential flattening of trends over time. Best-fitting models were identified using Monte Carlo cross-validation on 1991-2014 data, and predictions of population prevalence across five BMI categories were then validated using 2015-17 data. Both linear and non-linear models showed a close fit to observed data (mean absolute error <2%). In the best-case scenario, the proportion of the population at increased risk (BMI\u226525kg\/m2) is predicted to fall from 66% in 2017 to 53% (95% confidence interval: 41% to 64%) in 2035. In the worst-case scenario, this proportion is likely to remain relatively stable overall- 64% (37% to 90%) in 2035 -but with an increasing proportion of the population at highest risk (BMI\u226535kg\/m2). While obesity prediction depends on chosen modelling methods, even under optimistic assumptions it is likely that the majority of the English population will still be at increased risk of disease due to their weight until at least 2035, without greater allocation of resources to effective interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":32124623,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":12}}},"text":"Occlusal Stress Distribution on the Mandibular First Premolar - FEM Analysis.\nThe aim of this paper was to analyze the distribution of stress and deformation on the mandibular first premolar under two types of loading (axial and para-axial load of 200 N) using the FEM computer method. For this research a \u00b5CT scan of the first mandibular premolar was used, and the method used in this research was FEM analysis under two types of loading. The values of the von Mises stress measured in the cervical part of an intact tooth under axial load were up to 12 MPa, and under paraaxial load over 50 MPa. The values of the stress measured on the bottom of the noncarious lesion are very high \u2248 240 Mpa. Stress values in the cervical part of the intact tooth are higher in the zone of the sub-surface enamel. The deformation values of the tooth under para-axial loading were \u2248 10 times higher than the value of the deformation under axial load. The greatest deformations were seen in the area of the tooth crown. Occlusal loading leads to significant stress in the cervical part of teeth. The values of the measured stress are greater under the action of paraxial load. The values of stress in abfraction lesions measured under a paraxial load are extremely high. Exposing the lesion to further stress will lead to its deepening. The total deformation of the entire tooth under paraxial load was \u2248 10 times higher compared to the deformation value of the tooth under axial load.","subset":"pubmed_abstract"} +{"meta":{"pmid":10927849,"dup_signals":{"dup_doc_count":11}},"text":"Are child pedestrians at increased risk of injury on one-way compared to two-way streets?\nTo compare child pedestrian injury rates on one-way versus two-way streets in Hamilton, and examine whether the characteristics of child pedestrian injuries differ across street types. The rates of injury per child population, per kilometre, per year were calculated by age, sex and socio-economic status (SES). Child, environment and driver characteristics were investigated by street type. The injury rate was 2.5 times higher on one-way streets than on two-way streets and 3 times higher for children from the poorest neighbourhoods than for those from wealthier neighbourhoods. SES, injury severity, number of lanes, collision location and type of traffic control were also found to be significantly different across street types. One-way streets have higher rates of child pedestrian injuries than two-way streets in this community. Future risk factor and intervention studies should include the directionality of streets to further investigate its contribution to child pedestrian injuries.","subset":"pubmed_abstract"} +{"meta":{"pmid":28171565,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":8}}},"text":"Endometriosis risk alleles at 1p36.12 act through inverse regulation of CDC42 and LINC00339.\nGenome-wide association studies (GWAS) have identified markers within the WNT4 region on chromosome 1p36.12 showing consistent and strong association with increasing endometriosis risk. Fine mapping using sequence and imputed genotype data has revealed strong candidates for the causal SNPs within these critical regions; however, the molecular pathogenesis of these SNPs is currently unknown. We used gene expression data collected from whole blood from 862 individuals and endometrial tissue from 136 individuals from independent populations of European descent to examine the mechanism underlying endometriosis susceptibility. Association mapping results from 7,090 individuals (2,594 cases and 4,496 controls) supported rs3820282 as the SNP with the strongest association for endometriosis risk (P = 1.84 \u00d7 10\u22125, OR = 1.244 (1.126-1.375)). SNP rs3820282 is a significant eQTL in whole blood decreasing expression of LINC00339 (also known as HSPC157) and increasing expression of CDC42 (P = 2.0 \u00d710\u221254 and 4.5x10\u22124 respectively). The largest effects were for two LINC00339 probes (P = 2.0 \u00d710\u221254; 1.0 \u00d7 10\u221234). The eQTL for LINC00339 was also observed in endometrial tissue (P = 2.4 \u00d710\u22128) with the same direction of effect for both whole blood and endometrial tissue. There was no evidence for eQTL effects for WNT4. Chromatin conformation capture provides evidence for risk SNPs interacting with the promoters of both LINC00339 and CDC4 and luciferase reporter assays suggest the risk SNP rs12038474 is located in a transcriptional silencer for CDC42 and the risk allele increases expression of CDC42. However, no effect of rs3820282 was observed in the LINC00339 expression in Ishikawa cells. Taken together, our results suggest that SNPs increasing endometriosis risk in this region act through CDC42, but further functional studies are required to rule out inverse regulation of both LINC00339 and CDC42.","subset":"pubmed_abstract"} +{"meta":{"pmid":30662435,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":20}}},"text":"Genome Sequencing and Comparative Transcriptomics Provide a Holistic View of 4-Nitrophenol Degradation and Concurrent Fatty Acid Catabolism by Rhodococcus sp. Strain BUPNP1.\nRhodococcus sp.strain BUPNP1 can utilize the priority environmental pollutant 4-nitrophenol (4-NP) as its sole source of carbon and energy. In this study, genome and transcriptome sequencing were used to gain mechanistic insights into 4-NP degradation. The draft BUPNP1 genome is 5.56 Mbp and encodes 4,963 proteins, which are significantly enriched in hypothetical proteins compared to other Rhodococcus sp. A novel 4-NP catabolic 43 gene cluster \"nph\" was identified that encodes all the genes required for the conversion of 4-NP into acetyl-CoA and succinate, via 4-nitrocatechol. The cluster also encodes pathways for the catabolism of other diverse aromatic compounds. Comparisons between BUPN1 growing on either 4-NP or glucose resulted in significant changes in the expression of many nph cluster genes, and, during 4-NP growth, a loss of lipid inclusions. Moreover, fatty acid degradation\/synthesis genes were found within the nph cluster, suggesting fatty acids may be concurrently catabolised with 4-NP. A holistic model for the action of the nph gene cluster is proposed which incorporates genetic architecture, uptake and metabolism of aromatic compounds, enzymatic activities and transcriptional regulation. The model provides testable hypotheses for further biochemical investigations into the genes of the nph cluster, for potential exploitation in bioremediation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27777941,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A review of Rett syndrome (RTT) with induced pluripotent stem cells.\nHuman induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs. For these reasons, hiPSCs have huge potential in translational medicine such as disease modeling, drug screening, and cellular therapy. Indeed, patient-specific hiPSCs have been generated for a multitude of diseases, including many with a neurological basis, in which disease phenotypes have been recapitulated in vitro and proof-of-principle drug screening has been performed. As the techniques for generating hiPSCs are refined and these cells become a more widely used tool for understanding brain development, the insights they produce must be understood in the context of the greater complexity of the human genome and the human brain. Disease models using iPS from Rett syndrome (RTT) patient's fibroblasts have opened up a new avenue of drug discovery for therapeutic treatment of RTT. The analysis of X chromosome inactivation (XCI) upon differentiation of RTT-hiPSCs into neurons will be critical to conclusively demonstrate the isolation of pre-XCI RTT-hiPSCs in comparison to post-XCI RTT-hiPSCs. The current review projects on iPSC studies in RTT as well as XCI in hiPSC were it suggests for screening new potential therapeutic targets for RTT in future for the benefit of RTT patients. In conclusion, patient-specific drug screening might be feasible and would be particularly helpful in disorders where patients frequently have to try multiple drugs before finding a regimen that works.","subset":"pubmed_abstract"} +{"meta":{"pmid":37049502,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":2,"2024-18":1,"unknown":9}}},"text":"Association between Disability and Unmet Food Needs in the Venezuelan Migrant and Refugee Population: Analysis of a Population-Based Survey, 2022.\nIn Peru, Venezuelan migrants and refugees have been exposed to food shortages before their emigration. This problem could have worse outcomes in vulnerable populations (such as people with disabilities); however, the literature on the basic needs of this population is still scarce. The objective was to determine the association between the presence of disability and the unmet need for access to food in the household of the Venezuelan migrant and refugee population residing in Peru. A cross-sectional study was conducted using data from the Second Survey of the Venezuelan Population Residing in Peru (ENPOVE 2022). The outcome variable was unmet need for food, while the independent variable was the presence of disability. Poisson log generalized linear regression models (crude and adjusted for potential confounding variables) were fitted to evaluate the association between the variables of interest, reporting prevalence ratios (PR) and 95% confidence intervals (CIs). A total of 7739 migrants and refugees from Venezuela were included. The proportion of unmet need for access to food in the household was 45.2%, while the proportion of disability was 2.1%. People with disabilities were found to be more likely to have an unmet need for access to food at home (adjusted PR [aPR]: 1.25; 95% CI: 1.08-1.46; p = 0.003). According to our findings, almost half of Venezuelan households were found to have an unmet need for access to food. In addition, Venezuelan migrants and refugees with disabilities were more likely to have an unmet need for this basic need.","subset":"pubmed_abstract"} +{"meta":{"pmid":18929697,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Quantitative automated assessment of myocardial perfusion at cardiac catheterization.\nPerfusion assessed in the cardiac catheterization laboratory predicts outcomes after myocardial infarction. The aim of this study was to investigate a novel method of assessing perfusion using digital subtraction angiography to generate a time-density curve (TDC) of myocardial blush, incorporating epicardial and myocardial perfusion. Seven pigs underwent temporary occlusion of the left anterior descending coronary artery for 60 minutes. Angiography was performed in the same projections before, during, and after occlusion. Perfusion parameters were obtained from the TDC and compared with Thrombolysis In Myocardial Infarction (TIMI) frame count and myocardial perfusion grade. In addition, safety and feasibility were tested in 8 patients after primary percutaneous coronary intervention. The contrast density differential between the proximal artery and the myocardium derived from the TDC correlated well with TIMI myocardial perfusion grade (R = 0.54, p <0.001). The arterial transit time derived from the TDC correlated with TIMI frame count (R = 0.435, p = 0.011). Using a cutoff of 2.4, the density\/time ratio, a ratio of density differential to transit time, had sensitivity and specificity of 100% for coronary arterial occlusion. The positive and negative predictive values were 100%. The generation of a TDC was safe and feasible in 7 patients after acute myocardial infarctions, but the correlation between TDC-derived parameters and TIMI parameters did not reach statistical significance. In conclusion, this novel method of digital subtraction angiography with rapid, automated, quantitative assessment of myocardial perfusion in the cardiac catheterization laboratory correlates well with established angiographic measures of perfusion. Further studies to assess the prognostic value of this technique are warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":30978686,"dup_signals":{"dup_doc_count":26,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2023-14":2,"2022-40":1,"2020-24":1,"2019-22":2,"2019-18":14,"2023-40":1,"2024-10":1}}},"text":"Percutaneous glycerol rhizotomy for trigeminal neuralgia in patients with multiple sclerosis: a long-term retrospective cohort study.\nThe prevalence of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS-TN) is higher than in the general population (idiopathic TN [ITN]). Glycerol rhizotomy (GR) is a percutaneous lesioning surgery commonly performed for the treatment of medically refractory TN. While treatment for acute pain relief is excellent, long-term pain relief is poorer. The object of this study was to assess the efficacy of percutaneous retrogasserian GR for the treatment of MS-TN versus ITN. A retrospective chart review was performed, identifying 219 patients who had undergone 401 GR procedures from 1983 to 2018 at a single academic institution. All patients were diagnosed with medically refractory MS-TN (182 procedures) or ITN (219 procedures). The primary outcome measures of interest were immediate pain relief and time to pain recurrence following initial and repeat GR procedures. Secondary outcomes included medication usage and presence of periprocedural hypesthesia. The initial pain-free response rate was similar between groups (p = 0.726): MS-TN initial GR 89.6%; MS-TN repeat GR 91.9%; ITN initial GR 89.6%; ITN repeat GR 87.0%. The median time to recurrence after initial GR was similar between MS-TN (2.7 \u00b1 1.3 years) and ITN (2.1 \u00b1 0.6 years) patients (p = 0.87). However, there was a statistically significant difference in the time to recurrence after repeat GR between MS-TN (2.3 \u00b1 0.5 years) and ITN patients (1.2 \u00b1 0.2 years; p < 0.05). The presence of periprocedural hypesthesia was highly predictive of pain-free survival (p < 0.01). Patients with MS-TN achieve meaningful pain relief following GR, with an efficacy comparable to that following GR in patients with ITN. Initial and subsequent GR procedures are equally efficacious.","subset":"pubmed_abstract"} +{"meta":{"pmid":1410382,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":4,"unknown":6}}},"text":"CT angiography with spiral CT and maximum intensity projection.\nThe authors describe a technique for obtaining angiographic images by means of spiral computed tomography (CT), preprocessing of reconstructed three-dimensional sections to suppress bone, and maximum intensity projection. The technique has some limitations, but preliminary results in 48 patients have shown excellent anatomic correlation with conventional angiography in studies of the abdomen, the circle of Willis in the brain, and the extracranial carotid arteries. With continued development and evaluation, CT angiography may prove useful as a screening tool or replacement for conventional angiography in some patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":33654986,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Quantification of serum ovalbumin-specific immunoglobulin E titrevia in vivo passive cutaneous anaphylaxis assay.\nMurine models of allergic airway disease are frequently used as a tool to elucidate the cellular and molecular mechanisms of tissue-specific asthmatic disease pathogenesis. Paramount to the success of these models is the induction of experimental antigen sensitization, as indicated by the presence of antigen-specific serum immunoglobulin E. The quantification of antigen-specific serum IgE is routinely performed via enzyme-linked immunosorbent assay. However, the reproducibility of these in vitro assays can vary dramatically in our experience. Furthermore, quantifying IgE via in vitro methodologies does not enable the functional relevance of circulating IgE levels to be considered. As a biologically appropriate alternative method, we describe herein a highly reproducible in vivo passive cutaneous anaphylaxis assay using Sprague Dawley rats for the quantification of ovalbumin-specific IgE in serum samples from ovalbumin-sensitized murine models. Briefly, this in vivo assay involves subcutaneous injections of serum samples on the back of a Sprague Dawley rat, followed 24 h later by intravenous injection of ovalbumin and a blue detection dye. The subsequent result of antigen-IgE mediated inflammation and leakage of blue dye into the initial injection site indicates the presence of ovalbumin-specific IgE within the corresponding serum sample.","subset":"pubmed_abstract"} +{"meta":{"pmid":30139525,"dup_signals":{"dup_doc_count":14}},"text":"Physical Activity-Related Drivers of Perceived Health Status in Adults With Congenital Heart Disease.\nData on the differential impact of physical activity on perceived health status (PHS) in a large adult congenital heart disease (ACHD) patient population are lacking. We conducted a cross-sectional assessment of 4,028 ACHD patients recruited from 24 ACHD-specialized centers in 15 countries across 5 continents to examine the association between physical activity and PHS in a large international cohort of ACHD patients. A linear analog scale of the EuroQol-5D 3 level version and the 12-item Short Form Health Survey-version 2 were used to assess self-reported health status and the Health-Behavior Scale-Congenital Heart Disease was used as a subjective measurement of physical activity type, participation, and level. Correlation analyses and Wilcoxon Rank Sum tests examined bivariate relations between sample characteristics and PHS scores. Then, multivariable models were constructed to understand the impact of physical activity on PHS. Only 30% of our sample achieved recommended physical activity levels. Physically active patients reported better PHS than sedentary patients; however, the amount of physical activity was not associated with PHS. Further statistical analyses demonstrated that specifically sport participation regardless of physical activity level was a predictor of PHS. In conclusion, the majority of ACHD patients across the world are physically inactive. Sport participation appears to be the primary physical activity-related driver of PHS. By promoting sport-related exercise ACHD specialists thus may improve PHS in ACHD patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":22333912,"dup_signals":{"dup_doc_count":14}},"text":"Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1\/S genes.\nReprogramming gene expression is crucial for DNA replication stress response. We used quantitative proteomics to establish how the transcriptional response results in changes in protein levels. We found that expression of G1\/S cell-cycle targets are strongly up-regulated upon replication stress, and show that MBF, but not SBF genes, are up-regulated via Rad53-dependent inactivation of the MBF co-repressor Nrm1. A subset of G1\/S genes was found to undergo an SBF-to-MBF switch at the G1\/S transition, enabling replication stress-induced transcription of genes targeted by SBF during G1. This subset of G1\/S genes is characterized by an overlapping Swi4\/Mbp1-binding site and is enriched for genes that cause a cell cycle and\/or growth defect when overexpressed. Analysis of the prototypical switch gene TOS4 (Target Of SBF 4) reveals its role as a checkpoint effector supporting the importance of this distinct class of G1\/S genes for the DNA replication checkpoint response. Our results reveal that replication stress induces expression of G1\/S genes via the Rad53-MBF pathway and that an SBF-to-MBF switch characterizes a new class of genes that can be induced by replication stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":28261351,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"High Residual Tumor Rate for Early Breast Cancer Patients Receiving Vacuum-assisted Breast Biopsy.\nPurpose: The objective of study is aiming to investigate the residual tumor rate after Vacuum-assisted Breast Biopsy (VABB) for early breast cancer excision and the efficacy of mammogram and ultrasound in detecting residual tumor. Methods: Patients who underwent VABB and were confirmed with breast cancer in Sun Yat-sen University Cancer Center from 2010 to 2015 were reviewed retrospectively. The residual tumor rate determined by histological examination was calculated, and then was compared with the results estimated by mammogram and ultrasound which were performed post VABB but before subsequent surgery. Univariate and multivariate analysis (logistic regression) were carried out to identify the independent risk factors associated with residual tumor. Results: In total, 126 eligible patients with early breast cancer were recruited for this study, of whom 79 (62.7%) had residual tumor and 47 (37.3 %) underwent complete excision. The residual tumor rates for lesions < 10mm, lesions 10 to 20 mm and lesions >20mm in size were 55.0%, 68.9% and 53.1%, respectively. The complete excision rates estimated by mammogram and ultrasound were 76.5% and 73.9%, with a negative predictive value of only 46.2% and 50.6%, respectively. In the multivariate logistic regression analysis, no specific factors were found associated with risk of residual tumor (all P > 0.05). Conclusions: There was a high residual tumor rate after VABB in early breast cancer. Both mammogram and ultrasound could not effectively detect the residual tumor after VABB.","subset":"pubmed_abstract"} +{"meta":{"pmid":29150962,"dup_signals":{"dup_doc_count":46,"dup_dump_count":29,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":2,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-04":2,"2020-50":1,"2020-40":1,"2020-29":1,"2020-05":2,"2019-51":1,"2019-35":3,"2019-26":1,"2019-13":3,"2018-51":4,"2018-47":2,"2018-39":2,"2018-34":1,"2018-26":2,"2018-22":1,"2018-17":1,"2023-40":1,"2024-26":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance.\nInsects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":17122932,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"Bond-coating in plasma-sprayed calcium-phosphate coatings.\nThe influence of bond-coating on the mechanical properties of plasma-spray coatings of hydroxyatite on Ti was investigated. Plasma-spray powder was produced from human teeth enamel and dentine. Before processing the main apatite coating, a very thin layer of Al2O3\/TiO2 was applied on super clean and roughened, by Al2O3 blasting, Ti surface as bond-coating. The experimental results showed that bond-coating caused significant increase of the mechanical properties of the coating layer: In the case of the enamel powder from 6.66 MPa of the simple coating to 9.71 MPa for the bond-coating and in the case of the dentine powder from 6.27 MPa to 7.84 MPa, respectively. Both tooth derived powders feature high thermal stability likely due to their relatively high content of fluorine. Therefore, F-rich apatites, such those investigated in this study, emerge themselves as superior candidate materials for calcium phosphate coatings of producing medical devices. The methods of apatite powder production and shaping optimization of powder particles are both key factors of a successful coating. The methods used in this study can be adopted as handy, inexpensive and reliable ways to produce high quality of powders for plasma spray purposes.","subset":"pubmed_abstract"} +{"meta":{"pmid":31074062,"dup_signals":{"dup_doc_count":12}},"text":"Abnormal Amyloid Load in Mild Cognitive Impairment: The Effect of Reducing the PiB-PET Threshold.\nIn vivo detection of \u03b2-amyloid (A\u03b2) plaques in Alzheimer's disease (AD) is now possible with 11 C-PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4-1.5 has been used to categorize at-risk subjects as \"amyloid-positive\" and \"amyloid-negative.\" It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11 C-PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally. We serially determined the cortical amyloid load with 11 C-PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases. Twenty-four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty-seven \"raised amyloid\" MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow-up period. Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.","subset":"pubmed_abstract"} +{"meta":{"pmid":15944708,"dup_signals":{"dup_doc_count":24,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2024-10":1,"2015-18":3,"2015-11":3,"2015-06":1,"2014-10":4,"2013-48":1,"2013-20":3,"2024-30":1,"unknown":6}}},"text":"MicroRNA expression profiles classify human cancers.\nRecent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":12204832,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":18}}},"text":"Critical windows of exposure to household pesticides and risk of childhood leukemia.\nThe potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study. A total of 162 patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained during 1995-1999, and 162 matched control subjects were randomly selected from the birth registry. The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.4-5.7], and the exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI, 1.6-8.3). The ORs for exposure to insecticides during the 3 months before pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95% CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7-2.1), respectively. Insecticide exposures early in life appear to be more significant than later exposures, and the highest risk was observed for exposure during pregnancy. Additionally, more frequent exposure to insecticides was associated with a higher risk. In contrast to insecticides, the association between herbicides and leukemia was weak and nonsignificant. Pesticides were also grouped based on where they were applied. Exposure to indoor pesticides was associated with an increased risk, whereas no significant association was observed for exposure to outdoor pesticides. The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure.","subset":"pubmed_abstract"} +{"meta":{"pmid":30155150,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":10}}},"text":"Visible light amination\/Smiles cascade: access to phthalazine derivatives.\nWe report the synthesis of various phthalazines via a new cascade reaction, initiated by visible light photocatalysis, involving a radical hydroamination reaction followed by a radical Smiles rearrangement. Phthalazine derivatives are obtained in high yields and from a broad scope readily accessible ortho-alkynylsulfonohydrazone precursors. The mild photoredox conditions ensure an excellent functional group tolerance. Application of this strategy to a one-pot protocol starting from the corresponding carbonyl compounds, and subsequent functionalization allow the rapid synthesis of structurally diverse structures.","subset":"pubmed_abstract"} +{"meta":{"pmid":22018241,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":3,"unknown":8}}},"text":"The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries.\nPlasmodium falciparum and Toxoplasma gondii are obligate intracellular apicomplexan parasites that rapidly invade and extensively modify host cells. Protein phosphorylation is one mechanism by which these parasites can control such processes. Here we present a phosphoproteome analysis of peptides enriched from schizont stage P. falciparum and T. gondii tachyzoites that are either \"intracellular\" or purified away from host material. Using liquid chromatography-tandem mass spectrometry, we identified over 5,000 and 10,000 previously unknown phosphorylation sites in P. falciparum and T. gondii, respectively, revealing that protein phosphorylation is an extensively used regulation mechanism both within and beyond parasite boundaries. Unexpectedly, both parasites have phosphorylated tyrosines, and P. falciparum has unusual phosphorylation motifs that are apparently shaped by its A:T-rich genome. This data set provides important information on the role of phosphorylation in the host-pathogen interaction and clues to the evolutionary forces operating on protein phosphorylation motifs in both parasites.","subset":"pubmed_abstract"} +{"meta":{"pmid":33678808,"dup_signals":{"dup_doc_count":18}},"text":"Uniform Lipschitz Functions on the Triangular Lattice Have Logarithmic Variations.\nUniform integer-valued Lipschitz functions on a domain of size N of the triangular lattice are shown to have variations of order log N . The level lines of such functions form a loop O(2) model on the edges of the hexagonal lattice with edge-weight one. An infinite-volume Gibbs measure for the loop O(2) model is constructed as a thermodynamic limit and is shown to be unique. It contains only finite loops and has properties indicative of scale-invariance: macroscopic loops appearing at every scale. The existence of the infinite-volume measure carries over to height functions pinned at the origin; the uniqueness of the Gibbs measure does not. The proof is based on a representation of the loop O(2) model via a pair of spin configurations that are shown to satisfy the FKG inequality. We prove RSW-type estimates for a certain connectivity notion in the aforementioned spin model.","subset":"pubmed_abstract"} +{"meta":{"pmid":26823514,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Properties and physiological function of Ca2+-dependent K+ currents in uniglomerular olfactory projection neurons.\nCa(2+)-activated potassium currents [IK(Ca)] are an important link between the intracellular signaling system and the membrane potential, which shapes intrinsic electrophysiological properties. To better understand the ionic mechanisms that mediate intrinsic firing properties of olfactory uniglomerular projection neurons (uPNs), we used whole cell patch-clamp recordings in an intact adult brain preparation of the male cockroach Periplaneta americana to analyze IK(Ca) In the insect brain, uPNs form the principal pathway from the antennal lobe to the protocerebrum, where centers for multimodal sensory processing and learning are located. In uPNs the activation of IK(Ca) was clearly voltage and Ca(2+) dependent. Thus under physiological conditions IK(Ca) is strongly dependent on Ca(2+) influx kinetics and on the membrane potential. The biophysical characterization suggests that IK(Ca) is generated by big-conductance (BK) channels. A small-conductance (SK) channel-generated current could not be detected. IK(Ca) was sensitive to charybdotoxin (CTX) and iberiotoxin (IbTX) but not to apamin. The functional role of IK(Ca) was analyzed in occlusion experiments under current clamp, in which portions of IK(Ca) were blocked by CTX or IbTX. Blockade of IK(Ca) showed that IK(Ca) contributes significantly to intrinsic electrophysiological properties such as the action potential waveform and membrane excitability.","subset":"pubmed_abstract"} +{"meta":{"pmid":19933660,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Comparison of ultrasound and CT in the evaluation of pneumonia complicated by parapneumonic effusion in children.\nThe purpose of our study was to compare chest ultrasound and chest CT in children with complicated pneumonia and parapneumonic effusion. We retrospectively compared chest ultrasound and chest CT in 19 children (nine girls and 10 boys; age range, 8 months-17 years) admitted with complicated pneumonia and parapneumonic effusion between December 2006 and January 2009. Images were evaluated for effusion, loculation, fibrin strands, parenchymal consolidation, necrosis, and abscess. In the subset of patients who underwent surgical management, imaging findings were correlated with operative findings. Eighteen of 19 patients had an effusion on both chest ultrasound and chest CT. The findings of effusion loculation as well as parenchymal consolidation and necrosis or abscess were similar between the two techniques. Chest ultrasound was better able to visualize fibrin strands within the effusions. Of the 14 patients who underwent video-assisted thoracoscopy, five had surgically proven parenchymal abscess or necrosis. Preoperatively, chest ultrasound was able to show parenchymal abscess or necrosis in four patients, whereas chest CT was able to show parenchymal abscess or necrosis in three. In our series, chest ultrasound and chest CT were similar in their ability to detect loculated effusion and lung necrosis or abscess resulting from complicated pneumonia. Chest CT did not provide any additional clinically useful information that was not also seen on chest ultrasound. We suggest that the imaging workup of complicated pediatric pneumonia include chest radiography and chest ultrasound, reserving chest CT for cases in which the chest ultrasound is technically limited or discrepant with the clinical findings.","subset":"pubmed_abstract"} +{"meta":{"pmid":35254862,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Pathologic Findings on Hip Arthroscopy in High-Level Athletes Competing in Flexibility Sports.\nAthletes who compete in flexibility sports (FS) place unique demands on their hip joints because of the supraphysiologic range of motion required. To compare the pathologic features, outcomes, and return-to-sports (RTS) rates of high-level athletes participating in FS who underwent hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and labral tear against a propensity score-matched cohort of high-level athletes participating in non-flexibility sports (NFS). Cohort study; Level of evidence, 3. Data were prospectively collected and retrospectively reviewed for high-level athletes who underwent primary hip arthroscopy for FAIS from April 2008 to December 2018. Patients who participated in FS such as dancing, gymnastics, martial arts, figure skating, and cheerleading were propensity score matched by body mass index, age at time of surgery, sex, sports competition level, and labral treatment to a cohort of high-level athletes participating in all other sports, such as distance running, soccer, volleyball, and softball. Baseline patient characteristics, intraoperative findings, and surgical procedures were compared. Minimum 2-year patient-reported outcome measures were compared for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Sport Specific Subscale, and visual analog scale for pain and satisfaction. Rates of secondary surgery and RTS were compared. A total of 47 patients (50 hips) who participated in FS were included and propensity score matched to 130 patients (150 hips) who participated in NFS. Follow-up time was 37.5 \u00b1 10.4 months (mean \u00b1 SD). Most patients (96.0%) were female with a mean age of 19.5 \u00b1 7.3 years. FS athletes had significantly higher rates of femoral head cartilage lesions (Outerbridge \u22652; 12.0% vs 2.0%; P = .008) and ligamentum teres tears (48% vs 26%; P = .003). FS and NFS athletes demonstrated significant clinical improvements after surgery for all patient-reported outcome measures. Of the patients who attempted, 34 (75.6%) participating in FS were able to RTS while 11 (24.4%) were not because of ongoing hip issues. This was not significantly different than the NFS group (P = .073). High-level athletes who participated in FS and were treated for FAIS with hip arthroscopy exhibited higher rates of femoral head cartilage lesions and ligamentum teres tears requiring debridement when compared with a benchmark group of athletes who participated in other sports. Despite this, both groups demonstrated similar improvements in outcome scores and comparable rates of RTS at minimum 2-year follow-up.","subset":"pubmed_abstract"} +{"meta":{"pmid":16684231,"dup_signals":{"dup_doc_count":19,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2017-13":1,"unknown":9}}},"text":"Seduced by the dark side: integrating molecular and ecological perspectives on the influence of light on plant defence against pests and pathogens.\nPlants frequently suffer attack from herbivores and microbial pathogens, and have evolved a complex array of defence mechanisms to resist defoliation and disease. These include both preformed defences, ranging from structural features to stores of toxic secondary metabolites, and inducible defences, which are activated only after an attack is detected. It is well known that plant defences against pests and pathogens are commonly affected by environmental conditions, but the mechanisms by which responses to the biotic and abiotic environments interact are only poorly understood. In this review, we consider the impact of light on plant defence, in terms of both plant life histories and rapid scale molecular responses to biotic attack. We bring together evidence that illustrates that light not only modulates defence responses via its influence on biochemistry and plant development but, in some cases, is essential for the development of resistance. We suggest that the interaction between the light environment and plant defence is multifaceted, and extends across different temporal and biological scales.","subset":"pubmed_abstract"} +{"meta":{"pmid":37992146,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Chitosan for the treatment of inflammation of the oral mucosa: A systematic review.\nChitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosan applications in the dentistry field has been explored. This work aimed to conduct a systematic review to address the clinical efficacy of chitosan for the treatment of oral mucositis. The design of the included studies were observational studies, randomized clinical trials (RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies were excluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source, and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies were recorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Development, and Evaluation, GRADE) assessments were carried out. From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a total of 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibited a high risk of bias. The quality of the studies was between low and very low. The results of the included studies suggest that chitosan can diminish pain and improve the healing of ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oral mucositis compared with other current therapies.","subset":"pubmed_abstract"} +{"meta":{"pmid":28830753,"dup_signals":{"dup_doc_count":11}},"text":"Bladder Reconstruction Rates Differ among Centers Participating in National Spina Bifida Patient Registry.\nWe performed an exploratory analysis of data from the NSBPR (National Spina Bifida Patient Registry) to assess variation in the frequency of bladder reconstruction surgeries among NSBPR centers. We queried the 2009-2014 NSBPR to identify patients who had ever undergone bladder reconstruction surgeries. We evaluated demographic characteristics, spina bifida type, functional level, mobility and NSBPR center to determine whether any of these factors were associated with reconstructive surgery rates. Multivariable logistic regression was used to simultaneously adjust for the impact of these factors. We identified 5,528 patients with spina bifida enrolled in the NSBPR. Of these patients 1,129 (20.4%) underwent bladder reconstruction (703 augmentation, 382 continent catheterizable channel, 189 bladder outlet procedure). Surgical patients were more likely older, female, nonHispanic white, with a higher lesion level, myelomeningocele diagnosis, nonambulators (all p <0.001) and nonprivately insured (p=0.018). Bladder reconstruction surgery rates varied among NSBPR centers (range 12.1% to 37.9%, p <0.001). After correcting for known confounders NSBPR center, spina bifida type, mobility, gender and age (all p <0.001) were significant predictors of surgical intervention. Race (p=0.19) and insurance status (p=0.11) were not associated with surgical intervention. There is significant variation in rates of bladder reconstruction surgery among NSBPR centers. In addition to clinical factors such as mobility status, lesion type and lesion level, nonclinical factors such as patient age, gender and treating center are also associated with the likelihood of an individual undergoing bladder reconstruction.","subset":"pubmed_abstract"} +{"meta":{"pmid":28640917,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-22":1,"unknown":9}}},"text":"Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.\nHantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and\/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":22017940,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Effective use of radiation shields to minimize operator dose during invasive cardiology procedures.\nThis study sought to measure the protection from scatter radiation offered to the primary physician by a variety of available shields and to provide best practice guidelines for shield use during invasive cardiology procedures. It is accepted that exposure to radiation includes a predicted increase in cancer risk. In the cardiac interventional laboratories, radiation shields are widely available; however, proper use of the shields to optimize protection during cardiac interventional procedures is not well understood. The protection from scatter radiation offered by a variety of shields used alone and in combination was measured. Protection was assessed from air-kerma measurements of scatter radiation from a phantom performed without and with the shields. Protection was assessed for 3 patient- access locations (right jugular vein, right femoral artery, and left anterior chest) and for elevations ranging from 25 to 175 cm from the floor. The influence of precise placement of the ceiling-mounted upper body shield was specifically assessed. The utility and protection of shielding varied for the 3 access points and with elevation. For femoral artery access locations, the shields can provide at least 80% protection from scatter at all elevations; however, protection depends substantially on upper body shield position. A disposable radiation-absorbing pad can provide 35% to 70% upper body protection for procedures during which the upper body shield cannot be used effectively. Radiation shields can provide substantial protection from radiation during cardiac interventional procedures. Shields must be thoughtfully and actively managed to provide optimum protection. Best practice guidelines for shield use are provided.","subset":"pubmed_abstract"} +{"meta":{"pmid":21999157,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":3,"unknown":10}}},"text":"Robust RNAi-based resistance to mixed infection of three viruses in soybean plants expressing separate short hairpins from a single transgene.\nTransgenic plants expressing double-stranded RNA (dsRNA) of virus origin have been previously shown to confer resistance to virus infections through the highly conserved RNA-targeting process termed RNA silencing or RNA interference (RNAi). In this study we applied this strategy to soybean plants and achieved robust resistance to multiple viruses with a single dsRNA-expressing transgene. Unlike previous reports that relied on the expression of one long inverted repeat (IR) combining sequences of several viruses, our improved strategy utilized a transgene designed to express several shorter IRs. Each of these short IRs contains highly conserved sequences of one virus, forming dsRNA of less than 150 bp. These short dsRNA stems were interspersed with single-stranded sequences to prevent homologous recombination during the transgene assembly process. Three such short IRs with sequences of unrelated soybean-infecting viruses (Alfalfa mosaic virus, Bean pod mottle virus, and Soybean mosaic virus) were assembled into a single transgene under control of the 35S promoter and terminator of Cauliflower mosaic virus. Three independent transgenic lines were obtained and all of them exhibited strong systemic resistance to the simultaneous infection of the three viruses. These results demonstrate the effectiveness of this very straight forward strategy for engineering RNAi-based virus resistance in a major crop plant. More importantly, our strategy of construct assembly makes it easy to incorporate additional short IRs in the transgene, thus expanding the spectrum of virus resistance. Finally, this strategy could be easily adapted to control virus problems of other crop plants.","subset":"pubmed_abstract"} +{"meta":{"pmid":25274048,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Impact of adding therapeutic recommendations to risk assessments from a prediction model for postoperative nausea and vomiting.\nIn a large cluster-randomized trial on the impact of a prediction model, presenting the calculated risk of postoperative nausea and vomiting (PONV) on-screen (assistive approach) increased the administration of risk-dependent PONV prophylaxis by anaesthetists. This change in therapeutic decision-making did not improve the patient outcome; that is, the incidence of PONV. The present study aimed to quantify the effects of adding a specific therapeutic recommendation to the predicted risk (directive approach) on PONV prophylaxis decision-making and the incidence of PONV. A prospective before-after study was conducted in 1483 elective surgical inpatients. The before-period included care-as-usual and the after-period included the directive risk-based (intervention) strategy. Risk-dependent effects on the administered number of prophylactic antiemetics and incidence of PONV were analysed by mixed-effects regression analysis. During the intervention period anaesthetists administered 0.5 [95% confidence intervals (CIs): 0.4-0.6] more antiemetics for patients identified as being at greater risk of PONV. This directive approach led to a reduction in PONV [odds ratio (OR): 0.60, 95% CI: 0.43-0.83], with an even greater reduction in PONV in high-risk patients (OR: 0.45, 95% CI: 0.28-0.72). Anaesthetists administered more prophylactic antiemetics when a directive approach was used for risk-tailored intervention compared with care-as-usual. In contrast to the previously studied assistive approach, the increase in PONV prophylaxis now resulted in a lower PONV incidence, particularly in high-risk patients. When one aims for a truly 'PONV-free hospital', a more liberal use of prophylactic antiemetics must be accepted and lower-risk thresholds should be set for the actionable recommendations.","subset":"pubmed_abstract"} +{"meta":{"pmid":27562524,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2018-22":2,"2018-09":1,"2017-51":2,"2017-43":1,"2017-34":1,"2017-26":1,"2017-04":1,"2016-50":1,"2016-44":1,"2018-43":1,"2017-13":1}}},"text":"Lipid transfer proteins: classification, nomenclature, structure, and function.\nThe non-specific lipid transfer proteins (LTPs) constitute a large protein family found in all land plants. They are small proteins characterized by a tunnel-like hydrophobic cavity, which makes them suitable for binding and transporting various lipids. The LTPs are abundantly expressed in most tissues. In general, they are synthesized with an N-terminal signal peptide that localizes the protein to spaces exterior to the plasma membrane. The in vivo functions of LTPs are still disputed, although evidence has accumulated for a role in the synthesis of lipid barrier polymers, such as cuticular waxes, suberin, and sporopollenin. There are also reports suggesting that LTPs are involved in signaling during pathogen attacks. LTPs are considered as key proteins for the plant's survival and colonization of land. In this review, we aim to present an overview of the current status of LTP research and also to discuss potential future applications of these proteins. We update the knowledge on 3D structures and lipid binding and review the most recent data from functional investigations, such as from knockout or overexpressing experiments. We also propose and argument for a novel system for the classification and naming of the LTPs.","subset":"pubmed_abstract"} +{"meta":{"pmid":12801234,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives.\nA novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.","subset":"pubmed_abstract"} +{"meta":{"pmid":32119825,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.\nIsolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. Simulated outbreaks starting with five initial cases, an R0 of 1\u00b75, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2\u00b75 or 3\u00b75 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1\u00b75 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2\u00b75 more than 70% of contacts had to be traced, and for an R0 of 3\u00b75 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1\u00b75. For R0 values of 2\u00b75 or 3\u00b75, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.","subset":"pubmed_abstract"} +{"meta":{"pmid":33399455,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"Oxi-Redox Selective Breast Cancer Treatment: An In Vitro Study of Theranostic In-Based Oxide Nanoparticles for Controlled Generation or Prevention of Oxidative Stress.\nIn this article, we demonstrate that specifically engineered oxide nanoparticles (NPs) have the potential to act as theranostic materials that are able to generate or prevent oxidative stress through their oxi-redox activity in various types of malignant and nonmalignant cells. The oxi-redox activity is related to the type and presence of surface defects, which is modified with appropriate synthesis conditions. In the present work, we used MDA-MB-231 and MCF-7 human breast cancer cells and nonmalignant MCF-10A human breast cells to demonstrate how controlled oxidative stress mediated by specifically nanoengineered indium tin oxide (ITO) NPs can selectively induce cell death in the cancer cells while reducing the oxidative stress in the normal cells and supporting their proliferation. The ITO NPs are also promising nanotheranostic materials for cancer therapy and contrast agents because of their multimodal imaging capabilities. We demonstrate that the synthesized ITO NPs can selectively increase the generation of reactive oxygen species (ROS) in both breast tumor cell lines, resulting in activation of apoptosis, and can also greatly suppress the cellular proliferation in both types of tumor cells. In contrast, the ITO NPs exhibit ROS scavenging-like behavior, significantly decreasing the ROS levels in MCF-10A cells exposed to the additional ROS, hydrogen peroxide (H2O2), so that they protect the proliferation of nonmalignant MCF-10A cells from ROS damage. In addition, fluorescent microscopy images revealed that the ITO NPs emit strong fluorescence that could be used to reveal their location. Moreover, computed tomography imaging demonstrated that the ITO NPs exhibited a comparable capability toward anatomical contrast enhancement. These results suggest that the synthesized ITO NPs have the potential to be a novel selective therapeutic agent with a multimodal imaging property for anticancer treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":28798195,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Cross-sectional study to evaluate Trichomonas vaginalis positivity in women tested for Neisseria gonorrhoeae and Chlamydia trachomatis, attending genitourinary medicine and primary care clinics in Bristol, South West England.\nHighly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings. Samples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests. T. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24\/530, symptomatic) and 1.7% (27\/1584, asymptomatic); in primary care 2.7% (94\/3499, symptomatic) and 1.2% (41\/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost \u00a3260 per positive case diagnosed compared with \u00a3716 using current microbiological tests. Aptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.","subset":"pubmed_abstract"} +{"meta":{"pmid":22673905,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":2,"2020-45":1,"2018-17":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-26":1}}},"text":"Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.\nPoly(ADP-ribosyl)ation is a reversible post-translational protein modification involved in the regulation of a number of cellular processes including DNA repair, chromatin structure, mitosis, transcription, checkpoint activation, apoptosis and asexual development. The reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) (PAR) glycohydrolase (PARG), which specifically targets the unique PAR (1''-2') ribose-ribose bonds. Here we report the structure and mechanism of the first canonical PARG from the protozoan Tetrahymena thermophila. In addition, we reveal the structure of T. thermophila PARG in a complex with a novel rhodanine-containing mammalian PARG inhibitor RBPI-3. Our data demonstrate that the protozoan PARG represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors.","subset":"pubmed_abstract"} +{"meta":{"pmid":9006036,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Neisseria meningitidis tonB, exbB, and exbD genes: Ton-dependent utilization of protein-bound iron in Neisseriae.\nWe have recently cloned and characterized the hemoglobin (Hb) receptor gene, hmbR, from Neisseria meningitidis. To identify additional proteins that are involved in Hb utilization, the N. meningitidis Hb utilization system was reconstituted in Escherichia coli. Five cosmids from N. meningitidis DNA library enabled a heme-requiring (hemA), HmbR-expressing mutant of E. coli to use Hb as both porphyrin and iron source. Nucleotide sequence analysis of DNA fragments subcloned from the Hb-complementing cosmids identified four open reading frames, three of them homologous to Pseudomonas putida, E. coli, and Haemophilus influenzae exbB, exbD, and tonB genes. The N. meningitidis TonB protein is 28.8 to 33.6% identical to other gram-negative TonB proteins, while the N. meningitidis ExbD protein shares between 23.3 and 34.3% identical amino acids with other ExbD and TolR proteins. The N. meningitidis ExbB protein was 24.7 to 36.1% homologous with other gram-negative ExbB and TolQ proteins. Complementation studies indicated that the neisserial Ton system cannot interact with the E. coli FhuA TonB-dependent outer membrane receptor. The N. meningitidis tonB mutant was unable to use Hb, Hb-haptoglobin complexes, transferrin, and lactoferrin as iron sources. Insertion of an antibiotic cassette in the 3' end of the exbD gene produced a leaky phenotype. Efficient usage of heme by N. meningitidis tonB and exbD mutants suggests the existence of a Ton-independent heme utilization mechanism. E. coli complementation studies and the analysis of N. meningitidis hmbR and hpu mutants suggested the existence of another Hb utilization mechanism in this organism.","subset":"pubmed_abstract"} +{"meta":{"pmid":8639773,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Interferon-gamma constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent hematopoietic inhibition.\nClinical and laboratory studies have suggested involvement of interferon-gamma (IFN-gamma) in the pathophysiology of aplastic anemia. T cells from aplastic anemia (AA) patients secrete IFN-gamma in vitro, activated cytotoxic lymphocytes infiltrate aplastic bone marrow (BM), and IFN-gamma mRNA, not detected in normal BM, is present in BM from most AA patients. Many patients respond to immunosuppressive therapy with antithymocyte globulin and cyclosporine. Using long-term BM cultures (LTBMC) as a tissue culture model of hematopoiesis, we show that IFN-gamma is a potent inhibitor in the long-term culture-initiating cell (LTC-IC) assay, the best in vitro surrogate test for human hematopoietic stem cells, as well as of the output of committed progenitor cells (colony-forming unit-granulocyte-macrophage [CFU-GM] and burst-forming unit-erythroid [BFU-E]). In LTBMC, continuous addition of relatively high IFN-gamma concentrations (1,000 U\/mL weekly or 200 U\/mL every 2 days) was required for inhibition of secondary colony formation, a measure of LTC-IC number and clonogenicity. To mimick local production of IFN-gamma, human stromal cells were engineered by retroviral-mediated gene transfer to express a transduced IFN-gamma gene. IFN-gamma secreted by stromal cells was far more potent than exogenous IFN-gamma in its effects in the LTC-IC assay. For purified CD34+ cells culture in the presence of IFN-gamma stroma dramatically reduced secondary colony numbers as well as production of CFU-GM and BFU-E. Supernatants from these cultures contained only about 20 U\/mL of IFN-gamma; this quantity of cytokine, when added to LTBMC, had little effect on hematopoiesis. The mechanism of hematopoietic suppression was related to the inhibition of cell cycle progression and induction of apoptosis of CD34+ cells. There was no apparent effect of local low-level IFN-gamma production on stromal cell function, as reflected in cell morphology, cell surface phenotype, or expression of hematopoietic growth factor genes. LTBMC with genetically altered stromal cells offers an in vitro model of immune suppression of hematopoiesis in AA and may be helpful in testing certain therapeutic modalities. We infer from our data that local production of low levels of inhibitory cytokine is sufficient to markedly inhibit hematopoiesis and to destroy stem cells and more mature progenitor cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23915207,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-21":1,"2021-17":1,"2015-40":1,"2015-32":1,"2015-22":2,"2014-52":1,"2014-42":2,"2014-41":1,"2014-23":1,"2023-23":1,"2015-18":2,"2015-06":1,"2013-48":1,"2024-22":1}}},"text":"The burden of pediatric diarrhea: a cross-sectional study of incurred costs and perceptions of cost among Bolivian families.\nWorldwide, acute gastroenteritis represents an enormous public health threat to children under five years of age, causing one billion episodes and 1.9 to 3.2 million deaths per year. In Bolivia, which has one of the lower GDPs in South America, an estimated 15% of under-five deaths are caused by diarrhea. Bolivian caregiver expenses related to diarrhea are believed to be minimal, as citizens benefit from universal health insurance for children under five. The goals of this report were to describe total incurred costs and cost burden associated with caregivers seeking treatment for pediatric gastroenteritis, and to quantify relationships among costs, cost burden, treatment setting, and perceptions of costs. From 2007 to 2009, researchers interviewed caregivers (n=1,107) of pediatric patients (<5 years of age) seeking treatment for diarrhea in sentinel hospitals participating in Bolivia's diarrheal surveillance program across three main geographic regions. Data collected included demographics, clinical symptoms, direct costs (e.g. medication, consult fees) and indirect costs (e.g. lost wages). Patient populations were similar across cities in terms of gender, duration of illness, and age, but familial income varied significantly (p<0.05) when stratified on appointment type. Direct, indirect, and total costs to families were significantly higher for inpatients as compared to outpatients of urban (p<0.001) and rural (p<0.05) residence. Consult fees and indirect costs made up a large proportion of total costs. Forty-five percent of patients' families paid \u22651% of their annual household income for this single diarrheal episode. The perception that cost was affecting family finances was more frequent among those with higher actual cost burden. This study demonstrated that indirect costs due to acute pediatric diarrhea were a large component of total incurred familial costs. Additionally, familial costs associated with a single diarrheal episode affected the actual and perceived financial situation of a large number of caregivers. These data serve as a baseline for societal diarrheal costs before and immediately following the implementation of the rotavirus vaccine and highlight the serious economic importance of a diarrheal episode to Bolivian caregivers.","subset":"pubmed_abstract"} +{"meta":{"pmid":22969222,"dup_signals":{"dup_doc_count":12,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":4}}},"text":"Donation after cardio-circulatory death liver transplantation.\nThe renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.","subset":"pubmed_abstract"} +{"meta":{"pmid":18474368,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Influence of brain-derived neurotrophic factor (BDNF) on serotonin neurotransmission in the hippocampus of adult rodents.\nWhereas SSRIs produce rapid blockade of the serotonin transporter (SERT) in vitro and in vivo, the onset of an observable clinical effect takes longer to occur and a variety of pharmacological effects caused by antidepressants have been speculated to be involved either in initiating antidepressant effects and\/or enhancing their effects on serotonergic transmission so as to cause clinical improvement. Among such secondary factors is increased activity of brain-derived neurotrophic factor (BDNF), which requires the Tropomyosine-related kinase B receptor (TrkB) for its effects. To begin an analysis of the influence of BDNF on serotonergic activity, we studied the acute effects of BDNF on SERT activity. A single BDNF injection (either intracerebroventricularly or directly into the CA3 region of hippocampus) decreased the signal amplitude and clearance rate produced by exogenously applied 5-HT compared to what was measured in control rats, shown using in vivo chronoamperometry. It also reduced the ability of a locally applied SSRI to block the clearance of 5-HT. In awake freely moving mice, acute intrahippocampal injection of BDNF decreased extracellular levels of 5-HT in the hippocampus, as measured using microdialysis. In addition, perfusion with BDNF decreased KCl-evoked elevations of 5-HT. These effects of BDNF were blocked by the non-selective antagonist of TrkB receptors, K252a. Overall, it may be inferred that in the hippocampus, through TrkB activation, a single injection of BDNF enhances SERT function. Such acute effects of BDNF would be expected to counter early effects of SSRIs, which might, in part, account for some delay in therapeutic effect.","subset":"pubmed_abstract"} +{"meta":{"pmid":29309202,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-05":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2022-49":1,"2024-10":1}}},"text":"Alemtuzumab for the treatment of multiple sclerosis.\nAlemtuzumab is a monoclonal antibody that targets for the destruction CD52+ cells, particularly B and T cells. Alemtuzumab is approved in more than 50 countries around the world for the treatment of adult patients with relapsing remitting multiple sclerosis (MS). Areas covered: In this review, the authors summarize biological, clinical and safety data related to the use of alemtuzumab in patients with MS. The authors then provide their expert opinion on alemtuzumab and the field as of whole before providing their perspectives for the future. Expert opinion: Alemtuzumab is highly efficacious; more so than first line treatments but comparable to natalizumab. Treatment schedule makes alemtuzumab administration easy and attractive to patients. However, its safety profile makes it a choice for a very limited number of patients, in a specific disease window. As of now, a cure for MS remains elusive and there is an unmet need for a safe and highly potent agent at the level of and beyond the blood brain barrier.","subset":"pubmed_abstract"} +{"meta":{"pmid":11181907,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Gender differences in the effect of age on electrical field stimulation (EFS)-induced adrenergic vasoconstriction in rat mesenteric resistance arteries.\nThe objective of this study was to examine the effects of gender and age on electrical field stimulation (EFS)-induced vasoconstriction. Fisher 344 rats were studied: young females (YF, n = 38), young males (YM, n = 29), old females (OF, n = 33), and old males (OM, n = 30). Isolated mesenteric resistance arteries (endothelium-intact or denuded) were pressurized, and outer diameter was monitored. Dose-response curves were performed to KCl and phenylephrine (PE). EFS (0.1-16 Hz) responses were expressed as percentage of constriction from baseline. Area under the curve (AUC) was calculated and comparisons were made using analysis of variance and t tests. Females became less responsive to EFS-induced constriction with age, whereas constrictor responses among males were unaffected (AUC: YF = 454 +\/- 15, OF = 284 +\/- 22, p < 0.001; YM = 391 +\/- 35, OM = 357 +\/- 31, p = 0.22). Endothelial denudation produced a significant increase in EFS-induced constriction in OF and OM. Endothelium removal in OF increased the EFS constrictor response to the level seen in arteries from YF. BQ 123 (ET(A) receptor antagonist) significantly decreased EFS-induced constriction in YM and OM. In YM, SQ 29,548 [thromboxane A(2) (TXA(2))\/PGH(2) receptor antagonist] and indomethacin depressed constrictor responses. There were no differences among groups in the sensitivity to KCl, but YF were the most sensitive to PE. In conclusion, EFS-induced vasoconstriction declined with age among females but not males. The decrease in EFS constrictor responses in OF may be due to a selective decrease in vascular smooth muscle sensitivity to adrenergic agonists and an increase in the production of an endothelium-derived vasodilator. Among males there is also an endothelin-1 and TXA(2)\/PGH(2) component to EFS-induced constriction that is absent among females.","subset":"pubmed_abstract"} +{"meta":{"pmid":1962421,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"[The clinico-radiographic picture of pulmonary-pleural complications in sepsis].\nProceeding from the investigation and therapy of 106 patients with pleuropulmonary complications of sepsis the authors described clinical and x-ray features of different types of their course, complications and outcomes. In 58% of cases pulmonary lesions were detected at the stage of pyodestruction and pleural empyema; interstitial-focal and infiltrative pneumonias of considerable spreading with the development of a respiratory type of septic shock were observed less frequently. Pulmonary lesions in 24% were the only sign of septicopyemia, in 58% they prevailed in the clinical picture of polyorganic lesions; pleural complications developed in 32% of the patients. Convalescence was observed in 88 (83%) patients; they had residual bullous-sclerotic pulmonary changes. The lethality rate was 17%.","subset":"pubmed_abstract"} +{"meta":{"pmid":19000332,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Experimental evidence for a new transmission route in a parasitic mite and its mucus-dependent orientation towards the host snail.\nThe route of transmission and host finding behaviour are fundamental components of a parasite's fitness. Riccardoella limacum, a haematophagous mite, lives in the mantle cavity of helicid land snails. To date it has been assumed that this parasitic mite is transmitted during courtship and mating of the host. Here we present experimental evidence for a new transmission route in the host snail Arianta arbustorum. Parasite-free snails were kept on soil on which previously infected host snails had been maintained for 6 weeks. R. limacum was successfully transmitted via soil without physical contact among hosts in 10 out of 22 (45.5%) cases. In a series of experiments we also examined the off-host locomotion of R. limacum on snail mucus and control substrates using an automated camera system. Parasitic mites showed a preference to move on fresh mucus. Our results support the hypothesis that R. limacum uses mucus trails to locate new hosts. These findings should be considered in commercial snail farming and when examining the epidemiology of wild populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":11906445,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2023-23":1,"2023-06":1,"2021-31":1,"2021-17":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-39":1,"2023-50":1,"2013-20":2,"2024-18":1}}},"text":"Spiritual expression and immune status in women with metastatic breast cancer: an exploratory study.\nThis exploratory study examined relationships between spirituality and immune function in 112 women with metastatic breast cancer. Spirituality was assessed by patient reports of frequency of attendance at religious services and importance of religious or spiritual expression. White blood cell counts, absolute numbers of lymphocytes, T-lymphocyte subsets, and natural killer cells were assessed by flow cytometry. Assessments of natural killer cell activity and delayed-type hypersensitivity responses to skin test antigens provided two measures of functional immunity. In analyses controlling for demographic, disease status, and treatment variables, women who rated spiritual expression as more important had greater numbers of circulating white blood cells and total lymphocyte counts. Upon examination of relationships with lymphocyte subsets, both helper and cytotoxic T-cell counts were greater among women reporting greater spirituality.","subset":"pubmed_abstract"} +{"meta":{"pmid":31636614,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"Effects of Habitat Partitioning on the Distribution of Bacterioplankton in Deep Lakes.\nIn deep lakes, many investigations highlighted the existence of exclusive groups of bacteria adapted to deep oxygenated and hypoxic and anoxic hypolimnia. Nevertheless, the extent of bacterial strain diversity has been much less scrutinized. This aspect is essential for an unbiased estimation of genetic variation, biodiversity, and population structure, which are essential for studying important research questions such as biogeographical patterns, temporal and spatial variability and the environmental factors affecting this variability. This study investigated the bacterioplankton community in the epilimnetic layers and in the oxygenated and hypoxic\/anoxic hypolimnia of five large and deep lakes located at the southern border of the Alps using high throughput sequencing (HTS) analyses (16S rDNA) and identification of amplicon sequence variants (ASVs) resolving reads differing by as little as one nucleotide. The study sites, which included two oligomictic (Garda and Como) and three meromictic lakes (Iseo, Lugano, and Idro) with maximum depths spanning from 124 to 410 m, were chosen among large lakes to represent an oxic-hypoxic gradient. The analyses showed the existence of several unique ASVs in the three layers of the five lakes. In the case of cyanobacteria, this confirmed previous analyses made at the level of strains or based on oligotyping methods. As expected, the communities in the hypoxic\/anoxic monimolimnia showed a strong differentiation from the oxygenated layer, with the exclusive presence in single lakes of several unique ASVs. In the meromictic lakes, results supported the hypothesis that the formation of isolated monimolimnia sustained the development of highly diversified bacterial communities through ecological selection, leading to the establishment of distinctive biodiversity zones. The genera identified in these layers are well-known to activate a wide range of redox reactions at low O2 conditions. As inferred from 16S rDNA data, the highly diversified and coupled processes sustained by the monimolimnetic microbiota are essential ecosystem services that enhance mineralization of organic matter and formation of reduced compounds, and also abatement of undesirable greenhouse gasses.","subset":"pubmed_abstract"} +{"meta":{"pmid":10928319,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Role of catecholaminergic and cyclic AMP systems in psychological dependence on phencyclidine: a study in mutant mice.\nCatecholaminergic and\/or cyclic AMP (cAMP) systems have been demonstrated to be involved in the development of drug dependence. We investigated the involvement of both systems in psychological dependence on phencyclidine (PCP) by using tyrosine hydroxylase (TH) heterozygous (TH+\/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+\/-) mice. PCP (8 mg\/kg) induced place preference in wild-type mice pretreated with PCP (10 mg\/kg once a day for 28 days). In these mice, the level of cAMP in the striatum, but not in the thalamus, was increased one day after the last injection of PCP (10 mg\/kg). In TH+\/- and CBP+\/- mice pretreated with PCP (10 mg\/kg per day for 28 days), however, no PCP (8 mg\/kg)-induced place preference was observed. The level of cAMP in the striatum was increased in CBP+\/- mice, but not TH+\/- mice. Furthermore, we have demonstrated that the place preference induced by PCP is attenuated by 6-hydroxydopamine, a dopaminergic neurotoxin, and (+) SCH-23390, a dopamine-D1 receptor antagonist, but not by DSP-4, a noradrenergic neurotoxin, and (-) sulpiride, a dopamine-D2 receptor antagonist. These findings suggest that catecholamines and CBP are involved in the development of psychological dependence on PCP and that changes in dopaminergic and\/or cAMP systems induced by repeated PCP treatment play an important role in the addiction to PCP.","subset":"pubmed_abstract"} +{"meta":{"pmid":8840421,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2018-26":1,"2017-13":1}}},"text":"Suicides in Beijing, China, 1992-1993.\nAnalyzing the raw data of suicides reported to the Beijing Public Security Bureau in 1992 and 1993, this study reveals for the first time to the academic public in the West the rate, gender difference, the timing, causes, and means of Chinese suicides. In comparison with suicide patterns in Western societies, mainly reported by Durkheim (1897\/1951), Diekstra (1990) and the National Center for Health Statistics (1991), the findings of this study suggest more differences than similarities. The comparatively low suicide rate (4.8 per 100,000 population), the reversed gender effect (55.4% of suicides are female and 44.6% male), alleged causes, and reported means of suicides in China are explained in terms of history, culture, and social forces. However, the direct relationship of warm seasons to Chinese suicide rates is consistent with what is known about Western societies.","subset":"pubmed_abstract"} +{"meta":{"pmid":29061534,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":18}}},"text":"Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem Cell Transplantation: Comparison of Two Practices.\nAdministration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian\/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5 \u00d7 109\/L (ANC-driven). G-CSF was dosed at 300 \u00b5g in patients weighing <75 kg and 480 \u00b5g in those weighing \u226575 kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P < .0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P < .0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":11312557,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Coupling of cAMP\/PKA and MAPK signaling in neuronal cells is dependent on developmental stage.\nNeurite formation, an essential feature of neuronal development, is believed to involve participation of the ras-mitogen-activated protein kinase (MAPK) and cAMP-dependent protein kinase A (cAMP\/PKA)-mediated signaling pathways. These pathways have been studied extensively in the rat pheochromocytoma cell line PC12, and current hypotheses suggest a single effector mechanism resulting from the convergence of cAMP\/PKA and MAPK signaling. However, based on observations using a central neuronal progenitor cell line, AS583-8, there also exists evidence that the two signaling pathways may act independently resulting in neurites with differing dynamic features. In the present study, the upstream components of cAMP\/PKA signaling were examined in AS583-8 cells as well as possible interactions with the MAPK pathway. We found that activation of PKA is both necessary and sufficient for the elaboration of rapidly forming processes, typical of the cAMP response. In addition, blockade of the MAPK pathway has no effect on the cAMP response, suggesting that activation of the cAMP\/PKA pathway can stimulate neurite formation independent of the MAPK pathway. In order to evaluate which cell line model, PC12 vs AS583-8, best reflects the signaling features of developing central neurons, we examined interactions between cAMP\/PKA and MAPK signaling in primary neuronal cultures from several brain regions. In immature cultures (1-day-old), at a point where the initiation of neurite formation is maximal, no interaction was observed. In more mature cultures (7 days old), where synaptic contacts have been established, we found a weak but reproducible activation of MAPK following stimulation of the cAMP\/PKA pathway. These results suggest that cAMP\/PKA and MAPK signaling act independently at the initiation of neuritogenesis but become coupled during later stages of neuronal development. Therefore, the interaction of the two pathways may be cell stage (younger vs older) specific and may participate in cellular functions that take place after initial neurite formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28424870,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"High intensity interval training does not impair strength gains in response to resistance training in premenopausal women.\nTo compare the increases in upper- and lower-body muscle strength in premenopausal women performing resistance training (RT) alone or alongside concurrent high-intensity interval training (CT). Sixteen women (26-40 years) were randomly assigned into two groups that performed either RT or CT. Both groups performed the same RT program; however, CT performed additional high-intensity interval training (HIIT) on a bicycle ergometer before RT. The study lasted 8 weeks and the participants were tested for ten repetition maximum (10RM) load in elbow flexion (barbell biceps curl) and knee extension exercises pre- and post-intervention. RT was performed with 10-12 repetitions to self-determined repetition maximum in the first four weeks and then progressed to 8-10. During CT, HIIT was performed before RT with six 1-min bouts at 7-8 of perceived subjective exertion (RPE) and then progressed to eight bouts at 9-10 RPE. Analysis of variance revealed significant increases in upper and lower body strength for both the RT and CT groups. Biceps barbell curl 10RM load increased from 12.9 \u00b1 3.2 kg to 14 \u00b1 1.5 kg in CT (p < 0.05) and from 13 \u00b1 1.8 kg to 15.9 \u00b1 2.5 kg in RT (p < 0.05), with no significant between-groups differences. Knee extension 10RM increase from 31.9 \u00b1 11.6 kg to 37.5 \u00b1 8.5 kg for CT (p < 0.05) and from 30.6 \u00b1 8.6 kg to 41.2 \u00b1 7.4 kg for RT (p < 0.05). In conclusion, performing HIIT on a cycle ergometer before resistance training does not seem to impair muscle strength increases in the knee extensors or elbow flexors of pre-menopausal women. This information should be considered when prescribing exercise sessions, since both activities may be combined without negative effects in muscle strength.","subset":"pubmed_abstract"} +{"meta":{"pmid":28250799,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2022-21":1,"2018-05":1,"2017-34":2,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-40":1,"2023-40":1,"2024-10":1,"2024-30":1}}},"text":"Inhibition of cell proliferation does not slow down echinoderm neural regeneration.\nRegeneration of the damaged central nervous system is one of the most interesting post-embryonic developmental phenomena. Two distinct cellular events have been implicated in supplying regenerative neurogenesis with cellular material - generation of new cells through cell proliferation and recruitment of already existing cells through cell migration. The relative contribution and importance of these two mechanisms is often unknown. Here, we use the regenerating radial nerve cord (RNC) of the echinoderm Holothuria glaberrima as a model of extensive post-traumatic neurogenesis in the deuterostome central nervous system. To uncouple the effects of cell proliferation from those of cell migration, we treated regenerating animals with aphidicolin, a specific inhibitor of S-phase DNA replication. To monitor the effect of aphidicolin on DNA synthesis, we used BrdU immunocytochemistry. The specific radial glial marker ERG1 was used to label the regenerating RNC. Cell migration was tracked with vital staining with the lipophilic dye DiI. Aphidicolin treatment resulted in a significant 2.1-fold decrease in cell proliferation. In spite of this, the regenerating RNC in the treated animals did not differ in histological architecture, size and cell number from its counterpart in the control vehicle-treated animals. DiI labeling showed extensive cell migration in the RNC. Some cells migrated from as far as 2 mm away from the injury plane to contribute to the neural outgrowth. We suggest that inhibition of cell division in the regenerating RNC of H. glaberrima is compensated for by recruitment of cells, which migrate into the RNC outgrowth from deeper regions of the neuroepithelium. Neural regeneration in echinoderms is thus a highly regulative developmental phenomenon, in which the size of the cell pool can be controlled either by cell proliferation or cell migration, and the latter can neutralize perturbations in the former.","subset":"pubmed_abstract"} +{"meta":{"pmid":24008054,"dup_signals":{"dup_doc_count":55,"dup_dump_count":34,"dup_details":{"curated_sources":2,"2023-50":2,"2023-23":3,"2023-14":1,"2023-06":3,"2022-49":2,"2022-27":2,"2022-05":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":2,"2021-21":2,"2021-10":2,"2020-50":1,"2020-45":1,"2020-40":1,"2020-16":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-26":2,"2018-17":2,"2018-09":3,"2017-51":2,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2024-18":2,"2024-10":2,"2024-30":1}}},"text":"Reappraising entrapment neuropathies--mechanisms, diagnosis and management.\nThe diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies.","subset":"pubmed_abstract"} +{"meta":{"pmid":26585267,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"White Matter Abnormality Correlates with Developmental and Seizure Outcomes in West Syndrome of Unknown Etiology.\nWest syndrome is an epileptic encephalopathy characterized by epileptic spasms, a specific pattern on electroencephalography of hypsarrhythmia, and developmental regression. Our aim was to assess white matter abnormalities in West syndrome of unknown etiology. We hypothesized that diffusion tensor imaging reveals white matter abnormalities, especially in patients with poor seizure and developmental outcomes. We enrolled 23 patients with new-onset West syndrome of unknown etiology. DTI was performed at 12 and 24 months of age. Fractional anisotropy images were compared with those of controls by using tract-based spatial statistics. We compared axial, radial, and mean diffusivity between patients and controls in the fractional anisotropy skeleton. We determined correlations of these parameters with developmental quotient, electroencephalography, and seizure outcomes. We also compared DTI with hypometabolism on fluorodeoxyglucose positron-emission tomography. At 12 months of age, patients showed widespread fractional anisotropy reductions and higher radial diffusivity in the fractional anisotropy skeleton with a significant difference on tract-based spatial statistics. The developmental quotient at 12 months of age correlated positively with fractional anisotropy and negatively with radial and mean diffusivity. Patients with seizure and abnormal findings on electroencephalography after initial treatments had lower fractional anisotropy and higher radial diffusivity. At 24 months, although tract-based spatial statistics did not show significant differences between patients and controls, tract-based spatial statistics in the 10 patients with a developmental quotient of <70 had significant fractional anisotropy reduction. In patients with unilateral temporal lobe hypometabolism on PET, tract-based spatial statistics showed greater fractional anisotropy reduction in the temporal lobe ipsilateral to the side of PET hypometabolism. Diffuse abnormal findings on DTI at 12 months of age suggest delayed myelination as a key factor underlying abnormal findings on DTI. Conversely, asymmetric abnormal findings on DTI at 24 months may reflect underlying focal pathologies.","subset":"pubmed_abstract"} +{"meta":{"pmid":10723133,"dup_signals":{"dup_doc_count":11}},"text":"The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma.\nGene amplification is frequently present in human tumors, although specific target genes relevant to many amplified loci remain unidentified. An expression cloning assay enabled identification of a candidate oncogene derived from human chromosome 3p14.1. The cDNA retrieved from morphologically transformed cells contained the full-length protein coding region and detected an abundant transcript in the same cells. Sequence analysis revealed identity with the wild-type sequence of p44S10, a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6\/cop11 family of signaling molecules. p44S10 gene copy number and mRNA expression were increased in association with segmental 1.8 - 11-fold chromosomal gains in cutaneous malignant melanoma cell lines (5\/13; 40%) and tumors (2\/40; 5%), and in breast cancer MCF-7 cells. Likewise, malignant progression of human radial growth phase WM35 melanoma cells was associated with amplification and increased expression of endogenous p44S10, and increased expression of p44S10 was sufficient to induce proliferation of WM35 cells in vivo. The results demonstrate segmental copy number gains within chromosome 3p in cutaneous malignant melanoma and suggest that deregulation of a proteasome regulatory particle subunit may contribute to the malignant phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":12200379,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2013-48":1,"unknown":12}}},"text":"The immunophenotypic and immunogenotypic B-cell differentiation arrest in bone marrow of RAG-deficient SCID patients corresponds to residual recombination activities of mutated RAG proteins.\nThe protein products of the recombination activating genes (RAG1 and RAG2) initiate the formation of immunoglobulin (Ig) and T-cell receptors, which are essential for B- and T-cell development, respectively. Mutations in the RAG genes result in severe combined immunodeficiency disease (SCID), generally characterized by the absence of mature B and T lymphocytes, but presence of natural killer (NK) cells. Biochemically, mutations in the RAG genes result either in nonfunctional proteins or in proteins with partial recombination activity. The mutated RAG genes of 9 patients from 7 families were analyzed for their recombination activity using extrachromosomal recombination substrates, rearrangement of endogenous Ig loci in RAG gene-transfected nonlymphoid cells, or the presence of Ig gene rearrangements in bone marrow (BM). Recombination activity was virtually absent in all 6 patients with mutations in the RAG core domains, but partial activity was present in the other 3 RAG-deficient patients, 2 of them having Omenn syndrome with oligoclonal T lymphocytes. Using 4-color flow cytometry, we could define the exact stage at which B-cell differentiation was arrested in the BM of 5 RAG-deficient SCID patients. In 4 of 5 patients, the absence of recombination activity was associated with a complete B-cell differentiation arrest at the transition from cytoplasmic (Cy) Igmu(-) pre-B-I cells to CyIgmu(+) pre-B-II cells. However, the fifth patient showed low frequencies of precursor B cells with CyIgmu and surface membrane IgM, in line with the partial recombination activity of the patient's mutated RAG gene and the detection of in-frame Ig gene rearrangements in BM.","subset":"pubmed_abstract"} +{"meta":{"pmid":36048087,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":5,"unknown":7}}},"text":"Use of telemental health for VA family services before and during the COVID-19 pandemic.\nMilitary veterans experiencing relationship or family difficulties are able to access family services (i.e., couple and family therapy) through the Veterans Affairs (VA) Health Care System. Although family services have historically been provided face-to-face (F2F), the COVID-19 pandemic necessitated a sudden shift to the provision of care via telemental health, which includes videoconferencing (TMH-V) or audio-only phone appointments. This study demonstrated an unprecedented 16-fold increase in the number of TMH-V appointments for family services in VA during the first 9 months of the pandemic. The present study also examined demographic, mental health, and military variables associated with TMH-V utilization before and during the pandemic using a large national VA data set of 13,344 veterans who were referred to couple or family therapy from October 2017 through December 2020. Logistic regression was used to evaluate predictors of having any appointments via TMH-V before and during COVID-19, respectively, as well as predictors of having 50% or more of family service appointments via TMH-V versus phone versus face-to-face appointments during the COVID-19 era. Pre-COVID predictors of TMH-V utilization were limited to obsessive-compulsive disorder diagnosis and history of psychiatric hospitalization, suggesting that TMH-V usage was largely related to clinical indications. In the COVID-19 era, older and rural veterans were less likely to attend appointments via TMH-V than younger and suburban\/urban veterans, while Hispanic veterans were more likely to do so than non-Hispanic veterans. The findings from the present study may aid efforts to ensure equity in access to care among veterans in the VA Health Care System. (PsycInfo Database Record (c) 2022 APA, all rights reserved).","subset":"pubmed_abstract"} +{"meta":{"pmid":27616332,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":2,"2024-26":1,"unknown":12}}},"text":"Quantifying evolutionary dynamics from variant-frequency time series.\nFrom Kimura's neutral theory of protein evolution to Hubbell's neutral theory of biodiversity, quantifying the relative importance of neutrality versus selection has long been a basic question in evolutionary biology and ecology. With deep sequencing technologies, this question is taking on a new form: given a time-series of the frequency of different variants in a population, what is the likelihood that the observation has arisen due to selection or neutrality? To tackle the 2-variant case, we exploit Fisher's angular transformation, which despite being discovered by Ronald Fisher a century ago, has remained an intellectual curiosity. We show together with a heuristic approach it provides a simple solution for the transition probability density at short times, including drift, selection and mutation. Our results show under that under strong selection and sufficiently frequent sampling these evolutionary parameters can be accurately determined from simulation data and so they provide a theoretical basis for techniques to detect selection from variant or polymorphism frequency time-series.","subset":"pubmed_abstract"} +{"meta":{"pmid":8383014,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Platelet-activating factor receptor-dependent activation of the muscarinic K+ current in bullfrog atrial myocytes.\nPlatelet-activating factor (PAF), a potent signaling lipid implicated as a mediator of pathological responses, has both negative chronotropic and inotropic effects on the heart, although the mechanism(s) involved is not well defined. Because activation of the muscarinic acetylcholine-activated K+ current (IK(ACh)) also produces a negative chronotropic and inotropic response in myocardium, this study examines whether PAF has effects on IK(ACh) in isolated bullfrog atrial myocytes under whole-cell voltage-clamp conditions. We find that 2 microM PAF increases the rate of GTP-gamma-S-mediated IK(ACh) activation (from 0.30 +\/- 0.01 min-1 [n = 20] to 0.73 +\/- 0.07 min-1 [n = 12], p < 0.005, in the absence of acetylcholine). This effect of 2 microM PAF was blocked by the PAF antagonist CV-3988 (5 microM, 0.33 +\/- 0.14 min-1 [n = 12]), suggesting the presence of specific PAF receptors coupled to IK(ACh) activation. Further support for mediation by specific G protein-coupled PAF receptors derives from the inability of PAF to modulate IK(ACh) after maximal activation in the presence of GTP-gamma-S. Eicosatetraynoic acid (ETYA, an inhibitor of 5- and 12-lipoxygenases) did not prevent the PAF-mediated increase in the rate of IK(ACh) activation (10 microM ETYA, 0.28 +\/- 0.03 min-1 [n = 7]; 10 microM ETYA plus 2 microM PAF, 0.58 +\/- 0.13 min-1 [n = 8]; p < 0.05), suggesting that the observed PAF effect is not mediated by increases in arachidonic acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":31360772,"dup_signals":{"dup_doc_count":14,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2021-04":3,"2020-50":3,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2024-26":1}}},"text":"Three-spin solid effect and the spin diffusion barrier in amorphous solids.\nDynamic nuclear polarization (DNP) has evolved as the method of choice to enhance NMR signal intensities and to address a variety of otherwise inaccessible chemical, biological and physical questions. Despite its success, there is no detailed understanding of how the large electron polarization is transferred to the surrounding nuclei or where these nuclei are located relative to the polarizing agent. To address these questions we perform an analysis of the three-spin solid effect, and show that it is exquisitely sensitive to the electron-nuclear distances. We exploit this feature and determine that the size of the spin diffusion barrier surrounding the trityl radical in a glassy glycerol-water matrix is <6 \u00c5, and that the protons involved in the initial transfer step are on the trityl molecule. 1H ENDOR experiments indicate that polarization is then transferred in a second step to glycerol molecules in intimate contact with the trityl.","subset":"pubmed_abstract"} +{"meta":{"pmid":10515943,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2018-34":1,"2018-13":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Sequence and organization of pXO1, the large Bacillus anthracis plasmid harboring the anthrax toxin genes.\nThe Bacillus anthracis Sterne plasmid pXO1 was sequenced by random, \"shotgun\" cloning. A circular sequence of 181,654 bp was generated. One hundred forty-three open reading frames (ORFs) were predicted using GeneMark and GeneMark.hmm, comprising only 61% (110,817 bp) of the pXO1 DNA sequence. The overall guanine-plus-cytosine content of the plasmid is 32.5%. The most recognizable feature of the plasmid is a \"pathogenicity island,\" defined by a 44.8-kb region that is bordered by inverted IS1627 elements at each end. This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs. Nearly 70% of the ORFs on pXO1 do not have significant similarity to sequences available in open databases. Absent from the pXO1 sequence are homologs to genes that are typically required to drive theta replication and to maintain stability of large plasmids in Bacillus spp. Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species. Among the remaining ORFs, there are three sequences that may encode enzymes responsible for the synthesis of a polysaccharide capsule usually associated with serotype-specific virulent streptococci.","subset":"pubmed_abstract"} +{"meta":{"pmid":21790068,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2015-06":1,"unknown":19}}},"text":"Characterisation of two vitellogenins in the salmon louse Lepeophtheirus salmonis: molecular, functional and evolutional analysis.\nThe salmon louse Lepeophtheirus salmonis Kr\u00f8yer affects a variety of wild salmonoid hosts, but is also an important pest in aquaculture, which is a globally important and rapidly growing industry. Salmon lice have large reproductive outputs, and knowledge of reproductive processes may be crucial for the control of this parasite. Here, we report on the characterisation of 2 vitellogenins (LsVit1 and LsVit2), which are the precursors of salmon-louse egg-yolk glycoprotein. The structure of LsVit1 and LsVit2 was examined and compared to that in other oviparous animals. Phylogenetic analysis of LsVit1 and LsVit2 confirmed the view that crustaceans are a polyphyletic group. Transcriptional and translational analysis demonstrated production of LsVit1 and LsVit2 in the subcuticular tissue of the adult female lice. LsVit1 and LsVit2 could also be found in maturing oocytes and developing embryos and early larval stages. LsVit2 was found to be processed into 2 smaller fragments, whereas LsVit1 was found to be full length when deposited into the oocytes. Degradation of LsVit1 and LsVit2 was characterised through embryogenesis and the early non-feeding larval stages. Finally, protein content and the level of free amino acids were analysed in embryos and larval stages and their role in nutrition and osmoregulation discussed. In conclusion, our results confirm the role of vitellogenins in reproduction as providers of embryonic and larval nutrition.","subset":"pubmed_abstract"} +{"meta":{"pmid":21636318,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Human parainfluenza virus type 4 infection in Chinese children with lower respiratory tract infections: a comparison study.\nHuman parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Although HPIV-4 has been associated with mild ARTIs for years, recent investigations have also associated HPIV-4 infection with severe respiratory syndromes and with outbreaks of ARTIs in children. To characterize the role of HPIV-4 and its clinical features in children with acute lower respiratory tract infections (ALRTIs) in Beijing, China. Nasopharyngeal aspirates were collected from 2009 hospitalized children with ALRTIs between March 2007 and April 2010. RT-PCR and PCR analyses were used to identify HPIV types and other known respiratory viruses. HPIVs were detected in 246 (12.2%) patients, of whom 25 (10.2%) were positive for HPIV-4, 11 (4.5%) for HPIV-2, 51 (20.7%) for HPIV-1, 151 (61.4%) for HPIV-3, and 8 (3.3%) were co-detected with different types of HPIVs. Like HPIV-3, HPIV-4 was detected in spring, summer, and late fall over the study period. Seasonal incidence varied for HPIV-1 and -2. The median patient age was 20 months for HPIV-4 infections and 7-11 months for HPIV-1, -2, and -3 infections, but the clinical manifestations did not differ significantly between HPIV-1, -2, -3, and -4 infections. Moreover, co-detection of HPIV-4 (44%) with other respiratory viruses was lower than that of HPIV-1 (62.7%), HPIV-2 (63.6%), and HPIV-3 (72.7%). HPIV-4 plays an important role in Chinese paediatric ALRTIs. The epidemiological and clinical characteristics reported here improve our understanding of the pathogenesis associated with HPIV-4.","subset":"pubmed_abstract"} +{"meta":{"pmid":18446627,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":7}}},"text":"Histological characteristics of singleton placentas delivered before the 28th week of gestation.\nThe placenta is a record of the fetal environment and its examination may provide information about the baby's subsequent growth and development. We describe the histological characteristics of 947 singleton placentas from infants born between 23 and 27 weeks gestation. Consent was obtained from mothers who delivered before 28 weeks (clinical estimate). We evaluated the gross and histopathological features of the placenta and assessed pair-wise correlations between variables. Lesions of uteroplacental circulation (abruption, extensive infarction or thrombosis, marked basal or perivillous fibrin deposition, increased syncytial knots) were inversely related to those associated with inflammation of the membranes and cord. Earlier age favoured inflammatory variables, while older age favoured characteristics attributed to impaired blood flow. We observed inflammation of the chorionic plate in 43%, the cord in 19%, and of chorionic plate vessels in 30%. Of the placentas with umbilical cord inflammation, 8% had no inflammation of the chorionic plate. This study population is unique in its size and recruitment by gestational age rather than birth weight. Inflammation occurred frequently, but not in placentas that had characteristics of vasculopathy. The prevalence of inflammation decreased with increasing gestational age, while vasculopathy increased. Funisitis need not be accompanied by chorionic inflammation.","subset":"pubmed_abstract"} +{"meta":{"pmid":23796280,"dup_signals":{"dup_doc_count":19,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2022-33":2,"2021-49":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2023-06":1}}},"text":"Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force.\nPatient-reported outcome (PRO) instruments for children and adolescents are often included in clinical trials with the intention of collecting data to support claims in a medical product label. The purpose of the current task force report is to recommend good practices for pediatric PRO research that is conducted to inform regulatory decision making and support claims made in medical product labeling. The recommendations are based on the consensus of an interdisciplinary group of researchers who were assembled for a task force associated with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). In those areas in which supporting evidence is limited or in which general principles may not apply to every situation, this task force report identifies factors to consider when making decisions about the design and use of pediatric PRO instruments, while highlighting issues that require further research. Five good research practices are discussed: 1) Consider developmental differences and determine age-based criteria for PRO administration: Four age groups are discussed on the basis of previous research (<5 years old, 5-7 years, 8-11 years, and 12-18 years). These age groups are recommended as a starting point when making decisions, but they will not fit all PRO instruments or the developmental stage of every child. Specific age ranges should be determined individually for each population and PRO instrument. 2) Establish content validity of pediatric PRO instruments: This section discusses the advantages of using children as content experts, as well as strategies for concept elicitation and cognitive interviews with children. 3) Determine whether an informant-reported outcome instrument is necessary: The distinction between two types of informant-reported measures (proxy vs. observational) is discussed, and recommendations are provided. 4) Ensure that the instrument is designed and formatted appropriately for the target age group. Factors to consider include health-related vocabulary, reading level, response scales, recall period, length of instrument, pictorial representations, formatting details, administration approaches, and electronic data collection (ePRO). 5) Consider cross-cultural issues. Additional research is needed to provide methodological guidance for future studies, especially for studies involving young children and parents' observational reports. As PRO data are increasingly used to support pediatric labeling claims, there will be more information regarding the standards by which these instruments will be judged. The use of PRO instruments in clinical trials and regulatory submissions will help ensure that children's experience of disease and treatment are accurately represented and considered in regulatory decisions.","subset":"pubmed_abstract"} +{"meta":{"pmid":21795546,"dup_signals":{"dup_doc_count":37,"dup_dump_count":32,"dup_details":{"curated_sources":4,"2022-33":1,"2021-10":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2015-14":1,"2014-15":2,"2023-14":1,"2015-18":1,"2015-11":1,"2014-10":1,"2017-13":1}}},"text":"Abnormal presynaptic short-term plasticity and information processing in a mouse model of fragile X syndrome.\nFragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading genetic cause of autism. It is associated with the lack of fragile X mental retardation protein (FMRP), a regulator of protein synthesis in axons and dendrites. Studies on FXS have extensively focused on the postsynaptic changes underlying dysfunctions in long-term plasticity. In contrast, the presynaptic mechanisms of FXS have garnered relatively little attention and are poorly understood. Activity-dependent presynaptic processes give rise to several forms of short-term plasticity (STP), which is believed to control some of essential neural functions, including information processing, working memory, and decision making. The extent of STP defects and their contributions to the pathophysiology of FXS remain essentially unknown, however. Here we report marked presynaptic abnormalities at excitatory hippocampal synapses in Fmr1 knock-out (KO) mice leading to defects in STP and information processing. Loss of FMRP led to enhanced responses to high-frequency stimulation. Fmr1 KO mice also exhibited abnormal synaptic processing of natural stimulus trains, specifically excessive enhancement during the high-frequency spike discharges associated with hippocampal place fields. Analysis of individual STP components revealed strongly increased augmentation and reduced short-term depression attributable to loss of FMRP. These changes were associated with exaggerated calcium influx in presynaptic neurons during high-frequency stimulation, enhanced synaptic vesicle recycling, and enlarged readily-releasable and reserved vesicle pools. These data suggest that loss of FMRP causes abnormal STP and information processing, which may represent a novel mechanism contributing to cognitive impairments in FXS.","subset":"pubmed_abstract"} +{"meta":{"pmid":12662951,"dup_signals":{"dup_doc_count":21,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2022-49":1,"2022-40":1,"2022-33":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-21":2,"2020-45":2,"2020-40":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-30":1,"2019-18":1,"2019-13":1,"2023-14":1,"2024-30":1}}},"text":"Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan.\nTo evaluate the efficacy of peppermint oil in barium as a spasmolytic agent during a double-contrast barium enema (DCBE). A total of 383 DCBEs with positive results from occult blood tests were assessed. Patients were assigned to one of four groups: peppermint in barium (n=91), peppermint in tube (n=90), Buscopan (n=105), or no treatment (n=97). After a screening sigmoidoscopy, the DCBEs were performed using air as a distending gas. In the Buscopan group, the DCBE was performed with an intramuscular injection of 20mg Buscopan at the start of the examination. Patients in the no-treatment group underwent DCBE without any spasmolytic agent. A peppermint oil preparation (30ml) was mixed in the barium solution for patients in the peppermint-in-barium group, and the same dose of peppermint oil was included in the enema tube in the peppermint-in-tube group. The presence of spasm on a series of spot films was evaluated without information about the type of spasmolytic agent used. The percentage of patients in the four groups (no treatment, Buscopan, peppermint in tube, and peppermint in barium) with absence of spasm in the entire colon on the series of spot films was 13.4, 38.1, 41.8, and 37.8%, respectively. In the group using peppermint oil or Buscopan, the rate of patients with non-spasm examination was higher than that in no-treatment group (p<0.0005). Peppermint oil had the same spasmolytic effect as the systemic administration of Buscopan in the transverse and descending colon. Peppermint oil had a stronger effect in the caecum and the ascending colon than a Buscopan injection (p<0.005). There was no advantage to placing peppermint oil in the enema tube over mixing it in the barium solution. A total of 157 polyps were found during the DCBE procedures, and no differences were observed in the number of lesions among the four groups. Peppermint oil did not impair image quality. Barium solution mixed with peppermint oil was safe and effective for the elimination of colonic spasm during the DCBE procedure, and it could be used instead of Buscopan.","subset":"pubmed_abstract"} +{"meta":{"pmid":30608050,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":8}}},"text":"Impact of a Large-Scale Handwashing Intervention on Reported Respiratory Illness: Findings from a Cluster-Randomized Controlled Trial.\nWe assessed the impact of handwashing promotion on reported respiratory illness as a secondary outcome from among > 60,000 low-income households enrolled in a cluster-randomized trial conducted in Bangladesh. Ninety geographic clusters were randomly allocated into three groups: cholera-vaccine-only; vaccine-plus-behavior-change (handwashing promotion and drinking water chlorination); and control. Data on respiratory illness (fever plus either cough or nasal congestion or breathing difficulty within previous 2 days) and intervention uptake (presence of soap and water at handwashing station) were collected through monthly surveys conducted among a different subset of randomly selected households during the intervention period. We determined respiratory illness prevalence across groups and used log-binomial regression to examine the association between respiratory illness and presence of soap and water in the handwashing station. Results were adjusted for age, gender, wealth, and cluster-randomized design. The vaccine-plus-behavior-change group had more handwashing stations with soap and water present than controls (45% versus 25%; P < 0.001). Reported respiratory illness prevalence was similar across groups (vaccine-plus-behavior-change versus control: 2.8% versus 2.9%; 95% confidence interval [CI]: -0.008, 0.006; P = 0.6; cholera-vaccine-only versus control: 3.0% versus 2.9%; 95% CI: -0.006, 0.009; P = 0.4). Irrespective of intervention assignment, respiratory illness was lower among people who had soap and water present in the handwashing station than among those who did not (risk ratioadjusted: 0.82; 95% CI: 0.69-0.98). With modest uptake of the handwashing intervention, we found no impact of this large-scale intervention on respiratory illness. However, those who actually had a handwashing station with soap and water had less illness. This suggests improving the effectiveness of handwashing promotion in achieving sustained behavior change could result in health benefits.","subset":"pubmed_abstract"} +{"meta":{"pmid":9055162,"dup_signals":{"dup_doc_count":35,"dup_dump_count":26,"dup_details":{"curated_sources":3,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":1,"2014-15":3,"2016-50":1,"2015-11":1,"2015-06":1,"2013-48":1,"2015-18":1}}},"text":"Of persons and organisms: a reply to Howsepian.\nHowsepian has presented a number of thought experiments, which are designed to undermine my claim that our identity through time is grounded in the continued existence of those structures in our brains which directly underlie mental functioning. I argue that the conclusions which Howsepian draws from these thought experiments are mistaken, and that his discussion of them is vitiated, in particular, by his failure to distinguish between personal identity and the identity of the associated human organism.","subset":"pubmed_abstract"} +{"meta":{"pmid":30158877,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Triplet Excited Carbonyls and Singlet Oxygen Formation During Oxidative Radical Reaction in Skin.\nThe skin is the largest organ in the body and is consistently exposed to aggressive environmental attacks (biological\/physical\/chemical, etc.). Reactive oxygen species (ROS) are formed during the normal oxidative metabolism which enhances to a lethal level under stress conditions referred to as oxidative stress. While, under normal conditions, cells are capable of dealing with ROS using non-enzymatic and enzymatic defense system, it can lead to a critical damage to cell system via the oxidation of cellular components under stress condition. Lipid peroxidation is a well-established mechanism of cellular injury in all kinds of organisms and it is often used as an indicator of oxidative stress in cells and tissues. In the presence of metal ions, ROS such as hydrogen peroxide (H2O2) produces highly reactive hydroxyl radical (HO\u2022) via Fenton reaction. In the current study, we have used the porcine skin (intact pig ear\/skin biopsies) as an ex vivo\/in vitro model system to represent human skin. Experimental results have been presented on the participation of HO\u2022 in the initiation of lipid peroxidation and thereby leading to the formation of reactive intermediates and the formation of electronically excited species eventually leading to ultra-weak photon emission (UPE). To understand the participation of different electronically excited species in the overall UPE, the effect of a scavenger of singlet oxygen (1O2) on photon emission in the visible and near-infrared region of the spectrum was measured which showed its contribution. In addition, measurement with interference filter with a transmission in the range of 340-540 nm reflected a substantial contribution of triplet carbonyls (3L=O\u2217) in the photon emission. Thus, it is concluded that during the oxidative radical reactions, the UPE is contributed by the formation of both 3L=O\u2217 and 1O2. The method used in the current study is claimed to be a potential tool for non-invasive determination of the physiological and pathological state of human skin in dermatological research.","subset":"pubmed_abstract"} +{"meta":{"pmid":7476899,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Glycine modulates ethanol inhibition of heteromeric N-methyl-D-aspartate receptors expressed in Xenopus oocytes.\nEthanol inhibits N-methyl-D-aspartate (NMDA) receptor-mediated responses at pharmacologically relevant concentrations, suggesting that inhibition of NMDA receptors may underlie some of the actions of ethanol in the central nervous system. We examined the ability of glycine to modulate ethanol inhibition of four recombinant heteromeric NMDA receptors (NR1a\/NR2A through NR2D) expressed in Xenopus oocytes. Ethanol dose-response analysis revealed enhanced inhibitory efficacy of ethanol in the presence of subsaturating glycine concentrations at the NR1\/NR2A, NR1\/NR2C, and NR1\/NR2D receptors. When assayed over a range of glycine concentrations, ethanol exhibited both glycine-reversible and glycine-independent inhibition of NMDA receptors. In contrast, ethanol inhibition of recombinant NMDA receptors was independent of NMDA concentration. Glycine reversal of ethanol inhibition suggested that ethanol might lower the affinity of glycine for the NMDA receptor and thereby decrease response magnitude. Consistent with this hypothesis, ethanol significantly reduced glycine affinity at NR1\/NR2A and NR1\/NR2C receptors. Evaluation of the glycine-independent component of ethanol inhibition demonstrated that in the presence of saturating concentrations of glycine, the NR1\/NR2A and NR1\/NR2B receptors were more sensitive to ethanol than the NR1\/NR2C and NR1\/NR2D receptors. Activation of the NR1\/NR2D heteromers by NMDA and low concentrations of glycine elicited responses characterized by an initial peak followed by a lower-amplitude plateau response, which is consistent with glycine-sensitive desensitization as previously described for native NMDA receptors. In addition, nondesensitizing NR1\/NR2B responses elicited in the presence of subsaturating concentrations of glycine were frequently converted into desensitizing responses by the addition of ethanol, an effect that was reversed with increasing glycine concentrations. The ability of ethanol to promote glycine-sensitive desensitization further suggests an interaction between glycine and ethanol inhibition of the NMDA receptor. Taken together, the results of the present report demonstrate that ethanol inhibition of NMDA receptors has both glycine-reversible and glycine-independent components, suggesting two distinct molecular mechanisms for ethanol inhibition of NMDA receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":29061993,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":12}}},"text":"Live cell X-ray imaging of autophagic vacuoles formation and chromatin dynamics in fission yeast.\nSeeing physiological processes at the nanoscale in living organisms without labeling is an ultimate goal in life sciences. Using X-ray ptychography, we explored in situ the dynamics of unstained, living fission yeast Schizosaccharomyces pombe cells in natural, aqueous environment at the nanoscale. In contrast to previous X-ray imaging studies on biological matter, in this work the eukaryotic cells were alive even after several ptychographic X-ray scans, which allowed us to visualize the chromatin motion as well as the autophagic cell death induced by the ionizing radiation. The accumulated radiation of the sequential scans allowed for the determination of a characteristic dose of autophagic vacuole formation and the lethal dose for fission yeast. The presented results demonstrate a practical method that opens another way of looking at living biological specimens and processes in a time-resolved label-free setting.","subset":"pubmed_abstract"} +{"meta":{"pmid":9405613,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":2,"2024-26":1,"unknown":9}}},"text":"Thermodynamic stability of wild-type and mutant p53 core domain.\nSome 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn2+ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)\/mol at 25 degrees C and 9.8 kcal\/mol at 10 degrees C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal\/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":29318966,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?\nInflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and\/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-\u03b1 inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.","subset":"pubmed_abstract"} +{"meta":{"pmid":22267819,"dup_signals":{"dup_doc_count":28,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-40":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-05":1,"2019-39":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":2,"2023-50":1}}},"text":"Use of electronic documentation for quality improvement in hospice.\nLittle evidence exists about the use of electronic documentation (ED) in hospice and its relationship to quality improvement (QI) practices. The purposes of this study were to (1) estimate the prevalence of ED use in hospice, (2) identify organizational characteristics associated with use of ED, and (3) determine whether quality measurement practices differed based on documentation format (electronic vs nonelectronic). Surveys concerning the use of ED for QI practices and the monitoring of quality-related care and outcomes were collected from 653 hospices. Users of ED were able to monitor a wider range of quality-related data than users of non-ED. Quality components such as advanced care planning, cultural needs, experience during care of the actively dying, and the number\/types of care being delivered were more likely to be documented by users of ED. Use of ED may help hospices monitor quality and compliance.","subset":"pubmed_abstract"} +{"meta":{"pmid":33159782,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"On the connection between probability density analysis, QTAIM, and VB theory.\nClassification of bonds is essential for understanding and predicting the reactivity of chemical compounds. This classification mainly manifests in the bond order and the contribution of different Lewis resonance structures. Here, we outline a first principles approach to obtain these orders and contributions for arbitrary wave functions in a manner that is both, related to the quantum theory of atoms in molecules and consistent with valence bond theory insight: the Lewis structures arise naturally as attractors of the all-electron probability density |\u03a8|2. Doing so, we introduce a valence bond weight definition that does not collapse in the basis set limit.","subset":"pubmed_abstract"} +{"meta":{"pmid":24023788,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Gene network analysis in a pediatric cohort identifies novel lung function genes.\nLung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS) of four pulmonary function traits, including FVC, FEV1, FEV1\/FVC and FEF25-75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0 \u00d7 10(-3) from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta=1.41 \u00d7 10(-7)). The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta=6.29 \u00d7 10(-4) - 2.80 \u00d7 10(-8) on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":27917246,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-22":1,"unknown":11}}},"text":"Moral Bioenhancement, Freedom and Reason.\nIn this paper we reply to the most important objections to our advocacy of moral enhancement by biomedical means - moral bioenhancement - that John Harris advances in his new book How to be Good. These objections are to effect that such moral enhancement undercuts both moral reasoning and freedom. The latter objection is directed more specifically at what we have called the God Machine, a super-duper computer which predicts our decisions and prevents decisions to perpertrate morally atrocious acts. In reply, we argue first that effective moral bioenhancement presupposes moral reasoning rather than undermines it. Secondly, that the God Machine would leave us with extensive freedom and that the restrictions it imposes on it are morally justified by the prevention of harm to victims.","subset":"pubmed_abstract"} +{"meta":{"pmid":30626705,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Breast tumour organoids: promising models for the genomic and functional characterisation of breast cancer.\nUntil recently, established cancer cell lines have been used extensively in breast cancer research, due largely to the difficulties associated with the manipulation and long-term maintenance in culture of primary tumour cells from patients. The recent development of organoid cultures has provided new opportunities to model and analyse patient samples, allowing the propagation of malignant cells under conditions that resemble the three-dimensional growth of breast tumours. They have proved efficacious in preserving the heterogeneity of primary samples and are emerging as a new model to further characterise the molecular features of breast cancer. Organoids formed from patient-derived cells are now in use for the evaluation of drug sensitivity and to validate disease-causing genomic variations. Here, the advantages and limitations of organoid cultures will be discussed and compared with the parallel development of other two- and three-dimensional culture strategies and with patient-derived xenografts. In particular, we will focus on the molecular characterisation of breast cancer organoids and provide some examples of how they have been used in functional studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":12659285,"dup_signals":{"dup_doc_count":26,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2016-44":1,"2016-36":2,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":2,"2015-48":1,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":1,"2015-22":3,"2017-43":1,"2015-18":2}}},"text":"Highly sensitive direct characterization of femtosecond pulses by electro-optic spectral shearing interferometry.\nWe report what is to our knowledge the first experimental demonstration of spectral shearing interferometry by use of an electro-optic temporal phase modulator to generate the spectral shear. This approach achieves far better sensitivity than nonlinear optical pulse characterization techniques, including other versions of spectral shearing interferometry. Temporal phase modulation is conceptually simple and is implemented easily with telecommunication components. The technique is versatile, and a wide range of pulse durations can be measured with minimal changes in the setup. We demonstrate the accurate characterization of a 156-MHz train of 1540-nm pulses with durations ranging from 750 fs to more than 30 ps after various amounts of chirping, at average powers below 1 microW.","subset":"pubmed_abstract"} +{"meta":{"pmid":26497368,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":8}}},"text":"Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC.\nDysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.","subset":"pubmed_abstract"} +{"meta":{"pmid":18200483,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":1,"2024-10":1,"unknown":7}}},"text":"Fluorescence nanoscopy with optical sectioning by two-photon induced molecular switching using continuous-wave lasers.\nDuring the last decade far-field fluorescence microscopy methods have evolved that have resolution far below the wavelength of light. To outperform the limiting role of diffraction, all these methods, in one way or another, switch the ability of a molecule to emit fluorescence. Here we present a novel rhodamine amide that can be photoswitched from a nonfluorescent to a fluorescent state by absorption of one or two photons from a continuous-wave laser beam. This bright marker enables strict control of on\/off switching and provides single-molecule localization precision down to 15 nm in the focal plane. Two-photon induced nonlinear photoswitching of this marker with continuous-wave illumination offers optical sectioning with simple laser equipment. Future synthesis of similar compounds holds great promise for cost-effective fluorescence nanoscopy with noninvasive optical sectioning.","subset":"pubmed_abstract"} +{"meta":{"pmid":15460852,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-49":1,"2020-34":1,"2020-05":1,"2019-51":1,"2019-35":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-47":1,"2022-49":1,"2024-30":1}}},"text":"Multiple pathogens found in growth-retarded black tiger shrimp Penaeus monodon cultivated in Thailand.\nIn 2001-2002 throughout Thailand, black tiger shrimp Penaeus monodon farmers reported very unusual retarded growth. We have called this problem monodon slow growth syndrome (MSGS). Based on decreased national production, estimated losses due to this phenomenon were in the range of 13 000 million baht (approximately 300 million US dollars) in 2002. Since rearing practices had not changed, it was considered possible that the MSGS problem may have arisen from a new or existing pathogen. To examine this possibility, cultivated shrimp were sampled from 32 commercial rearing ponds that reported abnormally slow growth from eastern, central and southern regions of Thailand. Shrimp were randomly sampled from each pond and grouped into normal and small shrimp. Normal shrimp were defined as those with body weights (BW) of 24 g or more while small shrimp were defined as those that weighed 16.8 g or less. Pleopods were used for detection of monodon baculovirus (MBV), heptopancreatic parvovirus (HPV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) using specific polymerase chain reaction (PCR) assays. In addition, some shrimp were processed for normal histopathology and transmission electron microscopy (TEM). Most of the shrimp specimens were infected by at least 1 of these viruses but many had dual or multiple infections. Prevalence of HPV and combined HPV\/MBV infections in the small shrimp was significantly higher than in the normal shrimp. In addition to the viruses, a new microsporidian species, gregarines and bacteria were also observed but were not significantly associated with the MSGS problem. Some of the small shrimp gave negative results for all these pathogens by PCR and histology and no new and unique histopathology was recognized in any of the samples. The findings suggested that HPV infection was a contributing factor but not the overriding factor responsible for MSGS. It is possible that MSGS is caused by an unknown pathogen or by some other presently unknown, non-pathogenic factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":18302686,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Recombination and genetic differentiation among natural populations of the ectomycorrhizal mushroom Tricholoma matsutake from southwestern China.\nEffective conservation and utilization strategies for natural biological resources require a clear understanding of the natural populations of the target organisms. Tricholoma matsutake is an ectomycorrhizal mushroom that forms symbiotic associations with plants and plays an important ecological role in natural forest ecosystems in many parts of the world. It is also an economically very important gourmet mushroom. Because no artificial cultivation is available, natural populations of this species are under increasing threats, primarily from habitat disturbance and destruction. Despite its economical and ecological importance, little is known about its genetics and population biology. Here, using 14 polymerase chain reaction-restriction fragment length polymorphism markers, we analysed 154 strains from 17 geographical locations in southwestern China, a region where over 25% of the global T. matsutake harvest comes from. Our results revealed abundant genetic variation within individual populations. The analyses of gene and genotype frequencies within populations indicated that most loci did not deviate from Hardy-Weinberg equilibrium in most populations and that alleles among loci were in linkage equilibrium in the majority of the local populations. These results are consistent with the hypothesis that sexual reproduction and recombination play an important role in natural populations of this species. Our analyses indicated low but significant genetic differentiation among the geographical populations, with a significant positive correlation between genetic distance and geographical distance. We discuss the implications of our results to the ecology and resource management of this species.","subset":"pubmed_abstract"} +{"meta":{"pmid":14600032,"dup_signals":{"dup_doc_count":47,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":2,"2016-26":1,"2016-22":2,"2016-18":2,"2016-07":1,"2015-48":2,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":4,"2014-41":1,"2014-35":1,"2014-23":3,"2014-15":2,"2016-50":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":2,"2015-18":1}}},"text":"Water turnover in 458 American adults 40-79 yr of age.\nDespite recent interest in water intake, few data are available on water metabolism in adults. To determine the average and range of usual water intake, urine output, and total body water, we administered 2H oxide to 458 noninstitutionalized 40- to 79-yr-old adults living in temperate climates. Urine was collected in a subset of individuals (n = 280) to measure 24-h urine production using p-aminobenzoic acid to ensure complete collection. Preformed water intake was calculated from isotopic turnover and corrected for metabolic water and insensible water absorption from humidity. Preformed water intake, which is water from beverages and food moisture, averaged 3.0 l\/day in men (range: 1.4-7.7 l\/day) and 2.5 l\/day in women (range: 1.2-4.6 l\/day). Preformed water intake was lower in 70- to 79 (2.8 l\/day)- than in 40- to 49-yr-old men and was lower in 70- to 79 (2.3 l\/day)- than in 40- to 49- and 50- to 59-yr-old women. Urine production averaged 2.2 l\/day in men (range: 0.6-4.9 l\/day) and 2.2 l\/day in women (0.9-6.0 l\/day). There were no age-related differences in results in women, but 60- to 69-yr-old men had significantly higher urine output than 40- to 49- and 50- to 59-yr-old men. Only the 70- to 79-yr-old group included sufficient blacks for a racial analysis. Blacks in this age group showed significantly lower preformed water intake than did whites. Whites had significantly higher water turnover rates than blacks as well. Multivariate regression indicated that age, weight, height, and body mass index explained <12% of the gender-specific variance in water input or urine output, yet repeat measures indicated that within-individual coefficient of variation was 8% for preformed water intake (n = 22) and 9% for 24-h urine production (n = 222). These results demonstrate that water turnover is highly variable among individuals and that little of the variance is explained by anthropometric parameters.","subset":"pubmed_abstract"} +{"meta":{"pmid":26120894,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"E-Learning with virtual teammates: A novel approach to interprofessional education.\nThe Institute of Medicine identified interprofessional education (IPE) as a key innovation for achieving the triple aim of better care, better outcomes, and reduced healthcare costs. Yet, a shortage of qualified faculty and difficulty with aligning learners' schedules often prevent sustainable and scalable IPE. A virtual IPE intervention was developed to circumvent these barriers and compared to a blended-learning IPE intervention. We used a pre-test and post-test design with two comparison interventions to test the effects of these IPE interventions on changes in teamwork knowledge, skills, and attitudes. The interventions were delivered to pre-licensure learners at a large, metropolitan medical and a nursing school. We used one-sample and independent-sample t-tests to analyze data from 220 learners who received the blended-learning intervention in 2011 and 540 learners who received the virtual learning intervention in 2012. The students in the blended-learning intervention did not significantly (p < 0.05) outperform the students in the virtual learning intervention for any of the measured outcomes, except for medical students' attitudes around team value. Virtual IPE learning is an effective, scalable, and sustainable solution for imparting foundational teamwork knowledge in health profession students.","subset":"pubmed_abstract"} +{"meta":{"pmid":3049610,"dup_signals":{"dup_doc_count":12}},"text":"Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules.\nA novel Mr 28,000 integral membrane protein (\"28kDa\") was identified in human erythrocytes and found entirely associated with the Triton X-100 insoluble membrane skeletons. Antibodies to 28kDa reacted strongly on immunoblots with 28kDa and a diffuse region of Mr 35,000-60,000 (\"HMW-28kDa\"). Selective proteolytic digestions of membranes demonstrated that HMW-28kDa has an extracellular domain, and both 28kDa and HMW-28kDa have intracellular domains. 28kDa and HMW-28kDa were purified to homogeneity. Quantitative immunoblots indicate that each erythrocyte contains 120,000-160,000 copies of 28kDa. Two-dimensional iodopeptide maps of 28kDa and HMW-28kDa were nearly identical; peptide-N-glycosidase digestion of purified HMW-28kDa demonstrated that it is the N-glycosylated form of 28kDa. When concentrated, 28kDa formed a series of larger oligomers which were stable in sodium dodecyl sulfate. Of several nonerythroid tissues studied with anti-28kDa immunoblots, only kidney displayed immunoreactive 28kDa. Purified rat kidney 28kDa was nearly identical to rat erythrocyte 28kDa when compared by two-dimensional iodopeptide mapping. Immunohistochemical staining of human kidney with anti-28kDa demonstrated prominent staining over the apical brush borders of proximal convoluted tubules. A novel integral membrane protein has been purified from erythrocyte and kidney membranes. This new protein may play a role in linkage of the membrane skeleton to the lipid bilayer.","subset":"pubmed_abstract"} +{"meta":{"pmid":35252361,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":9}}},"text":"Agree to Disagree: Subjective Fairness in Privacy-Restricted Decentralised Conflict Resolution.\nFairness is commonly seen as a property of the global outcome of a system and assumes centralisation and complete knowledge. However, in real decentralised applications, agents only have partial observation capabilities. Under limited information, agents rely on communication to divulge some of their private (and unobservable) information to others. When an agent deliberates to resolve conflicts, limited knowledge may cause its perspective of a correct outcome to differ from the actual outcome of the conflict resolution. This is subjective unfairness. As human systems and societies are organised by rules and norms, hybrid human-agent and multi-agent environments of the future will require agents to resolve conflicts in a decentralised and rule-aware way. Prior work achieves such decentralised, rule-aware conflict resolution through cultures: explainable architectures that embed human regulations and norms via argumentation frameworks with verification mechanisms. However, this prior work requires agents to have full state knowledge of each other, whereas many distributed applications in practice admit partial observation capabilities, which may require agents to communicate and carefully opt to release information if privacy constraints apply. To enable decentralised, fairness-aware conflict resolution under privacy constraints, we have two contributions: 1) a novel interaction approach and 2) a formalism of the relationship between privacy and fairness. Our proposed interaction approach is an architecture for privacy-aware explainable conflict resolution where agents engage in a dialogue of hypotheses and facts. To measure the privacy-fairness relationship, we define subjective and objective fairness on both the local and global scope and formalise the impact of partial observability due to privacy in these different notions of fairness. We first study our proposed architecture and the privacy-fairness relationship in the abstract, testing different argumentation strategies on a large number of randomised cultures. We empirically demonstrate the trade-off between privacy, objective fairness, and subjective fairness and show that better strategies can mitigate the effects of privacy in distributed systems. In addition to this analysis across a broad set of randomised abstract cultures, we analyse a case study for a specific scenario: we instantiate our architecture in a multi-agent simulation of prioritised rule-aware collision avoidance with limited information disclosure.","subset":"pubmed_abstract"} +{"meta":{"pmid":23046741,"dup_signals":{"dup_doc_count":11}},"text":"A cross-sectional and semantic investigation of self-rated health in the northern Sweden MONICA-study.\nSelf-Rated Health (SRH) correlates with risk of illness and death. But how are different questions of SRH to be interpreted? Does it matter whether one asks: \"How would you assess your general state of health?\"(General SRH) or \"How would you assess your general state of health compared to persons of your own age?\"(Comparative SRH)? Does the context in a questionnaire affect the answers? The aim of this paper is to examine the meaning of two questions on self-rated health, the statistical distribution of the answers, and whether the context of the question in a questionnaire affects the answers. Statistical and semantic methodologies were used to analyse the answers of two different SRH questions in a cross-sectional survey, the MONICA-project of northern Sweden. The answers from 3504 persons were analysed. The statistical distributions of answers differed. The most common answer to the General SRH was \"good\", while the most common answer to the Comparative SRH was \"similar\". The semantic analysis showed that what is assessed in SRH is not health in a medical and lexical sense but fields of association connected to health, for example health behaviour, functional ability, youth, looks, way of life. The meaning and function of the two questions differ - mainly due to the comparing reference in Comparative SRH. The context in the questionnaire may have affected the statistics. Health is primarily assessed in terms of its sense-relations (associations) and Comparative SRH and General SRH contain different information on SRH. Comparative SRH is semantically more distinct. The context of the questions in a questionnaire may affect the way self-rated health questions are answered. Comparative SRH should not be eliminated from use in questionnaires. Its usefulness in clinical encounters should be investigated.","subset":"pubmed_abstract"} +{"meta":{"pmid":28797937,"dup_signals":{"dup_doc_count":18}},"text":"Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas.\nOncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p. To gauge the impact of antiviral defenses, we also compared the infectivity of the oncolytic adenoviruses in interferon (IFN)-pretreated cells with IFN-sensitive Semliki Forest virus (SFV). Immunostaining revealed generally low expression of HAd5 receptor CAR in both primary tumors and derived cell lines. HAd11p receptor CD46 levels were maintained at moderate levels in both primary tumor samples and derived cell lines. HAd3 receptor DSG-2 was reduced in the cell lines compared to the tumors. Yet, at equal multiplicities of infection, the oncolytic potency of HAd5 in vitro in tumor-derived cells was comparable to HAd11p, whereas HAd3 lysed fewer cells than either of the other two HAd serotypes in 72 hours. IFN blocked replication of SFV, while HAds were rather unaffected. Adenovirus receptor levels on glioma-derived cell lines did not correlate with infection efficacy and may not be a relevant indicator of clinical oncolytic potency. Adenovirus receptor analysis should be preferentially performed on biopsies obtained perioperatively.","subset":"pubmed_abstract"} +{"meta":{"pmid":27525823,"dup_signals":{"dup_doc_count":37,"dup_dump_count":30,"dup_details":{"curated_sources":2,"2022-21":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":2,"2020-40":1,"2020-34":1,"2020-29":1,"2020-16":2,"2020-05":1,"2019-47":2,"2019-35":2,"2019-26":1,"2019-22":1,"2019-18":1,"2019-09":2,"2018-51":1,"2018-47":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2023-14":1,"2024-18":1,"2017-13":1,"2024-30":1}}},"text":"Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity.\nPropofol (2,6-diisopropylphenol) is an anaesthetic widely used for human sedation. Due to its intrinsic antioxidant properties, rapid induction of anaesthesia and fast recovery, it is employed in paediatric anaesthesia and in the intensive care of premature infants. Recent studies have pointed out that exposure to anaesthesia in the early stage of life might be responsible of long-lasting cognitive impairment. The apoptotic neurodegeneration induced by general anaesthetics (GA) involves mitochondrial impairment due to the inhibition of the OXPHOS machinery. In the present work, we aim to identify the main mitochondrial respiratory chain target of propofol toxicity and to evaluate the possible protective effect of CoQ10 supplementation. The propofol effect on the mitochondrial functionality was assayed in isolated mitochondria and in two cell lines (HeLa and T67) by measuring oxygen consumption rate. The protective effect of CoQ10 was assessed by measuring cells viability, NADH-oxidase activity and ATP\/ADP ratio in cells treated with propofol. Our results show that propofol reduces cellular oxygen consumption rate acting mainly on mitochondrial Complex I. The kinetic analysis of Complex I inhibition indicates that propofol interferes with the Q module acting as a non-competitive inhibitor with higher affinity for the free form of the enzyme. Cells supplemented with CoQ10 are more resistant to propofol toxicity. Propofol exposure induces cellular damages due to mitochondrial impairment. The site of propofol inhibition on Complex I is the Q module. CoQ10 supplementation protects cells against the loss of energy suggesting its possible therapeutic role to minimizing the detrimental effects of general anaesthesia.","subset":"pubmed_abstract"} +{"meta":{"pmid":16710545,"dup_signals":{"dup_doc_count":15,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":7}}},"text":"Benchmarking progress in tackling the challenges of intellectual property, and access to medicines in developing countries.\nThe impact of intellectual property protection in the pharmaceutical sector on developing countries has been a central issue in the fierce debate during the past 10 years in a number of international fora, particularly the World Trade Organization (WTO) and WHO. The debate centres on whether the intellectual property system is: (1) providing sufficient incentives for research and development into medicines for diseases that disproportionately affect developing countries; and (2) restricting access to existing medicines for these countries. The Doha Declaration was adopted at WTO in 2001 and the Commission on Intellectual Property, Innovation and Public Health was established at WHO in 2004, but their respective contributions to tackling intellectual property-related challenges are disputed. Objective parameters are needed to measure whether a particular series of actions, events, decisions or processes contribute to progress in this area. This article proposes six possible benchmarks for intellectual property-related challenges with regard to the development of medicines and ensuring access to medicines in developing countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":19591201,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: metabolite quantification at 4T vs. 7T.\nA comprehensive comparative study of metabolite quantification from the human brain was performed on the same 10 subjects at 4T and 7T using MR scanners with identical consoles, the same type of RF coils, and identical pulse sequences and data analysis. Signal-to-noise ratio (SNR) was increased by a factor of 2 at 7T relative to 4T in a volume of interest selected in the occipital cortex using half-volume quadrature radio frequency (RF) coils. Spectral linewidth was increased by 50% at 7T, which resulted in a 14% increase in spectral resolution at 7T relative to 4T. Seventeen brain metabolites were reliably quantified at both field strengths. Metabolite quantification at 7T was less sensitive to reduced SNR than at 4T. The precision of metabolite quantification and detectability of weakly represented metabolites were substantially increased at 7T relative to 4T. Because of the increased spectral resolution at 7T, only one-half of the SNR of a 4T spectrum was required to obtain the same quantification precision. The Cram\u00e9r-Rao lower bounds (CRLB), a measure of quantification precision, of several metabolites were lower at both field strengths than the intersubject variation in metabolite concentrations, which resulted in a strong correlation between metabolite concentrations of individual subjects measured at 4T and 7T.","subset":"pubmed_abstract"} +{"meta":{"pmid":17985253,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-22":2,"2024-18":2,"2017-13":1,"2024-30":1,"unknown":8}}},"text":"REX: response exploration for neuroimaging datasets.\nNeuroimaging technologies produce large and complex datasets. The challenge of comprehensively analysing the recorded dynamics remains an important field of research. The whole-brain linear modelling of hypothesised response dynamics and experimental effects must utilise simple basis sets, which may not detect unexpected or complex signal effects. These unmodelled effects can influence statistical mapping results, and provide important additional clues to the underlying neural dynamics. They can be detected via exploration of the raw signal, however this can be difficult. Specialised visualisation tools are required to manage the huge number of voxels, events and scans. Many effects can be occluded by noise in individual voxel time-series. This paper describes a visualisation framework developed for the assessment of entire neuroimaging datasets. While currently available tools tend to be tied to a specific model of experimental effects, this framework includes a novel metadata schema that enables the rapid selection and processing of responses based on easily-adjusted classifications of scans, brain regions, and events. Flexible event-related averaging and process pipelining capabilities enable users to investigate the effects of preprocessing algorithms and to visualise power spectra and other transformations of the data. The framework has been implemented as a MATLAB package, REX (Response Exploration), which has been utilised within our lab and is now publicly available for download. Its interface enables the real-time control of data selection and processing, for very rapid visualisation. The concepts outlined in this paper have general applicability, and could provide significant further functionality to neuroimaging databasing and process pipeline environments.","subset":"pubmed_abstract"} +{"meta":{"pmid":3193171,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance.\nAmong other deficits, amygdalectomy impairs the ability of the animal to recognize the affective significance of a stimulus. In the present study, neuronal activity in the amygdala (AM) was recorded from alert monkeys while they performed tasks leading to the presentation of rewarding or aversive stimuli. Of 585 AM neurons tested, 312 (53.3%) responded to at least one stimulus in one or more of 5 major groups: 40 vision related, 26 audition related, 41 ingestion related, 117 multimodal, and 14 selective. Ingestion-related neurons were subdivided according to their responses to other stimuli: oral sensory, oral sensory plus vision, and oral sensory plus audition. Depending upon their responsiveness to the affective significance of the stimuli, neurons in the vision- and audition-related categories were divided into 2 subclasses: vis-I (26\/40), vis-II (14\/40), aud-I (8\/26), and aud-II (18\/26). All 4 subtypes usually responded to unfamiliar stimuli but seldom responded to neutral familiar stimuli. Types vis-I and aud-I responded to both positive and negative familiar stimuli. Types vis-II and aud-II responded to certain familiar negative stimuli but not to familiar positive stimuli. In vis-I neurons, responses were stronger for palatable foods than for less palatable foods. No neurons within vision-related, audition-related, and multimodal categories responded solely to positive or to negative stimuli. Of the 27 oral sensory neurons 9 were tested with saline or salted food, and 8 responded to normally aversive oral sensory stimuli in the same manner as they did to normal food or liquid (water or juice). In contrast to oral sensory neurons, all responses of 4 oral sensory-plus-vision and all of 4 selective neurons tested, as well as bar pressing behavior, were modulated by altering the affective significance of the food. These results suggest that the AM is one of the candidates for stimulus-affective association based on associative learning and memory.","subset":"pubmed_abstract"} +{"meta":{"pmid":30755717,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":12}}},"text":"PD-1 is expressed by and regulates human group 3 innate lymphoid cells in human decidua.\nGroup 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-\u03b1, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1\/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.","subset":"pubmed_abstract"} +{"meta":{"pmid":30940200,"dup_signals":{"dup_doc_count":22,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-40":2,"2023-23":1,"2023-06":1,"2022-49":1,"2022-21":1,"2021-39":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-35":1,"2019-30":2,"2019-22":2,"2019-13":1,"2024-30":1}}},"text":"Tick-borne pathogen detection in midgut and salivary glands of adult Ixodes ricinus.\nThe tick midgut and salivary glands represent the primary organs for pathogen acquisition and transmission, respectively. Specifically, the midgut is the first organ to have contact with pathogens during the blood meal uptake, while salivary glands along with their secretions play a crucial role in pathogen transmission to the host. Currently there is little data about pathogen composition and prevalence in Ixodes ricinus midgut and salivary glands. The present study investigated the presence of 32 pathogen species in the midgut and salivary glands of unfed I. ricinus males and females using high-throughput microfluidic real-time PCR. Such an approach is important for enriching the knowledge about pathogen distribution in distinct tick organs which should lead to a better understanding I. ricinus-borne disease epidemiology. Borrelia lusitaniae, Borrelia spielmanii and Borrelia garinii, were detected in both midgut and salivary glands suggesting that the migration of these pathogens between these two organs might not be triggered by the blood meal. In contrast, Borrelia afzelii was detected only in the tick midgut. Anaplasma phagocytophilum and Rickettsia helvetica were the most frequently detected in ticks and were found in both males and females in the midgut and salivary glands. In contrast, Rickettsia felis was only detected in salivary glands. Finally, Borrelia miyamotoi and Babesia venatorum were detected only in males in both midguts and salivary glands. Among all collected ticks, between 10-21% of organs were co-infected. The most common bacterial co-infections in male and female midgut and salivary glands were Rickettsia helvetica + Anaplasma phagocytophilum and Rickettsia helvetica + Borrelia lusitaniae, respectively. Analysing tick-borne pathogen (TBP) presence in specific tick organs enabled us to (i) highlight contrasting results with well-established transmission mechanism postulates; (ii) venture new hypotheses concerning pathogen location and migration from midgut to salivary glands; and (iii) suggest other potential associations between pathogens not previously detected at the scale of the whole tick. This work highlights the importance of considering all tick scales (i.e. whole ticks vs organs) to study TBP ecology and represents another step towards improved understanding of TBP transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":30448835,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer's Disease in Transgenic Mice at Different Ages.\nBackgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H2S), is decreased in the brain of Alzheimer's disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H2S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H2S injections are neuroprotective in an early phase of preclinical AD. This study focuses on the possible neuroprotection of a chronic treatment with an H2S donor and sulfurous water (rich of H2S) in a severe transgenic 3\u00d7Tg-AD mice model. 3\u00d7Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H2S donor and sulfurous water (rich of H2S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid\/tau cascade, excitotoxic, inflammatory and apoptotic responses. Three months of treatments with H2S significantly protected against impairment in learning and memory in a severe 3\u00d7Tg-AD mice model, at both ages studied, and reduced the size of Amyloid \u03b2 plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. Our findings indicate that appropriate treatments with various sources of H2S, might represent an innovative approach to counteract early and severe AD progression in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":1761481,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Intramuscular accumulation of prostaglandins during static contraction of the cat triceps surae.\nWe previously demonstrated that muscle afferent endings are sensitized by exogenous prostaglandins during static contraction of skeletal muscle. The purpose of this study was to determine whether 30 s of static hindlimb contraction, induced by electrical stimulation of the cat sciatic nerve, increases the concentration of immunoreactive prostaglandin E2 (iPGE2) and 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2) in muscle tissue. In addition, the role of ischemia in augmenting prostanoid production was examined. Gastrocnemius muscle was obtained by freeze-clamping tissue, and prostaglandins were extracted from muscle homogenates and measured by radioimmunoassay. Compared with precontraction values, high-intensity (68% of maximal tension) static contraction elevated gastrocnemius iPGE2 and i6-keto-PGF1 alpha by 45 and 53%, respectively (P less than 0.01). Likewise, when blood flow to the gastrocnemius was attenuated by arterial occlusion during and 2 min before low-intensity contraction (29% maximal tension), the intramuscular iPGE2 concentration was increased by 71% (P less than 0.01). Conversely, low-intensity contraction (30% of maximal tension) and arterial occlusion without contraction did not alter the concentration of either prostanoid. Our findings demonstrate that prostaglandins accumulate in muscle during static contraction. We believe that local muscle ischemia may provide a stimulus for this phenomenon. These prostaglandins therefore are available to sensitize afferent endings responsible for reflex adjustments during static muscle contraction.","subset":"pubmed_abstract"} +{"meta":{"pmid":28728620,"dup_signals":{"dup_doc_count":11}},"text":"Insulin Resistance and Hypertension in Obese Youth With Sleep-Disordered Breathing Treated With Positive Airway Pressure: A Prospective Multicenter Study.\nThere is evidence that cardiometabolic disease associated with obesity and sleep-disordered breathing (SDB) in adults is present in youth. SDB is often treated with positive airway pressure (PAP) in youth with obesity. Our aims were to determine: (1) the prevalence of cardiometabolic disease and (2) whether PAP improves markers of cardiometabolic disease, in youth with obesity and newly diagnosed moderate-severe SDB. A prospective multicenter cohort study was conducted in youth (8 to 16 years old) with obesity, prescribed PAP therapy for newly diagnosed moderate-severe SDB. Assessments occurred at baseline and at 6 and 12 months. Outcomes included markers of insulin resistance (change in homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months = primary outcome), hypertension (24-hour ambulatory\/blood pressure) and inflammation (high-sensitivity C-reactive protein: hs-CRP). Twenty-seven participants were enrolled. Of those with baseline testing available, 10\/25 (40%) had HOMA-IR above the 97th percentile, 10\/23 (44%) were hypertensive, 16\/23 (70%) had loss of nocturnal blood pressure dip and hs-CRP was elevated in 16\/27 (64%). There were no significant changes over time in markers of metabolic dysfunction or blood pressure, nor between PAP-adherent and non-adherent subgroups. In youth with obesity and SDB, metabolic dysfunction and hypertension were highly prevalent. There were no statistically significant improvements in cardiometabolic markers 1 year after the prescription of PAP therapy, although clinically relevant improvements were seen in insulin resistance and systolic blood pressure load, important predictors of future risk of cardiovascular disease. Larger, longer-term studies are needed to determine whether PAP improves cardiometabolic outcomes in obese youth. A commentary on this article appears in this issue on page 1025.","subset":"pubmed_abstract"} +{"meta":{"pmid":23970363,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2014-10":1,"2015-06":1,"unknown":12}}},"text":"Differential effects of nonselective versus selective \u03b2-blockers on cardiac sympathetic activity and hemostasis in patients with heart failure.\nCarvedilol, a nonselective \u03b2-blocker, may be more effective than the selective \u03b2-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either \u03b2-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability. In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16\/Gln27 (n = 13) or Gly16\/Glu27 haplotype (n = 8) of the \u03b22-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis. (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% \u00b1 3.9% vs. 22.1% \u00b1 2.8%, respectively, P = 0.003), irrespective of \u03b22-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% \u00b1 13% vs. 157% \u00b1 13%, respectively, P = 0.01), irrespective of \u03b22-adrenergic receptor haplotype. Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16\/Gln27 and Gly16\/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of \u03b22-receptor haplotype status.","subset":"pubmed_abstract"} +{"meta":{"pmid":30311621,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Interaction study of cancer cells and fibroblasts on a spatially confined oxygen gradient microfluidic chip to investigate the tumor microenvironment.\nThis paper reports a single-layered microfluidic device for studying the interaction of cancer cells and fibroblasts in an oxygen gradient. This gradient can be established from 1.9% to 18.8% using a spatially confined oxygen scavenging chemical reaction. Due to the spatial design of the chip, only cancer cells can sustain low oxygen conditions when co-cultured with fibroblasts in the adjacent channels, simulating the cell-cell interactions of the hypoxic cancer cells and the surrounding fibroblasts in tumor microenvironment in vivo. Moreover, a cell migration assay is performed on the chip for studying the tumor invasion ability. The results show that the migration speed of B16 cells is increased by hypoxia and the co-culture with L929 cells. In addition, we use ELISA to quantify the migration-related cytokines transforming growth factor-\u03b21 (TGF-\u03b21) in the microfluidic system. Our results confirm interaction between cancer cells and fibroblasts. This microfluidic device provides new insight for the investigation of tumor microenvironment and cell interactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30592746,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":9}}},"text":"A comparison study of five different methods to measure carotenoids in biofortified yellow cassava (Manihot esculenta).\nThe most commonly used method for measuring carotenoid concentration is high-performance liquid chromatography (HPLC). Nevertheless, easier, quicker, and less costly proxy methods exist. We aimed to determine the diagnostic performance of several proxy methods: the spectrophotometer, iCheck Carotene, and near-infrared spectroscopy using both a desktop (dNIRS) and a portable (pNIRS) device for the measurement of total carotenoid concentration (TCC) and all-trans-\u03b2-carotene concentration (trans-BC) in 30 fresh cassava (Manihot esculenta Crantz) storage roots in comparison with HPLC. The spectrophotometer presented the highest predictability for TCC, followed by iCheck, dNIRS, and pNIRS. The dNIRS showed the highest predictability and agreement for trans-BC. The pNIRS showed the poorest repeatability and greatest underestimations compared with HPLC. The agreement between all methods was lower for higher carotenoid concentration, with the exception of the spectrophotometer. According to our results, and for screening purposes, the measurement of carotenoids in fresh cassava roots can be carried out by spectrophotometer, iCheck Carotene and NIRS methods depending on the availability of equipment.","subset":"pubmed_abstract"} +{"meta":{"pmid":21534474,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Detection and identification of Phytophthora alni.\nIn 2004 Brasier et al. described new species--Phytophthora alni, which was especially aeggressive to alder. Now, this Phytophthora disease of alder is widely distributed in Europe as well as in Poland. In this research note we report on identification and detection of P. alni from water and soil samples using PCR method with species-specific primers. Dilution series of P. alni zoospore were used to test the potential sensitivity of the PCR detection methods. Zoospores of P. alni were produced by flooding of 1-week-old Frozen Pea Medium (FPM) cultures in Petri dishes with 30 ml distilled water. The dishes were incubated at 20 degrees C. After 5 days, sporangial production was checked using a binocular microscope and plates were placed at 4 degrees C for 1 h to enhance zoospore release. Zoospores were counted under the microscope using Burker's cabin. A dilution series of zoospores ranging from 5 to 5000 per 200 microl was prepared in autoclaved distilled water and in 1 g samples of autoclaved soil. DNA was extracted from artificially infected water and soil, and purified using the CleanUp Kit (A&A Biotechnology). Zoospores of P. alni in the water were detected by PCR in 5 x 10(3), 5 x 10(2), 5 x 10(1) concentrations. In case of detecting spores in the artificially infected soil it succeeded only for two highest concentrations, i.e. 5 x 10(3), 5 x 10(2) and only when the DNA was additionally purified.","subset":"pubmed_abstract"} +{"meta":{"pmid":35901680,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Natural history of posterior fetal cephaloceles and incidence of progressive cephalocele herniation.\nIn utero repair of fetal posterior cephaloceles (meningocele and encephalocele) is being performed based on the premise that fetal surgery prevents progressive herniation of neural tissue and brain damage during pregnancy. However, the extent to which progressive herniation occurs during pregnancy, specifically from prenatal diagnosis to after delivery, is not well known. The objective of this study was to describe the natural history of patients with fetal cephaloceles focusing on the incidence of progressive herniation. The authors conducted a retrospective cohort study of all patients referred to their center for posterior fetal cephalocele between 2006 and 2021. All patients underwent prenatal and postnatal MRI. Progressive herniation (primary outcome) was defined as an increase in the absolute volume of neural tissue within the cephalocele of > 5% or new herniation of a critical structure into the cephalocele. Total brain and cephalocele volumes were calculated to determine herniation progression from prenatal to postnatal MRI. Information on the presence of hydrocephalus, epilepsy, and developmental delay (secondary outcomes) was collected at 1 year of age. Twenty patients met all study criteria. Ten patients (50%; 95% CI 0.27-0.73) demonstrated progressive herniation from prenatal to postnatal MRI. Three patients with progressive herniation were diagnosed with a meningocele prenatally and had an encephalocele postnatally. Two patients without progression had meningocele identified prenatally that regressed and became atretic by birth. Both prenatal hindbrain herniation (p = 0.03) and prenatal microcephaly (p = 0.05) were predictive of progressive herniation. The rates of hydrocephalus (44%), epilepsy (44%), and developmental delay (63%) were not associated with the occurrence of progressive herniation in this study. In this study, progressive herniation was not a rare event (50%). Fetal hindbrain herniation and fetal microcephaly were associated with the occurrence of progressive herniation. These results support further investigations into why progressive herniation occurs in utero and if progressive cerebral herniation in utero plays a significant role in determining clinical outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":23037440,"dup_signals":{"dup_doc_count":28,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2015-18":1,"2024-18":1,"unknown":24}}},"text":"Method to map individual electromagnetic field components inside a photonic crystal.\nWe present a method to map the absolute electromagnetic field strength inside photonic crystals. We apply the method to map the dominant electric field component Ez of a two-dimensional photonic crystal slab at microwave frequencies. The slab is placed between two mirrors to select Bloch standing waves and a subwavelength spherical scatterer is scanned inside the resulting resonator. The resonant Bloch frequencies shift depending on the electric field at the position of the scatterer. To map the electric field component Ez we measure the frequency shift in the reflection and transmission spectrum of the slab versus the scatterer position. Very good agreement is found between measurements and calculations without any adjustable parameters.","subset":"pubmed_abstract"} +{"meta":{"pmid":7650462,"dup_signals":{"dup_doc_count":58,"dup_dump_count":37,"dup_details":{"curated_sources":4,"2023-50":6,"2023-40":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":2,"2021-39":2,"2021-25":2,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":1,"2019-09":2,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-13":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":1,"2017-22":1,"2014-23":1,"2014-15":3,"2024-22":1,"2024-18":2,"2024-26":1}}},"text":"Hormone replacement therapy: characteristics of users and non-users in a British general practice cohort identified through computerised prescribing records.\nTo assess the feasibility of recruiting a cohort of women, including long term users of postmenopausal hormone replacement therapy (HRT), through computerised general practice prescribing records, and to compare clinical and demographic characteristics of users and non-user controls. Cross sectional analysis of questionnaire data. Subjects were recruited through 17 general practices in the Oxfordshire, south west Thames, and north west Thames regions that contributed to the VAMP Research Database. A total of 2964 women aged 45-64 years were identified. Altogether 1482 were long term (> 1 year) users of HRT and 1482 were non-user controls: 1037 (70%) of the users and 819 (55.3%) of the controls agreed to participate and provided questionnaire data. Users of HRT were more likely to have undergone hysterectomy than controls. Most women with a history of hysterectomy used unopposed oestrogen, while those with intact uteri generally used a combination of oestrogen and a progestagen. Among women who had undergone hysterectomy, HRT users did not differ significantly from controls over a range of demographic and clinical characteristics but they were more likely to be past users of oral contraceptives. Among women with intact uteri, users were similar to controls in terms of reported clinical characteristics, but were of higher social class and were more likely to be past users of oral contraceptives and to have had a mammogram after the age of 50. Compared with the general population, all categories of women recruited to the study were of higher social class and exhibited more health conscious behaviours. Electronic general practice prescribing records provide a feasible and efficient method for recruiting women to a cohort of HRT. Women who agreed to participate in this study were not representative of the general population, emphasising the importance of internal controls in such a study. Among participants, HRT users who had not undergone hysterectomy showed evidence of better health than non-users on some dimensions. In the whole sample, however, there were no appreciable differences in social class and self reported health indicators between users and controls.","subset":"pubmed_abstract"} +{"meta":{"pmid":9064319,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-30":1,"unknown":9}}},"text":"A single T cell receptor recognizes structurally distinct MHC\/peptide complexes with high specificity.\nThe 2C T cell is a CD8+, alloreactive T cell, which recognizes cells bearing Ld and Kbm3 class I major histocompatability complex molecules. Here, we characterize an allopeptide, designated dEV-8, that is a ligand in the Kbm3 molecule for the 2C TCR but is not a ligand in the Ld molecule. By biochemical and immunological properties, dEV-8 is distinct from P2Ca, the Ld allopeptide that is also recognized by the 2C TCR. Using the deduced amino acid sequence of dEV-8, we isolate a candidate endogenous source of the peptide. The endogenous protein, MLRQ, contains a peptide sequence identical to dEV-8. This degenerate recognition of two distinct peptide\/MHC complexes by a single TCR has important implications for understanding allorecognition.","subset":"pubmed_abstract"} +{"meta":{"pmid":18357476,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-14":1,"2021-25":1,"2021-21":1,"2019-30":1,"2019-22":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-17":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2023-40":1,"2017-13":2,"2013-20":1,"2024-10":1}}},"text":"Do chimpanzees learn reputation by observation? Evidence from direct and indirect experience with generous and selfish strangers.\nCan chimpanzees learn the reputation of strangers indirectly by observation? Or are such stable behavioral attributions made exclusively by first-person interactions? To address this question, we let seven chimpanzees observe unfamiliar humans either consistently give (generous donor) or refuse to give (selfish donor) food to a familiar human recipient (Experiments 1 and 2) and a conspecific (Experiment 3). While chimpanzees did not initially prefer to beg for food from the generous donor (Experiment 1), after continued opportunities to observe the same behavioral exchanges, four chimpanzees developed a preference for gesturing to the generous donor (Experiment 2), and transferred this preference to novel unfamiliar donor pairs, significantly preferring to beg from the novel generous donors on the first opportunity to do so. In Experiment 3, four chimpanzees observed novel selfish and generous acts directed toward other chimpanzees by human experimenters. During the first half of testing, three chimpanzees exhibited a preference for the novel generous donor on the first trial. These results demonstrate that chimpanzees can infer the reputation of strangers by eavesdropping on third-party interactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":28001444,"dup_signals":{"dup_doc_count":42,"dup_dump_count":25,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":2,"2023-14":2,"2022-49":2,"2022-27":2,"2022-05":2,"2021-43":1,"2021-39":4,"2021-31":2,"2021-25":1,"2021-17":2,"2021-10":1,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":3,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2023-50":1,"2024-18":1,"2024-10":1,"2024-22":1}}},"text":"Vitamin D Receptor Expression in Plasmablastic Lymphoma and Myeloma Cells Confers Susceptibility to Vitamin D.\nPlasmablastic B-cell malignancies include plasmablastic lymphoma and subsets of multiple myeloma and diffuse large B-cell lymphomaDLBCL. These diseases can be difficult to diagnose and treat, and they lack well-characterized cell line models. Here, immunophenotyping and FOXP1 expression profiling identified plasmablastic characteristics in DLBCL cell lines HLY-1 and SU-DHL-9, associated with CTNNAL1, HPGD, RORA, IGF1, and\/or vitamin D receptor (VDR) transcription. We demonstrated VDR protein expression in primary plasmablastic tumor cells and confirmed in cell lines expression of both VDR and the metabolic enzyme CYP27B1, which catalyzes active vitamin D3 production. Although Vdr and Cyp27b1 transcription in normal B cells were activated by interleukin 4 (IL-4) and CD40 signaling, respectively, unstimulated malignant plasmablastic cells lacking IL-4 expressed both VDR and CYP27B1. Positive autoregulation evidenced intact VDR function in all plasmablastic lines, and inhibition of growth by active vitamin D3 was both dependent on MYC protein inhibition and could be enhanced by cotreatment with a synthetic ROR ligand SR-1078. Furthermore, a VDR polymorphism, FOK1, was associated with greater vitamin D3-dependent growth inhibition. In summary, HLY-1 provides an important model of strongly plasmablastic lymphoma, and disruption of VDR pathway activity may be of therapeutic benefit in both plasmablastic lymphoma and myeloma.","subset":"pubmed_abstract"} +{"meta":{"pmid":11697363,"dup_signals":{"dup_doc_count":39,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":4,"2024-22":5,"2024-18":4,"2024-10":3,"2024-30":1,"unknown":20}}},"text":"Diversity of Salmonella serotypes in cull (market) dairy cows at slaughter.\nTo determine the diversity of Salmonella serotypes isolated from a large population of cull (market) dairy cows at slaughter. Cross-sectional study. Salmonella organisms isolated from the cecal-colon contents of 5,087 market dairy cows. During winter and summer 1996, cecal-colon contents of cull dairy cows at slaughter were obtained from 5 US slaughter establishments. Specimens were subjected to microbiologic culturing for Salmonella spp at 1 laboratory. Identified isolates were compared with Salmonella isolation lists published by the Centers for Disease Control and Prevention (CDC) and the National Veterinary Services Laboratory (NVSL) for approximately the same period. The Simpson diversity index was used to calculate the likelihood that Salmonella isolates selected randomly by establishment were different. Of 58 Salmonella serotypes identified, Salmonella ser. Montevideo was the most prevalent. Two of the top 10 CDC serotypes identified from in 1996, Salmonella ser. Typhimurium and S Montevideo, appeared on our top 10 list; 8 of the top 10 were found on NVSL listings. Thirty-one of 59 S. Typhimurium isolates were identified as DT104 and found at a west slaughter establishment, 30 during the winter and 1 during the summer. The greatest diversity of serotypes was at a southeast establishment during the summer; the least diversity was at a central establishment in the winter. 58 Salmonella serotypes were isolated from market dairy cows at slaughter and could pose a threat for food-borne illness. Salmonella Montevideo was the most frequently isolated serotype and may contribute substantially to salmonellosis in dairy cattle.","subset":"pubmed_abstract"} +{"meta":{"pmid":16947423,"dup_signals":{"dup_doc_count":46,"dup_dump_count":39,"dup_details":{"curated_sources":3,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":1,"2014-15":1,"2018-26":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in type IX collagen.\nTo examine the pathogenetic mechanisms of osteoarthritis (OA)-like changes in Col9a1-\/- mice, which are deficient in type IX collagen. Knee joints and temporomandibular joints (TMJs) from Col9a1-\/- mice and their wild-type (Col9a1+\/+) littermates were examined by light microscopy. Immunohistochemical staining was performed to examine the expression of matrix metalloproteinase 3 (MMP-3) and MMP-13, degraded type II collagen, and the discoidin domain receptor 2 (DDR-2) in knee joints. Cartilage mechanics were also evaluated for compressive properties by microindentation testing of the tibial plateau and for tensile properties by osmotic loading of the femoral condyle. Histologic analysis showed age-dependent OA-like changes in the knee and TMJs of Col9a1-\/- mice starting at the age of 3 months. At the age of 6 months, enhanced proteoglycan degradation was observed in the articular cartilage of the knee and TMJs of the mutant mice. The expression of MMP-13 and DDR-2 protein and the amount of degraded type II collagen were higher in the knee joints of Col9a1-\/- mice than in their wild-type littermates at the age of 6 months. Changes in cartilage mechanics were observed in the femoral and tibial plateaus of Col9a1-\/- mice at 6 months, including a decrease in the compressive modulus and uniaxial modulus. At 3 and 6 months of age, tibial cartilage in Col9a1-\/- mice was found to be more permeable to fluid flow, with an associated compromise in the fluid pressurization mechanism of load support. All of these changes occurred only at medial sites. Lack of type IX collagen in Col9a1-\/- mice results in age-dependent OA-like changes in the knee joints and TMJs.","subset":"pubmed_abstract"} +{"meta":{"pmid":8286755,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Rapamycin, a potent inhibitor of T-cell function, prevents graft rejection in murine recipients of allogeneic T-cell-depleted donor marrow.\nWe investigated the ability of the macrolide antifungal agent rapamycin (RAPA) to inhibit the rejection of T-cell-depleted (TCD) donor bone marrow (BM) transplanted into major histocompatibility complex (MHC)-disparate irradiated recipients. RAPA (1.5 mg\/kg) was administered for 14 days beginning on the day of transplant. In the present study, we have tested RAPA administration in two types of fully allogeneic BM transplantation (BMT) systems in which host T cells mediate the rejection of TCD BM grafts (DBA\/1 transplanted into C57BL\/6 and BALB\/c transplanted into C57BL\/6). In both instances, RAPA administration prevented the rejection of the donor graft, accelerated post-BMT hematopoietic recovery, and did not compromise recipient survival. Sequential post-BMT fluorescence-activated cell sorter analysis of the spleen showed that RAPA administration inhibited host CD4+ and CD8+ T-cell expansion that leads to graft rejection. To further investigate the effect of RAPA on T-cell subpopulations, we used two congenic donor mouse stains with isolated MHC class I (bm1) or class II (bm12) mutations. In these studies, we showed that RAPA administration can inhibit MHC class I-restricted CD8+ or class II-restricted CD4+ T-cell-mediated graft rejection without compromising recipient survival. The RAPA-facilitated alloengraftment is multilineage and durable. We have also shown that RAPA speeds hematopoietic recovery post-BMT. We conclude that RAPA represents a new therapeutic modality for promoting alloengraftment and accelerating hematopoietic recovery.","subset":"pubmed_abstract"} +{"meta":{"pmid":21866998,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":17}}},"text":"Attosecond control in photoionization of hydrogen molecules.\nWe report experiments where hydrogen molecules were dissociatively ionized by an attosecond pulse train in the presence of a near-infrared field. Fragment ion yields from distinguishable ionization channels oscillate with a period that is half the optical cycle of the IR field. For molecules aligned parallel to the laser polarization axis, the oscillations are reproduced in two-electron quantum simulations, and can be explained in terms of an interference between ionization pathways that involve different harmonic orders and a laser-induced coupling between the 1s\u03c3(g) and 2p\u03c3(u) states of the molecular ion. This leads to a situation where the ionization probability is sensitive to the instantaneous polarization of the molecule by the IR electric field and demonstrates that we have probed the IR-induced electron dynamics with attosecond pulses.","subset":"pubmed_abstract"} +{"meta":{"pmid":23030654,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":8}}},"text":"Screening-level risk assessment for styrene-acrylonitrile (SAN) trimer detected in soil and groundwater.\nA screening-level risk assessment was conducted for styrene-acrylonitrile (SAN) Trimer detected at the Reich Farm Superfund site in Toms River, NJ. Consistent with a screening-level approach, on-site and off-site exposure scenarios were evaluated using assumptions that are expected to overestimate actual exposures and hazards at the site. Environmental sampling data collected for soil and groundwater were used to estimate exposure point concentrations. Several exposure scenarios were evaluated to assess potential on-site and off-site exposures, using parameter values for exposures to soil (oral, inhalation of particulates, and dermal contact) and groundwater (oral, dermal contact) to reflect central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. Three reference dose (RfD) values were derived for SAN Trimer for short-term, subchronic, and chronic exposures, based upon its effects on the liver in exposed rats. Benchmark (BMD) methods were used to assess the relationship between exposure and response, and to characterize appropriate points of departure (POD) for each RfD. An uncertainty factor of 300 was applied to each POD to yield RfD values of 0.1, 0.04, and 0.03 mg\/kg-d for short-term, subchronic, and chronic exposures, respectively. Because a chronic cancer bioassay for SAN Trimer in rats (NTP 2011a) does not provide evidence of carcinogenicity, a cancer risk assessment is not appropriate for this chemical. Potential health hazards to human health were assessed using a hazard index (HI) approach, which considers the ratio of exposure dose (i.e., average daily dose, mg\/kg-d) to toxicity dose (RfD, mg\/kg-d) for each scenario. All CTE and RME HI values are well below 1 (where the average daily dose is equivalent to the RfD), indicating that there is no concern for potential noncancer effects in exposed populations even under the conservative assumptions of this screening-level assessment.","subset":"pubmed_abstract"} +{"meta":{"pmid":18206866,"dup_signals":{"dup_doc_count":11}},"text":"Development of the proepicardial organ in the zebrafish.\nThe epicardium is the last layer of the vertebrate heart to form, surrounding the heart muscle during embryogenesis and providing signaling cues essential to the continued growth and differentiation of the heart. This outer layer of the heart develops from a transient structure, the proepicardial organ (PEO). Despite its essential roles, the early signals required for the formation of the PEO and the epicardium remain poorly understood. The molecular markers wt1 and tcf21 are used to identify the epicardial layer in the zebrafish heart, to trace its development and to determine genes required for its normal development. Disruption of lateral plate mesoderm (LPM) migration through knockdown of miles apart or casanova leads to cardia bifida with each bilateral heart associated with its own PEO, suggesting that the earliest progenitors of the epicardium lie in the LPM. Using a gene knockdown approach, a genetic framework for PEO development is outlined. The pandora\/spt6 gene is required for multiple cardiac lineages, the zinc-finger transcription factor wt1 is required for the epicardial lineage only and finally, the cell polarity genes heart and soul and nagie oko are required for proper PEO morphogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":7516474,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":1,"unknown":11}}},"text":"Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes.\nPeripheral blood T lymphocytes require two sequential mitogenic signals to reenter the cell cycle from their natural, quiescent state. One signal is provided by stimulation of the T-cell antigen receptor, and this induces the synthesis of both cyclins and cyclin-dependent kinases (CDKs) that are necessary for progression through G1. Antigen receptor stimulation alone, however, is insufficient to promote activation of G1 cyclin-Cdk2 complexes. This is because quiescent lymphocytes contain an inhibitor of Cdk2 that binds directly to this kinase and prevents its activation by cyclins. The second mitogenic signal, which can be provided by the cytokine interleukin 2, leads to inactivation of this inhibitor, thereby allowing Cdk2 activation and progression into S phase. Enrichment of the Cdk2 inhibitor from G1 lymphocytes by cyclin-CDK affinity chromatography indicates that it may be p27Kip1. These observations show how sequentially acting mitogenic signals can combine to promote activation of cell cycle proteins and thereby cause cell proliferation to start. CDK inhibitors have been shown previously to be induced by signals that negatively regulate cell proliferation. Our new observations show that similar proteins are down-regulated by positively acting signals, such as interleukin 2. This finding suggests that both positive and negative growth signals converge on common targets which are regulators of G1 cyclin-CDK complexes. Inactivation of G1 cyclin-CDK inhibitors by mitogenic growth factors may be one biochemical pathway underlying cell cycle commitment at the restriction point in G1.","subset":"pubmed_abstract"} +{"meta":{"pmid":23378693,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Hemodynamics of arterial and venous circulation in the intrauterine fetal evaluation.\nThe purpose of each antenatal control focuses on the detection and prevention of hypoxic-ischemic injury and fetal death (1)) using modern biophysical tests and Doppler parameters. This study examines the correlation of changes in arterial compared to venous hemodynamics of the fetus and is determined by the most sensitive and most specific Doppler parameter in the assessment of intrauterine fetal status. The study was conducted as prospective and included 119 pregnant women. All subjects underwent NST (nonstres test), and Doppler measurements of blood flow in the umbilical artery (Aum), fetal aorta (Ao) and the central cerebral artery (MCA). In case of borderline and pathological arterial flow was measured through the ductus venozus (DV) and umbilical vein (VU). At birth to the child was determined umbilical artery blood pH and Apgar score (AS) in the first minute. Based on the clinical condition of the newborn and outcome was calculated perinatal morbidity and mortality. In all cases with a pathological arterial flow, which is verified during measurement also the pathological venous flow and confirmed fetal acidemia at birth and low Apgar scores? In this group, the two neonates died in the first week. There is a justification for the analysis of venous flow in the event borderline and pathologic findings in fetal arterial system. It has been proven that the cerebroumbilical (C\/U) index is most effective parameter in predicting changes in the venous system and this the most sensitive Doppler parameter in predicting fetal acidosis and the most specific Doppler flow through the central cerebral artery.","subset":"pubmed_abstract"} +{"meta":{"pmid":29079526,"dup_signals":{"dup_doc_count":13,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2020-05":1,"2019-51":1,"2019-35":1,"2019-13":2,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2023-50":1}}},"text":"Synergistic enhancement of topotecan-induced cell death by ascorbic acid in human breast MCF-7 tumor cells.\nTopotecan, a derivative of camptothecin, is an important anticancer drug for the treatment of various human cancers in the clinic. While the principal mechanism of tumor cell killing by topotecan is due to its interactions with topoisomerase I, other mechanisms, e.g., oxidative stress induced by reactive free radicals, have also been proposed. However, very little is known about how topotecan induces free radical-dependent oxidative stress in tumor cells. In this report we describe the formation of a topotecan radical, catalyzed by a peroxidase-hydrogen peroxide system. While this topotecan radical did not undergo oxidation-reduction with molecular O2, it rapidly reacted with reduced glutathione and cysteine, regenerating topotecan and forming the corresponding glutathiyl and cysteinyl radicals. Ascorbic acid, which produces hydrogen peroxide in tumor cells, significantly increased topotecan cytotoxicity in MCF-7 tumor cells. The presence of ascorbic acid also increased both topoisomerase I-dependent topotecan-induced DNA cleavage complex formation and topotecan-induced DNA double-strand breaks, suggesting that ascorbic acid participated in enhancing DNA damage induced by topotecan and that the enhanced DNA damage is responsible for the synergistic interactions of topotecan and ascorbic acid. Cell death by topotecan and the combination of topotecan and ascorbic acid was predominantly due to necrosis of MCF-7 breast tumor cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":24870582,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Tibialis anterior moment arm: effects of measurement errors and assumptions.\nAccurate estimates of tibialis anterior (TA) muscle force are important in many contexts. Two approaches commonly used to estimate moment arms are the tendon excursion (TE) and geometric (GEO) methods. Previous studies report poor agreement between the two approaches. The purposes of this study were to 1) assess the effect of methodological variations in the two methods of moment arm estimation and 2) determine how these variations affect agreement between the methods. TA moment arms were determined using TE and GEO. Errors associated with tendon stretch\/hysteresis, talus rotation relative to the foot, and the location of the line of action were investigated. For TE, large errors in moment arm estimates across the range of motion were found when tendon length changes (P = 0.001) were not corrected for. For GEO, the estimated moment arm was reduced at an ankle angle of -15\u00b0 when discrepancies between talus and foot rotations were accounted for or when an alternative tendon line of action was used either separately (effect size (ES), 0.46 and 0.58, respectively; P > 0.05) or together (ES, 0.89; P > 0.05). TE-derived moment arms were smaller than GEO-derived moment arms (ES, 0.68-4.86, varying by angle) before accounting for sources of error. However, these differences decreased after error correction (ES, 0.09-1.20, P > 0.05). Nonetheless, the shape of the moment arm-joint angle relation was curvilinear for TE but linear for GEO. Of all methodological modifications, accounting for tendon length changes had the largest effect on TA moment arm estimates. We conclude that the TE method is viable to determine TA moment arms as long as changes in tendon length are accounted for.","subset":"pubmed_abstract"} +{"meta":{"pmid":28945469,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Pharmacologic Protection of Mitochondrial DNA Integrity May Afford a New Strategy for Suppressing Lung Ischemia-Reperfusion Injury.\nLung ischemia-reperfusion (IR) injury contributes to post-transplant complications, including primary graft dysfunction. Decades of reports show that reactive oxygen species generated during lung IR contribute to pulmonary vascular endothelial barrier disruption and edema formation, but the specific target molecule(s) that \"sense\" injury-inducing oxidant stress to activate signaling pathways culminating in pathophysiologic changes have not been established. This review discusses evidence that mitochondrial DNA (mtDNA) may serve as a molecular sentinel wherein oxidative mtDNA damage functions as an upstream trigger for lung IR injury. First, the mitochondrial genome is considerably more sensitive than nuclear DNA to oxidant stress. Multiple studies suggest that oxidative mtDNA damage could be transduced to physiologic dysfunction by pathways that are either a direct consequence of mtDNA damage per se or involve formation of proinflammatory mtDNA damage-associated molecular patterns. Second, transgenic animals or cells overexpressing components of the base excision DNA repair pathway in mitochondria are resistant to oxidant stress-mediated pathophysiologic effects. Finally, published and preliminary studies show that pharmacologic enhancement of mtDNA repair or mtDNA damage-associated molecular pattern degradation suppresses reactive oxygen species-induced or IR injury in multiple organs, including preclinical models of lung procurement for transplant. Collectively, these findings point to the interesting prospect that pharmacologic enhancement of DNA repair during procurement or ex vivo lung perfusion may increase the availability of lungs for transplant and reduce the IR injury contributing to primary graft dysfunction.","subset":"pubmed_abstract"} +{"meta":{"pmid":20849031,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The effect of causal chain length on counterfactual conditional reasoning.\nWe investigated German and Nichols' finding that 3-year-olds could answer counterfactual conditional questions about short causal chains of events, but not long. In four experiments (N = 192), we compared 3- and 4-year-olds' performance on short and long causal chain questions, manipulating whether the child could draw on general knowledge to answer. We failed to replicate German and Nichols' result, finding instead that in two experiments (Experiments 1 and 3) there was no difference in performance on short and long causal chain questions and in two experiments (Experiments 2 and 4) children showed the opposite pattern: short causal chain questions were more difficult than long. These two unexpected patterns of results were replicated in a fifth study (N = 97). Children with lower language ability found short causal chains more difficult than long. Performance by children with higher language ability was unaffected by the length of the causal chain they had to consider. We found no evidence that children showed precocious counterfactual thinking when asked about recent events in a causal chain and conclude that counterfactual thinking develops after 4 years of age.","subset":"pubmed_abstract"} +{"meta":{"pmid":20580214,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-24":1,"2019-43":1,"2023-23":1,"2024-26":2,"2024-22":1,"2024-18":1}}},"text":"Bacteria and MAMP-induced morphogenesis of the immune system.\nTo metazoans, bacteria are more than just potential pathogens. Many examples now document the role of bacterial symbionts in complementing the host for its full development and increasing its digestive and protective functions. Here, we discuss the role of Gram-negative bacteria in the development of intestinal lymphoid tissues and the impact of Segmented Filamentous Bacteria and Bacteroides on intestinal immunity and homeostasis. Furthermore, we discuss the potentially beneficial role of Helicobacter pylori on immunity of the stomach and beyond, even though this bacteria is primarily known for its pathogenicity. Altogether, these and other symbiotic bacteria may manipulate the host and the host immune system through the shedding of MAMPs that cross not only the epithelial barriers, but also permeate the circulation and impact every tissue and function of the host.","subset":"pubmed_abstract"} +{"meta":{"pmid":23575031,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-30":1,"unknown":11}}},"text":"Study protocol for iQuit in Practice: a randomised controlled trial to assess the feasibility, acceptability and effectiveness of tailored web- and text-based facilitation of smoking cessation in primary care.\nPrimary care is an important setting for smoking cessation interventions. There is evidence for the effectiveness of tailored interventions for smoking cessation, and text messaging interventions for smoking cessation show promise. The intervention to be evaluated in this trial consists of two components: (1) a web-based program designed to be used by a practice nurse or other smoking cessation advisor (SCA); the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker; and (2) a three-month programme of automated tailored text messages sent to the smoker's mobile phone. The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone. The design is a two parallel group randomised controlled trial (RCT). 600 smokers who want to quit will be recruited in up to 30 general practices in the East of England. During a consultation with an SCA, they will be individually randomised by computer program to usual care (Control) or to usual care plus the iQuit system (Intervention). At the four-week follow-up appointment, the SCA will record smoking status and measure carbon monoxide level. There will be two further follow-ups, at eight weeks and six months from randomisation date, by postal questionnaire sent from and returned to the study centre or by telephone interview conducted by a research interviewer. The primary outcome will be self-reported abstinence for at least two weeks at eight weeks. A sample size of 300 per group would give 80% power to detect an increase in quit rate from 20% to 30% (alpha = 0.05, 2-sided test). The main analyses of quit rates will be conducted on an intention-to-treat basis, making the usual assumption that participants lost to follow up are smoking. This trial will focus on acceptability, feasibility and short-term effectiveness. The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness. ISRCTN56702353.","subset":"pubmed_abstract"} +{"meta":{"pmid":23454414,"dup_signals":{"dup_doc_count":47,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2022-49":1,"2022-40":1,"2020-50":1,"2019-51":1,"2019-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":2,"2014-35":1,"2014-15":2,"2023-40":1,"2024-18":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2024-22":1}}},"text":"Assessing vulnerability of marine bird populations to offshore wind farms.\nOffshore wind farms may affect bird populations through collision mortality and displacement. Given the pressures to develop offshore wind farms, there is an urgent need to assess population-level impacts on protected marine birds. Here we refine an approach to assess aspects of their ecology that influence population vulnerability to wind farm impacts, also taking into account the conservation importance of each species. Flight height appears to be a key factor influencing collision mortality risk but improved data on flight heights of marine birds are needed. Collision index calculations identify populations of gulls, white-tailed eagles, northern gannets and skuas as of particularly high concern in Scottish waters. Displacement index calculations identify populations of divers and common scoters as most vulnerable to population-level impacts of displacement, but these are likely to be less evident than impacts of collision mortality. The collision and displacement indices developed here for Scottish marine bird populations could be applied to populations elsewhere, and this approach will help in identifying likely impacts of future offshore wind farms on marine birds and prioritising monitoring programmes, at least until data on macro-avoidance rates become available.","subset":"pubmed_abstract"} +{"meta":{"pmid":19703570,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-17":1,"2020-05":1,"2019-35":1,"2018-39":1,"2018-13":1,"2017-47":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-21":1,"2017-13":1,"2024-26":1}}},"text":"Cingulate activity and fronto-temporal connectivity in people with prodromal signs of psychosis.\nSchizophrenia is associated with fronto-temporal dysconnectivity, but it is not clear whether this is a risk factor for the disorder or is a consequence of the established illness. The aim of the present study was to use fMRI to investigate fronto-temporal connectivity in subjects with prodromal signs of schizophrenia using the Hayling Sentence Completion Task (HSCT). Thirty participants, 15 with an at risk mental state (ARMS) and 15 healthy controls were scanned whilst completing 80 sentence stems. The congruency and constraint of sentences varied across trials. Dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to compare alternative models of connectivity in a task related network. During the HSCT ARMS subjects did not differ from Healthy Controls in terms of fronto-temporal activation, i.e. there was neither a main effect of group nor a group-by-task interaction. However, there was both a significant main effect of group and a significant interaction in the anterior cingulate cortex (ACC), with greater ACC activity in the ARMS subjects. A systematic BMS procedure among 14 alternative DCMs including the ACC, middle frontal, and middle temporal gyri revealed intact task-dependent modulation of fronto-temporal effective connectivity in the ARMS group. However, ARMS subjects showed increased endogenous connection strength between the ACC and the middle temporal gyrus relative to healthy controls. Although task related fronto-temporal integration in the ARMS was intact, this may depend on increased engagement of the ACC which was not observed in healthy control subjects.","subset":"pubmed_abstract"} +{"meta":{"pmid":31381126,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2021-17":1,"2021-04":1,"2020-50":1,"2020-29":2,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":2,"2019-43":1,"2023-06":1,"2024-26":1}}},"text":"Characterisation and in vitro and in vivo evaluation of supercritical-CO2-foamed \u03b2-TCP\/PLCL composites for bone applications.\nMost synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable \u03b2-tricalciumphosphate\/poly(L-lactide-co-\u03b5-caprolactone) (\u03b2-TCP\/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 \u00b0C, tested samples returned to 95 % of their original height. Hydrolytic degradation of \u03b2-TCP\/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, \u03b2-TCP\/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the \u03b2-TCP\/PLCL composite. The elastic and highly porous \u03b2-TCP\/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.","subset":"pubmed_abstract"} +{"meta":{"pmid":27439350,"dup_signals":{"dup_doc_count":31,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2023-50":4,"2023-40":1,"2022-49":3,"2022-40":6,"2022-33":5,"2024-18":4,"2024-10":4}}},"text":"Eastern equine encephalomyelitis virus infection in six captive southern cassowaries (Casuarius casuarius).\nCASE DESCRIPTION Within a 2-week period, 4 southern cassowaries (Casuarius casuarius) at an exhibit at a Virginia zoo died acutely subsequent to eastern equine encephalitis virus (EEEV) infection. This prompted a search for other EEEV outbreaks in cassowaries, which resulted in the identification of 2 additional cassowaries that died of EEEV infection at a conservation center in Florida. CLINICAL FINDINGS Both juvenile and adult birds were affected. Three of the 6 birds died acutely with no premonitory signs. Clinical disease in the other 3 birds was characterized by lethargy and ataxia. Clinicopathologic findings typically included leukocytosis, hyperuricemia, abnormally high liver enzyme activities, and hyper-\u03b2 globulinemia, which was indicative of acute inflammation. TREATMENT AND OUTCOME The 3 birds with clinical disease died despite supportive treatment. Gross abnormalities commonly observed during necropsy included coelomitis and evidence of diarrhea. Frequently observed histologic abnormalities were encephalitis, vasculitis, hepatitis, nephritis, and splenitis. The diagnosis of EEEV infection was confirmed by detection of serum anti-EEEV antibodies or detection of viral RNA in brain tissue by use of a reverse-transcriptase PCR assay. CLINICAL RELEVANCE Findings suggested that EEEV can cause high morbidity and mortality rates in southern cassowaries. Clinical disease might be reduced or prevented by vaccination, isolation of ill birds, and mosquito control strategies.","subset":"pubmed_abstract"} +{"meta":{"pmid":29787357,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":15}}},"text":"Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer: A Randomized Phase III NVALT-11\/DLCRG-02 Study.\nPurpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging-were randomly assigned to either observation or PCI after concurrent\/sequential chemoradiotherapy with or without surgery. The primary end point-development of symptomatic brain metastases at 24 months-was defined as one or a combination of key symptoms that suggest brain metastases-signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms-and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases ( P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":336836,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2019-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2019-47":1,"2017-13":1}}},"text":"Arthritis in rats after systemic injection of streptococcal cells or cell walls.\nFurther investigation of the biological properties of streptococcal cells and their components has produced a model of erosive synovitis in rats. A single intraperitoneal injection of an aqueous suspension of whole cell sonicate of group A streptococci into Sprague-Dawley rats induced an acute arthritis which evolved into a prolonged inflammatory process characterized by several complete or partial remissions, joint deformity, and ankylosis. The toxic moiety is a peptidoglycan-polysaccharide fragment of the cell wall which persists in tissue. Histologic features of the arthritis include an acute exudative phase followed by an erosive synovitis that leads to destruction of cartilage and subchondral bone and fibrous ankylosis of the joints. The arthropathic properties of whole cell sonicates of several species of streptococci are compared along with studies of the ability of heat-killed, whole cells of groups A, B, and C streptococci to induce arthritis in rats. Whole cells induce arthritis after a latent period of 57-120 days when group A cells are injected and 7-10 days when group B cells are tested.","subset":"pubmed_abstract"} +{"meta":{"pmid":25002767,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Unilateral herpes zoster ophthalmicus with bilateral cerebral infarcts in human immunodeficiency virus seropositive patient.\nIschemic stroke is a recognized complication of herpes zoster ophthalmicus. Arterial involvement is usually seen on the side of the rash. It is thought to be due to vessel inflammation by the virus, which travels from the trigeminal ganglion. Few case reports of bilateral and distant site of zoster lesions with stroke in the brain have been described. These reports suggest possibility of contiguous vascular, cerebrospinal fluid (CSF) or hematogenous spread of the virus from the ganglion to the cerebral blood vessels. Therapeutically acyclovir, anticoagulation, and steroids have been used in the treatment of the zoster associated with stroke. We describe a case of immunocompromised patient with ipsilateral zoster ophthalmicus with bilateral anterior circulation strokes, who was treated with above measures and made successful recovery. This report also raises\/supports possible CSF\/vascular\/hematogenous spread of the virus from the ganglion to involve cerebral blood vessels leading to the stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":22938544,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Analysis of miRNA expression under stress in Arabidopsis thaliana.\nMicroRNAs (miRNAs) are a class of small, 21-24 nucleotides long, non-coding RNAs involved in the post-transcriptional regulation of gene expression. Using the array analysis on Arabidopsis thaliana infected with the Oil-seed Rape Mosaic Virus (ORMV), we have found 28 up-regulated miRNAs. From them, six were selected for further validation by Northern blot analysis: miRNA172a, miRNA161, miRNA167a&b, miRNA168a&b, miRNA171a, and miRNA159. In addition, 29 miRNAs were detected in plants exposed to drought stress, 13 of those detected miRNAs were up-regulated and 16 down-regulated miRNAs. Out of 29 differentially expressed miRNAs during the abiotic stress, six miRNAs (167a&b, 168a&b, 173, 171b&c, 399d and 447c) were chosen for Northern blot and RT-PCR analysis to confirm the array results. Interestingly, four out of these six miRNAs, 171b&c, 168a&b, 399d, and 447c, showed very high abundance of pri-miRNAs and pre-miRNAs. Furthermore, mature forms of miRNAs171b&c, 399d, and 447c, were not detectable in the rosette leaves, indicating that miRNA processing is tissue specific. In conclusion, using the array analysis we show that 28 miRNAs are involved in the plant response to viral infection and 29 miRNAs are involved in the regulation of drought stress. We also demonstrate that at least some miRNAs involved in the stress response in Arabidopsis thaliana are regulated at the maturation level. One such example is miRNA 171b&c. This miRNA is transcribed in all tissues, evidenced by its detected pri and pre-miRNA forms; however, its mature form is constitutively or transiently expressed depending on the tissue type.","subset":"pubmed_abstract"} +{"meta":{"pmid":10943858,"dup_signals":{"dup_doc_count":64,"dup_dump_count":37,"dup_details":{"curated_sources":4,"2023-40":5,"2023-23":1,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":2,"2021-49":2,"2021-39":1,"2021-31":2,"2021-21":2,"2021-17":3,"2021-10":2,"2021-04":1,"2020-50":2,"2020-45":2,"2020-40":3,"2019-09":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2024-26":3,"2024-22":1,"2024-18":1,"2024-10":2}}},"text":"Adenovirus-mediated gene transfer of CTLA-4Ig fusion protein in the suppression of experimental autoimmune arthritis.\nBlockade of CD28-B7 interactions with soluble CTLA-4Ig fusion protein (which binds and blocks both B7-1 and B7-2 costimulatory molecules on antigen-presenting cells) has been shown to ameliorate experimental autoimmune diseases such as lupus, experimental autoimmune encephalomyelitis, diabetes, and, in our laboratory, collagen-induced arthritis (CIA). Because prolonged inhibition of this costimulatory pathway may be required, and the adenovirus-mediated gene-transfer technology is very efficient in achieving sustained expression of proteins in vivo, we examined the effects of adenovirally delivered CTLA-4Ig in established murine CIA. Replication-deficient recombinant adenoviruses encoding a chimeric CTLA-4Ig fusion protein, or beta-galactosidase as control, were injected intravenously into male DBA\/1 mice once at arthritis onset. Disease activity was monitored by the assessment of clinical score, paw thickness, and type II collagen (CII)-specific cellular and humoral responses for 3 weeks. Groups of mice were also serially injected with a CTLA-4Ig fusion protein and an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody (mAb), and disease activity was compared with that in the adenovirally transfused groups. Both the adenovirally delivered and the recombinant CTLA-4Ig fusion protein suppressed established CIA, whereas anti-CTLA-4 mAb and the control beta-galactosidase adenovirus did not significantly affect the disease course. CII-specific lymphocyte proliferation, interferon-gamma production, and anti-CII antibody levels, both IgG1 and IgG2a, were significantly reduced by CTLA-4Ig treatment. Blockade of the B7-CD28 costimulatory pathway by adenovirus-mediated CTLA-4Ig gene transfer is as effective as the recombinant fusion protein in treating established CIA, without the need for repeated administrations. Significant reduction in pathogenic cellular and humoral responses is achieved even after the onset of arthritis, thus suggesting the valuable therapeutic potential of this gene-transfer method in human rheumatoid arthritis.","subset":"pubmed_abstract"} +{"meta":{"pmid":28267590,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2023-40":1,"2024-26":1}}},"text":"Unsupervised ensemble ranking of terms in electronic health record notes based on their importance to patients.\nAllowing patients to access their own electronic health record (EHR) notes through online patient portals has the potential to improve patient-centered care. However, EHR notes contain abundant medical jargon that can be difficult for patients to comprehend. One way to help patients is to reduce information overload and help them focus on medical terms that matter most to them. Targeted education can then be developed to improve patient EHR comprehension and the quality of care. The aim of this work was to develop FIT (Finding Important Terms for patients), an unsupervised natural language processing (NLP) system that ranks medical terms in EHR notes based on their importance to patients. We built FIT on a new unsupervised ensemble ranking model derived from the biased random walk algorithm to combine heterogeneous information resources for ranking candidate terms from each EHR note. Specifically, FIT integrates four single views (rankers) for term importance: patient use of medical concepts, document-level term salience, word co-occurrence based term relatedness, and topic coherence. It also incorporates partial information of term importance as conveyed by terms' unfamiliarity levels and semantic types. We evaluated FIT on 90 expert-annotated EHR notes and used the four single-view rankers as baselines. In addition, we implemented three benchmark unsupervised ensemble ranking methods as strong baselines. FIT achieved 0.885 AUC-ROC for ranking candidate terms from EHR notes to identify important terms. When including term identification, the performance of FIT for identifying important terms from EHR notes was 0.813 AUC-ROC. Both performance scores significantly exceeded the corresponding scores from the four single rankers (P<0.001). FIT also outperformed the three ensemble rankers for most metrics. Its performance is relatively insensitive to its parameter. FIT can automatically identify EHR terms important to patients. It may help develop future interventions to improve quality of care. By using unsupervised learning as well as a robust and flexible framework for information fusion, FIT can be readily applied to other domains and applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":23425579,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-20":1,"2013-48":1,"unknown":9}}},"text":"Simultaneous saccharification, filtration and fermentation (SSFF): a novel method for bioethanol production from lignocellulosic biomass.\nSimultaneous saccharification, filtration and fermentation (SSFF) was developed for lignocellulosic ethanol production. In SSFF, pretreated lignocellulosic material is enzymatically hydrolyzed in a reactor, while the suspension is continuously pumped through a cross-flow membrane. The retentate goes back to the hydrolysis vessel, while a clear sugar-rich filtrate continuously perfuses through the fermentation vessel before it is pumped back to the hydrolysis vessel. The capacity and life span of the cross-flow filter module was examined for 4 weeks using enzymatically hydrolyzed slurry, initially with 14.4% suspended solids, without clogging or fouling. An ethanol yield of 85.0% of the theoretical yield was obtained in SSFF and a flocculating strain of Saccharomyces cerevisiae was successfully reused for five cultivations of SSFF.","subset":"pubmed_abstract"} +{"meta":{"pmid":29320337,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Improving Resiliency in Healthcare Employees.\nThe high prevalence of stress at the workplace has been well documented; however, few studies have investigated the efficacy of worksite resiliency programs. Therefore, the objec- tive of this project was to examine the impact of a worksite resilience training program on improving resiliency and health behaviors in healthcare employees. Between 2012 and 2016, 137 adult wellness center members of a healthcare institution participating in a single-arm cohort study of a 12-week resiliency training program were assessed at baseline, end of intervention, and at 3-month follow-up. Statistically significant (p \u2264 .01) improvements were seen at the end of the intervention and extending to 3 months follow-up for resiliency, perceived stress, anxiety level, quality of life, and health behaviors. These results support the premise that worksite programs designed to improve resiliency in healthcare employees have efficacy in improving resiliency, quality of life and health behaviors. Given the importance of stress and burnout in healthcare employees, future randomized studies are warranted to determine more clearly the impacts of this type of resiliency intervention for improving the wellness of healthcare workers.","subset":"pubmed_abstract"} +{"meta":{"pmid":31462645,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Emerging epigenomic landscapes of pancreatic cancer in the era of precision medicine.\nGenetic studies have advanced our understanding of pancreatic cancer at a mechanistic and translational level. Genetic concepts and tools are increasingly starting to be applied to clinical practice, in particular for precision medicine efforts. However, epigenomics is rapidly emerging as a promising conceptual and methodological paradigm for advancing the knowledge of this disease. More importantly, recent studies have uncovered potentially actionable pathways, which support the prediction that future trials for pancreatic cancer will involve the vigorous testing of epigenomic therapeutics. Thus, epigenomics promises to generate a significant amount of new knowledge of both biological and medical importance.","subset":"pubmed_abstract"} +{"meta":{"pmid":32860703,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":7}}},"text":"Evaluating Trends in Novel Psychoactive Substances Using a Sentinel Population of Electronic Dance Music Festival Attendees.\nElectronic dance music (EDM) festivals have become a popular venue for recreational drug use, including the use of traditional stimulants like 3,4-methylenendioxymethamphetamine (MDMA) and novel psychoactive substances (NPS). Using this cohort of people who use drugs recreationally, this study sought to collect biological specimens and self-reported drug use data from EDM festival attendees in the United States to monitor regional and temporal trends related to NPS use and turnover between 2014 and 2017. Oral fluid samples were collected at three United States EDM festival locations, including Miami, Florida (2014 to 2017); Tampa, Florida (2017) and Atlanta, Georgia (2017). Samples were screened by liquid chromatography-quadrupole time-of-flight mass spectrometry and confirmed by liquid chromatography-tandem mass spectrometry. Over the 4 years, 1,233 oral fluid samples were collected. With respect to self-reported drug use, 63% of respondents reported medicinal and\/or recreational drug use within the last week. When comparing 4 years of data from Miami (2014 to 2017), NPS trends showed the disappearance of alpha-PVP after 2014 followed by a significant increase in ethylone positivity in 2015 and rapid decrease in 2016. Dibutylone was identified for the first time in Miami 2016, and N-ethyl pentylone was identified for the first time in Miami 2017. Additionally, 3,4-methylenendioxymethamphetamine positivity steadily increased from 2014 to 2017. A comparison across study sites (Miami, Tampa and Atlanta) and specific trends with respect to novel simulant use are described within. Using this opportunistic approach of monitoring drug trends, we have found that peak positivity of novel stimulants usually is within a year of their first detection. Understanding the dynamics of NPS drug markets will allow laboratories to plan for resource allocation and scope updates within a timely fashion to assist with the detection and confirmation of these emerging substances in samples submitted for forensic analysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":27060049,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Mechanical Pulmonary Valve Replacement.\nAlthough most valve operations performed annually address lesions of the aortic or mitral valves, the frequency of pulmonary valve replacement (PVR) is increasing because most patients with congenital heart disease are surviving into the adult years. The vast majority of patients, especially children that require PVR, obtain a tissue valve because of the relative good durability and the lack of a need for anticoagulation. Because the need for repeat operation is inevitable for most patients, and the population of adults with congenital heart disease continues to grow, there are increasing situations in which a mechanical pulmonary prosthesis may be appropriate. Most patients being considered for mechanical PVR have a congenital diagnosis and require multi-valve procedures, and quality of life and need for repeat operation(s) are major issues. Mechanical valves are durable but require anticoagulation, which carries its own inherent set of risks. There are conflicting reports regarding the late outcome of mechanical PVR. There are few reports that indicate that, in the pulmonary position, bileaflet valves are at higher risk for complications compared with monodisc valves; however, the majority of these patients were not anticoagulated with warfarin, but simply maintained on aspirin. There is a growing body of literature documenting low rates of thrombosis or pulmonary prosthesis dysfunction when proper anticoagulation and monitoring are applied.","subset":"pubmed_abstract"} +{"meta":{"pmid":31535432,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":11}}},"text":"Process trumps potential public good: better vaccine safety through linked cross-jurisdictional immunisation data in Australia.\nTo provide insights into complexities of seeking access to state and federal cross-jurisdictional data for linkage with the Australian Childhood Immunisation Register (ACIR). We provide recommendations for improving access and receipt of linked datasets involving Australian Government-administered data. We describe requirements for linking eleven federal and state data sources to establish a national linked dataset for safety evaluation of vaccines. The required data linkage methodology for integrating cross-jurisdictional data sources is also described. Extensive negotiation was required with 18 different agencies for 21 separate authorisations and 12 ethics approvals. Three variations of the 'best practice' linkage model were implemented. Australian Government approval requests spanned nearly four years from initial request for data, with a further year before ACIR data transfer to the linkage agency. Integration of immunisation registers with other data collections is achievable in Australia but infeasible for routine and rapid identification of vaccine safety concerns. Lengthy authorisation requirements, convoluted disparate application processes and inconsistencies in data supplied all contribute to delayed data availability. Implications for public health: Delayed data access for safety surveillance prevents timely epidemiological reviews. Poor responsiveness to safety concerns may erode public confidence, compromising effectiveness of vaccination programs through reduced participation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28409126,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Genomics and Comparative Genomic Analyses Provide Insight into the Taxonomy and Pathogenic Potential of Novel Emmonsia Pathogens.\nOver the last 50 years, newly described species of Emmonsia-like fungi have been implicated globally as sources of systemic human mycosis (emmonsiosis). Their ability to convert into yeast-like cells capable of replication and extra-pulmonary dissemination during the course of infection differentiates them from classical Emmonsia species. Immunocompromised patients are at highest risk of emmonsiosis and exhibit high mortality rates. In order to investigate the molecular basis for pathogenicity of the newly described Emmonsia species, genomic sequencing and comparative genomic analyses of Emmonsia sp. 5z489, which was isolated from a non-deliberately immunosuppressed diabetic patient in China and represents a novel seventh isolate of Emmonsia-like fungi, was performed. The genome size of 5z489 was 35.5 Mbp in length, which is ~5 Mbp larger than other Emmonsia strains. Further, 9,188 protein genes were predicted in the 5z489 genome and 16% of the assembly was identified as repetitive elements, which is the largest abundance in Emmonsia species. Phylogenetic analyses based on whole genome data classified 5z489 and CAC-2015a, another novel isolate, as members of the genus Emmonsia. Our analyses showed that divergences among Emmonsia occurred much earlier than other genera within the family Ajellomycetaceae, suggesting relatively distant evolutionary relationships among the genus. Through comparisons of Emmonsia species, we discovered significant pathogenicity characteristics within the genus as well as putative virulence factors that may play a role in the infection and pathogenicity of the novel Emmonsia strains. Moreover, our analyses revealed a novel distribution mode of DNA methylation patterns across the genome of 5z489, with >50% of methylated bases located in intergenic regions. These methylation patterns differ considerably from other reported fungi, where most methylation occurs in repetitive loci. It is unclear if this difference is related to physiological adaptations of new Emmonsia, but this question warrants further investigation. Overall, our analyses provide a framework from which to further study the evolutionary dynamics of Emmonsia strains and identity the underlying molecular mechanisms that determine the infectious and pathogenic potency of these fungal pathogens, and also provide insight into potential targets for therapeutic intervention of emmonsiosis and further research.","subset":"pubmed_abstract"} +{"meta":{"pmid":19283154,"dup_signals":{"dup_doc_count":50,"dup_dump_count":38,"dup_details":{"curated_sources":4,"2018-39":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":3,"2014-35":2,"2014-23":2,"2014-15":2,"2018-47":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Wheat Germ Agglutinin Bound to the Outer Cuticle of the Seed Gall Nematodes Anguina agrostis and A. tritici.\nThe presence of wheat germ agglutinin (WGA) on the cuticular surface of the seed gall nematodes Anguina agrostis and Anguina tritici was demonstrated, and the nature of its binding was examined. Crude extracts from the cuticles of A. tritici agglutinated human red blood cells, and only N-acetylglucosamine (GlucNAc) inhibited the agglutination. Distribution of the lectin was visualized by treating live infective juveniles (J2) with rabbit anti-WGA antibody and staining with fluorescein isothiocyanate (FITC)-conjugated goat anti-rabbit IgG. The lectin bound to the outer cuticular surface of the whole body wall. Pretreatment with GlucNAc oligomers did not reduce the fluorescence created by the anti-WGA-WGA binding, indicating at least a partial nonspeciflc adhesion of the WGA to the nematode surface. Proteolytic enzyme pretreatments diminished the fluorescence, whereas lipase and periodate pretreatments increased the fluorescence. Adult females and males were labeled only on the head and tail, whereas eggs were not labeled at all. It was concluded that the WGA on the J2 cuticle originates from the host.","subset":"pubmed_abstract"} +{"meta":{"pmid":32674657,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":12}}},"text":"Impairments in Dynamic Postural Control across Concussion Clinical Milestones.\nThe aim of this study was to assess gait initiation (GI) performance longitudinally across clinical concussion recovery milestones through return to participation (RTP). We recruited 54 collegiate student-athletes, 27 with concussions and 27 matched controls (15 female and 12 male per group). Participants performed five trials of GI at baseline and again at five post-concussion clinical milestones: 1) Acute, the day clinical tests achieved baseline values on the 2) Balance Error Scoring System (BESS), 3) Immediate Post-Concussion Assessment and Cognitive Test ImPACT, 4) Asymptomatic, and 5) RTP Day. GI performance on six outcome measures (anterior\/posterior and medial\/lateral center of pressure displacements and velocities during the anticipatory postural adjustment [APA] phase and initial step length and velocity) with repeated-measures mixed model and pair-wise post hoc. A reliable change index (RCI) was calculated, and post-concussion participant's performance was compared to the RCI at milestones. There were significant interactions for APA posterior and lateral displacement, APA posterior velocity, step length, and step velocity. The post-hoc tests identified significant deficits across clinical milestones and at RTP for APA posterior and lateral displacement, step length, and step velocity. There were no post-hoc differences for any outcome measure in the control group. At RTP, 85.2-88.9% of concussion participants had at least one outcome measure which exceeded the 80% or 95% RCI. The primary finding of this study was persistent impairments in dynamic postural control, suggesting ongoing neurophysiological impairment despite clinical recovery. These results suggest that collegiate student-athletes may be RTP before neurophysiological recovery and potentially exposing themselves to elevated risk of recurrent concussion or subsequent musculoskeletal injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":22018539,"dup_signals":{"dup_doc_count":41,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-50":2,"2022-49":1,"2021-43":1,"2021-31":1,"2020-29":1,"2019-35":4,"2019-22":3,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":3,"2018-30":4,"2018-13":3,"2018-09":1,"2017-51":3,"2017-43":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2017-13":1,"2024-22":1}}},"text":"Culture and geographic variation in orangutan behavior.\nAlthough geographic variation in an organism's traits is often seen as a consequence of selection on locally adaptive genotypes accompanied by canalized development [1], developmental plasticity may also play a role [2, 3], especially in behavior [4]. Behavioral plasticity includes both individual learning and social learning of local innovations (\"culture\"). Cultural plasticity is the undisputed and dominant explanation for geographic variation in human behavior. It has recently also been suggested to hold for various primates and birds [5], but this proposition has been met with widespread skepticism [6-8]. Here, we analyze parallel long-term studies documenting extensive geographic variation in behavioral ecology, social organization, and putative culture of orangutans [9] (genus Pongo). We show that genetic differences among orangutan populations explain only very little of the geographic variation in behavior, whereas environmental differences explain much more, highlighting the importance of developmental plasticity. Moreover, variation in putative cultural variants is explained by neither genetic nor environmental differences, corroborating the cultural interpretation. Thus, individual and cultural plasticity provide a plausible pathway toward local adaptation in long-lived organisms such as great apes and formed the evolutionary foundation upon which human culture was built.","subset":"pubmed_abstract"} +{"meta":{"pmid":10962861,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":4,"unknown":9}}},"text":"[Severe apnea: an early sign of Pneumocystis carinii pneumonia in an HIV-negative infant].\nA few reports in the medical literature suggest an association between Pneumocystis caring and apnea in small infants. This patient, a 1 month 20 days old, HIV negative, infant girl weighing 2,000 grams was admitted to hospital after presenting a severe episode of apnea with cyanosis and bradycardia. She progressively developed bronchopneumonia by P. carinii that required prolonged mechanical ventilation with high ventilatory parameters. The clinical course of this patient illustrates that apnea can be an early sign of P. carinii infection in small infants. Early diagnosis and specific therapy might prevent morbidity and mortality and also decrease the length of hospitalization.","subset":"pubmed_abstract"} +{"meta":{"pmid":8424029,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":16}}},"text":"Hyperbilirubinemia in the breast-fed newborn: a controlled trial of four interventions.\nA controlled clinical trial was conducted to compare the effect of four different interventions on hyperbilirubinemia in 125 full-term breast-fed infants. Of 1685 term infants who met the inclusion criteria, 126 (7.4%) had a serum bilirubin concentration > or = 291 mumol\/L (17 mg\/dL). When the bilirubin reached this level, babies were assigned at random to one of four interventions: (1) continue breast-feeding and observe; (2) discontinue breast-feeding, substitute formula; (3) discontinue breast-feeding, substitute formula and administer phototherapy; (4) continue breast-feeding, administer phototherapy. The serum bilirubin concentration reached 342 mumol\/L (20 mg\/dL) in 24% of infants in group 1, 19% in group 2, 3% in group 3, and 14% in group 4. When phototherapy was used, the decline in serum bilirubin was significantly larger and more rapid (compared with no phototherapy). In the majority of breast-fed infants whose serum bilirubin levels reach 291 mumol\/L (17 mg\/dL) the bilirubin will decline spontaneously and will not reach 342 mumol\/L (20 mg\/dL). If the infant is significantly jaundiced and a decision is made to intervene, parents can be given a number of options and can make an informed decision regarding which, if any, intervention they prefer.","subset":"pubmed_abstract"} +{"meta":{"pmid":28410215,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":14}}},"text":"Cardiac glycosides suppress the maintenance of stemness and malignancy via inhibiting HIF-1\u03b1 in human glioma stem cells.\nTissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1\u03b1)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1\u03b1, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1\u03b1 and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC. We found that DT at clinically achievable concentrations, suppressed HIF-1\u03b1 accumulation during hypoxic conditions in human GSC and established glioma cell lines. DT treatment also significantly attenuated hypoxia-induced expression of VEGF, a downstream target of HIF-1\u03b1. Exposure to DT also reduced hypoxia-induced activation of the extracellular signal-regulated kinase 1\/2 (ERK1\/2) signaling pathway. Furthermore, DT potently inhibited neurosphere formation, and decreased CD133 expression even at concentrations that were not overtly cytotoxic. Lastly, treatment with DT reduced GSC engraftment in an in vivo xenograft model of glioblastoma. Intraperitoneal injections of DT significantly inhibited the growth of established glioblastoma xenografts, and suppressed expression of HIF-1\u03b1 and carbonic anhydrase (CA9), a surrogate marker of hypoxia. Taken together, these results suggest that DT at clinically achievable concentration functions as an inhibitor of HIF-1\u03b1, worthy of further investigations in the therapy of glioblastoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":22535076,"dup_signals":{"dup_doc_count":28,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":3,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":3,"2015-35":2,"2015-32":3,"2015-27":1,"2015-22":2,"2017-39":1,"2015-18":2}}},"text":"Pump-seed synchronization for MHz repetition rate, high-power optical parametric chirped pulse amplification.\nWe report on an active synchronization between two independent mode-locked lasers using a combined electronic-optical feedback. With this scheme, seed pulses at MHz repetition rate were amplified in a non-collinear optical parametric chirped pulse amplifier (OPCPA). The amplifier was seeded with stretched 1.5 nJ pulses from a femtosecond Ti:Sapphire oscillator, while pumped with the 1 ps, 2.9 \u00b5J frequency-doubled output of an Yb:YAG thin-disk oscillator. The residual timing jitter between the two oscillators was suppressed to 120 fs (RMS), allowing for an efficient and broadband amplification at 11.5 MHz to a pulse energy of 700 nJ and an average power of 8 W. First compression experiment with 240 nJ amplified pulse energy resulted in a pulse duration of ~10 fs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26833520,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":8}}},"text":"Atopic eczema.\nAtopic eczema is an itchy inflammatory skin disease with a chronic relapsing-remitting course; it has increased in prevalence in recent decades and now affects up to 25% of school-aged children in the developed world and up to 10% of adults. Recent advances in understanding the aetiology of eczema have focused interest on skin barrier dysfunction as a common precursor and pathological feature. In addition, genetically determined skin barrier dysfunction (associated with mutations in the gene encoding filaggrin) is known to predispose to multiple systemic atopic diseases. First-line treatments for atopic eczema focus on maintaining and repairing the skin barrier (emollients) and reducing inflammation (topical steroids); allergen and irritant avoidance are also important to achieve disease control. Second and third-line treatments include topical calcineurin inhibitors, ultraviolet light and systemic immunosuppressant therapies of which only ciclosporin is licenced for the treatment of atopic eczema in adults. Novel biological therapies are in phase II-III clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":21625292,"dup_signals":{"dup_doc_count":40,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2023-50":2,"2023-23":3,"2022-49":2,"2022-27":1,"2022-05":1,"2021-39":1,"2021-31":3,"2021-21":3,"2021-10":2,"2020-50":1,"2020-29":2,"2020-16":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-09":1,"2018-39":1,"2018-22":1,"2018-13":1,"2017-43":1,"2017-26":1,"2017-09":1,"2024-18":2,"2017-13":1,"2024-26":1}}},"text":"MDPs with Non-Deterministic Policies.\nMarkov Decision Processes (MDPs) have been extensively studied and used in the context of planning and decision-making, and many methods exist to find the optimal policy for problems modelled as MDPs. Although finding the optimal policy is sufficient in many domains, in certain applications such as decision support systems where the policy is executed by a human (rather than a machine), finding all possible near-optimal policies might be useful as it provides more flexibility to the person executing the policy. In this paper we introduce the new concept of non-deterministic MDP policies, and address the question of finding near-optimal non-deterministic policies. We propose two solutions to this problem, one based on a Mixed Integer Program and the other one based on a search algorithm. We include experimental results obtained from applying this framework to optimize treatment choices in the context of a medical decision support system.","subset":"pubmed_abstract"} +{"meta":{"pmid":26123090,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma.\nTo analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead to this retinopathy. Prospective observational, cohort-based, cross-sectional study. Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib (CM) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin (UM). Extensive ophthalmic examination was performed, including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, applanation tonometry, slit-lamp examination, indirect ophthalmoscopy, digital color fundus photography, and optical coherence tomography (OCT). In selected cases, additional examinations were performed, including visual field testing and electro-oculography (EOG). Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins. Visual symptoms, visual acuity, fundus appearance, characteristics on OCT, fundus autofluorescence (FAF), and EOG. Six CM patients (20%) and 2 UM patients (40%) reported visual symptoms during the study. The median time to the onset of symptoms, which were all mild and transient, was 3.5 days (range, <1 hour to 3 weeks). On OCT, subretinal fluid (SRF) was detected in 77% of CM patients and 60% of UM patients. In the 26 patients with SRF, the fovea was affected in 85%. After the start of the medication, an EOG was performed in 19 eyes of 11 patients; 16 of these eyes (84%) developed SRF on OCT. Fifteen of these eyes (94%) showed an abnormal Arden ratio (<1.65). A broad pattern of anti-retinal antibodies was found in 3 CM patients and 2 UM patients tested, whereas anti-RPE antibodies were detected in all 6 tested patients. A time-dependent and reversible serous retinopathy can develop both in patients with metastatic CM and UM treated with binimetinib. A minority of patients develop visual symptoms, which are generally mild and transient. A cause of binimetinib-associated serous retinopathy may be toxicity of medication, but autoantibodies also may be involved.","subset":"pubmed_abstract"} +{"meta":{"pmid":23461319,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"MHC variation is related to a sexually selected ornament, survival, and parasite resistance in common yellowthroats.\nHamilton and Zuk proposed that females choose mates based on ornaments whose expression is dependent on their genetically based resistance to parasites. The major histocompatibility complex (MHC) plays an important role in pathogen recognition and is a good candidate for testing the relationships between immune genes and both ornament expression and parasite resistance. We tested the hypothesis that female common yellowthroats prefer to mate with more ornamented males, because it is a signal of their MHC-based resistance to parasites and likelihood of survival. In this species, females prefer males that have larger black facial masks as extrapair mates. Using pyrosequencing, we found that mask size was positively related to the number of different MHC class II alleles, as predicted if greater variation at the MHC allows for the recognition of a greater variety of pathogens. Furthermore, males with more MHC class II alleles had greater apparent survival, and resistance to malaria infection was associated with the presence of a particular MHC class II allele. Thus, extrapair mating may provide female warblers with immunity genes that are related to parasite resistance, survival, and the expression of a male ornament, consistent with good genes models of sexual selection.","subset":"pubmed_abstract"} +{"meta":{"pmid":11999136,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Preventive effects of a traditional Chinese formulation, Chaihu-jia-Longgu-Muli-tang, on intimal thickening of carotid artery injured by balloon endothelial denudation in rats.\nWe report here that the traditional Chinese formulation, Chaihu-jia-Longgu-Muli-tang (CLM), significantly inhibited the increase in intimal thickening in rat carotid artery injured by balloon endothelial denudation, which mimics many aspects of restenosis after percutaneous coronary intervention (PCI) in humans. CLM, Saiko-ka-Ryukotsu-Borei-to in Japanese, is commonly prescribed for symptoms accompanying hypertension and atherosclerosis in Japanese Kampo medical care. CLM administered orally 1 week before and 1, 4 and 8 weeks after balloon injury inhibited the increase in intimal area, intimal\/medial ratio and stenosis ratio. To our knowledge, this is the first report demonstrating inhibitory effects of a traditional Chinese formulation on intimal thickening of carotid artery after balloon injury. It is worth noting that CLM maintained its inhibitory effect up to 8 weeks after balloon injury. The reduction in intimal thickening by CLM could have resulted from inhibition of intimal smooth muscle cell proliferation, which was assessed by immuno-histochemical analysis using monoclonal antibody against proliferating cell nuclear antigen. Therefore, CLM may be a favourable candidate for prevention of restenosis after PCI. Moreover CLM may have a therapeutic value in the prevention of atherosclerosis, because restenosis after PCI is considered to be an accelerated atherosclerosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":20034937,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms.\nStatins may reduce abdominal aortic aneurysm (AAA) progression. We sought to measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase (MMP) expression and\/or activity in human AAA. Tissue from human AAAs at surgical repair was obtained from patients who were either not on statins (NST, n = 19) or treated with AT (n = 19). Immunoblots measured expression and zymography measured activity. Expression of most proteins was greater in the central compared with distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against Decapentaplegia (SMAD2) expression did not differ with treatment. There was a trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in the AT-treatment group. In contrast, AT-treated samples had significantly reduced MMP13 (P = .02), latent-transforming growth factor (TGF)-beta (P = .02), and phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that the AT-mediated decrease in MMP expression and activity reduces TGF-beta signaling in the central region of human AAAs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26860553,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Quantitative Live Single-cell Mass Spectrometry with Spatial Evaluation by Three-Dimensional Holographic and Tomographic Laser Microscopy.\nThe locations and volumes of the contents of a single HepG2 cell were visualized under three-dimensional (3D) holographic and tomographic (HT) laser microscopy, colored by refractive index, not staining. After trapping the specific area of a target cell in a nanospray tip, quantification was performed by live single-cell mass spectrometry. Comparison of the HepG2 cells' before and after 3D-HT images allowed the inference of the precise volume and original location of the trapped cell contents. The total amount of a trapped molecule was estimated. The images also revealed morphological changes in the cell structure caused by the manipulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":33759123,"dup_signals":{"dup_doc_count":11}},"text":"Simulation of Ligand Transport in Receptors Using CaverDock.\nInteractions between enzymes and small molecules lie in the center of many fundamental biochemical processes. Their analysis using molecular dynamics simulations have high computational demands, geometric approaches fail to consider chemical forces, and molecular docking offers only static information. Recently, we proposed to combine molecular docking and geometric approaches in an application called CaverDock. CaverDock is discretizing enzyme tunnel into discs, iteratively docking with restraints into one disc after another and searching for a trajectory of the ligand passing through the tunnel. Here, we focus on the practical side of its usage describing the whole method: from getting the application, and processing the data through a workflow, to interpreting the results. Moreover, we shared the best practices, recommended how to solve the most common issues, and demonstrated its application on three use cases.","subset":"pubmed_abstract"} +{"meta":{"pmid":30844867,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Hospitalists' Needs Assessment and Perceived Barriers in Wound Care Management: A Quality Improvement Project.\nThe purpose of this quality improvement project was to determine hospitalists' knowledge, practices, and perspectives related to management of pressure injuries and neuropathic\/diabetic foot complications (having a foot ulcer or subsequent development of a foot infection because of a foot ulcer). We also sought to identify resources for and knowledge-based barriers to management of these wounds. This quality improvement effort targeted an interdisciplinary group of 55 hospitalists in internal medicine that consisted of 8 nurse practitioners, 10 physician assistants, and 38 physicians. The site of this initiative was the Johns Hopkins Bayview Medical Center, a 342-bed academic hospital located in the mid-Atlantic United States (Baltimore Maryland). The first phase of our quality improvement project comprised an online survey to identify hospitalists' knowledge, practices, and opinions on inpatient management of pressure injuries and diabetic foot complications. The second phase involved semistructured focus groups attended by hospitalists to identify resource gaps and barriers inferred by survey results. Twenty-nine of 55 (52%) hospitalists responded to the survey; 72% indicated no formal training in wound care. Over 90% had little to no confidence in management of pressure injuries and diabetic foot complications. In a separate ranking section of the survey, respondents selected lack of knowledge\/confidence 12 of 29 (41.3%) and resources 9 of 29 (31.0%) as number 1 barriers to wound care. Managing patients with obesity was identified as a second major barrier from 10 of 29 selected options (34.5%). Eighteen of 55 (33%) hospitalists attended focus group sessions acknowledging barriers to wound care that included provider education, information technology, system factors, and interprofessional engagement. Attendees welcomed additional educational and ancillary resource support.","subset":"pubmed_abstract"} +{"meta":{"pmid":21551073,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":1,"2024-30":1,"unknown":17}}},"text":"The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells.\nPrevious studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":27918308,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction.\nMyocardial infarction (MI) results in the generation of dead cells in the infarcted area. These cells are swiftly removed by phagocytes to minimize inflammation and limit expansion of the damaged area. However, the types of cells and molecules responsible for the engulfment of dead cells in the infarcted area remain largely unknown. In this study, we demonstrated that cardiac myofibroblasts, which execute tissue fibrosis by producing extracellular matrix proteins, efficiently engulf dead cells. Furthermore, we identified a population of cardiac myofibroblasts that appears in the heart after MI in humans and mice. We found that these cardiac myofibroblasts secrete milk fat globule-epidermal growth factor 8 (MFG-E8), which promotes apoptotic engulfment, and determined that serum response factor is important for MFG-E8 production in myofibroblasts. Following MFG-E8-mediated engulfment of apoptotic cells, myofibroblasts acquired antiinflammatory properties. MFG-E8 deficiency in mice led to the accumulation of unengulfed dead cells after MI, resulting in exacerbated inflammatory responses and a substantial decrease in survival. Moreover, MFG-E8 administration into infarcted hearts restored cardiac function and morphology. MFG-E8-producing myofibroblasts mainly originated from resident cardiac fibroblasts and cells that underwent endothelial-mesenchymal transition in the heart. Together, our results reveal previously unrecognized roles of myofibroblasts in regulating apoptotic engulfment and a fundamental importance of these cells in recovery from MI.","subset":"pubmed_abstract"} +{"meta":{"pmid":28943777,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Addressing location uncertainties in GPS-based activity monitoring: A methodological framework.\nLocation uncertainty has been a major barrier in information mining from location data. Although the development of electronic and telecommunication equipment has led to an increased amount and refined resolution of data about individuals' spatio-temporal trajectories, the potential of such data, especially in the context of environmental health studies, has not been fully realized due to the lack of methodology that addresses location uncertainties. This article describes a methodological framework for deriving information about people's continuous activities from individual-collected Global Positioning System (GPS) data, which is vital for a variety of environmental health studies. This framework is composed of two major methods that address critical issues at different stages of GPS data processing: (1) a fuzzy classification method for distinguishing activity patterns; and (2) a scale-adaptive method for refining activity locations and outdoor\/indoor environments. Evaluation of this framework based on smartphone-collected GPS data indicates that it is robust to location errors and is able to generate useful information about individuals' life trajectories.","subset":"pubmed_abstract"} +{"meta":{"pmid":29675230,"dup_signals":{"dup_doc_count":12,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2022-49":2,"2021-49":1,"2018-51":1,"2018-39":2,"2018-26":1,"2018-13":2,"2018-05":1,"2023-40":1}}},"text":"Unsymmetrical difunctionalization of cyclooctadiene under continuous flow conditions: expanding the scope of ring opening metathesis polymerization.\nFunctionalized cyclooctenes (FCOEs) are important monomers in ring-opening metathesis polymerization (ROMP). Herein, a new library of disubstituted FCOEs bearing adjacent heteroatoms were synthesized and applied in ROMP. To address the issues associated with the handling of the reactive thienyl chloride intermediate, a two-step continuous flow method has been developed to prepare 5-thio-6-chlorocyclooctene compounds from abundant cyclooctadiene starting materials. These newly synthesized FCOE monomers were subsequently polymerized through ROMP, giving rise to a range of functionalized polymers with high molecular weights. Furthermore, we demonstrated that the thermal properties of these polymers could be fine-tuned by changing the functional groups in the FCOE monomers. We expect that this functionalization-polymerization strategy will enable the preparation of a range of polymeric materials with complex structures.","subset":"pubmed_abstract"} +{"meta":{"pmid":28642840,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":15}}},"text":"Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy.\nCytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2\/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.","subset":"pubmed_abstract"} +{"meta":{"pmid":26576254,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Evaluation of dental panoramic radiographic findings in edentulous jaws: A retrospective study of 743 patients \"Radiographic features in edentulous jaws\".\nThe aim of this study was to determine the frequency of significant panoramic radiographic findings and eventual treatment requirements before conventional or implant supported prosthetic treatment in asymptomatic edentulous patients. A total of 743 asymptomatic edentulous patients were retrospectively evaluated using a digital panoramic system. We analyzed the radiographic findings, including impacted teeth, retained root fragments, foreign bodies, severe atrophy of the posterior maxillary alveolar bone, mucous retention cysts, soft tissue calcifications and radiopaque-radiolucent conditions. Four-hundred-eighty-seven (65.6%) patients had no radiographic finding. A total of 331 radiographic findings were detected in 256 (34%) patients. In 52.9% (n=175) of these conditions, surgical treatment was required before application of implant-supported fixed prosthesis. However, before application of conventional removable prosthesis surgical treatment was required for 6% (n=20) of these conditions. The edentulous patients who will have implant placement for implant-supported fixed prosthesis can frequently require additional surgical procedures to eliminate pathological conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":25781659,"dup_signals":{"dup_doc_count":22,"dup_details":{"curated_sources":2,"unknown":20}}},"text":"Fuzzy decision tree to classify complex fractionated atrial electrograms.\nCatheter ablation has emerged as an effective treatment strategy for atrial fibrillation (AF) in recent years. During AF, complex fractionated atrial electrograms (CFAE) can be recorded and are known to be a potential target for ablation. Automatic algorithms have been developed to simplify CFAE detection, but they are often based on a single descriptor or a set of descriptors in combination with sharp decision classifiers. However, these methods do not reflect the progressive transition between CFAE classes. The aim of this study was to develop an automatic classification algorithm, which combines the information of a complete set of descriptors and allows for progressive and transparent decisions. We designed a method to automatically analyze CFAE based on a set of descriptors representing various aspects, such as shape, amplitude and temporal characteristics. A fuzzy decision tree (FDT) was trained and evaluated on 429 predefined electrograms. CFAE were classified into four subgroups with a correct rate of 81\u00b13%. Electrograms with continuous activity were detected with a correct rate of 100%. In addition, a percentage of certainty is given for each electrogram to enable a comprehensive and transparent decision. The proposed FDT is able to classify CFAE with respect to their progressive transition and may allow objective and reproducible CFAE interpretation for clinical use.","subset":"pubmed_abstract"} +{"meta":{"pmid":12093953,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Early management of craniosynostosis using endoscopic-assisted strip craniectomies and cranial orthotic molding therapy.\nTo assess the safety, efficacy, and results of the early treatment of infants with craniosynostosis using minimally invasive endoscopic strip craniectomies and postoperative helmet molding therapy. A total of 100 patients with documented diagnosis of craniosynostosis were prospectively studied and treated with endoscopic strip craniectomies. A total of 106 stenosed sutures were operated on with the following distribution: 61 sagittal, 23 coronal, 18 metopic, and 4 lambdoid sutures. Sixty-three patients were treated under 16 weeks of age. After surgery, all patients were treated with custom-made molding helmets for up to 7 months. Follow-up ranged between 4 months and 50 months. All patients underwent the surgical procedures successfully and without complications. The mean surgical operative time was 52.7 minutes. The mean estimated blood loss was 26.2 mL; only 1 patient underwent intraoperative blood transfusion, and 10 patients had a non- life-threatening postoperative blood transfusion. All but 3 patients were discharged on the first postoperative day. There were no infections, dural sinus tears, cerebrospinal fluid leaks, or neurologic injuries, and there were no significant complications related to the use of helmet therapy. Most patients have achieved or are in the process of reaching normalization of their craniofacial deformities. The results indicate that the early treatment of craniosynostosis with minimally invasive endoscopic strip craniectomies is a safe, efficacious, and valuable therapeutic alternative to the current extensive surgical treatment modalities. The significantly less blood loss, need for blood transfusions, and length of stay and decreased costs make this procedure an excellent early option for treating infants who present with craniosynostosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":21549147,"dup_signals":{"dup_doc_count":23,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2019-35":4,"2019-18":2,"2019-13":2,"2019-09":2,"2019-04":1,"2018-51":3,"2018-43":2,"2018-39":1,"2018-26":1,"2018-09":1,"2017-43":1,"2016-40":1,"2023-50":1}}},"text":"MRI-based age prediction using hidden Markov models.\nCortical thinning and intracortical gray matter volume losses are widely observed in normal ageing, while the decreasing rate of the volume loss in subjects with neurodegenerative disorders such as Alzheimer's disease is reported to be faster than the average speed. Therefore, neurodegenerative disease is considered as accelerated ageing. Accurate detection of accelerated ageing based on the magnetic resonance imaging (MRI) of the brain is a relatively new direction of research in computational neuroscience as it has the potential to offer positive clinical outcome through early intervention. In order to capture the faster structural alterations in the brain with ageing, we propose in this paper a computational approach for modelling the MRI-based structure of the brain using the framework of hidden Markov models, which can be utilized for age prediction. Experiments were carried out on healthy subjects to validate its accuracy and its robustness. The results have shown its ability of predicting the brain age with an average normalized age-gap error of two to three years, which is superior to several recently developed methods for brain age prediction.","subset":"pubmed_abstract"} +{"meta":{"pmid":31795667,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":3,"2024-18":1,"unknown":8}}},"text":"Dynamic imaging of a capillary-gravity wave in shallow water using amplitude variations of eigenbeams.\nDynamic acoustic imaging of a surface wave propagating at an air-water interface is a complex task that is investigated here at the laboratory scale through an ultrasonic experiment in a shallow water waveguide. Using a double beamforming algorithm between two source-receiver arrays, the authors isolate and identify each multi-reverberated eigenbeam that interacts with the air-water and bottom interfaces. The waveguide transfer matrix is recorded 100 times per second while a low-amplitude gravity wave is generated by laser-induced breakdown at the middle of the waveguide, just above the water surface. The controlled, and therefore repeatable, breakdown results in a blast wave that interacts with the air-water interface, which creates ripples at the surface that propagate in both directions. The amplitude perturbations of each ultrasonic eigenbeam are measured during the propagation of the gravity-capillary wave. Inversion of the surface deformation is performed from the amplitude variations of the eigenbeams using a diffraction-based sensitivity kernel approach. The accurate ultrasonic imaging of the displacement of the air-water interface is compared to simultaneous measurements with an optical camera, which provides independent validation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27914492,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":12}}},"text":"Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study.\nDual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.","subset":"pubmed_abstract"} +{"meta":{"pmid":18282341,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"End-of-life care in nursing home settings: do race or age matter?\nOne-quarter of all U.S. chronic-disease deaths occur in nursing homes, yet few studies examine palliative care quality in these settings. This study tests whether racial and\/or age-based differences in end-of-life care exist in these institutional settings. We abstracted residents' charts (N = 1133) in 12 nursing homes. Researchers collected data on indicators of palliative care in two domains of care--advance care planning and pain management--and on residents' demographic and health status variables. Analyses tested for differences by race and age. White residents were more likely than minorities to have DNR orders (69.5% vs. 37.3%), living wills (39% vs. 5%), and health care proxies (36.2% vs. 11.8%; p < .001 for each). Advance directives were highly and positively correlated with age. In-depth advance care planning discussions between residents, families, and health care providers were rare for all residents, irrespective of demographic characteristics. Nursing staff considered older residents to have milder and less frequent pain than younger residents. We found no disparities in pain management based on race. To the extent that advance care planning improves care at the end of life, racial minorities in nursing homes are disadvantaged compared to their white fellow residents. Focusing on in-depth discussions of values and goals of care can improve palliative care for all residents and may help to ameliorate racial disparities in end-of-life care. Staff should consider residents of all ages as appropriate recipients of advance care planning efforts and should be cognizant of the fact that individuals of all ages can experience pain. Nursing homes may do a better job than other health care institutions in eliminating racial disparities in pain management.","subset":"pubmed_abstract"} +{"meta":{"pmid":19726407,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Bladder dysfunction in hereditary spastic paraplegia: what to expect?\nHereditary spastic paraplegia (HSP) comprises a group of rare neurodegenerative disorders characterised by progressive spasticity and hyperreflexia of the legs. Neurogenic bladder dysfunction is a well recognised problem in patients with HSP but it has not yet been described systematically in the literature. The aim of this study was to provide an evidential overview of the ways in which urinary dysfunction presents in HSP. 49 patients with HSP were included and underwent evaluation. A history was followed by a semi-structured interview and, in those patients who consented, measurement of residual volume of urine (PVR) and urodynamic evaluation. 38 subjects (77.6%) reported some type of urinary symptom. Subjective complaints of bladder problems showed a correlation with verified urinary dysfunction. There were no significant differences in the occurrence of urinary disturbances between the pure and complex forms of HSP. The most frequent symptoms were incontinence (69.4%), hesitancy (59.2%), increased frequency of micturition (55.1%) and urgency (51.0%). Incomplete bladder emptying was the rarest (36.7%). The most common combination of symptoms was to have all of them (14.3%). Incomplete bladder emptying as a complaint was associated with an increased risk of PVR. Women had a higher risk of increased voiding frequency. To our knowledge, this work is the first systematic and disease oriented overview of neurogenic bladder disturbances in patients with HSP. Our results may be useful to the clinicians who work with HSP patients, allowing them to make appropriate screening and management decisions.","subset":"pubmed_abstract"} +{"meta":{"pmid":29529085,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":18}}},"text":"A non-invasive, quantitative study of broadband spectral responses in human visual cortex.\nCurrently, non-invasive methods for studying the human brain do not routinely and reliably measure spike-rate-dependent signals, independent of responses such as hemodynamic coupling (fMRI) and subthreshold neuronal synchrony (oscillations and event-related potentials). In contrast, invasive methods-microelectrode recordings and electrocorticography (ECoG)-have recently measured broadband power elevation in field potentials (~50-200 Hz) as a proxy for locally averaged spike rates. Here, we sought to detect and quantify stimulus-related broadband responses using magnetoencephalography (MEG). Extracranial measurements like MEG and EEG have multiple global noise sources and relatively low signal-to-noise ratios; moreover high frequency artifacts from eye movements can be confounded with stimulus design and mistaken for signals originating from brain activity. For these reasons, we developed an automated denoising technique that helps reveal the broadband signal of interest. Subjects viewed 12-Hz contrast-reversing patterns in the left, right, or bilateral visual field. Sensor time series were separated into evoked (12-Hz amplitude) and broadband components (60-150 Hz). In all subjects, denoised broadband responses were reliably measured in sensors over occipital cortex, even in trials without microsaccades. The broadband pattern was stimulus-dependent, with greater power contralateral to the stimulus. Because we obtain reliable broadband estimates with short experiments (~20 minutes), and with sufficient signal-to-noise to distinguish responses to different stimuli, we conclude that MEG broadband signals, denoised with our method, offer a practical, non-invasive means for characterizing spike-rate-dependent neural activity for addressing scientific questions about human brain function.","subset":"pubmed_abstract"} +{"meta":{"pmid":34400462,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":4,"2024-18":2,"2024-10":1,"unknown":4}}},"text":"Experiences of preparing children for a death of an important adult during the COVID-19 pandemic: a mixed methods study.\nThe objectives of this study were to investigate how families prepared children for the death of a significant adult, and how health and social care professionals provided psychosocial support to families about a relative's death during the COVID-19 pandemic. A mixed methods design; an observational survey with health and social care professionals and relatives bereaved during the COVID-19 pandemic in the UK, and in-depth interviews with bereaved relatives and professionals were conducted. Data were analysed thematically. A total of 623 participants completed the survey and interviews were conducted with 19 bereaved relatives and 16 professionals. Many children were not prepared for a death of an important adult during the pandemic. Obstacles to preparing children included families' lack of understanding about their relative's declining health; parental belief that not telling children was protecting them from becoming upset; and parents' uncertainty about how best to prepare their children for the death. Only 10.2% (n=11) of relatives reported professionals asked them about their deceased relative's relationships with children. This contrasts with 68.5% (n=72) of professionals who reported that the healthcare team asked about patient's relationships with children. Professionals did not provide families with psychosocial support to facilitate preparation, and resources were less available or inappropriate for families during the pandemic. Three themes were identified: (1) obstacles to telling children a significant adult is going to die, (2) professionals' role in helping families to prepare children for the death of a significant adult during the pandemic, and (3) how families prepare children for the death of a significant adult. Professionals need to: provide clear and honest communication about a poor prognosis; start a conversation with families about the dying patient's significant relationships with children; and reassure families that telling children someone close to them is dying is beneficial for their longer term psychological adjustment.","subset":"pubmed_abstract"} +{"meta":{"pmid":30285754,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Childbirth fear and related factors among pregnant and postpartum women in Malawi.\nChildbirth fear is a health concern in women living in high-income countries; however, little is known about childbirth fear among women living in low-income countries like Malawi. In this study, we explored childbirth fear and associated factors among pregnant and postpartum women in Malawi. A cross-sectional study of 152 pregnant and 153 postpartum women was conducted at a district hospital in Malawi. Participants were assessed for childbirth fear using the Wijma Delivery Expectancy\/Experience Questionnaire (WDEQ). Demographic and obstetric variables were collected using a structured questionnaire. The Multidimensional Scale of Perceived Social Support (MSPSS) was used to measure social support. Using a multinomial logistic regression, factors related to childbirth fears were examined, namely demographic and obstetric characteristics, and social support. The mean age of participants was 26 (standard deviation: 6.4) years. During pregnancy, 39% women reported a low level of fear, 41% reported moderate fear, and 20% reported high fear; while after birth, 49, 41, and 10% women reported low, moderate, and high fear, respectively. Pregnant women who were illiterate (odds ratio (OR): 5.0, p < 0.01) or unemployed (OR: 12.6, p < 0.01) were more likely to report moderate and high fear. Postpartum mothers who were illiterate (OR: 4.2, p < 0.01) or unemployed (OR: 11.8, p < 0.01) were more likely to have moderate and high fear. Furthermore, postpartum women who sustained perineal tears had significantly higher odds of experiencing moderate (OR: 5.3, p < 0.01) or high (OR: 19.9, p < 0.01) fear than their counterparts. Childbirth fear is common in Malawi, and pregnant women are more likely to experience high levels of fear than postpartum women. This study highlighted the connection between childbirth fear with mother's education, employment, and perineal tears during delivery. Identifying and developing interventions for women with these associated characteristics is of clinical importance for the reduction of childbirth fear before and after childbirth in Malawi.","subset":"pubmed_abstract"} +{"meta":{"pmid":10774841,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2022-21":2,"2021-43":1,"2020-50":2,"2020-45":1,"2020-05":1,"2019-39":1,"2019-22":2,"2019-04":1,"2023-50":1,"2024-22":1}}},"text":"The guilty but mentally ill verdict: a review and conceptual analysis of intent and impact.\nThe purpose of this article is to review the law and literature involving the guilty but mentally ill (GBMI) verdict to provide a clear conceptual examination of the actual intent and impact of the verdict. Such an examination may help to clarify continuing debates and confusion about the nature of GBMI and its success in addressing perceived problems with insanity acquittals. This review suggests that the actual intentions of the GBMI verdict are associated with minimal and largely unsuccessful results. In addition, the typical absence of treatment for defendants found GBMI appears unsurprising given that the provision of treatment for mentally ill offenders is not a legal intention of the GBMI verdict. Finally, the introduction of the GBMI verdict has had unintended negative consequences that include increased confusion among jurors and the legal profession and possible increased occurrence of inappropriate verdicts. In conclusion, significant problems can be noted with regard to both the intent and impact of the GBMI verdict.","subset":"pubmed_abstract"} +{"meta":{"pmid":31369969,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":3,"2021-43":2,"2021-31":1,"2020-45":1,"2020-34":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2023-23":1,"2024-10":1,"2024-18":1}}},"text":"Misdiagnosis and pitfalls in Panayiotopoulos syndrome.\nPanayiotopoulos syndrome (PS) is a frequent (6% among children of 1-15 years) and benign epileptic syndrome, characterized by predominantly autonomic symptoms (emesis, pallor, flushing, cyanosis, mydriasis\/miosis, cardiorespiratory and thermoregulatory alterations, incontinence of urine and\/or feces, hypersalivation, and modifications of intestinal motility) associated with simple motor focal seizures, which can be followed by secondary generalization. Panayiotopoulos syndrome can be extremely insidious, because it can mimic several condition, such as gastroenteritis, gastroesophageal reflux disease, encephalitis, syncope, migraine, sleep disorders, or even metabolic diseases. This peculiar pleiotropism should be kept in mind by child neurologists and pediatricians and general practitioners, because a wrong diagnosis may lead to inappropriate interventions. The consequences are high morbidity, costly mismanagement, and stress for children and their parents. The availability of electroencephalography (EEG) recording in pediatric Emergency Departments might be useful for a prompt and not-cost-consuming diagnosis. On the other hand, it is important to be aware of the possible, multifaceted, clinical presentations of PS and its clinical, radiological, and neurophysiological features in order to improve both recognition and management.","subset":"pubmed_abstract"} +{"meta":{"pmid":29192526,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Intelligence Assessment Instruments in Adult Prison Populations: A Systematic Review.\nDetection of intellectual disability (ID) in the penitentiary system is important for the following reasons: (a) to provide assistance to people with ID in understanding their legal rights and court proceedings; (b) to facilitate rehabilitation programs tailored to ID patients, which improves the enhancement of their quality of life and reduces their risk of reoffending; and (c) to provide a reliable estimate of the risk of offence recidivism. It requires a short assessment instrument that provides a reliable estimation of a person's intellectual functioning at the earliest possible stage of this process. The aim of this systematic review is (a) to provide an overview of recent short assessment instruments that provide a full-scale IQ score in adult prison populations and (b) to achieve a quality measurement of the validation studies regarding these instruments to determine which tests are most feasible in this target population. The Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement is used to ensure reliability. The Satz-M\u00f6gel, an item-reduction short form of the Wechsler Adult Intelligence Scale, shows the highest correlation with the golden standard and is described to be most reliable. Nevertheless, when it comes to applicability in prison populations, the shorter and less verbal Quick Test can be preferred over others. Without affecting these conclusions, major limitations emerge from the present systematic review, which give rise to several important recommendations for further research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22665009,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":5,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-05":1,"2022-40":1,"2013-20":1}}},"text":"Thoracic meningioma masquerading as chronic abdominal pain.\nChronic abdominal pain without a structural or metabolic gastroenterological etiology can be extremely challenging to diagnose. Patients presenting with an associated radicular pattern of pain may alert the clinician to a possible structural neurological cause of the symptoms. We present the case of a 70-year-old woman who presented to our institution with an 18-month history of right upper quadrant abdominal pain. She had no associated symptoms or provoking factors. She underwent an extensive gastroenterology evaluation, including colonoscopy that was unrevealing. Ultrasound demonstrated gallstones and she was evaluated for cholecystectomy. She subsequently developed right costal margin pain. Her symptoms remained stable over the course of the next year. Follow-up general surgical evaluation was still unconvincing that the gallstones were the etiology of her symptoms. A thoracic spinal MR demonstrated a large intradural extramedullary mass at T8. The patient's neurological exam was normal. She underwent a thoracic laminectomy and resection of meningioma with intraoperative electrophysiological monitoring. Her abdominal pain resolved. Patients can present with months to years of elusive abdominal symptoms only to be eventually found to be harboring an undiagnosed spinal tumor. We discuss the case and review the literature reports of spinal tumors masquerading as chronic abdominal pain.","subset":"pubmed_abstract"} +{"meta":{"pmid":18448895,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"The impact of increasing medical school class size on clinical clerkships: a national survey of internal medicine clerkship directors.\nTo determine the impact of increasing medical school class size on the internal medicine clerkship. In 2006, the Clerkship Directors in Internal Medicine surveyed its 110 institutional members to discover whether their medical school class size had increased (or would increase) and the impact of increasing class size on number of students per teaching site, number of clerkship sites needed, and resources needed. Respondents rated their agreement or disagreement with statements about increasing class size, and they provided free-text responses. Analyses included descriptive statistics and qualitative analysis. Response rate was 76% (83\/110). In the three years preceding the survey, one medical school decreased class size; 43% increased by a mean of 14 students per year (10%). Most respondents (51%) expected class size to increase by a mean of 17 students per year (12%) through 2009; none expected class size to decrease. Increasing class size by 15% would mean adding 3.7 (standard deviation = 2.2) students per inpatient site, 2.9 (2.9) new inpatient sites, 3.0 (2.2) students per ambulatory site, and 4.9 (5.5) ambulatory sites. Respondents disagreed with the questionnaire statements that they would have more resources, teachers, and protected time; they agreed with statements that recruiting teachers would be harder as class size increases. Free-text responses to the challenges of increasing class size revealed two themes: strain on resources (space, time, faculty), and the impact on the educational experience. Internal medicine clerkship directors believe increasing medical school class size will dramatically increase resources needed during clerkships and may adversely impact education.","subset":"pubmed_abstract"} +{"meta":{"pmid":20849271,"dup_signals":{"dup_doc_count":31,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2021-25":1,"2021-21":1,"2018-39":1,"2018-13":1,"2017-51":1,"2017-34":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2014-52":1,"2014-49":2,"2014-42":1,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":1,"2023-40":1,"2024-22":3,"2024-18":1,"2024-10":1,"2024-30":1}}},"text":"Hidden consequences of living in a wormy world: nematode\u2010induced immune suppression facilitates tuberculosis invasion in African buffalo.\nMost hosts are infected with multiple parasites, and responses of the immune system to co-occurring parasites may influence disease spread. Helminth infection can bias the host immune response toward a T-helper type 2 (Th2) over a type 1 (Th1) response, impairing the host's ability to control concurrent intracellular microparasite infections and potentially modifying disease dynamics. In humans, immune-mediated interactions between helminths and microparasites can alter host susceptibility to diseases such as HIV, tuberculosis (TB), and malaria. However, the extent to which similar processes operate in natural animal populations and influence disease spread remains unknown. We used cross-sectional, experimental, and genetic studies to show that gastrointestinal nematode infection alters immunity to intracellular microparasites in free-ranging African buffalo (Syncerus caffer). Buffalo that were more resistant to nematode infection had weaker Th1 responses, there was significant genotypic variation in nematode resistance, and anthelminthic treatment enhanced Th1 immunity. Using a disease dynamic model parameterized with empirical data, we found that nematode-induced immune suppression can facilitate the invasion of bovine TB in buffalo. In the absence of nematodes, TB failed to invade the system, illustrating the critical role nematodes may play in disease establishment. Our results suggest that helminths, by influencing the likelihood of microparasite invasion, may influence patterns of disease emergence in the wild.","subset":"pubmed_abstract"} +{"meta":{"pmid":22960953,"dup_signals":{"dup_doc_count":11}},"text":"Chemotactic steering of bacteria propelled microbeads.\nFlagellated bacteria have been embraced by the micro-robotics community as a highly efficient microscale actuation method, capable of converting chemical energy into mechanical actuation for microsystems that require a small payload and high rate of actuation. Along with being highly motile, Serratia marcescens (S. marcescens), our bacterium species of interest, is a highly agile biomotor capable of being steered via chemotaxis. In this paper, we attached S. marcescens bacteria to polystyrene microbeads towards creating biohybrid that can propel themselves towards an attractive chemical source. Using a three-channel microfluidic device, linear chemical gradients are generated to compare the behavior of bacteria-propelled beads in the presence and absence of a chemoattractant, L-aspartate. We tested and compared the behavior of three different bacteria-attached bead sizes (5, 10 and 20 \u03bcm diameter) using a visual particle-tracking algorithm, and noted their behavioral differences. The results indicate that in the presence of a chemoattractant, the S. marcescens-attached polystyrene beads exhibit a clear indication of directionality and steering control through the coordination of the bacteria present on each bead. This directionality is observed in all bead size cases, suggesting potential for targeted payload delivery using such a biohybrid micro-robotic approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":22467026,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"Sub-acute oral toxicity study with fullerene C60 in rats.\nTo obtain initial information on the possible repeated-dose oral toxicity of fullerene C60, Crl:CD(SD) rats were administered fullerene C60 by gavage once daily at 0 (vehicle: corn oil), 1, 10, 100, or 1,000 mg\/kg\/day for 29 days, followed by a 14-day recovery period. No deaths occurred in any groups, and there were no changes from controls in detailed clinical observations, body weights, and food consumption in any treatment groups. Moreover, no treatment-related histopathological changes were found in any organs examined at the end of the administration period and at the end of the recovery period. Blackish feces and black contents of the stomach and large intestine were observed in males and females at 1,000 mg\/kg\/day in the treatment group. There were no changes from controls in the liver and spleen weights at the end of the administration period, but those weights in males in the 1,000 mg\/kg\/day group increased at the end of the recovery period. Using liquid chromatography-tandem mass spectrometry, fullerene C60 were not detected in the liver, spleen or kidney at the end of the administration period and also at the end of the recovery period. In conclusion, the present study revealed no toxicological effects of fullerene C60; however, the slight increases in liver and spleen weights after the 14-day recovery period may be because of the influence of fullerene C60 oral administration. In the future, it will be necessary to conduct a long-term examination because the effects of fullerene C60 cannot be ruled out.","subset":"pubmed_abstract"} +{"meta":{"pmid":10327905,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Prospective analysis of the relation between DSM-III anxiety disorders and alcohol use disorders.\nCross-sectional studies show a robust association between anxiety disorders and alcohol use disorders (comorbidity); however, this methodology does not allow for the testing of causal models. The authors attempted to overcome this limitation by examining comorbid relationships prospectively. Male and female college students were assessed as freshmen (year 1), and then again at years 4 and 7, for selected 12-month anxiety disorders (generalized anxiety disorder, agoraphobia, and social phobia or panic) diagnosed according to the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and DSM-III and for 12-month DIS\/DSM-III alcohol use disorders (alcohol dependence alone and alcohol abuse or dependence). Cross-sectionally, the odds of having either an anxiety disorder or an alcohol use disorder were two- to fivefold greater when the other condition was present. Prospectively, the odds of developing a new alcohol dependence diagnosis at year 7 increased from 3.5 to five times for those diagnosed with an anxiety disorder at years 1 or 4. Conversely, the odds of developing a new anxiety disorder at year 7 increased by about four times for those diagnosed with alcohol dependence at years 1 or 4. When alcohol abuse and dependence were combined, the pattern of findings was similar, albeit weaker. Multivariate path models provide similar results and highlight the reciprocal influence of alcohol use disorders and anxiety disorders. Alcohol use disorders (especially alcohol dependence) and anxiety disorders demonstrate a reciprocal causal relationship over time, with anxiety disorders leading to alcohol dependence and vice versa.","subset":"pubmed_abstract"} +{"meta":{"pmid":26105667,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Statewide Longitudinal Hospital Use and Charges for Pediatric and Adolescent Patients With Cancer.\nWe investigated longitudinal hospitalization outcomes (total charges, hospital days and admissions) among pediatric and adolescent patients with cancer compared with individuals from the general population without cancer using a novel and efficient three-step regression procedure. The statewide Utah Population Database, with linkages to the Utah Cancer Registry, was used to identify 1,651 patients who were diagnosed with cancer from 1996 to 2009 at ages 0 to 21 years. A comparison group of 4,953 same-sex and -age individuals was generated from birth certificates. Claims-based hospitalization data from 1996 to 2012 were retrieved from the Utah Department of Health. Using the regression method, we estimated survival (differences due to survival) and intensity (differences due to resource accumulation) effects of the cancer diagnosis on hospitalization outcomes within 10 years after diagnosis. At 10 years after diagnosis, on average, patients with cancer incurred $51,723 (95% CI, $48,100 to $58,284) more in charges, spent 30 additional days (95% CI, 27.7 to 36.1 days) in the hospital, and had 5.7 (95% CI, 5.4 to 6.4) more admissions than the comparison group. Our analyses showed that the highest hospitalization burden occurred during the first 4 years of diagnosis. Patients with leukemia incurred the greatest hospitalization burden throughout the 10 years from diagnosis. Intensity effects explained the majority of differences in hospital outcomes. Our results suggest that children and adolescents who were diagnosed with cancer in 2014 in the United States will incur over $800 million more in hospital charges than individuals without cancer by 2024. Interventions to reduce this burden should be explored in conjunction with improving health and survival outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22674561,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2021-39":1,"2021-31":1,"2021-21":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":2,"2017-43":1,"2017-34":1,"2017-22":1,"2016-50":1,"2023-40":1}}},"text":"An eight-year study of online lecture use in a medical gross anatomy and embryology course.\nOnline lectures have been used in lieu of live lectures in our gross anatomy and embryology course for the past eight years. We examined patterns of online lecture use by our students and related that use to academic entry measures, gender and examination performance. Detailed access records identified by student were available from server logs. Total views per page of lecture material increased over the first six years, then decreased markedly between years seven and eight, possibly due to the recent availability of alternate forms of lecture audio. Lecture use peaked in midafternoon and again in the evening, although some use was seen at all hours. Usage was highest at midweek and lowest on Fridays as might be expected. Individual student's use varied widely from rates equivalent to less than one viewing\/page to more than three viewings per page. Overall use by male students was greater than that of females and gender-specific differences in the daily pattern were seen. Lecture use was correlated to the Medical College Admission Test(\u00ae) (MCAT(\u00ae)) Verbal Reasoning and Physical Sciences scores but not to composite MCAT scores or undergraduate grade point average. Overall use appeared to be driven by scheduled team-based learning (TBL) sessions and major examinations. Specific subsets of lecture material were most often viewed before related TBL sessions and again during review for examinations. A small but significant correlation between lecture use and examination and course performance was seen, specifically in the male student population. These findings, along with earlier observations, suggest that varied use of online lectures is attributable to multiple factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":28758273,"dup_signals":{"dup_doc_count":40,"dup_dump_count":30,"dup_details":{"curated_sources":4,"2023-40":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-27":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":2,"2020-50":1,"2020-40":2,"2020-29":1,"2020-16":1,"2020-05":1,"2019-39":1,"2019-30":2,"2019-22":1,"2019-18":1,"2019-13":1,"2019-04":2,"2018-43":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-13":1,"2018-09":1,"2023-50":1,"2024-18":2}}},"text":"Assessment of computed tomography derived cricoid cartilage and tracheal dimensions to evaluate degree of cricoid narrowing in brachycephalic dogs.\nThe aims of this observational, analytical, retrospective study were to (i) obtain computed tomographic (CT) cricoid dimensions (height, width, and transverse-sectional area), (ii) compare the cricoid dimensions between brachycephalic and mesaticephalic breeds, and (iii) compare cricoid cartilage dimensions between dogs without and affected with brachycephalic airway syndrome. The study is important to help to further evaluate and understand the anatomical components of brachycephalic airway syndrome. Measurements were performed in 147 brachycephalic and 59 mesaticephalic dogs. The cricoid cartilage was found to be significantly more oval in Pugs and French Bulldogs compared to mesaticephalic breeds. The cricoid cartilage transverse-sectional area was smallest for the Pug and, after adjusting for weight, significantly smaller for Pugs (P < 0.001), Boston Terriers (P = 0.001), and French Bulldogs (P < 0.001) compared to Jack Russell Terriers. The tracheal transverse-sectional area at C4 of English Bulldogs was significantly smaller than for Jack Russell Terriers (P = 0.005) and Labradors (P < 0.001). The cricoid cartilage transverse-sectional area:weight ratio was significantly lower in brachycephalic breeds compared to mesaticephalic breeds (P < 0.001). The cricoid cartilage:trachea at C4 transverse-sectional area for brachycephalic dogs was significantly larger than for mesaticephalic dogs (<0.001), demonstrating that the trachea was the narrowest part of the airway. No significant differences were found for cricoid dimensions between dogs affected with and without brachycephalic airway syndrome. However, large individual variation was found among the brachycephalic breeds and further studies investigating the relationship between cricoid cartilage size, laryngeal collapse, concurrent tracheal hypoplasia, and\/or severity of brachycephalic airway syndrome are warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":17237071,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-06":1,"2022-27":1,"2021-39":1,"2021-21":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-34":1,"2018-13":1,"2018-05":1,"2017-47":1,"2023-40":1}}},"text":"SBaddon: high performance simulation for the Systems Biology Toolbox for MATLAB.\nWe present the SBaddon package as an extension to the Systems Biology Toolbox for MATLAB (SBtoolbox). The goal of this extension is to provide the users of the SBtoolbox with important functionality that is needed for parameter estimation applications. While simulation in the SBtoolbox relies on the MATLAB ODE solvers, the SBaddon package provides considerably increased simulation performance through automatic generation of compiled simulation functions. Furthermore, the package contains improved optimization algorithms, forward parameter sensitivity analysis and basic numeric parameter identifiability analysis. The SBaddon package is open source and freely available for non-commercial use. Commercial use of SBaddon is only possible through a specific licensing agreement (contact email@example.com). SBaddon can be obtained from http:\/\/www.sbtoolbox.org\/SBaddon. The website also contains extensive documentation, and examples.","subset":"pubmed_abstract"} +{"meta":{"pmid":19481535,"dup_signals":{"dup_doc_count":67,"dup_dump_count":41,"dup_details":{"curated_sources":2,"2022-05":1,"2021-49":1,"2021-04":1,"2019-51":1,"2018-22":1,"2018-09":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":2,"2017-17":1,"2017-09":1,"2017-04":2,"2016-50":1,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":1,"2016-26":2,"2016-07":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":2,"2014-49":3,"2014-42":5,"2014-41":3,"2014-35":3,"2014-23":4,"2023-23":1,"2024-18":1,"2017-13":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":1,"2024-26":1}}},"text":"Extracellular norepinephrine, norepinephrine receptor and transporter protein and mRNA levels are differentially altered in the developing rat brain due to dietary iron deficiency and manganese exposure.\nManganese (Mn) is an essential trace element, but overexposure is characterized by Parkinson's like symptoms in extreme cases. Previous studies have shown that Mn accumulation is exacerbated by dietary iron deficiency (ID) and disturbances in norepinephrine (NE) have been reported. Because behaviors associated with Mn neurotoxicity are complex, the goal of this study was to examine the effects of Mn exposure and ID-associated Mn accumulation on NE uptake in synaptosomes, extracellular NE concentrations, and expression of NE transport and receptor proteins. Sprague-Dawley rats were assigned to four dietary groups: control (CN; 35 mg Fe\/kg diet), iron-deficient (ID; 6 mg Fe\/kg diet), CN with Mn exposure (via the drinking water; 1 g Mn\/L) (CNMn), and ID with Mn (IDMn). (3)H-NE uptake decreased significantly (R=-0.753, p=0.001) with increased Mn concentration in the locus coeruleus, while decreased Fe was associated with decreased uptake of (3)H-NE in the caudate putamen (R=0.436, p=0.033) and locus coeruleus (R=0.86; p<0.001). Extracellular concentrations of NE in the caudate putamen were significantly decreased in response to Mn exposure and ID (p<0.001). A diverse response of Mn exposure and ID was observed on mRNA and protein expression of NE transporter (NET) and alpha(2) adrenergic receptor. For example, elevated brain Mn and decreased Fe caused an approximate 50% decrease in NET and alpha(2) adrenergic receptor protein expression in several brain regions, with reductions in mRNA expression also observed. These data suggest that Mn exposure results in a decrease in NE uptake and extracellular NE concentrations via altered expression of transport and receptor proteins.","subset":"pubmed_abstract"} +{"meta":{"pmid":11089197,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Restorative neurology in movement disorders.\nCell replacement for restoration of neurological functions in patients with movement disorders has been investigated for more than 15 years. Initial attempts used autologous adrenal medulla grafts implanted into the denervated striatum of patients with Parkinson's disease (PD). This approach was soon abandoned in favor of intrastriatal implantation of human embryonic mesencephalic tissue, rich in dopaminergic neurons. Available data from grafted PD patients show long-term (up to 10 years) graft survival and clinical benefits. The pattern and magnitude of symptomatic relief following transplantation, however, are incomplete and the outcome varies among patients. The need for large amounts of human embryonic tissue has to be circumvented and a better understanding of the relationship between graft placement and symptomatic recovery is necessary before this procedure can be offered to larger groups of patients. Clinical trials in Huntington's disease have so far shown inconclusive results. Neural cell replacement therapy is still an experimental procedure, but has the potential to become a future restorative treatment in PD and other movement disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":28130170,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":2,"unknown":9}}},"text":"Identifying Children at Very Low Risk for Blunt Intra-Abdominal Injury in Whom CT of the Abdomen Can Be Avoided Safely.\nComputed tomography is commonly used to rule out intra-abdominal injury (IAI) in children, despite associated cost and radiation exposure. Our purpose was to derive a prediction rule to identify children at very low risk for IAI after blunt abdominal trauma (BAT) for whom a CT scan of the abdomen would be unnecessary. We prospectively enrolled children younger than 16 years of age who presented after BAT at 14 Level I pediatric trauma centers during 1 year. We excluded patients who presented more than 6 hours after injury or underwent abdominal CT before transfer. We used binary recursive partitioning to derive a prediction rule identifying children at very low risk of IAI and IAI requiring acute intervention (IAI-I) using clinical information available in the trauma bay. We included 2,188 children with a median age of 8 years. There were 261 patients with IAI (11.9%) and 62 patients with IAI-I (2.8%). The prediction rule consisted of (in descending order of significance): aspartate aminotransferase >200 U\/L, abnormal abdominal examination, abnormal chest x-ray, report of abdominal pain, and abnormal pancreatic enzymes. The rule had a negative predictive value of 99.4% for IAI and 100.0% for IAI-I in patients with none of the prediction rule variables present. The very-low-risk population consisted of 34% of the patients and 23% received a CT scan. Computed tomography frequency ranged from 4% to 96% by center. A prediction rule using history and physical examination, chest x-ray, and laboratory evaluation at the time of presentation after BAT identifies children at very low risk for IAI for whom CT can be avoided.","subset":"pubmed_abstract"} +{"meta":{"pmid":32105680,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":16}}},"text":"Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know.\nCoronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019's effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of \u223c5 days (range, 2-14 days). Average age of hospitalized patients has been 49-56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54-73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17-29% of hospitalized patients. Overall case fatality rate appears to be \u223c1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks' gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https:\/\/www.cdc.gov\/coronavirus\/2019-nCoV\/hcp\/index.html).","subset":"pubmed_abstract"} +{"meta":{"pmid":22472533,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":13}}},"text":"Enzyme activities in the oral fluids of patients suffering from bulimia: a controlled clinical trial.\nPatients with bulimia nervosa are at high risk for dental erosion. However, not all bulimic patients suffer from erosion, irrespective of the severity of their eating disorder. It is often speculated that differences in the saliva are important, however, little is known about salivary parameters in bulimic patients, particularly directly after vomiting. The aim of the clinical trial was to compare different salivary parameters of subjects suffering from bulimia with those of healthy controls. Twenty-eight subjects participated (14 patients with bulimia nervosa, 7 of them with erosion; 14 matched healthy controls). Resting and stimulated saliva of all participants was analysed as well as saliva collected from bulimic patients directly and 30 min after vomiting. Parameters under investigation were flow rate, pH, buffering capacity and the enzyme activities of proteases in general, collagenase, pepsin, trypsin, amylase, peroxidase, and lysozyme. Regarding flow rate, pH and buffering capacity only small differences were found between groups; buffering capacity directly after vomiting was significantly lower in bulimic subjects with erosion than in subjects without erosion. Differences in enzymatic activities were more pronounced. Activities of proteases, collagenase and pepsin in resting and proteases in stimulated saliva were significantly higher in bulimic participants with erosion than in controls. Peroxidase activity was significantly decreased by regular vomiting. Proteolytic enzymes seem to be relevant for the initiation and progression of dental erosion directly after vomiting, maybe by both hydrolysis of demineralized dentine structures as well as modulation of the pellicle layer.","subset":"pubmed_abstract"} +{"meta":{"pmid":19382852,"dup_signals":{"dup_doc_count":13,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":6}}},"text":"Density-dependent male mating harassment, female resistance, and male mimicry.\nGenetic variation in female resistance and tolerance to male mating harassment can affect the outcome of sexually antagonistic mating interactions. We investigated female mating rates and male mating harassment in natural populations of a damselfly (Ischnura elegans). This damselfly species has a heritable sex-limited polymorphism in females, where one of the morphs is a male mimic (androchrome females). The three female morphs differ in mating rates, and these differences are stable across populations and years. However, the degree of premating resistance toward male mating attempts varied across generations and populations. Male mating harassment of the female morphs changed in a density-dependent fashion, suggesting that male mate preferences are plastic and vary with the different morph densities. We quantified morph differences in male mating harassment and female fecundity, using path analysis and structural equation modeling. We found variation between the morphs in the fitness consequences of mating, with the fecundity of one of the nonmimetic morphs declining with increasing male mating harassment. However, androchrome females had lower overall fecundity, presumably reflecting a cost of male mimicry. Density-dependent male mating harassment on the morphs and fecundity costs of male mimicry are thus likely to contribute to the maintenance of this female polymorphism.","subset":"pubmed_abstract"} +{"meta":{"pmid":32792041,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Hydroxychloroquine and Coronavirus Disease 2019: A Systematic Review of a Scientific Failure.\nHydroxychloroquine (HCQ) emerged early in the course of the coronavirus disease 2019 (COVID-19) pandemic as a possible drug with potential therapeutic and prophylactic benefits. It was quickly adopted in China, Europe, and the USA. We systematically reviewed the existing clinical evidence of HCQ use for the prevention and treatment of COVID-19. We screened for clinical studies describing HCQ administration to treat or prevent COVID-19 in PubMed. We included randomized controlled trials (RCTs), non-randomized comparative cohorts, and case series studies that had all undergone peer review. A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included. A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality rates, observational studies provided conflicting results. As a whole, RCTs, including one large British RCT that has not yet been published, showed no significant effect of HCQ on mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure prophylactic agent was found to be ineffective in one RCT. There is no evidence supporting HCQ for prophylaxis or treatment of COVID-19. Many observational trials were methodologically flawed. Scientific efforts have been disappointingly fragmented, and well-conducted trials have only recently been completed, more than 7 months and 600,000 deaths into the pandemic.","subset":"pubmed_abstract"} +{"meta":{"pmid":29498972,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Comparing the Efficacy of Peritonsillar Injection of Tramadol With Honey in Controlling Post-Tonsillectomy Pain in Adults.\nThe authors investigated the effect of honey on post-tonsillectomy pain and compare its efficacy with tramadol. This clinical trial was performed on 60 patients with American Society of Anesthesia I and II aged between 18 and 55 years and underwent tonsillectomy. Induction of anesthesia was carried out using 2 mg\/kg propofol and 0.5 atracurium following 1.5 \u03bcg\/kg fentanyl administration. Group B was given tramadol at dose of 2 mg\/kg and with volume of 4 mL and Group A was given normal saline with the same volume 2 mL of medications were injected using needle (25) into tonsil bed and anterior old of each tonsil by an anesthesiologist. Three minutes after injection, the surgery was performed by the same ENT residents for all patients. In the recovery room Group B received antibiotics and oral acetaminophen. Group A was given antibiotics, oral acetaminophen, and honey dissolved in 40 mL warm water every 6 hours from when the patient was fully awake. Patients in Group A were told to eat honey 3 times a day 7 days postoperatively. Pain was scored using Numeric Rating Scale at the time points of 2, 6, 12, and 24 hours as well as 3 and 7 days postoperatively. Moreover, the healing status and epithelialization degree of tonsillar bed were considered on 1 and 7 days after the surgery by ENT specialist. The mean of pain score was significantly higher in Group A within 24 hours postoperatively as compared with Group B (P < 0.01). The mean of pain score was lower in Group B after 3 and 7 days but this difference was not statistically significant (P > 0.05). Considering restoration status and epithelialization degree of tonsillar bed on the 1st and 7th days, there was no statistically significant difference between 2 groups; however, tonsillar bed healing process was better in Group B on the 7th day. The current investigation confirmed the positive impact of tramadol on post-tonsillectomy pain relief in adults. The authors also found that honey can be used as a complementary treatment along with acetaminophen and other analgesics for reducing post-tonsillectomy pain. Considering honey impact on wound healing and its anti-inflammatory effect, it is suggested for relieving complications after surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":33033498,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":19}}},"text":"Substandard, falsified and unregistered medicines in Latin America, 2017-2018.\nTo assess all the incidents of substandard, falsified and unregistered medicines in 2017 and 2018 in Latin America, determining the types of products affected, stages of the supply chain in which incidents were detected, quality deviations identified in tested samples, and regulatory measures taken by authorities. A comprehensive search of the websites of the Latin American national regulatory authorities was conducted, identifying all eligible incidents during 2017-2018. Standardized values were collected from each incident for pre-determined variables: country, year, type of incident, therapeutic group, supply chain, regulatory measures and laboratory data. A total of 596 incidents in 13 countries were included (236 substandard, 239 falsified, 116 unregistered and 5 stolen). The therapeutic categories with the highest incidents were: anti-infectives, medicines for pain\/palliative care, hormones\/contraceptives, medicines for the respiratory tract, and medicines for mental\/behavioural disorders. The most common places where incidents were detected were commercial establishments, pharmacies, health services and manufacturers. The most recurrent quality deviations were failure in parameters (appearance or physicochemical), incorrect labelling, different quantity of active pharmaceutical ingredient, presence of unknown particles, and microbiological contamination. The most frequent regulatory measures identified were alerts, withdrawals, seizures, and prohibition of marketing\/distribution\/use. In Latin America, substandard, falsified and unregistered medicines persist as a highly prevalent problem. An advanced degree of regulatory development in countries is associated with higher incident detection\/reporting rates and a more comprehensive set of measures. The pharmaceutical supply chain is more vulnerable in its final node. Quality deviations identified in tested samples pose serious risks to public health.","subset":"pubmed_abstract"} +{"meta":{"pmid":18196164,"dup_signals":{"dup_doc_count":19,"dup_dump_count":10,"dup_details":{"curated_sources":6,"2016-44":2,"2016-40":1,"2016-36":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-32":2,"2015-27":1,"2015-22":1}}},"text":"Temperature effects in AgGaS2 nonlinear devices.\nRefractive indices of AgGaS2 crystal are measured at different temperatures using the classical minimum deviation technique and are fitted in appropriate dispersion relations. The variation of pump laser wavelength for noncritical upconversion of signal at 10.6 microm with the change in crystal temperature has been verified using the above data. Temperature tunable infrared generation by noncritically phase-matched difference- frequency mixing has been predicted from 3 to 18 microm.","subset":"pubmed_abstract"} +{"meta":{"pmid":29303323,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Gravitational Mechanisms to Self-Tune the Cosmological Constant: Obstructions and Ways Forward.\nGravitational models of self-tuning are those in which vacuum energy has no observable effect on spacetime curvature, even though it is a priori unsuppressed below the cutoff. We complement Weinberg's no-go theorem by studying field-theoretic completions of self-adjustment allowing for broken translations as well as other generalizations, and identify new obstructions. Our analysis uses a very general K\u00e4ll\u00e9n-Lehmann spectral representation of the exchange amplitude for conserved sources of energy-momentum and exploits unitarity and Lorentz invariance to show that a transition from self-tuning of long wavelength sources to near general relativity (GR) on shorter scales is generically not possible. We search for novel ways around our obstructions and highlight two interesting possibilities. The first is an example of a unitary field configuration on anti-de Sitter space with the desired transition from self-tuning to GR. A second example is motivated by vacuum energy sequestering.","subset":"pubmed_abstract"} +{"meta":{"pmid":12163376,"dup_signals":{"dup_doc_count":60,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":4,"2023-23":1,"2023-14":3,"2023-06":2,"2022-49":3,"2022-40":1,"2022-33":1,"2022-27":5,"2022-21":1,"2022-05":3,"2021-43":2,"2021-39":4,"2021-25":4,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":2,"2020-50":1,"2020-45":3,"2020-40":2,"2024-26":5,"2024-22":1,"2024-10":2,"2013-20":1}}},"text":"Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric.\nAlzheimer's disease (AD) is characterized by deposition of beta-amyloid (Abeta) in diffuse and senile plaques, and variably in vessels. Mutations in the Abeta-encoding region of the amyloid precursor protein (APP) gene are frequently associated with very severe forms of vascular Abeta deposition, sometimes also accompanied by AD pathology. We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores. The pathogenic basis of Flemish AD is unknown. By image and mass spectrometric Abeta analyses, we demonstrated that in contrast to other familial AD cases with predominant brain Abeta42, Flemish AD patients predominantly deposit Abeta40. On serial histological section analysis we further showed that the neuritic senile plaques in APP692 brains were centered on vessels. Of a total of 2400 senile plaque cores studied from various brain regions from three patients, 68% enclosed a vessel, whereas the remainder were associated with vascular walls. These observations were confirmed by electron microscopy coupled with examination of serial semi-thin plastic sections, as well as three-dimensional observations by confocal microscopy. Diffuse plaques did not associate with vessels, or with neuritic or inflammatory pathology. Together with earlier in vitro data on APP692, our analyses suggest that the altered biological properties of the Flemish APP and Abeta facilitate progressive Abeta deposition in vascular walls that in addition to causing strokes, initiates formation of dense-core senile plaques in the Flemish variant of AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":2573679,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Sensitization of hypoxic tumour cells--clinical experience.\nThere is substantial evidence for the presence of hypoxia in human tumours. This is documented by histopathological demonstration of vascular insufficiency, direct oxygen measurements in tumours, as well as by physiological imaging and mapping of hypoxic areas. As a consequence, clinical trials have focused on the hypoxia problem for more than 30 years. This includes the use of hyperbaric oxygen, hypoxic cell radiosensitizers, and, more recently, modification of the oxygen-unloading capacity of haemoglobin. Agents directed towards destruction of hypoxic cells have also been applied, such as hyperthermia and bio-reductive drugs. Despite decades of clinical trials, the results are still inconclusive, and although some trials have shown significant benefit, it has become apparent that hypoxia is a complex problem. Hypoxia appears to be especially a problem in certain tumour types (e.g. squamous cell carcinoma), but even within tumours of the same type, site, and stage, hypoxia does not occur to the same extent. Furthermore, there are increasing suggestions that hypoxia may occur in two principally different ways, namely acutely and chronically, yielding varying responses to modifying agents. Although improvement in hypoxic cell radiosensitizers and other agents is under way, a definitive solution to the hypoxia problem will not be found until the tumours in which hypoxia occurs can be identified. This will require detailed analysis of individual tumours and patients' parameters, and better knowledge of the mechanisms of reoxygenation in clonogenic tumour cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":7841721,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Zinc intake, zinc status and growth in a longitudinal study of healthy Danish infants.\nMild, growth-limiting zinc deficiency might be prevalent in otherwise healthy infants according to recent studies. We examined zinc intake and status in 91 healthy term infants from birth to 12 months, as part of the Copenhagen Cohort Study on Infant Nutrition and Growth. Zinc intake was recorded monthly and the amount of zinc absorbed was estimated. These estimates were below recently published FAO\/WHO\/IAEA values for basal requirements in 68%, 62% and 14% of the infants at 2, 4 and 9 months of age, respectively. Serum zinc decreased significantly (p < 0.01) from 10.6 mumol\/l at 6 months to 8.4 mumol\/l at 9 months of age (normal range 10-18 mumol\/l). Erythrocyte metallothionein values, a tentative indicator of long-term zinc status, decreased significantly from 2 to 6 months (p < 0.001) and from 6 to 9 months (p < 0.01). Serum zinc at 9 months was positively associated with growth velocity during the period from 6 to 9 months (weight: p = 0.05; knee-heel length: p = 0.002). The results provide descriptive data on zinc intake and zinc status in healthy Danish infants. Although some of our data suggest suboptimal zinc status during late infancy, evidence for this can only be obtained through a randomized intervention study.","subset":"pubmed_abstract"} +{"meta":{"pmid":24743752,"dup_signals":{"dup_doc_count":15}},"text":"Comparative effects of 2 aqua exercise programs on physical function, balance, and perceived quality of life in older adults with osteoarthritis.\nOsteoarthritis (OA) is a degenerative joint disease, which affects a large number of older adults. Many older adults with OA are physically inactive, which can contribute to reduced functional capability, quality of life, and an increased risk of falls. Although hydrotherapy is often recommended for older adults with OA, less is known about aqua fitness (AF), a widely available form of aqua-based exercise. To compare the effect of an AF program and a seated aqua-based exercise program on a range of functional measures and quality of life among older adults with OA. Thirty-five older adults with OA were allocated to an AF group or an active control group who performed seated exercises in warm water for 12 weeks. The primary outcome measure was the timed up-and-go (TUG) test; other measures included step test, sit-to-stand (STS) test, handgrip strength test, 400-m walk test, Arthritis Impact Measurement Scale-Short Form (AIMS2-SF), and Falls Efficacy Scale-International (FES-I). FES-I scores improved significantly in the AF group compared with the control group (P=0.04). Within-group analysis indicated both groups significantly improved their 400-m walk time (P=0.04) and that the AF group significantly improved its step test right (P=0.02) and left (P=0.00) and the AIMS2-SF total score (P=0.02). No significant change in TUG, STS, or handgrip strength was observed for either group. Aqua fitness may offer a number of positive functional and psychosocial benefits for older adults with OA, such as a reduced fear of falling and increased ability to perform everyday tasks.","subset":"pubmed_abstract"} +{"meta":{"pmid":21849560,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The control of mimicry by eye contact is mediated by medial prefrontal cortex.\nSpontaneous mimicry of other people's actions serves an important social function, enhancing affiliation and social interaction. This mimicry can be subtly modulated by different social contexts. We recently found behavioral evidence that direct eye gaze rapidly and specifically enhances mimicry of intransitive hand movements (Wang et al., 2011). Based on past findings linking medial prefrontal cortex (mPFC) to both eye contact and the control of mimicry, we hypothesized that mPFC might be the neural origin of this behavioral effect. The present study aimed to test this hypothesis. During functional magnetic resonance imaging (fMRI) scanning, 20 human participants performed a simple mimicry or no-mimicry task, as previously described (Wang et al., 2011), with direct gaze present on half of the trials. As predicted, fMRI results showed that performing the task activated mirror systems, while direct gaze and inhibition of the natural tendency to mimic both engaged mPFC. Critically, we found an interaction between mimicry and eye contact in mPFC, superior temporal sulcus (STS) and inferior frontal gyrus. We then used dynamic causal modeling to contrast 12 possible models of information processing in this network. Results supported a model in which eye contact controls mimicry by modulating the connection strength from mPFC to STS. This suggests that mPFC is the originator of the gaze-mimicry interaction and that it modulates sensory input to the mirror system. Thus, our results demonstrate how different components of the social brain work together to on-line control mimicry according to the social context.","subset":"pubmed_abstract"} +{"meta":{"pmid":27130838,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-30":1,"unknown":9}}},"text":"The KCC2 Cotransporter and Human Epilepsy: Getting Excited About Inhibition.\nThe cation-Cl- cotransporter KCC2, encoded by SLC12A5, is required for the emergence and maintenance of GABAergic fast synaptic inhibition in organisms across evolution. These findings have suggested that KCC2 deficiency might play a role in the pathogenesis human epilepsy, but this has only recently been substantiated by two lines of genetic evidence. The first is the discovery of heterozygous missense polymorphisms in SLC12A5, causing decreased KCC2-dependent Cl- extrusion capacity, in an Australian family with inherited febrile seizures and in a French-Canadian cohort with severe genetic generalized epilepsy (GGE). The second is the discovery of recessive loss-of-function mutations in SLC12A5 in patients with a severe, early-onset Mendelian disease termed \"epilepsy of infancy with migrating focal seizures\" (EIMFS). These findings collectively support the paradigm that precisely regulated KCC2 activity is required for synaptic inhibition in humans, and that genetically encoded impairment of KCC2 function, due to effects on gene dosage, intrinsic activity, or extrinsic regulation, can influence epilepsy phenotypes in patients. Accordingly, KCC2 could be a target for a novel antiepileptic strategies that aims to restore GABA inhibition by facilitating Cl- extrusion. Such drugs could have relevance for pharmaco-resistant epilepsies and possibly other diseases characterized by synaptic hyperexcitability, such as the spectrum autism disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":30407506,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":9}}},"text":"Drosophila suzukii (Diptera: Drosophilidae) Oviposition and Adult Emergence in Six Wine Grape Varieties Grown in Virginia.\nDrosophila suzukii (Matsumura) is a pest of small fruits and grapes in the United States and in its home range of Japan. Physiological and morphological laboratory testing was performed on six commonly grown wine grape varieties in Virginia. Skin thickness, penetration force, and \u00baBrix were analyzed to determine ovipositional preferences. Experiments were performed for three consecutive years from grapes collected at one Virginia vineyard. More eggs were laid in intact Viognier grapes than any other variety. Oviposition into intact grapes was not affected by skin thickness or \u00baBrix; however, oviposition increased when penetration force decreased. An ovipositional choice test determined no varietal preferences. Survivorship from egg to adulthood using uninjured and injured grapes was also assessed to determine varietal suitability as D. suzukii hosts, with more flies emerging from injured grapes than uninjured. However, D. suzukii adults did emerge from intact grapes and at higher percentages than previously recorded in other wine grape studies. All varieties had eggs oviposited into them when injured. Determining the time at which each grape variety became susceptible to oviposition was determined using a D. suzukii bioassay spanning 12 wk using grapes from the green pea stage until ripe. Susceptibility to D. suzukii oviposition was based upon ripening period and penetration force. Early ripening varieties may be more susceptible to D. suzukii oviposition in the field with later maturing, harder fleshed-varieties which may escape D. suzukii oviposition.","subset":"pubmed_abstract"} +{"meta":{"pmid":19014539,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2015-18":1,"2013-48":1,"2024-22":1,"unknown":14}}},"text":"Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria.\nInsecticide resistance in Anopheles mosquitoes is threatening the success of malaria control programmes. This is particularly true in Benin where pyrethroid resistance has been linked to the failure of insecticide treated bed nets. The role of mutations in the insecticide target sites in conferring resistance has been clearly established. In this study, the contribution of other potential resistance mechanisms was investigated in Anopheles gambiae s.s. from a number of localities in Southern Benin and Nigeria. The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes. All mosquitoes sampled belonged to the M form of An. gambiae s.s. There were high levels of permethrin resistance in an agricultural area (Akron) and an urban area (Gbedjromede), low levels of resistance in mosquito samples from an oil contaminated site (Ojoo) and complete susceptibility in the rural Orogun location. The target site mutation kdrW was detected at high levels in two of the populations (Akron f = 0.86 and Gbedjromede f = 0.84) but was not detected in Ojoo or Orogun. Microarray analysis using the Anopheles gambiae detox chip identified two P450s, CYP6P3 and CYP6M2 up regulated in all three populations, the former was expressed at particularly high levels in the Akron (12.4-fold) and Ojoo (7.4-fold) populations compared to the susceptible population. Additional detoxification and redox genes were also over expressed in one or more populations including two cuticular pre-cursor genes which were elevated in two of the three resistant populations. Multiple resistance mechanisms incurred in the different breeding sites contribute to resistance to permethrin in Benin. The cytochrome P450 genes, CYP6P3 and CYP6M2 are upregulated in all three resistant populations analysed. Several additional potential resistance mechanisms were also identified that warrant further investigation. Metabolic genes were over expressed irrespective of the presence of kdr, the latter resistance mechanism being absent in one resistant population. The discovery that mosquitoes collected from different types of breeding sites display differing profiles of metabolic genes at the adult stage may reflect the influence of a range of xenobiotics on selecting for resistance in mosquitoes.","subset":"pubmed_abstract"} +{"meta":{"pmid":15843466,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"2024-30":1,"unknown":14}}},"text":"Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link?\nHypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview\/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms\/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity\/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and\/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.","subset":"pubmed_abstract"} +{"meta":{"pmid":24075511,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2017-13":2,"2024-26":1,"unknown":10}}},"text":"Amino acid transporters expression in acinar cells is changed during acute pancreatitis.\nPancreatic acinar cells accumulate amino acids against a marked concentration gradient to synthesize digestive enzymes. Thus, the function of acinar cells depends on amino acid uptake mediated by active transport. Despite the importance of this process, pancreatic amino acid transporter expression and cellular localization is still unclear. We screened mouse pancreas for the expression of genes encoding amino acid transporters. We showed that the most highly expressed transporters, namely sodium dependent SNAT3 (Slc38a3) and SNAT5 (Slc38a5) and sodium independent neutral amino acids transporters LAT1 (Slc7a5) and LAT2 (Slc7a8), are expressed in the basolateral membrane of acinar cells. SNAT3 and SNAT5, LAT1 and LAT2 are expressed in acinar cells. Additional evidence that these transporters are expressed in mature acinar cells was gained using acinar cell culture and acute pancreatitis models. In the acute phase of pancreatic injury, when acinar cell loss occurs, and in an acinar cell culture model, which mimics changes occurring during pancreatitis, SNAT3 and SNAT5 are strongly down-regulated. LAT1 and LAT2 were down-regulated only in the in vitro model. At protein level, SNAT3 and SNAT5 expression was also reduced during pancreatitis. Expression of other amino acid transporters was also modified in both models of pancreatitis. The subset of transporters with differential expression patterns during acute pancreatitis might be involved in the injury\/regeneration phases. Further expression, localization and functional studies will follow to better understand changes occurring during acute pancreatitis. These findings provide insight into pancreatic amino acid transport in healthy pancreas and during acute pancreatitis injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":17608939,"dup_signals":{"dup_doc_count":19,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2015-18":1,"2015-06":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":13}}},"text":"A topological algorithm for identification of structural domains of proteins.\nIdentification of the structural domains of proteins is important for our understanding of the organizational principles and mechanisms of protein folding, and for insights into protein function and evolution. Algorithmic methods of dissecting protein of known structure into domains developed so far are based on an examination of multiple geometrical, physical and topological features. Successful as many of these approaches are, they employ a lot of heuristics, and it is not clear whether they illuminate any deep underlying principles of protein domain organization. Other well-performing domain dissection methods rely on comparative sequence analysis. These methods are applicable to sequences with known and unknown structure alike, and their success highlights a fundamental principle of protein modularity, but this does not directly improve our understanding of protein spatial structure. We present a novel graph-theoretical algorithm for the identification of domains in proteins with known three-dimensional structure. We represent the protein structure as an undirected, unweighted and unlabeled graph whose nodes correspond to the secondary structure elements and edges represent physical proximity of at least one pair of alpha carbon atoms from two elements. Domains are identified as constrained partitions of the graph, corresponding to sets of vertices obtained by the maximization of the cycle distributions found in the graph. When a partition is found, the algorithm is iteratively applied to each of the resulting subgraphs. The decision to accept or reject a tentative cut position is based on a specific classifier. The algorithm is applied iteratively to each of the resulting subgraphs and terminates automatically if partitions are no longer accepted. The distribution of cycles is the only type of information on which the decision about protein dissection is based. Despite the barebone simplicity of the approach, our algorithm approaches the best heuristic algorithms in accuracy. Our graph-theoretical algorithm uses only topological information present in the protein structure itself to find the domains and does not rely on any geometrical or physical information about protein molecule. Perhaps unexpectedly, these drastic constraints on resources, which result in a seemingly approximate description of protein structures and leave only a handful of parameters available for analysis, do not lead to any significant deterioration of algorithm accuracy. It appears that protein structures can be rigorously treated as topological rather than geometrical objects and that the majority of information about protein domains can be inferred from the coarse-grained measure of pairwise proximity between elements of secondary structure elements.","subset":"pubmed_abstract"} +{"meta":{"pmid":23955026,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":2,"2017-13":1,"2024-30":1,"unknown":10}}},"text":"Burden among partner caregivers of patients diagnosed with localized prostate cancer within 1 year after diagnosis: an economic perspective.\nInformal care plays an important role in the overall care for people with cancer. This study estimates lost productivity and informal caregiving and associated costs among partner caregivers of localized prostate cancer patients within 1 year after diagnosis. We applied data from the Family and Cancer Therapy Selection study, a three-wave self-administered survey among patients diagnosed with localized prostate cancer and their partner caregivers in multiple clinics in the USA. Time spent was measured by the sum of working hours lost, informal caregiving hours performed, and hours spent on household chores. The national median income for women 55 years or older was used to calculate costs associated with the time spent using the opportunity cost method. Descriptive and bivariate analyses were conducted. The average working hours decreased from 14.0 h\/week (SD = 17.6) to 10.9 h\/week (SD = 15.9), without a significant change in responsibility\/intensity at work. The mean annual time spent on informal caregiving and household chores was 65.9 h\/year (SD = 172.4) and 76.2 h\/year (SD = 193.3), respectively. The mean annual economic burden among partner caregivers was US$6,063 (range US$571-US$47,105) in 2009 dollars accounted for by a mean of 276.2 h (range 26-2,146) in the study sample. The time spent on informal caregiving and household chores varied by patient and caregiver characteristics. Pilot estimates on non-medical economic burden among partner caregivers (spouses) during the initial phase of the treatment provide important information for comprehensive estimation of disease burden and can be used in cost-effectiveness analyses of prostate cancer interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":31223041,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Impact of early rasburicase on incidence of clinical tumor lysis syndrome in lymphoma.\nEarly administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes in tumor lysis syndrome (TLS), specifically, the prevention of acute kidney injury (AKI). This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS. Excluded patients had AKI or were on dialysis at hospital admission. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. In 383 included patients, the incidence of new-onset AKI during hospitalization was 6%. Predictors included age, history of renal or cardiovascular disease, and UA >8 mg\/dL. Rasburicase use did not significantly impact the risk of developing AKI (HR 2.3; p = .11). The UA level at the time of administration did not modify the effect of rasburicase on prevention of AKI (p = .36 for the interaction term).","subset":"pubmed_abstract"} +{"meta":{"pmid":23082087,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Hesperidin-3'-o-methylether is more potent than hesperidin in phosphodiesterase inhibition and suppression of ovalbumin-induced airway hyperresponsiveness.\nHesperidin is present in the traditional Chinese medicine, \"Chen Pi,\" and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3'-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3'-O-methylether, but not hesperidin, at 30 \u03bcmol\/kg (p.o.) significantly attenuated the enhanced pause (P(enh)) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG(2a) in the serum of sensitized and challenged mice, suggesting that hesperidin-3'-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by \u03b2-glucosidase after oral administration. Neither influenced xylazine\/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3'-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4(H)\/PDE4(L)) ratio than hesperidin. Thus, hesperidin-3'-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":20844202,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Ability of IDO to attenuate liver injury in alpha-galactosylceramide-induced hepatitis model.\nIDO converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in \u03b1-galactosylceramide (\u03b1-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered \u03b1-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after \u03b1-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In \u03b1-GalCer-induced hepatitis models, TNF-\u03b1 is critical in the development of liver injury. The mRNA expression and protein level of TNF-\u03b1 in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with \u03b1-GalCer were analyzed by flow cytometry, and the numbers of CD49b(+) and CD11b(+) cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice injected with \u03b1-GalCer, TNF-\u03b1 secretion in these mice was greater than that in WT mice. Deficiency of IDO exacerbated liver injury in \u03b1-GalCer-induced hepatitis. IDO induced by proinflammatory cytokines may decrease the number of TNF-\u03b1-producing immune cells in the liver. Thus, IDO may suppress overactive immune response in the \u03b1-GalCer-induced hepatitis model.","subset":"pubmed_abstract"} +{"meta":{"pmid":11240905,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2023-40":1,"2021-25":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-45":1,"2019-51":2,"2019-43":1,"2019-35":2,"2019-30":1,"2016-36":1,"2015-35":1,"2023-50":1,"2024-26":1}}},"text":"A calreticulin-like molecule from the human hookworm Necator americanus interacts with C1q and the cytoplasmic signalling domains of some integrins.\nCalreticulin was recently identified as a hookworm (Necator americanus) allergen, implying secretion, and contact with cells of the immune system, or significant worm attrition in the tissues of the host. As human calreticulin has been shown to bind to and neutralize the haemolytic activity of the complement component C1q, and to be putatively involved in integrin-mediated intracellular signalling events in platelets, it was of interest to determine whether a calreticulin from a successful nematode parasite of humans, with known immune modulatory and antihaemostatic properties, exhibited a capacity to interfere with complement activation and to interact with integrin domains associated with cell signalling in platelets and other leucocytes. We can now report that recombinant calreticulin failed to demonstrate significant calcium binding capacity, which is a hallmark of calreticulins in general and may indicate inappropriate folding following expression in a prokaryote. Nevertheless, recombinant calreticulin retained sufficient molecular architecture to bind to, and inhibit the haemolytic capacity of, human C1q. Furthermore, recombinant calreticulin reacted in surface plasmon resonance analysis (SPR) with peptides corresponding to cytoplasmic signalling domains of the integrins alphaIIb and alpha5, in a calcium independent manner. SPR was also used to ratify the specificity of a polyclonal antibody to hookworm calreticulin, which was then used to assess the stage specificity of expression of the native molecule (in comparison with reverse transcriptase-polymerase chain reaction), to indicate its apparent secretion, and to purify native calreticulin from worm extracts by affinity chromatography. This development will allow the functional tests described above to be repeated for native calreticulin, to ascertain its role in the host-parasite relationship.","subset":"pubmed_abstract"} +{"meta":{"pmid":31317738,"dup_signals":{"dup_doc_count":13}},"text":"Breakdown of the Static Picture of Defect Energetics in Halide Perovskites: The Case of the Br Vacancy in CsPbBr3.\nWe consider the Br vacancy in CsPbBr3 as a prototype for the impact of structural dynamics on defect energetics in halide perovskites (HaPs). Using first-principles molecular dynamics based on density functional theory, we find that the static picture of defect energetics breaks down; the energy level associated with a Br vacancy is found to be intrinsically dynamic, oscillating by as much as 1 eV on the picosecond time scale at room temperature. These significant energy fluctuations are correlated with the distance between the neighboring Pb atoms across the vacancy and with the electrostatic potential at these Pb atomic sites. We expect this unusually strong coupling of structural dynamics and defect energetics to bear important implications for both experimental and theoretical analyses of defect characteristics in HaPs. It may also hold significant ramifications for carrier transport and defect tolerance in this class of photovoltaic materials.","subset":"pubmed_abstract"} +{"meta":{"pmid":17971530,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":9}}},"text":"Adaptive therapy for androgen-independent prostate cancer: a randomized selection trial of four regimens.\nPhysicians typically switch therapies unless clinically relevant thresholds of response are observed, and treatments that produce high-quality responses and that are active in the salvage setting are generally felt to be promising. With the goal of efficiently selecting promising regimens for more advanced trials, we conducted a randomized selection trial of four regimens to identify promising treatments for androgen-independent prostate cancer. Patients without prior exposure to cytotoxic therapy were randomly assigned to one of four regimens (i.e., cyclophosphamide, vincristine, and dexamethasone [CVD]; ketoconazole plus doxorubicin alternating with vinblastine plus estramustine [KA\/VE]; weekly paclitaxel, estramustine, and carboplatin [TEC]; paclitaxel, estramustine, and etoposide [TEE]). Patients were evaluated every 8 weeks to assess response and adverse events. Patients who responded continued with the same treatment; those who did not were randomly assigned to one of the other three treatments. Response was assessed by considering tumor-specific symptoms, tumor regression, and prostate-specific antigen (PSA) changes. Treatment was continued until two consecutive courses induced a response (i.e., overall success, the major criterion for which was 80% PSA reduction) or until patients were given two different regimens that failed to induce such a response. Median overall survival from registration among all 150 patients was 22 months (95% confidence interval [CI] = 19 to 26 months). Estimated survival at 3 and 5 years, respectively, was 26% (95% CI = 20% to 35%) and 10% (95% CI = 5% to 16%). Overall success was achieved in 35 patients with the initial treatment (i.e., four treated with CVD, seven with KA\/VE, 14 with TEC, and 10 with TEE) and in nine more patients with a second-line regimen (i.e., two with CVD, five with KA\/VE, and two with TEC). For all 44 (29%, 95% CI = 23% to 37%) patients with overall success, median survival was 30 months (95% CI = 26 to 40 months); for the other 106 patients, it was 19 months (95% CI = 17 to 22 months). TEC produced the greatest number and proportion of successful courses of treatment, and TEC followed by KA\/VE was the most promising two-stage strategy. Some patients responded to particular treatments, and responses to second-line treatments were not rare. We propose that TEC be considered for phase III evaluation.","subset":"pubmed_abstract"} +{"meta":{"pmid":29497914,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":10}}},"text":"Exploring the Link Between Daily Relationship Quality, Sexual Desire, and Sexual Activity in Couples.\nCurrent models of sexual responding emphasize the role of contextual and relational factors in shaping sexual behavior. The present study used a prospective diary design to examine the temporal sequence and variability of the link between sexual and relationship variables in a sample of couples. Studying sexual responding in the everyday context of the relationship is necessary to get research more aligned with the complex reality of having sex in a relationship, thereby increasing ecological validity and taking into account the dyadic interplay between partners. Over the course of 21 days, 66 couples reported every day on their sexual desire, sexual activity (every morning), and relationship quality (every evening). In addition, we examined whether the link between these daily variables was moderated by relationship duration, having children, general relationship satisfaction, and sexual functioning. Results showed that the sexual responses of women depended on the relationship context, mainly when having children and being in a longer relationship. Male sexual responding depended less on contextual factors but did vary by level of sexual functioning. Several cross-partner effects were found as well. These results verify that relational and sexual variables feed forward into each other, indicating the need to incorporate interpersonal dynamics into current models of sexual responding and to take into account variability and dyadic influences between partners.","subset":"pubmed_abstract"} +{"meta":{"pmid":23018296,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2013-48":1,"unknown":7}}},"text":"Prevalence of celiac disease among blood donors in S\u00e3o Paulo: the most populated city in Brazil.\nCeliac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immunemediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. S\u00e3o Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of S\u00e3o Paulo by collecting information on the ancestry of the population studied. The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Funda\u00e7\u00e3o Pr\u00f3-Sangue Blood Center of S\u00e3o Paulo, S\u00e3o Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. The prevalence of celiac disease is at least 1:286 among supposedly healthy blood bank volunteers in S\u00e3o Paulo, Brazil.","subset":"pubmed_abstract"} +{"meta":{"pmid":10751479,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2014-10":3,"2013-48":3,"unknown":9}}},"text":"Aortic aneurysmal disease: assessment of stent-graft treatment-CT versus conventional angiography.\nTo compare computed tomographic (CT) angiography and conventional angiography for determining the success of endoluminal stent-graft treatment of aortic aneurysms. Forty patients underwent conventional angiography and CT angiography following treatment of aortoiliac aneurysms with endoluminal stent-grafts. Six additional sets of conventional angiographic-CT angiographic examinations were performed in five patients after placement of additional stent-grafts or coil embolization to treat perigraft leakage. Three faculty CT radiologists who were blinded to patient clinical data and outcome independently interpreted the CT angiograms, and three faculty angiographers, who were not involved in the stent-graft deployment, interpreted the conventional angiograms. Images were assessed for the presence of postdeployment complications. A reference standard was developed by experienced radiologists using all available images and clinical data. Sensitivities, specificities, and kappa values were calculated. Perigraft leakage was the most commonly identified complication. Twenty perigraft leaks were detected in the results of 46 examinations. Sensitivities and specificities for detecting perigraft leakage were 63% and 77% for conventional angiography and 92% and 90% for CT angiography, respectively. The kappa value was 0. 41 for conventional angiography and 0.81 for CT angiography. CT angiography is the preferred method for establishing the presence of perigraft leakage following treatment of aortoiliac aneurysms with stent-grafts.","subset":"pubmed_abstract"} +{"meta":{"pmid":32610581,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover.\nThis study investigated the efficacy and safety of pimasertib (MEK1\/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc\/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg\/m2; intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively; hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42-0.83; p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00-4.98; p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively; HR 0.89, 95% CI 0.61-1.30); 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade \u22653 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068.","subset":"pubmed_abstract"} +{"meta":{"pmid":15936329,"dup_signals":{"dup_doc_count":28,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-14":1,"2022-40":1,"2022-33":1,"2020-40":2,"2020-29":1,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-18":1,"2018-51":1,"2018-47":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-26":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-50":1,"2017-13":1,"2024-10":1}}},"text":"Sid4: A secreted vertebrate immunoglobulin protein with roles in zebrafish embryogenesis.\nThe small members of the immunoglobulin superfamily (IGSF) are a molecularly diverse group of proteins composed solely of immunoglobulin domains. They may be secreted or tethered to the cell mebrane via GPI linkages and are proposed to have important functions in vivo. However, very few small IGSFs have been functionally characterized. During an ongoing in situ hybridization analysis of expressed sequence tags in zebrafish we identified secreted immunoglobulin domain 4 (sid4), a gene encoding a soluble vertebrate protein composed solely of four immunoglobulin domains. Throughout development, sid4 is expressed in regions of the embryo undergoing active cell division and migration. Functional analysis using morpholino antisense oligonucleotides demonstrates that timing of gene expression is normal in morphants, but these embryos are smaller and exhibit defects in epiboly and patterning of axial and prechordal mesoderm. Analyses of chordin, pax2, krox20, and dlx2 expression in morphants demonstrate that early brain patterning is normal but later organization of hindbrain neurons and development of cranial neural crest are perturbed. Levels of apoptosis in morphants were normal prior to 90% epiboly, but were elevated after 10 h post-fertilization (hpf). Apoptosis does not account for early patterning defects of axial mesoderm, but likely contributes to overall reduction in embryo size. Phylogenetic analysis demonstrates that Sid4 is strikingly similar to the fibronectin binding Ig domains of Perlecan\/HSPG2. Overall, our data demonstrate a fundamental role for sid4, possibly as a co-factor in extracellular matrix (ECM) interactions, in processes underlying tissue patterning and organogenesis in a vertebrate.","subset":"pubmed_abstract"} +{"meta":{"pmid":26339375,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"EPO protects M\u00fcller cell under high glucose state through BDNF\/TrkB pathway.\nNeurotrophic factor decreased in the early stage of diabetic retinal nerve cells. Neurons damage brain derived neurotrophic factor (BDNF) and receptor TrkB expression reduced. Erythropoietin (EPO) plays an important role in protecting early diabetic retinopathy. The rats were euthanized at 24 h after EPO vitreous injection and the retina was separated. HE staining was applied to observe the pathological tissue morphology. Immunohistochemistry, immunofluorescence, and Western blot were used to detect BDNF, TrkB, extracellular signal-regulated kinase (ERK), and glial fibrillary acidic portein (GFAP) expression. Retinal structure was clear in group C, while the retinal thickness and RGCs number decreased in group B at 24 w. Retinal thickness in group E was greater than in group B but lower than in group C. GFAP and ERK expression increased in both group B and E, whereas the latter was significantly lower than the former. TrkB protein level was in group E > B > C at 4 w, while it was in group C > group E > group B at 24 w. BDNF expression in group B was higher than in group C at 4 w, whereas it was opposite at 24 w. BDNF expression increased in group E at 4 w, and it was similar in group E compared with group C at 24 w. EPO vitreous injection can increase BDNF and TrkB expression, while reduce GFAP and ERK expression in diabetes rat retina. It could protect M\u00fcller cells through BDNF\/TrkB pathway to play a role of nerve nutrition.","subset":"pubmed_abstract"} +{"meta":{"pmid":29317940,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"ELISA Serology for Antibodies Against Chlamydia trachomatis in Crohn's Disease.\nRecently we reported IgA anti-Chlamydia antibodies in patients with Crohn's disease (CD), in particular in four patients from a single family of six with CD. We studied sera from four cohorts from the north of France. These were identified as: EPIMAD (80 pediatric onset CD and 20 pediatric onset ulcerative colitis), MINOTOR (148 adult onset sporadic CD and 50 adult onset ulcerative colitis), Grande Famillies (50) and matched controls for the Grande Famillies cohort (49). Sera were tested using commercial anti-Chlamydia trachomatis (LGV2:434) IgG and IgA human enzyme-linked immunosorbent assay (ELISA) kits. Cutoff for positivity was 11.0 standard units. Patients with sporadic CD, unaffected first degree relatives from multiplex families and ulcerative colitis patients had no greater serologic reactivity than controls. However, multiplex families' patients had twice as many positives as the other groups: for IgG 20% vs. 8%; for IgA 20% vs. 10%. Though not attaining statistical significance, the data showed that familial CD patients had greater exposure to C. trachomatis than sporadic CD patients, supporting our earlier results from one family from the north of France. More specific serologic tests based on outer membrane proteins will need to be employed against the various Chlamydia species with zoonotic potential.","subset":"pubmed_abstract"} +{"meta":{"pmid":23312358,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":9}}},"text":"High-frequency QRS analysis improves the specificity of exercise ECG testing in women referred for angiography.\nExercise ECG testing in women for the diagnosis of coronary artery disease (CAD) has a higher false-positive rate compared to men. Consequently, women referred for coronary angiography following a positive exercise test often have normal coronary arteries or non-obstructive lesions. Analysis of the high-frequency components of the QRS complexes (HFQRS) has been reported to provide a sensitive means of detecting myocardial ischemia, independent of gender. The aim of the present study was to prospectively test the diagnostic performance of HFQRS and conventional exercise ECG in detecting stress-induced ischemia in women referred for coronary angiography. The study included 113 female patients (age 64 \u00b1 9 years) referred for non-urgent angiography. Patients performed a symptom-limited treadmill exercise test prior to angiography. High-resolution ECG was acquired during the test and used for both HFQRS and conventional ST-segment analyses. HFQRS diagnosis was determined by computerized analysis, measuring the stress-induced reduction in HFQRS intensity. The diagnostic performance of HFQRS, ST-segment analysis and clinical interpretation of the exercise test were compared, using angiography as a gold standard. HFQRS provided sensitivity of 70% and specificity of 80% for detection of angiographically significant coronary obstruction (\u2265 70% stenosis in a single vessel or \u2265 50% in the left main artery). HFQRS was more specific than exercise ECG test (80% vs. 55%, P<.005), as well as more accurate (76% vs. 62%, P<.01). The number of ECG leads with ischemic HFQRS response correlated with the severity of CAD. HFQRS was highly specific (93%) in patients who achieved their age-predicted target heart rate, and retained its diagnostic accuracy in subgroups of patients with resting ECG abnormalities or inconclusive exercise ECG. HFQRS analysis, as an adjunct technology to exercise stress testing, may improve the diagnostic value of the ECG, and reduce the number of unnecessary imaging and invasive procedures.","subset":"pubmed_abstract"} +{"meta":{"pmid":9062372,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.\nFive lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1\/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.","subset":"pubmed_abstract"} +{"meta":{"pmid":8099067,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Piglet ileal mucus contains protein and glycolipid (galactosylceramide) receptors specific for Escherichia coli K88 fimbriae.\nThe aim of this study was to characterize the Escherichia coli K88-specific receptors in mucus from the small intestines of 35-day-old piglets with the isogenic strains E. coli K-12(pMK005) (K88+) and E. coli K-12(pMK002) (K88-). These strains differed only in that the latter one cannot produce intact K88 fimbriae because of a deletion in the gene coding for the major fimbrial subunit. Adhesion was studied by incubating 3H-labeled bacteria with crude mucus, pronase-treated whole mucus, mucus fractionated by gel filtration, delipidated mucus, or extracted lipids immobilized in microtiter wells. In addition, E. coli strains were tested for adhesion to glycolipids extracted from mucus by overlaying glycolipid chromatograms with 125I-labeled bacteria. The recently reported finding that K88 fimbriae bind to glycoproteins in mucus from the piglet small intestine was confirmed in two ways. Pronase treatment of immobilized mucus reduced adhesion by 82%, and adhesion to delipidated mucus was 14 times greater for the K88+ than for the K88- strain. E. coli K88+ adhered to several of the fractions collected after gel filtration of crude mucus, including the void volume (M(r), > 250,000). Receptor activity specific for the K88 fimbriae was demonstrated in the lipids extracted from mucus, as the neutral lipids contained six times as much receptor activity as the acidic lipid fraction. Specificity was confirmed by demonstrating that adhesion to the total lipids could be inhibited by pretreatment of the immobilized lipids with K88 fimbriae. Relative to K-12 (K88-), the K-12 (K88+) bacterial cells bound more avidly to galactosylceramide when the neutral lipids were separated on thin-layer chromatography plates. No adhesion to lipids in the acidic fraction separated on thin-layer plates was detected. Relative to adhesion of K-12 (K88-), adhesion of K-12 (K88+) to commercially available galactosylceramide immobilized in microtiter wells confirmed the results with the thin-layer plates. It can be concluded that 35-day-old piglet mucus contains both protein and glycolipid receptors specific for K88 fimbriae, the latter being galactosylceramide.","subset":"pubmed_abstract"} +{"meta":{"pmid":34157080,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":9}}},"text":"Surgical data recording in the operating room: a systematic review of modalities and metrics.\nOperating room recording, via video, audio and sensor-based recordings, is increasingly common. Yet, surgical data science is a new field without clear guidelines. The purpose of this study is to examine existing published studies of surgical recording modalities to determine which are available for use in the operating room, as a first step towards developing unified standards for this field. Medline, EMBASE, CENTRAL and PubMed databases were systematically searched for articles describing modalities of data collection in the operating room. Search terms included 'video-audio media', 'bio-sensing techniques', 'sound', 'movement', 'operating rooms' and others. Title, abstract and full-text screening were completed to identify relevant articles. Descriptive statistical analysis was performed for included studies. From 3756 citations, 91 studies met inclusion criteria. These studies described 10 unique data-collection modalities for 17 different purposes in the operating room. Data modalities included video, audio, kinematic and eye-tracking among others. Data-collection purposes described included surgical trainee assessment, surgical error, surgical team communication and operating room efficiency. Effective data collection and utilization in the operating room are imperative for the provision of superior surgical care. The future operating room landscape undoubtedly includes multiple modalities of data collection for a plethora of purposes. This review acts as a foundation for employing operating room data in a way that leads to meaningful benefit for patient care.","subset":"pubmed_abstract"} +{"meta":{"pmid":22369775,"dup_signals":{"dup_doc_count":34,"dup_dump_count":31,"dup_details":{"curated_sources":1,"2022-33":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-29":2,"2020-24":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-35":1,"2019-26":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-22":1,"2022-49":1}}},"text":"Arachidonic acid regulation of the cytosolic phospholipase A 2\u03b1\/cyclooxygenase-2 pathway in mouse endometrial stromal cells.\nTo investigate the role of arachidonic acid (AA) in mouse endometrial stromal cells. Experimental animal study. University research laboratory. Sexually mature female CD1-strain mice. Primary culture of endometrial stromal cells. Western blot and real-time polymerase chain reaction for gene expression and\/or phosphorylation analysis. Luciferase assay for Cox-2 promoter analysis. AA-derived prostaglandins play important roles during embryo implantation and decidualization. However, the function of AA itself in reproduction is largely unknown. In this study, exogenous AA stimulated cPLA(2\u03b1) phosphorylation and COX-2 expression, mainly through ERK1\/2 in mouse endometrial stromal cells, and p38 inhibitor modestly inhibited cPLA(2\u03b1) phosphorylation induced by AA. The induction of COX-2 by AA was diminished by short interfering RNA against C\/EBP\u03b2 and inhibitory C\/EBP\u03b2 (LIP). C\/EBP\u03b2 binding site at -872--864 of Cox-2 promoter contributes to Cox-2 promoter activation induced by C\/EBP\u03b2 transfection. The expression of C\/EBP\u03b2 protein induced by AA was inhibited by p38 inhibitor, and the phosphorylation of C\/EBP\u03b2 induced by AA was inhibited by p38 inhibitor and ERK1\/2 inhibitor. A nonmetabolized analogue of AA (ETYA) also enhanced cPLA(2\u03b1) phosphorylation and COX-2 expression. The activation of cPLA(2\u03b1)\/COX-2 by AA was not inhibited by COX inhibitor indomethacin. AA can induce cPLA(2\u03b1)\/COX-2 pathway activation in mouse endometrial stromal cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":25901427,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Prednisolone or pentoxifylline for alcoholic hepatitis.\nAlcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).","subset":"pubmed_abstract"} +{"meta":{"pmid":27903493,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Cancer Detection in Human Tissue Samples Using a Fiber-Tip pH Probe.\nIntraoperative detection of tumorous tissue is an important unresolved issue for cancer surgery. Difficulty in differentiating between tissue types commonly results in the requirement for additional surgeries to excise unremoved cancer tissue or alternatively in the removal of excess amounts of healthy tissue. Although pathologic methods exist to determine tissue type during surgery, these methods can compromise postoperative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis, and are restricted to excised tissue. In this work, we report the development of an optical fiber probe that could potentially find use as an aid for margin detection during surgery. A fluorophore-doped polymer coating is deposited on the tip of an optical fiber, which can then be used to record the pH by monitoring the emission spectra from this dye. By measuring the tissue pH and comparing with the values from regular tissue, the tissue type can be determined quickly and accurately. The use of a novel lift-and-measure technique allows for these measurements to be performed without influence from the inherent autofluorescence that commonly affects fluorescence-based measurements on biological samples. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration, which could find use in the operating theater. Use of this probe in surgery either on excised or in vivo tissue has the potential to improve success rates for complete removal of cancers. Cancer Res; 76(23); 6795-801. \u00a92016 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":33811473,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"A NIR fluorescent smart probe for imaging tumor hypoxia.\nTumor hypoxia is a characteristic of paramount importance due to low oxygenation levels in tissue negatively correlating with resistance to traditional therapies. The ability to noninvasively identify such could provide for personalized treatment(s) and enhance survival rates. Accordingly, we recently developed an NIR fluorescent hypoxia-sensitive smart probe (NO2 -Rosol) for identifying hypoxia via selectively imaging nitroreductase (NTR) activity, which could correlate to oxygen deprivation levels in cells, thereby serving as a proxy. We demonstrated proof of concept by subjecting a glioblastoma (GBM) cell line to extreme stress by evaluating such under radiobiological hypoxic (pO2 \u2264 ~0.5%) conditions, which is a far cry from representative levels for hypoxia for brain glioma (pO2 = ~1.7%) which fluctuate little from physiological hypoxic (pO2 = 1.0-3.0%) conditions. We aimed to evaluate the robustness, suitability, and feasibility of NO2 -Rosol for imaging hypoxia in vitro and in vivo via assessing NTR activity in diverse GBM models under relevant oxygenation levels (pO2 = 2.0%) within physiological hypoxic conditions that mimic oxygenation levels in GBM tumor tissue in the brain. We evaluated multiple GBM cell lines to determine their relative sensitivity to oxygenation levels via measuring carbonic anhydrase IX (CAIX) levels, which is a surrogate marker for indirectly identifying hypoxia by reporting on oxygen deprivation levels and upregulated NTR activity. We evaluated for hypoxia via measuring NTR activity when employing NO2 -Rosol in in vitro and tumor hypoxia imaging studies in vivo. The GBM39 cell line demonstrated the highest CAIX expression under hypoxic conditions representing that of GBM in the brain. NO2 -Rosol displayed an 8-fold fluorescence enhancement when evaluated in GBM39 cells (pO2 = 2.0%), thereby establishing its robustness and suitability for imaging hypoxia under relevant physiological conditions. We demonstrated the feasibility of NO2 -Rosol to afford tumor hypoxia imaging in vivo via it demonstrating a tumor-to-background of 5 upon (i) diffusion throughout, (ii) bioreductive activation by NTR activity in, and (iii) retention within, GBM39 tumor tissue. We established the robustness, suitability, and feasibility of NO2 -Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.","subset":"pubmed_abstract"} +{"meta":{"pmid":22916880,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Fortification of cheese with vitamin D3 using dairy protein emulsions as delivery systems.\nVitamin D is an essential vitamin that is synthesized when the body is exposed to sunlight or after the consumption of fortified foods and supplements. The purpose of this research was to increase the retention of vitamin D(3) in Cheddar cheese by incorporating it as part of an oil-in-water emulsion using a milk protein emulsifier to obtain a fortification level of 280 IU\/serving. Four oil-in-water vitamin D emulsions were made using sodium caseinate, calcium caseinate, nonfat dry milk (NDM), or whey protein. These emulsions were used to fortify milk, and the retention of vitamin D(3) in cheese curd in a model cheesemaking system was calculated. A nonemulsified vitamin D(3) oil was used as a control to fortify milk. Significantly more vitamin D(3) was retained in the curd when using the emulsified vitamin D(3) than the nonemulsified vitamin D(3) oil (control). No significant differences were observed in the retention of vitamin D(3) when emulsions were formulated with different emulsifiers. Mean vitamin D(3) retention in the model system cheese curd was 96% when the emulsions were added to either whole or skim milk compared with using the nonemulsified oil, which gave mean retentions of only 71% and 64% when added to whole and skim milk, respectively. A similar improvement in retention was achieved when cheese was made from whole and reduced-fat milk using standard manufacturing procedures on a small scale. When sufficient vitamin D(3) was added to produce cheese containing a target level of approximately 280 IU per 28-g serving, retention was greater when the vitamin D(3) was emulsified with NDM than when using nonemulsified vitamin D(3) oil. Only 58\u00b13% of the nonemulsified vitamin D(3) oil was retained in full-fat Cheddar cheese, whereas 78\u00b18% and 74\u00b11% were retained when using the vitamin D(3) emulsion in full-fat and reduced-fat Cheddar cheese, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":23333104,"dup_signals":{"dup_doc_count":15}},"text":"Helicobacter pylori eradication on iatrogenic ulcer by endoscopic resection of gastric tumour: a prospective, randomized, placebo-controlled multi-centre trial.\nThe role of Helicobacter pylori (H. pylori) eradication has not been clarified in the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm. The aim of this study was to evaluate whether H. pylori eradication could facilitate the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm. A total of 232 patients with H. pylori-positive early gastric cancer or gastric adenoma underwent endoscopic resection and were randomly allocated to eradication or placebo group in a prospective, double-blinded, and placebo-controlled manner. The primary outcome was measured by healing rate of ulcer, and the secondary outcomes by reduction rate of ulcer size, relief rate from ulcer-related symptoms, and adverse event rates. The healing rate of ulcer was 53% in eradication group and 51.6% in placebo group, respectively (p value=0.95). The reduction rate of ulcer size, relief rate from ulcer-related symptoms and adverse event rates were also not different between two groups. In multivariate analysis, initial ulcer size more than 3 cm and histology of cancer were significant factors affecting iatrogenic ulcer healing. H. pylori eradication did not facilitate iatrogenic ulcer healing at early and late phase after endoscopic resection of gastric neoplasm.","subset":"pubmed_abstract"} +{"meta":{"pmid":2304461,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.\nThe mechanism of ribosome binding to eucaryotic mRNAs is not well understood, but it requires the participation of eucaryotic initiation factors eIF-4A, eIF-4B, and eIF-4F and the hydrolysis of ATP. Evidence has accumulated in support of a model in which these initiation factors function to unwind the 5'-proximal secondary structure in mRNA to facilitate ribosome binding. To obtain direct evidence for initiation factor-mediated RNA unwinding, we developed a simple assay to determine RNA helicase activity, and we show that eIF-4A or eIF-4F, in combination with eIF-4B, exhibits helicase activity. A striking and unprecedented feature of this activity is that it functions in a bidirectional manner. Thus, unwinding can occur either in the 5'-to-3' or 3'-to-5' direction. Unwinding in the 5'-to-3' direction by eIF-4F (the cap-binding protein complex), in conjunction with eIF-4B, was stimulated by the presence of the RNA 5' cap structure, whereas unwinding in the 3'-to-5' direction was completely cap independent. These results are discussed with respect to cap-dependent versus cap-independent mechanisms of ribosome binding to eucaryotic mRNAs.","subset":"pubmed_abstract"} +{"meta":{"pmid":28954615,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"Randomised clinical trials in perinatal health care: a cost-effective investment.\nTo compare the health and economic impacts of implementing efficacious treatment interventions with maintaining standard practice in maternal and perinatal health care. We identified randomised clinical trials (RCTs) in the Perinatal Society of Australia and New Zealand trials database that commenced recruitment during 2008 and had completed recruitment by 2015. Data from clinical trial registries and publications were collated to calculate the potential cost savings achievable by implementing efficacious treatment interventions. Projected net cost savings over 5 years. Twenty-three eligible RCTs covering a range of behavioural and clinical interventions were identified, of which six reported interventions superior to standard practice (four trials) or placebo (two). The outcomes (but not the costs) of 17 trials were excluded from analysis (no difference between intervention and comparator groups in seven trials, recruitment problems in six, findings not yet published in four). The total funding amount for the 23 trials was $20.3 million; the potential cost savings over 5 years if the findings of the six trials reporting superior interventions were implemented was estimated to be $26.3 million if 10% of the eligible populations received the effective interventions, and $262.8 million with 100% implementation. Our retrospective analysis highlights the value of research in perinatal care and the importance of implementing positive findings for realising its value. Future trials in maternal and perinatal health care may provide significant returns on investment by informing clinical practice, improving patient outcomes and reducing health care costs.","subset":"pubmed_abstract"} +{"meta":{"pmid":18311789,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"ADAM-12 (meltrin alpha) is involved in chondrocyte proliferation via cleavage of insulin-like growth factor binding protein 5 in osteoarthritic cartilage.\nADAMs are a gene family of multifunctional proteins. We undertook this study to determine which ADAM species is up-regulated in osteoarthritic (OA) cartilage and to examine its pathobiologic function. Expression of the 13 different metalloproteinase-type ADAMs was screened by reverse transcription-polymerase chain reaction (PCR), and expression levels of prototype membrane-anchored ADAM-12 (ADAM-12m) were determined by real-time PCR. ADAM-12m expression in articular cartilage was examined by in situ hybridization, immunohistochemistry, and immunoblotting. Chondrocytes were used for functional analyses of ADAM-12m. ADAM-12m was selectively expressed in 87% of OA cartilage, and the expression level was significantly higher in OA cartilage than in normal cartilage. In situ hybridization showed that OA chondrocytes were responsible for the expression. ADAM-12m was immunolocalized on the membranes of OA chondrocytes, and its immunoreactivity correlated directly with the Mankin score and with degrees of chondrocyte cloning and proliferation. Immunoblotting analysis of OA chondrocytes demonstrated an active form of ADAM-12m. ADAM-12m expression in OA chondrocytes was selectively enhanced by transforming growth factor beta (TGFbeta), which also induced chondrocyte proliferation and degradation of insulin-like growth factor binding protein 5 (IGFBP-5). TGFbeta-induced chondrocyte proliferation was inhibited by suppression of IGF-1 signaling. In addition, TGFbeta-induced chondrocyte proliferation, chondrocyte cloning in agarose gel culture, and digestion of IGFBP-5 were inhibited with ADAM inhibitor, anti-ADAM-12 antibody, and small interfering RNA for ADAM-12. These data suggest a novel function of ADAM-12m in chondrocyte proliferation and cloning in OA cartilage through enhanced bioavailability of IGF-1 from the IGF-1-IGFBP-5 complex by selective IGFBP-5 digestion.","subset":"pubmed_abstract"} +{"meta":{"pmid":30627710,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Microfluidic fabrication of vesicles with hybrid lipid\/nanoparticle bilayer membranes.\nHybrid lipid\/nanoparticle membranes are suitable model systems both to study the complex interactions between nanoparticles and biological membranes, and to demonstrate technological concepts in cellular sensing and drug delivery. Unfortunately, embedding nanoparticles into the bilayer membrane of lipid vesicles is challenging due to the poor control over the vesicle fabrication process of conventional methodologies and the fragility of the modified lipid bilayer assembly. Here, the utility of water-in-oil-in-water double emulsion drops with ultrathin oil shells as templates to form vesicles with hybrid lipid\/nanoparticle membranes is reported. Moreover, upon bilayer formation, which occurs through dewetting of the oil solvent from the double emulsion drops, a phase separation is observed in the vesicle membrane, with solid-like nanoparticle-rich microdomains segregated into a continuous fluid-like nanoparticle-poor phase. This phase coexistence evidences the complex nature of the interactions between nanoparticles and lipid membranes. In this context, this microfluidic-assisted fabrication strategy may play a crucial role in thoroughly understanding such interactions given the uniform membrane properties of the resulting productions. Furthermore, the high encapsulation efficiency of both the vesicle membrane and core endows these vesicles with great potential for sensing applications and drug delivery.","subset":"pubmed_abstract"} +{"meta":{"pmid":28077390,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Reversible temperature-dependent differences in brown adipose tissue respiration during torpor in a mammalian hibernator.\nAlthough seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal and interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage. As predicted, maximal ETS enzyme activities of isolated BAT mitochondria did not differ between torpor and IBE. In contrast to this pattern, respiration rates of mitochondria isolated from torpid individuals were suppressed by ~60% compared with rates from IBE individuals when measured at 37\u00b0C. At 10\u00b0C, however, mitochondrial respiration rates tended to be greater in torpor than IBE. As a result, the temperature sensitivity (Q10) of mitochondrial respiration was significantly lower in torpor (~1.4) than IBE (~2.4), perhaps facilitating energy savings during entrance into torpor and thermogenesis at low body temperatures. Despite the observed differences in isolated mitochondria, norepinephrine-stimulated respiration rates of isolated BAT adipocytes did not differ between torpor and IBE, perhaps because the adipocyte isolation requires lengthy incubation at 37\u00b0C, potentially reversing any changes that occur in torpor. Such changes may include remodeling of BAT mitochondrial membrane phospholipids, which could change in situ enzyme activities and temperature sensitivities.","subset":"pubmed_abstract"} +{"meta":{"pmid":28339816,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Post-mortem toxicology in young sudden cardiac death victims: a nationwide cohort study.\nSeveral drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and\/or illicit). All toxicological findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac death with positive toxicology had higher rates of sudden arrhythmic death syndrome (SADS), compared with SCD with negative toxicology (56% vs. 42%, P < 0.01). In total, 752 agents were detected, and polypharmacy (defined as the presence of more than one drug) was present in 61% (n = 164), all substances combined. Psychotropic drugs were the most frequent (62%, n = 467), and 82% (n = 385) were in pharmacological or subpharmacological levels. We found that more than half of all toxicologically investigated SCD victims have positive post-mortem toxicological findings, and polypharmacy is displayed in a considerable proportion. SCD with positive toxicology had higher rate of SADS, suggesting that the compounds may play a proarrhythmic role in these cases.","subset":"pubmed_abstract"} +{"meta":{"pmid":16831655,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":9}}},"text":"Fracture and nonunion of the olecranon in total elbow arthroplasty.\nWhile fracture and nonunion of the olecranon have been reported in patients undergoing total elbow arthroplasty, little information exists about the management and outcome of these cases. Twenty-four patients (twenty-five elbows) were studied; fifteen (sixteen elbows) with rheumatoid arthritis and nine with post-traumatic elbow disorders. Twenty-three of the twenty-five elbows presented with an olecranon fracture or nonunion prior to the reported arthroplasty. During arthroplasty the olecranon fragment was initially treated by tension band in sixteen elbows, excision in four, suture fixation in two and three with stable fibrous union were left alone. At an average follow-up of 66 months (range, 18 to 242), there were twelve excellent, nine good, three fair and one poor results. The mean pre-operative Mayo Elbow Performance Score improved from 42 (range, 20 to 62) points pre-operatively to 86 (range, 50 to 100) points post-operatively (p < 0.001). Of the eighteen patients undergoing an attempt at union, nine (50%) obtained osseous union, eight (45%) developed a stable fibrous union and one patient underwent subsequent excision of the fragment due a superficial infection (5%). Fifteen of twenty-one could extend the hand above the head against gravity. A functional arc of motion and satisfactory clinical outcome can be achieved with osseous or a stable fibrous nonunion.","subset":"pubmed_abstract"} +{"meta":{"pmid":28970142,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-40":2,"2022-40":1,"2022-33":1,"2022-05":1,"2021-43":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-34":1,"2020-29":1,"2020-16":1,"2024-30":1}}},"text":"Pathological findings in explanted vaginal mesh.\nIn light of the legal issues and the shortage of data on histopathological findings, we summarized our experience on how explanted vaginal mesh specimens were managed in a surgical pathology practice during the last 5 years. Clinical history and pathology reports were collected from 155 women undergoing transvaginal tape excision. The degree of chronic inflammation, fibrosis, foreign-body giant cell reactions, the number of capillary vessels and nerve fibers, and the presence or absence of adipose tissue were recorded. Among the 155 patients, 65 (41.9%) were active medicolegal cases, with a significant increase in recent years. The main medical indications for mesh excision were pelvic pain, mesh erosion, voiding dysfunction, genital organ prolapse, and vaginal bleeding. In most cases, mild to moderate chronic inflammation with a mild degree of foreign-body giant cell reaction and minimal to mild fibrosis were found in explanted mesh specimens. The specimens were well vascularized without any evidence of nerve abnormality. Patient age correlated negatively with vaginal pain (P = .007) but positively with erosion (P = .005). In addition, the presence of adipose tissue within the explanted mesh correlated significantly with pelvic pain (P = .016). Overall, there was good tissue integration in all specimens. Considering the significant increase in the number of lawsuits in recent years, we recommend that all explanted vaginal mesh specimens be examined microscopically as well as grossly. A list of microscopic findings, including the presence or absence of adipose tissue, is suggested.","subset":"pubmed_abstract"} +{"meta":{"pmid":28588019,"dup_signals":{"dup_doc_count":18,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":2,"2024-22":2,"2024-18":1,"2024-10":2,"unknown":7}}},"text":"Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response.\nRecurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including \u223c12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221\/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed\/refractory AML (rrAML) patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear. Here, we measured 2-HG, mIDH2 allele burden, and co-occurring somatic mutations in sequential patient samples from the clinical trial and correlated these with clinical response. Furthermore, we used flow cytometry to assess inhibition of mIDH2 on hematopoietic differentiation. We observed potent 2-HG suppression in both R140 and R172 mIDH2 AML subtypes, with different kinetics, which preceded clinical response. Suppression of 2-HG alone did not predict response, because most nonresponding patients also exhibited 2-HG suppression. Complete remission (CR) with persistence of mIDH2 and normalization of hematopoietic stem and progenitor compartments with emergence of functional mIDH2 neutrophils were observed. In a subset of CR patients, mIDH2 allele burden was reduced and remained undetectable with response. Co-occurring mutations in NRAS and other MAPK pathway effectors were enriched in nonresponding patients, consistent with RAS signaling contributing to primary therapeutic resistance. Together, these data support differentiation as the main mechanism of enasidenib efficacy in relapsed\/refractory AML patients and provide insight into resistance mechanisms to inform future mechanism-based combination treatment studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":19066545,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Interview: HIV-1 proviral DNA excision using an evolved recombinase.\nHIV-1 integrates into the host chromosome of infected cells and persists as a provirus flanked by long terminal repeats. Current treatment strategies primarily target virus enzymes or virus-cell fusion, suppressing the viral life cycle without eradicating the infection. Since the integrated provirus is not targeted by these approaches, new resistant strains of HIV-1 may emerge. Here, we report that the engineered recombinase Tre (see Molecular evolution of the Tre recombinase, Buchholz, F., Max Planck Institute for Cell Biology and Genetics, Dresden) efficiently excises integrated HIV-1 proviral DNA from the genome of infected cells. We produced loxLTR containing viral pseudotypes and infected HeLa cells to examine whether Tre recombinase can excise the provirus from the genome of HIV-1 infected human cells. A virus particle-releasing cell line was cloned and transfected with a plasmid expressing Tre or with a parental control vector. Recombinase activity and virus production were monitored. All assays demonstrated the efficient deletion of the provirus from infected cells without visible cytotoxic effects. These results serve as proof of principle that it is possible to evolve a recombinase to specifically target an HIV-1 LTR and that this recombinase is capable of excising the HIV-1 provirus from the genome of HIV-1-infected human cells. Before an engineered recombinase could enter the therapeutic arena, however, significant obstacles need to be overcome. Among the most critical issues, that we face, are an efficient and safe delivery to targeted cells and the absence of side effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":11309208,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2018-26":1,"2017-13":1}}},"text":"Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization.\nPlasma membrane-anchored proteases have key roles in cell signaling, migration and refashioning the cell surface and its surroundings. We report the first example of a plasma membrane-anchored protease on mature sperm, testase 1 (ADAM 24). Unlike other studied sperm ADAMs (fertilin alpha and beta, cyritestin) whose metalloprotease domains are removed during sperm development, we found testase 1 retains an active metalloprotease domain, suggesting it acts as a protease on mature sperm. Testase 1 is a glycoprotein (molecular mass 88 kDa), localized to the equatorial region of the plasma membrane of cauda epididymal sperm. Typically, proteolytic removal of the pro-domain is an initial activation step for ADAM proteases. The pro-domain of the testase 1 precursor (108 kDa) is proteolytically removed as sperm transit the caput epididymis to produce processed (mature) testase 1 (88 kDa). Testase 1 is unique among all studied ADAMs in that its proteolytic processing occurs on the sperm plasma membrane instead of at an intracellular site (the Golgi). Using GST-fusion proteins and a synthetic testase 1 C-terminal peptide, we found that the cytoplasmic tail of testase 1 could be phosphorylated in vitro by protein kinase C (PKC). Thus testase 1 apparently has a cytoplasmic PKC phosphorylation site(s). Protein kinase C is known to stimulate other ADAMs' protease activity. Because events of the acrosome reaction include PKC activation, we speculate that testase 1 protease function could be important in sperm penetration of the zona pellucida after sperm PKC is activated during the acrosome reaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":24804263,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Dose distributions of an \u00b9\u2079\u00b2Ir brachytherapy source in different media.\nThis study used MCNPX code to investigate the brachytherapy (192)Ir dose distributions in water, bone, and lung tissue and performed radiophotoluminescent glass dosimeter measurements to verify the obtained MCNPX results. The results showed that the dose-rate constant, radial dose function, and anisotropy function in water were highly consistent with data in the literature. However, the lung dose near the source would be overestimated by up to 12%, if the lung tissue is assumed to be water, and, hence, if a tumor is located in the lung, the tumor dose will be overestimated, if the material density is not taken into consideration. In contrast, the lung dose far from the source would be underestimated by up to 30%. Radial dose functions were found to depend not only on the phantom size but also on the material density. The phantom size affects the radial dose function in bone more than those in the other tissues. On the other hand, the anisotropy function in lung tissue was not dependent on the radial distance. Our simulation results could represent valid clinical reference data and be used to improve the accuracy of the doses delivered during brachytherapy applied to patients with lung cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":17317665,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta.\nMammalian DNA polymerase (Pol) delta is essential for DNA replication. It consists of four subunits, p125, p50, p68, and p12. We report the discovery that the p12 subunit is rapidly degraded in cultured human cells by DNA damage or replication stress brought about by treatments with UV, methyl methanesulfonate, hydroxyurea, and aphidicolin. The degradation of p12 is due to an accelerated rate of proteolysis that is inhibited by the proteasome inhibitors, MG132 and lactacystin. UV treatment converts Pol delta in vivo to the three-subunit form lacking p12. This was demonstrated by its isolation using immunoaffinity chromatography. The three-subunit enzyme retains activity on poly(dA)\/oligo(dT) templates but is impaired in its ability to extend singly primed M13 templates, clearly indicating that its in vivo functions are likely to be compromised. This transformation of Pol delta by modification of its quaternary structure is reversible in vitro by the addition of the p12 subunit and could represent a novel in vivo mechanism for the modulation of Pol delta function. UV and hydroxyurea-triggered p12 degradation is blocked in ATR(-\/-) cells but not in ATM(-\/-) cells, thereby demonstrating that p12 degradation is regulated by ATR, the apical kinase that regulates the damage response in S-phase. These findings reveal a novel addition to the cellular repertoire of DNA damage responses that also impacts our understanding of the role of Pol delta in both DNA replication and DNA repair.","subset":"pubmed_abstract"} +{"meta":{"pmid":30838928,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-22":1,"unknown":7}}},"text":"The Space-Time Continuum of Cortical Dysplasia.\nSomatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias D'Gama AM, Woodworth MB, Hossain AA, Bizzotto S, Hatem NE, LaCoursiere CM, Najm I, Ying Z, Yang E, Barkovich AJ, Kwiatkowski DJ, Vinters HV, Madsen JR, Mathern GW, Bl\u00fcmcke I, Poduri A, Walsh CA. Cell Rep. 2017;21:3754-3766. Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are epileptogenic neurodevelopmental malformations caused by mutations in mTOR pathway genes. Deep sequencing of these genes in FCD\/HME brain tissue identified an etiology in 27 (41%) of 66 cases. Radiographically indistinguishable lesions are caused by somatic activating mutations in AKT3, MTOR, and PIK3CA and germline loss-of-function mutations in DEPDC5, NPRL2, and TSC1\/2, including TSC2 mutations in isolated HME demonstrating a \"two-hit\" model. Mutations in the same gene cause a disease continuum from FCD to HME to bilateral brain overgrowth, reflecting the progenitor cell and developmental time when the mutation occurred. Single-cell sequencing demonstrated mTOR activation in neurons in all lesions. Conditional Pik3ca activation in the mouse cortex showed that mTOR activation in excitatory neurons and glia, but not interneurons, is sufficient for abnormal cortical overgrowth. These data suggest that mTOR activation in dorsal telencephalic progenitors, in some cases specifically the excitatory neuron lineage, causes cortical dysplasia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28431988,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Time trends in births and cesarean deliveries among women with disabilities.\nAlthough it is likely that childbearing among women with disabilities is increasing, no empirical data have been published on changes over time in the numbers of women with disabilities giving birth. Further, while it is known that women with disabilities are at increased risk of cesarean delivery, temporal trends in cesarean deliveries among women with disabilities have not been examined. To assess time trends in births by any mode and in primary cesarean deliveries among women with physical, sensory, or intellectual\/developmental disabilities. We conducted a retrospective cohort study using linked vital records and hospital discharge data from all deliveries in California, 2000-2010 (n = 4,605,061). We identified women with potential disabilities using ICD-9 codes. We used descriptive statistics and visualizations to examine time patterns. Logistic regression analyses assessed the association between disability and primary cesarean delivery, stratified by year. Among all women giving birth, the proportion with a disability increased from 0.27% in 2000 to 0.80% in 2010. Women with disabilities had significantly elevated odds of primary cesarean delivery in each year, but the magnitude of the odds ratio decreased over time from 2.60 (95% CI = 2.25 = 2.99) in 2000 to 1.66 (95% CI = 1.51-1.81) in 2010. Adequate clinician training is needed to address the perinatal care needs of the increasing numbers of women with disabilities giving birth. Continued efforts to understand cesarean delivery patterns and reasons for cesarean deliveries may help guide further reductions in proportions of cesarean deliveries among women with disabilities relative to women without disabilities.","subset":"pubmed_abstract"} +{"meta":{"pmid":18208925,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Histamine H1-receptor blockade in humans affects psychomotor performance but not memory.\nResults from recent animal studies suggest an important role for histamine in memory functioning. Histaminergic drugs might prove beneficial for people suffering from memory impairment. To determine if histamine is involved in memory functioning this study evaluates the effects of histaminergic dysfunction on memory performance by administrating a H1-antagonist to humans. The study was conducted according to a 4-way, double-blind, crossover design in 20 healthy female volunteers, aged 18-45 years. On each test day subjects completed three test sessions: before and around 2 and 4 h after administration of single oral doses of dexchlorpheniramine 2 mg or 4 mg, scopolamine 1 mg or placebo. Drug effects were assessed using tests of memory, psychomotor and attention performance, and subjective alertness. Results showed that dexchlorpheniramine impaired performance in tests of spatial learning, reaction time, tracking and divided attention but showed no effects on working memory, visual memory, word learning or memory scanning. Scopolamine induced a similar pattern of effects. In addition, both drugs decreased subjective alertness. In conclusion results show that dexchlorpheniramine and scopolamine clearly impaired performance on psychomotor and attention tasks but do not suggest a specific role of the histaminergic system in learning and memory in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":17605449,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A pilot study of changes in cerebral blood flow velocity, resistance, and vital signs following a painful stimulus in the premature infant.\nThe purpose of this pilot study was to determine the cerebral blood flow velocity and resistance changes and vital signs following a painful stimulus in the premature infant. A convenience sample of 12 infants was randomly assigned to one of 2 treatment groups. In the final analysis, there were 10 infants younger than 24 hours of age and between 25 and 32 weeks' gestational age. A randomized 2-period, 2-group, crossover design was used. Cerebral blood flow velocity and resistance were measured via a Doppler head ultrasound transducer placed over the anterior fontanel. Vital signs were measured with a cardiorespiratory monitor. The infant then received the heel stick procedure or the sham procedure (heel preparation with no heel puncture). Each infant served as his or her own control. After each procedure, there was ultrasound and vital sign measurement at 15, 60, 120, 180, 240, and 300 seconds. Thereafter, the alternate treatment was used and 6 more measurements were taken. Cerebral values: peak systolic velocity (PSV) and resistive index (RI); vital signs: heart rate, respiratory rate, oxygen saturation (SpO2), and blood pressure. Treatment groups were similar at baseline except for gestational age. There were no carryover or period effects in the crossover design for the primary outcomes except for SpO2. There was a significant group effect (heel stick compared with sham) (P = .009) for peak systolic velocity; however, there were no significant differences between groups at each time point. Two subjects had a distinctive pattern based on simultaneous changes in flow and resistance: when flow velocity increased, resistance decreased. This may be reflective of risk for intraventricular hemorrhage (IVH). Mean arterial blood pressure (MAP) was not significant. However, heart rate was significantly different between stick and sham at 15 seconds (P = .022); respiratory rate was significant at 180 seconds (P = .029); and SpO2 was significant at 3 different time points. There were no significant correlations between PSV and mean arterial blood pressure and PSV and SpO2 when comparing stick to sham. This is a study based on a small sample size. However, the Doppler-measured peak systolic velocity increases significantly after a painful stimulus. The clinical implication of this finding needs to be established.","subset":"pubmed_abstract"} +{"meta":{"pmid":23607590,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Homologous critical behavior in the molecular frameworks Zn(CN)2 and Cd(imidazolate)2.\nUsing a combination of single-crystal and powder X-ray diffraction measurements, we study temperature- and pressure-driven structural distortions in zinc(II) cyanide (Zn(CN)2) and cadmium(II) imidazolate (Cd(im)2), two molecular frameworks with the anticuprite topology. Under a hydrostatic pressure of 1.52 GPa, Zn(CN)2 undergoes a first-order displacive phase transition to an orthorhombic phase, with the corresponding atomic displacements characterized by correlated collective tilts of pairs of Zn-centered tetrahedra. This displacement pattern sheds light on the mechanism of negative thermal expansion in ambient-pressure Zn(CN)2. We find that the fundamental mechanical response exhibited by Zn(CN)2 is mirrored in the temperature-dependent behavior of Cd(im)2. Our results suggest that the thermodynamics of molecular frameworks may be governed by considerations of packing efficiency while also depending on dynamic instabilities of the underlying framework topology.","subset":"pubmed_abstract"} +{"meta":{"pmid":22537019,"dup_signals":{"dup_doc_count":11,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-06":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":6}}},"text":"Using routine data to monitor inequalities in an acute trust: a retrospective study.\nReducing inequalities is one of the priorities of the National Health Service. However, there is no standard system for monitoring inequalities in the care provided by acute trusts. We explore the feasibility of monitoring inequalities within an acute trust using routine data. A retrospective study of hospital episode statistics from one acute trust in London over three years (2007 to 2010). Waiting times, length of stay and readmission rates were described for seven common surgical procedures. Inequalities by age, sex, ethnicity and social deprivation were examined using multiple logistic regression, adjusting for the other socio-demographic variables and comorbidities. Sample size calculations were computed to estimate how many years of data would be ideal for this analysis. This study found that even in a large acute trust, there was not enough power to detect differences between subgroups. There was little evidence of inequalities for the outcome and process measures examined, statistically significant differences by age, sex, ethnicity or deprivation were only found in 11 out of 80 analyses. Bariatric surgery patients who were black African or Caribbean were more likely than white patients to experience a prolonged wait (longer than 64 days, aOR = 2.47, 95% CI: 1.36-4.49). Following a coronary angioplasty, patients from more deprived areas were more likely to have had a prolonged length of stay (aOR = 1.66, 95% CI: 1.25-2.20). This study found difficulties in using routine data to identify inequalities on a trust level. Little evidence of inequalities in waiting time, length of stay or readmission rates by sex, ethnicity or social deprivation were identified although some differences were identified which warrant further investigation. Even with three years of data from a large trust there was little power to detect inequalities by procedure. Data will therefore need to be pooled from multiple trusts to detect inequalities.","subset":"pubmed_abstract"} +{"meta":{"pmid":23433269,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-18":1,"unknown":9}}},"text":"Recruitment, retention, and blinding in clinical trials.\nThe recruitment and retention of participants and the blinding of participants, health care providers, and data collectors present challenges for clinical trial investigators. This article reviews challenges and alternative strategies associated with these three important clinical trial activities. Common recruiting pitfalls, including low sample size, unfriendly study designs, suboptimal testing locations, and untimely recruitment are discussed together with strategies for overcoming these barriers. The use of active controls, technology-supported visit reminders, and up-front scheduling is recommended to prevent attrition and maximize retention of participants. Blinding is conceptualized as the process of concealing research design elements from key players in the research process. Strategies for blinding participants, health care providers, and data collectors are suggested.","subset":"pubmed_abstract"} +{"meta":{"pmid":8393193,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Functional alterations in the aorta of the spontaneously hypertensive rat: pharmacological assessment with cyclopiazonic acid.\nOne of the changes in vascular smooth muscle membranes associated with hypertension is an alteration in Ca2+ handling. It has been unclear as to whether changes occurred at the plasma membrane or at the endoplasmic reticulum (ER) or both. Recently, cyclopiazonic acid (CPA) has been reported to inhibit selectively the ER Ca2+ pump. We aimed at determining the effect of ER Ca2+ pump inhibition by CPA on the contractility of aortic smooth muscle from 4- to 5-month-old SHR and age- and weight-matched WKY control rats. The responsiveness of the SHR tissues to phenylephrine or K+ was significantly reduced as compared with controls, although the sensitivity was not altered. Stimulation with phenylephrine (10 mumol\/l) in Ca2(2+)-free medium caused a significantly reduced transient contraction in SHR as compared with control tissues. After pretreatment with CPA (30 mumol\/l), this contraction was suppressed in SHR and WKY tissues. On the restoration of Ca2+, CPA induced a nifedipine (5 mumol\/l) sensitive contraction, significantly larger in SHR than in WKY tissues. The relaxation rate to nifedipine of K(+)-induced contraction in CPA-treated SHR tissue was also reduced. We conclude that the ER Ca2+ pump in SHR aorta is less effective as compared with WKY tissue. The significantly greater CPA-induced contraction together with the reduced relaxation rate in the presence of CPA in SHR tissues as compared with controls suggests that Ca2+ handling was also altered at the plasma membrane.","subset":"pubmed_abstract"} +{"meta":{"pmid":19953837,"dup_signals":{"dup_doc_count":33,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":2,"2014-35":1,"2014-23":1,"2014-15":1,"2020-16":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2015-18":1}}},"text":"A path analysis to identify the psychosocial factors influencing physical activity and bone health in middle-school girls.\nThe purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1\/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (beta = 0.20, P < .05) and bone health and (beta = 0.13, P < .05). The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":26451484,"dup_signals":{"dup_doc_count":12}},"text":"Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila.\nStem cells reside in specialized microenvironments known as niches. During Drosophila development, glial cells provide a niche that sustains the proliferation of neural stem cells (neuroblasts) during starvation. We now find that the glial cell niche also preserves neuroblast proliferation under conditions of hypoxia and oxidative stress. Lipid droplets that form in niche glia during oxidative stress limit the levels of reactive oxygen species (ROS) and inhibit the oxidation of polyunsaturated fatty acids (PUFAs). These droplets protect glia and also neuroblasts from peroxidation chain reactions that can damage many types of macromolecules. The underlying antioxidant mechanism involves diverting PUFAs, including diet-derived linoleic acid, away from membranes to the core of lipid droplets, where they are less vulnerable to peroxidation. This study reveals an antioxidant role for lipid droplets that could be relevant in many different biological contexts.","subset":"pubmed_abstract"} +{"meta":{"pmid":16676011,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Post-traumatic growth and psychosocial adjustment of daughters of breast cancer survivors.\nTo examine post-traumatic growth, or positive life changes, and its correlates among adult daughters of breast cancer survivors and to compare their psychosocial adjustment to women with healthy parents. Descriptive, cross-sectional survey. Outpatient oncology units in two urban hospitals and two breast cancer organizations. 30 adult daughters of breast cancer survivors (mean age = 38.1 years) and 16 women with healthy parents. Participants were recruited by hospital or research staff or responded to an announcement in a newsletter. Respondents completed the Post-Traumatic Growth Inventory and standardized assessments of psychosocial adjustment. Post-traumatic growth and demographic, stressor, and psychosocial variables. Women who cared for their mothers following breast cancer diagnosis and perceived their mothers' illness to be stressful reported greater post-traumatic growth. Life satisfaction, social support, emotional processing strategies, and problem-focused coping strategies also were positively associated with growth. Women with maternal histories of breast cancer and those with healthy parents did not differ in psychosocial well-being, including affect, life satisfaction, and social support. Findings suggest that some daughters of breast cancer survivors experience positive life changes following their mothers' illness. For nurses seeking to adopt a holistic approach to practice, the personal growth of women following life-threatening familial illness warrants attention.","subset":"pubmed_abstract"} +{"meta":{"pmid":23307957,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.\nTo assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate. Ex vivo porcine corneal penetration of timolol maleate, sotalol hydrochloride, or brinzolamide incubated with or without Y-27632 was determined in vertical Franz diffusion cells. The effect of ROCK inhibition on the vasodilation of porcine conjunctival vasculature was assessed by scanning electron microscopy (SEM) and immunohistochemical staining with subsequent laser-scanning confocal microscopy (LSCM). Experiments were conducted in New Zealand White (NZW) rabbits to assess the effect of ROCK inhibition on the intraocular distribution of timolol maleate. ROCK inhibition resulted in minimal alteration of ex vivo porcine corneal drug penetration of timolol, sotalol, or brinzolamide. SEM and LSCM experiments conducted with conjunctiva and sclera tissue in Franz diffusion cells suggested vasodilation in the conjunctival vasculature in the presence of Y-27632. Pretreatment of the eyes of NZW rabbits with Y-27632 resulted in aggregate fold reductions (1 hour, 0.25-fold; 4 hours, 0.45-fold) of timolol maleate drug concentrations in intraocular tissues (aqueous humor, lens, and iris) versus eyes not receiving Y-27632 pretreatment. Pretreatment with a vasoconstrictor, phenylephrine, resulted in a reversal of the effect of Y-27632 on diminished timolol maleate intraocular penetration in NZW rabbits. ROCK inhibition reduced the intraocular penetration of administered timolol maleate presumably due to increased systemic elimination through the conjunctival vasculature. It is anticipated that care in order and timing of ROCK inhibitor administration will be warranted for those patients who may be on a multiple topical drug regimen for primary open-angle glaucoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":30746303,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":2,"unknown":10}}},"text":"Predictive Model for Macular Hole Closure Speed: Insights From Intraoperative Optical Coherence Tomography.\nTo establish a predictive model of macular hole (MH) closure speed. This study was a post hoc analysis of eyes that underwent full-thickness MH repair in the prospective PIONEER intraoperative optical coherence tomography (iOCT) study. The Bioptigen SDOIS system was used for iOCT imaging. All patients underwent standard small-gauge vitrectomy with internal limiting membrane (ILM) peeling, gas tamponade, and postoperative facedown positioning. Before vitrectomy and after ILM peeling, various quantitative OCT measures related to MH were obtained, including MH geometry alterations and outer retinal features. Trans-gas OCT was performed on postoperative day 1 to evaluate MH closure. Univariate and multivariate analyses were conducted to identify predictors of early MH closure (i.e., postoperative day 1 [POD 1] closure). Thirty-two (86%) out of 37 eyes were confirmed for MH closure at POD 1. At 3 months, MH closure was achieved in 35 (95%) eyes. After multivariate logistic regression analyses, seven covariates were determined as predictors for MH closure. These seven covariates included age, ellipsoid zone-retinal pigment epithelium expansion following ILM peel, preincision minimal width, post-ILM peel MH depth, change in MH volume, change in minimum MH width, and change in MH depth. Using these seven covariates, the area under the curve was 0.974. Cross-validation analysis indicated that intraoperative change in MH volume, intraoperative change in minimal width, and preincision minimal width were the most robust predictors for early MH. This study suggests that iOCT may be important in predicting MH closure speed and may be a surrogate for tissue properties\/behavior. A future prospective clinical trial is needed to validate this model. This study provides unique insights into the potential role of iOCT imaging in predicting retinal tissue behavior during MH repair.","subset":"pubmed_abstract"} +{"meta":{"pmid":32663699,"dup_signals":{"dup_doc_count":11}},"text":"A randomized control trial of activity scheduling for caring for older adults with dementia and its impact on their spouse care-givers.\nParticipating in meaningful activities is important for any individual's wellbeing. Activity scheduling enables older adults with dementia and their spouse caregivers to structure their activities in accordance with the things they value. In examining the effectiveness of activity scheduling, this report details the results of a 12-week single-blinded randomized control trial using a parallel group experimental design. From August 2018 to August 2019, 100 community-dwelling older adults with mild to moderate dementia and their spouses completed this study. The experimental group (n = 50) practicing activity scheduling showed improvements than in control group (n = 50), with respect to alleviating the impact of the caregiving role, reducing the behavioural and psychological symptoms of dementia, decreasing the caring demand and generally improving the quality of life, with Cohen's d = .61, .45, .50 and 43 respectively. Moreover, there were significant differences between the groups indicated that over time, the experimental group showed an improvement with regard to alleviating the role of caring, with Cohen's d = .64, and alleviating disruptive and depressive behavior, with an effect size of .45 and .50 respectively. The number of caring hours needed dropped from 6.98 to 5.98 h in the experimental group. There were more activities that older adults with dementia and their spouse caregivers would like to do, and could participate in, than we had expected. Activity scheduling can facilitate their participation. This is a very important topic as non-pharmacological interventions are needed for this even-growing segment of the population.","subset":"pubmed_abstract"} +{"meta":{"pmid":20961840,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump.\nThe management of acute myocardial infarction with resultant acute ischemic mitral regurgitation and acute multi-organ failure can prove to be a very challenging scenario. The presence of concomitant vascular disease can only serve to further compromise the complexity of the situation. We demonstrate a new indication for the transthoracic intra-aortic balloon pump as a preoperative means of unloading the heart and improving clinical outcome in such high-risk patients with severe vascular disease. We present the case of a 75-year-old man with a history of severe vascular disease who was transferred emergently to Vanderbilt University Medical Center with an acute inferolateral wall myocardial infarction resulting in severe acute ischemic mitral regurgitation and acute multi-organ failure. He presented with shock liver (serum glutamic-oxaloacetic transaminase [SGOT] of 958), renal failure (creatinine of 3.0), and respiratory failure with a pH of 7.18. Emergent cardiac catheterization revealed 100% occlusion of the left circumflex artery as well as severe ileofemoral disease. The advanced nature of his ileofemoral disease was such that the arterial access catheter occluded the right femoral artery. The duration of time that the catheter was in the artery led to transient limb ischemia with an elevation of his creatine phosphokinase (CPK) to 10,809. Balloon angioplasty followed by stent placement was successfully performed, which restored flow to the coronary vessel. Given the grave nature of the patient's condition, we were very concerned that immediate operative intervention for his condition would entail prohibitively high risk. In fact, the Society of Thoracic Surgeons predicted risk adjusted mortality was calculated to be 56%. In order to minimize patient mortality and morbidity, it was critical to help restore perfusion and organ recovery. Therefore, we decided that the chances for this patient's survival would improve if his condition could be optimized by placement of an intra-aortic balloon pump before undergoing surgery. Given the limb ischemia following arterial sheath insertion, femoral placement of an intra-aortic balloon pump was not an option. Placement of the intra-aortic balloon pump was attempted via a left subclavian artery cutdown, but was not successful. Therefore, a sternotomy was performed, and we placed a transthoracic intra-aortic balloon pump in order to stabilize the patient's hemodynamics and allow for organ recovery. The patient showed immediate improvement, and 4 days later, the multi-organ failure resolved and he successfully underwent mitral valve replacement. The patient was ultimately discharged to a local rehabilitation facility in satisfactory condition. This case demonstrates the utility of a transthoracic intra-aortic balloon pump as a preoperative means of stabilization in very high risk patients with severe peripheral vascular disease in whom the conventional approaches are not possible.","subset":"pubmed_abstract"} +{"meta":{"pmid":7059257,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Improving hypertension control in a private medical practice.\nHypertension is one of the most common diseases seen by the practicing physician. Yet, because of noncompliance, conditions of many hypertensive patients are not effectively controlled by treatment. The purpose of this study was to test the efficacy of a patient education program in reducing the blood pressure (BP) of hypertensive patients in a private, solo medical practice. The intervention program focused on three behavioral objectives-pill taking, appointment keeping, and dietary sodium reduction while stressing the need for taking responsibility for one's own care. It was hypothesized that patients receiving an educational intervention stressing self-care would benefit more than those receiving the usual medical care. A substantial reduction in BP was considered to be the measure of successful treatment. Thirty-nine hypertensive patients receiving drug therapy from a private, solo medical practice were randomized into either a treatment group or a control group. A comparison of means disclosed no pretreatment differences between the groups' average BPs. After following up both groups for six months, mean changes in BP were compared for both treatment and control patients using a two-sample t test for independent samples. The BP fell in the treatment group (-13 mm Hg, systolic; -8 mm Hg, diastolic) but rose slightly in the control group (3 mm Hg, systolic 0.5 mm Hg, diastolic). The difference in changes was significant for both the systolic and diastolic BP.","subset":"pubmed_abstract"} +{"meta":{"pmid":22330383,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":17}}},"text":"Spatial distributions of cone inputs to cells of the parvocellular pathway investigated with cone-isolating gratings.\nReceptive fields of midget ganglion cells and parvocellular lateral geniculate nucleus (LGN) neurons show color-opponent responses because they receive antagonistic input from the middle- and long-wavelength sensitive cones. It has been controversial as to whether this opponency can derive from random connectivity; if receptive field centers of cells near the fovea are cone-specific due to midget morphology, this would confer some degree of color opponency even with random cone input to the surround. A simple test of this mixed surround hypothesis is to compare spatial frequency tuning curves for luminance gratings and gratings isolating cone input to the receptive field center. If tuning curves for luminance gratings were bandpass, then with the mixed surround hypothesis tuning curves for gratings isolating the receptive field center cone class should also be bandpass, but to a lesser extent than for luminance. Tuning curves for luminance, chromatic, and cone-isolating gratings were measured in macaque retinal ganglion cells and LGN cells. We defined and measured a bandpass index to compare luminance and center cone-isolating tuning curves. Midget retinal ganglion cells and parvocellular LGN cells had bandpass indices between 0.1 and 1 with luminance gratings, but the index was usually near 1 (meaning low-pass tuning) when the receptive field center cone class alone was modulated. This is strong evidence for a considerable degree of cone-specific input to the surround. A fraction of midget and parvocellular cells showed evidence of incomplete specificity. Fitting the data with receptive field models revealed considerable intercell variability, with indications in some cells of a more complex receptive structure than a simple difference of Gaussians model.","subset":"pubmed_abstract"} +{"meta":{"pmid":21226978,"dup_signals":{"dup_doc_count":15,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2023-06":1,"2022-40":1,"2020-40":1,"2020-24":1,"2018-47":1,"2018-43":1,"2018-22":1,"2018-17":1,"2018-09":1,"2017-47":1,"2023-14":1,"2024-30":1}}},"text":"Multiple incursions and putative species revealed using a mitochondrial and nuclear phylogenetic approach to the Trogoderma variabile (Coleoptera: Dermestidae) trapping program in Australia.\nThe Warehouse beetle, Trogoderma variabile (Coleoptera: Dermestidae), is an internationally significant invasive pest of packed goods and stored grain. When it was first documented in Australia at Griffith, New South Wales, in 1977, an eradication campaign was initiated. After several years and considerable effort, the eradication campaign was abandoned. To monitor the presence and spread of T. variabile, surveys were carried out by government agencies in 1992 and 2002. When survey data was compared, it was concluded that the distribution of morphologically identified T. variabile had doubled in most Australian states. Here, we used samples from the 2002 survey to conduct a phylogenetic study using partial sequences of mitochondrial genes Cytochrome oxidase I and Cytochrome B, and the nuclear gene 18S, to examine the distribution and dispersal of T. variabile and detect the presence of misidentified species. Based on our molecular results, we show that only 47% of the samples analysed were T. variabile, and the remaining were a mixture of six putative species. In addition, T. variabile was found in only 78% of the trapping sites. We discuss the importance of correct diagnosis in relation to the eradication campaign.","subset":"pubmed_abstract"} +{"meta":{"pmid":28857069,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-26":1,"unknown":8}}},"text":"The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain.\nA great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (that is, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that 'medicinal' cannabis or cannabinoid-based medications relieve pain in human diseases such as cancer, multiple sclerosis, and fibromyalgia. However, clinical data have yet to demonstrate the analgesic efficacy of inhibitors of endocannabinoid-regulating enzymes. Likewise, the question of whether pharmacotherapies aimed at the endocannabinoid system promote opioid-sparing effects in the treatment of pain reflects an important area of research. Here we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":16129560,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2015-18":1,"2024-22":1,"unknown":12}}},"text":"Global and regional gray matter reductions in ADHD: a voxel-based morphometric study.\nAttention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children\/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children\/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior\/middle\/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.","subset":"pubmed_abstract"} +{"meta":{"pmid":33395277,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Target, Nontarget, and Suspect Screening and Temporal Trends of Per- and Polyfluoroalkyl Substances in Marine Mammals from the South China Sea.\nPer- and polyfluoroalkyl substances (PFASs) have been manufactured and widely used for over 60 years. Currently, there are thousands of marketed PFASs, but only dozens of them are routinely monitored. This work involved target, nontarget, and suspect screening of PFASs in the liver of Indo-Pacific humpback dolphin (Sousa chinensis) and finless porpoise (Neophocaena phocaenoides), two resident marine mammals in the South China Sea, stranded between 2012 and 2018. Among the 21 target PFASs, perfluorooctane sulfonate and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA) predominated in the samples, accounting for 46 and 30% of the total PFASs, respectively. Significantly higher total target PFAS concentrations (p < 0.05) were found in dolphin liver samples [3.23 \u00d7 103 \u00b1 2.63 \u00d7 103 ng\/g dry weight (dw)] than in porpoise liver samples (2.63 \u00d7 103 \u00b1 1.10 \u00d7 103 ng\/g dw). Significant increasing temporal trends (p < 0.05) were found in the concentrations of two emerging PFASs, perfluoroethylcyclohexane sulfonate and 2,3,3,3-tetrafluoro-2-propanoate in porpoises, indicating increasing pollution by these emerging PFASs. Forty-four PFASs from 9 classes were additionally identified by nontarget and suspect screening, among which 15 compounds were reported for the first time in marine mammals. A primary risk assessment showed that the emerging PFAS 6:2 Cl-PFESA could have possible adverse effects in terms of reproductive injury potential on most of the investigated cetaceans.","subset":"pubmed_abstract"} +{"meta":{"pmid":19075221,"dup_signals":{"dup_doc_count":21,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-18":1,"2013-48":1,"2013-20":2,"2024-22":1,"unknown":14}}},"text":"A transitional endogenous lentivirus from the genome of a basal primate and implications for lentivirus evolution.\nLentiviruses chronically infect a broad range of mammalian species and have been transmitted from primates to humans, giving rise to multiple outbreaks of HIV infection over the past century. Although the circumstances surrounding these recent zoonoses are becoming clearer, the nature and timescale of interaction between lentiviruses and primates remains unknown. Here, we report the discovery of an endogenous lentivirus in the genome of the gray mouse lemur (Microcebus murinus), a strepsirrhine primate from Madagascar, demonstrating that lentiviruses are capable of invading the primate germ line. Phylogenetic analysis places gray mouse lemur prosimian immunodeficiency virus (pSIVgml) basal to all known primate lentiviruses and, consistent with this, its genomic organization is intermediate between the nonprimate lentiviruses and their more derived primate counterparts. Thus, pSIVgml represents the first unambiguous example of a viral transitional form, revealing the acquisition and loss of genomic features during lentiviral evolution. Furthermore, because terrestrial mammal populations in Madagascar and Africa are likely to have been isolated from one another for at least 14 million years, the presence of pSIVgml in the gray mouse lemur genome indicates that lentiviruses must have been infecting primates for at least this period of time, or have been transmitted between Malagasy and African primate populations by a vector species capable of traversing the Mozambique channel. The discovery of pSIVgml illustrates the utility of endogenous sequences for the study of contemporary retroviruses and indicates that primate lentiviruses may be considerably older and more broadly distributed than previously thought.","subset":"pubmed_abstract"} +{"meta":{"pmid":30950431,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005-2010.\nApproximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok. The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes. The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%). The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.","subset":"pubmed_abstract"} +{"meta":{"pmid":23607497,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"50 years of publication in the field of medical education.\nThe advent of new medical education (ME) journals makes evident the growth of the field of ME. However, the nature and context of growth is undefined. To analyze the evolution of publication in ME. MEDLINE retrieval using medical subject headings was used to analyze patterns of ME publications from 1960-2010: changes in number of ME publications; number of journals publishing ME articles; co-topics occurring frequently in ME articles; differences among journals' publication of co-topics. Annual publication of ME articles increased from 279 in 1960 to 3760 in 2010. 81,531 articles were published in 4208 different journals. 104 journals published ME articles in 1960, 855 in 2010. Despite an increase in journals in all fields, ME journals now account for a larger proportion of all journals indexed in MEDLINE than in 1960. One-quarter of all ME articles were indexed as internship\/residency; 16% as graduate ME; 15% as undergraduate ME; and 14% as continuing ME. The five journals that published the most ME articles distinguished themselves by publishing some topics with greater or less frequency. The increase in the number of ME publications and in the number of journals publishing ME articles suggests a supportive environment for a growing field; but variation in journals' foci has implications for readers, editors and authors.","subset":"pubmed_abstract"} +{"meta":{"pmid":24591571,"dup_signals":{"dup_doc_count":40,"dup_dump_count":29,"dup_details":{"curated_sources":2,"2021-43":1,"2020-16":1,"2019-51":1,"2019-47":1,"2019-43":1,"2019-30":1,"2019-22":2,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":2,"2018-30":1,"2018-26":2,"2018-22":1,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":3,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":1,"2017-17":1,"2017-09":1,"2023-23":1,"2017-13":1}}},"text":"Computational analysis of Ca2+ dynamics in isolated cardiac mitochondria predicts two distinct modes of Ca2+ uptake.\nCardiac mitochondria can act as a significant Ca(2+) sink and shape cytosolic Ca(2+) signals affecting various cellular processes, such as energy metabolism and excitation-contraction coupling. However, different mitochondrial Ca(2+) uptake mechanisms are still not well understood. In this study, we analysed recently published Ca(2+) uptake experiments performed on isolated guinea pig cardiac mitochondria using a computer model of mitochondrial bioenergetics and cation handling. The model analyses of the data suggest that the majority of mitochondrial Ca(2+) uptake, at physiological levels of cytosolic Ca(2+) and Mg(2+), occurs through a fast Ca(2+) uptake pathway, which is neither the Ca(2+) uniporter nor the rapid mode of Ca(2+) uptake. This fast Ca(2+) uptake component was explained by including a biophysical model of the ryanodine receptor (RyR) in the computer model. However, the Mg(2+)-dependent enhancement of the RyR adaptation was not evident in this RyR-type channel, in contrast to that of cardiac sarcoplasmic reticulum RyR. The extended computer model is corroborated by simulating an independent experimental dataset, featuring mitochondrial Ca(2+) uptake, egress and sequestration. The model analyses of the two datasets validate the existence of two classes of Ca(2+) buffers that comprise the mitochondrial Ca(2+) sequestration system. The modelling study further indicates that the Ca(2+) buffers respond differentially depending on the source of Ca(2+) uptake. In particular, it suggests that the Class 1 Ca(2+) buffering capacity is auto-regulated by the rate at which Ca(2+) is taken up by mitochondria.","subset":"pubmed_abstract"} +{"meta":{"pmid":22020328,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2016-44":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2019-47":1,"2015-18":1}}},"text":"F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest.\nDysregulated behavior of cell cycle proteins and their control by ubiquitin E3 ligases is an emerging theme in human lung cancer. Here, we identified and characterized the activity of a novel F-box protein, termed FBXL2, belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family. Ectopically expressed FBXL2 triggered G2\/M-phase arrest, induced chromosomal anomalies and increased apoptosis of transformed lung epithelia by mediating polyubiquitination and degradation of the mitotic regulator, cyclin D3. Unlike other F-box proteins that target phosphodegrons within substrates, FBXL2 uniquely recognizes a canonical calmodulin (CaM)-binding motif within cyclin D3 to facilitate its polyubiquitination. CaM bound and protected cyclin D3 from FBXL2 by direct intermolecular competition with the F-box protein for access within this motif. The chemotherapeutic agent vinorelbine increased apoptosis of human lung carcinoma cells by inducing FBXL2 expression and cyclin D3 degradation, an effect accentuated by CaM knockdown. Depletion of endogenous FBXL2 stabilized cyclin D3 levels, accelerated cancer cell growth and increased cell viability after vinorelbine treatment. Last, ectopic expression of FBXL2 significantly inhibited the growth and migration of tumorogenic cells and tumor formation in athymic nude mice. These observations implicate SCF(FBXL2) as an indispensible regulator of mitosis that serves as a tumor suppressor.","subset":"pubmed_abstract"} +{"meta":{"pmid":28032831,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Commentary: Optimizing Advanced Practice Nursing Roles in Canada.\nThe optimization of the health workforce is perhaps one of the most critical actions that health reform initiatives need to address moving forward. The optimization of advanced practice nursing roles is no exception. In general, scopes of practice tend to be organized on the basis of tradition and politics rather than how best they can meet shifting population health needs. Health workforce optimization is now both the language adopted internationally and a key area of focus for health reform.","subset":"pubmed_abstract"} +{"meta":{"pmid":21534610,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":11}}},"text":"Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands.\nMarijuana is the most widely abused illegal drug, and its spectrum of effects suggests that several receptors are responsible for the activity. Two cannabinoid receptor subtypes, CB1 and CB2, have been identified, but the complex pharmacological properties of exogenous cannabinoids and endocannabinoids are not fully explained by their signaling. The orphan receptor GPR55 binds a subset of CB1 and CB2 ligands and has been proposed as a cannabinoid receptor. This designation, however, is controversial as a result of recent studies in which lysophosphatidylinositol (LPI) was identified as a GPR55 agonist. Defining a biological role for GPR55 requires GPR55 selective ligands that have been unavailable. From a \u03b2-arrestin, high-throughput, high-content screen of 300000 compounds run in collaboration with the Molecular Libraries Probe Production Centers Network initiative (PubChem AID1965), we identified potent GPR55 selective agonists. By modeling of the GPR55 activated state, we compared the GPR55 binding conformations of three of the novel agonists obtained from the screen, CID1792197, CID1172084, and CID2440433 (PubChem Compound IDs), with that of LPI. Our modeling indicates the molecular shapes and electrostatic potential distributions of these agonists mimic those of LPI; the GPR55 binding site accommodates ligands that have inverted-L or T shapes with long, thin profiles that can fit vertically deep in the receptor binding pocket while their broad head regions occupy a horizontal binding pocket near the GPR55 extracellular loops. Our results will allow the optimization and design of second-generation GPR55 ligands and provide a means for distinguishing GPR55 selective ligands from those interacting with cannabinoid receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":35702582,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Atrial invasion from primary lung adenocarcinoma extension via the pulmonary vein.\nIntravascular extension of lung adenocarcinoma is one of the four defined routes of metastasis to the heart but is rarely described in the literature. This is a rare case of primary lung adenocarcinoma with intravenous extension to the left atrium via the pulmonary vein. A 56-year-old female presented to the hospital with chest tightness and dyspnea. Chest computed tomography revealed a right hilar mass extending through the right superior pulmonary vein into the left atrium. Transthoracic echocardiography revealed a large, partially mobile left atrial mass occupying the entire atrial cavity and affecting mitral valve closure. Endobronchial ultrasound with transbronchial biopsy of the right middle lobe of the lung histologically showed a poorly differentiated adenocarcinoma compatible with the primary lung cancer. The patient was deemed a poor surgical candidate by cardiothoracic surgery due to the extent of metastasis and was started on chemoradiation. The patient's left atrial tumor mass started shrinking in size after starting the treatment. This unique case displaying intravascular extension of lung cancer to the left atrium has rarely been described in the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":19495091,"dup_signals":{"dup_doc_count":67,"dup_dump_count":34,"dup_details":{"curated_sources":4,"2020-40":1,"2020-34":1,"2020-16":1,"2019-51":2,"2019-47":1,"2019-35":1,"2018-17":3,"2018-09":2,"2018-05":1,"2017-47":2,"2017-39":2,"2017-34":1,"2017-30":2,"2017-26":1,"2017-22":3,"2017-17":1,"2017-09":2,"2017-04":3,"2016-50":1,"2016-44":3,"2016-36":3,"2016-30":2,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":3,"2015-40":2,"2015-35":2,"2015-32":3,"2015-27":2,"2015-22":2,"2021-39":1,"2015-18":2,"2024-22":1}}},"text":"Radiation pressure on a dielectric wedge.\nThe force of electromagnetic radiation on a dielectric medium may be derived by a direct application of the Lorentz law of classical electrodynamics. While the light's electric field acts upon the (induced) bound charges in the medium, its magnetic field exerts a force on the bound currents. We use the example of a wedge-shaped solid dielectric, immersed in a transparent liquid and illuminated at Brewster's angle, to demonstrate that the linear momentum of the electromagnetic field within dielectrics has neither the Minkowski nor the Abraham form; rather, the correct expression for momentum density has equal contributions from both. The time rate of change of the incident momentum thus expressed is equal to the force exerted on the wedge plus that experienced by the surrounding liquid.","subset":"pubmed_abstract"} +{"meta":{"pmid":7939633,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family.\nIn this study, a protein that interacts with sequences encoded by the first exon of the protein kinase Bcr was cloned. The Bcr-associated protein 1 (Bap-1) is a member of the 14-3-3 family of proteins. Bap-1 interacts with full-length c-Bcr and with the chimeric Bcr-Abl tyrosine kinase of Philadelphia chromosome (Ph1)-positive human leukemias. Bap-1 is a substrate for the Bcr serine-threonine kinase and is also phosphorylated on tyrosine by Bcr-Abl but not by c-Abl. Bap-1 may function in the regulation of c-Bcr and may contribute to the transforming activity of Bcr-Abl in vivo. 14-3-3 proteins are essential for cell proliferation and have a role in determining the timing of mitosis in yeast. Through direct binding to sequences present in Bcr and in other proteins implicated in signaling, the mammalian 14-3-3 proteins may link specific signaling protein components to mitogenic and cell-cycle control pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":28424303,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Distribution of genotype network sizes in sequence-to-structure genotype-phenotype maps.\nAn essential quantity to ensure evolvability of populations is the navigability of the genotype space. Navigability, understood as the ease with which alternative phenotypes are reached, relies on the existence of sufficiently large and mutually attainable genotype networks. The size of genotype networks (e.g. the number of RNA sequences folding into a particular secondary structure or the number of DNA sequences coding for the same protein structure) is astronomically large in all functional molecules investigated: an exhaustive experimental or computational study of all RNA folds or all protein structures becomes impossible even for moderately long sequences. Here, we analytically derive the distribution of genotype network sizes for a hierarchy of models which successively incorporate features of increasingly realistic sequence-to-structure genotype-phenotype maps. The main feature of these models relies on the characterization of each phenotype through a prototypical sequence whose sites admit a variable fraction of letters of the alphabet. Our models interpolate between two limit distributions: a power-law distribution, when the ordering of sites in the prototypical sequence is strongly constrained, and a lognormal distribution, as suggested for RNA, when different orderings of the same set of sites yield different phenotypes. Our main result is the qualitative and quantitative identification of those features of sequence-to-structure maps that lead to different distributions of genotype network sizes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27123468,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":7}}},"text":"Analogs of LDL Receptor Ligand Motifs in Dengue Envelope and Capsid Proteins as Potential Codes for Cell Entry.\nIt is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and \u03a8B\u03a8XB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1-4 (DENV1-4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using HeLa cells. DENV2 envelope peptide, Dsp2EP, 0564Gly-Gly0595, was shown to bind and remain at the cell surface. In contrast, DENV3 capsid protein peptide, Dsp3CP, 0002Asn-Gln0028, readily enters HeLa cells and accumulates at discrete loci in the nucleus. FITC-labeled dengue synthetic peptides colocalize with Low Density Lipoprotein-CM-DiI and Apo E-CM-DiI to a degree that suggests that Dengue viruses may utilize cell entry pathways used by LLPs.","subset":"pubmed_abstract"} +{"meta":{"pmid":25550536,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Enlargement and multinucleation of u937 leukemia and MCF7 breast carcinoma cells by antineoplastic agents to enhance sensitivity to low frequency ultrasound and to DNA-directed anticancer agents.\nCytochalasin B is a mycogenic toxin that preferentially damages malignant cells through multiple mechanisms. The microfilament-disrupting agent inhibits cytokinesis, producing enlarged and multinucleated neoplastic cells without enlarging or producing multinucleated normal cells. In addition, cytochalasin B has been shown to induce apoptosis and to increase the mitochondrial activity of malignant cells. In spite of these pharmacological properties potentially exploitable in cancer chemotherapy, no cytochalasin congener or derivative and indeed no microfilament-directed agent has yet been examined in the clinic. Nevertheless, it will likely be necessary to combine microfilament-directed agents with other chemotherapeutic agents, and potentially with other anti-neoplastic modalities to amplify the mechanisms by which microfilament-directed agents inflict damage. These combinations could increase the likelihood of obtaining clinically useful activities with microfilament-directed agents and decrease the often inevitable emergence of drug resistance. Therefore, this study intends to determine appropriate chemotherapeutic agents to use concurrently with cytochalasin B and with other microfilament-directed agents. Since cytochalasin B has shown in vitro efficacy against anchorage-independent growth, as well as against attached malignancies, both U937 human monocytic leukemia and MCF7 human breast carcinoma cells were evaluated. These cell lines were assessed for their sensitivity to a comprehensive array of chemotherapeutic agents that could amplify the cytoskeletal effects of microfilament-directed agents or that could themselves be potentiated by the cellular effects of such agents. In addition, clinically-approved microtubule-directed agents, as well as clinically-active anti-neoplastic agents not specifically cytoskeletal-directed, were examined for their ability to potentiate cell enlargement, one of the hallmark features of microfilament-directed agents. Conditions for inducing optimal enlargement and multinucleation of neoplastic cells with cytochalasin B were also defined. U937 and MCF7 cells have differing sensitivities to chemotherapeutic agents indicating that different regimens will likely be needed for various cell types in concomitant cytochalasin B-mediated chemotherapy. It was noted that microtubule-directed agents (paclitaxel and vincristine) would likely have a synergistic effect with cytochalasin B as they produced a substantial enlargement in viable cells at their 50% inhibitory (IC50) values. Interestingly, doxorubicin and mitomycin C also produced considerable cell enlargement, suggesting that nucleic acid-directed agents may be used to further enhance the cell-enlargement and multinucleation effects of microfilament-directed agents if appropriate sequences and concentrations can be found for the combination of agents. A subsequent publication in this series will examine the optimal combinations of chemotherapeutic agents with microfilament-directed agents in regards to drug concentrations and sequential timing. U937 cells exposed to cytochalasin B exhibited substantial cell enlargement and multinucleation that was still prevalent 8 days post-administration depending on the concentration used. Taken together, it appears that cytochalasin B has substantial synergistic potential with microtubule- and nucleic acid-directed agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":27064141,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Do On-Site Mental Health Professionals Change Pediatricians' Responses to Children's Mental Health Problems?\nTo assess the availability of on-site mental health professionals (MHPs) in primary care; to examine practice\/pediatrician characteristics associated with on-site MHPs; and to determine whether the presence of on-site MHPs is related to pediatricians' comanaging or more frequently identifying, treating\/managing, or referring mental health (MH) problems. Analyses included American Academy of Pediatrics (AAP) members who participated in an AAP Periodic Survey in 2013 and who practiced general pediatrics (n = 321). Measures included sociodemographics, practice characteristics, questions about on-site MHPs, comanagement of MH problems, and pediatricians' behaviors in response to 5 prevalent MH problems. Weighted univariate, bivariate, and multivariable analyses were performed. Thirty-five percent reported on-site MHPs. Practice characteristics (medical schools, universities, health maintenance organizations, <100 visits per week, <80% of patients privately insured) and interactions of practice location (urban) with visits and patient insurance were associated with on-site MHPs. There was no overall association between colocation and comanagement, or whether pediatricians usually identified, treated\/managed, or referred 5 common child MH problems. Among the subset of pediatricians who reported comanaging, there was an association with comanagement when the on-site MHP was a child psychiatrist, substance abuse counselor, or social worker. On-site MHPs are more frequent in settings where low-income children are served and where pediatricians train. Pediatricians who comanage MH problems are more likely to do so when the on-site MHP is a child psychiatrist, substance abuse counselor, or social worker. Overall, on-site MHPs were not associated with comanagement or increased likelihood of pediatricians identifying, treating\/managing, or referring children with 5 common child MH problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":11231560,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":5}}},"text":"Fingerprinting polysaccharides with single-molecule atomic force microscopy.\nWe report the use of an atomic force microscopy (AFM)-based force spectroscopy technique to identify, at the single-molecule level, the components of mixtures of polysaccharides. Previously, we showed that the elasticity of certain types of polysaccharides is governed by force-induced conformational transitions of the pyranose ring. These transitions produce atomic fingerprints in the force-extension spectrum that are characteristic of the ground-energy conformation of the pyranose ring and the type of glycosidic linkages. Using this approach we find that commercially available agarose and lambda-carrageenan contain molecules that, when stretched in an atomic force microscope, produce a force spectrum characteristic of alpha-(1-->4) d-glucans. We have identified these molecules as amylopectin or floridean starch, a storage polysaccharide in algae. Our methodology can identify individual polysaccharide molecules in solution, which is not possible by any other spectroscopic technique, and therefore is an important addition to the arsenal of analytical techniques used in carbohydrate research.","subset":"pubmed_abstract"} +{"meta":{"pmid":11395022,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta.\nIn the early atherosclerotic lesion, monocytes accumulate at sites of inflammation and endothelial injury. Platelet-derived growth factor (PDGF), produced for example by macrophages, is a chemoattractant for smooth muscle cells and possibly also for macrophages. During early differentiation into macrophages, human monocytes (early hMDM) showed lower expression of PDGF alpha-receptor (PDGF-Ralpha) than beta-receptor (PDGF-Rbeta) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BB(L)) but not short (BB(S)) B-chain homodimer. Neither PDGF-AA(S) nor PDGF-AA(L) affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) on PDGF-R expression and migratory response were studied. Only PDGF-Ralpha mRNA was highly upregulated by IFN-gamma. TGF-beta only had minor effects on receptor mRNAs. Upregulation of PDGF-Ralpha levels by IFN-gamma was accompanied by significantly increased migration (chemotaxis) towards PDGF-AA(L) only. Consequently, IFN-gamma modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA(L) on IFN-gamma-stimulated early hMDM. This suggests that PDGF-AA(L) may be involved in attracting activated monocytes to sites of inflammation and injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":31602210,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Angelicin inhibits the malignant behaviours of human cervical cancer potentially via inhibiting autophagy.\nAngelicin is an active compound isolated from the Chinese herb Angelica archangelica, which has been reported to exert antitumor effects by inhibiting malignant behaviors in several types of tumor, including proliferation, colony formation, migration and invasion. However, the effects of angelicin on human cervical cancer cells is yet to be elucidated. The present study evaluated the antitumor effects of angelicin on cervical cancer cells. The results demonstrated that cervical cancer cells were more sensitive to angelicin than cervical epithelial cells. At its IC30, angelicin inhibited the proliferation of HeLa and SiHa cells by blocking the cell cycle at the G1\/G0 phase and inhibiting other malignant behaviors, including colony formation, tumor formation in soft agar, migration and invasion. At the IC50, angelicin induced cell death potentially by promoting apoptosis. By identifying the hallmarks of autophagy, it was observed that angelicin treatment caused the accumulation of microtubule associated protein 1 light chain 3-\u03b2 (LC3B) in the cytoplasm of HeLa and SiHa cells. Western blotting results demonstrated that cleaved LC3B-II and autophagy related proteins (Atg)3, Atg7 and Atg12-5 were upregulated following angelicin treatment. It was also determined that the phosphorylation of mTOR was induced by angelicin treatment. Furthermore, the inhibition of angelicin-induced mTOR phosphorylation did not disrupt its inhibitory effect on autophagy, indicating that angelicin inhibited autophagy in an mTOR-independent manner. Taken together, the present results suggested that angelicin regulated malignant behaviors in cervical cancer cells by inhibiting autophagy in an mTOR-independent manner. Findings suggested that autophagy might be a potential therapeutic target for cervical cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":27793085,"dup_signals":{"dup_doc_count":15}},"text":"Genome sequence of Phormia regina Meigen (Diptera: Calliphoridae): implications for medical, veterinary and forensic research.\nBlow flies (Diptera: Calliphoridae) are important medical, veterinary and forensic insects encompassing 8 % of the species diversity observed in the calyptrate insects. Few genomic resources exist to understand the diversity and evolution of this group. We present the hybrid (short and long reads) draft assemblies of the male and female genomes of the common North American blow fly, Phormia regina (Diptera: Calliphoridae). The 550 and 534 Mb draft assemblies contained 8312 and 9490 predicted genes in the female and male genomes, respectively; including > 93 % conserved eukaryotic genes. Putative X and Y chromosomes (21 and 14 Mb, respectively) were assembled and annotated. The P. regina genomes appear to contain few mobile genetic elements, an almost complete absence of SINEs, and most of the repetitive landscape consists of simple repetitive sequences. Candidate gene approaches were undertaken to annotate insecticide resistance, sex-determining, chemoreceptors, and antimicrobial peptides. This work yielded a robust, reliable reference calliphorid genome from a species located in the middle of a calliphorid phylogeny. By adding an additional blow fly genome, the ability to tease apart what might be true of general calliphorids vs. what is specific of two distinct lineages now exists. This resource will provide a strong foundation for future studies into the evolution, population structure, behavior, and physiology of all blow flies.","subset":"pubmed_abstract"} +{"meta":{"pmid":7399996,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Physiological and pharmacological properties of canine trachealis muscle in vivo.\nIn 23 dogs anesthetized with chloralose and urethan, we developed a preparation that premitted measurement of isometric tension in segments of the tracheal posterior membrane in situ. Length-tension studies showed an optimal length for contraction in each of 5 segments; in all 5 segments, length was optimal when resting tension was 22-35 g\/cm. In 8 other segments, stimuli were delivered by systemic intravenous injections, by electrical stimulation of nerves, or by selective injections into the tracheal circulation; the time between delivery of repeated stimuli required for reproducible responses differed for each form of stimulation. Hypoxemia increased tension by 23.1 +\/- 5.5 (SE) g\/cm in 10 out of 10 other segments; these increases were the results of reflexes, not direct effects. Because the innervation and vascular supply of these segments were largely intact, we concluded that this preparation permits the study of neurohumoral mechanisms which modulate smooth muscle contraction in a prototypic central airway in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":31816235,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Tuning Catalytic Bias of Hydrogen Gas Producing Hydrogenases.\nHydrogenases display a wide range of catalytic rates and biases in reversible hydrogen gas oxidation catalysis. The interactions of the iron-sulfur-containing catalytic site with the local protein environment are thought to contribute to differences in catalytic reactivity, but this has not been demonstrated. The microbe Clostridium pasteurianum produces three [FeFe]-hydrogenases that differ in \"catalytic bias\" by exerting a disproportionate rate acceleration in one direction or the other that spans a remarkable 6 orders of magnitude. The combination of high-resolution structural work, biochemical analyses, and computational modeling indicates that protein secondary interactions directly influence the relative stabilization\/destabilization of different oxidation states of the active site metal cluster. This selective stabilization or destabilization of oxidation states can preferentially promote hydrogen oxidation or proton reduction and represents a simple yet elegant model by which a protein catalytic site can confer catalytic bias.","subset":"pubmed_abstract"} +{"meta":{"pmid":23431116,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":11}}},"text":"Duplication and maintenance of the Myb genes of vertebrate animals.\nGene duplication is an important means of generating new genes. The major mechanisms by which duplicated genes are preserved in the face of purifying selection are thought to be neofunctionalization, subfunctionalization, and increased gene dosage. However, very few duplicated gene families in vertebrate species have been analyzed by functional tests in vivo. We have therefore examined the three vertebrate Myb genes (c-Myb, A-Myb, and B-Myb) by cytogenetic map analysis, by sequence analysis, and by ectopic expression in Drosophila. We provide evidence that the vertebrate Myb genes arose by two rounds of regional genomic duplication. We found that ubiquitous expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, was lethal in Drosophila. Expression of any of these genes during early larval eye development was well tolerated. However, expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, during late larval eye development caused drastic alterations in adult eye morphology. Mosaic analysis implied that this eye phenotype was cell-autonomous. Interestingly, some of the eye phenotypes caused by the retroviral v-Myb oncogene and the normal c-Myb proto-oncogene from which v-Myb arose were quite distinct. Finally, we found that post-translational modifications of c-Myb by the GSK-3 protein kinase and by the Ubc9 SUMO-conjugating enzyme that normally occur in vertebrate cells can modify the eye phenotype caused by c-Myb in Drosophila. These results support a model in which the three Myb genes of vertebrates arose by two sequential duplications. The first duplication was followed by a subfunctionalization of gene expression, then neofunctionalization of protein function to yield a c\/A-Myb progenitor. The duplication of this progenitor was followed by subfunctionalization of gene expression to give rise to tissue-specific c-Myb and A-Myb genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19378969,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Water dynamics in salt solutions studied with ultrafast two-dimensional infrared (2D IR) vibrational echo spectroscopy.\nWater is ubiquitous in nature, but it exists as pure water infrequently. From the ocean to biology, water molecules interact with a wide variety of dissolved species. Many of these species are charged. In the ocean, water interacts with dissolved salts. In biological systems, water interacts with dissolved salts as well as charged amino acids, the zwitterionic head groups of membranes, and other biological groups that carry charges. Water plays a central role in a vast number of chemical processes because of its dynamic hydrogen-bond network. A water molecule can form up to four hydrogen bonds in an approximately tetrahedral arrangement. These hydrogen bonds are continually being broken, and new bonds are being formed on a picosecond time scale. The ability of the hydrogen-bond network of water to rapidly reconfigure enables water to accommodate and facilitate chemical processes. Therefore, the influence of charged species on water hydrogen-bond dynamics is important. Recent advances in ultrafast coherent infrared spectroscopy have greatly expanded our understanding of water dynamics. Two-dimensional infrared (2D IR) vibrational echo spectroscopy is providing new observables that yield direct information on the fast dynamics of molecules in their ground electronic state under thermal equilibrium conditions. The 2D IR vibrational echoes are akin to 2D nuclear magnetic resonance (NMR) but operate on time scales that are many orders of magnitude shorter. In a 2D IR vibrational echo experiment (see the Conspectus figure), three IR pulses are tuned to the vibrational frequency of interest, which in this case is the frequency of the hydroxyl stretching mode of water. The first two pulses \"label\" the initial molecular structures by their vibrational frequencies. The system evolves between pulses two and three, and the third pulse stimulates the emission of the vibrational echo pulse, which is the signal. The vibrational echo pulse is heterodyne, detected by combining it with another pulse, the local oscillator. Heterodyne detection provides phase and amplitude information, which are both necessary to perform the two Fourier transforms that take the data from the time domain to a two-dimensional frequency domain spectrum. The time dependence of a series of 2D IR vibrational echo spectra provides direct information on system dynamics. Here, we use two types of 2D IR vibrational echo experiments to examine the influence that charged species have on water hydrogen-bond dynamics. Solutions of NaBr and NaBF(4) are studied. The NaBr solutions are studied as a function of the concentration using vibrational echo measurements of spectral diffusion and polarization-selective IR pump-probe measurements of orientational relaxation. Both types of measurements show the slowing of hydrogen-bond network structural evolution with an increasing salt concentration. NaBF(4) is studied using vibrational echo chemical-exchange spectroscopy. In these experiments, it is possible to directly observe the chemical exchange of water molecules switching their hydrogen-bond partners between BF(4)(-) and other water molecules. The results demonstrate that water interacting with ions has slower hydrogen-bond dynamics than pure water, but the slowing is a factor of 3 or 4 rather than orders of magnitude.","subset":"pubmed_abstract"} +{"meta":{"pmid":19596630,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-14":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-10":3,"2024-26":1}}},"text":"Identification of faecal transmission of Toxoplasma gondii: Small science, large characters.\nThe first clue to the elucidation of the complete life cycle of Toxoplasma gondii was the identification of an infectious form in cat faeces that could be transmitted orally and could survive in the external environment for extended periods. This personal review describes the scientist (W.M. Hutchison) and the background to the initial discovery and covers the period to the complete elucidation of the life cycle of T. gondii.","subset":"pubmed_abstract"} +{"meta":{"pmid":18350321,"dup_signals":{"dup_doc_count":12}},"text":"Treatment of the neurogenic bladder in spina bifida.\nRenal damage and renal failure are among the most severe complications of spina bifida. Over the past decades, a comprehensive treatment strategy has been applied that results in minimal renal scaring. In addition, the majority of patients can be dry for urine by the time they go to primary school. To obtain such results, it is mandatory to treat detrusor overactivity from birth onward, as upper urinary tract changes predominantly start in the first months of life. This means that new patients with spina bifida should be treated from birth by clean intermittent catheterization and pharmacological suppression of detrusor overactivity. Urinary tract infections, when present, need aggressive treatment, and in many patients, permanent prophylaxis is indicated. Later in life, therapy can be tailored to urodynamic findings. Children with paralyzed pelvic floor and hence urinary incontinence are routinely offered surgery around the age of 5 years to become dry. Rectus abdominis sling suspension of the bladder neck is the first-choice procedure, with good to excellent results in both male and female patients. In children with detrusor hyperactivity, detrusorectomy can be performed as an alternative for ileocystoplasty provided there is adequate bladder capacity. Wheelchair-bound patients can manage their bladder more easily with a continent catheterizable stoma on top of the bladder. This stoma provides them extra privacy and diminishes parental burden. Bowel management is done by retrograde or antegrade enema therapy. Concerning sexuality, special attention is needed to address expectations of adolescent patients. Sensibility of the glans penis can be restored by surgery in the majority of patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":15758802,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Highly potent and moderately potent topical steroids are effective in treating phimosis: a prospective randomized study.\nWe report a prospective randomized study comparing the effects of highly potent and moderately potent topical steroids in treating pediatric phimosis. A total of 70 boys 1 to 12 years old with phimosis were randomly assigned to receive topical application of either betamethasone valerate 0.06% (a highly potent steroid) or clobetasone butyrate 0.05% (a moderately potent steroid). Parents of the boys were instructed to retract the foreskin gently without causing pain, and to apply the topical steroids over the stenotic opening of the prepuce twice daily for 4 weeks, then for another 4 weeks if no improvement was achieved. Retractibility of the prepuce was graded from 0 to 5. Response to treatment was arbitrarily defined as improvement in the retractibility score of more than 2 points. Mean treatment and followup periods were 4.3 and 19.1 weeks, respectively. The response rates in boys treated with betamethasone valerate and clobetasone butyrate were 81.3% and 77.4%, respectively (p = 0.63). Mean retractibility score decreased from 3.9 +\/- 1.0 to 1.7 +\/- 1.1, and 4.2 +\/- 1.0 to 1.9 +\/- 1.0 in the betamethasone and clobetasone groups, respectively. Both steroids were effective in all age groups. Pretreatment retractibility score did not affect treatment outcomes. No adverse effect was encountered. Highly potent and moderately potent topical steroids are of comparable effectiveness in treating phimosis. A less potent steroid may be considered first to decrease the risk of the potential adverse effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":8020804,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":6}}},"text":"Endomysium antibodies in coeliac disease: an improved method.\nThe ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":17562077,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2020-45":1,"2019-30":1,"2019-09":1,"2018-34":1,"2018-13":1,"2017-51":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2021-43":1,"2017-13":1}}},"text":"Factors influencing the efficacy of intra-articular steroid injections in patients with juvenile idiopathic arthritis.\nA retrospective chart review was performed of all patients with juvenile idiopathic arthritis (JIA) followed at our clinic who had an intra-articular steroid injection between 1 January 1997 and 31 December 2001. The aim of the study was to evaluate the outcome of intra-articular steroid injections (iaS) and determine prognostic factors. During the study period, 202 iaS were performed in 60 patients, of whom 37 had oligoarticular JIA, 15 had polyarticular, rheumatoid factor-negative JIA and four each had systemic and enthesitis-related JIA. The median duration of remission was 23.1 months (range: 0-69 months). At last follow-up, 103 joints (51%) of 47 patients were still in remission after a median follow-up time of 28 months (range: 1-69 months). For the total cohort, the remission was longer for wrist and finger joints [risk ratio (RR): 0.2], with concomitant treatment with methotrexate (RR: 0.28) and for enthesitis-related arthritis (RR: 0.34). For the group of knee joints, remission was longer with concomitant treatment with methotrexate (RR: 0.37), with triamcinolone hexacetonide (RR: 0.77) and with general anaesthesia for the procedure (RR: 0.56). Mild side effects were observed in 45 iaS (22.3%), and skin atrophy occurred at the injection site in 2% of injections, but no major adverse event occurred in our cohort. In conclusion, iaS is a safe procedure with a median duration of remission of 23.1 months. The remission was longer in the joints of the upper extremity, with concomitant treatment with methotrexate and when the injection was performed under general anaesthesia.","subset":"pubmed_abstract"} +{"meta":{"pmid":24737486,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"Notoriety bias in a database of spontaneous reports: the example of osteonecrosis of the jaw under bisphosphonate therapy in the French national pharmacovigilance database.\nThe purpose of this study was to identify a notoriety bias in a database of spontaneous reports and its consequences on the calculation of the reporting odds ratio (ROR). We used the case\/noncase methodology to calculate the ROR for bisphosphonates and osteonecrosis of the jaw (ONJ) in the French national pharmacovigilance database (from 1985 to 2013). To evaluate notoriety bias, drug-related risk factors for ONJ [as specified in the summary of product characteristics (SPC) of bisphosphonates] were systematically scanned for notifications of reports of ONJ occurring under bisphosphonate therapy. When a risk factor was present, the ONJ was considered as not due to bisphosphonates, and a second ROR was calculated under the hypothesis of maximum bias. In total, 148 cases of ONJ were reported (143 with bisphosphonates and five without). The raw ROR was 3448 (95% confidence interval 1413-8417). After analysis of the reports, only 86 had no mention of a risk factor for ONJ. The ROR under the maximum bias hypothesis was 87 (95% confidence interval 63-121). Among ONJ where chemotherapy was being administered simultaneously to bisphosphonates, 27 reports did not consider the chemotherapy to be implicated, despite seven of these occurring in cases where ONJ was mentioned in the summary of product characteristics. The existence of a notoriety bias has an impact on measures of disproportionality. The detection of pharmacovigilance signals might be delayed. It is advisable to list all drugs being taken when an adverse drug reaction occurs, and not only those known to be associated with the observed reaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":16214601,"dup_signals":{"dup_doc_count":61,"dup_dump_count":36,"dup_details":{"curated_sources":2,"2023-40":3,"2023-23":2,"2023-06":2,"2022-49":1,"2022-40":1,"2022-27":2,"2022-21":3,"2021-43":3,"2021-31":3,"2021-25":1,"2021-17":3,"2021-10":1,"2021-04":2,"2020-50":2,"2020-45":3,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":2,"2018-17":1,"2018-13":1,"2018-09":2,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":2,"2017-39":1,"2017-34":2,"2017-26":1,"2017-17":1,"2023-50":1,"2024-26":2,"2024-18":1,"2024-10":2}}},"text":"Suicides in male prisoners in England and Wales, 1978-2003.\nThe number of suicides in English and Welsh prisons is increasing, but the excess compared with the general population has not been reliably quantified. We therefore compared, in narrow age bands, all 1312 suicides of male prisoners in England and Wales between 1978 and 2003 with suicide rates in the general male population. The overall standardised mortality ratio for suicide was 5.1 (95% CI, 4.8-5.3), suggesting a five-fold excess of suicides in male prisoners, with a particularly striking excess in boys aged 15-17 years (standardised mortality ratio 18 [13-26]). The proportional excess of suicides of male prisoners has been increasing during the past quarter of a century, which underscores the need for substantial improvements in suicide prevention in prisons.","subset":"pubmed_abstract"} +{"meta":{"pmid":7927706,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-34":1,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":3,"2019-30":1,"2021-04":1}}},"text":"Anthrax edema toxin differentially regulates lipopolysaccharide-induced monocyte production of tumor necrosis factor alpha and interleukin-6 by increasing intracellular cyclic AMP.\nBacillus anthracis exotoxins mediate most of the symptomatology of severe anthrax. In addition to a clinical syndrome reminiscent of septic shock, which may be mediated by cytokines produced by macrophages stimulated with lethal toxin, infected patients show profound edema at sites of infection. Edema is mediated by edema toxin (ET), which comprises of a binding molecule, protective antigen, and an active moiety, edema factor, which possesses intrinsic adenylyl cyclase activity. Intracellular cyclic AMP (cAMP) regulates the production of several cytokines that modulate edema formation and play important roles in host defense against invading bacteria. To determine whether ET enhanced the accumulation of cAMP in monocytes and thereby influenced cytokine production, we cultured human monocytes with endotoxin (lipopolysaccharide [LPS]) and dilutions of ET and determined the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in culture supernatant fluids. We further estimated cytokine-specific mRNA accumulation in monocytes by reverse transcription PCR and examined intracellular cAMP concentrations following treatment with ET. ET and LPS each induced monocytes to secrete comparable amounts of IL-6. ET did not inhibit and in most experiments modestly enhanced LPS-induced IL-6 production. In contrast to this stimulatory effect on IL-6 production, ET induced little or no TNF-alpha production. Moreover, ET profoundly inhibited LPS-induced TNF-alpha synthesis. These regulatory phenomena were also observed at the mRNA level in association with dose-related enhancement of intracellular cAMP in ET-treated monocytes. Monocytes treated with dibutyryl cAMP, an active analog of cAMP, produced cytokines in a pattern identical to that of cells treated with ET. The disruption of cytokine networks as a consequence of unregulated, ET-induced cAMP accumulation in human monocytes may impair cellular antimicrobial responses and contribute to clinical signs and symptoms.","subset":"pubmed_abstract"} +{"meta":{"pmid":12446723,"dup_signals":{"dup_doc_count":80,"dup_dump_count":32,"dup_details":{"curated_sources":3,"2023-40":3,"2023-23":5,"2023-14":5,"2023-06":2,"2022-49":1,"2022-40":2,"2022-33":2,"2022-27":2,"2022-21":3,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":3,"2021-25":2,"2021-21":3,"2021-17":2,"2021-10":3,"2021-04":2,"2020-50":3,"2020-45":2,"2020-40":4,"2020-29":2,"2020-24":1,"2020-16":1,"2019-51":2,"2019-47":2,"2024-26":1,"2024-22":2,"2024-18":6,"2024-10":4,"2024-30":1}}},"text":"Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.\nThe activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":34419185,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":4,"2024-22":1,"unknown":5}}},"text":"Effectiveness of psychological interventions in prison to reduce recidivism: a systematic review and meta-analysis of randomised controlled trials.\nRepeat offending, also known as criminal recidivism, in people released from prison has remained high over many decades. To address this, psychological treatments have been increasingly used in criminal justice settings; however, there is little evidence about their effectiveness. We aimed to evaluate the effectiveness of interventions in prison to reduce recidivism after release. For this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, Global Health, MEDLINE, PsycINFO, and Google Scholar for articles published from database inception to Feb 17, 2021, without any language restrictions. We searched for randomised controlled trials (RCTs) that evaluated the effect of psychological interventions, delivered to adolescents and adults during incarceration, on recidivism outcomes after release. We excluded studies of solely pharmacological interventions and of participants in secure psychiatric hospitals or special residential units, or attending therapies mainly delivered outside of the prison setting. We extracted summary estimates from eligible RCTs. Data were extracted and appraised according to a prespecified protocol, with effect sizes converted to odds ratios. We used a standardised form to extract the effects of interventions on recidivism and estimated risk of bias for each RCT. Planned sensitivity analyses were done by removing studies with fewer than 50 participants. Our primary outcome was recidivism. Data from individual RCTs were combined in a random-effects meta-analysis as pooled odds ratios (ORs) and we explored sources of heterogeneity by comparing effect sizes by study size, control group, and intervention type. The protocol was pre-registered with PROSPERO, CRD42020167228. Of 6345 articles retrieved, 29 RCTs (9443 participants, 1104 [11\u00b77%] females, 8111 [85\u00b79%] males, and 228 [2\u00b74%] unknown) met the inclusion criteria for the primary outcome. Mean ages were 31\u00b74 years (SD 4\u00b79, range 24\u00b75-41\u00b75) for adult participants and 17\u00b75 years (SD 1\u00b79; range 14\u00b76-20\u00b72) for adolescent participants. Race or ethnicity data were not sufficiently reported to be aggregated. If including all 29 RCTs, psychological interventions were associated with reduced reoffending outcomes (OR 0\u00b772, 95% CI 0\u00b756-0\u00b792). However, after excluding smaller studies (<50 participants in the intervention group), there was no significant reduction in recidivism (OR 0.87, 95% CI 0\u00b768-1\u00b711). Based on two studies, therapeutic communities were associated with decreased rates of recidivism (OR 0\u00b764, 95% CI 0\u00b746-0\u00b791). These risk estimates did not significantly differ by type of control group and other study characteristics. Widely implemented psychological interventions for people in prison to reduce offending after release need improvement. Publication bias and small-study effects appear to have overestimated the reported modest effects of such interventions, which were no longer present when only larger studies were included in analyses. Findings suggest that therapeutic communities and interventions that ensure continuity of care in community settings should be prioritised for future research. Developing new treatments should focus on addressing modifiable risk factors for reoffending. Wellcome Trust, Fonds de recherche du Qu\u00e9bec - Sant\u00e9.","subset":"pubmed_abstract"} +{"meta":{"pmid":21750952,"dup_signals":{"dup_doc_count":20,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2022-05":1,"2021-10":1,"2020-34":1,"2020-29":1,"2020-16":1,"2019-51":1,"2019-35":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-22":1,"2018-17":1,"2018-05":2,"2017-47":1,"2017-39":1,"2023-06":1,"2024-26":1}}},"text":"The reward of a good joke: neural correlates of viewing dynamic displays of stand-up comedy.\nHumor is enjoyable, yet few studies to date have reported that humor engages brain regions involved in reward processing (i.e., the mesolimbic reward system). Even fewer have investigated socially relevant, dynamic displays of real actors telling jokes. Instead, many studies have focused on responses to static cartoons or written jokes in isolation. In the present investigation, we used functional magnetic resonance imaging (fMRI) to examine brain activation in response to video clips of comedians performing stand-up comedy, a more socially relevant task than reading jokes or cartoons in isolation. Participants watched video clips of eight stand-up comedians, half female\/half male, that were prerated by a separate group of participants from the same population as eliciting either high or low levels of amusement, thereby allowing us to control for comedian attributes and comedic style. We found that high-funny clips elicited more activation in several brain regions involved with reward responses, including the nucleus accumbens, caudate, and putamen. A regression with participants' own ratings of humor revealed similar activity in reward areas as well as in regions involved in theory of mind. These findings indicate that dynamic social displays of humor do engage reward responses. The rewarding nature of humor may help explain why it is so valued socially.","subset":"pubmed_abstract"} +{"meta":{"pmid":12000654,"dup_signals":{"dup_doc_count":30,"dup_details":{"curated_sources":2,"unknown":28}}},"text":"Measles in suburban Khartoum: an epidemiological and clinical study.\nClinical and epidemiological data were collected from 187 clinically diagnosed measles patients in Haj Yousif area, suburban Khartoum. Laboratory tests confirmed the diagnosis in 141 (75%) of the cases, but demonstrated that in 46 (25%) patients the clinical symptoms were not caused by an acute measles virus (MV) infection. According to their vaccination card, 59% of the laboratory-confirmed measles cases had been vaccinated for measles. Compared with non-measles rash disease cases, confirmed measles cases more often had severe illness (P < 0.0001), were dehydrated (P=0.01) at presentation and less likely to recover without complications [OR 0.19 (95% CI 0.09, 0.39)]. There was no difference in death rate (P=0.20). Underweight [weight-for-age Z score (WAZ) 200 \u00b0C). In this research, we successfully designed an effective strategy to fully convert methanol to hydrogen for at least 1900 min (\u223c32 h) at near-room temperature. The strategy involves two main procedures, which are CH3OH \u2192 HCOOH \u2192 H2 and CH3OH \u2192 NADH \u2192 H2. HCOOH and the reduced form of nicotinamide adenine dinucleotide (NADH) are simultaneously produced through the dehydrogenation of methanol by the cooperation of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Subsequently, HCOOH is converted to H2 by a new iridium polymer complex catalyst and an enzyme mimic is used to convert NADH to H2 and nicotinamide adenine dinucleotide (NAD+). NAD+ can then be reconverted to NADH by repeating the dehydrogenation of methanol. This strategy and the catalysts invented in this research can also be applied to hydrogen production from other small organic molecules (e.g. ethanol) or biomass (e.g. glucose), and thus will have a high impact on hydrogen storage and applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":24607387,"dup_signals":{"dup_doc_count":17,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2022-33":1,"2022-27":1,"2021-39":1,"2021-21":1,"2020-50":1,"2020-29":1,"2020-24":1,"2019-35":1,"2019-26":1,"2019-13":1,"2019-09":1,"2018-30":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-06":1}}},"text":"Early Austronesians: into and out of Taiwan.\nA Taiwan origin for the expansion of the Austronesian languages and their speakers is well supported by linguistic and archaeological evidence. However, human genetic evidence is more controversial. Until now, there had been no ancient skeletal evidence of a potential Austronesian-speaking ancestor prior to the Taiwan Neolithic ~6,000 years ago, and genetic studies have largely ignored the role of genetic diversity within Taiwan as well as the origins of Formosans. We address these issues via analysis of a complete mitochondrial DNA genome sequence of an ~8,000-year-old skeleton from Liang Island (located between China and Taiwan) and 550 mtDNA genome sequences from 8 aboriginal (highland) Formosan and 4 other Taiwanese groups. We show that the Liangdao Man mtDNA sequence is closest to Formosans, provides a link to southern China, and has the most ancestral haplogroup E sequence found among extant Austronesian speakers. Bayesian phylogenetic analysis allows us to reconstruct a history of early Austronesians arriving in Taiwan in the north ~6,000 years ago, spreading rapidly to the south, and leaving Taiwan ~4,000 years ago to spread throughout Island Southeast Asia, Madagascar, and Oceania.","subset":"pubmed_abstract"} +{"meta":{"pmid":17626631,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":2,"2015-18":1,"unknown":11}}},"text":"Does a referral from home to hospital affect satisfaction with childbirth? A cross-national comparison.\nThe Belgian and Dutch societies present many similarities but differ with regard to the organisation of maternity care. The Dutch way of giving birth is well known for its high percentage of home births and its low medical intervention rate. In contrast, home births in Belgium are uncommon and the medical model is taken for granted. Dutch and Belgian maternity care systems are compared with regard to the influence of being referred to specialist care during pregnancy or intrapartum while planning for a home birth. We expect that a referral will result in lower satisfaction with childbirth, especially in Belgium. Two questionnaires were filled out by 605 women, one at 30 weeks of pregnancy and one within the first two weeks after childbirth, either at home or in a hospital. Of these, 563 questionnaires were usable for analysis. Women were invited to participate in the study by independent midwives and obstetricians during antenatal visits in 2004-2005. Satisfaction with childbirth was measured by the Mackey Satisfaction with Childbirth Rating Scale, which takes into account the multidimensional nature of the concept. Belgian women are more satisfied than Dutch women and home births are more satisfying than hospital births. Women who are referred to the hospital while planning for a home birth are less satisfied than women who planned to give birth in hospital and did. A referral has a greater negative impact on satisfaction for Dutch women. There is no reason to believe Dutch women receive hospital care of lesser quality than Belgian women in case of a referral. Belgian and Dutch attach different meaning to being referred, resulting in a different evaluation of childbirth. In the Dutch maternity care system home births lead to higher satisfaction, but once a referral to the hospital is necessary satisfaction drops and ends up lower than satisfaction with hospital births that were planned in advance. We need to understand more about referral processes and how women experience them.","subset":"pubmed_abstract"} +{"meta":{"pmid":30251720,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Plutonium environmental chemistry: mechanisms for the surface-mediated reduction of Pu(v\/vi).\nIn recent decades, interest in plutonium mobility has increased significantly due to the need of the United States, as well as other nations, to deal with commercial spent nuclear fuel, nuclear weapons disarmament, and the remediation of locations contaminated by nuclear weapons testing and production. Although there is a global consensus that geologic disposal is the safest existing approach to dealing with spent nuclear fuel and high-level nuclear waste, only a few nations are moving towards implementing a geologic repository due to technical and political barriers. Understanding the factors that affect the mobility of plutonium in the subsurface environment is critical to support the development of such repositories. The importance of redox chemistry in determining plutonium mobility cannot be understated. While Pu(iv) is generally assumed to be immobile in the subsurface environment due to sorption or precipitation, Pu(v) tends to be mobile due to its relatively low effective charge and weak complex formation. This review highlights one particularly important aspect of plutonium behaviour at the mineral-water interface-the concept of surface-mediated reduction, which describes the reduction of plutonium on a mineral surface. It provides a conceptual model for and evidence supporting or refuting each proposed mechanism for surface-mediated reduction including (i) radiolysis at the mineral surface, (ii) electron transfer via ferrous iron or manganese in the mineral structure, (iii) electron shuttling due to the semiconducting properties of the mineral, (iv) disproportionation of Pu(v), (v) facilitation by proton exchange sites, (vi) stabilisation of Pu(iv) due to the increased concentration gradient within the electrical double layer, and (vii) a Nernstian favourability of Pu(iv) surface complexes and colloids. It also provides new perspectives on future research directions.","subset":"pubmed_abstract"} +{"meta":{"pmid":3519587,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Regions in Bacteroides plasmids pBFTM10 and pB8-51 that allow Escherichia coli-Bacteroides shuttle vectors to be mobilized by IncP plasmids and by a conjugative Bacteroides tetracycline resistance element.\nBacteroides-Escherichia coli shuttle vectors containing a nonmobilizable pBR322 derivative and either pBFTM10 (pDP1, pCG30) or pB8-51 (pEG920) were mobilized by IncP plasmid R751 or pRK231 (an ampicillin-sensitive derivative of RK2) between E. coli strains and from E. coli to Bacteroides recipients. IncI alpha R64 drd-ll transferred these vectors 1,000 times less efficiently than did the IncP plasmids. pDP1, pCG30, and pEG920 could be mobilized from B. uniformis donors to both E. coli and Bacteroides recipients by a conjugative Bacteroides Tcr (Tcr ERL) element which was originally found in a clinical Bacteroides fragilis strain (B. fragilis ERL). However, the shuttle vector pE5-2, which contains pB8-51 cloned in a restriction site that prevents its mobilization by IncP or IncI alpha plasmids, also was not mobilized at detectable frequencies from Bacteroides donors by the Tcr ERL element. The mobilization frequencies of pCG30, pDP1, and pEG920 by the Tcr ERL element in B. uniformis donors to E. coli recipients was about the same as those to isogenic B. uniformis recipients. Transfer of the shuttle vectors from B. uniformis donors to E. coli occurred at the same frequencies when the matings were done aerobically or anaerobically. Growth of the B. uniformis donors in tetracycline (1 microgram\/ml) prior to conjugation increased the mobilization frequencies of the vectors to both E. coli and Bacteroides recipients 50 to 100 times.","subset":"pubmed_abstract"} +{"meta":{"pmid":34037798,"dup_signals":{"dup_doc_count":24,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-50":4,"2023-23":2,"2023-14":2,"2022-49":2,"2022-40":2,"2022-33":2,"2022-27":1,"2022-21":1,"2024-26":1,"2024-18":2,"2024-30":1}}},"text":"CPA: a web-based platform for consensus pathway analysis and interactive visualization.\nIn molecular biology and genetics, there is a large gap between the ease of data collection and our ability to extract knowledge from these data. Contributing to this gap is the fact that living organisms are complex systems whose emerging phenotypes are the results of multiple complex interactions taking place on various pathways. This demands powerful yet user-friendly pathway analysis tools to translate the now abundant high-throughput data into a better understanding of the underlying biological phenomena. Here we introduce Consensus Pathway Analysis (CPA), a web-based platform that allows researchers to (i) perform pathway analysis using eight established methods (GSEA, GSA, FGSEA, PADOG, Impact Analysis, ORA\/Webgestalt, KS-test, Wilcox-test), (ii) perform meta-analysis of multiple datasets, (iii) combine methods and datasets to accurately identify the impacted pathways underlying the studied condition and (iv) interactively explore impacted pathways, and browse relationships between pathways and genes. The platform supports three types of input: (i) a list of differentially expressed genes, (ii) genes and fold changes and (iii) an expression matrix. It also allows users to import data from NCBI GEO. The CPA platform currently supports the analysis of multiple organisms using KEGG and Gene Ontology, and it is freely available at http:\/\/cpa.tinnguyen-lab.com.","subset":"pubmed_abstract"} +{"meta":{"pmid":17651493,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2015-18":1,"2017-13":1,"unknown":17}}},"text":"V1R promoters are well conserved and exhibit common putative regulatory motifs.\nThe mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, LogoAlign, designed for this context and more generally for searching large, hierarchical datasets, suggest the existence of common information-rich regulatory motifs that are shared across otherwise divergent V1R subfamilies.","subset":"pubmed_abstract"} +{"meta":{"pmid":21356129,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":1,"2013-20":1,"2024-18":1,"unknown":7}}},"text":"Exploring the effect of biological delays in kinetic models of influenza within a host or cell culture.\nFor a typical influenza infection in vivo, viral titers over time are characterized by 1-2 days of exponential growth followed by an exponential decay. This simple dynamic can be reproduced by a broad range of mathematical models which makes model selection and the extraction of biologically-relevant infection parameters from experimental data difficult. We analyze in vitro experimental data from the literature, specifically that of single-cycle viral yield experiments, to narrow the range of realistic models of infection. In particular, we demonstrate the viability of using a normal or lognormal distribution for the time a cell spends in a given infection state (e.g., the time spent by a newly infected cell in the latent state before it begins to produce virus), while exposing the shortcomings of ordinary differential equation models which implicitly utilize exponential distributions and delay-differential equation models with fixed-length delays. By fitting published viral titer data from challenge experiments in human volunteers, we show that alternative models can lead to different estimates of the key infection parameters.","subset":"pubmed_abstract"} +{"meta":{"pmid":18235121,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT.\nThe outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg\/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status. Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned (1:1) to receive imatinib 400 versus 600 mg\/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months. One hundred forty-seven patients were enrolled: 73 were in arm A (imatinib 400 mg\/d), and 74 were in arm B (imatinib 600 mg\/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall (28%) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival. Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg\/d starting dose.","subset":"pubmed_abstract"} +{"meta":{"pmid":10722915,"dup_signals":{"dup_doc_count":25,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2019-43":2,"2019-18":3,"2019-09":2,"2019-04":1,"2018-51":2,"2018-47":1,"2018-43":1,"2018-39":2,"2018-30":2,"2018-26":2,"2018-17":1,"2018-13":1,"2018-05":2,"2017-51":1,"2016-44":1}}},"text":"Doppler flow measurement using surface integration of velocity vectors (SIVV): in vitro validation.\nBlood flow measurement using an improved surface integration of velocity vectors (SIVV) technique was tested in in vitro phantoms. SIVV was compared with true flow (12-116 mL\/s) in a steady-state model using two angles of insonation (45 degrees and 60 degrees ) and two vessel sizes (internal diameter = 11 and 19 mm). Repeatability of the method was tested at various flow rates for each angle of insonation and vessel. In a univentricular pulsatile model, SIVV flow measured at the mitral inlet was compared to true flow (29-61 mL\/s). Correlation was excellent for the 19-mm vessel (r(2)= 0.99). There was a systematic bias but close limits of agreement (mean +\/- 2 SD = -24.1% +\/- 7.6% at 45 degrees; +16.4% +\/- 11.0% at 60 degrees ). Using the 11-mm vessel, a quadratic relationship was demonstrated between between SIVV and true flow (r(2) = 0.98-0.99), regardless of the angle of insonation. In the pulsatile system, good agreement and correlation were shown (r(2) = 0.94, mean +\/- 2 SD = -4.7 +\/- 10.1%). The coefficients of variation for repeated SIVV measurements ranged from 0.9% to 10.3%. This method demonstrates precision and repeatability, and is potentially useful for clinical measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":23961869,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Interview with daniel C. Dennett.\nDaniel Dennett was educated at Harvard and Oxford, receiving his D.Phil. in 1965. After six years at University of California Irvine, he moved to Tufts, where he is Distinguished Professor of Arts and Sciences and Director of the Center for Cognitive Studies. It is the author of articles on many issues in artificial intelligence, psychology, and cognitive ethology, as well as in philosophy. His books are Content and Consciousness (1969), Brainstorms (1978), The Mind's I (with Douglas Hofstadter, 1981). Elbow Room (1984), The Intentional Stance (1987), and Consciousness Explained (1991). His new book, Darwin's Dangerous Idea, will be published by Simon & Schuster in spring, 1995.","subset":"pubmed_abstract"} +{"meta":{"pmid":29507814,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"HIV-TB Coinfection among 57 Million Pregnant Women, Obstetric Complications, Alcohol Use, Drug Abuse, and Depression.\nHIV and tuberculosis represent diseases of major public health importance worldwide. Very little is known about HIV-TB coinfection among pregnant women, especially from industrialized settings. In this study, we examined the association between TB, HIV, and HIV-TB coinfection among pregnant mothers and obstetric complications, alcohol use, drug abuse, and depression. We examined inpatient hospital discharges in the United States from January 1, 2002, through December 31, 2014. We employed multivariable survey logistic regression to generate adjusted estimates for the association between infection status and study outcomes. We analyzed approximately 57 million records of pregnant women and their delivery information. HIV-TB coinfection was associated with the highest risks for several obstetric complications, alcohol use, and drug abuse. The risk for alcohol abuse was more than twice as high among HIV-monoinfected as compared to TB-monoinfected mothers. That risk gap more than doubled with HIV-TB coinfection. Both HIV-monoinfected and HIV-TB coinfected mothers experienced similarly increased risks for depression. Mothers with HIV-TB coinfection experienced relatively heightened risks for obstetric complications, alcohol use, and drug abuse. The findings of this study underscore the importance of augmenting and enhancing social and structural support systems for HIV-TB coinfected pregnant women.","subset":"pubmed_abstract"} +{"meta":{"pmid":26817392,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":14}}},"text":"Consumption of fruits and vegetables among adolescents: a multi-national comparison of eleven countries in the Eastern Mediterranean Region.\nRegional cross-country profile of fruit and vegetable (F&V) consumption is lacking in the Eastern Mediterranean Region (EMR). This study examines the prevalence and differences of consuming F&V \u22655 times\/d among adolescents in eleven EMR countries, and also describes differences in the proportions of taking F&V \u22655 times\/d by sex, age and BMI. The study included 26 328 school adolescents (13-15 years) with complete data on consumption of F&V, age, sex, weight and height taken from the Global School-based Student Health Survey conducted in the EMR between 2005 and 2009. Overall, only 19\u00b74 % of adolescents reported consuming F&V \u22655 times\/d. The highest prevalence was reported in Djibouti (40\u00b74 %) and the lowest was reported in Pakistan (10\u00b70 %). Statistically significant differences in prevalence were observed across countries (P<0\u00b705). With the exception of Oman, Libya and Djibouti, significantly more males than females ate F&V \u22655 times\/d. Proportion of students consuming F&V \u22655 times\/d also varied significantly in all counties based on BMI (P<0\u00b70001), with students within normal BMI having the highest frequency. A negative trend was observed between age and the prevalence of taking F&V \u22655 times\/d in most of the eleven EMR countries but Jordan, Djibouti and Morocco. The prevalence of adequate intake of F&V was low in the eleven EMR countries. There is a need for interventions to increase the prevalence of adolescents consuming F&V \u22655 times\/d. Interventions should take into consideration psychosocial, environmental and socio-environmental factors influencing F&V intake within countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":27215295,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2020-40":1,"2020-24":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-22":1,"2019-13":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2021-39":1}}},"text":"Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide.\nInexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (\u223c500 seropositive antigens) and mainly low level, with a small number of stronger \"hits,\" whereas the profile in U.S. adults was < 1\/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid\/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":22051683,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Parents' alcohol use: gender differences in the impact of household and family chores.\nSocial roles influence alcohol use. Nevertheless, little is known about how specific aspects of a given role, here parenthood, may influence alcohol use. The research questions for this study were the following: (i) are family-related indicators (FRI) linked to the alcohol use of mothers and fathers? and (ii) does the level of employment, i.e. full-time, part-time employment or unemployment, moderate the relationship between FRI and parental alcohol use? Survey data of 3217 parents aged 25-50 living in Switzerland. Mean comparisons and multiple regression models of annual frequency of drinking and risky single occasion drinking, quantity per day on FRI (age of the youngest child, number of children in the household, majority of child-care\/household duties). Protective relationships between FRI and alcohol use were observed among mothers. In contrast, among fathers, detrimental associations between FRI and alcohol use were observed. Whereas maternal responsibilities in general had a protective effect on alcohol use, the number of children had a detrimental impact on the quantity of alcohol consumed per day when mothers were in paid employment. Among fathers, the correlations between age of the youngest child, number of children and frequency of drinking was moderated by the level of paid employment. The study showed that in Switzerland, a systematic negative relationship was more often found between FRI and women's drinking than men's. Evidence was found that maternal responsibilities per se may protect from alcohol use but can turn into a detrimental triangle if mothers are additionally in paid employment.","subset":"pubmed_abstract"} +{"meta":{"pmid":28178440,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Comorbidities in Patients with Psoriatic Arthritis.\nEpidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":8575171,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":7}}},"text":"Transplantation of corneal tissue from donors with diseases of the central nervous system.\nA great deal of controversy and concern exists over potential transmission of central nervous system diseases by corneal transplant. The purpose of this study was to evaluate the available data relative to this question, pertaining especially to transmission of infectious dementia. From these data, determination of conveyance risks are possible, and rational policies for donor inclusion criteria can be constructed. Retrospective analysis of available published data regarding transmission of infectious dementias was performed. Risk of disease transmission was calculated from population data. Of the various forms of dementia, only rabies, hepatitis B, and Creutzfeldt-Jakob disease (CJD) have been transmitted by corneal transplantation. Transmission of the first two viruses is preventable by serologic testing. Prevention of CJD transmission relies on clinical history. Despite the possibility of transmission and the lack of available testing, slow virus disease (CJD) has been transmitted only once. That this case represents an extremely rare event is supported by a lack of successful transmission via corneal transplant in monkeys; lower levels of infectious agent in cornea than in brain; lack of successful transmission of similar human dementias, including Alzheimer's disease to primates; the apparent requirement for homozygosity at codon 129 of chromosome 20 for transmission; lack of transmission in 5-10% of CJD cases even after brain inoculation; and low numerical risk of transmission based on population data. Only 0.5-4 CJD infected donors per year would be expected. Current Eye Bank Association of America criteria for donor exclusion based on suspicious history are adequate to protect against accidental conveyance of transmissible dementia.","subset":"pubmed_abstract"} +{"meta":{"pmid":23749818,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"An unusual presentation of MEN2A.\nA 35-year-old woman presented with non-specific symptoms of fatigue and weight loss. Radiological investigations diagnosed a metastatic process and large bilateral adrenal masses. Histology from a liver biopsy and skin biopsy confirmed a diagnosis of metastatic medullary thyroid cancer. Further biochemical investigations revealed a positive 24-h urinary metanephrine collection and evidence of primary hyperparathyroidism. Genetic testing confirmed a mutant RET oncogene, confirming our clinical suspicion of multiple endocrine neoplasia type 2 (MEN2A) syndrome. The patient had no family history of endocrine disease and presented with widespread metastatic disease, making this an unusual presentation of MEN2A syndrome. Furthermore cutaneous metastases are rarely encountered in conjunction with metastatic medullary thyroid cancer. This case draws attention to the importance of genetic counselling in first-degree relatives of patients with confirmed MEN2A. This allows for timely diagnosis and reduced morbidity and mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":22385964,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2021-04":4,"2020-50":2,"2020-45":1,"2020-24":1,"2019-51":1,"2019-22":2,"2018-51":1,"2018-43":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1}}},"text":"A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage.\nCheckpoints that limit stem cell self-renewal in response to DNA damage can contribute to cancer protection but may also promote tissue aging. Molecular components that control stem cell responses to DNA damage remain to be delineated. Using in vivo RNAi screens, we identified basic leucine zipper transcription factor, ATF-like (BATF) as a major component limiting self-renewal of hematopoietic stem cells (HSCs) in response to telomere dysfunction and \u03b3-irradiation. DNA damage induces BATF in a G-CSF\/STAT3-dependent manner resulting in lymphoid differentiation of HSCs. BATF deletion improves HSC self-renewal and function in response to \u03b3-irradiation or telomere shortening but results in accumulation of DNA damage in HSCs. Analysis of bone marrow from patients with myelodysplastic syndrome supports the conclusion that DNA damage-dependent induction of BATF is conserved in human HSCs. Together, these results provide experimental evidence that a BATF-dependent differentiation checkpoint limits self-renewal of HSCs in response to DNA damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":26101043,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":14}}},"text":"Trends and socioeconomic differences in roll-your-own tobacco use: findings from the ITC Europe Surveys.\nTo examine if exclusive Roll-Your-Own (RYO) tobacco use relative to factory-made (FM) cigarette use has been rising over time, to determine the extent to which economic motives and perceptions that RYO cigarettes are less harmful act as primary motivations for use, and to examine the association of income and education with the level of RYO tobacco use among smokers in four European countries. Data were obtained from the International Tobacco Control (ITC) Europe Surveys, and a cohort sample of 7070 smokers from the Netherlands, Germany, France and UK were interviewed between June 2006 and December 2012. Generalised estimating equations (GEE) were used to assess trends in RYO use, and whether RYO consumption varied by socioeconomic variables. Exclusive RYO use over the study period has increased significantly in the UK from 26.4% in 2007 to 32.7% in 2010 (p<0.001); France from 12.2% in 2006 to 19.1% in 2012 (p<0.001); and Germany from 12.7% in 2007 to 18.6% in 2011 (p=0.031), with increased borderline significantly in the Netherlands (31.7% to 34.3%, p=0.052), from 2008 to 2010. Over three-quarters of users in each of the study countries indicated that lower price was a reason why they smoked RYO. Just over a fourth of smokers in the UK, less than a fifth in France, and around a tenth in Germany and the Netherlands believed that RYO is healthier. Compared with exclusive FM users, exclusive RYO users were more likely to have lower incomes and lower education. Effective tobacco tax regulation is needed in the European Union and elsewhere to eliminate or reduce the price advantage of RYO tobacco. Additional health messages are also required to correct the misperception that RYO tobacco is healthier than FM cigarettes.","subset":"pubmed_abstract"} +{"meta":{"pmid":28555839,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2022-49":1,"2021-49":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-24":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1}}},"text":"Promotion of endocytosis efficiency through an ATP-independent mechanism at rat calyx of Held terminals.\nAt rat calyx of Held terminals, ATP was required not only for slow endocytosis, but also for rapid phase of compensatory endocytosis. An ATP-independent form of endocytosis was recruited to accelerate membrane retrieval at increased activity and temperature. ATP-independent endocytosis primarily involved retrieval of pre-existing membrane, which depended on Ca2+ and the activity of neutral sphingomyelinase but not clathrin-coated pit maturation. ATP-independent endocytosis represents a non-canonical mechanism that can efficiently retrieve membrane at physiological conditions without competing for the limited ATP at elevated neuronal activity. Neurotransmission relies on membrane endocytosis to maintain vesicle supply and membrane stability. Endocytosis has been generally recognized as a major ATP-dependent function, which efficiently retrieves more membrane at elevated neuronal activity when ATP consumption within nerve terminals increases drastically. This paradox raises the interesting question of whether increased activity recruits ATP-independent mechanism(s) to accelerate endocytosis at the same time as preserving ATP availability for other tasks. To address this issue, we studied ATP requirement in three typical forms of endocytosis at rat calyx of Held terminals by whole-cell membrane capacitance measurements. At room temperature, blocking ATP hydrolysis effectively abolished slow endocytosis and rapid endocytosis but only partially inhibited excess endocytosis following intense stimulation. The ATP-independent endocytosis occurred at calyces from postnatal days 8-15, suggesting its existence before and after hearing onset. This endocytosis was not affected by a reduction of exocytosis using the light chain of botulinum toxin C, nor by block of clathrin-coat maturation. It was abolished by EGTA, which preferentially blocked endocytosis of retrievable membrane pre-existing at the surface, and was impaired by oxidation of cholesterol and inhibition of neutral sphingomyelinase. ATP-independent endocytosis became more significant at 34-35\u00b0C, and recovered membrane by an amount that, on average, was close to exocytosis. The results of the present study suggest that activity and temperature recruit ATP-independent endocytosis of pre-existing membrane (in addition to ATP-dependent endocytosis) to efficiently retrieve membrane at nerve terminals. This less understood endocytosis represents a non-canonical mechanism regulated by lipids such as cholesterol and sphingomyelinase.","subset":"pubmed_abstract"} +{"meta":{"pmid":28841399,"dup_signals":{"dup_doc_count":40,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2021-31":2,"2021-17":2,"2021-04":1,"2020-40":1,"2020-16":1,"2019-47":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-09":2,"2019-04":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-30":2,"2018-22":1,"2018-17":2,"2018-09":3,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":1,"2017-39":1,"2021-49":1}}},"text":"Infant and Young Child Feeding Decision Making and Practices: Malawian Mothers' and Fathers' Roles in the Context of HIV.\nFew studies in low- and middle-income countries have examined the roles of couples in infant and young child feeding decision making and practices, and there is no corresponding data in the context of human immunodeficiency virus (HIV). Research aim: This study aimed to explore mothers' and fathers' perceptions of their roles in feeding decision making and practices. The authors conducted in-depth interviews with 15 mothers and their male partners, recruited from the catchment areas of two urban and two rural government clinics in Lilongwe District, Malawi. The mothers were \u2265 18 years of age, were HIV positive, and had a child < 24 months of age. Twelve of the 15 fathers were also HIV positive. The interviews were analyzed using content analysis. Mothers were responsible for child care, including breastfeeding and complementary feeding. Fathers provided monetary support for purchasing food and offered verbal support to encourage mothers to implement recommended feeding practices. Many fathers found it difficult to support adequate complementary feeding because of household food insecurity. Mothers were advised on child feeding during prevention of mother-to-child transmission clinic visits. No fathers in this study accompanied women to clinic appointments, so they were less well-informed about feeding than mothers. Fathers usually deferred to mothers in feeding decision making. One-third of mothers wanted fathers to be more involved in child feeding. Malawian mothers' and fathers' roles in feeding decision making in the context of HIV align with local gender norms. Strategies are needed to improve fathers' knowledge of and involvement in child feeding, as desired by mothers.","subset":"pubmed_abstract"} +{"meta":{"pmid":26123351,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2021-21":1,"2021-04":1,"2020-40":2,"2020-29":1,"2020-16":1,"2020-10":1,"2020-05":2,"2019-51":1,"2019-43":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2022-49":1}}},"text":"Geriatric assessment findings independently associated with clinical depression in 1092 older patients with cancer: the ELCAPA Cohort Study.\nWe aim to assess the prevalence and associated factors of clinical depression in older patients with cancer. We studied a prospective cohort of cancer patients aged \u2265 70 years and referred to geriatric oncology clinics between 2007 and 2012. A multidimensional geriatric assessment was performed before choosing the cancer-treatment strategy. Clinical depression was diagnosed by senior geriatricians by a semi-structured interview. It encompassed criteria of the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) and of the International Classification of Diseases (10th edition). Multivariate logistic regression was performed. Of 1121 consecutive patients, 1092 had available data (mean age, 80.4 years; women, 48.8%; metastases, 51.3%; cancer location: colorectal 21.1%, breast 16.8%, kidney, bladder or urinary tract 14.0%, and prostate 11.4%). The overall prevalence of clinical depression was 28.4% (95% confidence interval, 25.7-31.2). Factors independently associated with clinical depression by multivariate analysis adjusting for all following factors plus gender, and metastasis were impaired mobility (adjusted odds ratio [aOR], 2.35; 1.59-3.46), impaired functional status defined as Eastern Cooperative Oncology Group Performance Status \u2265 2 (aOR, 2.39; 1.66-3.43) or as activities of daily living < 6 (aOR, 2.43; 1.73-3.41), inpatient status (aOR, 1.68; 1.20-2.37), inadequate social support (aOR, 1.66; 1.16-2.37), cognitive impairment (aOR, 1.76; 1.24-2.49), polypharmacy defined as five or more non-antidepressant drugs (aOR, 1.65; 1.14-2.38), multimorbidity (aOR additional CIRS-G point , 1.08; 1.04-1.12), and cancer-related pain (aOR, 1.76; 1.26-2.46). In older patients with as-yet untreated cancer at various sites and stages, clinical depression was highly prevalent. Clinical depression was independently associated with several geriatric assessment findings (impaired mobility and function, inadequate social support, cognitive impairment, polypharmacy, and multimorbidity) independently from gender, tumor site, and metastatic status.","subset":"pubmed_abstract"} +{"meta":{"pmid":18158962,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2023-50":1,"2024-22":1}}},"text":"Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020.\nIntensive chemotherapy for human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) has resulted in durable remissions in a substantial proportion of patients. High-dose chemotherapy and autologous stem cell transplantation (AuSCT), moreover, has resulted in sustained complete remissions in selected patients with recurrent chemosensitive disease. Based on a favorable experience with dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT for older patients with non-HIV-associated aggressive lymphomas, an AIDS Malignancy Consortium multicenter trial was undertaken using the same dose-reduced busulfan and cyclophosphamide preparative regimen with AuSCT for recurrent HIV-associated NHL and HL. Of the 27 patients in the study, 20 received an AuSCT. The median time to achievement of an absolute neutrophil count (ANC) of >or= 0.5 x 10(9)\/L was 11 days (range, 9-16 days). The median time to achievement of an unsupported platelet count of >or= 20 x 10(9)\/L was 13 days (range, 6-57 days). One patient died on day +33 posttransplantation from hepatic veno-occlusive disease (VOD) and multiorgan failure. No other fatal regimen-related toxicity occurred. Ten of 19 patients (53%) were in complete remission at the time of their day +100 post-AuSCT evaluation. Of the 20 patients, 10 were alive and event-free at a median of 23 weeks post-AuSCT. Median overall survival (OS) was not reached by 13 of the 20 patients alive at the time of last follow-up. This multi-institutional trial demonstrates that a regimen of dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT is well tolerated and is associated with favorable disease-free survival (DFS) and OS probabilities for selected patients with HIV-associated NHL and HL.","subset":"pubmed_abstract"} +{"meta":{"pmid":15909336,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Application of derivative ratio spectrophotometry for determination of beta-carotene and astaxanthin from Phaffia rhodozyma extract.\nA derivative ratio spectrophotometric method was used for the simultaneous determination of beta-carotene and astaxanthin produced from Phaffia rhodozyma. Absorbencies of a series of the standard carotenoids in the range of 441 nm to 490 nm demonstrated that their absorptive spectra accorded with Beer's law and that the additivity when the concentrations of beta-carotene and astaxanthin and their mixture were within the range of 0 to 5 microg\/ml, 0 to 6 microg\/ml, and 0 to 6 microg\/ml, respectively. When the wavelength interval (lambda) at 2 nm was selected to calculate the first derivative ratio spectra values, the first derivative amplitudes at 461 nm and 466 nm were suitable for quantitatively determining beta-carotene and astaxanthin, respectively. Effect of divisor on derivative ratio spectra could be neglected; any concentration used as divisor in range of 1.0 to 4.0 microg\/ml is ideal for calculating the derivative ratio spectra values of the two carotenoids. Calibration graphs were established for beta-carotene within 0-6.0 microg\/ml and for astaxanthin within 0-5.0 microg\/ml with their corresponding regressive equations in: y=-0.0082x-0.0002 and y=0.0146x-0.0006, respectively. R-square values in excess of 0.999 indicated the good linearity of the calibration graphs. Sample recovery rates were found satisfactory (>99%) with relative standard deviations (RSD) of less than 5%. This method was successfully applied to simultaneous determination of beta-carotene and astaxanthin in the laboratory-prepared mixtures and the extract from the Phaffia rhodozyma culture.","subset":"pubmed_abstract"} +{"meta":{"pmid":25576332,"dup_signals":{"dup_doc_count":12}},"text":"Peripheral facial palsy as an initial symptom of Lyme neuroborreliosis in an Austrian endemic area.\nThe objective of this study was to analyze the percentage as well as clinical and laboratory characteristics of Lyme neuroborreliosis (LNB) in patients admitted with peripheral facial palsy. Additionally, we looked for diagnostic criteria to distinguish Bell's palsy from facial palsy due to LNB. Data collection was done retrospectively from 2007 until 2012. We identified 278 consecutive patients, who were admitted to the department of Neurology due to peripheral facial palsy. Patients were routinely investigated for LNB including clinical neurological examination and cerebral spinal fluid (CSF) analysis. Demographic and clinical data were analyzed according to a standardized protocol. In 19 (male (m) = 14\/female (f) = 5) out of 278 patients (7 %), a diagnosis of LNB was established. There were 8 patients (3 %) identified with varicella zoster (VZV) (m = 7\/f = 1) and 13 patients (5 %) with facial palsy due to diabetic mononeuropathy (m = 5\/f = 8). A total of 207 patients (75 %) were diagnosed as Bell's palsy (m = 110\/f = 97). Compared with CSF of patients with facial palsy due to VZV and diabetic mononeuropathy, patients with LNB showed higher cell count, protein and lactate levels, whereas patients with facial palsy due to diabetic mononeuropathy showed higher glucose level. With respect to seasonal clustering, an accumulation of 74 % of the LNB cases was detected from June to October, whereas in the rest of the year there were only 26 % of the LNB cases. Patients with Bell's palsy are more evenly distributed over the year. Regarding neurological signs and symptoms, radicular symptoms were only reported in the LNB group. Despite radicular symptoms for LNB, no specific signs or symptoms were found for facial palsy due to VZV, Bell's palsy, or diabetic mononeuropathy. According to the results of our study, we recommend CSF testing in any case for patients with facial palsy in an endemic area from June to October especially if additional radicular symptoms are present. To establish recommendations for a diagnostic workup in patients with facial palsy in areas endemic for Borrelia, the seasonal clustering of LNB as well as specific clinical features should also be confirmed in a future prospective trial.","subset":"pubmed_abstract"} +{"meta":{"pmid":28740125,"dup_signals":{"dup_doc_count":28,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":26}}},"text":"APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome.\nMetabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3\/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":34058765,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Racial and Ethnic Disparities in Adverse Perinatal Outcomes at Term.\nThis study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by \u2265 3 days), brachial plexus palsy, or facial nerve palsy. Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic). Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. \u00b7 Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. \u00b7 After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. \u00b7 Disparities in outcomes are strongly related to insurance status..","subset":"pubmed_abstract"} +{"meta":{"pmid":12468733,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":7}}},"text":"A gain-of-function mutation in an Arabidopsis Toll Interleukin1 receptor-nucleotide binding site-leucine-rich repeat type R gene triggers defense responses and results in enhanced disease resistance.\nIn a screen for suppressors of npr1-5-based salicylic acid (SA) insensitivity, we isolated a semidominant gain-of-function mutation, designated ssi4, that confers constitutive expression of several PR (pathogenesis-related) genes, induces SA accumulation, triggers programmed cell death, and enhances resistance to bacterial and oomycete pathogens. Through map-based cloning, ssi4 was identified and found to encode a putative protein belonging to the TIR-NBS-LRR (Toll Interleukin1 Receptor-Nucleotide Binding Site-Leu-Rich Repeat) class of R (resistance) proteins. Comparison between ssi4 and the corresponding wild-type sequence revealed a single amino acid substitution in the NBS. Epistasis analysis indicated that SA and EDS1 are required for ssi4-induced PR-1 expression and enhanced disease resistance; they also are required for the increased accumulation of SSI4 and EDS1 transcripts detected in the ssi4 mutant. Although high levels of ssi4 transcripts correlate with the appearance of the mutant phenotype, overexpression of the wild-type SSI4 gene failed to induce stunting, spontaneous lesion formation, or increased PR-1 expression associated with the ssi4 mutation. Thus, the ssi4 phenotype does not appear to be caused by overexpression of this R gene; rather, we propose that the NBS substitution generates a constitutively activated R protein. Furthermore, because SA treatment induced the expression of SSI4 and the closely related TIR-NBS-LRR genes RPP1 and RPS4 but had little effect on the expression of the coiled-coil NBS-LRR genes RPM1 and RPS2, we suggest that SA not only functions as a critical signal for downstream resistance events but also upregulates the expression of certain R genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29477734,"dup_signals":{"dup_doc_count":12}},"text":"CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris.\nHeterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-\u03b1 inhibitors. We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14. Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed. We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab. Relatively small sample size. Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.","subset":"pubmed_abstract"} +{"meta":{"pmid":29486878,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"African swine fever: A re-emerging viral disease threatening the global pig industry.\nAfrican swine fever (ASF) recently has spread beyond sub-Saharan Africa to the Trans-Caucasus region, parts of the Russian Federation and Eastern Europe. In this new epidemiological scenario, the disease has similarities, but also important differences, compared to the situation in Africa, including the substantial involvement of wild boar. A better understanding of this new situation will enable better control and prevent further spread of disease. In this article, these different scenarios are compared, and recent information on the pathogenesis of ASF virus strains, the immune response to infection and prospects for developing vaccines is presented. Knowledge gaps and the prospects for future control are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":28422718,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine workflow for BRCA1 and BRCA2 genetic testing.\nIn this study, we validated the analytical performance of BRCA1\/2 sequencing using Ion Torrent's new bench-top sequencer with amplicon panel with optimized bioinformatics pipelines. Using 43 samples that were previously validated by Illumina's MiSeq platform and\/or by Sanger sequencing\/multiplex ligation-dependent probe amplification, we amplified the target with the Oncomine\u2122 BRCA Research Assay and sequenced on Ion Torrent S5 XL (Thermo Fisher Scientific, Waltham, MA, USA). We compared two bioinformatics pipelines for optimal processing of S5 XL sequence data: the Torrent Suite with a plug-in Torrent Variant Caller (Thermo Fisher Scientific), and commercial NextGENe software (Softgenetics, State College, PA, USA). All expected 681 single nucleotide variants, 15 small indels, and three copy number variants were correctly called, except one common variant adjacent to a rare variant on the primer-binding site. The sensitivity, specificity, false positive rate, and accuracy for detection of single nucleotide variant and small indels of S5 XL sequencing were 99.85%, 100%, 0%, and 99.99% for the Torrent Variant Caller and 99.85%, 99.99%, 0.14%, and 99.99% for NextGENe, respectively. The reproducibility of variant calling was 100%, and the precision of variant frequency also showed good performance with coefficients of variation between 0.32 and 5.29%. We obtained highly accurate data through uniform and sufficient coverage depth over all target regions and through optimization of the bioinformatics pipeline. We confirmed that our platform is accurate and practical for diagnostic BRCA1\/2 testing in a clinical laboratory.","subset":"pubmed_abstract"} +{"meta":{"pmid":11098125,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy.\nRecent evidence suggests that lactate could be a preferential energy substrate transferred from astrocytes to neurons. This would imply the presence of specific transporters for lactate on both cell types. We have investigated the immunohistochemical localization of two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Using specific antibodies raised against MCT1 and MCT2, we found strong immunoreactivity for each transporter in glia limitans, ependymocytes and several microvessel-like elements. In addition, small processes distributed throughout the cerebral parenchyma were immunolabeled for monocarboxylate transporters. Double immunofluorescent labeling and confocal microscopy examination of these small processes revealed no co-localization between glial fibrillary acidic protein and monocarboxylate transporters, although many glial fibrillary acidic protein-positive processes were often in close apposition to elements labeled for monocarboxylate transporters. In contrast, several elements expressing the S100beta protein, another astrocytic marker found to be located in distinct parts of the same cell when compared with glial fibrillary acidic protein, were also strongly immunoreactive for MCT1, suggesting expression of this transporter by astrocytes. In contrast, MCT2 was expressed in a small subset of microtubule-associated protein-2-positive elements, indicating a neuronal localization. In conclusion, these observations are consistent with the possibility that lactate, produced and released by astrocytes (via MCT1), could be taken up (via MCT2) and used by neurons as an energy substrate.","subset":"pubmed_abstract"} +{"meta":{"pmid":17987573,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Minimally invasive approaches to prostate cancer: a review of the current literature.\nWhile radical retropubic prostatectomy has been the gold standard surgical approach, the explosion of minimally invasive methods has led to the search for less invasive treatment options. We offer an overview of the evolution of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RALP) in terms of the landmark publications and recent head-to-head comparisons, and we review our own experience. A Medline search was performed using the keywords prostate cancer, prostatectomy, laparoscopic, and robotic. All pertinent articles concerning localized prostate cancer were reviewed. The Montefiore experience consisted of a retrospective review of a prospectively maintained confidential database. Several laparoscopic and robotic series were identified including review articles of each modality as well as studies directly comparing the two. Both LRP and RALP compare very favorably with conventional open surgery in terms of safety and oncologic efficacy. Both minimally invasive approaches offer decreased blood loss, transfusion rate, and length of hospital stay when contrasted with open surgery. When compared directly, LRP and RALP offer similar surgical, oncologic, and functional outcomes. However, RALP likely requires a shorter learning curve. The use of minimally invasive techniques has revolutionized the surgical treatment of prostate cancer. Pure LRP has been shown to be feasible and reproducible. However, it has a steep learning curve and is difficult to learn. In contrast, RALP is easier to learn and is now the surgical treatment of choice in most centers of excellence in the United States. The superior optics with respect to visualization and magnification translates into a procedure that is equivalent, if not superior, with respect to perioperative parameters, oncologic outcomes, and functional outcomes to its open counterpart.","subset":"pubmed_abstract"} +{"meta":{"pmid":26124866,"dup_signals":{"dup_doc_count":32,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2023-14":2,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-43":1,"2023-50":1,"2024-30":2,"2024-10":1}}},"text":"Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors.\nIn this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten-Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3\u00b7DMF complex was optimized. It was crucial to follow this process by 700 MHz (1)H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.","subset":"pubmed_abstract"} +{"meta":{"pmid":20473093,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"A case-oriented approach exploring the relationship between visual and vestibular disturbances and problems of higher-level mobility in persons with traumatic brain injury.\nDizziness and impaired balance are common complaints after traumatic brain injury as a result of injuries to many systems. Ambient visual and vestibular system impairments are strong contributors to imbalance and dizziness, often leading to problems with spatial orientation and gaze stability during movement. The purpose of this review is to provide an overview of visual-vestibular impairments common to traumatic brain injury and summarize the contribution impairments in these systems will have on higher-level mobility. Standard visual and vestibular tests and measures are described and summarized, followed by several case presentations discussing the examination and evaluation processes and interventions chosen for visual-vestibular difficulties and their relationship to higher-level mobility.","subset":"pubmed_abstract"} +{"meta":{"pmid":24962181,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Evaluating the thermal effects of translocation in a large-bodied pitviper.\nAcute stressors can be costly, often requiring alteration of normal physiological processes to mitigate their effects. Animal translocation may be a very stressful event and result in a reduced ability to maintain homeostasis. The impacts of translocation on the thermal ecology of ectothermic vertebrates, which may rely on preferred habitats for thermoregulation, are currently unknown. In this study, 22 adult male Northern Pacific rattlesnakes (Crotalus oreganus oreganus) were implanted with automated temperature loggers and radio-tracked. Snakes were assigned to one of three treatments: translocation, handling control, and undisturbed control. Short-distance translocation (SDT) and handling treatments were applied weekly for 6 weeks. Hourly body temperature (Tb ) was recorded during the course of the study. Mean Tb was impacted in a time-dependent fashion, where translocated snakes had lower mean Tb than handled controls during the first week of the study only, especially the first 24 hr after translocation. Separating the dataset into day and night revealed that this effect was localized to Tb variation during the day only. Variance in temperature was not impacted by translocation or handling. Snake body mass and time of year were the major factors influencing the thermal profiles of these rattlesnakes. Thermal ecology in male rattlesnakes is resilient to SDT, suggesting that they quickly resume normal behaviors following repeated bouts of acute capture stress and disturbance of their spatial ecology. This study provides support for SDT as a safe measure for mitigating human-snake interactions and facilitating conservation practices regarding male snakes, which are the most frequently encountered sex.","subset":"pubmed_abstract"} +{"meta":{"pmid":29734881,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Effect of ubiquinol supplementation on biochemical and oxidative stress indexes after intense exercise in young athletes.\nPhysical exercise significantly impacts the biochemistry of the organism. Ubiquinone is a key component of the mitochondrial respiratory chain and ubiquinol, its reduced and active form, is an emerging molecule in sport nutrition. The aim of this study was to evaluate the effect of ubiquinol supplementation on biochemical and oxidative stress indexes after an intense bout of exercise. 21 male young athletes (26 + 5 years of age) were randomized in two groups according to a double blind cross-over study, either supplemented with ubiquinol (200 mg\/day) or placebo for 1 month. Blood was withdrawn before and after a single bout of intense exercise (40 min run at 85% maxHR). Physical performance, hematochemical parameters, ubiquinone\/ubiquinol plasma content, intracellular reactive oxygen species (ROS) level, mitochondrial membrane depolarization, paraoxonase activity and oxidative DNA damage were analyzed. A single bout of intense exercise produced a significant increase in most hematochemical indexes, in particular CK and Mb while, on the contrary, normalized coenzyme Q10 plasma content decreased significantly in all subjects. Ubiquinol supplementation prevented exercise-induced CoQ deprivation and decrease in paraoxonase activity. Moreover at a cellular level, in peripheral blood mononuclear cells, ubiquinol supplementation was associated with a significant decrease in cytosolic ROS while mitochondrial membrane potential and oxidative DNA damage remained unchanged. Data highlights a very rapid dynamic of CoQ depletion following intense exercise underlying an increased demand by the organism. Ubiquinol supplementation minimized exercise-induced depletion and enhanced plasma and cellular antioxidant levels but it was not able to improve physical performance indexes or markers of muscular damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":31058097,"dup_signals":{"dup_doc_count":53,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":3,"2023-23":2,"2023-06":2,"2022-49":1,"2022-40":2,"2022-33":1,"2022-27":2,"2022-21":1,"2022-05":2,"2021-49":2,"2021-43":3,"2021-39":2,"2021-31":1,"2021-25":2,"2021-17":3,"2021-10":2,"2021-04":1,"2020-50":2,"2020-45":1,"2020-40":3,"2020-34":1,"2019-39":1,"2019-26":1,"2024-22":1,"2024-10":3,"2024-26":1}}},"text":"A P. falciparum NF54 Reporter Line Expressing mCherry-Luciferase in Gametocytes, Sporozoites, and Liver-Stages.\nTransgenic malaria parasites expressing fluorescent and bioluminescent proteins are valuable tools to interrogate malaria-parasite biology and to evaluate drugs and vaccines. Using CRISPR\/Cas9 methodology a transgenic Plasmodium falciparum (Pf) NF54 line was generated that expresses a fusion of mCherry and luciferase genes under the control of the Pf etramp10.3 gene promoter (line email@example.com). Pf etramp10.3 is related to rodent Plasmodium uis4 and the uis4 promoter has been used to drive high transgene expression in rodent parasite sporozoites and liver-stages. We examined transgene expression throughout the complete life cycle and compared this expression to transgenic lines expressing mCherry-luciferase and GFP-luciferase under control of the constitutive gapdh and eef1a promoters. The email@example.com parasites express mCherry in gametocytes, sporozoites, and liver-stages. While no mCherry signal was detected in asexual blood-stage parasites above background levels, luciferase expression was detected in asexual blood-stages, as well as in gametocytes, sporozoites and liver-stages, with the highest levels of reporter expression detected in stage III-V gametocytes and in sporozoites. The expression of mCherry and luciferase in gametocytes and sporozoites makes this transgenic parasite line suitable to use in in vitro assays that examine the effect of transmission blocking inhibitors and to analyse gametocyte and sporozoite biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":19717522,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2022-49":1,"2022-27":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-51":1,"2019-35":1,"2023-23":1,"2024-18":1,"2024-10":1,"2024-26":1}}},"text":"The two groups of zebrafish virus-induced interferons signal via distinct receptors with specific and shared chains.\nBecause the availability of fish genomic data, the number of reported sequences for fish type II helical cytokines is rapidly growing, featuring different IFNs including virus-induced IFNs (IFNphi) and IFN-gamma, and IL-10 with its related cytokines (IL-20, IL-22, and IL-26). Many candidate receptors exist for these cytokines and various authors have postulated which receptor chain would be involved in which functional receptor in fish. To date, only the receptor for zebrafish IFNphi1 has been identified functionally. Three genes encoding virus-induced IFNphis have been reported in zebrafish. In addition to these genes clustered on chromosome 3, we have identified a fourth IFNphi gene on chromosome 12. All these genes possess the intron-exon organization of mammalian lambda IFNs. In the zebrafish larva, all induce the expression of reporter antiviral genes; protection in a viral challenge assay was observed for IFNphi1 and IFNphi2. Using a combination of gain- and loss-of-function experiments, we also show that all zebrafish IFNphis do not bind to the same receptor. Two subgroups of fish virus-induced IFNs have been defined based on conserved cysteines, and we find that this subdivision correlates with receptor usage. Both receptor complexes include a common short chain receptor (CRFB5) and a specific long chain receptor (CRFB1 or CRFB2).","subset":"pubmed_abstract"} +{"meta":{"pmid":8628318,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Analysis of the galactose signal transduction pathway in Saccharomyces cerevisiae: interaction between Gal3p and Gal80p.\nThe GAL3 gene plays a critical role in galactose induction of the GAL genes that encode galactose- metabolizing enzymes in Saccharomyces cerevisiae. Defects in GAL3 result in a long delay in GAL gene induction, and overproduction of Gal3p causes constitutive expression of GAL. Here we demonstrate that concomitant overproduction of the negative regulator, Gal80p, and Gal3p suppresses this constitutive GAL expression. This interplay between Gal80p and Gal3p is direct, as tagged Gal3p coimmunoprecipitated with Gal80p. The amount of coprecipitated Gal80p increased when GAL80 yeast cells were grown in the presence of galactose. When both GAL80 and GAL3 were overexpressed, the amount of coprecipitated Gal80p was not affected by galactose. Tagged gal3 mutant proteins bound to purified Gal80p, but only poorly in comparison with the wild type, suggesting that formation of the Gal80p-Gal3p complex depends on the normal function of Gal3p. Gal3p appeared larger in Western blots (immunoblots) than predicted by the published nucleic acid sequence. Reexamination of the DNA sequence of GAL3 revealed several mistakes, including an extension at the 3' end of another predicted 97 amino acids.","subset":"pubmed_abstract"} +{"meta":{"pmid":22275218,"dup_signals":{"dup_doc_count":27,"dup_dump_count":12,"dup_details":{"curated_sources":3,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":2,"2017-09":1,"2017-04":1,"2016-50":4,"2016-44":3,"2016-40":3,"2016-36":2,"2015-22":1,"2017-13":2}}},"text":"A pseudokinase debut at the mycobacterial cell wall.\nMycobacterium tuberculosis, the causative agent of tuberculosis, has a complex cellular envelope that comprises both the cytoplasmic membrane and the outer cell wall. Despite advances in elucidating the structural and biochemical composition of these features, the processes that ensure cell wall homeostasis remain poorly understood. New findings implicate the essential mycobacterial serine-threonine protein kinase (STPK), PknB, in regulating the formation of a regulatory complex that includes the integral membrane protein MviN, which is required for peptidoglycan biosynthesis, and a forkhead-associated (FHA) domain protein, FhaA. A model has emerged in which a peptidoglycan-derived muropeptide signal triggers the PknB-mediated phosphorylation of the MviN pseudokinase domain, which in turn recruits the FHA-containing regulatory protein to inhibit peptidoglycan biosynthesis at the cell poles and septum. In establishing PknB as central regulator of this pathway, the model reinforces the major role of this STPK network in the orchestration of fundamental mycobacterial processes, and, with the identification of MviN as having a catalytically inactive and highly divergent kinase homology domain, the model establishes a pseudokinase as a key player in cell wall metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":17620356,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Influence of the Cpx extracytoplasmic-stress-responsive pathway on Yersinia sp.-eukaryotic cell contact.\nThe extracytoplasmic-stress-responsive CpxRA two-component signal transduction pathway allows bacteria to adapt to growth in extreme environments. It controls the production of periplasmic protein folding and degradation factors, which aids in the biogenesis of multicomponent virulence determinants that span the bacterial envelope. This is true of the Yersinia pseudotuberculosis Ysc-Yop type III secretion system. However, despite using a second-site suppressor mutation to restore Yop effector secretion by yersiniae defective in the CpxA sensor kinase, these bacteria poorly translocated Yops into target eukaryotic cells. Investigation of this phenotype herein revealed that the expression of genes which encode several surface-located adhesins is also influenced by the Cpx pathway. In particular, the expression and surface localization of invasin, an adhesin that engages beta1-integrins on the eukaryotic cell surface, are severely restricted by the removal of CpxA. This reduces bacterial association with eukaryotic cells, which could be suppressed by the ectopic production of CpxA, invasin, or RovA, a positive activator of inv expression. In turn, these infected eukaryotic cells then became susceptible to intoxication by translocated Yop effectors. In contrast, bacteria harboring an in-frame deletion of cpxR, which encodes the cognate response regulator, displayed an enhanced ability to interact with cell monolayers, as well as elevated inv and rovA transcription. This phenotype could be drastically suppressed by providing a wild-type copy of cpxR in trans. We propose a mechanism of inv regulation influenced by the direct negative effects of phosphorylated CpxR on inv and rovA transcription. In this fashion, sensing of extracytoplasmic stress by CpxAR contributes to productive Yersinia sp.-eukaryotic cell interactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":10036243,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Regulation of the start of DNA replication in Schizosaccharomyces pombe.\nCells of Schizosaccharomyces pombe were grown in minimal medium with different nitrogen sources under steady-state conditions, with doubling times ranging from 2.5 to 14 hours. Flow cytometry and fluorescence microscopy confirmed earlier findings that at rapid growth rates, the G1 phase was short and cell separation occurred at the end of S phase. For some nitrogen sources, the growth rate was greatly decreased, the G1 phase occupied 30-50% of the cell cycle, and cell separation occurred in early G1. In contrast, other nitrogen sources supported low growth rates without any significant increase in G1 duration. The method described allows manipulation of the length of G1 and the relative cell cycle position of S phase in wild-type cells. Cell mass was measured by flow cytometry as scattered light and as protein-associated fluorescence. The extensions of G1 were not related to cell mass at entry into S phase. Our data do not support the hypothesis that the cells must reach a certain fixed, critical mass before entry into S. We suggest that cell mass at the G1\/S transition point is variable and determined by a set of molecular parameters. In the present experiments, these parameters were influenced by the different nitrogen sources in a way that was independent of the actual growth rate.","subset":"pubmed_abstract"} +{"meta":{"pmid":22556257,"dup_signals":{"dup_doc_count":51,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2017-43":2,"2017-39":2,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":4,"2017-17":1,"2017-09":5,"2017-04":2,"2016-50":1,"2016-44":4,"2016-40":4,"2016-36":5,"2016-30":5,"2016-22":2,"2016-18":2,"2016-07":5,"2017-13":2}}},"text":"Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice.\nMedical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":30681997,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":13}}},"text":"Artist Impact: Effects of Live Art on Patients and Staff in an Outpatient Chemotherapy Treatment Environment.\nVisual art and music have been found to improve the emotions and moods of patients and healthcare staff, and attendance of live performances has been shown to foster social interaction. The aim of the study was to explore the effects of a visual artist on patients and nursing staff in an outpatient chemotherapy treatment environment. During an eight-week period, an artist painted in an outpatient chemotherapy treatment room, either interacting with patients (six weeks) or quietly painting while wearing headphones (two weeks). A total of 73 surveys were completed by patients and staff, providing quantitative and qualitative data about anxiety, distraction, enjoyment, and social interaction. Patients evaluated the experience positively, whether the artist was interacting with them or not. However, according to patient- and staff-reported data, greater social interaction occurred during the interaction weeks. Nurses reported that the artist's presence made their job easier, with a stronger effect observed during the interaction weeks.","subset":"pubmed_abstract"} +{"meta":{"pmid":27777234,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evaluation of computed tomography in patients with atypical angina or chest pain clinically referred for invasive coronary angiography: randomised controlled trial.\nTo evaluate whether invasive coronary angiography or computed tomography (CT) should be performed in patients clinically referred for coronary angiography with an intermediate probability of coronary artery disease. Prospective randomised single centre trial. University hospital in Germany. 340 patients with suspected coronary artery disease and a clinical indication for coronary angiography on the basis of atypical angina or chest pain. 168 patients were randomised to CT and 172 to coronary angiography. After randomisation one patient declined CT and 10 patients declined coronary angiography, leaving 167 patients (88 women) and 162 patients (78 women) for analysis. Allocation could not be blinded, but blinded independent investigators assessed outcomes. The primary outcome measure was major procedural complications within 48 hours of the last procedure related to CT or angiography. Cardiac CT reduced the need for coronary angiography from 100% to 14% (95% confidence interval 9% to 20%, P<0.001) and was associated with a significantly greater diagnostic yield from coronary angiography: 75% (53% to 90%) v 15% (10% to 22%), P<0.001. Major procedural complications were uncommon (0.3%) and similar across groups. Minor procedural complications were less common in the CT group than in the coronary angiography group: 3.6% (1% to 8%) v 10.5% (6% to 16%), P=0.014. CT shortened the median length of stay in the angiography group from 52.9 hours (interquartile range 49.5-76.4 hours) to 30.0 hours (3.5-77.3 hours, P<0.001). Overall median exposure to radiation was similar between the CT and angiography groups: 5.0 mSv (interquartile range 4.2-8.7 mSv) v 6.4 mSv (3.4-10.7 mSv), P=0.45. After a median follow-up of 3.3 years, major adverse cardiovascular events had occurred in seven of 167 patients in the CT group (4.2%) and six of 162 (3.7%) in the coronary angiography group (adjusted hazard ratio 0.90, 95% confidence interval 0.30 to 2.69, P=0.86). 79% of patients stated that they would prefer CT for subsequent testing. The study was conducted at a University hospital in Germany and thus the performance of CT may be different in routine clinical practice. The prevalence was lower than expected, resulting in an underpowered study for the predefined primary outcome. CT increased the diagnostic yield and was a safe gatekeeper for coronary angiography with no increase in long term events. The length of stay was shortened by 22.9 hours with CT, and patients preferred non-invasive testing.Trial registration ClinicalTrials.gov NCT00844220.","subset":"pubmed_abstract"} +{"meta":{"pmid":24022913,"dup_signals":{"dup_doc_count":51,"dup_dump_count":38,"dup_details":{"curated_sources":4,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":2,"2019-26":1,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-43":3,"2018-34":1,"2018-30":1,"2018-22":1,"2018-13":3,"2018-09":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":2,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":2,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2014-35":2,"2014-23":2,"2021-49":1,"2017-13":1,"2014-10":1,"2013-48":1,"2024-22":1}}},"text":"Carbon emissions performance of commercial logging in East Kalimantan, Indonesia.\nAdoption of reduced-impact logging (RIL) methods could reduce CO2 emissions by 30-50% across at least 20% of remaining tropical forests. We developed two cost effective and robust indices for comparing the climate benefits (reduced CO2 emissions) due to RIL. The indices correct for variability in the volume of commercial timber among concessions. We determined that a correction for variability in terrain slope was not needed. We found that concessions certified by the Forest Stewardship Council (FSC, N = 3), when compared with noncertified concessions (N = 6), did not have lower overall CO2 emissions from logging activity (felling, skidding, and hauling). On the other hand, FSC certified concessions did have lower emissions from one type of logging impact (skidding), and we found evidence of a range of improved practices using other field metrics. One explanation of these results may be that FSC criteria and indicators, and associated RIL practices, were not designed to achieve overall emissions reductions. Also, commonly used field metrics are not reliable proxies for overall logging emissions performance. Furthermore, the simple distinction between certified and noncertified concessions does not fully represent the complex history of investments in improved logging practices. To clarify the relationship between RIL and emissions reductions, we propose the more explicit term 'RIL-C' to refer to the subset of RIL practices that can be defined by quantified thresholds and that result in measurable emissions reductions. If tropical forest certification is to be linked with CO2 emissions reductions, certification standards need to explicitly require RIL-C practices.","subset":"pubmed_abstract"} +{"meta":{"pmid":29372305,"dup_signals":{"dup_doc_count":15}},"text":"Genomic diversity and population structure of three autochthonous Greek sheep breeds assessed with genome-wide DNA arrays.\nIn the present study, genome-wide genotyping was applied to characterize the genetic diversity and population structure of three autochthonous Greek breeds: Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant livestock species in Greece numbering approximately 9 million animals which are characterized by large phenotypic variation and reared under various farming systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K microarray beadchip, to study the population structure of the breeds and develop a specialized panel of single-nucleotide polymorphisms (SNPs), which could distinguish one breed from the others. Quality control on the dataset resulted in 46,125 SNPs, which were used to evaluate the genetic structure of the breeds. Population structure was assessed through principal component analysis (PCA) and admixture analysis, whereas inbreeding was estimated based on runs of homozygosity (ROHs) coefficients, genomic relationship matrix inbreeding coefficients (FGRM) and patterns of linkage disequilibrium (LD). Associations between SNPs and breeds were analyzed with different inheritance models, to identify SNPs that distinguish among the breeds. Results showed high levels of genetic heterogeneity in the three breeds. Genetic distances among breeds were modest, despite their different ancestries. Chios and Karagouniko breeds were more genetically related to each other compared to Boutsko. Analysis revealed 3802 candidate SNPs that can be used to identify two-breed crosses and purebred animals. The present study provides, for the first time, data on the genetic background of three Greek indigenous dairy sheep breeds as well as a specialized marker panel that can be applied for traceability purposes as well as targeted genetic improvement schemes and conservation programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26598975,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases.\nProtein arginine methyltransferases (PRMTs) play a crucial role in a variety of biological processes. Overexpression of PRMTs has been implicated in various human diseases including cancer. Consequently, selective small-molecule inhibitors of PRMTs have been pursued by both academia and the pharmaceutical industry as chemical tools for testing biological and therapeutic hypotheses. PRMTs are divided into three categories: type I PRMTs which catalyze mono- and asymmetric dimethylation of arginine residues, type II PRMTs which catalyze mono- and symmetric dimethylation of arginine residues, and type III PRMT which catalyzes only monomethylation of arginine residues. Here, we report the discovery of a potent, selective, and cell-active inhibitor of human type I PRMTs, MS023, and characterization of this inhibitor in a battery of biochemical, biophysical, and cellular assays. MS023 displayed high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but was completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. A crystal structure of PRMT6 in complex with MS023 revealed that MS023 binds the substrate binding site. MS023 potently decreased cellular levels of histone arginine asymmetric dimethylation. It also reduced global levels of arginine asymmetric dimethylation and concurrently increased levels of arginine monomethylation and symmetric dimethylation in cells. We also developed MS094, a close analog of MS023, which was inactive in biochemical and cellular assays, as a negative control for chemical biology studies. MS023 and MS094 are useful chemical tools for investigating the role of type I PRMTs in health and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":22550179,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Force-specific activation of Smad1\/5 regulates vascular endothelial cell cycle progression in response to disturbed flow.\nVascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress, but the mechanism of force-specific activation of their signaling to modulate cellular function remains unclear. We have demonstrated that bone morphogenetic protein receptor (BMPR)-specific Smad1\/5 can be force-specifically activated by oscillatory shear stress (OSS) in ECs to cause cell cycle progression. Smad1\/5 is highly activated in ECs of atherosclerotic lesions in diseased human coronary arteries from patients with end-stage heart failure undergoing heart transplantation and from apolipoprotein E-deficient mice. Application of OSS (0.5 \u00b1 4 dyn\/cm(2)) causes the sustained activation of Smad1\/5 in ECs through activations of mammalian target of rapamycin and p70S6 kinase, leading to up-regulation of cyclin A and down-regulations of p21(CIP1) and p27(KIP1) and, hence, EC cycle progression. En face examination of rat aortas reveals high levels of phospho-Smad1\/5 in ECs of the inner, but not the outer, curvature of aortic arch, nor the straight segment of thoracic aorta [corrected]. Immunohistochemical and en face examinations of the experimentally stenosed abdominal aorta in rats show high levels of phospho-Smad1\/5 in ECs at poststenotic sites, where OSS occurs. These OSS activations of EC Smad1\/5 in vitro and in vivo are not inhibited by the BMP-specific antagonist Noggin and, hence, are independent of BMP ligand. Transfecting ECs with Smad1\/5-specific small interfering RNAs inhibits the OSS-induced EC cycle progression. Our findings demonstrate the force-specificity of the activation of Smad1\/5 and its contribution to cell cycle progression in ECs induced by disturbed flow.","subset":"pubmed_abstract"} +{"meta":{"pmid":32863323,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"MicroRNA analysis of NCI-60 human cancer cells indicates that miR-720 and miR-887 are potential therapeutic biomarkers for breast cancer.\nMicroRNAs (miRNAs) play a vital role in many biological processes, including cell growth, differentiation, apoptosis, development, differentiation, and carcinogenesis. Since miRNAs might play a part in cancer initiation and progression, they comprise an original class of promising diagnostic and prognostic molecular markers. In order to systematically understand the regulation of miRNA expression in cancers, the current study analyzed the miRNA expression profile in NCI-60 human cancer cell lines. Over 300 miRNAs exhibited unique expression profiles in cell lines derived from the same lineage. This study identified 9 lineage-specific miRNA expression patterns. Moreover, results indicated that miR-720 and miR-887 are expressed at relatively high levels in breast cancer cell lines compared to other types of cancer. Ultimately, matching NCI-60 drug response data to miR-720 and miR-887 expression profiles revealed that several FDA-approved drugs were inversely related to miR-720 and miR-887. Furthermore, the anti-cancer effect of perifosine was significantly enhanced by inhibiting miR-720 and decreased by miR-720 precursor treatment in breast cancer cell lines. 5-Fu treatment was enhanced by inhibiting miR-887 and decreased by miR-887 precursor treatment. The current results offer insight into the relationship between miRNA expression and their lineage types, and the approach used here represents a potential cancer therapy with the help of miRNAs.","subset":"pubmed_abstract"} +{"meta":{"pmid":19893639,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":12}}},"text":"Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharide and interferon-gamma stimulated macrophages.\nAzithromycin (AZM), a 15-member macrolide antibiotic, possesses anti-inflammatory activity. Macrophages are important in innate and acquired immunity, and produce pro-inflammatory cytokines such as interleukin (IL)-12, which are composed of subunit p40 and p35. The key function of IL-12 is the induction and maintenance of T-helper-1 responses, which is associated with the pathogenesis of chronic inflammatory diseases. We investigated the effect of azithromycin on IL-12p40 production in macrophages after lipopolysaccharide (LPS)\/interferon (IFN)-gamma stimulation. RAW264.7 macrophage cell line was pre-treated with vehicle or AZM, followed by the stimulation with LPS\/IFN-gamma. We measured IL-12 production by RT-PCR and ELISA. IL-12 transcriptional regulation was assessed by electrophoretic mobility shift assay and reporter assay. Phosphorylation of activator protein (AP)-1 and interferon consensus sequence binding protein (ICSBP) was assessed by immunoprecipitation using phosphotyrosine antibody, and immunoblotting using specific antibodies against JunB and ICSBP. AZM reduced the induction of IL-12p40 by LPS\/IFN-gamma in a dose dependent manner. AZM inhibited the binding of AP-1, nuclear factor of activated T cells (NFAT), and ICSBP, to the DNA binding site in the IL-12p40 promoter. AZM also reduced LPS\/IFN-gamma-induced IL-12p40 promoter activity. Phosphorylation of JunB and ICSBP was inhibited by azithromycin-treatment in stimulated cells. In conclusion, AZM reduced IL-12p40 transcriptional activity by inhibiting the binding of AP-1, NFAT, and ICSBP to the promoter site. This may represent an important mechanism for regulating the anti-inflammatory effects of AZM in macrophages.","subset":"pubmed_abstract"} +{"meta":{"pmid":24872418,"dup_signals":{"dup_doc_count":11}},"text":"The polypeptide transport-associated (POTRA) domains of TpsB transporters determine the system specificity of two-partner secretion systems.\nThe two-partner secretion (TPS) systems of Gram-negative bacteria secrete large TpsA exoproteins by a dedicated TpsB transporter in the outer membrane. TpsBs contain an N-terminal module located in the periplasm that includes two polypeptide transport-associated (POTRA) domains. These are thought to initiate secretion of a TpsA by binding its N-terminal secretion signal, called the TPS domain. Neisseria meningitidis encodes up to five TpsA proteins that are secreted via only two TpsB transporters: TpsB1 and TpsB2. Of these two, the TpsB2 recognizes the TPS domains of all TpsAs, despite their sequence diversity. By contrast, the TpsB1 shows a limited recognition of a TPS domain that is shared by two TpsAs. The difference in substrate specificity of the TpsBs enabled us to investigate the role of the POTRA domains in the selection of TPS domains. We tested secretion of TPS domains or full-length TpsAs by TpsB mutants with deleted, duplicated, and exchanged POTRA domains. Exchanging the two POTRA domains of a TpsB resulted in a switch in specificity. Furthermore, exchanging a single POTRA domain showed that each of the two domains contributed to the cargo selection. Remarkably, the order of the POTRA domains could be reversed without affecting substrate selection, but this aberrant order did result in an alternatively processed secretion product. Our results suggest that secretion of a TpsA is initiated by engaging both POTRA domains of a TpsB transporter and that these select the cognate TpsAs for secretion.","subset":"pubmed_abstract"} +{"meta":{"pmid":28814743,"dup_signals":{"dup_doc_count":20,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-16":3,"2020-05":1,"2019-51":1,"2019-47":1,"2019-35":1,"2018-39":2,"2018-26":2,"2018-09":1,"2017-51":1,"2017-43":1,"2022-21":1}}},"text":"Nutritional status and the influence of TV consumption on female body size ideals in populations recently exposed to the media.\nTelevision consumption influences perceptions of attractive female body size. However, cross-cultural research examining media influence on body ideals is typically confounded by differences in the availability of reliable and diverse foodstuffs. 112 participants were recruited from 3 Nicaraguan villages that differed in television consumption and nutritional status, such that the contribution of both factors could be revealed. Participants completed a female figure preference task, reported their television consumption, and responded to several measures assessing nutritional status. Communities with higher television consumption and\/or higher nutritional status preferred thinner female bodies than communities with lower television consumption and\/or lower nutritional status. Bayesian mixed models estimated the plausible range of effects for television consumption, nutritional status, and other relevant variables on individual preferences. The model explained all meaningful differences between our low-nutrition villages, and television consumption, after sex, was the most likely of these predictors to contribute to variation in preferences (probability mass >95% when modelling only variables with zero-order associations with preferences, but only 90% when modelling all possible predictors). In contrast, we found no likely link with nutritional status. We thus found evidence that where media access and nutritional status are confounded, media is the more likely predictor of body ideals.","subset":"pubmed_abstract"} +{"meta":{"pmid":29325025,"dup_signals":{"dup_doc_count":16}},"text":"Towards an understanding of resilience: responding to health systems shocks.\nThe recent outbreak of Ebola Virus Disease (EVD) in West Africa has drawn attention to the role and responsiveness of health systems in the face of shock. It brought into sharp focus the idea that health systems need not only to be stronger but also more 'resilient'. In this article, we argue that responding to shocks is an important aspect of resilience, examining the health system behaviour in the face of four types of contemporary shocks: the financial crisis in Europe from 2008 onwards; climate change disasters; the EVD outbreak in West Africa 2013-16; and the recent refugee and migration crisis in Europe. Based on this analysis, we identify '3 plus 2' critical dimensions of particular relevance to health systems' ability to adapt and respond to shocks; actions in all of these will determine the extent to which a response is successful. These are three core dimensions corresponding to three health systems functions: 'health information systems' (having the information and the knowledge to make a decision on what needs to be done); 'funding\/financing mechanisms' (investing or mobilising resources to fund a response); and 'health workforce' (who should plan and implement it and how). These intersect with two cross-cutting aspects: 'governance', as a fundamental function affecting all other system dimensions; and predominant 'values' shaping the response, and how it is experienced at individual and community levels. Moreover, across the crises examined here, integration within the health system contributed to resilience, as does connecting with local communities, evidenced by successful community responses to Ebola and social movements responding to the financial crisis. In all crises, inequalities grew, yet our evidence also highlights that the impact of shocks is amenable to government action. All these factors are shaped by context. We argue that the '3 plus 2' dimensions can inform pragmatic policies seeking to increase health systems resilience.","subset":"pubmed_abstract"} +{"meta":{"pmid":35222262,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":2,"2024-10":1,"unknown":10}}},"text":"Medications Activating Tubular Fatty Acid Oxidation Enhance the Protective Effects of Roux-en-Y Gastric Bypass Surgery in a Rat Model of Early Diabetic Kidney Disease.\nRoux-en-Y gastric bypass surgery (RYGB) improves biochemical and histological parameters of diabetic kidney disease (DKD). Targeted adjunct medical therapy may enhance renoprotection following RYGB. The effects of RYGB and RYGB plus fenofibrate, metformin, ramipril, and rosuvastatin (RYGB-FMRR) on metabolic control and histological and ultrastructural indices of glomerular and proximal tubular injury were compared in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of DKD. Renal cortical transcriptomic (RNA-sequencing) and urinary metabolomic (1H-NMR spectroscopy) responses were profiled and integrated. Transcripts were assigned to kidney cell types through in silico deconvolution in kidney single-nucleus RNA-sequencing and microdissected tubular epithelial cell proteomics datasets. Medication-specific transcriptomic responses following RYGB-FMRR were explored using a network pharmacology approach. Omic correlates of improvements in structural and ultrastructural indices of renal injury were defined using a molecular morphometric approach. RYGB-FMRR was superior to RYGB alone with respect to metabolic control, albuminuria, and histological and ultrastructural indices of glomerular injury. RYGB-FMRR reversed DKD-associated changes in mitochondrial morphology in the proximal tubule to a greater extent than RYGB. Attenuation of transcriptomic pathway level activation of pro-fibrotic responses was greater after RYGB-FMRR than RYGB. Fenofibrate was found to be the principal medication effector of gene expression changes following RYGB-FMRR, which led to the transcriptional induction of PPAR\u03b1-regulated genes that are predominantly expressed in the proximal tubule and which regulate peroxisomal and mitochondrial fatty acid oxidation (FAO). After omics integration, expression of these FAO transcripts positively correlated with urinary levels of PPAR\u03b1-regulated nicotinamide metabolites and negatively correlated with urinary tricarboxylic acid (TCA) cycle intermediates. Changes in FAO transcripts and nicotinamide and TCA cycle metabolites following RYGB-FMRR correlated strongly with improvements in glomerular and proximal tubular injury. Integrative multi-omic analyses point to PPAR\u03b1-stimulated FAO in the proximal tubule as a dominant effector of treatment response to combined surgical and medical therapy in experimental DKD. Synergism between RYGB and pharmacological stimulation of FAO represents a promising combinatorial approach to the treatment of DKD in the setting of obesity.","subset":"pubmed_abstract"} +{"meta":{"pmid":27574295,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Advanced endoscopic ultrasound management techniques for preneoplastic pancreatic cystic lesions.\nPancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":30226831,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Chromatin regulator Asxl1 loss and Nf1 haploinsufficiency cooperate to accelerate myeloid malignancy.\nASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with other gene mutations. However, the molecular mechanisms underlying the leukemogenesis associated with ASXL1 and cooperating mutations remain to be elucidated. Here, we report that Asxl1 loss cooperated with haploinsufficiency of Nf1, a negative regulator of the RAS signaling pathway, to accelerate the development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic stem and progenitor cells resulted in a gain-of-function transcriptional activation of multiple pathways such as MYC, NRAS, and BRD4 that are critical for leukemogenesis. The hyperactive MYC and BRD9 transcription programs were correlated with elevated H3K4 trimethylation at the promoter regions of genes involving these pathways. Furthermore, pharmacological inhibition of both the MAPK pathway and BET bromodomain prevented leukemia initiation and inhibited disease progression in Asxl1\u0394\/\u0394 Nf1\u0394\/\u0394 mice. Concomitant mutations of ASXL1 and RAS pathway genes were associated with aggressive progression of myeloid malignancies in patients. This study sheds light on the effect of cooperation between epigenetic alterations and signaling pathways on accelerating the progression of myeloid malignancies and provides a rational therapeutic strategy for the treatment of myeloid malignancies with ASXL1 and RAS pathway gene mutations.","subset":"pubmed_abstract"} +{"meta":{"pmid":22962333,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Winogradskyella litorisediminis sp. nov., isolated from coastal sediment.\nA Gram-staining-negative, non-flagellated, non-gliding, aerobic, rod-shaped bacterium, designated DPS-8(T), was isolated from coastal sediment of Geoje island in the South Sea, South Korea, and subjected to a polyphasic study. Strain DPS-8(T) grew optimally at 30 \u00b0C, at pH 7.0-7.5 and in the presence of 2 % (w\/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain DPS-8(T) joined the clade comprising the type strains of Winogradskyella species with a high bootstrap resampling value of 93.5 %. Phylogenetic trees constructed using maximum-likelihood and maximum-parsimony algorithms revealed that strain DPS-8(T) belonged to the genus Winogradskyella. Strain DPS-8(T) exhibited 94.1-96.5 % 16S rRNA gene sequence similarity to the type strains of species of the genus Winogradskyella. Strain DPS-8(T) contained MK-6 as the predominant menaquinone and iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH and C16 : 1\u03c97c and\/or iso-C15 : 0 2-OH as the major fatty acids. The major polar lipids of strain DPS-8(T) were phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of strain DPS-8(T) was 34.7 mol%. Differential phenotypic properties, together with its phylogenetic distinctiveness, revealed that strain DPS-8(T) is separate from recognized species of the genus Winogradskyella. On the basis of the data presented, strain DPS-8(T) is considered to represent a novel species of the genus Winogradskyella, for which the name Winogradskyella litorisediminis sp. nov. is proposed. The type strain is DPS-8(T) ( = KCTC 32110(T) = CCUG 62215(T)).","subset":"pubmed_abstract"} +{"meta":{"pmid":22368912,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Anaesthetic challenges in emergency surgical repair of acute aortic dissection rupturing into the pericardium in a pregnant patient.\nAcute aortic dissection in pregnancy is a serious situation, because rapid and appropriate surgical decision making is required to save the life of both mother and baby. Aortic dissection is rare in young women but is likely during pregnancy (third trimester) secondary to the hyperdynamic and hypervolaemic circulatory state associated with pregnancy. A 35 years old 27 weeks pregnant patient weighing 90 kg presented in the emergency with severe chest pain. In the immediate post cardiopulmonary bypass period, the patient started bleeding profusely from the anastamotic sites irrespective of utilization of all the conventional methods of haemostasis including multiple units of whole blood, fresh frozen plasma, platelets, calcium and cryoprecipitates. As a last resort she was given low dose r FVIIa (1.2 mg containing 60 KIU of Factor VII). This stopped the bleeding and the haemodyramics were stabilized.","subset":"pubmed_abstract"} +{"meta":{"pmid":33120607,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":4,"unknown":9}}},"text":"The interferon-induced protein kinase R: the base of a riboprotein scaffolding regulating the human immunodeficiency virus.\nThe interferon-induced RNA-activated Protein Kinase (PKR) targets the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2\u03b1) whose phosphorylation blocks translation initiation of cellular and viral mRNAs. PKR is activated at the beginning of human immunodeficiency virus (HIV) infection by low levels of the HIV Transactivation Response (TAR) RNA and by the cellular PKR Activator (PACT), which contributes to a reduced viral replication. During HIV replication, the viral Tat protein and high production of TAR RNA decrease PKR activation. The cellular TAR RNA Binding Protein (TRBP) and Adenosine Deaminase Acting on RNA (ADAR1) also prevent PKR activation, while HIV expression changes PACT function to become a PKR inhibitor. Therefore, HIV recruits viral and cellular factors to counteract PKR antiviral activity. In addition, PKR antiviral function was positively selected during evolution due to contacts with viral factors inhibiting its function. The riboprotein scaffolding such as the one that inhibits PKR during HIV replication may exist for other antiviral factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":22713998,"dup_signals":{"dup_doc_count":36,"dup_dump_count":26,"dup_details":{"curated_sources":2,"2023-40":1,"2023-14":2,"2022-49":1,"2022-27":1,"2022-21":2,"2021-49":2,"2021-43":2,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2019-26":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-22":3,"2024-18":1,"2024-26":1}}},"text":"Does genetic diversity limit disease spread in natural host populations?\nIt is a commonly held view that genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. The underlying idea, known as the 'monoculture effect,' is well documented in agricultural studies. Low genetic diversity in the wild can result from bottlenecks (that is, founder effects), biparental inbreeding or self-fertilization, any of which might increase the risk of epidemics. Host genetic diversity could buffer populations against epidemics in nature, but it is not clear how much diversity is required to prevent disease spread. Recent theoretical and empirical studies, particularly in Daphnia populations, have helped to establish that genetic diversity can reduce parasite transmission. Here, we review the present theoretical work and empirical evidence, and we suggest a new focus on finding 'diversity thresholds.'","subset":"pubmed_abstract"} +{"meta":{"pmid":32663912,"dup_signals":{"dup_doc_count":46,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-23":2,"2023-14":1,"2023-06":2,"2022-40":1,"2022-27":1,"2022-21":3,"2022-05":4,"2021-43":1,"2021-39":2,"2021-31":2,"2021-17":2,"2021-10":1,"2021-04":6,"2020-45":5,"2020-40":2,"2020-34":5,"2023-50":1,"2024-26":1}}},"text":"An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.\nThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 \u03bcg, 100 \u03bcg, or 250 \u03bcg. There were 15 participants in each dose group. After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-\u03bcg group, 109,209 in the 100-\u03bcg group, and 213,526 in the 250-\u03bcg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-\u03bcg dose group reported one or more severe adverse events. The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).","subset":"pubmed_abstract"} +{"meta":{"pmid":26830000,"dup_signals":{"dup_doc_count":34,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2022-21":1,"2020-34":1,"2020-10":1,"2019-18":2,"2018-51":2,"2018-47":1,"2018-39":2,"2018-30":2,"2018-17":2,"2018-09":1,"2017-51":2,"2017-47":1,"2017-43":2,"2017-34":2,"2017-26":2,"2017-22":1,"2017-17":1,"2023-23":1,"2024-10":2,"2017-13":1,"2024-22":1}}},"text":"The range and nature of effective interactions in hard-sphere solids.\nColloidal systems observed in video microscopy are often analysed using the displacements correlation matrix of particle positions. In non-thermal systems, the inverse of this matrix can be interpreted as a pair-interaction potential between particles. If the system is thermally agitated, however, only an effective interaction is accessible from the correlation matrix. We show how this effective interaction differs from the non-thermal case by comparing with high-statistics numerical data from hard-sphere crystals.","subset":"pubmed_abstract"} +{"meta":{"pmid":15940615,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.\nDespite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab\/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Infliximab 4-5 mg\/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":19012484,"dup_signals":{"dup_doc_count":15,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":1,"2022-40":1,"2022-05":1,"2021-43":1,"2021-25":2,"2021-10":1,"2021-04":1,"2020-34":1,"2023-40":1}}},"text":"A stereotactic near-infrared probe for localization during functional neurosurgical procedures: further experience.\nThe authors previously developed an optical stereotactic probe employing near-infrared (NIR) spectroscopy to provide intraoperative localization by distinguishing gray matter from white matter. In the current study they extend and further validate this technology. Near-infrared probes were inserted 203 times during 138 procedures for movement disorders. Detailed validation with postoperative imaging was obtained for 121 of these procedures and with microelectrode recording (MER) for 30 procedures. Probes were constructed to interrogate tissue perpendicular to the probe path and to incorporate hollow channels for microelectrodes, deep brain stimulation (DBS) electrodes, and other payloads. The NIR data were highly correlated to imaging and MER recordings for thalamic targets. The NIR data were highly sensitive but less specific relative to imaging for subthalamic targets, confirming the ability to detect the subthalamic nucleus and to provide warnings of inaccurate localization. The difference between the NIR- and MER-detected midpoints of the subthalamic nucleus along the chosen tracks was 1.1 +\/- 1.2 mm (SD). Data obtained during insertion and withdrawal of the NIR probe suggested that DBS electrodes may push their targets ahead of their paths. There was one symptomatic morbidity. Detailed NIR data could be obtained from a 7-cm track in less than 10 minutes. The NIR probe is a straightforward, quick, and robust tool for intraoperative localization during functional neurosurgery. Potential future applications include localization of targets for epilepsy and psychiatric disorders, and incorporation of NIR guidance into probes designed to convey various payloads.","subset":"pubmed_abstract"} +{"meta":{"pmid":25865919,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Incidence of HIV-1 infection and changes in prevalence of reproductive tract infections and sexual risk behaviours: a population-based longitudinal study in rural Tanzania.\nThis study aimed at describing the prevalence and incidence of HIV-1 and change in the prevalence of reproductive tract infections (RTIs) and sexual risk behaviours in the rural Kilimanjaro region of Tanzania. Two cross-sectional surveys among the total village population of Oria were conducted in 1991 and 1993. All individuals with a permanent address in the village were registered and invited to participate. After informed consent, participants gave blood for HIV-1 testing. Participants aged 15-44 years were interviewed regarding their socio-demographic characteristics and sexual risk behaviours and underwent genital examination and testing for RTIs. In 1991 and 1993, respectively, 3 239 (83.6%) and 2 191 (76.9%) individuals in the village participated. Prevalence of HIV-1 increased from 1.3% to 1.8%, but the difference was not significant (p = 0.17). HIV-1 incidence was 13.0\/1000 person-years-at-risk (PYAR) for women and 4.3\/1000 PYAR for men (relative risk was 3.0; 95% CI: 1.12-8.16). There was a significant increase in the prevalence of gonorrhoea, bacterial vaginosis and vaginal candidiasis (p < 0.001). The percentage of individuals who reported having multiple sexual partners during the 12 months preceding the survey increased from 12.9% to 24.1% (p < 0.001). The results suggest that RTIs and HIV-1 infections increased in this population in the early 1990s. Women were at higher risk of HIV-1 infection as compared to men. Sexual risk behaviours and RTIs may have contributed to HIV-1 transmission in this community. The data collected may help to inform the future design and evaluation of various intervention measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":2065355,"dup_signals":{"dup_doc_count":24,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":2,"2017-51":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2019-13":1,"2017-13":1}}},"text":"Cytotoxic activity against trophoblast and choriocarcinoma cells of large granular lymphocytes from human early pregnancy decidua.\nLarge granular lymphocytes (LGL) are the most abundant cell type in first trimester human pregnancy decidua. We have shown previously that CD56-positive decidual LGL have cytotoxic activity against the natural killer (NK) target K562, and that this cytotoxicity is augmented by pretreatment with interleukin-2 (IL-2). We now report that flow cytometrically purified populations of CD56-positive decidual LGL have no cytotoxic activity against either the BeWo choriocarcinoma cell line or freshly isolated term trophoblast. Incubation of unfractionated decidual cells with IL-2 induced cytotoxicity against BeWo, but term trophoblast remained resistant to lysis. Both BeWo and trophoblast showed much lower binding frequencies to decidual or peripheral blood cells than K56 targets, and excess trophoblast did not inhibit cytotoxic activity against K562. This suggests that the resistance of trophoblast to lysis by either decidual or peripheral blood LGL is due to the lack of accessible NK target structures on the surface of trophoblast.","subset":"pubmed_abstract"} +{"meta":{"pmid":2118994,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.\nA dominant inhibitory mutation of Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21 (Asn-17)Ha-ras] has been used to investigate the role of ras in neuronal differentiation of PC12 cells. The growth of PC12 cells, in contrast to NIH 3T3 cells, was not inhibited by p21(Asn-17)Ha-ras expression. However, PC12 cells expressing the mutant Ha-ras protein showed a marked inhibition of morphological differentiation induced by nerve growth factor (NGF) or fibroblast growth factor (FGF). These cells, however, were still able to respond with neurite outgrowth to dibutyryl cyclic AMP and 12-O-tetradecanoylphorbol-13-acetate (TPA). Induction of early-response genes (fos, jun, and zif268) by NGF and FGF but not by TPA was also inhibited by high levels of p21(Asn-17)Ha-ras. However, lower levels of p21(Asn-17) expression were sufficient to block neuronal differentiation without inhibiting induction of these early-response genes. Induction of the secondary-response genes SCG10 and transin by NGF, like morphological differentiation, was inhibited by low levels of p21(Asn-17) whether or not induction of early-response genes was blocked. Therefore, although inhibition of ras function can inhibit early-response gene induction, this is not required to block morphological differentiation or secondary-response gene expression. These results suggest that ras proteins are involved in at least two different pathways of signal transduction from the NGF receptor, which can be distinguished by differential sensitivity to p21(Asn-17)Ha-ras. In addition, ras and protein kinase C can apparently induce early-response gene expression by independent pathways in PC12 cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":29322223,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":8}}},"text":"Is the timed loaded standing test a valid measure of back muscle endurance in people with vertebral osteoporosis?\nTimed loaded standing (TLS) is a suggested measure of back muscle endurance for people with vertebral osteoporosis. Surface electromyography revealed back muscles work harder and fatigue during TLS. The test end-point and total time were associated with back fatigue. The findings help demonstrate the concurrent validity of the TLS test. The TLS test is suggested as a measure of back muscle endurance for patients with vertebral osteoporosis. However, to date, no study has demonstrated that TLS does measure back extensor or erector spinae (ES) muscle endurance. We used surface electromyography (sEMG) to investigate the performance of the thoracic ES muscles during TLS. Thirty-six people with vertebral osteoporosis with a mean age of 71.6 (range 45-86) years participated. sEMG recordings were made of the ES at T3 and T12 bilaterally during quiet standing (QS) and TLS. The relative (%) change in sEMG amplitude between conditions was compared. Fatigue was evaluated by analysing the change in median frequency (MF) of the sEMG signal during TLS, and the correlation between maximal TLS time and rate of MF decline was examined. Activity in the ES increased significantly during TLS at all electrode locations. During TLS, the MF declined at a mean rate of -24.2% per minute (95% C.I. -26.5 to -21.9%). The MF slope and test time were strongly correlated (r2 = 0.71), and at test end, the final MF dropped to an average 89% (95% C.I. 85 to 93%) of initial MF. Twenty-eight participants (78%) reported fatigue was the main reason for stopping, and for eight (22%), it was pain. This study demonstrates that TLS challenges the ES muscles in the thoracic region and results in ES fatigue. Endurance time and the point at which the TLS test ends are strongly related to ES fatigue.","subset":"pubmed_abstract"} +{"meta":{"pmid":12241195,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Ferroelectric-chiral-antiferroelectric-racemic liquid crystal phase transition of bent-shape molecules.\nDetailed dielectric, polarization current, electro-optical, and textural observations are reported on an asymmetric banana-shaped compound 1,3-biphenylene-bis[4-(3-fluoro-4-octyloxyphenyliminomethyl)benzoate]. The material possesses a chiral-ferroelectric-racemic-antiferroelectric phase transition. Our studies reveal that the higher temperature ferroelectric phase has a polar double-tilted smectic structure, where both the molecular plane and the long axis are tilted with respect to the layer normal. Accordingly, it has a chiral triclinic structure with an out-of-plane polarization component. The lower temperature phase has a monoclinic symmetry, which is higher than that of the higher temperature phase. To our knowledge, among liquid crystals such situations were previously observed only in reentrant phases.","subset":"pubmed_abstract"} +{"meta":{"pmid":8165650,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Adenosine diphosphate-induced aggregation of human platelets in flow through tubes: III. Shear and extrinsic fibrinogen-dependent effects.\nThe effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23 degrees C was studied using a previously described double infusion technique and resistive particle counter size analysis. Using suspensions of multiple-centrifuged and -washed cells in Tyrodes-albumin [3 x 10(5) microliters-1; (17)] with [fibrinogen] from 0 to 1.2 microM, the rate and extent of aggregation with 0.7 microM ADP in Tyrodes-albumin were measured over a range of mean transit times from 0.2 to 43 s, and at mean tube shear rates, G, = 41.9, 335 and 1,335 s-1. As measured by the decrease in singlet concentration, aggregation at 1.2 microM fibrinogen increased with increasing G up to 1,335 s-1, in contrast to that previously reported in citrated plasma, in which aggregation reached a maximum at G = 335 s-1. Without added fibrinogen, there was no aggregation at G = 41.9 s-1; at G = 335 s-1, there was significant aggregation but with an initial lag time, aggregation increasing further at G = 1,335 s-1. Without added fibrinogen, aggregation was abolished at all G upon incubation with the hexapeptide GRGDSP, but was almost unaffected by addition of an F(ab')2 fragment of an antibody to human fibrinogen. Aggregation in the absence of added fibrinogen was also observed at 37 degrees C. The activation of the multiple-washed platelets was tested using flow cytometry with the fluorescently labelled monoclonal antibodies FITC-PAC1 and FITC-9F9. It was shown that 57% of single cells in unactivated PRT expressed maximal GPIIb-IIIa fibrinogen receptors (MoAb PAC1) and 54% expressed pre-bound fibrinogen (MoAb 9F9), with further increases on ADP activation. However, incubation with GRGDSP and the F(ab')2 fragment did not inhibit the prebound fibrinogen. Moreover, relatively unactivated cells (8% expressing receptor, 14% prebound fibrinogen), prepared from acidified cPRP by single centrifugation with 50 nM of the stable prostacyclin derivative, ZK 36,374, and resuspension in Tyrodes-albumin at 5 x 10(4) microliters-1, aggregated with 2 and 5 microM ADP at G = 335 and 1,335 s-1 in the absence of added fibrinogen. We therefore postulate that a protein such as von Willebrand factor, secreted during platelet isolation or in flow at sufficiently high shear rates, may yield the observed shear-rate dependent aggregation without fibrinogen.","subset":"pubmed_abstract"} +{"meta":{"pmid":17011713,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":14}}},"text":"Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?\nAnecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse.","subset":"pubmed_abstract"} +{"meta":{"pmid":25491313,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":14}}},"text":"The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans.\nThe integrin-adhesome network, which contains >150 proteins, is mechano-transducing and located at discreet positions along the cell-cell and cell-extracellular matrix interface. A small subset of the integrin-adhesome is known to maintain normal muscle morphology. However, the importance of the entire adhesome for muscle structure and function is unknown. We used RNA interference to knock down 113 putative Caenorhabditis elegans homologs constituting most of the mammalian adhesome and 48 proteins known to localize to attachment sites in C. elegans muscle. In both cases, we found >90% of components were required for normal muscle mitochondrial structure and\/or proteostasis vs. empty vector controls. Approximately half of these, mainly proteins that physically interact with each other, were also required for normal sarcomere and\/or adhesome structure. Next we confirmed that the dystrophy observed in adhesome mutants associates with impaired maximal mitochondrial ATP production (P < 0.01), as well as reduced probability distribution of muscle movement forces compared with wild-type animals. Our results show that the integrin-adhesome network as a whole is required for maintaining both muscle structure and function and extend the current understanding of the full complexities of the functional adhesome in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":28937226,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.\nSynthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only \u223c20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.","subset":"pubmed_abstract"} +{"meta":{"pmid":16969683,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-30":2,"2024-18":2,"unknown":11}}},"text":"Differential involvement of the endocannabinoid system in short- and long-term expression of incentive learning supported by nicotine in rats.\nWe previously reported that the CB1 cannabinoid receptor antagonist, rimonabant, impaired the acquisition and the short-term (24 h), but not long-term (3 weeks), expression of conditioned place preference (CPP) induced by nicotine in rats. To assess the time interval of efficacy of a single pretest injection of rimonabant to abolish nicotine-CPP, and the effects of chronic CB1 receptor blockade on long-term expression of nicotine-CPP. Wistar rats were conditioned to nicotine (0.06 mg\/kg, subcutaneous) using an unbiased one-compartment procedure. Two test sessions were conducted 24 h (without injection) and 1, 2, or 3 weeks later. Rimonabant (3 mg\/kg, intraperitoneal) or vehicle was administered daily between the two test sessions. In addition, the CB1-stimulated [(35)S]GTP-gamma-S binding was assessed in rats from the 3-week experiment. The capacity of a single injection of rimonabant (3 mg\/kg, 30 min pretest) to block the expression of nicotine-CPP disappeared within 1 week after conditioning. Daily administrations of rimonabant for 6, 13, or 20 days post-acquisition did not impair nicotine-CPP but allowed an additional pretest injection of rimonabant to retain its capacity to abolish long-term expression of nicotine-CPP. The CB1 receptor-mediated G-protein signaling was not altered in various brain areas of rats given rimonabant for 3 weeks. The endocannabinoid system is essential to the expression of nicotine-CPP during less than 1 week after conditioning but not later. However, endocannabinoid-dependent mechanisms are critically involved in the development of the neuroadaptive changes responsible for the shift from CB1-dependent to CB1-independent expression of nicotine incentive learning.","subset":"pubmed_abstract"} +{"meta":{"pmid":29777062,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":2,"unknown":7}}},"text":"Brock malignancy risk calculator for pulmonary nodules: validation outside a lung cancer screening population.\nTo assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting. In two academic centres in the Netherlands, we established a list of patients aged \u226540 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case-control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model. After the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p<0.001). At 10% malignancy risk, the threshold suggested by the British Thoracic Society, sensitivity of the full model was 75% and 81%, specificity was 85% and 84%, positive predictive values were 14% and 10% at negative predictive value (NPV) of 99%. The optimal threshold was 6% for centre A and 8% for centre B, with NPVs >99%. The Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations.","subset":"pubmed_abstract"} +{"meta":{"pmid":35179210,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-22":1,"unknown":8}}},"text":"Modular-Level Functional Connectome Alterations in Individuals With Hallucinations Across the Psychosis Continuum.\nFunctional connectome alterations, including modular network organization, have been related to the experience of hallucinations. It remains to be determined whether individuals with hallucinations across the psychosis continuum exhibit similar alterations in modular brain network organization. This study assessed functional connectivity matrices of 465 individuals with and without hallucinations, including patients with schizophrenia and bipolar disorder, nonclinical individuals with hallucinations, and healthy controls. Modular brain network organization was examined at different scales of network resolution, including (1) global modularity measured as Qmax and Normalised Mutual Information (NMI) scores, and (2) within- and between-module connectivity. Global modular organization was not significantly altered across groups. However, alterations in within- and between-module connectivity were observed for higher-order cognitive (e.g., central-executive salience, memory, default mode), and sensory modules in patients with schizophrenia and nonclinical individuals with hallucinations relative to controls. Dissimilar patterns of altered within- and between-module connectivity were found bipolar disorder patients with hallucinations relative to controls, including the visual, default mode, and memory network, while connectivity patterns between visual, salience, and cognitive control modules were unaltered. Bipolar disorder patients without hallucinations did not show significant alterations relative to controls. This study provides evidence for alterations in the modular organization of the functional connectome in individuals prone to hallucinations, with schizophrenia patients and nonclinical individuals showing similar alterations in sensory and higher-order cognitive modules. Other higher-order cognitive modules were found to relate to hallucinations in bipolar disorder patients, suggesting differential neural mechanisms may underlie hallucinations across the psychosis continuum.","subset":"pubmed_abstract"} +{"meta":{"pmid":11180840,"dup_signals":{"dup_doc_count":25,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2018-30":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-26":3,"2024-22":1}}},"text":"An amphioxus netrin gene is expressed in midline structures during embryonic and larval development.\nMembers of the netrin gene family have been identified in vertebrates, Drosophila and Caenorhabditis elegans and found to encode secreted molecules involved in axon guidance. Here I use the conserved function of netrins in triploblasts, coupled with the phylogenetic position of amphioxus (the closest living relative of the vertebrates), to investigate the evolution of an axon guidance cue in chordates. A single amphioxus netrin gene was isolated by PCR and cDNA library screening and named AmphiNetrin. The predicted AmphiNetrin protein showed high identity to other netrin family members but differed in that the third of three EGF repeats found in other netrins was absent. Molecular phylogene-tic analysis showed that despite the absent EGF repeat AmphiNetrin is most closely related to the vertebrate netrins. AmphiNetrin expression was identified in embryonic notochord and floor plate, a pattern similar to that of vertebrate netrin-1 expression. AmphiNetrin expression was also identified more widely in the posterior larval brain, and in the anterior extension of the notochord that underlies the anterior of the amphioxus brain. All of these areas of expression are correlated with developing axon trajectories: The floor plate with ventrally projecting somatic motor neurons and Rohde cell projections, the posterior brain with the ventral commissure and primary motor centre and the anterior extension of the notochord with ventrally projecting neurons associated with the median eye. Amphioxus is naturally cyclopaedic and also lacks the ventral brain cells that the induction of which results in the splitting of the vertebrate eye field and, when missing, result in cyclopaedia. These cells normally express netrins required for developing axon tracts in the brain, and the expression of AmphiNetrin in the anterior extension of the notochord underlying the brain may explain how amphioxus is able to maintain ventral guidance cues while lacking these cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":11241940,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"[Gender and cutaneous leishmaniasis in Colombia].\nLeishmaniasis in Colombia has traditionally been seen as a health risk for adult males, as they become infected when they enter the vector's biotopes to tap natural resources. National health statistics seem to confirm this theory. However, during field studies, the Program for the Study and Control of Tropical Diseases (PECET) observed both equal proportions of men and women with active leishmaniasis and delayed hypersensitivity skin tests and equal proportions of males and females having had contact with the parasite from early childhood. Several factors that have not been analyzed in depth in Colombia thus far appear to distort the disease's epidemiological pattern in the country, and gender-linked differences in access to health care appear to exist. As a consequence, no relief is provided for this source of human suffering, and socioeconomic repercussions for households are significant. Preventive measures by the Colombian Ministry of Health (MOH) systematically underestimate the magnitude of intra- and peridomiciliary transmission, and female patients are excluded from active case detection. Further research should be devoted to this phenomenon. The MOH should be encouraged to improve leishmaniasis control programs, especially with regard to active case detection, training, and teaching, so that quicker diagnosis can be performed. Meanwhile, the MOH should retrain its health personnel.","subset":"pubmed_abstract"} +{"meta":{"pmid":24480151,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results.\nChrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h\/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile\/brake dust exposure groups. The long chrysotile fibers (>20 \u03bcm) cleared quickly with T(\u00bd) estimated as 30 and 33 days, respectively in the brake dust and the chrysotile\/brake dust exposure groups. In contrast, the long crocidolite fibers had a T(\u00bd)>1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation.","subset":"pubmed_abstract"} +{"meta":{"pmid":18364837,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Uncertainty analysis of absolute concentration measurement with continuous-wave cavity ringdown spectroscopy.\nTo evaluate the uncertainty of concentration measurement using cavity ringdown spectroscopy, we analytically derived expressions for uncertainty for parameters, such as temperature, laser frequency, and ringdown time deviation, from the model equation. The uncertainties that are due to systematic errors in a practical cavity ringdown system were assessed through an experimental study of the PQ(35) transition in an A band of molecular oxygen. We found that, except for the line strength that is regarded as a reference value independent of the measurement, the laser frequency jitter is the largest uncertainty source in the system. Some practical requirements for minimizing the uncertainty in concentration measurements are discussed. We also demonstrated determination of the line strength of the PQ(35) transition line of oxygen to be 8.63(3) x 10(-27) cm(-1) with a relative uncertainty of less than 0.4%.","subset":"pubmed_abstract"} +{"meta":{"pmid":9017236,"dup_signals":{"dup_doc_count":53,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":3,"2023-23":3,"2023-14":3,"2023-06":2,"2022-49":1,"2022-40":3,"2022-33":2,"2022-27":1,"2022-21":2,"2022-05":1,"2021-43":3,"2021-31":3,"2021-17":3,"2021-04":4,"2020-50":1,"2020-45":2,"2020-40":3,"2024-26":1,"2024-22":1,"2024-18":4,"2024-10":2,"2024-30":1}}},"text":"Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a rat model of mononeuropathy.\nWe have previously described the changes in spinal cord neuropeptides in the unilateral sciatic chronic constriction injury (CCI) model of Bennett and Xie [Pain, 33 (1988) 87-108] at 28 days, a time of maximum mechanical hyperalgesia. In this study we examine the same model 100-120 days post injury by which time resolution of the hyperalgesia and peripheral nerve injury has occurred according to previous studies. Rats underwent either CCI of the sciatic nerve (n = 12) or else sham operation (n = 8) which involved exposure but no ligation of the nerve. Mechanical hyperalgesia was assessed with a Ugo-Basile analgesymeter and immunohistochemistry performed on the spinal cord sections of the animals and quantified using a confocal microscope. At this late time point CCI rats were no longer significantly mechanically hyperalgesic compared to the sham animals (P > or = 0.09). However, examination of the lumbar spinal cord revealed the following changes. (i) The neuropeptides substance P (SP) (P < 0.0001) and galanin (P < 0.003) both showed decreases of about 30% ipsilaterally in immunoreactivity in laminae 1 and 2 of the dorsal horn compared to the sham operated animals. (ii) Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in laminae 1 and 2 showed no significant changes compared to sham animals. (iii) NPY levels in laminae 3 and 4 of the spinal cord showed a 15% increase in immunoreactivity compared to sham animals (P = 0.008). These results indicate that changes in neuronal markers in the spinal cord can persist after apparent resolution of a peripheral nerve injury. We suggest that these changes may form a substrate for subsequent development of abnormal pain states.","subset":"pubmed_abstract"} +{"meta":{"pmid":10535321,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-30":1,"unknown":9}}},"text":"Dopamine in the developing kidney.\nThe adult kidney has a high rate of dopamine (DA) production, metabolism, and signalling. The non-neuronal DA system in the adult kidney is of utmost importance for the regulation of salt metabolism. DA may also act as a transcription factor and may be of importance for tissue differentiation. In the central nervous system, D1 receptors require the dopamine- and cAMP-regulated phosphoprotein with a molecular weight of 32,000 Dalton (DARPP-32) to mediate their actions. The renal D1 mediates DARPP-32 activation via a cascade involving cAMP and PKA, and protein kinase C (PKC) activation via phospholipase C. Active DARPP-32 has a specific inhibitory effect on protein phosphatase 1 (PP1), leaving, e.g. Na+,K+-ATPase in a phosphorylated, inactive, state. Thus, dopamine acts as a natriuretic hormone in the mature kidney. Here, we discuss the age-dependent distribution and some functional aspects of several parts of the renal dopamine system (dopamine, AADC, COMT, D1 receptor, and DARPP-32) during renal morphogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":15459896,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":18}}},"text":"Expression of a dominant negative form of Daxx in vivo rescues motoneurons from Fas (CD95)-induced cell death.\nFas-induced death of motoneurons in vitro has been shown to involve two signaling cascades that act together to execute the death program: a Fas-Daxx-ASK-1-p38 kinase-nNOS branch, which controls transcriptional and post-translational events, and the second classical Fas-FADD-caspase-8 branch. To analyze the role of Daxx in the developmental motoneuron cell death, we studied Fas-dependent cell death in motoneurons from transgenic mice that overexpress a dominant-negative form of Daxx. Motoneurons purified from these transgenic mice are resistant to Fas-induced death. This protective effect is specific to Fas because ultraviolet irradiation-triggered death is not affected by the transgene. The Daxx and the FADD pathways work in parallel because only Daxx, but not FADD, is involved in the transcriptional control of neuronal nitric oxide synthase and nitric oxide production. Nevertheless, we do not observe involvement of Daxx in developmental motoneuronal cell death, as the pattern of naturally occurring programmed cell death in vivo is normal in transgenic mice overexpressing the dominant negative form of Daxx, suggesting that Daxx-independent pathways are used during development.","subset":"pubmed_abstract"} +{"meta":{"pmid":18951344,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-06":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-49":1,"2021-10":1,"2021-04":1,"2020-40":1,"2020-10":1,"2023-40":1}}},"text":"[The epidemiology of depression in Belgium. A review and some reflections for the future].\nLittle is known on epidemiological aspects of depression in the Belgian general population, despite the fact that this disorder is known as a burdensome disorder. To present the results of a systematic literature search on the epidemiological aspects of depression in Belgium: prevalence, impact on daily life, and service use. A systematic literature search was performed using 'epidemiology', 'prevalence' and 'depression', 'Belgium' in PubMed, PsychInfo, International Bibliography of the Social Sciences (IBSS), the (interactive) database of the National Health Survey and in so-called 'grey literature'. results Twenty two reports were included in the study. Depression is a common disorder that yields an enormous impact on daily life, on both work loss and suicidality. The proportion of persons seeking help was generally very low, with only 14% making a first treatment contact in the year of the disorder onset. Lifetime treatment rates were about 94%. Despite the high prevalence and significant impact of depression in daily life, delays between disorder onset and seeking help are impressive. Primary prevention of depression seems rather limited. Secondary preventative strategies may be focused on the delays in helpseeking.","subset":"pubmed_abstract"} +{"meta":{"pmid":31917673,"dup_signals":{"dup_doc_count":60,"dup_dump_count":35,"dup_details":{"curated_sources":4,"2022-49":1,"2022-33":1,"2022-05":1,"2021-49":1,"2021-43":2,"2021-39":3,"2021-31":1,"2021-25":2,"2021-21":1,"2021-17":2,"2021-10":2,"2021-04":1,"2020-45":1,"2020-40":2,"2020-34":2,"2020-24":1,"2020-16":2,"2020-10":3,"2020-05":2,"2019-51":5,"2019-47":1,"2019-43":3,"2019-35":2,"2019-30":1,"2019-26":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-34":2,"2023-50":1}}},"text":"Mending the Cracks: A Case Study in Using Technology to Assist with Transitional Care for Persons with Dementia.\nTransitions between hospital and community are particularly challenging for vulnerable adults experiencing behavioural and psychological symptoms (BPSD) of dementia. Too often, miscommunication results in triggering a recurrence of disruptive behaviours leading to frustration of staff and families. As part of the implementation of Health Quality Ontario (HQO) Quality Standards, this project involved improving transitions using an electronic-based care plan on a 23-bed geriatric dementia unit in a mental health hospital. \"My Dementia Careplan,\" is an interprofessional care plan that was developed in the electronic medical record (EMR) to enhance communication of information between healthcare providers when patients are being discharged to the community. It is written from the patient's perspective in collaboration with the family and interprofessional team. It describes strategies to manage behavioural challenges along with the standardized tools to objectively monitor progress. This care planning will help to support transition of knowledge between hospital and community.","subset":"pubmed_abstract"} +{"meta":{"pmid":33166150,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Modulation Doping via a Two-Dimensional Atomic Crystalline Acceptor.\nTwo-dimensional nanoelectronics, plasmonics, and emergent phases require clean and local charge control, calling for layered, crystalline acceptors or donors. Our Raman, photovoltage, and electrical conductance measurements combined with ab initio calculations establish the large work function and narrow bands of \u03b1-RuCl3 enable modulation doping of exfoliated single and bilayer graphene, chemical vapor deposition grown graphene and WSe2, and molecular beam epitaxy grown EuS. We further demonstrate proof of principle photovoltage devices, control via twist angle, and charge transfer through hexagonal boron nitride. Short-ranged lateral doping (\u226465 nm) and high homogeneity are achieved in proximate materials with a single layer of \u03b1-RuCl3. This leads to the best-reported monolayer graphene mobilities (4900 cm2\/(V s)) at these high hole densities (3 \u00d7 1013 cm-2) and yields larger charge transfer to bilayer graphene (6 \u00d7 1013 cm-2).","subset":"pubmed_abstract"} +{"meta":{"pmid":12409761,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Reconstructive breast surgery: referring physician knowledge and learning needs.\nDespite the positive impact that reconstructive breast surgery can have on a woman's quality of life, the percentage of eligible candidates that have this procedure remains surprisingly low. The authors hypothesized that this may be attributable to inadequate knowledge, inadequate information, and\/or misinformation available to physicians caring for these patients. A needs assessment of primary care physicians, general surgeons, oncologists, and plastic surgeons was conducted to determine referring physicians' current level of knowledge of reconstructive breast surgery and to discover potential learning needs. This comprised a survey, focus groups, and individual interviews. Referring physicians rated their own knowledge of reconstructive breast surgery as low. Plastic surgeons rated their referring physicians' knowledge as even lower. Specific learning needs were identified, as large discrepancies between referring physicians' self-reported knowledge of individual breast reconstruction topics and their own opinion of their relevance were revealed. In addition, despite evidence to the contrary, more than one-third of referring physicians indicated a belief that a breast reconstruction delayed the detection of local cancer recurrence and adversely interfered with adjuvant oncologic therapy. This lack of knowledge and misinformation may be negatively affecting patient referrals to plastic surgeons, as more than one-third of referring physicians and 90 percent of plastic surgeons believed that eligible candidates were not being offered referrals because of inadequate referring physician knowledge of this topic. Furthermore, patients older than 49 years were not being referred despite the fact that plastic surgeons would consider these patients as potential surgical candidates. Referring physician gender affected both referral patterns and perceived importance of reconstructive breast surgery. Finally, personal beliefs and past experiences played a role both in physicians' decisions to refer patients and in patients' decisions to have breast reconstructions. These deficiencies in information, knowledge, and learning needs should be addressed by educational interventions during residency training and through continuing education endeavors.","subset":"pubmed_abstract"} +{"meta":{"pmid":29669769,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Nasal septal schwannoma: a rare sinonasal tumour with certain peculiarities.\nSinonasal schwannomas constitute 4% of head and neck nerve sheath tumours; however, schwannomas involving the nasal septum are quite rare. We present a 57-year-old male patient with nasal septal schwannoma who was managed successfully by endoscopic excision. 32 cases of septal schwannoma have been reported so far in the literature. This report discusses certain peculiar features exhibited by schwannomas of the nasal septum. Septal schwannoma does not show any age, sex or side predilection. However, they tend to involve posterior part of the septum and presumed to arise from the nasopalatine branch of the trigeminal nerve. Imaging findings of the sinonasal schwannoma are non-specific, but the histopathological characteristics are diagnostic, with seldom need for immunohistochemistry. Endoscopic excision is the safe and effective treatment option for the septal schwannoma of any size and location. Recurrence has not been reported in the literature following endoscopic excision.","subset":"pubmed_abstract"} +{"meta":{"pmid":9829724,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Expression of p21WAF1 predicts outcome of esophageal cancer patients treated by surgery alone or by combined therapy modalities.\nThe p21WAF1 protein is an important regulator of the cell cycle. Its expression and prognostic significance were investigated immunohistochemically in samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 20), carcinoma in situ (n = 14), permanent esophageal squamous cell carcinoma cell lines (n = 3), and invasive squamous cell carcinomas treated either by potentially curative resection (n = 172) or by combined modality therapy (radiochemotherapy +\/- surgery; n = 38). Whereas p21WAF1 expression in the normal epithelium was restricted to a few cells adjacent to the basal cell layer, p21WAF1 overexpression was frequently found in preneoplasias and invasive carcinomas. Expression of p21WAF1 in invasive carcinomas was not correlated with tumor differentiation, pT category, or pN category. Among carcinomas treated by potential curative resection, univariate (P = 0.0025) and multivariate (P = 0.0081) survival analysis showed significant correlation of strong p21WAF1 expression (> or =50% p21WAF1-positive tumor cells) with poor overall survival. Univariate survival analysis (P = 0.0006) revealed the same prognostic influence in the group of patients treated by combined modality therapy. We conclude that overexpression of p21WAF1 protein is a frequent event in preneoplasias and neoplasias of the esophagus. Immunohistochemical examination of p21WAF1 expression may provide important prognostic information for decision-making in the treatment of patients with esophageal cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":28636048,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Supramolecular surface functionalization via catechols for the improvement of cell-material interactions.\nOptimization of cell-material interactions is crucial for the success of synthetic biomaterials in guiding tissue regeneration. To do so, catechol chemistry is often used to introduce adhesiveness into biomaterials. Here, a supramolecular approach based on ureido-pyrimidinone (UPy) modified polymers is combined with catechol chemistry in order to achieve improved cellular adhesion onto supramolecular biomaterials. UPy-modified hydrophobic polymers with non-cell adhesive properties are developed that can be bioactivated via a modular approach using UPy-modified catechols. It is shown that successful formulation of the UPy-catechol additive with the UPy-polymer results in surfaces that induce cardiomyocyte progenitor cell adhesion, cell spreading, and preservation of cardiac specific extracellular matrix production. Hence, by functionalizing supramolecular surfaces with catechol functionalities, an adhesive supramolecular biomaterial is developed that allows for the possibility to contribute to biomaterial-based regeneration.","subset":"pubmed_abstract"} +{"meta":{"pmid":17301046,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"Effect of subclinical status in functional limitation and disability on adverse health outcomes 3 years later.\nThis article examines the effect of self-reported, baseline subclinical status (i.e., independent but adaptive performance) for functional limitation and disability on adverse health outcomes. Nine hundred ninety-eight African-American men and women aged 49-65 years received in-home evaluations at baseline, and 853 were re-evaluated 3 years later. Baseline subclinical status was ascertained for five lower body tasks and seven activities of daily living (ADLs)\/instrumental ADLs (IADLs). Outcomes included difficulty with lower body limitations, ADLs\/IADLs, physical performance, physician visits, hospitalization, nursing home placement, and mortality. The baseline proportion of subclinical status evidence for the five lower body items was 0.33 (standard deviation [SD] = 0.20), and for the seven ADLs\/IADLs was 0.20 (SD = 0.30). Significant independent effects of subclinical status for lower body limitations were observed on physician visits and hospitalization. Significant independent effects of subclinical status for ADLs\/IADLs were observed on ADLs\/IADLs and physician visits. Subclinical status for functional limitation and disability independently predicts several subsequent adverse health outcomes, although the effects of the latter (ADLs\/IADLs) are stronger. Interventions to reduce frailty should focus on self-reported subclinical status as an early warning system.","subset":"pubmed_abstract"} +{"meta":{"pmid":24797692,"dup_signals":{"dup_doc_count":34,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2023-50":1,"2024-18":1,"2017-13":1,"2024-30":1}}},"text":"Mental health and social networks in early adolescence: a dynamic study of objectively-measured social interaction behaviors.\nHow are social interaction dynamics associated with mental health during early stages of adolescence? The goal of this study is to objectively measure social interactions and evaluate the roles that multiple aspects of the social environment--such as physical activity and food choice--may jointly play in shaping the structure of children's relationships and their mental health. The data in this study are drawn from a longitudinal network-behavior study conducted in 2012 at a private K-8 school in an urban setting in California. We recruited a highly complete network sample of sixth-graders (n = 40, 91% of grade, mean age = 12.3), and examined how two measures of distressed mental health (self-esteem and depressive symptoms) are positionally distributed in an early adolescent interaction network. We ascertained how distressed mental health shapes the structure of relationships over a three-month period, adjusting for relevant dimensions of the social environment. Cross-sectional analyses of interaction networks revealed that self-esteem and depressive symptoms are differentially stratified by gender. Specifically, girls with more depressive symptoms have interactions consistent with social inhibition, while boys' interactions suggest robustness to depressive symptoms. Girls higher in self-esteem tended towards greater sociability. Longitudinal network behavior models indicate that gender similarity and perceived popularity are influential in the formation of social ties. Greater school connectedness predicts the development of self-esteem, though social ties contribute to more self-esteem improvement among students who identify as European-American. Cross-sectional evidence shows associations between distressed mental health and students' network peers. However, there is no evidence that connected students' mental health status becomes more similar in their over time because of their network interactions. These findings suggest that mental health during early adolescence may be less subject to mechanisms of social influence than network research in even slightly older adolescents currently indicates.","subset":"pubmed_abstract"} +{"meta":{"pmid":11906258,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Conjugates bearing multiple formyl-methionyl peptides display enhanced binding to but not activation of phagocytic cells.\nN-Formyl-methionyl peptides can specifically bind to surface receptors on phagocytic cells. A single copy of N-formyl-methionine-leucine-phenylalanine (fMLF) covalently linked to a poly(ethylene glycol)-based polymer displayed reduced binding avidity (K(d) = 190 nM) for differentiated HL-60 cells relative to free fMLF (K(d) = 28 nM). Increasing the number of fMLF residues (up to eight) attached to a single polymer results in enhanced avidity for these cells (K(d) = 0.18 nM), which appears to be independent of whether the polymer backbone is linear or branched. However, no conjugate showed enhanced ability to activate phagocytic cells, relative to the free peptide (EC(50) = 5 nM), as measured by transient stimulation of release of calcium ions from intracellular stores into the cytoplasm. A polymer bearing four fMLF and four digoxigenin residues showed specific enhancement in binding to differentiated HL-60 cells and mouse peritoneal macrophages in situ relative to a polymer lacking fMLF; no such enhancement was seen in binding to receptor-negative lymphocytic Jurkat cells. These results suggest that multiple fMLF residues linked to a drug-delivery polymer can be used to target appended drugs to phagocytic cells with relatively little toxicity due to cellular activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28982073,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-30":1,"unknown":13}}},"text":"Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure.\nLipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte hypertrophy based on analysis of cell surface area. We found that lack of Lpp3 signaling was mediated through the activation of Rho and phospho-ERK pathways. There are increased levels of fetal genes Natriuretic Peptide A and B (Nppa and Nppb) expression indicating myocardial dysfunction. These mice also demonstrate mitochondrial dysfunction as evidenced by a significant decrease (P < 0.001) in the basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity as measured through mitochondrial bioenergetics. Histology and transmission electron microscopy of these hearts showed disrupted sarcomere organization and intercalated disc, with a prominent disruption of the cristae and vacuole formation in the mitochondria. Our findings suggest that LPA\/LPP3-signaling nexus plays an important role in normal function of cardiomyocytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22181668,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Clearance of topically-applied PVP-iodine as a solution or gel in periodontal pockets in men.\nThe aim of the study was to investigate the clearance of PVP-iodine applied as a gel or solution in periodontal pockets. Teeth of 12 subjects with at least eight periodontal pockets of \u22655 mm probing depth were isolated with a rubber dam to allow contamination-free access to the pockets. In each subject, three pockets were filled with PVP-iodine gel (10%) and three with PVP-iodine solution (10%). One pocket of each subject without iodine application served as a negative control. The treatment allocation was assigned randomly. Any excess material was removed subsequently. After 1, 5 and 15 min, a paper point was used to collect the sulcus liquid and the concentration of PVP-iodine was chemically determined. In addition, PVP-iodine gel was administered into 12 periodontal pockets immediately after sub-gingival ultrasound debridement and the concentration of PVP-iodine was determined after 1 min. Descending concentrations of PVP-iodine were determined at 1, 5 and 15 min after the application. No PVP-iodine was found in the pockets serving as negative controls. The mean concentrations of the gel and solution were 6.14 \u03bcg\/ml and 4.44 \u03bcg\/ml (1 min; p \u2265 0.028), 3.20 \u03bcg\/ml and 1.44 \u03bcg\/ml (5 min; p \u2265 0.126), 0.69 \u03bcg\/ml and 0.23 \u03bcg\/ml (15 min; p \u2264 0.019), respectively. In the pockets with previous debridement the mean concentration was 1.68 \u00b1 1.97 \u03bcg\/ml. The application of PVP-iodine gel in periodontal pockets allows a prolonged remnant effect as compared to that of the solution formula.","subset":"pubmed_abstract"} +{"meta":{"pmid":19874723,"dup_signals":{"dup_doc_count":11,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":2}}},"text":"Testicular descent, sperm maturation and capacitation. Lessons from our most distant relatives, the monotremes.\nThe present review examines whether monotremes may help to resolve three questions relating to sperm production in mammals: why the testes descend into a scrotum in most mammals, why spermatozoa are infertile when they leave the testes and require a period of maturation in the specific milieu provided by the epididymides, and why ejaculated spermatozoa cannot immediately fertilise an ovum until they undergo capacitation within the female reproductive tract. Comparisons of monotremes with other mammals indicate that there is a need for considerable work on monotremes. It is hypothesised that testicular descent should be related to epididymal differentiation. Spermatozoa and ova from both groups share many of the proteins that are thought to be involved in gamete interaction, and although epididymal sperm maturation is significant it is probably less complex in monotremes than in other mammals. However, the monotreme epididymis is unique in forming spermatozoa into bundles of 100 with greatly enhanced motility compared with individual spermatozoa. Bundle formation involves a highly organised interaction with epididymal proteins, and the bundles persist during incubation in vitro, except in specialised medium, in which spermatozoa separate after 2-3 h incubation. It is suggested that this represents an early form of capacitation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22462641,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed-tomographic observations.\nThis study investigates the effects of chitosan (CS) on the opening of epithelial tight junctions (TJs) and paracellular transport at microscopic, ultrastructural, and computed-tomographic levels in Caco-2 cell monolayers and animal models. Using immunofluorescence staining, CS treatment was observed to be associated with the translocation of JAM-1 (a trans-membrane TJ protein), resulting in the disruption of TJs; the removal of CS was accompanied by the recovery of JAM-1. Ultrastructural observations by TEM reveal that CS treatment slightly opened the apical intercellular space, allowing lanthanum (an electron-dense tracer) to stain the intercellular surface immediately beneath the TJs, suggesting the opening of TJs. Following the removal of CS, the TJs were completely recovered. Similar microscopic and ultrastructural findings were obtained in animal studies. CS nanoparticles were prepared as an insulin carrier. The in vivo fluorescence-microscopic results demonstrate that insulin could be absorbed into the systemic circulation, while most CS was retained in the microvilli scaffolds. These observations were verified in a biodistribution study following the oral administration of isotope-labeled nanoparticles by single-photon emission computed tomography. Above results reveal that CS is a safe permeation enhancer and is an effective carrier for oral protein delivery.","subset":"pubmed_abstract"} +{"meta":{"pmid":25579890,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":3,"2024-18":3,"2024-26":1,"unknown":5}}},"text":"Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces.\nCalcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation.","subset":"pubmed_abstract"} +{"meta":{"pmid":9514845,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Peptide growth factors modulate prostaglandin E and F production by goldfish ovarian follicles.\nThis study examines the effect of epidermal growth factor (EGF) on prostaglandin synthesis by goldfish ovarian follicles at different developmental stages. Early vitellogenic follicles (EVIT), vitellogenic follicles (VIT), and prematurational full-grown follicles (PMFG) were examined. EGF alone had no effect on prostaglandin synthesis whereas production of PGE2 and PGF2alpha was enhanced in the presence of the eicosaniod precursor arachidonic acid (AA) in all three follicle classes. EGF enhanced AA stimulation of PGE2 production in both VIT and PMFG follicles. In the same follicles, AA-induced PGF2alpha production either was reduced or was unaffected by EGF. This suggests regulation of prostaglandin synthesis at a point downstream of the conversion of AA to PGH2: the precursor for both PGE2 and PGF2alpha. EGF had no effect on AA stimulation of either PGE2 or PGF2alpha in EVIT follicles. While only VIT and PMFG follicles were responsive to EGF, Western blotting with an antibody to the human EGF-receptor (EGF-R) suggests that all three classes of follicle may possess the receptor protein. Additional tests showed that insulin-like growth factor-I (IGF-I) had no effect on the production of either PGE2 or PGF2alpha by PMFG follicles. By comparison both TGFalpha (which binds to the EGF receptor) and TGFbeta (which acts through a different receptor) enhanced AA-stimulated PGE2 production while having no effect on AA-stimulated PGF2alpha production. In summary, this study demonstrates that several growth factors (EGF, TGFalpha, TGFbeta) may play a role in the regulation of ovarian prostaglandin synthesis and that the actions of EGF change during ovarian follicular development in the goldfish.","subset":"pubmed_abstract"} +{"meta":{"pmid":1768164,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Rheumatic symptoms following an outbreak of campylobacter enteritis: a five year follow up.\nEighty six of 106 (81%) guests attending a party were followed up after an outbreak of Campylobacter jejuni enterocolitis. Acute diarrhoeal illness was reported in 35 subjects (33%), of whom seven showed acute rheumatic symptoms either alone or with other symptoms of infection with C jejuni. The antibody response to C jejuni corresponded well with the intensity of the disease. In the early phase of the gastrointestinal disease the patients with acute rheumatic symptoms displayed significantly higher IgM antibody levels in serum samples than the other patients in this study. Levels of antibodies to C jejuni were increased in serum samples from 31 patients (29%) without symptoms of infection with C jejuni. At a follow up after five and a half years, four of these patients suffered from chronic rheumatic disorders. One HLA-B27 positive woman developed reactive arthritis with a relapse seven years later. The remaining 20 subjects (19%) remained healthy and their antibody tests and stool cultures were negative for C jejuni. It is concluded that C jejuni enterocolitis is significantly associated with rheumatic symptoms in the early phase and may also cause chronic rheumatic disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":23390548,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Striatal glutamate release in L-DOPA-induced dyskinetic animals.\nL-DOPA-induced dyskinesia is a common side effect developed after chronic treatment with 3,4-dihydroxyphenyl-l-alanine (l-DOPA) in Parkinson's disease. The biological mechanisms behind this side effect are not fully comprehended although involvement of dopaminergic, serotonergic, and glutamatergic systems has been suggested. The present study utilizes in vivo amperometry to investigate the impact from unilateral 6-hydroxydopamine lesions and l-DOPA (4 mg\/kg, including benserazide 15 mg\/kg) -induced dyskinetic behavior on striatal basal extracellular glutamate concentration and potassium-evoked glutamate release in urethane-anesthetized rats. Recordings were performed before and after local L-DOPA application in the striatum. In addition, effects from the 5-HT(1A) receptor agonist (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OHDPAT; 1 mg\/kg) was assessed on glutamate release and on dyskinetic behavior. The results revealed a bilateral \u2248 30% reduction of basal extracellular glutamate concentration and attenuated potassium-evoked glutamate release after a unilateral dopamine-depletion in L-DOPA na\u00efve animals. In dyskinetic subjects, basal glutamate concentration was comparable to normal controls, although potassium-evoked glutamate release was reduced to similar levels as in drug na\u00efve dopamine-lesioned animals. Furthermore, acute striatal L-DOPA administration attenuated glutamate release in all groups, except in the dopamine-lesioned striatum of dyskinetic animals. Co-administration of 8-OHDPAT and L-DOPA decreased dyskinesia in dopamine-lesioned animals, but did not affect potassium-evoked glutamate release, which was seen in normal animals. These findings indicate altered glutamate transmission upon dopamine-depletion and dyskinesia.","subset":"pubmed_abstract"} +{"meta":{"pmid":1970766,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":14}}},"text":"Pharmacokinetics and metabolism of the pharmacologically active 4'-hydroxylated metabolite of propranolol in the dog.\nThe disposition of 4'-hydroxypropranolol (HOP) was determined after iv administration to dogs (2 mg\/kg; N = 5) and the pharmacokinetic parameters were calculated from plasma measurements. The clearance of HOP, 66 +\/- 6 ml\/min\/kg (mean +\/- SE), was considerably higher than that of propranolol previously determined, suggesting extrahepatic as well as hepatic clearance of HOP. The plasma half-life of HOP, 77 +\/- 6 min, was shorter than that of propranolol. Although HOP is considerably less lipophilic than propranolol, its volume of distribution, 6.4 +\/- 0.8 liter\/kg, surprisingly, was larger. Like propranolol, HOP appeared to be cleared entirely by metabolism. Whereas propranolol is metabolized mainly by oxidation, HOP was metabolized to sulfate (HOPS) and glucuronic acid (HOPG) conjugates. The plasma half-lives of these conjugates were 2 to 3 times longer than for HOP, reflecting a slow, continuous formation from HOP. This was established for HOPS by iv administration of synthetic HOPS. Morover, after HOP administration both formation and renal clearance of HOPS were stereoselective in favor of the R-enantiomer. In summary, the main conclusion of this study is that the large volume of distribution as well as high clearance through sulfation and glucuronidation may explain the low plasma HOP levels observed during propranolol therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":22670860,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models.\nValsartan is a potent, orally active non-peptide tetrazole derivative and selectively inhibits angiotensin II receptor type 1 which causes reduction in blood pressure and is used in treatment of hypertension. The risk of heart disease mortality decreased significantly as flavonoid intake increased. Interestingly, the flavonoid-containing foods contain a high amount of Quercetin. The objective of this study was to evaluate the influence of quercetin on the pharmacokinetics of valsartan. In vivo studies were performed on rats. Rats were treated with quercetin (10 mg\/kg) and valsartan (10 mg\/kg), blood samples were collected at 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 h. Plasma concentration of valsartan was estimated by Reverse Phase (RP-HPLC). Quercetin significantly increases the plasma concentration of valsartan and peak concentration (70.45 \u00b5g\/mL) was achieved at 3.5 h. In vitro studies were performed on rat intestinal everted sacs. The transport of valsartan from serosal side to mucosal side decreased from 53.12 \u00b1 1.27 to 40.15 \u00b1 0.45 \u00b5g\/mL in the presence of quercetin and from 53.12 \u00b1 1.27 to 28.68 \u00b1 0.31 \u00b5g\/mL in the presence of verapamil (standard P-glycoprotein (P-gp) inhibitor) at 120 min. Verapamil is a potent P-gp and CYP3A4 inhibitor. Quercetin is a P-gp inhibitor and may be an inhibitor of CYP3A4. The simultaneous administration of quercetin significantly increases the intestinal absorption and decreases the efflux of valsartan. The observed effect may be beneficial to develop oral valsartan dosage forms using safe P-gp inhibitor (quercetin) to improve its oral bioavailability.","subset":"pubmed_abstract"} +{"meta":{"pmid":31534971,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Dietary Fatty Acid Saturation Modulates Sphingosine-1-Phosphate-Mediated Vascular Function.\nSphingolipids, modified by dietary fatty acids, are integral components of plasma membrane and caveolae that are also vasoactive compounds. We hypothesized that dietary fatty acid saturation affects vasoconstriction to sphingosine-1-phosphate (S1P) through caveolar regulation of rho kinase. Wild type (WT) and caveolin-1-deficient (cav-1 KO) mice which lack vascular caveolae were fed a low-fat diet (LF), 60% high-saturated fat diet (lard, HF), or 60% fat diet with equal amounts of lard and n-3 polyunsaturated menhaden oil (MO). Weight gain of WT on HF and MO diets was similar while markedly blunted in cav-1 KO. Neither high-fat diet affected the expression of cav-1, rho, or rho kinase in arteries from WT. In cav-1 KO, MO increased the vascular expression of rho but had no effect on rho kinase. HF had no effect on rho or rho kinase expression in cav-1 KO. S1P produced a concentration-dependent constriction of gracilis arteries from WT on LF that was reduced with HF and restored to normal with MO. Constriction to S1P was reduced in cav-1 KO and no longer affected by a high-saturated fat diet. Inhibition of rho kinase which reduced constriction to PE independent of diet in arteries from WT and cav-1 KO only reduced constriction to S1P in arteries from WT fed MO. The data suggest that dietary fatty acids modify vascular responses to S1P by a caveolar-dependent mechanism which is enhanced by dietary n-3 polyunsaturated fats.","subset":"pubmed_abstract"} +{"meta":{"pmid":2829845,"dup_signals":{"dup_doc_count":42,"dup_dump_count":32,"dup_details":{"curated_sources":4,"2021-25":1,"2020-50":1,"2020-24":1,"2020-05":1,"2018-05":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":3,"2014-42":2,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":1,"2023-06":1}}},"text":"Specific antibodies and the selective inhibitor ICI 118233 demonstrate that the hormonally stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases display distinct tissue distributions in the rat.\nPolyclonal-antibody preparations DV1 and PM1, raised against purified preparations of rat liver insulin-stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases, were used to analyse rat liver homogenates by Western-blotting techniques. The antibody DV1 identified only the 63 kDa native subunit of the 'dense-vesicle' enzyme, and the antibody PM1 only the 52 kDa subunit of the plasma-membrane enzyme. These antibodies also detected the subunits of these two enzymes in homogenates of kidney, heart and white adipose tissue from rat. Quantitative immunoblotting demonstrated that the amount of these enzymes (by wt.) varied in these different tissues, as did the expression of these two enzymes, relative to each other, by a factor of as much as 7-fold. The ratio of the dense-vesicle enzyme to the peripheral-plasma-membrane enzyme was lowest in liver and kidney and highest in heart and white adipose tissue. ICI 118233 was shown to inhibit selectively the 'dense-vesicle' cyclic AMP phosphodiesterase in liver. It did this in a competitive fashion, with a Ki value of 3.5 microM. Inhibition of tissue-homogenate cyclic AMP phosphodiesterase activity by ICI 118233 was used as an index of the contribution to activity by the 'dense-vesicle' enzyme. By this method, a tissue distribution of the 'dense-vesicle' enzyme was obtained which was similar to that found by using the immunoblotting technique. The differential expression of isoenzymes of cyclic AMP phosphodiesterase activity in various tissues might reflect a functional adaptation, and may provide the basis for the different physiological actions of compounds which act as selective inhibitors.","subset":"pubmed_abstract"} +{"meta":{"pmid":32284564,"dup_signals":{"dup_doc_count":14,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2023-50":4,"2023-40":5,"2023-14":1,"2022-27":2,"2021-25":1}}},"text":"Bacterial colonization reprograms the neonatal gut metabolome.\nInitial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life. Gut bacteria became detectable using molecular methods by 16 h after birth. Detailed analysis of the three most common species, Escherichia coli, Enterococcus faecalis and Bacteroides vulgatus, did not suggest a genomic signature for neonatal gut colonization. The appearance of bacteria was associated with reduced abundance of approximately 50 human proteins, decreased levels of free amino acids and an increase in products of bacterial fermentation, including acetate and succinate. Using flux balance modelling and in vitro experiments, we provide evidence that fermentation of amino acids provides a mechanism for the initial growth of E. coli, the most common early colonizer, under anaerobic conditions. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance.","subset":"pubmed_abstract"} +{"meta":{"pmid":21209418,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-43":2,"2021-17":1,"2021-04":1,"2020-40":1,"2023-40":1,"2024-18":1,"2017-13":1,"2024-26":1}}},"text":"Testicular signaling is the potential target of perfluorooctanesulfonate-mediated subfertility in male mice.\nPerfluorooctanesulfonate (PFOS) was produced and used by various industries and in consumer products. Because of its persistence, it is ubiquitous in air, water, soil, wildlife, and humans. Although the adverse effects of PFOS on male fertility have been reported, the underlying mechanisms have not yet been elucidated. Here, for the first time, the effects of PFOS on testicular signaling, such as gonadotropin, growth hormone, insulin-like growth factor, and inhibins\/activins were shown to be directly related to male subfertility. Sexually mature 8-wk-old CD1 male mice were administered by gavages in corn oil daily with 0, 1, 5, or 10 mg\/kg PFOS for 7, 14, or 21 days. Serum concentrations of testosterone and epididymal sperm counts were significantly lower in the mice after 21 days of the exposure to the highest dose compared with the controls. The expression levels of testicular receptors for gonadotropin, growth hormone, and insulin-like growth factor 1 were considerably reduced on Day 21 in mice exposed daily to 10 or 5 mg\/kg PFOS. The transcript levels of the subunits of the testicular factors (i.e., inhibins and activins), Inha, Inhba, and Inhbb, were significantly lower on Day 21 of daily exposure to 10, 5, or 1 mg\/kg PFOS. The mRNA expression levels of steroidogenic enzymes (i.e., StAR, CYP11A1, CYP17A1, 3beta-HSD, and 17beta-HSD) were notably reduced. Therefore, PFOS-elicited subfertility in male mice is manifested as progressive deterioration of testicular signaling.","subset":"pubmed_abstract"} +{"meta":{"pmid":26583164,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":13}}},"text":"Biomarker detection technologies and future directions.\nBiomarkers play a vital role in disease detection and treatment follow-up. It is important to note that diseases in the early stage are typically treated with the greatest probability of success. However, due to various technical difficulties in current technologies for the detection of biomarkers, the potential of biomarkers is not explored completely. Therefore, the developments of technologies, which can enable the accurate detection of prostate cancer at an early stage with simple, experimental protocols are highly inevitable. This critical review evaluates the current methods and technologies used in the detection of biomarkers. The aim of this article is to provide a comprehensive review covering the advantages and disadvantages of the biomarker detection methods. Future directions for the development of technologies to achieve highly selective and sensitive detection of biomarkers for point-of-care applications are also commented on.","subset":"pubmed_abstract"} +{"meta":{"pmid":26488006,"dup_signals":{"dup_doc_count":23,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2021-31":1,"2020-45":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2022-21":1,"2017-13":1}}},"text":"Update in genetic susceptibility in melanoma.\nMelanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual.","subset":"pubmed_abstract"} +{"meta":{"pmid":1720938,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Chemotherapy agents and the induction of late lethal defects.\nRadiation is now known to be capable of producing both lethal and non lethal lesions in a variety of mammalian cells which may not be expressed for several cell divisions after the initial insult. The mechanism by which such an effect occurs is unknown. Because of the possible implications for cancer treatment, if such an effect also occurred following chemotherapy exposure, cells were exposed to various cytotoxic chemotherapy agents with known and well characterised effects on DNA or other areas of cell function or structure. The results indicate that late lethal defects are not detectable after treatment with appropriate ranges of doses of cisplatinum, vincristine, BCNU or adriamycin, but that they are induced by Bleomycin and to a lesser extent by 5-Fluorouracil. Bleomycin is known to cause strand breaks and is regarded as a radiomimetic agent. 5-Fluorouracil may act by preventing efficient and faithful synthesis of DNA, allowing mutations to become integrated into the genome. The occurrence of lethal mutations with both these agents supports previous suggestions that error-prone repair of DNA base sequence abnormalities may be fundamental to the process of late lethal damage production in mammalian cells. The cloning efficiency of cells which survived exposure to Vincristine or BCNU over a wide dose range was found to be significantly increased; this may represent an adaptive response to the drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":30767047,"dup_signals":{"dup_doc_count":13,"dup_dump_count":10,"dup_details":{"curated_sources":1,"2022-21":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-21":2,"2021-10":1,"2020-50":2,"2020-40":1,"2019-43":1,"2022-27":1}}},"text":"Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a oral spray for children with recurrent streptococcal pharyngotonsillitis: a randomized placebo-controlled clinical study.\nGroup A beta-hemolytic Streptococcus (GABHS) causes a recurrent acute pharyngotonsillitis (RAPT) in children. Moreover, the repeated use of antibiotics contributes to its resistance. However, S. Salivarius 24SMB and S. oralis 89a were effective probiotics in other infections. Thus, we decided to evaluate this combination efficacy compared to placebo in RAPT. Patients with microbiologically confirmed GABHS were enrolled in this randomized, placebo-controlled trial. They received the aforementioned combination or placebo as an oral spray. We investigated episodes of frequency and duration, need for antibiotics, school days lost, the treatment impact on life quality, treatment compliance and side effects during a 90-day treatment and a 6-month follow-up. We included 41 patients in each group. The mean number of GABHS infection was significantly lower during both study periods for the two groups. However, our treatment group showed a lower rate. Moreover, the probiotic group had a lower mean number and a shorter median duration of GABHS episodes during both study periods than controls. Furthermore, the mean duration of antibiotic treatment was lower in the probiotic group during the 90-day and 6-month follow-up periods. Similarly, patients in the probiotic group showed a significantly lower mean number of absence days from school but higher EQ-VAS score. Indeed, all patients included were compliant to treatment. We identified potential probiotics, possessing desirable features against GABHS pharyngotonsillitis. Our findings represent the first evidence which throws the light on using these probiotics that can reduce antibiotics use which did not have efficient results regarding recurrence.","subset":"pubmed_abstract"} +{"meta":{"pmid":22379086,"dup_signals":{"dup_doc_count":84,"dup_dump_count":33,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":4,"2023-23":3,"2023-14":2,"2023-06":3,"2022-49":2,"2022-40":2,"2022-27":3,"2022-21":6,"2022-05":1,"2021-49":2,"2021-43":4,"2021-31":5,"2021-21":3,"2021-17":4,"2021-10":1,"2021-04":4,"2020-50":1,"2020-45":2,"2020-40":3,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2024-30":2,"2024-26":4,"2024-22":4,"2024-18":1,"2024-10":3,"2015-06":1,"2014-10":1}}},"text":"Widespread impact of HLA restriction on immune control and escape pathways of HIV-1.\nThe promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-\u03b3) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine.","subset":"pubmed_abstract"} +{"meta":{"pmid":24879432,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Efficient purging of deleterious mutations in plants with haploid selfing.\nIn diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here, we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly more nonsynonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale.","subset":"pubmed_abstract"} +{"meta":{"pmid":28848986,"dup_signals":{"dup_doc_count":20,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-05":1,"2021-10":1,"2020-24":2,"2018-47":1,"2018-34":1,"2018-26":1,"2018-09":1,"2018-05":2,"2017-47":1,"2017-39":3,"2023-06":1,"2024-26":1}}},"text":"Rapid assessment of crystal orientation in semi-crystalline polymer films using rotational zone annealing and impact of orientation on mechanical properties.\nCrystal orientation in semi-crystalline polymers tends to enhance their performance, such as increased yield strength and modulus, along the orientation direction. Zone annealing (ZA) orients the crystal lamellae through a sharp temperature gradient that effectively directs the crystal growth, but the sweep rate (VZA) of this gradient significantly impacts the extent of crystal orientation. Here, we demonstrate rotational zone annealing (RZA) as an efficient method to elucidate the influence of VZA on the crystal morphology of thin films in a single experiment using isotactic poly(1-butene), PB-1, as a model semi-crystalline polymer. These RZA results are confirmed using standard, serial linear ZA to tune the structure from an almost unidirectional oriented morphology to weakly oriented spherulites. The overall crystallinity is only modestly changed in comparison to isothermal crystallization (maximum of 55% from ZA vs. 48% for isothermal crystallization). However, the average grain size increases and the spherulites become anisotropic from ZA. Due to these structural changes, the Young's modulus of the oriented films, both parallel and perpendicular to the spherulite orientation direction, is significantly increased by ZA. The modulus does become anisotropic after ZA due to the directionality in the crystal structure, with more than a threefold increase in the modulus parallel to the orientation direction for the highest oriented film in comparison to the modulus from isothermal crystallization. RZA enables rapid identification of conditions to maximize orientation of crystals in thin polymer films, which could find utility in determining conditions to improve crystallinity and performance in organic electronics.","subset":"pubmed_abstract"} +{"meta":{"pmid":23988563,"dup_signals":{"dup_doc_count":23,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-23":1,"2022-49":3,"2022-33":1,"2022-27":1,"2021-39":2,"2021-31":1,"2021-25":1,"2021-04":1,"2018-43":1,"2018-13":2,"2017-43":2,"2017-22":1,"2023-50":1,"2024-30":1}}},"text":"The spectre of race in American medicine.\nControversies and debates surrounding race have long been a fixture in American medicine. In the past, the biological concept of race-the idea that race is biologically determined and meaningful-has served to justify the institution of slavery and the conduct of unethical research trials. Although these days may seem far behind, contemporary debates over the race-specific approval of drugs and the significance of genetic differences are evidence that race still yields tremendous influence on medical research and clinical practice. In many ways, the use of race in medicine today reflects the internalisation of racial hierarchies borne out of the history of slavery and state-mandated segregation, and there is still much uncertainty over its benefits and harms. Although using race in research can help elucidate disparities, the reflexive use of race as a variable runs the risk of reifying the biological concept of race and blinding researchers to important underlying factors such as socioeconomic status. Similarly, in clinical practice, the use of race in assessing a patient's risk of certain conditions (eg, sickle cell) turns harmful when the heuristic becomes a rule. Through selected historical and contemporary examples, I aim to show how the biological concept of race that gave rise to past abuses remains alive and harmful, and propose changes in medical education as a potential solution. By learning from the past, today's physicians will be better armed to discern-and correct-the ways in which contemporary medicine perpetuates historical injustices.","subset":"pubmed_abstract"} +{"meta":{"pmid":29763414,"dup_signals":{"dup_doc_count":52,"dup_dump_count":22,"dup_details":{"curated_sources":4,"2021-17":1,"2021-10":1,"2020-34":1,"2020-24":2,"2020-16":4,"2020-10":3,"2020-05":3,"2019-51":1,"2019-47":5,"2019-43":3,"2019-18":1,"2019-09":1,"2019-04":4,"2018-47":1,"2018-43":3,"2018-39":1,"2018-34":3,"2018-30":1,"2018-26":2,"2018-22":4,"2022-21":1,"2024-10":2}}},"text":"CD93 promotes \u03b21 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis.\nTumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is upregulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates \u03b21 integrin signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytic cleavage. The CD93-MMRN2 complex was required for activation of \u03b21 integrin, phosphorylation of focal adhesion kinase (FAK), and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of \u03b21 integrin and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":20173842,"dup_signals":{"dup_doc_count":21,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2021-31":1,"2020-34":1,"2016-44":2,"2016-36":2,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-40":1,"2015-35":1,"2015-32":1,"2022-33":1,"2024-10":1,"2024-26":1}}},"text":"Random process estimator for laser speckle imaging of cerebral blood flow.\nIn this paper, we develop a random process theory to explain the laser speckle phenomena. The relation between the probability distribution of speckle's integrated intensity random process Y(t) and the relative velocity v(t) is derived. Based on the random process theory, traditional spatial or temporal laser speckle contrast analysis (i.e. spatial or temporal LASCA) can be derived as the spatial or temporal estimators respectively. Both spatial LASCA and temporal LASCA suffer from noise due to insufficient statistics and nonstationarity in either spatial or temporal domain. Furthermore, either LASCA results in a reduction of spatial or temporal resolution. A new random process estimator is proposed and able to overcome these drawbacks. In an in-vitro study, random process estimator outperforms either spatial LASCA or temporal LASCA by providing much higher SNR (random process estimator vs. spatial LASCA vs. temporal LASCA: 33.64+\/-6.87 (mean+\/-s.t.d.) vs. 9.08+\/-2.85 vs. 3.83+\/-1.05). In an in-vivo structural imaging study, random process estimator efficiently suppresses the noise in contrast image and thus improves the distinguishability of small vessels. In a functional imaging study of cerebral blood flow change in the somatosensory cortex induced by rat's hind paw stimulation, random process estimator provides much lower estimation errors in single trial data (random process estimator vs. temporal LASCA: 0.31+\/-0.03 vs. 1.36+\/-0.09) and finally leads to higher resolution spatiotemporal patterns of cerebral blood flow.","subset":"pubmed_abstract"} +{"meta":{"pmid":29767295,"dup_signals":{"dup_doc_count":26,"dup_dump_count":24,"dup_details":{"curated_sources":2,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2023-40":1,"2024-18":1}}},"text":"Violation of expectations about movement and goal achievement leads to Sense of Agency reduction.\nThe control of one's own movements and of their impact on the external world generates a feeling of control referred to as Sense of Agency (SoA). SoA is experienced when actions match predictions and is reduced by unpredicted events. The present study investigated the contribution of monitoring two fundamental components of action-movement execution and goal achievement-that have been most often explored separately in previous research. We have devised a new paradigm in which participants performed goal-directed actions while viewing an avatar's hand in a mixed-reality scenario. The hand performed either the same action or a different one, simultaneously or after various delays. Movement of the virtual finger and goal attainment were manipulated, so that they could match or conflict with the participants' expectations. We collected judgments of correspondence (an explicit index of SoA that overcomes the tendency to over-attribute actions to oneself) by asking participants if the observed action was synchronous or not with their action. In keeping with previous studies, we found that monitoring both movement execution and goal attainment is relevant for SoA. Moreover, we expanded previous findings by showing that movement information may be a more constant source of SoA modulation than goal information. Indeed, an incongruent movement impaired SoA irrespective of delay duration, while a missed goal did so only when delays were short. Our novel paradigm allowed us to simultaneously manipulate multiple action features, a characteristic that makes it suitable for investigating the contribution of different sub-components of action in modulating SoA in healthy and clinical populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":22274516,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":5,"unknown":9}}},"text":"High-speed scattering medium characterization with application to focusing light through turbid media.\nWe introduce a phase-control holographic technique to characterize scattering media with the purpose of focusing light through it. The system generates computer-generated holograms implemented via a deformable mirror device (DMD) based on micro-electro-mechanical technology. The DMD can be updated at high data rates, enabling high speed wavefront measurements using the transmission matrix method. The transmission matrix of a scattering material determines the hologram required for focusing through the scatterer. We demonstrate this technique measuring a transmission matrix with 256 input modes and a single output mode in 33.8 ms and creating a focus with a signal to background ratio of 160. We also demonstrate focusing through a temporally dynamic, strongly scattering sample with short speckle decorrelation times.","subset":"pubmed_abstract"} +{"meta":{"pmid":37359298,"dup_signals":{"dup_doc_count":17,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-30":5,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":2,"unknown":6}}},"text":"Who Am I? The Influence of Knowledge Networks on PhD Students' Formation of a Researcher Role Identity.\nHigher education institutes both foster the advancement of knowledge and address society's socioeconomic and environmental challenges. To fulfil these multiple missions requires significant changes to how the role of a researcher is perceived e.g. a researcher identity that is congruent with the objective of contributing to fundamental knowledge while also engaging with non-academic actors, broadly, and entrepreneurship, in particular. We argue that the early stages of an academic career-namely the PhD training trajectory-and the knowledge networks formed during this period have a major influence on the scientist's future capacity to develop an appropriate researcher role identity. We draw on knowledge network and identity theories to investigate how the knowledge networks (i.e. business, scientific and career knowledge networks) of PhD students promote changes to, reinforce or conflict with the perception of a researcher role identity. Our longitudinal qualitative network study includes PhD students and their supervisors funded by the H2020 FINESSE project. At the network level, we show that scientific knowledge is distributed equally throughout young academics' networks but that entrepreneurial (business) and career knowledge tend to be concentrated around certain individuals in these networks. On the PhD student level, we observe different pronunciations of the researcher role identity linked to students' interactions with their knowledge networks. We distinguish identity conflicts due to misalignment between ego and alters which leads to withdrawal from the network. Our findings have practical implications and suggest that universities and PhD student supervisors should support PhD students to develop a researcher identity which is in line with the individual PhD student's expectations.","subset":"pubmed_abstract"} +{"meta":{"pmid":36457464,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Associations of Masticatory Muscles Asymmetry and Oral Health with Postural Control and Leg Injuries of Elite Junior Soccer Players.\nThe influence of asymmetry between masticatory muscles on postural control is still under debate and only few studies examined the impact of oral health on injury risk. The present study investigated the relationships between masticatory muscles asymmetry, oral health, postural control and the prevalence of (non-contact or traumatic) leg injuries in a sample of 144 male elite junior soccer players. sEMG of the masseter and temporal muscles was performed during maximum teeth clenching, postural control was tested by measuring sway velocity during the unipedal stance with eyes closed, while oral health and the number of leg injuries were assessed using a questionnaire. The time-1 assessment was repeated in a subgroup of 69 players after one year. Pearson and partial correlation coefficients and adjusted odds ratios (OR) were used to assess associations. Asymmetry between the masseter and temporalis muscles (AMTM, quantified as anteroposterior coefficient, APC) was associated with higher sway velocity on the dominant leg (using time-1 data partial r = -0.24, p = 0.004, using longitudinal data partial r = -0.40, p = 0.005). Higher prevalence of two or more leg injuries throughout a competitive season was associated with poor oral health (adjusted OR (95%CI) using time-1 data = 2.14 (1.02-4.46), using longitudinal data = 4.47 (1.25-15.96)). These results indicate that AMTM has a negative influence on the sway velocity of the dominant leg only, possibly because frequent balancing exercises on the non-dominant leg may counteract negative influences of AMTM. The association of oral health with leg injuries underlines the need for oral health promotion and monitoring strategies in sports.","subset":"pubmed_abstract"} +{"meta":{"pmid":21627427,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Factors affecting pregnancy outcome of intrauterine insemination cycles in couples with favourable female characteristics.\nThe aim of the presented study is to determine the effect of different sperm parameters on the pregnancy rate of intrauterine insemination (IUI) cycles in women with favourable fertility characteristics treated for infertility. Medical records of 212 infertile couples who had undergone a total of 253 cycles were reviewed retrospectively. Inclusion criteria for women were age <35 years, antral follicle count >5, FSH <15 IU\/ml, and at least one patent tube documented by HSG or laparoscopy. Clinical pregnancy rates were achieved as 15.8% per cycle, and 18.8% per couple. Woman's age, partner's age, total number of motile sperm (TMS) and motility, significantly influenced pregnancy rate. Pregnancy rate was the highest when women were aged <25 and TMS >10 \u00d7 10(6). Partner's age significantly affected the pregnancy rate per cycle in women aged <30 years and TMS >10 \u00d7 10(6). Woman's age (OR: 5.4 95% CI: 1.2-24.3) and TMS (OR: 0.06 95% CI: 0.003-0.89) were predictor variables as regards to pregnancy. Pregnancy rate was the highest in IUI cycles when woman was <25 years old, TMS was >10 \u00d7 10(6), and morphology was >4%. Male age was found to be another determining factor for IUI success, even if they had a normal spermiogram.","subset":"pubmed_abstract"} +{"meta":{"pmid":10755408,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas.\nOur analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in colorectal cancers compared to control mucosa (P = 0.003; n = 77). Highest specific activities and cancer\/normal ratios (C\/N) for activity were measured in Dukes' B and C stage carcinomas, cancers involved in local spread and invasion to lymph nodes. In contrast, cathepsin B and L activities analysed in the same paired extracts had been shown to be most frequently elevated in earlier stage carcinomas (Dukes' A and B), confirming that cathepsin H demonstrates a distinct pattern of expression during colorectal cancer progression. Although cathepsin H activities were most commonly elevated in Dukes' C cancers at all colon sites, both specific activity and C\/N ratios were significantly higher for cancers of the left colon compared to other colon locations. A subset of 43 paired extracts analysed on Western blots also revealed consistent changes in cathepsin H protein forms in cancers. Normal mucosa typically showed a strong protein doublet at 31 and 29 kDa while cancers demonstrated decreased expression or total loss of the 31 kDa protein (90% of cases), equal or increased expression of the 29-kDa protein (67% of cases) and the new appearance or up-regulation of a cathepsin H band at 22 kDa (78% of cases). C\/N ratios for cathepsin H enzyme activity correlated significantly with C\/N ratios for the 29 kDa mature single-chain protein form (P < 0.001), with increased activity most commonly associated with elevated expression of 29-kDa cathepsin H but also with up-regulation of the 22-kDa band, suggesting a shift to more fully processed, mature active cathepsin H protein forms in cancers. Changes in cathepsin H expression were also detected by immunohistochemistry as elevated cathepsin H staining in tumour epithelial cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23802990,"dup_signals":{"dup_doc_count":41,"dup_dump_count":36,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":1,"2022-40":1,"2022-27":2,"2022-05":1,"2021-49":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":2,"2020-24":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":2,"2019-26":1,"2019-22":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2023-23":1,"2017-13":1}}},"text":"Bound to Succeed: transcription factor binding-site prediction and its contribution to understanding virulence and environmental adaptation in bacterial plant pathogens.\nBacterial plant pathogens rely on a battalion of transcription factors to fine-tune their response to changing environmental conditions and to marshal the genetic resources required for successful pathogenesis. Prediction of transcription factor binding sites (TFBS) represents an important tool for elucidating regulatory networks and has been conducted in multiple genera of plant-pathogenic bacteria for the purpose of better understanding mechanisms of survival and pathogenesis. The major categories of TFBS that have been characterized are reviewed here, with emphasis on in silico methods used for site identification and challenges therein, their applicability to different types of sequence datasets, and insights into mechanisms of virulence and survival that have been gained through binding-site mapping. An improved strategy for establishing E-value cutoffs when using existing models to screen uncharacterized genomes is also discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":19480362,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Religious and spiritual factors and the consequences of trauma: a review and model of the interrelationship.\nAn increasing body of literature examines the association of religious factors with posttraumatic stress as well as posttraumatic growth. This review of selected empirical studies describes religious and spiritual factors that have been examined in their association with the consequences of trauma. A comprehensive model is proposed to explain the complex interrelationship. We performed a qualitative review of empirical research in August 2006, updated in February 2008, using Medline (1950-present), PsychInfo (1806-present), Web of Science (1900-present), and PILOTS (1960-present). We searched the terms posttraumatic, posttraumatic stress, posttraumatic growth, and religion, religious, spirituality, spiritual, meditation, and forgiveness. Based on supporting data from reviewed literature, we then developed a model for key religious factors derived from this review predictive of the response to trauma over time. Twenty-three studies were identified that describe religious pre-trauma characteristics, religious trauma-appraisal and post-trauma adjustment factors. The association of these factors with posttraumatic stress and growth is described. Intrinsic religious orientation, in particular, appears to be a useful construct in measuring religiosity in the association with the consequences of trauma. There are preliminary indications that the association between intrinsic religiosity and the consequences of trauma may change depending on the time after the event. Future studies should stratify outcome by the time after trauma or use longitudinal designs.","subset":"pubmed_abstract"} +{"meta":{"pmid":32609970,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":6}}},"text":"Sonoelastic response of median nerve to rehabilitation in carpal tunnel syndrome.\nAim of the study: To evaluate the sonoelastic response of the median nerve in patients with carpal tunnel syndrome following conservative rehabilitation with splint plus exercise regimens. Materials and methods: A total of thirty-five patients diagnosed with mild carpal tunnel syndrome and treated with splint plus exercise therapy; hand resting splint all day for 3 weeks and then only at nights along with nerve gliding exercises in 10 repetitions 3 times a day. The median nerve was evaluated clinically prior to the treatment and at week 6 of therapy using physical examination, electrodiagnostic neurophysiology tests and radiological imaging; Boston Scores, electromyogram, ultrasonography and sonoelastography. Results: Following the 6-week treatment protocol on 35 subjects with mild carpal tunnel syndrome, sonoelastography showed significantly softer median nerve, while the traditional parameters based on Boston Scores and cross-sectional area based on ultrasonography remained nearly unresponsive. Such early indication of biomechanical changes in the nerve may be of clinical importance if it can offer a prognostic value of the applied treatment, while tissue softening suggests the alleviation of nerve compression. Conclusions: Sonoelasticity of the median nerve can serve as a reliable marker for assessing therapeutic changes in median nerve stiffness and potentially the outcome early on in mild carpal tunnel syndrome. Aim of the study: To evaluate the sonoelastic response of the median nerve in patients with carpal tunnel syndrome following conservative rehabilitation with splint plus exercise regimens. Materials and methods: A total of thirty-five patients diagnosed with mild carpal tunnel syndrome and treated with splint plus exercise therapy; hand resting splint all day for 3 weeks and then only at nights along with nerve gliding exercises in 10 repetitions 3 times a day. The median nerve was evaluated clinically prior to the treatment and at week 6 of therapy using physical examination, electrodiagnostic neurophysiology tests and radiological imaging; Boston Scores, electromyogram, ultrasonography and sonoelastography. Results: Following the 6-week treatment protocol on 35 subjects with mild carpal tunnel syndrome, sonoelastography showed significantly softer median nerve, while the traditional parameters based on Boston Scores and cross-sectional area based on ultrasonography remained nearly unresponsive. Such early indication of biomechanical changes in the nerve may be of clinical importance if it can offer a prognostic value of the applied treatment, while tissue softening suggests the alleviation of nerve compression. Conclusions: Sonoelasticity of the median nerve can serve as a reliable marker for assessing therapeutic changes in median nerve stiffness and potentially the outcome early on in mild carpal tunnel syndrome.","subset":"pubmed_abstract"} +{"meta":{"pmid":29067302,"dup_signals":{"dup_doc_count":98,"dup_dump_count":48,"dup_details":{"curated_sources":2,"2023-50":5,"2023-40":1,"2023-23":2,"2023-14":3,"2023-06":1,"2022-49":3,"2022-27":5,"2022-21":1,"2022-05":3,"2021-43":1,"2021-39":6,"2021-31":4,"2021-25":1,"2021-17":4,"2021-10":1,"2021-04":3,"2020-50":1,"2020-45":1,"2020-40":3,"2020-29":1,"2020-24":1,"2020-10":1,"2020-05":1,"2019-47":1,"2019-13":2,"2019-09":1,"2018-51":3,"2018-43":2,"2018-39":2,"2018-30":3,"2018-26":1,"2018-22":1,"2018-17":2,"2018-13":2,"2018-09":2,"2017-51":3,"2017-43":3,"2017-34":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-26":2,"2024-22":2,"2024-10":2,"2017-13":1}}},"text":"B-vitamins are potentially a cost-effective population health strategy to tackle dementia: Too good to be true?\nTo respond to the threat of dementia to public health and the economy, we need to prioritize research resources on strategies that would be the most effective. In relation to the prevention of dementia, this article considers whether lowering plasma homocysteine by B-vitamin supplementation is one of the top priority and cost-effective treatments. A decision model was constructed to calculate the lifetime costs and quality-adjusted life years (QALYs) of providing B-vitamin treatment to people in the United Kingdom over 60 years with high levels (>13 \u03bcmol\/L) of plasma homocysteine, which was compared to the lifetime costs and outcomes of not providing them with the treatment. Treatment with B-vitamins will save \u00a360,021 per QALY gained and so is highly cost-effective. We anticipate that this provocative finding will be debated by scientists, clinicians, and policy makers and eventually be tested in future clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":28737609,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"The Effects of Supplementary Low-Load Blood Flow Restriction Training on Morphological and Performance-Based Adaptations in Team Sport Athletes.\nScott, BR, Peiffer, JJ, and Goods, PSR. The effects of supplementary low-load blood flow restriction training on morphological and performance-based adaptations in team sport athletes. J Strength Cond Res 31(8): 2147-2154, 2017-Low-load resistance training with blood flow restriction (BFR) may be a method to enhance muscular development even in trained athletes. This study aimed to assess whether supplemental low-load BFR training can improve muscle size, strength, and physical performance characteristics in team sport athletes. Twenty-one semiprofessional Australian football athletes were assessed for 3-repetition maximum (3RM) and muscular endurance in the back squat, vastus lateralis muscle architecture, and performance in sprint and vertical jump tasks. Participants then undertook a 5-week training program, consisting of normal high-load resistance training supplemented by low-load squats with (LLBFR) or without (LL) BFR. Participants also performed regular conditioning and football training during this period. After the training intervention, participants again completed the pretraining testing battery. Squat 3RM and endurance increased from pretraining levels in both LL (3RM = 12.5% increase; endurance = 24.1% increase; p \u2264 0.007) and LLBFR (3RM = 12.3% increase; endurance = 21.2% increase; p = 0.007) groups, though there were no between-group differences. No post-training changes were observed for muscle architecture, or performance in sprinting and jumping tasks. Although squat 3RM and endurance performance increased in both groups, adding BFR during supplemental exercise did not enhance these responses. Similarly, there were no large differences in the assessments of sprint, acceleration, and jumping performance between the groups after training. These findings suggest that although LLBFR did not negatively affect adaptive responses to resistance training, this training strategy may not provide added benefit for healthy Australian football athletes already undertaking a rigorous training schedule.","subset":"pubmed_abstract"} +{"meta":{"pmid":29181503,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":13}}},"text":"Anticipatory smooth pursuit eye movements evoked by probabilistic cues.\nAnticipatory smooth eye movements (ASEM; smooth eye movements in the direction of anticipated target motion) are elicited by cues that signal the direction of future target motion with high levels of certainty. Natural cues, however, rarely convey information with perfect certainty, and responses to uncertainty provide insights about how predictive behaviors are generated. Subjects smoothly pursued targets that moved to the right or left with varying cued probabilities. ASEM strength in a given direction increased with the probability level. The type of cue also played a role. ASEM elicited by symbolic visual cues tended to underweight low probabilities and overweight high probabilities. Cues based on memory (varying the proportion of trials with left or right motion) produced the opposite pattern, overweighting low probabilities and underweighting high probabilities. Finally, cues whose perceptual structure depicted the motion path produced a bias in ASEM in the depicted direction that was maintained across levels of cue congruency. The results show that the smooth pursuit system relies on a combination of signals, including memory for recent target motions, interpretation of cues, and prior beliefs about the relationship between the perceptual configuration and the motion path to determine the anticipatory response in the presence of uncertainty.","subset":"pubmed_abstract"} +{"meta":{"pmid":22385148,"dup_signals":{"dup_doc_count":20,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":6,"2024-22":5,"2024-18":1,"2017-13":1,"unknown":3}}},"text":"Chemical genetics and its potential in cardiac stem cell therapy.\nOver the last decade or so, intensive research in cardiac stem cell biology has led to significant discoveries towards a potential therapy for cardiovascular disease; the main cause of morbidity and mortality in humans. The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. A major bottleneck with all of these approaches is the low efficiency of cardiomyocyte differentiation alongside their relative functional immaturity. Chemical genetics, and the application of phenotypic screening with small molecule libraries, represent a means to enhance understanding of the molecular pathways controlling cardiovascular cell differentiation and, moreover, offer the potential for discovery of new drugs to invoke heart repair and regeneration. Here, we review the potential of chemical genetics in cardiac stem cell therapy, highlighting not only the major contributions to the field so far, but also the future challenges.","subset":"pubmed_abstract"} +{"meta":{"pmid":29662290,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm.\nNon celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.","subset":"pubmed_abstract"} +{"meta":{"pmid":16118362,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Single-channel kinetic analysis of chimeric alpha7-5HT3A receptors.\nThe receptor chimera alpha7-5HT3A has served as a prototype for understanding the pharmacology of alpha7 neuronal nicotinic receptors, yet its low single channel conductance has prevented studies of the activation kinetics of single receptor channels. In this study, we show that introducing mutations in the M3-M4 cytoplasmic linker of the chimera alters neither the apparent affinity for the agonist nor the EC50 but increases the amplitude of agonist-evoked single channel currents to enable kinetic analysis. Channel events appear as single brief openings flanked by long closings or as bursts of several openings in quick succession. Both the open and closed time distributions are described as the sum of multiple exponential components, but these do not change over a wide range of acetylcholine (ACh), nicotine, or choline concentrations. Bursts elicited by a saturating concentration of ACh contain brief and long openings and closings, and a cyclic scheme containing two open and two closed states is found to adequately describe the data. The analysis indicates that once fully occupied, the receptor opens rapidly and efficiently, and closes and reopens several times before it desensitizes. Channel closing and desensitization occur at similar rates and account for the invariant open and closed time distributions.","subset":"pubmed_abstract"} +{"meta":{"pmid":26527195,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Revealing the working mechanism of polymer photodetectors with ultra-high external quantum efficiency.\nWe report polymer photodetectors (PPDs) with an evident photomultiplication (PM) phenomenon, based on a sandwich structure ITO\/PEDOT:PSS\/P3HT:PC71BM(100:1)\/Al. A similar device structure has been reported in our previous work, showing great potential as a new type of high performance PPD. However, we found more interesting new phenomena from these PPDs. Solid evidence is provided to prove the existence of photogenerated electron transport in the almost hole-only active layer under an applied bias. The transport of photogenerated electrons leads to electron accumulation near the Al electrode and the electron redistribution, which strongly affect the EQE spectral shape and the transient response of the PPDs. Our conclusion is further confirmed by confirmatory devices with a structure of Al(1)\/P3HT:PC71BM(100:1)\/Al(2). EQE spectra and transient Jph curves of the confirmatory devices accord well with our speculation. This discovery may provide a new insight to increase the response speed of PM type PPDs by adjusting the photogenerated electron distribution in the active layer. Considering that the PM type PPDs have much higher EQE than the traditional organic photodetectors, the improvement may further extend its potential applications with low cost.","subset":"pubmed_abstract"} +{"meta":{"pmid":24996823,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"unknown":6}}},"text":"Galectin-3 promotes HIV-1 budding via association with Alix and Gag p6.\nGalectin-3 has been reported to regulate the functions of a number of immune cell types. We previously reported that galectin-3 is translocated to immunological synapses in T cells upon T-cell receptor engagement, where it associates with ALG-2-interacting protein X (Alix). Alix is known to coordinate with the endosomal sorting complex required for transport (ESCRT) to promote human immunodeficiency virus (HIV)-1 virion release. We hypothesized that galectin-3 plays a role in HIV-1 viral budding. Cotransfection of cells of the Jurkat T line with galectin-3 and HIV-1 plasmids resulted in increased HIV-1 budding, and suppression of galectin-3 expression by RNAi in Hut78 and primary CD4+ T cells led to reduced HIV-1 budding. We used immunofluorescence microscopy to observe the partial colocalization of galectin-3, Alix and Gag in HIV-1-infected cells. Results from co-immunoprecipitation experiments indicate that galectin-3 expression promotes Alix-Gag p6 association, whereas the results of Alix knockdown suggest that galectin-3 promotes HIV-1 budding through Alix. HIV-1 particles released from galectin-3-expressing cells acquire the galectin-3 protein in an Alix-dependent manner, with proteins primarily residing inside the virions. We also found that the galectin-3 N-terminal domain interacts with the proline-rich region of Alix. Collectively, these results suggest that endogenous galectin-3 facilitates HIV-1 budding by promoting the Alix-Gag p6 association.","subset":"pubmed_abstract"} +{"meta":{"pmid":26806884,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":7}}},"text":"Biothermal sensing of a torsional artificial muscle.\nBiomolecule responsive materials have been studied intensively for use in biomedical applications as smart systems because of their unique property of responding to specific biomolecules under mild conditions. However, these materials have some challenging drawbacks that limit further practical application, including their speed of response and mechanical properties, because most are based on hydrogels. Here, we present a fast, mechanically robust biscrolled twist-spun carbon nanotube yarn as a torsional artificial muscle through entrapping an enzyme linked to a thermally sensitive hydrogel, poly(N-isopropylacrylamide), utilizing the exothermic catalytic reaction of the enzyme. The induced rotation reached an equilibrated angle in less than 2 min under mild temperature conditions (25-37 \u00b0C) while maintaining the mechanical properties originating from the carbon nanotubes. This biothermal sensing of a torsional artificial muscle offers a versatile platform for the recognition of various types of biomolecules by replacing the enzyme, because an exothermic reaction is a general property accompanying a biochemical transformation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28957731,"dup_signals":{"dup_doc_count":15,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2022-21":1,"2021-39":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-26":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2023-14":1}}},"text":"Chemical genomics reveals mechanistic hypotheses for uncharacterized bioactive molecules in bacteria.\nIn an effort to combat the perpetual emergence of new antibiotic-resistant human pathogens, research in industry and academe aims to find new means of controlling infection. The discovery of new antimicrobial chemicals is not the bottleneck in an era where high-throughput screening rapidly uncovers new bioactive compounds. Rather, the rate-limiting step in antimicrobial discovery pipelines is identifying mechanisms of action (MOA) of bioactive molecules produced by these increasingly large-scale efforts. Chemical genomics has proven to be of high value in providing mechanistic hypotheses for novel bioactive chemical matter. Several techniques fall under this blanket term, including interactions with deletion or transposon libraries, fluorescent or luminescent reporter library profiles, or deep sequencing approaches. Each of these provide unique and complementary outputs, and have high value in generating target lists for chemical screens, or assisting in downstream MOA discovery. We review here the broad usefulness of this technique to aid in MOA determination, to identify targets for new lead molecules, and to expand our mechanistic understanding of existing drugs.","subset":"pubmed_abstract"} +{"meta":{"pmid":23597299,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":4,"2024-26":1,"unknown":15}}},"text":"Heart failure in sub-Saharan Africa.\nThe heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in sub-Saharan African for many decades. Seminal knowledge regarding heart failure in the region came from case reports and case series of the early 20th century which identified infectious, nutritional and idiopathic causes as the most common. With increasing urbanization, changes in lifestyle habits, and ageing of the population, the spectrum of causes of HF has also expanded resulting in a significant burden of both communicable and non-communicable etiologies. Heart failure in sub-Saharan Africa is notable for the range of etiologies that concurrently exist as well as the healthcare environment marked by limited resources, weak national healthcare systems and a paucity of national level data on disease trends. With the recent publication of the first and largest multinational prospective registry of acute heart failure in sub-Saharan Africa, it is timely to review the state of knowledge to date and describe the myriad forms of heart failure in the region. This review discusses several forms of heart failure that are common in sub-Saharan Africa (e.g., rheumatic heart disease, hypertensive heart disease, pericardial disease, various dilated cardiomyopathies, HIV cardiomyopathy, hypertrophic cardiomyopathy, endomyocardial fibrosis, ischemic heart disease, cor pulmonale) and presents each form with regard to epidemiology, natural history, clinical characteristics, diagnostic considerations and therapies. Areas and approaches to fill the remaining gaps in knowledge are also offered herein highlighting the need for research that is driven by regional disease burden and needs.","subset":"pubmed_abstract"} +{"meta":{"pmid":10410401,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Predicting outcome of military basic training for individuals referred for psychological evaluation.\nWe examined outcome data for 632 U.S. Air Force personnel who were referred for psychological evaluation during Basic Military Training (BMT) but who were subsequently returned to BMT to determine what proportion graduated. We analyzed motivational, biographical, and psychological testing variables, using logistic regression to develop a model predictive of training outcome. The results demonstrated that a relatively small number of variables could predict outcome with close to 70% accuracy. Level of optimism regarding training, history of physical abuse, and frequency of visits to the trainee health clinic were major contributors to the model. MMPI-2 (Hathaway & McKinley, 1989) Scales D and Sc also remained in the model but added little to its power. The findings are generally consistent with prior research on normal military populations, except that some factors previously linked to adjustment, such as sex and ethnicity, were found to be unrelated to training outcome in this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":24593745,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A set of 4D pediatric XCAT reference phantoms for multimodality research.\nThe authors previously developed an adult population of 4D extended cardiac-torso (XCAT) phantoms for multimodality imaging research. In this work, the authors develop a reference set of 4D pediatric XCAT phantoms consisting of male and female anatomies at ages of newborn, 1, 5, 10, and 15 years. These models will serve as the foundation from which the authors will create a vast population of pediatric phantoms for optimizing pediatric CT imaging protocols. Each phantom was based on a unique set of CT data from a normal patient obtained from the Duke University database. The datasets were selected to best match the reference values for height and weight for the different ages and genders according to ICRP Publication 89. The major organs and structures were segmented from the CT data and used to create an initial pediatric model defined using nonuniform rational B-spline surfaces. The CT data covered the entire torso and part of the head. To complete the body, the authors manually added on the top of the head and the arms and legs using scaled versions of the XCAT adult models or additional models created from cadaver data. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from a template XCAT phantom (male or female 50th percentile adult) to the target pediatric model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. The masses of the organs in each phantom were matched to the reference values given in ICRP Publication 89. The new reference models were checked for anatomical accuracy via visual inspection. The authors created a set of ten pediatric reference phantoms that have the same level of detail and functionality as the original XCAT phantom adults. Each consists of thousands of anatomical structures and includes parameterized models for the cardiac and respiratory motions. Based on patient data, the phantoms capture the anatomic variations of childhood, such as the development of bone in the skull, pelvis, and long bones, and the growth of the vertebrae and organs. The phantoms can be combined with existing simulation packages to generate realistic pediatric imaging data from different modalities. The development of patient-derived pediatric computational phantoms is useful in providing variable anatomies for simulation. Future work will expand this ten-phantom base to a host of pediatric phantoms representative of the public at large. This can provide a means to evaluate and improve pediatric imaging devices and to optimize CT protocols in terms of image quality and radiation dose.","subset":"pubmed_abstract"} +{"meta":{"pmid":24763467,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy.\nAutonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia and atrial fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review, we focus on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches, and biological therapies. Although the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":35700979,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Acceleration and deceleration demands during training sessions in football: a systematic review.\nThe aim of this review is to summarize the current scientific knowledge about acceleration and deceleration demands during football training. A systematic search of three electronic databases (PubMed, SPORTDiscus, Web of Science) was performed to identify peer-reviewed relevant English-language articles, following PRISMA guidelines. All acceleration and deceleration data were analyzed and organized into four categories: i) training drills variables (i.e. manipulated drills variables such as number of players in small-sided games), ii) training exercises (i.e. different drills such small games or circuit training), iii) players' positions (i.e. demands for each playing position) and iv) training schedule (i.e. training sessions presented as microcycles, season sections or full season). Full-text articles of 42 studies were included in the final analysis. Players' level included: amateur, youth, semi-professional, professional and elite players. All playing positions were considered, including goalkeepers. Six different global position systems brands were used, with the majority measuring data at 10 Hz. Different thresholds and intensities were used in several papers. Lower acceleration and deceleration intensities occurred more often than higher intensities in all four categories. Different exercises elicit different demands and small-sided games presented higher acceleration and deceleration demands than circuit training and other running based drills. Furthermore, manipulating drills variables, as reducing or increasing number of players in small-sided games increase or decrease demands, respectively. Additionally, wide playing positions, such as fullbacks, are generally exposed to higher acceleration and deceleration demands. From a planning point of view, acceleration and deceleration demands decrease as match day approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":23446769,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters.\nMulticenter randomized controlled trial. To compare the efficacy and safety of balloon kyphoplasty (BKP) with nonsurgical management (NSM) during 24 months in patients with painful vertebral compression fractures (VCFs). Recently, several large randomized controlled trials have been conducted and reported how vertebral augmentation compares with NSM for patients with acute VCFs. Few of these trials report on the surgical aspects and radiographical vertebral deformity results. Adults with 1 to 3 VCFs were randomized within 3 months of pain to undergo bilateral BKP (n = 149) or NSM (n = 151). Surgical parameters, subjective quality of life assessments and objective functional (timed up and go) and radiographical assessments were collected. Compared with NSM, the BKP group had greater improvements in SF-36 physical component summary (PCS) scores at 1 month (5.35 points; 95% CI, 3.41-7.30; P < 0.0001) and when averaged across the 24 months (overall treatment effect 2.71 points; 95% CI, 1.34-4.09; P = 0.0001). The kyphoplasty group also had greater functionality by assessing timed up and go (overall treatment effect -2.49 s; 95% CI, -0.82 to -4.15; P = 0.0036). At 24 months, the change in index fracture kyphotic angulation was statistically significantly improved in the kyphoplasty group (average 3.13\u00b0 of correction for kyphoplasty compared with 0.82\u00b0 in the control, P = 0.003). Number of baseline prevalent fractures (P = 0.0003) and treatment assignment (P = 0.004) are the most predictive variables for PCS improvement; however, in patients who underwent BKP, there may also be a link with kyphotic angulation. In BKP, the highest quart for kyphotic angulation correction had higher PCS improvement (13.4 points) than the quart having lowest correction of angulation (7.40 points, P = 0.0146 for difference). The most common adverse events temporally related to surgery (i.e., within 30 d) were back pain (20 BKP, 11 NSM) new VCF (11 BKP, 7 NSM), nausea\/vomiting (12 BKP, 4 NSM), and urinary tract infection (10 BKP, 3 NSM). Several other adverse events were possibly related to patient positioning in the operating room. Compared with NSM, BKP improves patient quality of life and pain averaged during 24 months and results in better improvement of index vertebral body kyphotic angulation. Perioperative complications may be reduced with more care in patient positioning. 2.","subset":"pubmed_abstract"} +{"meta":{"pmid":9822948,"dup_signals":{"dup_doc_count":40,"dup_dump_count":34,"dup_details":{"curated_sources":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-24":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":2,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2023-14":1}}},"text":"The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers.\nTo examine the hypothesis that a sustained rise in plasma acylation stimulating protein (ASP, C3a desarg) accompanies the elevation in triacylglycerol that follows the ingestion of an oral fat load. Following an overnight fast, blood samples were obtained from healthy volunteers while fasting and 15 min, 1, 2, 4, 6 and 8 h following ingestion of: (i) a liquid meal, rich in dairy fat (eight subjects) and (ii) a semi-liquid meal, with higher total fat content and rich in polyunsaturated fat (six subjects). Four male and four female volunteers (age range: 22-51 y; body mass index (BMI): 17.9-26.9 kg\/m2) received the first meal. Six subjects (age range: 32-60 y; BMI: 18.0-28.4 kg\/m2), including three from the first study, received the second meal using the same protocol. ASP and C5a were measured by radioimmunoassay (RIA) and the complement proteins C3, factor B and C5 by radial immunodiffusion or nephelometry. Tumour necrosis factor (TNF)-alpha was measured by enhanced ELISA, and plasma cholesterol and triacylglycerol by an automated enzymatic method. The presence of chylomicrons was assessed in post-prandial plasma samples taken after the second meal. There was no significant change in mean ASP concentration in either group at any time point, following ingestion of either meal. However, there was a significant positive linear trend in ASP following the second fat challenge (ANOVA; P < 0.05). There was also no change in complement proteins, plasma cholesterol or TNF-alpha. Plasma triacylglycerol rose significantly after the first and second meals (P < 0.05 and P < 0.001 at 2 h post-prandially); the mean maximum rise above the fasting level was 58 +\/- 41% and 89 +\/- 38% respectively (mean +\/- s.d.). Chylomicrons were detected in samples taken from each subject after the second meal. Analysis of individual ASP data showed a sustained rise in one subject after the first meal and two subjects after the second meal. Substantial variation in ASP concentration was observed in samples taken in the first 2 h post-prandially. There was no significant change in ASP nor other complement proteins for either group of subjects following ingestion of the lipid loads. Individual data showed substantial variation in post-prandial ASP, but multiple plasma sampling did not define the basis for this variation.","subset":"pubmed_abstract"} +{"meta":{"pmid":2522881,"dup_signals":{"dup_doc_count":45,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":4,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":3,"2022-05":3,"2021-39":3,"2021-31":1,"2021-25":1,"2021-21":3,"2021-17":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":2,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-30":4,"2024-26":1,"2024-10":2}}},"text":"The improved lytic function and in vivo efficacy of monovalent monoclonal CD3 antibodies.\nA series of hybrid-hybridomas were derived by the cell fusion of a CD3 antibody-secreting hybridoma with other Ig-producing cell lines. The Ig molecules secreted by these hybrid-hybridomas were fractionated by ion-exchange chromatography, and fractions containing monovalent CD3 antibodies were tested for complement-mediated lysis of T cells. Two monovalent CD3 antibodies with mixed heavy chain isotypes were very poor in lysis but, in contrast, a monovalent antibody possessing two identical rat gamma 2b heavy chains but two non-identical light chains was found to be more lytic with human complement than the parental bivalent CD3 antibody. The difference in lysis was not readily explicable in terms of a difference in complement activation at the level of C1q binding or cell-associated C3. A highly purified batch of this lytic monovalent CD3 antibody was prepared in a form suitable for in vivo therapy. In a preliminary clinical study in one patient with a T lymphoma in leukemic phase this monovalent CD3 antibody was found to be very effective in depleting CD3+ tumor cells in the peripheral blood and bone marrow. The cells in the peripheral blood were completely cleared and there was no evidence for antigenic modulation. In addition the antibody was able to reverse cell-mediated kidney rejection in three kidney graft patients. These results suggest that monovalent antibody may be effective in vivo as well as in vitro and that a fuller clinical evaluation is justified.","subset":"pubmed_abstract"} +{"meta":{"pmid":19958855,"dup_signals":{"dup_doc_count":46,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-06":1,"2022-33":1,"2022-05":1,"2021-25":1,"2021-17":1,"2021-10":1,"2017-43":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":2,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2023-40":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-18":1}}},"text":"Rationale and design of the Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT): randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation.\nDrug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis. PROTECT is a randomized, open-label trial comparing the long-term safety of the zotarolimus-eluting stent and the sirolimus-eluting stent. The trial has enrolled 8,800 patients representative of those seen in routine clinical practice, undergoing elective, unplanned, or emergency procedures in native coronary arteries in 196 centers in 36 countries. Indications for the procedure and selection of target vessel and lesion characteristics were at the operator's discretion. Procedures could be staged, but no more than 4 target lesions could be treated per patient. Duration of dual antiplatelet therapy was prespecified to achieve similar lengths of treatment in both study arms. The shortest predefined duration was 3 months, as per the manufacturer's instructions. The primary outcome measure is the composite rate of definite and probable stent thrombosis at 3 years, centrally adjudicated using Academic Research Consortium definitions. The main secondary end points are 3-year all-cause mortality, cardiac death, large nonfatal myocardial infarction, and all myocardial infarctions. This large, international, randomized, controlled trial will provide important information on comparative rates of stent thrombosis between 2 different DES systems and safety as assessed by patient-relevant long-term clinical outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":28274335,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"Continuity of medication management in Medicaid patients with chronic comorbid conditions: An examination by mental health status.\nPatients with serious mental illness (SMI) often have comorbid cardiometabolic conditions (CMCs) that may increase the number of prescribers involved in treatment. This study examined whether patients with SMI (depression and schizophrenia) and comorbid CMCs experience greater discontinuity of prescribing than patients with CMCs alone. 2009 Medicaid data were used to compare number and types of prescribers (primary care, cardiometabolic, psychiatric, other) in individuals with 1-3 CMCs (diabetes, hypertension, dyslipidemia) alone (n=76.451); with CMC and schizophrenia (n=6507); and with CMC and depression (n=23.510) and the degree of prescribing within a provider's area of specialty. 44%, 61%, and 71% of individuals with CMCs only, with CMCs and schizophrenia, and with CMCs and depression had medications from these classes prescribed by 5 or more providers respectively. >35% of patients with CMCs alone or CMCs and schizophrenia had prescriptions provided by 3 or more PCP providers, which increased to 49.1% for patients with CMCs and depression. In the schizophrenia cohort, 29% of antipsychotics were PCP-prescribed while psychiatrists prescribed 10%, 9%, and 9% of antihypertensive, antihyperlipidemic, and antidiabetic medications respectively. The presence of SMI increases the number of prescribers treating individuals with CMCs. The impact of this fragmentation in medication management on health outcomes is unknown.","subset":"pubmed_abstract"} +{"meta":{"pmid":33804189,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Metabolism in the Zebrafish Retina.\nRetinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":19912626,"dup_signals":{"dup_doc_count":14}},"text":"Expectations, perceptions, and physiotherapy predict prolonged sick leave in subacute low back pain.\nBrief intervention programs for subacute low back pain (LBP) result in significant reduction of sick leave compared to treatment as usual. Although effective, a substantial proportion of the patients do not return to work. This study investigates predictors of return to work in LBP patients participating in a randomized controlled trial comparing a brief intervention program (BI) with BI and physical exercise. Predictors for not returning to work was examined in 246 patients sick listed 8-12 weeks for low back pain. The patients had participated in a randomized controlled trial, with BI (n = 122) and BI + physical exercise (n = 124). There were no significant differences between the two intervention groups on return to work. The groups were therefore merged in the analyses of predictors. Multiple logistic regression analysis was used to identify predictors for non return to work at 3, 12, and 24 months of follow-up. At 3 months of follow-up, the strongest predictors for not returning to work were pain intensity while resting (OR = 5.6; CI = 1.7-19), the perception of constant back strain when working (OR = 4.1; CI = 1.5-12), negative expectations for return to work (OR = 4.2; CI = 1.7-10), and having been to a physiotherapist prior to participation in the trial (OR = 3.3; CI = 1.3-8.3). At 12 months, perceived reduced ability to walk far due to the complaints (OR = 2.6; CI = 1.3-5.4), pain during activities (OR = 2.4; CI = 1.1-5.1), and having been to a physiotherapist prior to participation in the trial (OR = 2.1; CI = 1.1-4.3) were the strongest predictors for non return to work. At 24 months age below 41 years (OR = 2.9; CI = 1.4-6.0) was the only significant predictor for non return to work. It appears that return to work is highly dependant on individual and cognitive factors. Patients not returning to work after the interventions were characterized by negative expectations, perceptions about pain and disability, and previous physiotherapy treatment. This is the first study reporting that previous treatment by physiotherapists is a risk factor for long-term sick leave. This has not been reported before and is an interesting finding that deserves more scrutiny.","subset":"pubmed_abstract"} +{"meta":{"pmid":27632669,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Vitamin D Deficiency in Human and Murine Sepsis.\nVitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis. Sixty-one patients with sepsis and severe sepsis from two large U.K. hospitals and 20 healthy controls were recruited. Murine models of cecal ligation and puncture and intratracheal lipopolysaccharide were undertaken in normal and vitamin D deficient mice to address the issue of causality. Patients with severe sepsis had significantly lower concentrations of 25-hydroxyvitamin D3 than patients with either mild sepsis or age-matched healthy controls (15.7 vs 49.5 vs 66.5 nmol\/L; p = 0.0001). 25-hydroxyvitamin D3 concentrations were significantly lower in patients who had positive microbiologic culture than those who were culture negative (p = 0.0023) as well as those who died within 30 days of hospital admission (p = 0.025). Vitamin D deficiency in murine sepsis was associated with increased peritoneal (p = 0.037), systemic (p = 0.019), and bronchoalveolar lavage (p = 0.011) quantitative bacterial culture. This was associated with reduced local expression of the cathelicidin-related antimicrobial peptide as well as evidence of defective macrophage phagocytosis (p = 0.029). In the intratracheal lipopolysaccharide model, 1,500 IU of intraperitoneal cholecalciferol treatment 6 hours postinjury reduced alveolar inflammation, cellular damage, and hypoxia. Vitamin D deficiency is common in severe sepsis. This appears to contribute to the development of the condition in clinically relevant murine models and approaches to correct vitamin D deficiency in patients with sepsis should be developed.","subset":"pubmed_abstract"} +{"meta":{"pmid":1752423,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":3,"2021-04":1,"2020-10":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":1,"2019-35":1,"2018-26":1,"2017-47":1,"2017-26":1,"2021-31":1}}},"text":"Two genetically and molecularly distinct functions involved in early neurogenesis reside within the Enhancer of split locus of Drosophila melanogaster.\nMolecular correlation of the genetic aspects of the function of the neurogenic gene Enhancer of split [E(spl)] has previously been hampered by the densely transcribed nature of the chromosomal region within which it resides. We present data indicating that two distinct molecular species contribute to E(spl) function. Analysis of new E(spl) alleles has allowed us to define two complementing functions within the locus. Subsequent phenotypic analysis of different E(spl) deficiencies combined with P element-transformed constructs has demonstrated that these two functions correspond to: (1) a family of helix-loop-helix (HLH) protein-encoding genes and (2) the single copy gene E(spl) m9\/10, whose product shares homology with G-protein beta subunits. The zygotically active E(spl) HLH genes can, at least partially, substitute for one another's functions and their total copy number determines the activity of the locus. E(spl) m9\/10 acts synergistically with the E(spl) HLH genes and other neurogenic genes in the process of neurogenesis. The maternal component of E(spl) m9\/10 has the most pronounced effect in neurogenesis, while its zygotic component is predominantly required during postembryonic development. The lethality of trans-heterozygotes of null E(spl) deficiency alleles with a strong Delta point mutation is a result of the concomitant reduction in activity of both E(spl) HLH and m9\/10 functions. Immunocytochemical localization of the E(spl) m9\/10 protein has revealed that it is a ubiquitously distributed nuclear component in embryonic, larval and imaginal tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":8241054,"dup_signals":{"dup_doc_count":43,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2023-50":2,"2023-40":1,"2023-23":5,"2023-14":3,"2023-06":1,"2022-49":3,"2022-27":2,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-17":3,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":2,"2024-22":2,"2024-18":4,"2024-10":1,"2024-30":1}}},"text":"ER-MP12 antigen, a new cell surface marker on mouse bone marrow cells with thymus-repopulating ability: II. Thymus-homing ability and phenotypic characterization of ER-MP12-positive bone marrow cells.\nIn the accompanying paper we showed that six distinct subsets of bone marrow (BM) cells can be identified using the mAb ER-MP12 and ER-MP20 in two-colour immunofluorescence analysis. Upon intrathymic transfer into sublethally irradiated mice thymus-repopulating ability was restricted to ER-MP20- BM cells expressing either high or intermediate levels of the ER-MP12 antigen (1-2% and approximately 30% of BM nucleated cells respectively). The highest frequency of thymus-repopulating cells was found in the minor subset of ER-MP12(+)+20- BM cells. In the present study we demonstrate that upon intravenous transfer, thymus-homing and -repopulating BM cells are exclusively confined to the ER-MP12(+)+20- and ER-MP12+20- subpopulations, the highest frequency being detected among ER-MP12(+)+20- BM cells. Analysis of the peripheral blood leucocytes of reconstituted mice showed that not only prothymocytes but also progenitor cells of the B cell lineage as well as the myeloid lineage were present within both subsets. Three-colour flow cytometric analysis revealed that ER-MP12(+)+20- BM cells in particular were phenotypically heterogeneous with respect to the expression of the cell surface markers Thy-1, Sca-1, CD44, B220 and c-kit. Taken together our data demonstrate that ER-MP12 positively identifies BM cells with the ability to home to and repopulate the thymus. The phenotypic heterogeneity displayed by the ER-MP12(+)+20- BM subset, containing the highest frequency of thymus-homing and -repopulating cells, provides a basis for further separation of prothymocyte activity from other haematopoietic activities in the BM of the mouse.","subset":"pubmed_abstract"} +{"meta":{"pmid":19082142,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Inferring Boolean networks with perturbation from sparse gene expression data: a general model applied to the interferon regulatory network.\nDue to the large number of variables required and the limited number of independent experiments, the inference of genetic regulatory networks from gene expression data is a challenge of long standing within the microarray field. This report investigates the inference of Boolean networks with perturbation (BNp) from simulated data and observed microarray data. We interpret the discrete expression levels as attractor states of the underlying network and use the sequence of attractor states to determine the model. We consider the case where a complete sequence of attractors is known and the case where the known attractor states are arrived at by sampling from an underlying sequence of attractors. In the former case, a BNp can be inferred trivially, for an arbitrary number of genes and attractors. In the latter case, we use the constraints posed by the distribution of attractor states and the need to conserve probability to arrive at one of three possible solutions: an unique, exact network; several exact networks or a 'most-likely' network. In the case of several exact networks we use a robustness requirement to select a preferred network. In the case that an exact option is not found, we select the network that best fits the observed attractor distribution. We apply the resulting algorithm to the interferon regulatory network using expression data taken from murine bone-derived macrophage cells infected with cytomegalovirus.","subset":"pubmed_abstract"} +{"meta":{"pmid":28152212,"dup_signals":{"dup_doc_count":21,"dup_dump_count":10,"dup_details":{"curated_sources":3,"2023-50":2,"2023-23":2,"2023-06":2,"2022-40":2,"2022-21":2,"2021-43":2,"2021-31":2,"2021-17":2,"2021-04":1,"2024-22":1}}},"text":"Indian nurses in Italy: a qualitative study of their professional and social integration.\nTo investigate the lived subjective experiences of immigrant Indian nurses in Italy and specifically their professional and social integration. To study the worldwide, nursing flux is a health priority in the globalised world. The growth in migration trends among nurses, not only from Philippines or India, has proliferated in recent years. The research on nurses' mobility for Southern European countries is underexplored, and in Italy, the out-migration flows of Indian nurses were never analysed. Qualitative methodological approach. Semi-structured interviews (n = 20) were completed with Indian clinical nurses working in Italy for more than one year mainly in private organisations. A purposive sampling technique was used for recruitment. The data were then content-analysed using an inductive method. The findings were categorised into four themes: (1) aspects of professional integration and working experience, (2) intra- and interprofessional relationships and perceptions of the IPASVI Regulatory Nursing Board, (3) initial nursing education and continuous professional development and (4) perceptions of social integration. The results show that for Indian nurses in Italy emigration is important to gain opportunities to expand economic and social privileges as well as escape from historical assumptions of stigma associated with nursing work, especially for women. However, these conclusions have to be seen in wider socio-cultural complexities that are at the basis of transnational fluxes (Prescott & Nichter ). The research offers an insight into the complicated reasons for Indian nurses out-migration to Italy. Without comprehending the interwoven textures of the political and social relations that are continually constructed and re-constructed among different nations, it is difficult to understand nurses out-migration and consequently have a better and safer collaborative teamwork in the host countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":24787858,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2015-18":1,"unknown":10}}},"text":"Characterization and control of peak intensity distribution at the focus of a spatiotemporally focused femtosecond laser beam.\nWe report on experimental examination of two-photon fluorescence excitation (TPFE) at the focus of a spatially chirped femtosecond laser beam, which reveals an unexpected tilted peak intensity distribution in the focal spot. Our theoretical calculation shows that the tilting of the peak intensity distribution originates from the fact that along the optical axis of objective lens, the spatiotemporally focused pulse reaches its shortest duration exactly at the focal plane. However, when moving away from the optical axis along the direction of spatial chirp of the incident pulse, the pulse reaches its shortest duration either before or after the focal plane, depending on whether the pulse duration is measured above or below the optical axis as well as the sign of the spatial chirp. The tilting of the peak intensity distribution in the focal spot of the spatiotemporally focused femtosecond laser beam can play important roles in applications such as femtosecond laser micromachining and bio-imaging.","subset":"pubmed_abstract"} +{"meta":{"pmid":8162381,"dup_signals":{"dup_doc_count":38,"dup_dump_count":26,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-27":2,"2022-21":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-10":2,"2020-50":2,"2020-40":1,"2018-43":1,"2018-30":2,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":1,"2017-43":2,"2017-34":2,"2024-30":2,"2024-26":2,"2024-22":1,"2024-10":1}}},"text":"The development of a questionnaire to assess knowledge of epilepsy: 1--General knowledge of epilepsy.\nIt is well documented that knowledge is a vital factor in the ability to cope successfully with epilepsy. Misconceptions and deficits in knowledge have implications not only for psychosocial well-being but also for medical compliance. However, at present there is no commonly accepted objective measure of knowledge of epilepsy. The development of the Epilepsy Knowledge Profile--General (E.K.P.--G) is presented in this paper. Fifty-five true\/false items (34 medical knowledge items, 21 social knowledge items) were selected by a range of experts in the field of epilepsy. A clinical trial of the questionnaire was then completed by 82 people with epilepsy attending a city centre outpatient clinic. Results indicated that the scale has both good internal reliability and test-retest reliability. Also the range of scores indicates that it is sensitive to differences in knowledge. Potential uses of the questionnaire are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":23971575,"dup_signals":{"dup_doc_count":17,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":2,"2018-26":1}}},"text":"Nonequilibrium chaos of disordered nonlinear waves.\nDo nonlinear waves destroy Anderson localization? Computational and experimental studies yield subdiffusive nonequilibrium wave packet spreading. Chaotic dynamics and phase decoherence assumptions are used for explaining the data. We perform a quantitative analysis of the nonequilibrium chaos assumption and compute the time dependence of main chaos indicators--Lyapunov exponents and deviation vector distributions. We find a slowing down of chaotic dynamics, which does not cross over into regular dynamics up to the largest observed time scales, still being fast enough to allow for a thermalization of the spreading wave packet. Strongly localized chaotic spots meander through the system as time evolves. Our findings confirm for the first time that nonequilibrium chaos and phase decoherence persist, fueling the prediction of a complete delocalization.","subset":"pubmed_abstract"} +{"meta":{"pmid":2079184,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"[Syncope caused by paroxysmal atrial fibrillation and flutter: diagnostic usefulness of electrophysiological studies in the erect and supine positions].\nIn this study, we verified if the induction of atrial fibrillation\/flutter, during the electrophysiological study, could be useful for the evaluation of syncope of unknown origin. Of 292 patients who underwent an electrophysiological study for unexplained symptoms, we selected 15 patients (5.1%) affected by syncope and pre-syncope. In these, the induction of atrial fibrillation (14 patients) or flutter (1 patient) just at the onset caused, the reproduction of the spontaneous symptoms. No other cause could be identified. These patients were affected by: 1) syncope or pre-syncope without electrocardiographic documentation of paroxysmal atrial fibrillation\/flutter 2) syncope or presyncope and documented asymptomatic episodes of paroxysmal atrial fibrillation\/flutter. Palpitations closely preceded or followed the syncope in 11\/15 patients. Symptom reproduction was obtained in the supine position in 3 patients (heart rate 180 +\/- 82 beat\/min, systolic blood pressure 53 +\/- 6 mmHg) and in the upright position in 12 patients (heart rate 177 +\/- 24, systolic blood pressure 65 +\/- 18 mmHg). The arrhythmia was induced by incremental atrial pacing or premature atrial beats in 3 cases, ramp in 3 cases and burst--mean rate 339 +\/- 48 beat\/min--in 9 cases. The arrhythmia lasted for a period of time ranging from a minimum of 1 mm to a maximum of 24 hours (median 1 hour). During sinus rhythm, an abnormal vasodepressor reflex (with a systolic blood pressure fall greater than or equal to 50 mmHg) could be induced in 7\/9 patients by carotid sinus massage or 60 degrees tilt test.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":25886062,"dup_signals":{"dup_doc_count":22}},"text":"Child survival and BCG vaccination: a community based prospective cohort study in Uganda.\nData on non-specific effects of BCG vaccination in well described, general population African cohorts is scanty. We report the effects of BCG vaccination on post-neonatal infant and post-infancy mortality in a cohort of children in Mbale, Eastern Uganda. A community-based prospective cohort study was conducted between January 2006 and February 2014. A total of 819 eligible pregnant women were followed up for pregnancy outcomes and survival of their children up to 5 years of age. Data on the children's BCG vaccination status was collected from child health cards at multiple visits between 3 weeks and 7 years of age. Data was also collected on mothers' residence, age, parity, household income, self-reported HIV status as well as place of birth. Multivariable Cox proportional hazards regression models taking into account potential confounders were used to estimate the association between BCG vaccination and child survival. The neonatal mortality risk was 22 (95% CI: 13, 35), post-neonatal infant mortality 21 (12, 34) per 1,000 live births and the mortality risk among children between 1 and 5 years of age (post-infancy) was 63 (47, 82) per 1,000 live births. The median age at BCG vaccination was 4 days. Out of 819 children, 647 (79%) had received the BCG vaccine by 24 weeks of age. In the adjusted analysis, the rate of post-neonatal death among infants vaccinated with BCG tended to be nearly half of that among those who had not received the vaccine (adjusted HR: 0.47; 95% CI: 0.14, 1.53). BCG vaccination was associated with a lower rate of death among children between 1 and 5 years of age (adjusted HR: 0.26; 95% CI: 0.14, 0.48). The risk of early childhood death in Mbale, Uganda is unacceptably high. BCG vaccination was associated with an increased likelihood of child survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":21904781,"dup_signals":{"dup_doc_count":13}},"text":"Impact of remifentanil introduction on practice patterns in general anesthesia.\nThe introduction of new medicine can change clinical practice patterns and may affect patient outcomes. In the present study, we investigated whether introduction of remifentanil in Japan affected the practice patterns of anesthesia. Using the Japanese Diagnosis Procedure Combination database, we extracted records of 423,491 patients who underwent surgery with general anesthesia in 243 hospitals before (2006) and after (2007) the introduction of remifentanil, and identified anesthetic agents used for each patient. A hierarchical mixed-effects logistic regression analysis was performed to analyze the factors that affected selection of remifentanil. Further, we compared postoperative length of stay (LOS), in-hospital mortality, and total costs between 2006 and 2007. In 2007, remifentanil was used for up to 41.4% of all general anesthesia, accompanied by a reduction in nitrous oxide use and an increase in total intravenous anesthesia. Female gender, increasing age, and preoperative comorbidities including diabetes mellitus, hypertension, liver cirrhosis, and chronic renal failure were positively associated with the use of remifentanil, whereas accompanying cardiac disease and co-application of epidural anesthesia were negatively associated. In 2007, a similar in-hospital death rate, similar or decreased total costs, slightly reduced duration of anesthesia, and substantially reduced postoperative LOS were seen compared to those in 2006. Our data revealed rapid changes in practice patterns in anesthesia after the introduction of remifentanil in Japan. Remifentanil was used more often in patients with comorbidities and without epidural anesthesia, and its introduction did not affect increase in total medical costs.","subset":"pubmed_abstract"} +{"meta":{"pmid":20218143,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"House-to-house survey of disabilities in rural communities in the north of the West Bank.\nTo identify the prevalence of disability and characteristics, conditions and needs of those with disabilities in rural communities in the north of the West Bank, 10 147 families were screened in a cross-sectional survey. Prevalence was 1.7% (806 persons with disabilities). Physical (34.0%), mental (15.9%) and speech (11.4%) disabilities were the commonest. The major cause as perceived by the families was heredity (30.5%): parental consanguinity was 50.8%. Economic conditions were the major problem for 41.1%, and the main barrier to receiving care: only 49.3% were receiving some kind of care. Integration in educational, work and social activities was low. Pressing needs included medical care, support equipment, and educational, physiotherapy and rehabilitation services.","subset":"pubmed_abstract"} +{"meta":{"pmid":3511091,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Regulation of C-myc expression during growth and differentiation of normal and leukemic human myeloid progenitor cells.\nC-myc proto-oncogene transcripts from serially harvested, colony-stimulating activity (CSA)-stimulated, normal progenitor-enriched human bone marrow cells were compared to those of the promyelocytic leukemia cell line HL-60 and to those of freshly obtained human myeloid leukemic cells. During the early culture period both normal and leukemic cells expressed the c-myc oncogene. In normal cells maximal expression occurred after 24 h of culture and did not occur in the absence of CSA. At this time, progranulocytes predominated in the cultured cells. Although cellular proliferation occurred for 96 h in vitro, c-myc expression ceased after 24-36 h. Terminally differentiated cells predominated in these cultures by 120 h. In contrast, although leukemic cells also expressed c-myc in vitro, transcription persisted throughout the culture period and, in the case of HL-60 cells, occurred in the absence of exogenous CSA. We also noted that normal cells with only one diploid gene copy exhibited, after 24 h of culture, only twofold fewer transcripts than did HL-60 cells in which there were 16 myc copies. Furthermore, c-myc mRNA degradation rates were similar in normal cells and in HL-60 cells. We conclude that c-myc transcription is a normal event in granulopoiesis linked to proliferative activity as well as to primitive developmental stage. Furthermore, the most consistent abnormality in leukemic cells in vitro is their failure to suppress transcriptional activity of this gene. We suggest that c-myc transcription in HL-60 cells may be appropriate for cells arrested at that developmental stage and that the amplified genes in HL-60 cells are quiescent relative to c-myc in normal cells at the same differentiation stage. The techniques described herein may be of value in identifying mechanisms by which normal hematopoietic cells suppress c-myc expression and aberrancies of these mechanisms in leukemic cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":19493435,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2014-10":1,"unknown":9}}},"text":"Predictive value of RIFLE classification on prognosis of critically ill patients with acute kidney injury treated with continuous renal replacement therapy.\nThe optimal timing to start continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) patients has not been accurately established. The recently proposed risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria for diagnosis and classification of AKI may provide a method for clinicians to decide the \"optimal timing\" for starting CRRT under uniform guidelines. The present study aimed: (1) to analyze the correlation between RIFLE stage at the start of CRRT and 90-day survival rate after CRRT start, (2) to further investigate the correlation of RIFLE stage with the malignant kidney outcome in the 90-day survivors, and (3) to determine the influence of the timing of CRRT defined by RIFLE classification on the 90-day survival and malignant kidney outcome in 90-day survivors. A retrospective cohort analysis was performed on the data of 106 critically ill patients with AKI, treated with CRRT during a 6-year period in a university affiliated surgical intensive care unit (SICU). Information such as sex, age, RIFLE stage, sepsis, sepsis-related organ failure assessment (SOFA) score, number of organ failures before CRRT, CRRT time during SICU, survival, and kidney outcome conditions at 90 days after CRRT start was collected. According to their baseline severity of AKI at the start of CRRT, the patients were assigned to three groups according to the increasing severity of RIFLE stages: RIFLE-R (risk of renal dysfunction, R), RIFLE-I (injury to the kidney, I) and RIFLE-F (failure of kidney function, F) using RIFLE criteria. The malignant kidney outcome was classified as RIFLE-L (loss of kidney function, L) or RIFLE-E (end-stage kidney disease, E) using RIFLE criteria. The correlation between RIFLE stage and 90-day survival rate was analyzed among these three RIFLE-categorized groups. Additionally, the association between RIFLE stage and the malignant kidney outcome (RIFLE-L + RIFLF-E) in the 90-day survivors was analyzed. Fifty-three of the overall 106 patients survived to 90 days after the start of CRRT. There were 16, 22 and 68 patients in RIFLE-R, RIFLE-I and RIFLE-F groups respectively with corresponding 90-day survival rate of 75.0% (12\/16), 63.6% (14\/22) and 39.7% (27\/68) (P < 0.01, compared among groups). The percentage of the malignant kidney outcome of 90-day survivors in the RIFLE-R, RIFLE-I, and RIFLE-F groups was 16.7% (2\/12), 21.4% (3\/14) and 55.6% (15\/27), respectively (P for trend < 0.01). After adjustment for other baseline risk factors, the relative risk (RR) for the 90-day mortality significantly increased with baseline RIFLE stage. Patients in RIFLE-F had a higher RR of 1.96 (95% confidence interval (CI): 1.06 - 3.62) than patients in RIFLE-I (RR: 1.09, 95% CI: 0.55 - 2.15) compared with patients in RIFLE-R (P for trend < 0.01). Similarly, baseline RIFLE stage also significantly correlated with the odds ratio (OR) for the malignant kidney outcome in 90-day survivors (P for trend < 0.05). Ninety-day survivors in the RIFLE-F group had a borderline significantly highest OR of 6.88 (95% CI: 0.85 - 55.67). The RIFLE classification may be used to predict 90-day survival after starting CRRT and the malignant kidney outcome of 90-day survivors in the critically ill patients with AKI treated with CRRT. Starting CRRT prior to RIFLE-F stage may be the optimal timing. Prospective, multi-center, randomized controlled trials are needed to confirm its predictive value in these patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":7271989,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":16}}},"text":"The normal organization of the lateral posterior nucleus in the golden hamster and its reorganization after neonatal superior colliculus lesions.\nWe have studied the normal organization of the hamster lateral posterior nucleus and its reorganization after neonatal superior colliculus lesions. First, we divided the lateral posterior nucleus into rostrolateral, rostromedial and caudal subdivisions and determined the normal distributions of terminals contributed to each division by the ipsilateral and contralateral superior colliculi, the ipsilateral posterior neocortex and the contralateral retina. Since the rostrolateral subdivision receives most of the projections from the ipsilateral superior colliculus, our studies concentrated on this region. The rostrolateral subdivision contains synaptic clusters formed primarily by medium-sized M-terminals synapsing around a central dendrite. Electron microscopic observations showed that the majority of M-terminals are from the ipsilateral colliculus, although a few are contributed by the contralateral colliculus and retina. Therefore, after an ipsilateral neonatal colliculus lesion the synaptic clusters must develop in the absence of their major input. The next step was to examine the distributions of the remaining afferents to the rostrolateral subdivision in adult animals which had received ipsilateral neonatal colliculus lesions. In the cases, the normally restricted projection fields of the contralateral colliculus and the retina expand until they share a border in the rostrolateral subdivision. In contrast the cortical projection, which normally extends throughout the lateral posterior nucleus, is reduced in the region containing retinal terminals. At the ultrastructural level, we found morphologically normal synaptic clusters and showed the M-terminals now occupying the clusters are contributed by the remaining colliculus and the retina. The results suggested that the afferents to the lateral posterior nucleus normally compete for synaptic space and that this competition continues after a neonatal colliculus lesion. In our final experiments, we performed various combinations of neonatal lesions (bilateral superior colliculus, superior colliculus and retina, superior colliculus and cortex) and found that the remaining afferent expand their terminal fields still further in the absence of two inputs.","subset":"pubmed_abstract"} +{"meta":{"pmid":8719737,"dup_signals":{"dup_doc_count":22,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2020-34":2,"2019-26":1,"2019-13":1,"2019-04":2,"2018-34":1,"2018-30":2,"2018-26":1,"2018-17":1,"2018-13":2,"2017-47":3,"2017-39":3,"2017-34":1,"2021-04":1}}},"text":"Digestibility of dietary fiber components in vegetarian men.\nDigestibility of fiber components namely neutral detergent fiber (total content of cellwall) cellulose, hemicellulose and lignin are estimated in 14 healthy vegetarian men during adlibitum feeding and at 3 energy levels namely 2526, 2868 and 3290 kcals\/day. Values of digestibility for adlibitum experiments were 34.17 +\/- 2.3 for neutral detergent fiber (NDF), 30.1 +\/- 3.9 for cellulose and 53.4 +\/- 3.0 for hemicellulose and 8.1 +\/- 2.6 for lignin. There was a considerable variability in digestibility of fiber components between individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":8534918,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Functional expression of a vertebrate inwardly rectifying K+ channel in yeast.\nWe describe the expression of gpIRK1, an inwardly rectifying K+ channel obtained from guinea pig cardiac cDNA. gpIRK1 is a homologue of the mouse IRK1 channel identified in macrophage cells. Expression of gpIRK1 in Xenopus oocytes produces inwardly rectifying K+ current, similar to the cardiac inward rectifier current IK1. This current is blocked by external Ba2+ and Cs+. Plasmids containing the gpIRK1 coding region under the transcriptional control of constitutive (PGK) or inducible (GAL) promoters were constructed for expression in Saccharomyces cerevisiae. Several observations suggest that gpIRK1 forms functional ion channels when expressed in yeast. gpIRK1 complements a trk1 delta trk2 delta strain, which is defective in potassium uptake. Expression of gpIRK1 in this mutant restores growth on low potassium media. Growth dependent on gpIRK1 is inhibited by external Cs+. The strain expressing gpIRK1 provides a versatile genetic system for studying the assembly and composition of inwardly rectifying K+ channels.","subset":"pubmed_abstract"} +{"meta":{"pmid":8370122,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Malondialdehyde and glutathione production in isolated perfused human and rat hearts.\nA number of studies show the relation between oxygen-derived free radicals and cardiac ischemia\/reperfusion injury. However, little is known about oxidative stress in the human heart, which can be measured by oxidized glutathione (GSSG) and malondialdehyde (MDA) formation. Furthermore, data on MDA production by rat hearts are controversial, possibly because of the use of the aspecific thiobarbituric acid assay. Therefore, GSSG and MDA were measured, with colorimetric and high-performance liquid chromatographic assays, respectively, in buffer-perfused explanted human hearts and normal rat hearts made temporarily ischemic. Human hearts received cardioplegia; rat hearts were studied in a control and an ischemic group with or without cardioplegia. Baseline GSSG release was < 0.01 nmol.min-1.g wet wt-1 in both species. During reperfusion, GSSG release from human hearts and from ischemic and cardioplegic\/ischemic rat hearts peaked at 0.24 +\/- 0.12, 1.1 +\/- 0.4, and 0.19 +\/- 0.04 nmol.min-1.g-1, respectively. MDA was undetectable (< 0.02 nmol.min-1.g-1) in the effluent of both species and in human hearts (< 4 nmol\/g protein). Rat heart reduced glutathione levels decreased 32% as a consequence of cardioplegia and ischemia. Cardioplegia induced a 41% (P = .08) decrease in rat heart MDA content, whereas cumene hydroperoxide increased it 3.6 times (P < .01). Thus, after ischemia human and rat hearts release GSSG, indicating that oxidative stress has occurred. Apparently, lipid peroxidation takes place in normal rat hearts, decreases after cardioplegia, but does not increase after ischemia\/reperfusion. Human hearts lack MDA under normoxic and ischemic conditions. This novel finding seems to reflect a low MDA-forming potential in both situations.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":16053955,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-30":1,"unknown":8}}},"text":"Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease.\nIn the present study, we analyzed the clinical outcome of patients with multivessel coronary artery disease in whom at least one vessel was treated by percutaneous coronary intervention (PCI) and at least one other vessel was deferred on the basis of fractional flow reserve (FFR) measurements during the same session. Myocardial FFR is an established tool for assessing the severity of epicardial stenoses. It has been shown that it is safe to defer an intervention in single vessel disease patients when FFR >0.75. One hundred two patients (66 +\/- 10 years) with multivessel coronary artery disease were included in the study. In all patients, PCI of at least two vessels was contemplated. Yet in all of them at least one vessel was treated by PCI, whereas at least one other vessel was deferred based on an FFR >0.75. Major adverse cardiac events (MACE) were recorded during an average follow-up of 29 +\/- 18 months. In 102 patients, 113 coronary arteries underwent PCI. In these arteries FFR was 0.57 +\/- 0.13 and mean diameter stenosis was 68 +\/- 14%. One hundred twenty-seven coronary arteries had an FFR >0.75 and PCI was deferred. In these arteries FFR was 0.86 +\/- 0.06 and mean diameter stenosis was 47 +\/- 12%. No death occurred during the follow-up. A MACE occurred in 9% and 13% of patients after 12 and 36 months, respectively. These MACE were related to 22 (9.2%) arteries. Among them, 8 (6.3%) MACE were related to one of the initially deferred vessels, whereas 14 (12.3%) MACE were related to one of the initially treated coronary artery. In patients with multivessel disease, PCI of hemodynamically non-significant stenoses can be safely deferred, even if initially planned on the basis of the angiogram.","subset":"pubmed_abstract"} +{"meta":{"pmid":30764796,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":2,"unknown":8}}},"text":"Identifying on admission patients likely to develop acute kidney injury in hospital.\nThe incidence of Acute Kidney Injury (AKI) continues to increase in the UK, with associated mortality rates remaining significant. Approximately one fifth of hospital admissions are associated with AKI and approximately a third of patients with AKI in hospital develop AKI during their time in hospital. A fifth of these cases are considered avoidable. Early risk detection remains key to decreasing AKI in hospitals, where sub-optimal care was noted for half of patients who developed AKI. Electronic anonymised data for adults admitted into the Royal Cornwall Hospitals Trust (RCHT) between 18th March and 31st December 2015 was trimmed to that collected within the first 24 h of hospitalisation. These datasets were split according to three separate time periods: data used for training the Takagi-Sugeno Fuzzy Logic Systems (FLS) and the multivariable logistic regression (MLR) models; data used for testing; and data from a later patient spell used for validation. Three fuzzy logic models and three MLR models were developed to link characteristics of patients diagnosed with a maximum stage AKI within 7 days of admission: the first models to identify any AKI Stage (FLS I, MLR I), the second for patterns of AKI Stage 2 or 3 (FLS II, MLR II), and the third to identify AKI Stage 3 (FLS III, MLR III). Model accuracy is expressed by area under the curve (AUC). Accuracy for each model during internal validation was: FLS I and MLR I (AUC 0.70, 95% CI: 0.64-0.77); FLS II (AUC 0.77, 95% CI: 0.69-0.85) and MLR II (AUC 0.74, 95% CI: 0.65-0.83); FLS III and MLR III (AUC 0.95, 95% CI: 0.92-0.98). FLS II and FLS III (and the respective MLR models) can identify with a high level of accuracy patients at high risk of developing AKI in hospital. These two models cannot be properly assessed against prior studies as this is the first attempt at quantifying the risk of developing specific Stages of AKI for a broad cohort of both medical and surgical inpatients. FLS I and MLR I performance is comparable to other existing models.","subset":"pubmed_abstract"} +{"meta":{"pmid":22217538,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Have renal dietitians successfully implemented evidence-based guidelines into practice? A survey of dietitians across Australia and New Zealand.\nSuccessful implementation of evidence-based practice (EBP) guidelines has been shown to improve the nutrition status of dialysis patients. This study aimed to establish use of EBP guidelines and implementation of key recommendations for nutrition assessment of dialysis patients, as well as to identify barriers and enablers associated with EBP guideline adherence. A survey of nutrition assessment practices and barriers to implementation of EBP guidelines was developed and piloted. The survey measured implementation of guidelines regarding frequency of nutrition assessment and use of the subjective global assessment (SGA) to diagnose malnutrition. Barriers to guideline implementation were measured using agreement with statements rated on a Likert scale. Data were summarized as counts and percentages and analyzed using chi-squared tests of association, with P < .05 indicating statistical significance. The survey targeted specialist renal dietitians across Australian and New Zealand. Sixty-five renal dietitians from Australia and New Zealand responded to the survey. Most were females (89%, n = 58 of 65), aged <35 years (72%, n = 47 of 65), with one-third (n = 22 of 65) working in renal dietetics for longer than 4 years. Nearly all participants (n = 62 of 65) reported routinely using EBP guidelines; however, only 55% and 66% indicated they had successfully implemented the guidelines regarding minimum 6-monthly nutrition assessment of dialysis patients (n = 36 of 65) and use of the SGA (n = 43 of 65), respectively. Barriers related to time, skills\/self-efficacy, and an inefficient referral system were related to lower rates of guideline implementation. These findings indicate an evidence-practice gap in the nutritional management of dialysis patients. A standardized approach to EBP guideline implementation including structured 6-monthly nutrition assessment of dialysis patients and group training for use of the SGA tool may assist in closing this evidence-practice gap.","subset":"pubmed_abstract"} +{"meta":{"pmid":32727605,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Management of failed UKA to TKA: conventional versus robotic-assisted conversion technique.\nFailure of unicompartmental knee arthroplasty (UKA) is a distressing and technically challenging complication. Conventional conversion techniques (CCT) with rods and jigs have produced varying results. A robotic-assisted conversion technique (RCT) is an unexplored, though possibly advantageous, alternative. We compare our reconstructive outcomes between conventional and robotic methods in the management of failed UKA. Thirty-four patients with a failed UKA were retrospectively reviewed. Patients underwent conversion total knee arthroplasty (TKA) with either a CCT or RCT. Seventeen patients were included in each group. All procedures were done by a single surgeon at a single institution, with a mean time to follow-up of 3.6 years (range, 1 to 12). The primary outcome measures were the need for augments and polyethylene thickness. Secondary outcome measures were complications, need for revision, estimated blood loss (EBL), length of stay, and operative time. The mean polyethylene thickness was 12 mm (range, 9 to 15) in the CCT group and 10 mm (range, 9 to 14) in the RCT groups, with no statistical difference between the two groups (P = 0.07). A statistically significant difference, however, was present in the use of augments. In the CCT group, five out of 17 knees required augments, whereas none of the 17 knees in the RCT group required augments (P = 0.04). Procedurally, robotic-assisted surgery progressed uneventfully, even with metal artifact noted on the preoperative computerized tomography (CT) scans. Computer mapping of the residual bone surface after implant removal was a helpful guide in minimizing resection depth. No further revisions or reoperations were performed in either group. Robotic-assisted conversion TKA is technically feasible and potentially advantageous. In the absence of normal anatomic landmarks to guide conventional methods, the preoperative CT scans were unexpectedly helpful in establishing mechanical alignment and resection depth. In this limited series, RCT does not seem to be inferior to CCT. Further investigation of outcomes is warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":17123981,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Changes in bacterial profile during amebiasis: demonstration of anaerobic bacteria in ALA pus samples.\nLittle is known about the changes in gut resident flora during amebic colitis and amebic liver abscess (ALA) caused by Entamoeba histolytica infection. Fecal samples from ALA patients, from healthy E. histolytica negative and positive (asymptomatic) individuals, and from pre- and post-metronidazole-treated healthy volunteers and pus samples from ALA patients were tested for the presence of various bacterial genera using 16S rRNA-based primers. Statistically significant reduction in Lactobacillus due to E. histolytica infection was observed in asymptomatic individuals and ALA patients. On the other hand, reduction in Bacteroides, Bifidobacterium, and Clostridium in the same samples was due to metronidazole treatment. Two anaerobic genera, viz. Bacteroides and Peptostreptococcus, were detected in ALA pus samples, and this observation is unprecedented. In addition, PCR revealed metronidazole resistance genes in fecal and pus samples of metronidazole-treated individuals. Re-examination of the ameba-bacterium relationship in amebiasis is suggested.","subset":"pubmed_abstract"} +{"meta":{"pmid":32302978,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2024-10":1,"unknown":8}}},"text":"Minimally invasive foramen magnum durectomy and obexostomy for treatment of craniocervical junction-related syringomyelia in adults: case series and midterm follow-up.\nCraniocervical junction-related syringomyelia (CCJS) is the most common form of syringomyelia. Approximately 30% of patients treated with foramen magnum decompression (FMD) will show persistence, recurrence, or progression of the syrinx. The authors present a pilot study with a new minimally invasive surgery technique targeting the pathophysiology of CCJS in adult patients. The authors retrospectively analyzed the clinical and radiological features of a consecutive series of patients treated for CCJS. An FMD and FM durectomy were performed through a 1.5- to 2-cm skin incision. Then arachnoid adhesions were cleared, creating a permanent communication from the fourth ventricle to the new paraspinal extradural cavity (obexostomy) and with the spinal subarachnoid space. The hypothesis was that the new CSF pouch acts like a pressure leak, interrupting the CCJS pathogenesis. Twenty-four patients (13 female, 21-61 years old) were treated between 2014 and 2018. The etiology of CCJS was Chiari malformation type I (CM-I) in 20 patients (83.3%), Chiari malformation type 0 (CM-0) in 2 patients (8.3%), and CCJ arachnoiditis in 2 patients (8.3%). Two patients underwent reoperations after failed FMD for CM-I at other institutions. No major surgical complication occurred. One patient had postoperative meningitis with no CSF fistula. On postoperative MRI, shrinkage of the syrinx was seen in all patients. No patients experienced recurrence of the CCJS. No patient required a subsequent operation. The mean duration of surgery was 72 \u00b1 11 minutes (mean \u00b1 SD), and blood loss was 35-80 ml (mean 51 ml). Follow-up ranged from 12 to 58 months. The average overall improvement in modified Japanese Orthopaedic Association scores was 10% (p < 0.001). The Odom scale showed that 19 patients (79.1%) were satisfied, 4 (16.7%) remained the same, and 1 (4.2%) reported a poor outcome. All patients experienced postoperative improvement in perception of quality of life (p < 0.001). Minimally invasive FM durectomy and obexostomy is a safe and effective treatment for CCJS and for patients who have not responded to other treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":30009668,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Long-Term Engraftment Promotes Differentiation of Alveolar Epithelial Cells from Human Embryonic Stem Cell Derived Lung Organoids.\nHuman embryonic stem cell (hESC) derived 3D human lung organoids (HLOs) provide a promising model to study human lung development and disease. HLOs containing proximal or\/and immature distal airway epithelial cells have been successfully generated in vitro, such as early staged alveolar type 2 (AT2) cells (SPC+\/SOX9+) and immature alveolar type 1 (AT1) cells (HOPX+\/SOX9+). When HLOs were transplanted into immunocompromised mice for further differentiation in vivo, only few distal epithelial cells could be observed. In this study, we transplanted different stages of HLOs into immunocompromised mice to assess whether HLOs could expand and mature in vivo. We found that short-term transplanted HLOs contained lung progenitor cells (NKX2.1+, SOX9+, and P63+), but not SPC+ AT2 cells or AQP5+ AT1 cells. Meanwhile, long-term engrafted HLOs could differentiate into lung distal bipotent progenitor cells (PDPN+\/SPC+\/SOX9+), AT2 cells (SPC+, SPB+), and immature AT1 cells (PDPN+, AQP5-). However, HLOs at late in vitro stage turned into mature AT1-like cells (AQP5+\/SPB-\/SOX9-) in vivo. Immunofluorescence staining and transmission electron microscopy (TEM) results revealed that transplanted HLOs contained mesenchymal cells (collagen I+), vasculature (ACTA2+), neuroendocrine-like cells (PGP9.5+), and nerve fiber structures (myelin sheath structure). Together, these data reveal that hESC-derived HLOs would be useful for human lung development modeling, and transplanted HLOs could mimic lung organ-like structures in vivo by possessing vascular network and neuronal network.","subset":"pubmed_abstract"} +{"meta":{"pmid":18956088,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2024-26":1,"unknown":8}}},"text":"Origin of repulsive force and structure\/dynamics of interfacial water in OEG-protein interactions: a molecular simulation study.\nMolecular simulations were performed to investigate the origin of the strong repulsive force acting on a protein as the protein approaches an oligo (ethylene glycol) self-assembled monolayer (OEG-SAM) surface. Since the repulsive force is mainly generated from water molecules, the force from the water molecules near the surface was calculated layer by layer to further identify the molecular origin of the repulsive force. Results show that the strong repulsive force acting on the protein near the OEG-SAM surface is dominantly generated by the interfacial water molecules located between the OEG-SAM surface and lysozyme. A hydroxyl-terminated SAM (OH-SAM) surface was used for comparison. No significant repulsive force was observed from the water molecules between the protein and OH-SAM surface. Further studies show that the dipole distribution of the interfacial water molecules is significantly affected by the OEG-SAM surface, as opposed to the negligible impact from the OH-SAM surface. The interfacial water molecules above the OEG-SAM surface stay longer and reorient more slowly than those above the OH-SAM surface. These results from this work support the hypothesis that the OEG-SAM surface interacts strongly with interfacial water molecules and creates a stable hydration layer that prevents proteins from adsorbing to the surface.","subset":"pubmed_abstract"} +{"meta":{"pmid":17095551,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":3,"2024-10":1,"unknown":7}}},"text":"Neuropsychiatric symptoms in past users of sheep dip and other pesticides.\nTo explore the prevalence and pattern of neuropsychiatric symptoms in past users of sheep dip and other pesticides. From a postal survey of men born between 1933 and 1977 and resident in three rural areas of England and Wales (response rate 31%), data were obtained on lifetime history of work with pesticides, neurological symptoms in the past month, current mental health and tendency to be troubled by non-neurological somatic symptoms (summarised as a somatising tendency score). Risk factors for current neuropsychiatric symptoms were assessed by modified Cox regression. Data were available for 9844 men, including 1913 who had worked with sheep dip, 832 with other insecticides but not sheep dip and 990 with other pesticides but never with sheep dip or insecticides. Neurological symptoms were consistently 20-60% more common in past users of sheep dip than in men who had never worked with pesticides, but their prevalence was also higher in men who had worked only with pesticides other than sheep dip or insecticides. They clustered strongly within individuals, but this clustering was not specific to men who had worked with sheep dip. Reporting of three or more neurological symptoms was associated with somatising tendency (prevalence ratio (PR) 15.0, 95% CI 11.4 to 19.5, for the highest vs the lowest category of somatisation) and was more common in users of sheep dip (PR 1.3, 95% CI 1.0 to 1.6), other insecticides (PR 1.4, 95% CI 1.0 to 1.8) and other pesticides (PR 1.3, 95% CI 1.0 to 1.7) than in non-users. Among users of sheep dip, prevalence was higher in men who had dipped most often, but not in those who had worked with sheep dip concentrate. Past use of pesticides was not associated with current anxiety or depression. Neurological symptoms are more common in men who have worked with sheep dip, but the association is not specific to sheep dip or insecticides. A toxic cause for the excess cannot be ruled out, but several features of our observations suggest that psychological mechanisms have a role.","subset":"pubmed_abstract"} +{"meta":{"pmid":29052132,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":11}}},"text":"Current Progress in EBV-Associated B-Cell Lymphomas.\nEpstein-Barr virus (EBV) was the first human tumor virus discovered more than 50 years ago. EBV-associated lymphomagenesis is still a significant viral-associated disease as it involves a diverse range of pathologies, especially B-cell lymphomas. Recent development of high-throughput next-generation sequencing technologies and in vivo mouse models have significantly promoted our understanding of the fundamental molecular mechanisms which drive these cancers and allowed for the development of therapeutic intervention strategies. This review will highlight the current advances in EBV-associated B-cell lymphomas, focusing on transcriptional regulation, chromosome aberrations, in vivo studies of EBV-mediated lymphomagenesis, as well as the treatment strategies to target viral-associated lymphomas.","subset":"pubmed_abstract"} +{"meta":{"pmid":28290620,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Changes on microsatellites of expressed sequence tag of sugarcane (Saccharum spp) during vegetative propagation.\nThe reduction in sugarcane productivity in subsequent cutting stages may be related to a gradual decrease of the allele number and mean observed heterozygosity (HO) in the sugarcane ratoon. This hypothesis was tested assessing the number of alleles and HO values in 10 expressed sequence tag microsatellites (Est-SSR loci) of the sugarcane varieties RB72454 and RB867515 in different cutting stages. Changes of allele numbers in samples of different cutting stages were observed in seven and six EstSSR loci of the RB72454 and RB867515 varieties, respectively. Reduction of allele numbers was observed in the samples collected in the fourth and sixth cutting stages of the RB72454 variety. In contrast, an increase of the allele numbers was detected in the samples collected on fourth, sixth, and seventh cutting stages of the RB867515 variety. Unchanged allele numbers were observed only in EstB41, EstC84, and EstB130 loci of the RB72454 variety, and EstB41, EstC67, EstA68, and EstB130 loci of the RB867515 variety. The variety RB867515 has lower polymorphism and values of HO than the RB72454 variety in different stages of cutting. At molecular level, in Est-SSR loci, the RB72454 variety showed higher changes in subsequent stages of cutting than RB867515. The similarities and divergences at molecular level between varieties RB72454 and RB867515 observed in the 10 Est-SSR loci during subsequent cutting stages can not explain the reduced productivity frequently observed after subsequent cutting stages but showed that phenotypic and physiological changes after each cutting stage are also accompanied by changes at genomic level.","subset":"pubmed_abstract"} +{"meta":{"pmid":27514016,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-30":2,"2024-10":1,"unknown":6}}},"text":"Elemental and molecular profiling of licit, illicit, and niche tobacco.\nThe recognition of differences between regulated large-scale mass manufactured products and the uncontrolled cultivation of tobaccos for illicit purposes plays a significant role within identification of provenance. This research highlights X-ray fluorescence and Fourier transform infrared spectroscopy as useful analytical techniques for the rapid identification of tobacco samples of unknown provenance. Identification of key discriminative features within each technique allowed for the development of typical characteristic profiles for each type of tobacco. Analysis using X-ray fluorescence highlights chlorine, potassium, calcium and iron as key elemental indicators of tobacco provenance. Significant levels of chlorine seen within Sn\u00fcs samples prompted attempts to visualise chlorine containing regions and structures within the sample. Scanning electron microscopy images showed crystalline structures visible within the Sn\u00fcs tobacco, structures which Energy dispersive X-ray spectroscopy qualitatively confirmed to contain chlorine. Chloride levels within Sn\u00fcs samples were quantified using ion chromatography with levels found to range between 0.87mgmL(-1) and 1.28mg. Additionally, FTIR indicated that absorbances attributed to carbonyl stretching at 1050-1150cm(-1), alkane bending at 1350-1480cm(-1) and amide I stretching at 1600-1700cm(-1) highlighting a spectral fingerprint region that allowed for the clear differentiation between different types of tobaccos using PCA analysis, but was limited by differentiation between provenance of cigarettes and hand rolled tobacco. X-ray fluorescence and Fourier transform infrared spectroscopy yielded different information with regards tobacco discrimination and provenance, however both methods overall analysis time and cost reduced indicating usefulness as potential handheld analytical techniques in the field.","subset":"pubmed_abstract"} +{"meta":{"pmid":12434964,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Does primary medical practitioner involvement with a specialist team improve patient outcomes? A systematic review.\nPatients with chronic or complex medical or psychiatric conditions are treated by many practioners, including general practitioners (GPs). Formal liaison between primary and specialist is often assumed to offer benefits to patients. The aim of this study was to assess the efficacy of formal liaison of GPs with specialist service providers on patient health outcomes, by conducting a systematic review of the published literature in MEDLINE, EMBASE, PsychINFO, CINAHL and Cochrane Library databases using the following search terms: 'family physician': synonyms of 'patient care planning', 'patient discharge' and 'patient care team'; and synonyms of 'randomised controlled trials'. Seven studies were identified, involving 963 subjects and 899 controls. Most health outcomes were unchanged, although some physical and functional health outcomes were improved by formal liaison between GPs and specialist services, particularly among chronic mental illness patients. Some health outcomes worsened during the intervention. Patient retention rates within treatment programmes improved with GP involvement, as did patient satisfaction. Doctor (GP and specialist) behaviour changed with reports of more rational use of resources and diagnostic tests, improved clinical skills, more frequent use of appropriate treatment strategies, and more frequent clinical behaviours designed to detect disease complications. Cost effectiveness could not be determined. In conclusion, formal liaison between GPs and specialist services leaves most physical health outcomes unchanged, but improves functional outcomes in chronically mentally ill patients. It may confer modest long-term health benefits through improvements in patient concordance with treatment programmes and more effective clinical practice.","subset":"pubmed_abstract"} +{"meta":{"pmid":26812043,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.\nImprovement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus-pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS.","subset":"pubmed_abstract"} +{"meta":{"pmid":24625201,"dup_signals":{"dup_doc_count":18,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2022-27":1,"2022-05":1,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-10":1,"2019-51":1,"2018-26":1,"2018-09":1,"2017-47":1,"2017-39":1,"2022-49":1,"2017-13":1}}},"text":"The prevalence of psychosis in epilepsy; a systematic review and meta-analysis.\nEpilepsy has long been considered to be a risk factor for psychosis. However there is a lack of consistency in findings across studies on the effect size of this risk which reflects methodological differences in studies and changing diagnostic classifications within neurology and psychiatry. The aim of this study was to assess the prevalence of psychosis in epilepsy and to estimate the risk of psychosis among individuals with epilepsy compared with controls. A systematic review and meta-analysis was conducted of all published literature pertaining to prevalence rates of psychosis in epilepsy using electronic databases PUBMED, OVIDMEDLINE, PsychINFO and Embase from their inception until September 2010 with the following search terms: prevalence, incidence, rate, rates, psychosis, schizophrenia, schizophreniform illness, epilepsy, seizures, temporal lobe epilepsy. The literature search and search of reference lists yielded 215 papers. Of these, 58 (27%) had data relevant to the review and 157 were excluded following a more detailed assessment. 10% of the included studies were population based studies. The pooled odds ratio for risk of psychosis among people with epilepsy compared with controls was 7.8. The pooled estimate of prevalence of psychosis in epilepsy was found to be 5.6% (95% CI: 4.8-6.4). There was a high level of heterogeneity. The prevalence of psychosis in temporal lobe epilepsy was 7% (95% CI: 4.9-9.1). The prevalence of interictal psychosis in epilepsy was 5.2% (95% CI: 3.3-7.2). The prevalence of postictal psychosis in epilepsy was 2% (95% CI: 1.2-2.8). Our systematic review found that up to 6% of individuals with epilepsy have a co-morbid psychotic illness and that patients have an almost eight fold increased risk of psychosis. The prevalence rate of psychosis is higher in temporal lobe epilepsy (7%). We suggest that further investigation of this association could give clues to the aetiology of psychosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24364615,"dup_signals":{"dup_doc_count":43,"dup_dump_count":27,"dup_details":{"curated_sources":3,"2023-50":2,"2023-23":4,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2019-09":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-30":3,"2018-17":2,"2018-13":1,"2018-05":2,"2017-51":1,"2017-43":3,"2017-34":3,"2017-26":1,"2017-17":1,"2017-13":1,"2024-22":1}}},"text":"Cognitive factors maintaining persecutory delusions in psychosis: the contribution of depression.\nDepression is common in people with schizophrenia, but how it might directly contribute to the persistence of psychotic symptoms has rarely been tested. The key aim of the present study was to test whether depression and associated cognitive processes predict the maintenance of persecutory delusions. Three groups of participants were tested at baseline: 60 patients with persecutory delusions in the context of a schizophrenia spectrum diagnosis, 30 patients with depression, and 30 nonclinical controls. They completed interviewer and self-report assessments of depression and paranoia, and measures of six cognitive factors (schematic beliefs, experiential avoidance, autobiographical memory, problem solving, rumination, worry style). The patients with persecutory delusions were then assessed again, six months later. It was found that 50% of the patients with persecutory delusions met diagnostic criteria for major depression. Cognitive processes found to be associated with depression across the groups were negative schematic beliefs about the self, experiential avoidance and rumination, but not autobiographical memory or problem solving. The severity of initial depression in patients with persecutory delusions predicted the persistence of paranoia over six months. A number of cognitive factors also predicted the persistence of persecutory delusions, including negative schematic beliefs about the self, worry, and problem-solving difficulties. In conclusion, depression is common in patients with current persecutory delusions, and it shows similar cognitive features to major depressive disorder. The results of this study indicate that depression and related processes may contribute to the maintenance of paranoia. Trials are warranted of depression-related therapeutic techniques for people with persecutory delusions.","subset":"pubmed_abstract"} +{"meta":{"pmid":2165521,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Functional characteristics and sites of gene expression of the alpha 1, beta 1, gamma 2-isoform of the rat GABAA receptor.\nGABAA receptors, the major synaptic targets for the neurotransmitter GABA, constitute gated chloride channels. By their allosteric, drug-induced modulation, they serve as control elements for the regulation of anxiety, vigilance, and epileptiform activity. The structural requirements of fully functional GABAA receptors in the mammalian brain have remained elusive so far. We report here on the cloning of the gamma 2-subunit cDNA of rat brain and its functional analysis by coexpression with the alpha 1- and beta 1-subunits in Xenopus oocytes, and on the sites of gene expression of the 3 subunits in the rat brain. The recombinant receptor displayed GABA-inducible currents (Imax = 6 microA; Ka = 75 microM) which were allosterically modulated by benzodiazepine receptor ligands (enhancement and inhibition by diazepam and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, respectively). In the absence of GABA, pentobarbital elicited a maximal current amplitude similar to that of GABA. A minor population of channels is expressed which is open in the absence of GABA or pentobarbital. Mapping subunit gene expression by in situ hybridization histochemistry suggests that the alpha 1-, beta 1-, and gamma 2-subunits are likely receptor constituents in some neuronal populations, e.g., mitral cells of the olfactory bulb, pyramidal cells of the hippocampus, and granule cells of the dentate gyrus and cerebellum.","subset":"pubmed_abstract"} +{"meta":{"pmid":4121646,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2017-13":1,"unknown":4}}},"text":"Discriminant value of thyroid function tests.\nDifferent thyroid function tests permitted a final classification of 204 consecutive patients with suspected thyroid disorders into three populations (thyrotoxic, euthyroid, and hypothyroid). Linear discriminant analysis was applied to all test results (10 variates) on adjacent population pairs. Two invitro tests (serum protein bound iodine (P.B.I.) and tri-iodothyronine (T-3) uptake values) gave good separation of thyrotoxic from euthyroid patients and fairly good distinction of hypothyroid patients. If a (131)I uptake figure was then added to the in-vitro results most patients (95.5%), including thse initially classified as equivocal, were correctly diagnosed. Other tests, including clinical questionnaires, were poor discriminants.Two new techniques of utilizing the test data were devised. Firstly, the data from the two in-vitro tests were also displayed graphically, and oblique boundary lines derived from the discriminant functions gave better separation of patients than previously used limits or mathematical expressions of \"free thyroxine.\" Secondly, a nomogram incorporating the best four discriminants was designed as a diagnostic aid and proved to be the best means of interpreting the tests.Discriminant analysis of this kind can be used in the interpretation of diagnostic tests in any branch of medicine, and it allows the best use to be made of the available data.","subset":"pubmed_abstract"} +{"meta":{"pmid":22327406,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"The effects of parent-child relationships on later life mental health status in two national birth cohorts.\nAbusive and neglectful parenting is an established determinant of adult mental illness, but longitudinal studies of the impact of less severe problems with parenting have yielded inconsistent findings. In the face of growing interest in mental health promotion, it is important to establish the impact of this potentially remediable risk factor. 8,405 participants in the 1958 UK birth cohort study, and 5,058 in the 1970 birth cohort study questionnaires relating to the quality of relationships with parents completed at age 16 years. 12-item General Health Questionnaire and the Malaise Inventory collected at age 42 years (1958 cohort) and 30 years (1970 cohort). Statistical methodology: logistic regression analyses adjusting for sex, social class and teenage mental health problems. 1958 cohort: relationships with both mother and father predicted mental health problems in adulthood; increasingly poor relationships were associated with increasing mental health problems at age 42 years. 1970 cohort: positive items derived from the Parental Bonding Instrument predicted reduced risk of mental health problems; negative aspects predicted increased risk at age 30 years. Odds of mental health problems were increased between 20 and 80% in fully adjusted models. Results support the hypothesis that problems with parent-child relationships that fall short of abuse and neglect play a part in determining adult mental health and suggest that interventions to support parenting now being implemented in many parts of the Western world may reduce the prevalence of mental illness in adulthood.","subset":"pubmed_abstract"} +{"meta":{"pmid":27028098,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2017-13":1,"2024-18":1,"unknown":16}}},"text":"Record linkage is feasible with non-identifiable trauma and rehabilitation datasets.\n1) Describe probabilistic linkage (PL) for road trauma and rehabilitation records in New South Wales (NSW) Australia. 2) Determine the accuracy of linkage for these records. Data were extracted from the NSW Trauma Registry for all road trauma admissions for the years 2009-2012 and from Australasian Rehabilitation Outcomes Centre for January 2009 to June 2013. PL was performed using: age; sex; residential postcode; and date of acute discharge = date of admission to rehabilitation. False matches were cases that linked but were not true matches; they were determined by manual review. Reasons for incomplete linkages were explored. The benefits and limitations of the linked study dataset are described. Of 3,256 road trauma records, 683 were matched to rehabilitation records. Using the field of 'discharge destination' from the trauma records, 265 patients with unmatched records were discharged to inpatient rehabilitation (missed matches). This gave an overall 72% linkage rate (or sensitivity) using PL. There were 16 cases of false matches, giving a specificity of 99%. It was feasible to use PL to link road trauma and rehabilitation datasets in the absence of identifiers. However, this needed to be combined with careful manual review before the linked dataset could be used to make inferences on trauma rehabilitation outcomes. PL may be a cost-effective way to capture inpatient rehabilitation outcomes of multi-trauma patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":31231347,"dup_signals":{"dup_doc_count":20,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":17}}},"text":"The Emergence of Chromosomally Located bla CTX-M-55 in Salmonella From Foodborne Animals in China.\nThe emergence and increase in prevalence of resistance to cephalosporins amongst isolates of Salmonella from food animals imposes a public health threat. The aim of the present study was to investigate the prevalence and characteristics of CTX-M-producing Salmonella isolates from raw meat and food animals. 27 of 152 (17.76%) Salmonella isolates were ESBL-positive including 21\/70 (30%) from food animals and 6\/82 (7.32%) from raw meat. CTX-M-55 was the most prevalent ESBL type observed (12\/27, 44.44%). 7 of 12 CTX-M-55-positive Salmonella isolates were Salmonella Indiana, 2 were Salmonella Typhimurium, 2 were Salmonella Chester, and the remaining isolate was not typeable. Eight CTX-M-55-positive Salmonella isolates were highly resistant to fluoroquinolones (MICCIP = 64 ug\/mL) and co-harbored aac(6')-Ib-cr and oqxAB. Most of the CTX-M-55 positive isolates (11\/12) carried bla CTX-M-55 genes on the chromosome, with the remaining isolate carrying this gene on a transferable 280 kb IncHI2 plasmid. A chromosomal bla CTX-M-55 gene from one isolate transferred onto a 250 kb IncHI2 plasmid which was subsequently conjugated into recipient strain J53. PFGE and MLST profiles showed a wide range of strain types were carrying bla CTX-M-55. Our study demonstrates the emergence and prevalence of foodborne Salmonella harboring a chromosomally located bla CTX-M-55 in China. The co-existence of PMQR genes with bla CTX-M-55 in Salmonella isolates suggests co-selection and dissemination of resistance to both fluoroquinolones and cephalosporins in Salmonella via the food chain in China represents a public health concern.","subset":"pubmed_abstract"} +{"meta":{"pmid":7841811,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Assessment of frontal lobe functions.\nThe authors describe methods for conducting a thorough assessment of functions subserved by the frontal lobes, employing both bedside and psychometric methods of assessing frontal subsystems. Qualitative or process aspects of frontal behavior observable from formal testing, interview, and social behavior are noted. It is argued that the skilled clinician must be guided by a knowledge of frontal lobe subsystems and their roles in determining specific types of abnormal behavior. The clinician will then be alert to changes in incidental behaviors that indicate frontal impairment, and bedside maneuvers can be designed to discriminate dysfunction. Given the complexity of the behaviors involved and the profound effects of maturation and aging on frontal functions, neuropsychological assessment can provide an invaluable tool for testing these functions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30700599,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1.\nThe humoral response to invading mucosal pathogens comprises multiple antibody isotypes derived from systemic and mucosal compartments. To understand the contribution of each antibody isotype\/source to the mucosal humoral response, parallel investigation of the specificities and functions of antibodies within and across isotypes and compartments is required. The role of IgA against HIV-1 is complex, with studies supporting a protective role as well as a role for serum IgA in blocking effector functions. Thus, we explored the fine specificity and function of IgA in both plasma and mucosal secretions important to infant HIV-1 infection, i.e., breast milk. IgA and IgG were isolated from milk and plasma from 20 HIV-1-infected lactating Malawian women. HIV-1 binding specificities, neutralization potency, inhibition of virus-epithelial cell binding, and antibody-mediated phagocytosis were measured. Fine-specificity mapping showed IgA and IgG responses to multiple HIV-1 Env epitopes, including conformational V1\/V2 and linear V2, V3, and constant region 5 (C5). Env IgA was heterogeneous between the milk and systemic compartments (Env IgA, \u03c4 = 0.00 to 0.63, P = 0.0046 to 1.00). Furthermore, IgA and IgG appeared compartmentalized as there was a lack of correlation between the specificities of Env-specific IgA and IgG (in milk, \u03c4 = -0.07 to 0.26, P = 0.35 to 0.83). IgA and IgG also differed in functions: while neutralization and phagocytosis were consistently mediated by milk and plasma IgG, they were rarely detected in IgA from both milk and plasma. Understanding the ontogeny of the divergent IgG and IgA antigen specificity repertoires and their effects on antibody function will inform vaccination approaches targeted toward mucosal pathogens.IMPORTANCE Antibodies within the mucosa are part of the first line of defense against mucosal pathogens. Evaluating mucosal antibody isotypes, specificities, and antiviral functions in relationship to the systemic antibody profile can provide insights into whether the antibody response is coordinated in response to mucosal pathogens. In a natural immunity cohort of HIV-infected lactating women, we mapped the fine specificity and function of IgA in breast milk and plasma and compared these with the autologous IgG responses. Antigen specificities and functions differed between IgG and IgA, with antiviral functions (neutralization and phagocytosis) predominantly mediated by the IgG fraction in both milk and plasma. Furthermore, the specificity of milk IgA differed from that of systemic IgA. Our data suggest that milk IgA and systemic IgA should be separately examined as potential correlates of risk. Preventive vaccines may need to employ different strategies to elicit functional antiviral immunity by both antibody isotypes in the mucosa.","subset":"pubmed_abstract"} +{"meta":{"pmid":33755582,"dup_signals":{"dup_doc_count":44,"dup_dump_count":14,"dup_details":{"curated_sources":3,"2023-50":3,"2023-40":2,"2023-23":3,"2023-14":7,"2023-06":3,"2022-49":2,"2022-40":3,"2022-33":1,"2022-27":2,"2022-21":4,"2024-22":6,"2024-18":2,"2024-10":2,"2024-30":1}}},"text":"Case Report: Typhoid Fever Complicated by Ileal Perforation in an Urban Slum of Dhaka, Bangladesh.\nIntestinal perforation is one of the most dangerous complications of typhoid fever and demands urgent hospitalization, diagnosis, and surgical management to reduce morbidity and prevent mortality. Here, we report a case of typhoidal intestinal perforation in a 19 year-old young man detected by passive surveillance during a cluster-randomized trial with Vi-tetanus toxoid conjugate vaccine (Typhoid Vaccine Acceleration Consortium: TyVAC) in an urban slum area in Mirpur, Dhaka, Bangladesh. The patient presented with a high-grade fever, lower abdominal pain, and vomiting and was admitted to a healthcare facility. Physical examination and preoperative investigations of the patient suggested a presumptive diagnosis of intestinal perforation, and the patient was transferred to a tertiary-level hospital for surgical management. A positive blood culture, intraoperative findings, and histopathology of an intestinal biopsy confirmed ileal perforation due to typhoid fever. This case report highlights the need for prompt diagnosis and appropriate pre- and postoperative management of patients who appear with the symptoms of typhoidal intestinal perforation. This report further demonstrates the importance of systematic surveillance and proper evaluation to determine the true incidence rate of typhoid fever and intestinal perforation in Bangladesh.","subset":"pubmed_abstract"} +{"meta":{"pmid":21439059,"dup_signals":{"dup_doc_count":22,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-06":1,"2019-26":1,"2019-13":1,"2018-39":1,"2018-26":1,"2018-17":2,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-40":1,"2024-10":1,"2017-13":1,"2024-22":1}}},"text":"Good practice in health care for migrants: views and experiences of care professionals in 16 European countries.\nHealth services across Europe provide health care for migrant patients every day. However, little systematic research has explored the views and experiences of health care professionals in different European countries. The aim of this study was to assess the difficulties professionals experience in their service when providing such care and what they consider constitutes good practice to overcome these problems or limit their negative impact on the quality of care. Structured interviews with open questions and case vignettes were conducted with health care professionals working in areas with high proportion of migrant populations in 16 countries. In each country, professionals in nine primary care practices, three accident and emergency hospital departments, and three community mental health services (total sample = 240) were interviewed about their views and experiences in providing care for migrant patients, i.e. from first generation immigrant populations. Answers were analysed using thematic content analysis. Eight types of problems and seven components of good practice were identified representing all statements in the interviews. The eight problems were: language barriers, difficulties in arranging care for migrants without health care coverage, social deprivation and traumatic experiences, lack of familiarity with the health care system, cultural differences, different understandings of illness and treatment, negative attitudes among staff and patients, and lack of access to medical history. The components of good practice to overcome these problems or limit their impact were: organisational flexibility with sufficient time and resources, good interpreting services, working with families and social services, cultural awareness of staff, educational programmes and information material for migrants, positive and stable relationships with staff, and clear guidelines on the care entitlements of different migrant groups. Problems and good care components were similar across the three types of services. Health care professionals in different services experience similar difficulties when providing care to migrants. They also have relatively consistent views on what constitutes good practice. The degree to which these components already are part of routine practice varies. Implementing good practice requires sufficient resources and organisational flexibility, positive attitudes, training for staff and the provision of information.","subset":"pubmed_abstract"} +{"meta":{"pmid":9347298,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Biomechanical evaluation of polylactide absorbable screws used for syndesmosis injury repair.\nSimulated syndesmosis injuries were created in 12 fresh-frozen, below-knee cadaver specimens. Six specimens were repaired with a 4.5 mm stainless steel screw, and six were repaired with a 4.5 mm polylactide screw. Three specimens of each group were tested in load to failure by axially loading with 1400 N and externally rotating to 90 degrees. Three specimens in each group underwent fatigue testing by axially loading with 700 N and applying 2.5 N-m of torque for 57,700 cycles. Radiographs and computed tomography scans were evaluated. None of the screws broke or failed. Similar load to failure was noted in polylactide and control groups. Fatigue testing revealed no significant change in stiffness. No significant screw damage was evident on radiographic or computed tomography evaluation. The data suggest that a polylactide screw has sufficient fatigue and failure strength to allow for healing of this injury in a clinical situation.","subset":"pubmed_abstract"} +{"meta":{"pmid":10754613,"dup_signals":{"dup_doc_count":11}},"text":"The effect of anesthetic technique on postoperative outcomes in hip fracture repair.\nThe impact of anesthetic choice on postoperative mortality and morbidity has not been determined with certainty. The authors evaluated the effect of type of anesthesia on postoperative mortality and morbidity in a retrospective cohort study of consecutive hip fracture patients, aged 60 yr or older, who underwent surgical repair at 20 US hospitals between 1983 and 1993. The primary outcome was defined as death within 30 days of the operative procedure. The secondary outcomes were postoperative 7-day mortality, postoperative myocardial infarction, postoperative pneumonia, postoperative congestive heart failure, and postoperative change in mental status. Numerous comorbid conditions were controlled for individually and by several comorbidity indices using logistic regression. General anesthesia was used in 6,206 patients (65.8%) and regional anesthesia in 3,219 patients (3,078 spinal anesthesia and 141 epidural anesthesia). The 30-day mortality rate in the general anesthesia group was 4.4%, compared with 5.4% in the regional anesthesia group (unadjusted odds ratio = 0.80; 95% confidence interval = 0.66-0.97). However, the adjusted odds ratio for general anesthesia increased to 1.08 (0.84-1.38). The adjusted odds ratios for general anesthesia versus regional anesthesia for the 7-day mortality was 0.90 (0.59-1.39) and for postoperative morbidity outcomes were as follows: myocardial infarction: adjusted odds ratio = 1.17 (0.80-1.70); congestive heart failure: adjusted odds ratio = 1.04 (0.80-1.36); pneumonia: adjusted odds ratio = 1.21 (0.87-1.68); postoperative change in mental status: adjusted odds ratio = 1.08 (0.95-1.22). The authors were unable to demonstrate that regional anesthesia was associated with better outcome than was general anesthesia in this large observational study of elderly patients with hip fracture. These results suggest that the type of anesthesia used should depend on factors other than any associated risks of mortality or morbidity.","subset":"pubmed_abstract"} +{"meta":{"pmid":32368713,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"\u00a1S\u00ed, Yo Puedo Vivir Sano con Diabetes! A Self-Management Randomized Controlled Pilot Trial for Low-Income Adults with Type 2 Diabetes in Mexico City.\nType 2 diabetes (T2D) is a worldwide epidemic and a leading cause of death in Mexico, with a prevalence of 15.9%, and >70% of diagnosed adults have poor glycemic control [glycated hemoglobin (HbA1c) >7.5%]. We developed a diabetes self-management education program contextualized to the study population, including dietary preferences, health literacy, and health system. We aimed to evaluate the efficacy of a self-management + text message program (\u00a1S\u00ed, Yo Puedo Vivir Sano con Diabetes!) on primary (HbA1c), and secondary behavioral (self-management), clinical, and psychosocial outcomes in adults with T2D in Mexico City. Participants were recruited at public primary healthcare centers (Seguro Popular), and randomly allocated to treatment (n = 26) or wait-list control groups (n = 21) with data collected at 3 and 6 mo. The program included 7 weekly sessions and 6 mo of daily text\/picture messages. Descriptive statistics and a generalized linear mixed model with intent-to-treat analysis were calculated. Participants were 55.5 \u00b1 8.8 y of age (mean \u00b1 SD), 68% female, 88.6% overweight\/obese, and 57% lived in food-insecure households. Mean \u00b1 SD T2D duration was 11.9 \u00b1 7.8 y and HbA1c was 9.2% \u00b1 1.5%. There was 89% attendance at sessions and 6.4% attrition across both groups at 6 mo. Group-by-time effects were seen in self-monitoring of blood glucose (P < 0.01) and diabetes self-efficacy (P < 0.04); and a trend for lower HbA1c was seen in the intervention group at 6 mo (P = 0.11). Significant improvements in dietary behavior (P < 0.01) were demonstrated in the intervention group over time, but this did not reach statistical significance compared with the control group. The program was associated with clinically significant improvements in T2D self-management, self-efficacy, and HbA1c over time. Thus, T2D self-management skills, including diet, were improved in a vulnerable metropolitan population.This trial was registered at clinicaltrials.gov as NCT03159299.","subset":"pubmed_abstract"} +{"meta":{"pmid":22222980,"dup_signals":{"dup_doc_count":53,"dup_dump_count":44,"dup_details":{"curated_sources":2,"2021-17":1,"2019-43":1,"2019-13":1,"2019-04":1,"2018-51":1,"2018-26":1,"2018-17":1,"2018-13":1,"2017-47":2,"2017-43":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-42":4,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2022-27":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2015-18":1}}},"text":"Bleach gel: a simple agarose gel for analyzing RNA quality.\nRNA-based applications requiring high-quality, non-degraded RNA are a foundational element of many research studies. As such, it is paramount that the integrity of experimental RNA is validated prior to cDNA synthesis or other downstream applications. In the absence of expensive equipment such as microfluidic electrophoretic devices, and as an alternative to the costly and time-consuming standard formaldehyde gel, RNA quality can be quickly analyzed by adding small amounts of commercial bleach to TAE buffer-based agarose gels prior to electrophoresis. In the presence of low concentrations of bleach, the secondary structure of RNA is denatured and potential contaminating RNases are destroyed. Because of this, the 'bleach gel' is a functional approach that addresses the need for an inexpensive and safe way to evaluate RNA integrity and will improve the ability of researchers to rapidly analyze RNA quality.","subset":"pubmed_abstract"} +{"meta":{"pmid":11833397,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":3,"2024-22":1,"2017-13":1,"2024-30":1,"unknown":7}}},"text":"Effectiveness of school-based occupational therapy intervention on handwriting.\nThis study investigated the effects of school-based occupational therapy services on students' handwriting. Students 7 to 10 years of age with poor handwriting legibility who received direct occupational therapy services (n = 29) were compared with students who did not receive services (n = 9) on handwriting legibility and speed and associated performance components. Visual-motor, visual-perception, in-hand manipulation, and handwriting legibility and speed were measured at the beginning and end of the academic year. The intervention group received a mean of 16.4 sessions and 528 min of direct occupational therapy services during the school year. According to the therapists, visual-motor skills and handwriting practice were emphasized most in intervention. Students in the intervention group showed significant increases in in-hand manipulation and position in space scores. They also improved more in handwriting legibility scores than the students in the comparison group. Fifteen students in the intervention group demonstrated greater than 90% legibility at the end of the school year. On average, legibility increased by 14.2% in the students who received services and by 5.8% in the students who did not receive services. Speed increased slightly more in the students who did not receive services. Students who received occupational therapy services demonstrated improved letter legibility, but speed and numeral legibility did not demonstrate positive intervention effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":33111374,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"NAFLD: Reporting Histologic Findings in Clinical Practice.\nThe role of liver biopsy in NASH has evolved along with the increased recognition of the significance of this disease, and the unmet medical need it presents. Drug development and clinical trials are rapidly growing, as are noninvasive tests for markers of steatosis, inflammation, injury, and fibrosis. Liver biopsy evaluation remains necessary for both drug development and clinical trials as the most specific means of diagnosis and patient identification for appropriate intervention. This White Paper, sponsored by the American Association for the Study of Liver Disease NASH Task Force, is a focused review of liver biopsy evaluation in fatty liver disease in subjects with presumed NAFLD for practicing clinical hepatologists and pathologists. The goal is to provide succinct and specific means for reporting the histopathologic elements of NASH, distinguishing NASH from nonalcoholic fatty liver without steatohepatitis, and from alcohol-associated steatohepatitis when possible. The discussion includes the special situations of NASH in advanced fibrosis or cirrhosis, and in the pediatric population. Finally, there is discussion of semiquantitative methods of evaluation of lesions of \"disease activity\" and fibrosis. Tables are presented for scoring and a suggested model for final reporting. Figures are presented to highlight the histopathologic elements of NASH.","subset":"pubmed_abstract"} +{"meta":{"pmid":27639665,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-22":1,"unknown":13}}},"text":"Upholding science in health, safety and environmental risk assessments and regulations.\nA public appeal has been advanced by a large group of scientists, concerned that science has been misused in attempting to quantify and regulate unmeasurable hazards and risks.1 The appeal recalls that science is unable to evaluate hazards that cannot be measured, and that science in such cases should not be invoked to justify risk assessments in health, safety and environmental regulations. The appeal also notes that most national and international statutes delineating the discretion of regulators are ambiguous about what rules of evidence ought to apply. Those statutes should be revised to ensure that the evidence for regulatory action is grounded on the standards of the scientific method, whenever feasible. When independent scientific evidence is not possible, policies and regulations should be informed by publicly debated trade-offs between socially desirable uses and social perceptions of affordable precaution. This article explores the premises, implications and actions supporting the appeal and its objectives.","subset":"pubmed_abstract"} +{"meta":{"pmid":29058059,"dup_signals":{"dup_doc_count":28,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2019-18":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-05":1,"2023-50":1,"2024-22":2}}},"text":"Correlates of Level and Loss of Grip Strength in Later Life: Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.\nCharacterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.","subset":"pubmed_abstract"} +{"meta":{"pmid":15556197,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":3,"unknown":11}}},"text":"Anthropogenic iodine-129 in seawater along a transect from the Norwegian coastal current to the North Pole.\nVariation in the concentrations of iodine-129 (129I, T1\/2=15.7 Myr), a low-level radioactive component of nuclear fuel waste, is documented in surface waters and depth profiles collected during 2001 along a transect from the Norwegian Coastal Current to the North Pole. The surface waters near the Norwegian coast are found to have 20 times higher 129I concentration than the surface waters of the Arctic Ocean. The depth profiles of 129I taken in the Arctic Ocean reveal a sharp decline in the concentration to a depth of about 300-500 m followed by a weaker gradient extending down to the bottom. A twofold increase in the 129I concentration is observed in the upper 1000 m since 1996. Based on known estimates of marine transient time from the release sources (the nuclear reprocessing facilities at La Hague, France, and Sellafield, UK), a doubling in the 129I inventory of the top 1000 m of the Arctic Ocean is expected to occur between the years 2001 and 2006. As 129I of polar mixed layer and Atlantic layer of the Arctic Ocean is ventilated by the East Greenland Current into the Nordic Seas and North Atlantic Ocean, further dispersal and increase of the isotope concentration in these regions will be encountered in the near future.","subset":"pubmed_abstract"} +{"meta":{"pmid":6605145,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Etiological factors in space motion sickness.\nWe compared susceptibility to motion sickness during exposure to sudden-stop stimulation as a function of gravitoinertial force level. Our findings show that susceptibility is greatly enhanced, both with eyes-closed and eyes-open, for zero-g and 2-g conditions in parabolic flight compared with 1-g test conditions. The change in susceptibility is likely related to three factors: alterations in vestibulo-ocular function which result from variations in gravitoinertial force level (28,29); the altered pattern of otolithic activity resulting during variations in gravitoinertial force level; and the altered canal-otolith response synergies that result during exposure to gravitoinertial force levels greater or less than terrestrial levels. These factors are shown to be related to the etiology of space motion sickness and to the alterations in performance and vestibular function that are experienced by astronauts during reentry. An explanation is also proposed for the decrease in susceptibility to motion sickness exhibited by the Skylab astronauts inflight and for some period postflight during exposure to cross-coupled angular accelerations.","subset":"pubmed_abstract"} +{"meta":{"pmid":23300586,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Consistent temperature coupling with thermal fluctuations of smooth particle hydrodynamics and molecular dynamics.\nWe propose a thermodynamically consistent and energy-conserving temperature coupling scheme between the atomistic and the continuum domain. The coupling scheme links the two domains using the DPDE (Dissipative Particle Dynamics at constant Energy) thermostat and is designed to handle strong temperature gradients across the atomistic\/continuum domain interface. The fundamentally different definitions of temperature in the continuum and atomistic domain - internal energy and heat capacity versus particle velocity - are accounted for in a straightforward and conceptually intuitive way by the DPDE thermostat. We verify the here-proposed scheme using a fluid, which is simultaneously represented as a continuum using Smooth Particle Hydrodynamics, and as an atomistically resolved liquid using Molecular Dynamics. In the case of equilibrium contact between both domains, we show that the correct microscopic equilibrium properties of the atomistic fluid are obtained. As an example of a strong non-equilibrium situation, we consider the propagation of a steady shock-wave from the continuum domain into the atomistic domain, and show that the coupling scheme conserves both energy and shock-wave dynamics. To demonstrate the applicability of our scheme to real systems, we consider shock loading of a phospholipid bilayer immersed in water in a multi-scale simulation, an interesting topic of biological relevance.","subset":"pubmed_abstract"} +{"meta":{"pmid":30971599,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Perioperative anesthesia management for pulmonary endarterectomy: Adopting an established European Protocol for the Asian Population.\nAnesthesia for pulmonary endarterectomy (PEA) has always been one of the challenges of anesthesia. As one of the leading cardiothoracic institutions in Southeast Asia, our hospital has vast interest in this subject. A local multidisciplinary team was deployed to an expert center in the United Kingdom (UK), and the experience was then integrated to the care of our patients. We present a case series of ten patients undergoing anesthesia for PEA, a first for our institution, and discuss techniques as well as potential complications. Patients with chronic thromboembolic pulmonary hypertension were reviewed by a multidisciplinary team, and those who were suitable for surgical intervention subsequently underwent PEA. A total of ten patients were identified and operated on. The perioperative management and conduction of anesthesia for all patients followed a protocol adapted from the expert center in the UK, with revisions to cater to our Asian population. In the ten patients operated on, eight of them were successfully extubated on the first postoperative day. Apart from one incident of prolonged ventilator usage due to reperfusion lung injury and pneumonia, there were no major respiratory or hemodynamic complications. Certainly, six of the ten patients developed subdural hemorrhage after the commencement of enoxaparin, although none of them sustained any permanent neurological deficits. We have demonstrated that with careful planning and a well-outlined protocol, anesthesia for PEA in an Asian population can be achieved with favorable outcomes. Further fine-tuning of the protocol is still required based on local expertise.","subset":"pubmed_abstract"} +{"meta":{"pmid":27590288,"dup_signals":{"dup_doc_count":51,"dup_dump_count":30,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":2,"2023-14":2,"2023-06":1,"2022-49":1,"2022-27":2,"2022-05":4,"2021-49":2,"2021-31":2,"2021-17":2,"2021-04":3,"2020-50":1,"2020-40":1,"2019-13":1,"2019-09":1,"2018-51":2,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":2,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":3,"2017-43":2,"2017-34":2,"2024-18":1,"2024-26":1}}},"text":"Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: A meta-analysis.\nTo determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during \u22653 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and \u22655 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. We included 5,068 patients from 15 studies. There were 115\/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212\/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49\/1,142 (4.3%) ICH events in those with CMBs vs 17\/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and \u22655 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and \u22655 CMBs, respectively). CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories.","subset":"pubmed_abstract"} +{"meta":{"pmid":22642713,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-06":1,"2013-48":3,"2013-20":1,"2015-18":1,"unknown":9}}},"text":"Statistical challenges in the development and evaluation of marker-based clinical tests.\nExciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a 'signature', have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision-making.","subset":"pubmed_abstract"} +{"meta":{"pmid":23965118,"dup_signals":{"dup_doc_count":54,"dup_dump_count":26,"dup_details":{"curated_sources":4,"2023-50":2,"2023-14":1,"2023-06":2,"2022-49":4,"2022-33":2,"2022-27":3,"2022-05":2,"2021-49":2,"2021-43":2,"2021-25":2,"2021-17":3,"2021-10":1,"2021-04":3,"2020-45":2,"2020-40":1,"2020-29":3,"2020-16":2,"2020-05":2,"2019-51":1,"2019-47":2,"2019-43":1,"2019-35":2,"2019-26":2,"2019-18":1,"2019-09":1,"2024-10":1}}},"text":"What Is Special about Face Recognition? Nineteen Experiments on a Person with Visual Object Agnosia and Dyslexia but Normal Face Recognition.\nIn order to study face recognition in relative isolation from visual processes that may also contribute to object recognition and reading, we investigated CK, a man with normal face recognition but with object agnosia and dyslexia caused by a closed-head injury. We administered recognition tests of up right faces, of family resemblance, of age-transformed faces, of caricatures, of cartoons, of inverted faces, and of face features, of disguised faces, of perceptually degraded faces, of fractured faces, of faces parts, and of faces whose parts were made of objects. We compared CK's performance with that of at least 12 control participants. We found that CK performed as well as controls as long as the face was upright and retained the configurational integrity among the internal facial features, the eyes, nose, and mouth. This held regardless of whether the face was disguised or degraded and whether the face was represented as a photo, a caricature, a cartoon, or a face composed of objects. In the last case, CK perceived the face but, unlike controls, was rarely aware that it was composed of objects. When the face, or just the internal features, were inverted or when the configurational gestalt was broken by fracturing the face or misaligning the top and bottom halves, CK's performance suffered far more than that of controls. We conclude that face recognition normally depends on two systems: (1) a holistic, face-specific system that is dependent on orientationspecific coding of second-order relational features (internal), which is intact in CK and (2) a part-based object-recognition system, which is damaged in CK and which contributes to face recognition when the face stimulus does not satisfy the domain-specific conditions needed to activate the face system.","subset":"pubmed_abstract"} +{"meta":{"pmid":28010112,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Peptide engineered microcantilevers for selective chemical force microscopy and monitoring of nanoparticle capture.\nEngineered peptides capable of binding to silica have been used to provide contrast in chemical force microscopy and tested for their capacity to selectively capture silica nanoparticles (NPs). Gold coated atomic force microscopy (AFM) microcantilevers with integrated tips and colloidal probes were functionalized with engineered peptides through a thiol group of a terminal cysteine which was linked via a glycine trimer to a 12-mer binding sequence. The functionalized probes demonstrated a significantly increased binding force on silicon oxide areas of a gold-patterned silicon wafer, whereas plain gold probes, and those functionalized with a random permutation of the silica binding peptide motif or an all-histidine sequence displayed similar adhesion forces to gold and silicon oxide. As the functionalized probes also allowed contact mode imaging subsequently to the adhesion mapping, also the associated friction contrast was measured and found to be similar to the adhesion contrast. Furthermore, the adsorption of silica NPs onto planar gold surfaces functionalized in the same manner was observed to be selective. Notably, the surface coverage with silica NPs was found to decrease with increasing pH, implying the importance of electrostatic interactions between the peptide and the NPs. Finally, the adsorption of silica NPs was monitored via the decrease in fundamental resonance frequency of an AFM microcantilever functionalized with silica binding peptides.","subset":"pubmed_abstract"} +{"meta":{"pmid":7920972,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Influence of the autonomic nervous system on calcium homeostasis in the rat.\nThe local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29165043,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2022-21":1,"2021-49":1,"2021-25":2,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":2,"2020-16":2,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2023-50":1}}},"text":"Autophagy balances inflammation in innate immunity.\nMacroautophagy\/autophagy is a homeostatic process with multiple effects on immunity. One of the pivotal contributions of autophagy in immunity is the cell autonomous control of inflammation. This property leads to systemic consequences and thereby influences the development of innate and adaptive immunity, which promotes or suppresses pathology in various disease contexts. In this review we focus on the intersections between autophagy and inflammasome activation, autophagy and interferons, and autophagy and inflammation in association with infection.","subset":"pubmed_abstract"} +{"meta":{"pmid":7713407,"dup_signals":{"dup_doc_count":28,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2021-43":2,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":3,"2020-34":2,"2020-29":1,"2020-24":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-13":1,"2018-43":1,"2018-30":1,"2018-26":1,"2017-47":1,"2017-26":1,"2021-49":1}}},"text":"Statistical analysis of crossover interference using the chi-square model.\nThe chi-square model (also known as the gamma model with integer shape parameter) for the occurrence of crossovers along a chromosome was first proposed in the 1940's as a description of interference that was mathematically tractable but without biological basis. Recently, the chi-square model has been reintroduced into the literature from a biological perspective. It arises as a result of certain hypothesized constraints on the resolution of randomly distributed crossover intermediates. In this paper under the assumption of no chromatid interference, the probability for any single spore or tetrad joint recombination pattern is derived under the chi-square model. The method of maximum likelihood is then used to estimate the chi-square parameter m and genetic distances among marker loci. We discuss how to interpret the goodness-of-fit statistics appropriately when there are some recombination classes that have only a small number of observations. Finally, comparisons are made between the chi-square model and some other tractable models in the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":28806301,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity.\nTo longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome. ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome. ALPPS centers of the International ALPPS Registry having performed \u226510 cases over a period of \u22653 years were assessed for 90-day mortality and major interstage complications (\u22653b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies. Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P < 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers. Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":15929892,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Perinatal exposure to low levels of the environmental antiandrogen vinclozolin alters sex-differentiated social play and sexual behaviors in the rat.\nIn this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg\/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg\/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg\/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs.","subset":"pubmed_abstract"} +{"meta":{"pmid":26585929,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"LC-MS\/MS for Identifying Patients with CYP24A1 Mutations.\nPatients have been described with loss-of-function CYP24A1 (cytochrome P450, family 24, subfamily A, polypeptide 1) mutations that cause a high ratio of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D [25(OH)D\/24,25(OH)2D], increased serum 1,25-dihydroxyvitamin D, and resulting hypercalcemia, hypercalciuria and nephrolithiasis. A 25(OH)D\/24,25(OH)2D ratio that can identify patients who are candidates for confirmatory CYP24A1 genetic testing would be valuable. We validated an LC-MS\/MS assay for 24,25(OH)2D (D3 and D2) and determined a 25(OH)D\/24,25(OH)2D cutoff to identify candidates for confirmatory genetic testing. After addition of isotope-labeled internal standard, serum samples were extracted by solid-phase extraction, derivatized with 4-phenyl-1,2,4,-triazoline-3,5-dione, and quantified by LC-MS\/MS. We measured 25(OH)D\/24,25(OH)2D in 91 healthy patients and 34 patients with clinically suspected CYP24A1-mediated hypercalcemia. The limits of detection and quantification were 0.03 (0.2) and 0.1 (0.24) nmol\/L, respectively, for 24,25(OH)2D3, and 0.1 (0.23) and 0.5 (1.16) nmol\/L for 24,25(OH)2D2. Intra- and interassay imprecision was 4%-15% across the analytical measurement range of 0.1-25 ng\/mL (0.2-60 nmol\/L). No interference was observed with 25(OH)D and 1,25(OH)2D. 25(OH)D\/24,25(OH)2D of 7-35 was observed in healthy patients, whereas in 2 patients with CYP24A1 mutations, 25(OH)D\/24,25(OH)2D was significantly increased (99-467; P < 0.001). A 25(OH)D\/24,25(OH)2D ratio \u226599 identified patients who were candidates for CYP24A1 genetic testing. Increased 25(OH)D\/24,25(OH)2D supports the diagnosis of reduced CYP24A1 activity due to mutations in CYP24A1. Measurement of 25(OH)D\/24,25(OH)2D should be considered a part of the clinical workup in patients with hypercalcemia of otherwise unknown etiology.","subset":"pubmed_abstract"} +{"meta":{"pmid":27447649,"dup_signals":{"dup_doc_count":20,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2019-47":2,"2019-39":1,"2019-30":1,"2019-22":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-13":1,"2017-51":2,"2017-43":1,"2017-34":1,"2017-26":1,"2017-13":1}}},"text":"Transcriptome of the Australian Mollusc Dicathais orbita Provides Insights into the Biosynthesis of Indoles and Choline Esters.\nDicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that produce these secondary metabolites in D. orbita are not known. Illumina HiSeq 2000 transcriptome sequencing of hypobranchial glands, prostate glands, albumen glands, capsule glands, and mantle and foot tissues of D. orbita generated over 201 million high quality reads that were de novo assembled into 219,437 contigs. Annotation with reference to the Nr, Swiss-Prot and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases identified candidate-coding regions in 76,152 of these contigs, with transcripts for many enzymes in various metabolic pathways associated with secondary metabolite biosynthesis represented. This study revealed that D. orbita expresses a number of genes associated with indole, sulfur and histidine metabolism pathways that are relevant to Tyrian purple precursor biosynthesis, and many of which were not found in the fully annotated genomes of three other molluscs in the KEGG database. However, there were no matches to known bromoperoxidase enzymes within the D. orbita transcripts. These transcriptome data provide a significant molecular resource for gastropod research in general and Tyrian purple producing Muricidae in particular.","subset":"pubmed_abstract"} +{"meta":{"pmid":16710058,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Structure prediction of ordered and disordered multiple octahedral cation perovskites using SPuDS.\nThe software package SPuDS has previously been shown to accurately predict crystal structures of AMX(3) and A(1 - x)A'(x)MX(3) perovskites that have undergone octahedral tilting distortions. This paper describes the extension of this technique and its accuracy for A(2)MM'X(6) ordered double perovskites with the aristotype Fm\\overline 3m cubic structure, as well as those that have undergone octahedral tilting distortions. A survey of the literature shows that roughly 70% of all ordered double perovskites undergo octahedral tilting distortions. Of the 11 distinct types of octahedral tilting that can occur in ordered perovskites, five tilt systems account for approximately 97% of the reported structures. SPuDS can calculate structures for the five dominant tilt systems, Fm\\overline 3m (a(0)a(0)a(0)), I4\/m (a(0)a(0)c(-)), R\\overline 3 (a(-)a(-)a(-)), I2\/m (a(0)b(-)b(-)) and P2(1)\/n (a(-)a(-)b(+)), as well as two additional tilt systems, Pn\\overline 3 (a(+)a(+)a(+)) and P4\/mnc (a(0)a(0)c(+)). Comparison with reported crystal structures shows that SPuDS is quite accurate at predicting distortions driven by octahedral tilting. The favored modes of octahedral tilting in ordered double perovskites are compared and contrasted with those in AMX(3) perovskites. Unit-cell pseudosymmetry in Sr- and Ca-containing double perovskites is also examined. Experimentally, Sr(2)MM'O(6) compounds show a much stronger tendency toward pseudosymmetry than do Ca(2)MM'O(6) compounds with similar tolerance factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":29312534,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"The PAX8 cistrome in epithelial ovarian cancer.\nPAX8 is a lineage-restricted transcription factor that is expressed in epithelial ovarian cancer (EOC) precursor tissues, and in the major EOC histotypes. Frequent overexpression of PAX8 in primary EOCs suggests this factor functions as an oncogene during tumorigenesis, however, the biological role of PAX8 in EOC development is poorly understood. We found that stable knockdown of PAX8 in EOC models significantly reduced cell proliferation and anchorage dependent growth in vitro, and attenuated tumorigenicity in vivo. Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and transcriptional profiling were used to create genome-wide maps of PAX8 binding and putative target genes. PAX8 binding sites were significantly enriched in promoter regions (p < 0.05) and superenhancers (p < 0.05). MEME-ChIP analysis revealed that PAX8 binding sites overlapping superenhancers or enhancers, but not promoters, were enriched for JUND\/B and ARNT\/AHR motifs. Integrating PAX8 ChIP-seq and gene expression data identified PAX8 target genes through their associations within shared topological association domains. Across two EOC models we identified 62 direct regulatory targets based on PAX8 binding in promoters and 1,330 putative enhancer regulatory targets. SEPW1, which is involved in oxidation-reduction, was identified as a PAX8 target gene in both cell line models. While the PAX8 cistrome exhibits a high degree of cell-type specificity, analyses of PAX8 target genes and putative cofactors identified common molecular targets and partners as candidate therapeutic targets for EOC.","subset":"pubmed_abstract"} +{"meta":{"pmid":26109166,"dup_signals":{"dup_doc_count":11}},"text":"Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training.\nTo investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP\/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1\u03b1 (PDH-E1\u03b1) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice. These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":12003231,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Activation of microcomponents with light for micro-electro-mechanical systems and micro-optical-electro-mechanical systems applications.\nWe examine the light-activation properties of micrometer-sized gear structures fabricated with polysilicon surface micromachining techniques. The gears are held in place on a substrate through a capped anchor post and are free to rotate about the post. The light-activation technique is modeled on photon radiation pressure, and the equation of motion of the gear is solved for this activation technique. Experimental measurements of torque and damping are found to be consistent with expected results for micrometer-scale devices. Design optimization for optically actuated microstructures is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":14730449,"dup_signals":{"dup_doc_count":45,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2023-23":2,"2022-49":2,"2022-33":1,"2022-27":3,"2022-21":2,"2022-05":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":5,"2020-16":1,"2020-10":1,"2019-18":3,"2019-13":1,"2019-09":3,"2019-04":1,"2018-51":2,"2018-17":1,"2018-05":1,"2017-30":1,"2017-17":1,"2023-50":1,"2024-30":2,"2024-22":1,"2024-10":1,"2017-13":1}}},"text":"Modeling of stimulation-secretion coupling in a chromaffin cell.\nWe constructed a chromaffin cell model for analysis of stimulation-secretion coupling in computer simulation studies. The model includes mechanisms involved in the excitatory synapse, voltage-dependent Na(+), K(+) and Ca(2+) channels, Ca(2+)-activated K(+) channels (SK type), buffered Ca(2+) diffusion, Ca(2+) extrusion, fluorescent Ca(2+) indicators and Ca(2+)-triggered exocytosis. Calculations of the modeled mechanisms were carried out using the NEURON simulation environment (Hines and Carnevale, Neural Computation 9:1179-1209, 1997). A set of parameter values was determined so as to fit basic experimental results reported in the literature. The model was also applied to simulate our experimental results obtained from chromaffin cells in the perfused rat adrenal medulla. Observed profiles of Ca(2+)responses induced by electrically stimulating the splanchnic nerve with various frequencies (1-50 Hz) were adequately simulated with minor readjustments of parameter values for Ca(2+)influx and extrusion. Secretory responses measured at the same time as the Ca(2+)responses were also simulated with consideration of a time constant to detect catecholamines in the experiment. Similarly, model simulations reproduced both Ca(2+)responses and secretory responses evoked by elevations of the extracellular K(+) concentration for different periods. The results suggest that the presented model provides a useful tool for analyzing and predicting quantitative relations in various events occurring in stimulation-secretion coupling in chromaffin cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":23388107,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":7}}},"text":"Pharmacological, antioxidant, genotoxic studies and modulation of rat splenocyte functions by Cyperus rotundus extracts.\nCyperus rotundus Linn. (Cyperaceae) is a Tunisian medicinal plant used in folkloric (traditional) medicine to treat stomach disorders and inflammatory diseases. The present study explored the analgesic, anti-inflammatory and genotoxic activities of extracts from the aerial parts of C. rotundus. The antioxidant capacity and the modulation of splenocyte functions by these extracts were also investigated in mice. The phytochemical analysis was carried out using standard methods. Aqueous, ethyl acetate, methanol and TOF-enriched extracts (300, 150, and 50 \u03bcg\/ml) were evaluated for their analgesic and anti-inflammatory activities. 4, 2, and 1 mg\/ml of each extract were tested to investigate their effect on lipid peroxidation. The genotoxic study was monitored by measuring the structural chromosome aberrations of mice treated with 300 mg\/kg of extract. The proliferation of lymphocytes in the absence and presence of mitogens was assessed at a concentration range 1-1000 \u03bcg\/ml. The tested extracts were able to decrease the mouse ear oedema induced by xylene. Furthermore, it was shown that the same extracts reduced the number of abdominal contractions caused by acetic acid in mice, revealing the peripheral analgesic activity of these extracts. It is worth noting that mice treated with doses up to 300 mg\/kg b.w. of Cyperus rotundus extracts did not exhibit any toxicity. The tested extracts significantly enhance lymphocyte proliferation at 1 mg\/ml. It appears that C. rotundus extracts contain potent components such as flavonoids that may potentially be useful for modulating the immune cell functions, provoking analgesic, anti-inflammatory and antioxidant effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":38072185,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":6,"unknown":6}}},"text":"Octopamine is involved in TRP- induced thermopreference responses in American cockroach.\nInsects' thermoregulatory processes depend on thermosensation and further processing of thermal information in the nervous system. It is commonly known that thermosensation involves thermoreceptors, including members of the TRP receptor family, but the involvement of neurotransmitters in thermoregulatory pathways remains unstudied. We conducted test to determine whether octopamine, a biogenic amine that acts as a neurotransmitter and neurohormone in insects, is involved in TRP-induced thermoregulatory responses in Periplaneta americana. We used capsaicin, an activator of the heat-sensitive TRP channel, Painless, to induce thermoregulatory response in cockroaches. Then, we evaluated the behavioural (thermal preferences and grooming), physiological (heart rate) and biochemical responses of insects to capsaicin, octopamine and phentolamine - octopaminergic receptor blocker. Capsaicin, similar to octopamine, increased cockroaches' grooming activity and heart rate. Moreover, octopamine level and protein kinase A (PKA) activity significantly increased after capsaicin treatment. Blocking octopaminergic receptors with phentolamine diminished cockroaches' response to capsaicin - thermoregulatory behaviour, grooming and heart rate were abolished. The results indicate that octopamine is a neurotransmitter secreted in insects after the activation of heat receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":17106405,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":7}}},"text":"Reading with central scotomas: is there a binocular gain?\nThe purpose of this study was to compare reading performance under binocular versus monocular viewing conditions in patients with bilateral age-related macular degeneration (AMD). Twenty-two patients with AMD participated. Distance acuity, reading acuity, and contrast sensitivity were recorded binocularly and monocularly with the better eye. An infrared eye tracker recorded eye movements during reading. Reading speed and reading eye movement parameters, including number of fixations and regressions, fixation duration, and number of saccades to find the next line, were calculated for both viewing conditions. The difference between binocular and monocular performance (binocular gain) was computed. Regression analysis was used to determine whether intraocular differences in distance and reading acuity and contrast sensitivity were predictive of binocular gain. Reading speed when using both eyes was highly correlated with the reading speed for the better eye. There was a small, but not significant, advantage of binocular viewing (6.9 words\/minute, p = 0.33). No significant difference was detected in any eye movement parameters when comparing both eyes with the better eye. Although some patients showed either positive or negative binocular gain, the amount of gain was not predicted by intraocular differences in acuity or contrast sensitivity. Overall, there was no significant difference between binocular and monocular reading performance in patients with AMD.","subset":"pubmed_abstract"} +{"meta":{"pmid":7026125,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Characterization of aggression-provoked renin from an unknown source in male mice.\n1. In male mice without kidneys and submaxillary, as well as sublingual, glands aggressive behaviour causes a vast release of renin [J. Bing & K. Poulsen (1979) Acta Physiologica Scandinavica, 107, 251-256]. 2. This resulted in about an 800-fold increase in plasma renin concentration from the control level of 0.52 (range 0.15-0.8) Goldblatt unit (G.U.) x 10(-3)\/ml to 430 (range 300-500) G.U. x 10(-3)\/ml after aggression. 3. The aggression-provoked renin fulfil all the criteria so far studied for being active renin, identical with normal mouse plasma renin and pure submaxillary mouse renin. 4. It generates angiotensin I with renin substrate and Km (1.2 mumol\/l) is the same. It is neutralized by pepstatin but not by inhibitors of metallo-, thiol and serine proteinases, indicating that it is an aspartate proteinase (acidic proteinase). 5. It is a 40 000-mol.wt. renin, which has full enzymatic activity with a specific enzymatic activity of 0.32 G.U.\/micrograms, identical with that of normal plasma renin. 6. Its enzymatic activity is neutralized by a specific antibody against pure submaxillary renin. It is measureable in the direct renin radioimmunoassay with a dilution curve which parallels that of the standards. It demonstrates complete antigenic identity with pure submaxillary renin in crossed immunoelectrophoresis. 7. Its origin is unknown.","subset":"pubmed_abstract"} +{"meta":{"pmid":9453689,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Early predictors of bladder recovery and urodynamics after spinal cord injury.\nOur purpose was to determine if intact perianal (S4-5) pin sensation (PPS) and bulbocavernosus (S2-4) reflex (BCR) shortly after spinal cord injury (SCI) are predictive of bladder function recovery. Twenty-eight SCI patients (aged 18-68 years, Frankel Classification A-D, spinal injury level C4-T12), admitted within 72 hours of injury, underwent evaluation of initial PPS and BCR. The presence of intact PPS and BCR were correlated with the patient's voiding function and urodynamic evaluation results 1 year postinjury. Of the 28 patients within 72 hours of SCI, PPS was intact in 17 (60%) and absent in 11(40%), while 15 patients (54%) demonstrated a positive BCR and 13 (46%) did not. One year after SCI, no patient with absent PPS voided unassisted, while of the 17 patients with preserved PPS, 11 (65%) were voiding spontaneously. Of these 11 patients, urodynamic evaluation revealed detrusor areflexia in 1 (9%), normal detrusor function in 2 (18%), and detrusor hyperreflexia in 8 (73%), with 3 of these 8 patients (38%) also demonstrating detrusor-sphincter dyssynergia. At 1 year postinjury, only 2 of 13 patients (15%) with an absent BCR voided spontaneously, while 9 of 15 patients (60%) with an intact BCR were able to void. Although PPS and BCR are moderately sensitive in predicting the return of spontaneous voiding, they cannot predict detrusor hyperreflexia and sphincter dyssynergia. Therefore, urodynamic study remains an essential component of initial urologic evaluation after SCI.","subset":"pubmed_abstract"} +{"meta":{"pmid":7924017,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":4,"unknown":11}}},"text":"Renal pathology in pre-eclampsia.\nPre-eclampsia affects the kidney both functionally and morphologically. Renal haemodynamics decrease and urinary protein excretion increases, in part due to lesions affecting the glomerulus, where a combination of changes produces a characteristic appearance and permits differentiation of pre-eclamptic nephropathy from other glomerular alterations associated with hypertension in pregnancy. In pre-eclampsia the glomerulus is diffusely enlarged and bloodless, due not to proliferation, but to hypertrophy of the intracapillary cells. These alterations, best described ultrastructurally, include hypertrophy of the cytoplasmic organelles in endothelial and occasionally mesangial cells, particularly the lysosomes, which undergo marked enlargement and vacuolization (due to accumulation of free neutral lipids). These reactive changes have been termed 'glomerular capillary endotheliosis'. Other lesions, observed occasionally, include subendothelial and mesangial electron-dense deposits, as well as interposition of mesangial cell cytoplasm or mesangial matrix along an otherwise normal basement membrane. Some investigators have described immunohistological findings (presence of IgM, IgG and fibrin) which they believe specific for pre-eclampsia, and others have claimed the disease may cause focal segmental glomerulosclerosis (FSGS). We believe the immunohistological findings are non-specific and insudative, and that FSGS when present predates the pre-eclamptic complication. Finally, the renal lesions appear fully reversible and the disease has no remote cardiorenal effects on its patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":12667548,"dup_signals":{"dup_doc_count":21,"dup_dump_count":20,"dup_details":{"curated_sources":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-31":1,"2020-50":1,"2020-24":1,"2020-05":1,"2019-47":1,"2019-35":1,"2019-18":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2023-40":1}}},"text":"Bone mineral density and the risk of breast cancer: the Rotterdam Study.\nEstrogens play an important role in the development of breast cancer, but studies on serum levels of estrogens have shown inconsistent results. Bone mineral density is considered to be a marker for lifetime estrogen exposure. Some studies have suggested that a higher bone mass is associated with an increase in breast cancer risk. We investigated the association between bone mineral density (BMD), as measured at the lumbar spine and femoral neck, and the risk of breast cancer in women age 55 or older in the Rotterdam Study, a population-based cohort study in the Netherlands. Information on baseline lumbar spine and femoral neck BMD, as measured by DEXA (Lunar DPX-L), and cancer incidence was available for 3,107 women. The Rotterdam Cancer Registry provided information on follow-up of incident cancer. After an average follow-up time of 6.5 years, 74 new cases of breast cancer occurred. Z-scores of lumbar spine and femoral neck BMD were divided into tertiles and risk estimates for breast cancer were computed by the Cox proportional hazards model, using the middle tertile as a reference. Breast cancer risk in the upper tertile of lumbar spine BMD was doubled compared to the reference after adjustment for age, body mass index, and age at menopause (hazards ratio = 2.1 [1.1-3.7]), whereas risk estimates for women in the lower tertile did not significantly differ from the reference (hazards ratio = 1.5 [0.8-2.9]). Women with either a low intertrochanteric or femoral neck BMD appeared to have a somewhat decreased breast cancer risk, although this was not statistically significant. The results of this study suggest that in elderly women an association between especially lumbar spine BMD and incident breast cancer exists. Stimulating effects of estrogen on both trabecular bone and mammary cells may be responsible.","subset":"pubmed_abstract"} +{"meta":{"pmid":29521190,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"BMPR2 mutations and endothelial dysfunction in pulmonary arterial hypertension (2017 Grover Conference Series).\nDespite the discovery more than 15 years ago that patients with hereditary pulmonary arterial hypertension (HPAH) inherit BMP type 2 receptor ( BMPR2) mutations, it is still unclear how these mutations cause disease. In part, this is attributable to the rarity of HPAH and difficulty obtaining tissue samples from patients with early disease. However, in addition, limitations to the approaches used to study the effects of BMPR2 mutations on the pulmonary vasculature have restricted our ability to determine how individual mutations give rise to progressive pulmonary vascular pathology in HPAH. The importance of understanding the mechanisms by which BMPR2 mutations cause disease in patients with HPAH is underscored by evidence that there is reduced BMPR2 expression in patients with other, more common, non-hereditary form of PAH, and that restoration of BMPR2 expression reverses established disease in experimental models of pulmonary hypertension. In this paper, we focus on the effects on endothelial function. We discuss some of the controversies and challenges that have faced investigators exploring the role of BMPR2 mutations in HPAH, focusing specifically on the effects different BMPR2 mutation have on endothelial function, and whether there are qualitative differences between different BMPR2 mutations. We discuss evidence that BMPR2 signaling regulates a number of responses that may account for endothelial abnormalities in HPAH and summarize limitations of the models that are used to study these effects. Finally, we discuss evidence that BMPR2-dependent effects on endothelial metabolism provides a unifying explanation for the many of the BMPR2 mutation-dependent effects that have been described in patients with HPAH.","subset":"pubmed_abstract"} +{"meta":{"pmid":7153115,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Measurement of regional bronchial arterial blood flow and bronchovascular resistance in dogs.\nLittle is known about normal variations and control of bronchial blood flow and bronchovascular resistance. We have used the reference-flow technique and 15-microns-diameter microspheres to measure bronchial blood flow under physiological conditions. Dogs (n = 13) were anesthetized and ventilated, and their chests were opened. A ligature was placed loosely around the left main pulmonary artery, and the left atrium was cannulated. In six dogs three sets of microspheres were injected simultaneously into the left atrium, and in another seven dogs the three sets of microspheres were injected sequentially at 0.5-h intervals. Prior to each injection measurements of pulmonary arterial, left atrial, and aortic pressures, cardiac output, and blood gases were made. Five seconds after injection the left main pulmonary artery was transiently occluded to prevent recirculation. After the final injection, dogs were killed, the lungs were removed, and the parenchyma was stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the reference flow blood and also the aortic and left atrial pressures, we calculated bronchial blood flow (ml X min-1 X g dry lung-1) and bronchovascular resistance (cmH2O X ml-1 X min X 100 g dry lung). Results showed that there were no significant differences between the three measurements of bronchial blood flow when microspheres were injected simultaneously or sequentially. Bronchial blood flow to the left lung was 0.4% of cardiac output; 55% of the total flow went to lung parenchyma and 45% to trachea and bronchi. Expressed as flow\/g dry lung the greatest flow was to the airways.","subset":"pubmed_abstract"} +{"meta":{"pmid":29437047,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Public Health Approach to Addressing the Needs of Children Affected by Congenital Zika Syndrome.\nWe have learned much about the short-term sequelae of congenital Zika virus (ZIKV) infection since the Centers for Disease Control and Prevention activated its ZIKV emergency response in January 2016. Nevertheless, gaps remain in our understanding of the full spectrum of adverse health outcomes related to congenital ZIKV infection and how to optimize health in those who are affected. To address the remaining knowledge gaps, support affected children so they can reach their full potential, and make the best use of available resources, a carefully planned public health approach in partnership with pediatric health care providers is needed. An essential step is to use population-based data captured through surveillance systems to describe congenital Zika syndrome. Another key step is using collected data to investigate why some children exhibit certain sequelae during infancy and beyond, whereas others do not, and to describe the clustering of anomalies and the timing of when these anomalies occur, among other research questions. The final critical step in the public health framework for congenital Zika syndrome is an intervention strategy with evidence-based best practices for longer-term monitoring and care. Adherence to recommended evaluation and management procedures for infants with possible congenital ZIKV infection, including for those with less obvious developmental and medical needs at birth, is essential. It will take many years to fully understand the effects of ZIKV on those who are congenitally infected; however, the lifetime medical and educational costs as well as the emotional impact on affected children and families are likely to be substantial.","subset":"pubmed_abstract"} +{"meta":{"pmid":31807739,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Temporal evolution of concentration and microstructure of colloidal films during vertical drying: a lattice Boltzmann simulation study.\nWe study the temporal and structural development of colloid films during vertical drying using the lattice Boltzmann (LB) simulation. The dispersed particles moving in Brownian motion have excluded volume and hydrodynamic interactions in the film. The concentrated colloidal film formed by solvent evaporation is modeled as an uniaxial compression of colloids with a planar moving interface. The simulation studies are carried out over a wide range of P\u00e9clet number (Pe), the relative ratio between the evaporation rate and the diffusion rate of colloids. The results clearly demonstrate a temporal variation of colloid concentration as the evaporation rate increases. In the case of high Pe, the increase of colloid concentration in the top layer creates structural features that can be distinguished along the height of the film, and eventually can induce a large tensile stress in the layer. However, surprisingly, the colloids are maximally crystallized in the case of moderate Pe. The LB simulation results are further compared with those from previous studies of the Brownian Dynamics (BD) simulation and the continuum model for the evaporation film. The LB and BD results match well both at low and high Pe limits. The qualitatively significant differences between LB and BD simulations at a moderate Pe indicate that hydrodynamic interactions (HIs) play an important role in this Pe. The presence of HIs induces a greater reduction of diffusion than under geometrical restriction alone, and the effect is conspicuous when particles are driven both by diffusion and by advection.","subset":"pubmed_abstract"} +{"meta":{"pmid":24006224,"dup_signals":{"dup_doc_count":16,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2021-17":1,"2020-50":1,"2020-40":1,"2020-24":1,"2019-43":1,"2019-26":1,"2019-09":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2021-31":1}}},"text":"Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer.\nLong noncoding RNAs (lncRNAs) have emerged recently as major players in governing fundamental biological processes, and many of which are altered in expression and likely to have a functional role in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA associated with various human cancers. However, its biological role and clinical significance in gastric cancer development and progression are unknown. In this study, to investigate the lncRNA MEG3 expression in gastric cancer, quantitative reverse-transcription polymerase chain reaction was conducted. We found that MEG3 levels were markedly decreased in gastric cancer tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, depth of invasion, and tumor size. Moreover, patients with low levels of MEG3 expression had a relatively poor prognosis. Furthermore, knockdown of MEG3 expression by siRNA could promote cell proliferation, while ectopic expression of MEG3 inhibited cell proliferation, promoted cell apoptosis, and modulated p53 expression in gastric cancer cell lines. By 5-aza-CdR treatment, we also observed that MEG3 expression can be modulated by DNA methylation. Our findings present that MEG3 downexpression can be identified as a poor prognostic biomarker in gastric cancer and regulate cell proliferation and apoptosis in vitro.","subset":"pubmed_abstract"} +{"meta":{"pmid":26494858,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo.\nDespite recent advances in the development of novel therapies against castration-resistant prostate cancer, the advanced form of the disease remains a major treatment challenge. Aberrant sphingolipid signaling through sphingosine kinases and their product, sphingosine-1-phosphate, can promote proliferation, drug resistance, angiogenesis, and inflammation. The sphingosine kinase 2 inhibitor ABC294640 is undergoing clinical testing in cancer patients, and in this study we investigated the effects this first-in-class inhibitor in castration-resistant prostate cancer. In vitro, ABC294640 decreased prostate cancer cell viability as well as the expression of c-Myc and the androgen receptor, while lysosomal acidification increased. ABC294640 also induced a greater than 3-fold increase in dihydroceramides that inversely correlated with inhibition of dihydroceramide desaturase (DEGS) activity. Expression of sphingosine kinase 2 was dispensable for the ABC294640-mediated increase in dihydroceramides. In vivo, ABC294640 diminished the growth rate of TRAMP-C2 xenografts in syngeneic hosts and elevated dihydroceramides within tumors as visualized by MALDI imaging mass spectroscopy. The plasma of ABC294640-treated mice contained significantly higher levels of C16- and C24:1-ceramides (but not dihydro-C16-ceramide) compared with vehicle-treated mice. In summary, our results suggest that ABC294640 may reduce the proliferative capacity of castration-resistant prostate cancer cells through inhibition of both sphingosine kinase 2 and dihydroceramide desaturase, thereby providing a foundation for future exploration of this small-molecule inhibitor for the treatment of advanced disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":22361702,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Defensive spending on tap water substitutes: the value of reducing perceived health risks.\nWe examine factors that explain consumer spending on tap water substitutes using information from a national survey undertaken with a representative set of Canadian respondents. We develop a model to predict the percentage of households that undertake such spending for the purpose of reducing perceived health risks from tap water consumption. Using results from the model we estimate the magnitude of defensive expenditures to be over half a billion dollars (2010 US$) per year for Canada, as a whole. This is equivalent to approximately $48 per household per year or about $19 per person per year. Residents of Ontario, the province in which an Escherichia coli incident took place in 2000, have the highest willingness-to-pay of approximately $60 per household per year.","subset":"pubmed_abstract"} +{"meta":{"pmid":29080067,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Interventions Targeting the Prescribing and Monitoring of Vancomycin for Hospitalized Patients: A Systematic Review Protocol.\nVancomycin remains one of our essential antibiotics after fifty years of treating serious infections such as methicillin-resistant Staphylococcus aureus. Vancomycin, unlike many other antibiotic agents, requires individualized dosing and monitoring of serum drug levels to ensure it is efficacious, to minimize toxicity, and to limit the development of antibiotic resistance. These issues have led to numerous vancomycin clinical practice guidelines being published in recent years including several key national guidelines. Significant resources are invested during the development of such guidelines; however, there is often little or no information about how such guidelines or other vancomycin practice improvement initiatives should be implemented. The aim of this systematic review is to identify and evaluate the effect of interventions using education, guideline implementation, and dissemination of educational resources that have sought to improve therapeutic drug monitoring and dosing of vancomycin. A systematic review of the literature will be conducted for RCTs and observational studies where a vancomycin guideline or practice improvement initiative has been implemented. Electronic databases to be searched are PubMed, Medline, CINAHL, EMBASE and the Cochrane Library of Systematic Reviews. The population will be patients who have had intravenous vancomycin prescribed and monitored in hospital. The interventions will be education, implementation of guidelines or protocols, dissemination of educational materials (printed or electronic) or multifaceted interventions of the above. The comparator will be patients who have had standard-care prescribing and monitoring of vancomycin. Outcomes will be changes in prescribing and ordering of vancomycin serum tests, and serum levels attained in patients as well as reported nephrotoxicity. Two reviewers will be involved in the quality assessment and extraction of data. The Scottish Intercollegiate Guidelines Network checklist for RCTs will be used. Studies that are not randomized will be assessed for quality using the validated ROBINS-I (risk of bias in non-randomized studies of interventions) tool. This systematic review will identify interventions that have been used to implement guidelines and clinical practice initiatives for vancomycin. The findings of this review may be informative to those involved with the implementation of vancomycin clinical practice guidelines. Systematic review registration: PROSPERO: CRD42016049147.","subset":"pubmed_abstract"} +{"meta":{"pmid":23322356,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Bayesian nonparametric centered random effects models with variable selection.\nIn a linear mixed effects model, it is common practice to assume that the random effects follow a parametric distribution such as a normal distribution with mean zero. However, in the case of variable selection, substantial violation of the normality assumption can potentially impact the subset selection and result in poor interpretation and even incorrect results. In nonparametric random effects models, the random effects generally have a nonzero mean, which causes an identifiability problem for the fixed effects that are paired with the random effects. In this article, we focus on a Bayesian method for variable selection. We characterize the subject-specific random effects nonparametrically with a Dirichlet process and resolve the bias simultaneously. In particular, we propose flexible modeling of the conditional distribution of the random effects with changes across the predictor space. The approach is implemented using a stochastic search Gibbs sampler to identify subsets of fixed effects and random effects to be included in the model. Simulations are provided to evaluate and compare the performance of our approach to the existing ones. We then apply the new approach to a real data example, cross-country and interlaboratory rodent uterotrophic bioassay.","subset":"pubmed_abstract"} +{"meta":{"pmid":31796753,"dup_signals":{"dup_doc_count":14}},"text":"Eyasi Plateau Paleontological Expedition, Laetoli, Tanzania, fossil specimen database 1998-2005.\nThe Eyasi Plateau Paleontological Expedition (EPPE) Laetoli specimen database contains 13716 records of plant and animal fossils (ca. 28248 specimens) collected by EPPE field teams working at Laetoli, Tanzania between 1998 and 2005. This dataset is a digital version of the original hard-copy specimen catalog, and it documents the discovery, stratigraphic provenience and taxonomic diversity of Plio-Pleistocene fauna and flora in northern Tanzania between 4.4 Ma and >200 ka. Laetoli is renowned for the discovery of important hominin fossils, including the lectotype for Australopithecus afarensis, one of our early hominin ancestors, the first record of Paranthropus aethiopicus outside Kenya-Ethiopia, and an early record of our own species Homo sapiens. This database is one of the few publicly available palaeoanthropological fossil datasets and serves as an example for expanding open access to primary fossil occurrence data in palaeoanthropology. The taxonomic identifications appearing in this dataset are the original field identifications and are provisional. Any taxonomic analysis employing this dataset should refer to updated taxonomic identifications published by specialists.","subset":"pubmed_abstract"} +{"meta":{"pmid":15929890,"dup_signals":{"dup_doc_count":11,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":2,"2015-11":2,"2015-06":1,"2024-10":1,"unknown":2}}},"text":"Climate factors influencing coccidioidomycosis seasonality and outbreaks.\nAlthough broad links between climatic factors and coccidioidomycosis have been established, the identification of simple and robust relationships linking climatic controls to seasonal timing and outbreaks of the disease has remained elusive. Using an adaptive data-oriented method for estimating date of exposure, in this article I analyze hypotheses linking climate and dust to fungal growth and dispersion, and evaluate their respective roles for Pima County, Arizona. Results confirm a strong bimodal disease seasonality that was suspected but not previously seen in reported data. Dispersion-related conditions are important predictors of coccidioidomycosis incidence during fall, winter, and the arid foresummer. However, precipitation during the normally arid foresummer 1.5-2 years before the season of exposure is the dominant predictor of the disease in all seasons, accounting for half of the overall variance. Cross-validated models combining antecedent and concurrent conditions explain 80% of the variance in coccidioidomycosis incidence. .","subset":"pubmed_abstract"} +{"meta":{"pmid":21990537,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Iatrogenic dissection during neurointerventional procedures: a retrospective analysis.\nRetrospective analysis of patients suffering iatrogenic dissection during neurointervention is reported. The circumstances surrounding the occurrence, early detection, clinical course and management options are discussed. 18 iatrogenic dissections over 11 years were retrospectively analyzed. Data were gathered from patient records, run sheets, morbidity records and imaging studies. All procedures were done by operators trained to operate according to institution standards. Total cases were 6981, with 3925 angiograms and 3056 interventions. Incidence was 0.26%, with 0.25% during diagnostic and 0.26% during intervention. 1031 pediatric cases had no dissections. Beyond 35 years, dissection rate increased to 0.35%. There was no difference between men and women. Carotid dissection was more common than vertebral. Most were minimal intimal tear (67%) and others flow limiting (33%). All cases were managed with heparin in the acute stage and later with aspirin and Plavix or Coumadin, except in two cases. Cases having >70% luminal narrowing with poor intracranial cross circulation were stented. None presented with neurologic deficits acutely or on follow-up. 94% of patients were followed for a variable period, with variable imaging modalities, being a retrospective study. Angiogram, MRI brain with MR angiography (MRA), Doppler ultrasonogram and CT angiograms were used for follow-up. There was good outcome in 94% of the followed-up cases. Iatrogenic dissection is a random event with a benign clinical course. Early detection and aggressive management result in excellent outcome. Angiography is the best modality to follow-up. Non-invasive imaging like MRI with MRA and duplex ultrasonography are good tools to follow dissections.","subset":"pubmed_abstract"} +{"meta":{"pmid":22969201,"dup_signals":{"dup_doc_count":16,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":3,"unknown":3}}},"text":"Alginate controls heartburn in patients with erosive and nonerosive reflux disease.\nTo evaluate the effect of a novel alginate-based compound, Faringel, in modifying reflux characteristics and controlling symptoms. In this prospective, open-label study, 40 patients reporting heartburn and regurgitation with proven reflux disease (i.e., positive impedance-pH test\/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal. They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel. In both sessions, measurements were obtained in right lateral and supine decubitus positions. Patients also completed a validated questionnaire consisting of a 2-item 5-point (0-4) Likert scale and a 10-cm visual analogue scale (VAS) in order to evaluate the efficacy of Faringel in symptom relief. Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good (1) to very poor (6). Faringel decreased significantly (P < 0.001), in both the right lateral and supine decubitus positions, esophageal acid exposure time [median 10 (25th-75th percentil 6-16) vs 5.8 (4-10) and 16 (11-19) vs 7.5 (5-11), respectively] and acid refluxes [5 (3-8) vs 1 (1-1) and 6 (4-8) vs 2 (1-2), respectively], but increased significantly (P < 0.01) the number of nonacid reflux events compared with baseline [2 (1-3) vs 3 (2-5) and 3 (2-4) vs 6 (3-8), respectively]. Percentage of proximal migration decreased in both decubitus positions (60% vs 32% and 64% vs 35%, respectively; P < 0.001). Faringel was significantly effective in controlling heartburn, based on both the Likert scale [3.1 (range 1-4) vs 0.9 (0-2); P < 0.001] and VAS score [7.1 (3-9.8) vs 2 (0.1-4.8); P < 0.001], but it had less success against regurgitation, based on both the Likert scale [2.6 (1-4) vs 2.2 (1-4); P = not significant (NS)] and VAS score [5.6 (2-9.6) vs 3.9 (1-8.8); P = NS]. Overall, the tolerability of Faringel was very good 5 (2-6), with only two patients reporting modest adverse events (i.e., nausea and bloating). Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time, number of acid refluxes and their proximal migration.","subset":"pubmed_abstract"} +{"meta":{"pmid":22530252,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":13}}},"text":"Offspring sex preference in frontier America.\nAnalysis of the fertility histories of women born between 1850 and 1900, as given in the Utah Population Database (UPDB), reveals the effect of the number, as well as the sex composition, of previous children on birth-stopping and birth-spacing decisions. Specifically, agricultural and Church of Jesus Christ of Latter-day Saints (LDS) households\u2014two sub-populations that might have placed different values on male and female children for economic, social, and\/or cultural reasons\u2014showed a distinct preference for male children, as expressed by birth stopping after the birth of a male child and shorter birth intervals in higher-parity births when most previous children were female. Remarkably, women in both the early \"natural fertility\" and the later contraceptive eras used spacing behavior to achieve a desired sex mix. Although the LDS population had relatively high fertility rates, it had the same preferences for male children as the non-LDS population did. Farmers, who presumably had a need for family labor, were more interested in the quantity than in the sex mix of their children.","subset":"pubmed_abstract"} +{"meta":{"pmid":24921357,"dup_signals":{"dup_doc_count":34,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2022-27":1,"2021-49":1,"2021-31":1,"2021-17":1,"2020-40":1,"2020-24":1,"2020-05":1,"2019-51":2,"2019-39":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":2,"2017-04":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2015-48":1,"2015-32":1,"2015-27":1,"2015-22":1,"2023-06":1,"2024-10":1,"2024-18":1}}},"text":"Enhancement of light extraction efficiency of OLEDs using Si\u2083N\u2084-based optical scattering layer.\nAn optical scattering layer, consisting of a Si3N4 nano-pillar array and a spin-coated hydrogen silsesquioxane (HSQ) planarization layer, was introduced to an organic light-emitting diode (OLED) substrate to increase the out-coupling efficiency. After plasma enhanced chemical vapor deposition (PECVD) of the Si3N4 layer, the nano-pillar array was created using nanoimprint lithography and reactive ion etching. As the Si3N4 pillar array has a refractive index of 2.0, photons generated in the organic layer are scattered by the Si3N4 structures and thus have a higher chance of being emitted from the device. The spin-coated HSQ planarization layer produces a flat substrate, which is essential for depositing a uniform organic material layer and assuring the electric conductivity of the transparent conducting oxide (TCO) layer. In this study, Si3N4 nano-structures with a height of 100 or 300 nm were used to enhance the out-coupling efficiency of the OLED devices. Although the electrical conductivity of the TCO layer deposited on the light scattering layer was slightly degraded, the OLED devices formed with the light scattering layer exhibited a higher luminous power at given electrical power. Consequently, the use of a planarized 300-nm-thick Si3N4 layer increased the external quantum efficiency of the OLED device by 50% at 10,000 cd\/m2 compared to the reference OLED device fabricated on a flat glass substrate.","subset":"pubmed_abstract"} +{"meta":{"pmid":27396919,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":2,"2017-13":1,"unknown":12}}},"text":"Natural Products Combating Neurodegeneration: Parkinson's Disease.\nParkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":12795613,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2024-18":1,"unknown":8}}},"text":"An in vitro assay using overexpressed yeast SRP demonstrates that cotranslational translocation is dependent upon the J-domain of Sec63p.\nThe signal recognition particle (SRP) is required for co-translational targeting of polypeptides to the endoplasmic reticulum (ER). Once at the membrane, the precursor interacts with a complex proteinaceous machinery that mediates its translocation across the bilayer. Genetic studies in yeast have identified a number of genes whose products are involved in this complex process. These mutants offer a potentially valuable resource with which to analyze the biochemical role played by each component in the pathway. However, such analyses have been hampered by the failure to reconstitute an efficient in vitro assay for SRP-dependent translocation. We report the construction of two multicopy vectors that allow overexpression of all seven gene products required to make SRP in the yeast Saccharomyces cerevisiae. The overexpressed subunits assemble into intact and functional SRP particles, and we further demonstrate that in vitro reconstitution of co-translational translocation is greatly enhanced using cytosol from the overexpression strain. We use this assay to demonstrate that Sec63p is required for co-translational translocation in vitro and specifically identify the \"J-domain\" of Sec63p as crucial for this pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":27229103,"dup_signals":{"dup_doc_count":28,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2022-33":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-29":1,"2019-47":1,"2019-35":1,"2019-26":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-47":1,"2017-34":1,"2017-26":1,"2023-40":1,"2024-30":2,"2024-18":1,"2024-10":1}}},"text":"Effects of hydrogen-rich saline on aquaporin 1, 5 in septic rat lungs.\nAquaporin 1(AQP1) and AQP5 have an important role in eliminating extravascular lung water, an increase of which contributes to lung injury in patients with sepsis and its consequent mortality. It has been reported that hydrogen-rich saline (HRS) has protective effects against sepsis-related lung injury. In this study, we hypothesized that the protective effect occurred by preserving the expression of AQP1 and AQP5. To test this hypothesis, male Sprague-Dawley rats received intratracheal administration of lipopolysaccharide (LPS) followed by intraperitoneal injection of HRS. Lung function, wet-to-dry weight ratio, and histopathology scores were determined. The expression of AQP1 and AQP5 at the messenger RNA and protein levels, as well as the involved pathways, was explored by quantitative polymerase chain reaction and Western blot. LPS significantly impaired lung function and downregulated the expression of AQP1 and AQP5 in the rat lung, all of which were attenuated by HRS treatment. Moreover, HRS treatment inhibited LPS-induced activation of p38 mitogen-activated protein kinase and jun N-terminal kinase, which is associated with LPS-induced downregulation of AQP1 and AQP5.","subset":"pubmed_abstract"} +{"meta":{"pmid":23433656,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":14}}},"text":"The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP) during a single bout of high resistance exercise in resistance trained young men.\nRecombinant human growth hormone (rhGH) is used by some athletes and body builders with the aim of enhancing performance, building muscle and improving physique. Detection of the misuse of rhGH has proved difficult for a number of reasons. One of these is the effect of preceding exercise. In this randomised, double blind placebo-controlled study, we determined the effects of rhGH administration in male amateur athletes on two candidate markers of rhGH abuse, IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP), following a bout of weightlifting exercise. Sixteen men entered a four-week general weight training programme to homogenise their activity profile. They then undertook repeated bouts of standardised leg press weightlifting exercise (AHRET-acute heavy resistance exercise test). Blood samples were taken before and up to one hour after the AHRET. After the first laboratory visit (Test 1), the subjects were randomly assigned to receive daily injections of either rhGH (0.1 IU kg(-1) day(-1)) or placebo for two weeks. The AHRET was repeated after the two-week dosing period (Test 2) and a further test was undertaken following a one-week washout (Test 3). There was no effect of exercise on either IGF-I or P-III-NP in any test. Both markers were markedly elevated at Test 2 (p<0.001), with P-III-NP remaining elevated at Test 3 in the GH administration group (p<0.05). Application of the GH-2000 discriminant function positively identified GH administration in 17 of 40 blood samples taken at Test 2 from the rhGH group and none from the placebo group. The data show that rhGH results in elevated levels of IGF-I and P-III-NP in well-trained individuals and that leg press weightlifting exercise does not affect these markers. The GH-2000 discriminant function identified four of eight subjects taking rhGH with no false positive results.","subset":"pubmed_abstract"} +{"meta":{"pmid":9111347,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Exonuclease I of Saccharomyces cerevisiae functions in mitotic recombination in vivo and in vitro.\nWe previously described a 5'-3' exonuclease required for recombination in vitro between linear DNA molecules with overlapping homologous ends. This exonuclease, referred to as exonuclease I (Exo I), has been purified more than 300-fold from vegetatively grown cells and copurifies with a 42-kDa polypeptide. The activity is nonprocessive and acts preferentially on double-stranded DNA. The biochemical properties are quite similar to those of Schizosaccharomyces pombe Exo I. Extracts prepared from cells containing a mutation of the Saccharomyces cerevisiae EXO1 gene, a homolog of S. pombe exo1, had decreased in vitro recombination activity and when fractionated were found to lack the peak of activity corresponding to the 5'-3' exonuclease. The role of EXO1 on recombination in vivo was determined by measuring the rate of recombination in an exo1 strain containing a direct duplication of mutant ade2 genes and was reduced sixfold. These results indicate that EXO1 is required for recombination in vivo and in vitro in addition to its previously identified role in mismatch repair.","subset":"pubmed_abstract"} +{"meta":{"pmid":20448882,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Temporal patterns and oscillatory voltage perturbation during an electrochemical process.\nThe response of electrodissolution dynamics of nickel in sulfuric acid electrolyte was studied and categorized using efficient signal processing techniques. Time-frequency and phase analysis revealed complex dynamical patterns in anodic currents observed in the system. These patterns which respond to three-dimensional changes in the electrolyte and surface conditions, have a multitude of spatio-temporal properties which proved sensitive to oscillatory voltage perturbations, allowing signal recognition through distinct response patterns. Experimental work included studies on identification of control parameters, characterization of subsequent temporal patterns and examination of system response to information in the form of oscillatory voltage perturbations. Various data processing and pattern recognition techniques revealed the complexity and dynamics of these distinctive responses, which illustrate the capacity of the system to store information, with varying memory lengths. These patterns can be recalled upon excitation with particular perturbation cues.","subset":"pubmed_abstract"} +{"meta":{"pmid":23278615,"dup_signals":{"dup_doc_count":11}},"text":"Merkel cell carcinoma with sarcomatous differentiation: is it a poor prognostic factor?\nPoor prognostic factors in Merkel cell carcinoma include male sex, advanced stage at diagnosis, large tumor size (>5 mm), diffuse growth pattern, heavy lymphocytic infiltrate, and high mitotic rate. To date only six cases of Merkel cell carcinoma with sarcomatous or pseudosarcomatous differentiation and poor prognosis have been documented. We present a new case of Merkel cell carcinoma with sarcomatous differentiation. The immunohistochemical staining patterns reflected the morphologic differentiation of the epithelial and sarcomatous pattern. After two months of follow-up, there were no signs of local recurrence or metastases. In all cases of merkelomas with sarcomatous differentiation described to date, lymph node metastases have been found, except in the presented case. However, larger series of cases will be required to determine if sarcomatous differentiation represents another negative prognostic factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":3279437,"dup_signals":{"dup_doc_count":22,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2024-10":1,"2017-13":2,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":11}}},"text":"Effects of soft tissue mobilization (Rolfing pelvic lift) on parasympathetic tone in two age groups.\nThe effects of a soft tissue mobilization procedure, the Rolfing pelvic lift, on parasympathetic tone was studied in healthy adult men. Parasympathetic tone was assessed 1) by quantifying the amplitude of the respiratory sinus arrhythmia from the heart rate pattern and 2) by measuring heart rate. Heart rate patterns were assessed during the pelvic lift and during the durational touch and baseline control conditions. Two groups of healthy subjects were tested: Group 1 contained 20 subjects aged 26 to 41 years, and Group 2 contained 10 subjects aged 55 to 68 years. In Group 1, the pelvic lift elicited a somatovisceral-parasympathetic reflex characterized by a significant increase in parasympathetic tone relative to durational touch and baseline conditions. Group 2 did not exhibit a parasympathetic change during the pelvic lift. The results of this study contribute to our understanding of pelvic mobilization techniques and may help to explain why these techniques have been clinically successful in treating myofascial pain syndromes and other musculoskeletal dysfunctions characterized by reduced parasympathetic tone and excessive sympathetic activity.","subset":"pubmed_abstract"} +{"meta":{"pmid":22238476,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Extraction, isolation and characterization of bioactive compounds from plants' extracts.\nNatural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. Due to an increasing demand for chemical diversity in screening programs, seeking therapeutic drugs from natural products, interest particularly in edible plants has grown throughout the world. Botanicals and herbal preparations for medicinal usage contain various types of bioactive compounds. The focus of this paper is on the analytical methodologies, which include the extraction, isolation and characterization of active ingredients in botanicals and herbal preparations. The common problems and key challenges in the extraction, isolation and characterization of active ingredients in botanicals and herbal preparations are discussed. As extraction is the most important step in the analysis of constituents present in botanicals and herbal preparations, the strengths and weaknesses of different extraction techniques are discussed. The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays, chromatographic techniques such as HPLC and, TLC as well as non-chromatographic techniques such as immunoassay and Fourier Transform Infra Red (FTIR) are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":31142129,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Salivary Clear Cell Carcinoma Clinicopathologic Characteristics and Outcomes: A Population-Based Analysis.\nSalivary clear cell carcinoma is an uncommon, low-grade malignancy for which limited data describing predictive clinicopathologic factors and treatment outcomes exist because of rarity. The authors queried the Surveillance, Epidemiology, and End Results database from 1982 to 2014. Multivariate Cox and Kaplan-Meier analyses were performed to determine disease-specific survival (DSS) and predictive clinicopathologic factors. One hundred ninety-eight patients with salivary clear cell carcinoma were included. Overall incidence was 0.011 per 100 000 individuals, with no significant annual percentage change across years (-0.93%, P = .632). Five-, 10-, and 20-year DSS rates were 81.3% (n = 117), 69.6% (n = 94), and 55.3% (n = 68), respectively. Men (hazard ratio, 4.74; P = .0087) and patients with regional (hazard ratio, 5.59; P = .018) or distant (hazard ratio, 8.9; P = .01) metastases carried a worse prognosis. Five-year DSS was greater in patients with localized disease (96.36%, P < .0001) than those with regional or distant metastases. Treatment with surgery alone had better 10-year DSS (86.3%) compared with treatment with combination radiation and surgery (57.6%) or radiation monotherapy (18.75%, P < .0001). Salivary clear cell carcinoma carries an overall good prognosis. Patients with localized disease and those treated with surgery alone have more favorable prognoses. Male patients and those with regional or distant metastatic disease at time of presentation carry a worse prognosis. N\/A.","subset":"pubmed_abstract"} +{"meta":{"pmid":35625483,"dup_signals":{"dup_doc_count":26,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":3,"2023-23":3,"2023-14":2,"2023-06":2,"2022-49":2,"2022-33":2,"2022-27":3,"2024-26":2,"2024-18":2}}},"text":"Spatiotemporal Epidemiology of Tuberculosis in Thailand from 2011 to 2020.\nTuberculosis is a leading cause of infectious disease globally, especially in developing countries. Better knowledge of spatial and temporal patterns of tuberculosis burden is important for effective control programs as well as informing resource and budget allocation. Studies have demonstrated that TB exhibits highly complex dynamics in both spatial and temporal dimensions at different levels. In Thailand, TB research has been primarily focused on surveys and clinical aspects of the disease burden with little attention on spatiotemporal heterogeneity. This study aimed to describe temporal trends and spatial patterns of TB incidence and mortality in Thailand from 2011 to 2020. Monthly TB case and death notification data were aggregated at the provincial level. Age-standardized incidence and mortality were calculated; time series and global and local clustering analyses were performed for the whole country. There was an overall decreasing trend with seasonal peaks in the winter. There was spatial heterogeneity with disease clusters in many regions, especially along international borders, suggesting that population movement and socioeconomic variables might affect the spatiotemporal distribution in Thailand. Understanding the space-time distribution of TB is useful for planning targeted disease control program activities. This is particularly important in low- and middle-income countries including Thailand to help prioritize allocation of limited resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":8254193,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity.\nRabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS. Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment. This fragment, designated CAP18(106-142), inhibits many activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS-induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality. CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.","subset":"pubmed_abstract"} +{"meta":{"pmid":29734865,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":10}}},"text":"Peripheral artery disease, calf skeletal muscle mitochondrial DNA copy number, and functional performance.\nIn people without lower extremity peripheral artery disease (PAD), mitochondrial DNA copy number declines with aging, and this decline is associated with declines in mitochondrial activity and functional performance. However, whether lower extremity ischemia is associated with lower mitochondrial DNA copy number and whether mitochondrial DNA copy number is associated with the degree of functional impairment in people with PAD is unknown. In people with and without PAD, age 65 years and older, we studied associations of the ankle-brachial index (ABI) with mitochondrial DNA copy number and associations of mitochondrial DNA copy number with functional impairment. Calf muscle biopsies were obtained from 34 participants with PAD (mean age: 73.5 years (SD 6.4), mean ABI: 0.67 (SD 0.15), mean 6-minute walk distance: 1191 feet (SD 223)) and 10 controls without PAD (mean age: 73.1 years (SD 4.7), mean ABI: 1.14 (SD 0.07), mean 6-minute walk distance: 1387 feet (SD 488)). Adjusting for age and sex, lower ABI values were associated with higher mitochondrial DNA copy number, measured in relative copy number (ABI<0.60: 914, ABI 0.60-0.90: 731, ABI 0.90-1.50: 593; p trend=0.016). The association of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity differed significantly between participants with versus without PAD ( p-value for interaction=0.001 and p=0.015, respectively). The correlation coefficient between mitochondrial DNA copy number and the 6-minute walk distance was 0.653 ( p=0.056) among people without PAD and -0.254 ( p=0.154) among people with PAD and ABI < 0.90. In conclusion, lower ABI values are associated with increased mitochondrial DNA copy number. Associations of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity significantly differed between people with versus without PAD, with stronger positive associations observed in people without PAD than in people with PAD. The cross-sectional and exploratory nature of the analyses precludes conclusions regarding causal inferences. ClinicalTrials.gov Identifier: NCT02246660.","subset":"pubmed_abstract"} +{"meta":{"pmid":21979803,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Inspiratory muscle training lowers the oxygen cost of voluntary hyperpnea.\nThe purpose of this study was to determine if inspiratory muscle training (IMT) alters the oxygen cost of breathing (Vo(2RM)) during voluntary hyperpnea. Sixteen male cyclists completed 6 wk of IMT using an inspiratory load of 50% (IMT) or 15% placebo (CON) of maximal inspiratory pressure (Pi(max)). Prior to training, a maximal incremental cycle ergometer test was performed to determine Vo(2) and ventilation (V(E)) at multiple workloads. Pre- and post-training, subjects performed three separate 4-min bouts of voluntary eucapnic hyperpnea (mimic), matching V(E) that occurred at 50, 75, and 100% of Vo(2 max). Pi(max) was significantly increased (P < 0.05) by 22.5 \u00b1 8.7% from pre- to post-IMT and remained unchanged in the CON group. The Vo(2RM) required during the mimic trial corresponded to 5.1 \u00b1 2.5, 5.7 \u00b1 1.4, and 11.7% \u00b1 2.5% of the total Vo(2) (Vo(2T)) at ventilatory workloads equivalent to 50, 75, and 100% of Vo(2 max), respectively. Following IMT, the Vo(2RM) requirement significantly decreased (P < 0.05) by 1.5% (4.2 \u00b1 1.4% of Vo(2T)) at 75% Vo(2 max) and 3.4% (8.1 \u00b1 3.5% of Vo(2T)) at 100% Vo(2 max). No significant changes were shown in the CON group. IMT significantly reduced the O(2) cost of voluntary hyperpnea, which suggests that a reduction in the O(2) requirement of the respiratory muscles following a period of IMT may facilitate increased O(2) availability to the active muscles during exercise. These data suggest that IMT may reduce the O(2) cost of ventilation during exercise, providing an insight into mechanism(s) underpinning the reported improvements in whole body endurance performance; however, this awaits further investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28642069,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":13}}},"text":"Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.\nCholine, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life.","subset":"pubmed_abstract"} +{"meta":{"pmid":12901449,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"The impact of smoking and other substance use by urban women on the birthweight of their infants.\nThe impact of maternal smoking and other substance use during pregnancy on infant birthweight is demonstrated in a sample of 766 urban women, using data collected in the Washington, D.C. Metropolitan Area Drug Study (DC*MADS). Women residing and giving birth in the District of Columbia were interviewed in 1992. A multivariable linear regression model was used to quantify the association between birthweight and the mother's use of cigarettes, alcohol, or illicit drugs during pregnancy, while controlling for possible confounding variables. The analysis focused on factors, including prenatal care and substance use during pregnancy that may contribute to low birthweight infants born to this sample of urban, predominantly black women. A woman's use of cigarettes, marijuana, and heroin during pregnancy was related to infant birthweight, but her use of alcohol and cocaine during pregnancy was not significantly related. Smoking during pregnancy was a strong predictor for low birthweight, suggesting that targeting more smoking cessation programs for pregnant women, particularly those who may also be illicit drug users, could help reduce adverse health consequences for low birthweight infants.","subset":"pubmed_abstract"} +{"meta":{"pmid":10886912,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"[Analysis of the work process in health research laboratories: a proposal for investigation]\nThis article presents a proposal for analyzing the work process involved in building technoscientific knowledge in the health field, focusing on the work developed by research laboratory technicians in the Oswaldo Cruz Foundation. Beginning with an in-depth description of the technicians' laboratory activities, we discuss the relationship between the various stages of work and the different actors, the technicians' value as actors in the process of building knowledge, and various actors' perceptions of how essential this work is. We attempt to outline the context in which the work processes in health sciences laboratories were incorporated into an analysis of the work process in health. By establishing a dialogue with the sociology of science, we present our proposal as an attempt to introduce new social sciences approaches for analyzing the work process, specifically as applicable to an analysis of work in the health field.","subset":"pubmed_abstract"} +{"meta":{"pmid":27506172,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Acute Administration of Methionine Affects Performance of Swiss Mice in Learning and Memory Paradigms.\nMethionine, an essential amino acid, plays an essential role in the central nervous system CNS development. It serves as a crucial intermediate in the methylation, trans-sulfuration and amino- phosphorylationpathways,necessary for the synthesis of nucleic acids, phospholipids, hormones, neurotransmitters, antioxidants, polyamines, catecholamines and other biogenic amines. The effect of methionine on learning and memory in mice was investigated using Morris water maze (MWM), Elevated plus maze(EPM) and Y maze (YM). Animals were administered with distilled water (control), methionine (1,700mg\/kg); folate (3mg\/kg) or methionine (1700mg\/kg) plus folate (3mg\/kg) for 14 days. Escape latency and time spent in target quadrants; transfer latency and percentage spontaneous alternations were measured in the MWM, EPM and YM respectively. The animals were anaesthetized with inhalational chloroform and their brains subsequently harvested, homogenized and assayed for acetylcholinesterase24 hours after the experiment.Folate significantly(p<0.05) increased transfer latency (53.33 \u00b1 12.62) as compared to control (20.1 \u00b1 5.01) and reduced spontaneous alternations significantly (25.0 \u00b1 8.9) when compared to control (44.33 \u00b1 3.07). When folate was combined with methionine there was also a significant increase in transfer latency (43.0 \u00b1 14.39) when compared with control (20.1 \u00b1 5.01). Folate-methionine combination also significantly reduced spontaneous alternations (20.4 \u00b1 8.4) as compared to the control (44.33 \u00b1 3.07) much more than folate alone. Acetylcholinesterase activities in all groups were not statistically significant. It can be concluded that acute methionine administration has some benefits in memory enhancement. However, a short course folate supplementation impairslearning and working memory especially when combined with methioninewhich may be as a result of sudden overwhelming of the methylation cycle, leading to homocysteinemia which is pro-dementia.","subset":"pubmed_abstract"} +{"meta":{"pmid":21628706,"dup_signals":{"dup_doc_count":30,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2022-27":1,"2021-21":1,"2020-24":1,"2020-16":1,"2019-43":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":3,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2023-40":1,"2015-18":1,"2013-20":1,"2024-30":1}}},"text":"Cannabis use before age 15 and subsequent executive functioning.\nMany studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.","subset":"pubmed_abstract"} +{"meta":{"pmid":22547821,"dup_signals":{"dup_doc_count":22,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":1,"2023-14":2,"2023-06":1,"2022-40":1,"2022-27":2,"2022-21":2,"2022-05":1,"2020-40":1,"2023-50":1,"2024-22":1,"2024-18":1,"2024-10":2,"2017-13":1,"2024-26":1}}},"text":"Brain anomalies in children exposed prenatally to a common organophosphate pesticide.\nPrenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure \u00d7 IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.","subset":"pubmed_abstract"} +{"meta":{"pmid":21550254,"dup_signals":{"dup_doc_count":99,"dup_dump_count":52,"dup_details":{"curated_sources":2,"2023-50":5,"2023-40":1,"2023-23":2,"2023-14":2,"2023-06":1,"2022-49":1,"2022-40":1,"2022-33":2,"2022-27":3,"2022-21":3,"2022-05":1,"2021-49":3,"2021-43":2,"2021-39":1,"2021-31":3,"2021-25":1,"2021-21":2,"2021-17":1,"2021-10":3,"2021-04":2,"2020-50":1,"2020-45":2,"2020-40":2,"2020-29":2,"2019-51":1,"2019-47":1,"2019-13":1,"2019-04":1,"2018-51":2,"2018-43":3,"2018-39":1,"2018-34":3,"2018-26":2,"2018-22":2,"2018-17":2,"2018-13":2,"2018-09":2,"2018-05":1,"2017-51":4,"2017-43":5,"2017-34":5,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-30":2,"2024-26":1,"2024-22":1,"2024-10":1,"2017-13":1}}},"text":"Possible seizure suppression via deep brain stimulation of the thalamic ventralis oralis posterior nucleus.\nSurgical treatment of intractable epilepsy with deep brain stimulation (DBS) has been shown to be of therapeutic benefit in some patients and with the recent publication of a randomised control study its use is likely to increase in the future. We describe a patient who developed a focal epileptic seizure within a few seconds of momentarily turning off the DBS stimulator in the nucleus ventralis oralis posterior, with which she was successfully treated for tremor. The seizure was the result of a newly diagnosed primary brain tumor. We suggest that the nucleus ventralis oralis posterior may be another thalamic target of DBS in epilepsy.","subset":"pubmed_abstract"} +{"meta":{"pmid":7352303,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Tissue specificity of enzyme expression regulated by diffusible factors: evidence in Drosophila hybrids.\nPairs of hybridizable species of Hawaiian picture-winged Drosophila differ qualitatively in the distributions of specific enzymes in their tissues. An examination of the patterns of enzyme expression in the hybrids showed that, in three instances, absence of an enzyme from a specific tissue was dominant to presence. Since other developmental features indicated that both parental genomes were functioning, these results suggest that, in these cases, the pattern differences in the parental species were due to diffusible factors that affected expression of the relevant structural genes rather than to differences in the genes themselves or in cis-acting regulatory sites.","subset":"pubmed_abstract"} +{"meta":{"pmid":16661343,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Alterations in source-sink patterns by modifications of source strength.\nBean plants, trimmed to a simplified \"double source, double sink\" translocation system (the paired primary leaves serving as the double source and the paired lateral leaflets of the immature first trifoliate leaf as the double sink) were used to study the magnitude and short-term time course of change in the allocation ratio (partition ratio) of assimilates translocated from the labeled primary leaf to its respective \"near\" and \"far leaflet\" sinks in response to an increase or decrease in the source strength of the opposite primary leaf (the \"control\" leaf). If the rates of net photosynthesis in the two primary leaves were similar, assimilates from the labeled source leaf partitioned to the leaflet sinks in the ratio of 5:1 or higher, the dominant sink being the leaflet \"nearer\" to the labeled source leaf. If the rate of net photosynthesis in the control leaf was increased substantially above that of the labeled source leaf, the rate of translocation from the labeled source to either the near leaflet sink or far leaflet sink remained unaffected, despite, presumably, a higher translocation rate from the control leaf, and hence a higher phloem pressure gradient (or increased cross-sectional area) in the transport pathway from the control leaf to the leaflet sinks. If the control leaf was excised, thus reducing the source leaf area by about a half, the translocation rate from the remaining source leaf rapidly doubled, the partition ratio becoming equal to unity. If the control leaf was darkened, the partition ratio adjusted to an intermediate value. Although export rates from the labeled source leaf were increased either by excising or darkening the control leaf, the rate of net photosynthesis in the labeled leaf remained constant.","subset":"pubmed_abstract"} +{"meta":{"pmid":23966819,"dup_signals":{"dup_doc_count":25,"dup_dump_count":8,"dup_details":{"curated_sources":2,"2024-26":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-30":1,"unknown":15}}},"text":"Review of the medicinal effects of tualang honey and a comparison with manuka honey.\nTualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The honey is produced by the rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees located mainly in the north-western region of Peninsular Malaysia. This review collates the results of the various studies of TH that range from research on tissue culture to randomised control clinical trials. Findings thus far show that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic, antitumor, and antidiabetic properties, in addition to wound-healing attributes. Some of its properties are similar to the well-researched Manuka honey (New Zealand and\/or Australian monofloral honey). Distinct differences include higher phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka honey, TH is also more effective against some gram-negative bacterial strains in burn wounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":27529575,"dup_signals":{"dup_doc_count":17,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"Patient Satisfaction with In-Home Telerehabilitation After Total Knee Arthroplasty: Results from a Randomized Controlled Trial.\nBackground and Introduction: Telerehabilitation after total knee arthroplasty (TKA) is supported by strong evidence on the effectiveness of such intervention and from a cost-benefit point of view. Satisfaction of patients toward in-home telerehabilitation after TKA has not yet been examined thoroughly in large-scale clinical trials. This study aims to compare satisfaction level of patients following in-home telerehabilitation (TELE) after TKA to one of the patients following a usual face-to-face home visit (STD) rehabilitation. Secondarily, to determine if any clinical or personal variables were associated to the level of satisfaction. This study was embedded in a multicenter randomized controlled trial with 205 patients randomized into two groups. Rehabilitation intervention was the same for both groups; only approach for service delivery differed (telerehabilitation or home visits). Participants were assessed at baseline (before TKA), at hospital discharge, and at 2 and 4 months postdischarge (E4) using functional outcomes. Patient satisfaction was measured using the validated Health Care Satisfaction Questionnaire (HCSQ) at E4. Characteristics of all participants were similar at baseline. Satisfaction level of both groups did not differ and was very high (over 85%). It was neither correlated to personal characteristics nor to improvements of functional level from preoperative to E4. Satisfaction was rather found associated to walking and stair-climbing performances. These results, in conjunction with evidences of clinical effectiveness and cost benefits demonstrated in the same sample of patients, strongly support the use of telerehabilitation to improve access to rehabilitation services and efficiency of service delivery after TKA.","subset":"pubmed_abstract"} +{"meta":{"pmid":1967900,"dup_signals":{"dup_doc_count":43,"dup_dump_count":26,"dup_details":{"curated_sources":4,"2023-40":2,"2023-23":2,"2023-06":2,"2022-27":1,"2022-21":1,"2022-05":1,"2021-49":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-17":2,"2021-04":3,"2020-50":1,"2020-40":2,"2019-13":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-26":2,"2024-22":2,"2024-10":4}}},"text":"Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.\nThe segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None of the 38 pedigrees showed evidence of recombination between the OI gene and both collagen loci, suggesting that the frequency of unlinked loci in the population must be low. From these results, approximate 95% confidence limits for the proportion of families linked to the type I collagen genes can be set between .91 and 1.00. This is high enough to base prenatal diagnosis of dominantly inherited OI on linkage to these genes even in families which are too small for the linkage to be independently confirmed to high levels of significance. When phenotypic features were compared with the concordant collagen locus, all eight pedigrees with Sillence OI type IV segregated with COL1A2. On the other hand, Sillence OI type I segregated with both COL1A1 (17 pedigrees) and COL1A2 (7 pedigrees). The concordant locus was uncertain in the remaining six OI type I pedigrees. Of several other features, the presence or absence of presenile hearing loss was the best predictor of the mutant locus in OI type I families, with 13 of the 17 COL1A1 segregants and none of the 7 COL1A2 segregants showing this feature.","subset":"pubmed_abstract"} +{"meta":{"pmid":7989547,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Typing of group A streptococci by random amplified polymorphic DNA analysis.\nRandom amplified polymorphic DNA (RAPD) analysis was evaluated in comparison with restriction endonuclease analysis (REA) of genomic DNA and serotyping in the typing of 160 epidemiologically unrelated group A streptococci (GAS). Amplification of genomic DNA of GAS was performed with a single primer with an arbitrarily selected nucleotide sequence of 12 nucleotides. In total, 31 RAPD patterns and 15 REA patterns were observed among the isolates studied. The results of RAPD analysis were in accordance with the results of REA for 86% of the isolates, as both methods identified 15 different strains among 138 isolates. However, RAPD analysis differentiated 16 additional strains among 22 isolates. RAPD analysis was somewhat better than REA for differentiation of isolates of the same and different serotypes. However, not all of the serotypes were differentiated by RAPD analysis either. In conclusion, RAPD analysis provides a practical alternative for genomic typing of GAS. It can be recommended for the typing of GAS, especially if used in parallel with serotyping.","subset":"pubmed_abstract"} +{"meta":{"pmid":27583404,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":19}}},"text":"A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.\nIntensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain. To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes. Pragmatic, multicentre, cluster-randomised, parallel-group trial. Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK. Individuals aged 40-69 years with screen-detected diabetes. Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol. The primary end point was a composite of first cardiovascular event (cardiovascular mortality\/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009\/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (\u00a9) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk\/outcomesmodel (accessed 27 January 2016)]. We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml\/minute; RC 6.44 ml\/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost \u00a3981 per patient and was not cost-effective at costs \u2265 \u00a3631 per patient. Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted. ClinicalTrials.gov NCT00237549. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.","subset":"pubmed_abstract"} +{"meta":{"pmid":21858000,"dup_signals":{"dup_doc_count":27,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2024-10":1,"unknown":23}}},"text":"Chasing Jenner's vaccine: revisiting cowpox virus classification.\nCowpox virus (CPXV) is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe \"cowpox\" as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5) species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of \"cowpox\" isolates. These data support the elevation of as many as four new species within the traditional \"cowpox\" group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.","subset":"pubmed_abstract"} +{"meta":{"pmid":30590600,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":15}}},"text":"When is it appropriate to stop non-vitamin K antagonist oral anticoagulants before catheter ablation of atrial fibrillation? A multicentre prospective randomized study.\nAlthough a recent expert consensus statement has recommended periprocedural uninterrupted (UI) non-vitamin K antagonist oral anticoagulants (NOACs) during catheter ablation of atrial fibrillation (AF) as a Class I indication, there have been no clear randomized trials. We investigated the safety and efficacy of UI, procedure day single-dose skipped (SDS), and 24-hour skipped (24S) NOACs in patients undergoing AF ablation. In this prospective, open-label, randomized multicentre trial, 326 patients (75% male, 58 \u00b1 11 years old) scheduled for AF catheter ablation were randomly assigned in a 1:1:1 ratio to UI, SDS, and 24S at three tertiary hospitals. Bridging with low molecular weight heparin was carried out in the patients with persistent AF who were assigned to the 24S group. Dabigatran, rivaroxaban, and apixaban were assigned in order after randomization. The primary endpoint was the incidence of bleeding events within 1 month after ablation. The secondary endpoints included thrombo-embolic and other procedure-related complications. The intra-procedural heparin requirement was higher in the 24S group than others (P < 0.001), and the mean activated clotting time was comparable among the groups (P = 0.139). The incidence of major bleeding up to 1 month after ablation and a post-procedural reduction in the haemoglobin levels did not significantly differ among the treatment groups and different NOACs (P > 0.05). There were no fatal events or thrombo-embolic complications in all the three groups. In patients undergoing AF ablation, UI NOACs and SDS or double dose skipped NOACs had a comparable efficacy and safety, regardless of the type of NOAC.","subset":"pubmed_abstract"} +{"meta":{"pmid":21622791,"dup_signals":{"dup_doc_count":22,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-25":1,"2020-45":1,"2020-34":1,"2020-24":1,"2019-51":1,"2019-39":1,"2019-26":1,"2023-50":1,"2024-18":1,"2024-26":1}}},"text":"Development of a multilocus sequence typing tool for high-resolution genotyping of Enterocytozoon bieneusi.\nThus far, genotyping of Enterocytozoon bieneusi has been based solely on DNA sequence analysis of the internal transcribed spacer (ITS) of the rRNA gene. Both host-adapted and zoonotic (human-pathogenic) genotypes of E. bieneusi have been identified. In this study, we searched for microsatellite and minisatellite sequences in the whole-genome sequence database of E. bieneusi isolate H348. Seven potential targets (MS1 to MS7) were identified. Testing of the seven targets by PCR using two human-pathogenic E. bieneusi genotypes (A and Peru10) led to the selection of four targets (MS1, MS3, MS4, and MS7). Further analysis of the four loci with an additional 24 specimens of both host-adapted and zoonotic E. bieneusi genotypes indicated that most host-adapted genotypes were not amplified by PCR targeting these loci. In contrast, 10 or 11 of the 13 specimens of the zoonotic genotypes were amplified by PCR at each locus. Altogether, 12, 8, 7, and 11 genotypes of were identified at MS1, MS3, MS4, and MS7, respectively. Phylogenetic analysis of the nucleotide sequences obtained produced a genetic relationship that was similar to the one at the ITS locus, with the formation of a large group of zoonotic genotypes that included most E. bieneusi genotypes in humans. Thus, a multilocus sequence typing tool was developed for high-resolution genotyping of E. bieneusi. Data obtained in the study should also have implications for understanding the taxonomy of Enterocytozoon spp., the public health significance of E. bieneusi in animals, and the sources of human E. bieneusi infections.","subset":"pubmed_abstract"} +{"meta":{"pmid":9028408,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-24":1,"2020-05":1,"2023-40":1,"2024-10":1,"2024-30":1}}},"text":"Schistosomiasis in women: manifestations in the upper reproductive tract.\nFemale genital schistosomiasis (FGS) is a neglected disease entity which may give rise to considerable suffering among women of child-bearing age in areas where schistosomiasis (especially due to Schistosoma haematobium) is prevalent. The close relation between the vessels in genital organs and the urinary bladder enables the parasite to easily change location to virtually any organs in the female pelvic area. Symptoms concur with the anatomical location of worm pairs and their ova. Lesions of the lower female genital tract can easily be investigated by cytology, histology or direct demonstration of eggs in scrapings or biopsies whereas schistosomiasis of the upper genital tract is clinically indecipherable and less accessible for examination. In the literature there are references to FGS as a cause of infertility, complications of pregnancy, menstrual disorders, problems related to sexual intercourse, diagnostic similarities to STDs and cancer, unspecified complaints related to blood loss, chronic abdominal pain, social segregation and related psychological problems. The diagnosis of female upper genital schistosomiasis is difficult and the authors point out possible diagnostic procedures which might be helpful for further understanding of this complex entity.","subset":"pubmed_abstract"} +{"meta":{"pmid":12799432,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"OligoArray 2.0: design of oligonucleotide probes for DNA microarrays using a thermodynamic approach.\nThere is a substantial interest in implementing bioinformatics technologies that allow the design of oligonucleotides to support the development of microarrays made from short synthetic DNA fragments spotted or in situ synthesized on slides. Ideally, such oligonucleotides should be totally specific to their respective targets to avoid any cross-hybridization and should not form stable secondary structures that may interfere with the labeled probes during hybridization. We have developed OligoArray 2.0, a program that designs specific oligonucleotides at the genomic scale. It uses a thermodynamic approach to predict secondary structures and to calculate the specificity of targets on chips for a unique probe in a mixture of labeled probes. Furthermore, OligoArray 2.0 can adjust the oligonucleotide length, according to user input, to fit a narrow T(m) range compatible with hybridization requirements. Combined with on chip oligonucleotide synthesis, this program makes it feasible to perform expression analysis on a genomic scale for any organism for which the genome sequence is known. This is without relying on cDNA or oligonucleotide libraries. OligoArray 2.0 was used to design 75 764 oligonucleotides representing 26 140 transcripts from Arabidopsis thaliana. Among this set, we provide at least one specific oligonucleotide for 93% of these transcripts.","subset":"pubmed_abstract"} +{"meta":{"pmid":26031210,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2023-14":1,"2022-05":1,"2021-04":1,"2020-16":1,"2019-18":2,"2019-09":1,"2018-30":2,"2018-17":1,"2023-40":1}}},"text":"The effects of antidepressants appear to be rapid and at environmentally relevant concentrations.\nThe effects of antidepressants on wildlife are currently raising some concern because of an increased number of publications indicating biological effects at environmentally relevant concentrations (<100 ng\/L). These results have been met with some scepticism because of the higher concentrations required to detect effects in some species and the perceived slowness to therapeutic effects recorded in humans and other vertebrates. Because their mode of action is thought to be by modulation of the neurotransmitters serotonin, dopamine, and norepinephrine, aquatic invertebrates that possess transporters and receptors sensitive to activation by these pharmaceuticals are potentially affected by them. The authors highlight studies on the effects of antidepressants, particularly on crustacean and molluskan groups, showing that they are susceptible to a wide variety of neuroendocrine disruptions at environmentally relevant concentrations. Interestingly, some effects observed in these species can be observed within minutes to hours of exposure. For example, exposure of amphipod crustaceans to several selective serotonin reuptake inhibitors can invoke changes in swimming behavior within hours. In mollusks, exposure to selective serotonin reuptake inhibitors can induce spawning in male and female mussels and foot detachment in snails within minutes of exposure. In the light of new studies indicating effects on the human brain from selective serotonin reuptake inhibitors using magnetic resonance imaging scans, the authors discuss possible reasons for the discrepancy in former results in relation to the read-across hypothesis, variation in biomarkers used, modes of uptake, phylogenetic distance, and the affinity to different targets and differential sensitivity to receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":27004457,"dup_signals":{"dup_doc_count":22,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2019-51":1,"2019-47":1,"2019-43":3,"2019-35":1,"2019-18":3,"2019-09":2,"2019-04":1,"2018-39":1,"2018-22":1,"2018-05":1,"2017-43":1,"2016-40":1,"2020-16":1}}},"text":"Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden.\nLittle is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24183993,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":15}}},"text":"Diet-induced weight loss: the effect of dietary protein on bone.\nHigh-protein (>30% of energy from protein or >1.2 g\/kg\/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g\/kg\/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":22227886,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Support vector machine classification and characterization of age-related reorganization of functional brain networks.\nMost of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org\/projects\/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in negative correlations between the default and sensorimotor networks, are the distinguishing characteristics of age-related reorganization.","subset":"pubmed_abstract"} +{"meta":{"pmid":27124735,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Does Celiac Disease Influence Survival in Sepsis? A Nationwide Longitudinal Study.\nIndividuals with celiac disease (CD) are at increased risk of sepsis. The aim of this study was to examine whether CD influences survival in sepsis of bacterial origin. Nationwide longitudinal registry-based study. Through data on small intestinal biopsies from Sweden's 28 pathology departments, we identified 29,096 individuals with CD (villous atrophy, Marsh stage III). Each individual with CD was matched with five population-based controls. Among these, 5,470 had a record of sepsis according to the Swedish Patient Register (1,432 celiac individuals and 4,038 controls). Finally we retrieved data on mortality in sepsis patients through the Swedish Cause of Death Registry. CD was associated with a 19% increase in overall mortality after sepsis (95% confidence interval (CI) = 1.09-1.29), with the highest relative risk occurring in children (adjusted hazard ratio (aHR) = 1.62; 95%CI = 0.67-3.91). However, aHR for death from sepsis was lower (aHR = 1.10) and failed to reach statistical significance (95%CI = 0.72-1.69). CD did not influence survival within 28 days after sepsis (aHR = 0.98; 95%CI = 0.80-1.19). Although individuals with CD seem to be at an increased risk of overall death after sepsis, that excess risk does not differ from the general excess mortality previously seen in celiac patients in Sweden. CD as such does not seem to influence short-term or sepsis-specific survival in individuals with sepsis and therefore is not an independent risk factor for poor prognosis in sepsis.","subset":"pubmed_abstract"} +{"meta":{"pmid":32565592,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"COVID-19-related conspiracy beliefs and their relationship with perceived stress and pre-existing conspiracy beliefs.\nPrevious studies have down that erroneous Conspiracy Theory (CT) beliefs develop more strongly in people who have underlying conspiratorial reasoning styles and psychopathological traits and particularly when they are faced with stressful external events (Swami et al., 2013; van Prooijen, 2018). In this study, we test this proposition by examining the individual differences associated with the development of COVID-19-related CT beliefs during the pandemic. A total of 660 adults completed a survey that captured COVID-related CT beliefs and broader conspiracy beliefs, education, perceived stress and attitudes towards government responses. The results showed that COVID-19 related CT beliefs were: strongly related to broader CT beliefs, higher in those with lower levels of education; and, positively (although weakly) correlated with more negative attitudes towards government responses. However, no relationship was found between COVID-19 beliefs and self-reported stress. These findings hold implications for why some people are more likely to be resistant to public health interventions relating to COVID-19. The findings encourage more detailed exploration of the causes and sources of CTs and, in particular, the role of social media use and other information sources in the development and perpetuation of health-related CT beliefs.","subset":"pubmed_abstract"} +{"meta":{"pmid":29739430,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2022-49":1,"2021-49":1,"2021-43":1,"2021-31":2,"2021-21":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":1,"2023-14":1,"2024-22":3,"2024-18":1,"2024-26":1}}},"text":"RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial.\nEvidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population. METHODS\/DESIGN: The \"REstricted versus Liberal positive end-expiratory pressure in patients without ARDS\" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h. RELAx will run in 13 ICUs in the Netherlands to enroll 980 patients under invasive ventilation. In all patients, low tidal volumes are used. Patients assigned to ventilation with low PEEP will receive the lowest possible PEEP between 0 and 5 cm H2O, while patients assigned to ventilation with high PEEP will receive PEEP of 8 cm H2O. The primary endpoint is the number of ventilator-free days and being alive at day 28, a composite endpoint for liberation from the ventilator and mortality until day 28, with a noninferiority margin for a difference between groups of 0.5 days. Secondary endpoints are length of stay (LOS), mortality, and occurrence of pulmonary complications, including severe hypoxemia, major atelectasis, need for rescue therapies, pneumonia, pneumothorax, and development of acute respiratory distress syndrome (ARDS). Hemodynamic support and sedation needs will be collected and compared. RELAx will be the first sufficiently sized randomized controlled trial in invasively ventilated, critically ill patients with uninjured lungs using a clinically relevant and objective endpoint to determine whether invasive, low-tidal-volume ventilation with low PEEP is noninferior to ventilation with high PEEP. ClinicalTrials.gov , ID: NCT03167580 . Registered on 23 May 2017.","subset":"pubmed_abstract"} +{"meta":{"pmid":29168714,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evaluation of nutrient retention in vegetated filter strips using the SWAT model.\nNutrient fluxes in stream basins need to be controlled to achieve good water quality status. In stream basins with intensive agricultural activities, nutrients predominantly come from diffuse sources. Therefore, best management practices (BMPs) are increasingly implemented to reduce nutrient input to streams. The objective of this study is to evaluate the impact of vegetated filter strip (VFS) application as an agricultural BMP. For this purpose, SWAT is chosen, a semi-distributed water quality assessment model that works at the watershed scale, and applied on the Nif stream basin, a small-sized basin in Western Turkey. The model is calibrated with an automated procedure against measured monthly discharge data. Nutrient loads for each sub-basin are estimated considering basin-wide data on chemical fertilizer and manure usage, population data for septic tank effluents and information about the land cover. Nutrient loads for 19 sub-basins are predicted on an annual basis. Average total nitrogen and total phosphorus loads are estimated as 47.85 t\/yr and 13.36 t\/yr for the entire basin. Results show that VFS application in one sub-basin offers limited retention of nutrients and that a selection of 20-m filter width is most effective from a cost-benefit perspective.","subset":"pubmed_abstract"} +{"meta":{"pmid":8540733,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2020-24":1}}},"text":"Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus.\nMacrolide antibiotics are clinically important antibiotics which are effective inhibitors of protein biosynthesis in bacterial cells. We have recently shown that some of these compounds also inhibit 50S ribosomal subunit formation in Escherichia coli. Now we show that certain macrolides have the same effect in two gram-positive organisms, Bacillus subtilis and Staphylococcus aureus. Assembly in B. subtilis was prevented by erythromycin, clarithromycin, and azithromycin but not by oleandomycin. 50S subunit formation in S. aureus was prevented by each of seven structurally related 14-membered macrolides but not by lincomycin or two streptogramin antibiotics. Erythromycin treatment did not stimulate the breakdown of performed 50S subunits in either organism. The formation of the 30S ribosomal subunit was also unaffected by these compounds. Assembly was also inhibited in a B. subtilis strain carrying a plasmid with the ermC gene that confers macrolide resistance by rRNA methylation. These results suggest that ribosomes contain an additional site for the inhibitory functions of macrolide antibiotics.","subset":"pubmed_abstract"} +{"meta":{"pmid":7161379,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Effect of incubation conditions on anaerobic susceptibility testing results.\nWe determined the effect of performing antimicrobial susceptibility tests in five different anaerobic incubation systems: GasPak jar, large GasPak jar, evacuated-gassed anaerobic jar, anaerobic chamber, and Bio-Bag. Growth of the anaerobes was equivalent in all five incubation systems. The results of testing 38 anaerobes against 11 antimicrobial agents were comparable for the anaerobic jars and anaerobic chamber. However, discordant results were observed for metronidazole and cefamandole tests when incubated in the Bio-Bag.","subset":"pubmed_abstract"} +{"meta":{"pmid":3132319,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":4,"unknown":8}}},"text":"Effects of estradiol on estrogen receptor, progesterone receptor, and tyrosinase in hamster melanoma transplanted into athymic mice.\nNuclear estrogen binding was characterized in HM-1, a malignant hamster melanoma cell line transplanted into male and female athymic mice following acute, subchronic, and chronic injection of estradiol. Nuclear binding was saturable, of high affinity (10(10) M-1) and readily soluble in low salt buffer. Saturation analyses revealed that [3H]estradiol in excess of 5.0 nM apparently bound to a second class of lower affinity (10(9) M-1), higher capacity cytosol sites. Enzyme-linked immunoassay with a specific monoclonal antibody (H222 Sp gamma) directed against the human estrogen receptor protein was in excellent agreement (r = 0.93) with values obtained using hydroxyapatite to separate bound from free ligand. Nuclear estrogen receptor content in HM-1 cells was increased maximally 1 h after acute s.c. injection of a low dose (0.1 microgram) of estradiol. The increase in nuclear receptor content was accompanied by an apparent rapid reduction in cytosol binding. Subchronic (3 days) and chronic exposure (35 days) to estradiol also produced a significant, dose-related increase in tumor nuclear estrogen receptor content. Cytosol binding for progestin was low (less than or equal to 2 fmol) to absent in HM-1 xenografts not exposed to estradiol. Subchronic and chronic exposure to estradiol induced a dose-related, specific, high affinity (10(9) M-1) cytosol binding protein for progestin(s) in HM-1 xenografts carried in male and female athymic mice. In contrast, progestin binding to nuclear receptor was not increased in estrogen-primed animals, nor did acute injection of progesterone (100 micrograms s.c.) increase the amount of saturable, high affinity (10(9) M-1) nuclear progestin receptor in control or estradiol-primed athymic mice. In contrast to the induction of progestin binding, tyrosinase activity was not altered by a similar exposure to estradiol when assayed at a saturating concentration of tyrosine. These observations suggest that the estrogen receptor in HM-1 cells may be functional but that pigmentary changes observed in mammals following chronic exposure to estradiol may not be mediated by a direct effect on the rate limiting enzyme of melanin synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":20306371,"dup_signals":{"dup_doc_count":16,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2017-13":1,"unknown":10}}},"text":"Items on the left are better remembered.\nNeurologically intact individuals show a spatial processing bias in perception tasks, specifically showing a bias towards the left in bisecting lines. We present evidence for a novel finding that a leftwards bias occurs in short-term memory for recently presented arbitrary bindings of visual features. Three experiments are reported, two of which involve a total of over 60,000 participants with a small number of trials for each. Experiment 3 involved a larger number of trials for each of 144 participants. Participants reproduced from immediate memory arrays of shape-colour-location bindings. In all three experiments, significantly more errors were observed in reproduction of items presented on the right of the array than on the left. Results could not be accounted for by perceptual errors, or by order of presentation or order of reproduction. Findings suggest that items presented on the left are better remembered, indicating a spatial asymmetry in forming or retrieving feature bindings in visual short-term memory.","subset":"pubmed_abstract"} +{"meta":{"pmid":28562470,"dup_signals":{"dup_doc_count":41,"dup_dump_count":23,"dup_details":{"curated_sources":4,"2023-50":3,"2023-23":1,"2023-14":2,"2023-06":3,"2022-40":2,"2022-27":3,"2022-21":3,"2022-05":1,"2021-43":2,"2021-39":1,"2021-31":1,"2021-21":1,"2021-17":3,"2021-10":1,"2020-45":1,"2020-40":1,"2020-24":1,"2020-16":1,"2018-26":1,"2024-22":1,"2024-18":1,"2024-10":2,"2024-26":1}}},"text":"A Comparison of Dye Versus Fluorescence Methods for Sentinel Lymph Node Mapping in Endometrial Cancer.\nSentinel nodes (SNs) have been observed in several reports from Japan and overseas in cases with endometrial cancer; however, no consensus has been reached regarding the types of tracers or the method of their injection. A combination of the radioisotope (RI) and dye method is considered to be desirable. We assessed SN mapping using either dye or near-infrared fluorescence imaging to clarify a suitable method in cases of endometrial cancer. Patients were enrolled from 92 patients diagnosed with endometrial cancer and having no extrauterine metastasis by the preoperative imaging between 2009 and 2014 at our institution. To identify the SNs, we performed 3 methods using either dye or fluorescence solutions in conjunction with a RI method. In the dye method, we injected indocyanine green in the uterine subserosa, visually identifying SNs as stained green. In the fluorescence method, a dilute indocyanine green solution (0.5 mg, fluorescence A or 0.25 mg, fluorescence B, each per 10 mL of solvent) was injected and the SN identified by the HyperEye Medical System. The SN detection rates were 100%, 100%, and 96% using dye and fluorescence A or B solution, respectively. Pelvic SNs were detected by the 3 methods in 98%, 100%, and 96% of cases and para-aortic SNs in 65%, 88%, and 74%, respectively. Fluorescence A solution was somewhat better than dye in detecting para-aortic SNs, although not significantly so (P = 0.07). The sensitivity and negative predictive values for detecting SNs with metastases with the dye method were 92% and 98% compared with 100% and 100%, respectively, for both fluorescence solutions. Although both dye and fluorescence methods performed well, no method perfectly identified para-aortic SNs. The concomitant use of the RI method is required to detect para-aortic SNs.","subset":"pubmed_abstract"} +{"meta":{"pmid":24007133,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":2,"unknown":9}}},"text":"Low-dose phase contrast mammography with conventional x-ray sources.\nTo provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. Following the adaptation of our \"edge-illumination\" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.","subset":"pubmed_abstract"} +{"meta":{"pmid":23096553,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"[Historical notes on Infectious Diseases Hospital Francisco Javier Mu\u00f1iz in Buenos Aires, Argentina].\nThe Infectious Diseases Hospital Francisco Javier Mu\u00f1iz, Buenos Aires, Argentina, is the oldest in Latin America. It is over 100 years old and has a history worthy of pride. It became known as \"Hospital of the pests\" and was preceded by the old House of Insulation, which served as a quarantine station during epidemics of cholera, yellow fever and smallpox. The new House of Insulation, built in the neighborhood of Parque Patricios (\"Barracks Hospital\"), was renamed in 1904 in memory of Francisco Javier Mu\u00f1iz, a former military doctor, naturalist and paleontologist. Its technical name is \"Porte\u00f1o Care Centre and National Reference Regional Infectious-Contagious Disease\". It receives numerous national and foreign undergraduate and postgraduate students in its Departments of Infectious Diseases and Respiratory Diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":24207061,"dup_signals":{"dup_doc_count":33,"dup_dump_count":27,"dup_details":{"curated_sources":2,"2020-40":2,"2020-29":1,"2020-16":1,"2020-10":2,"2019-51":1,"2019-43":1,"2019-35":2,"2019-26":2,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-26":1,"2021-04":1,"2024-22":1}}},"text":"Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring.\nSerum biomarkers can improve diagnosis and treatment of malignant pleural mesothelioma (MPM). However, the evaluation of potential new serum biomarker candidates is hampered by a lack of assay technologies for their clinical evaluation. Here we followed a hypothesis-driven targeted proteomics strategy for the identification and clinical evaluation of MPM candidate biomarkers in serum of patient cohorts. Based on the hypothesis that cell surface exposed glycoproteins are prone to be released from tumor-cells to the circulatory system, we screened the surfaceome of model cell lines for potential MPM candidate biomarkers. Selected Reaction Monitoring (SRM) assay technology allowed for the direct evaluation of the newly identified candidates in serum. Our evaluation of 51 candidate biomarkers in the context of a training and an independent validation set revealed a reproducible glycopeptide signature of MPM in serum which complemented the MPM biomarker mesothelin. Our study shows that SRM assay technology enables the direct clinical evaluation of protein-derived candidate biomarker panels for which clinically reliable ELISA's currently do not exist.","subset":"pubmed_abstract"} +{"meta":{"pmid":30823160,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Effects of Water Stress on Symptomatology and Growth of Parthenocissus quinquefolia Infected by Xylella fastidiosa.\nA greenhouse study was conducted to test the hypothesis that bacterial leaf scorch symptoms, caused by Xylella fastidiosa, are more severe during periods of drought stress. A two-by-two complete factorial design with two pathogen treatments (control and infected) and two soil moisture levels (high and low) was used with Parthenocissus quinquefolia vines in 1999 and 2000. In each year, a high percentage of P. quinquefolia plants inoculated with X. fastidiosa expressed typical bacterial leaf scorch symptoms, with the outer scorched portion of the leaf separated from green tissue by a chlorotic halo. X. fastidiosa was detected in all symptomatic plants using an immunomagnetic capture and nested polymerase chain reaction technique, and was reisolated and cultured in modified periwinkle wilt liquid media. In both years, symptoms progressed further along the stem and were more severe at corresponding leaf positions in low-water-infected plants compared to high-water-infected plants. Total leaf area, shoot length, and number of nodes on the longest shoot per plant were all reduced due to drought and X. fastidiosa infection. This study is the first to verify the hypothesis that bacterial leaf scorch symptoms are enhanced during drought stress. Maintaining plant vigor with regular watering can be used to sustain plants infected by X. fastidiosa, particularly during periods of water stress.","subset":"pubmed_abstract"} +{"meta":{"pmid":18239660,"dup_signals":{"dup_doc_count":11}},"text":"BMI vs. waist circumference for identifying vascular risk.\nCurrent guidelines recommend measurement of both BMI and waist circumference (WC) in individuals with BMI between 25.0 and 34.9 kg\/m(2). We investigated the relative contributions of BMI and WC toward identifying risk of adverse vascular events in a community-based sample. We evaluated Framingham Study participants (n = 4,195 person-examinations, 53% women) using pooled logistic regression to assess the incremental prognostic utility of WC in predicting risk of a first cardiovascular disease (CVD) event in the three BMI categories (normal, <25 kg\/m(2); overweight, 25 to <30 kg\/m(2); obese, > or =30 kg\/m(2)) and to assess the incremental prognostic utility of BMI and WC separately for predicting risk of a first cardiovascular event. On follow-up (16 years), 430 participants (158 women) had experienced a first CVD event. In overweight women, but not in overweight men, larger WC was found to be an independent predictor of CVD incidence, longitudinally (in women, multivariable-adjusted odds ratio (OR) per s.d. increment in WC 1.86, 95% confidence interval (CI) = 1.03-3.36, P = 0.04; in men adjusted OR per s.d. increment in WC 0.91, 95% CI 0.60-1.38, P = 0.66). In obese individuals and in those with normal BMI, WC was not associated independently with incident CVD. When BMI and WC were analyzed separately for predicting risk of a first cardiovascular event, the c statistics associated with the multivariable CVD models incorporating BMI vs. WC were nearly identical in men and women. Knowledge of WC aids identification of vascular risk among overweight women. Among normal weight or obese women and men (regardless of BMI category) WC did not appear to substantially add to prediction of risk of vascular events.","subset":"pubmed_abstract"} +{"meta":{"pmid":20190788,"dup_signals":{"dup_doc_count":19,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2021-49":1,"2020-50":1,"2019-51":1,"2019-30":1,"2018-39":1,"2018-13":1,"2017-47":2,"2017-34":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2022-49":1,"2017-13":1,"2024-10":1}}},"text":"Protein aggregation diseases: pathogenicity and therapeutic perspectives.\nA growing number of diseases seem to be associated with inappropriate deposition of protein aggregates. Some of these diseases--such as Alzheimer's disease and systemic amyloidoses--have been recognized for a long time. However, it is now clear that ordered aggregation of pathogenic proteins does not only occur in the extracellular space, but in the cytoplasm and nucleus as well, indicating that many other diseases may also qualify as amyloidoses. The common structural and pathogenic features of these diverse protein aggregation diseases is only now being fully understood, and may provide novel opportunities for overarching therapeutic approaches such as depleting the monomeric precursor protein, inhibiting aggregation, enhancing aggregate clearance or blocking common aggregation-induced cellular toxicity pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":28935712,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Macrophages are required to coordinate mouse digit tip regeneration.\nIn mammals, macrophages are known to play a major role in tissue regeneration. They contribute to inflammation, histolysis, re-epithelialization, revascularization and cell proliferation. Macrophages have been shown to be essential for regeneration in salamanders and fish, but their role has not been elucidated in mammalian epimorphic regeneration. Here, using the regenerating mouse digit tip as a mammalian model, we demonstrate that macrophages are essential for the regeneration process. Using cell-depletion strategies, we show that regeneration is completely inhibited; bone histolysis does not occur, wound re-epithelialization is inhibited and the blastema does not form. Although rescue of epidermal wound closure in the absence of macrophages promotes blastema accumulation, it does not rescue cell differentiation, indicating that macrophages play a key role in the redifferentiation of the blastema. We provide additional evidence that although bone degradation is a component, it is not essential to the overall regenerative process. These findings show that macrophages play an essential role in coordinating the epimorphic regenerative response in mammals.","subset":"pubmed_abstract"} +{"meta":{"pmid":17351614,"dup_signals":{"dup_doc_count":37,"dup_dump_count":31,"dup_details":{"curated_sources":2,"2018-13":1,"2017-39":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2018-22":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-11":1}}},"text":"Exploration of nanostructured channel systems with single-molecule probes.\nMolecular movement in confined spaces is of broad scientific and technological importance in areas ranging from molecular sieving and membrane separation to active transport through ion channels. Whereas measurements of ensemble diffusion provide information about the overall behaviour of the guest in a porous host, tracking individual molecules provides insight into both the heterogeneity and the mechanistic details of molecular diffusion as well as into the structure of the host. Here, we show how single dye molecules can be used as nanoscale probes to map out the structure of mesoporous silica channel systems prepared as thin films via cooperative self-assembly of surfactant molecules with polymerizable silicate species. The dye molecules act as beacons while they diffuse through the different structural phases of the host: the structure of the trajectories, the diffusivities and the orientation of single molecules are distinctive for molecules travelling in the lamellar and the hexagonal mesophases. These experiments reveal unprecedented details of the host structure, its domains and the accessibility as well as the connectivity of the channel system.","subset":"pubmed_abstract"} +{"meta":{"pmid":10416615,"dup_signals":{"dup_doc_count":21,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-10":1,"unknown":15}}},"text":"Mouse model for the DNA repair\/basal transcription disorder trichothiodystrophy reveals cancer predisposition.\nPatients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD encodes a helicase subunit of the dually functional DNA repair\/basal transcription complex TFIIH. The pleiotropic disease phenotype is hypothesized to be, in part, derived from a repair defect causing UV sensitivity and, in part, from a subtle, viable basal transcription deficiency accounting for the cutaneous, developmental, and the typical brittle hair features of TTD. To understand the relationship between deficient NER and tumor susceptibility, we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline. Like the fibroblasts from the patient, mouse cells exhibit a partial NER defect, evident from the reduced UV-induced DNA repair synthesis (residual repair capacity approximately 25%), limited recovery of RNA synthesis after UV exposure, and a relatively mild hypersensitivity to cell killing by UV or 7,12-dimethylbenz[a]anthracene. In accordance with the cellular studies, TTD mice exhibit a modestly increased sensitivity to UV-induced inflammation and hyperplasia of the skin. In striking contrast to the human syndrome, TTD mice manifest a dear susceptibility to UV- and 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis, albeit not as pronounced as the totally NER-deficient XPA mice. These findings open up the possibility that TTD is associated with a so far unnoticed cancer predisposition and support the notion that a NER deficiency enhances cancer susceptibility. These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":33761980,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells.\nDrawing genotype-to-phenotype maps in tumors is of paramount importance for understanding tumor heterogeneity. Assignment of single cells to their tumor clones of origin can be approached by matching the genotypes of the clones to the mutations found in RNA sequencing of the cells. The confidence of the cell-to-clone mapping can be increased by accounting for additional measurements. Follicular lymphoma, a malignancy of mature B cells that continuously acquire mutations in parallel in the exome and in B cell receptor loci, presents a unique opportunity to join exome-derived mutations with B cell receptor sequences as independent sources of evidence for clonal evolution. Here, we propose CACTUS, a probabilistic model that leverages the information from an independent genomic clustering of cells and exploits the scarce single cell RNA sequencing data to map single cells to given imperfect genotypes of tumor clones. We apply CACTUS to two follicular lymphoma patient samples, integrating three measurements: whole exome, single-cell RNA, and B cell receptor sequencing. CACTUS outperforms a predecessor model by confidently assigning cells and B cell receptor-based clusters to the tumor clones. The integration of independent measurements increases model certainty and is the key to improving model performance in the challenging task of charting the genotype-to-phenotype maps in tumors. CACTUS opens the avenue to study the functional implications of tumor heterogeneity, and origins of resistance to targeted therapies. CACTUS is written in R and source code, along with all supporting files, are available on GitHub ( https:\/\/github.com\/LUMC\/CACTUS ).","subset":"pubmed_abstract"} +{"meta":{"pmid":20576852,"dup_signals":{"dup_doc_count":12}},"text":"Switched magnetospheric regulation of pulsar spin-down.\nPulsars are famed for their rotational clocklike stability and their highly repeatable pulse shapes. However, it has long been known that there are unexplained deviations (often termed timing noise) from the rate at which we predict these clocks should run. We show that timing behavior often results from two different spin-down rates. Pulsars switch abruptly between these states, often quasi-periodically, leading to the observed spin-down patterns. We show that for six pulsars the timing noise is correlated with changes in the pulse shape. Many pulsar phenomena, including mode changing, nulling, intermittency, pulse-shape variability, and timing noise, are therefore linked and are caused by changes in the pulsar's magnetosphere. We consider the possibility that high-precision monitoring of pulse profiles could lead to the formation of highly stable pulsar clocks.","subset":"pubmed_abstract"} +{"meta":{"pmid":25984284,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Persistent psychosis after abuse of high dose of zolpidem.\nZolpidem is a non-benzodiazepine medication which selectively affects GABA A receptors and treats insomnia. There are numerous reports of psychosis following the consumption of zolpidem all of which recovered after stopping the medication. A 27 year old male law student, who was treated with 10 mg zolpidem due to insomnia, increased the dosage to 500 mg during 3 months. Not only was his insomnia remained untreated, but also he gradually became isolated, suspicious, and aggressive, and dropped out of university. He was then hospitalized in a psychiatric ward for 2 months, and was treated with antipsychotics and gradual discontinuation of zolpidem. With no improvement in psychosis and sleep improvement he was discharged. After two weeks he was hospitalized again and went under electroconvulsive therapy (ECT) and antipsychotic therapy, and was discharged with relative improvement. Now, after three years, he is diagnosed with schizophrenia and with modest improvements he is under care and treatment. Zolpidem is a fairly useful medication for treating sleep problems, especially improving beginning of sleep. However, physicians \u00fdand clinicians should consider the conditions, predispositions, and personal and family history of types of psychosis, alcohol and drug abuse in the comprehensive assessment and treatment plan for patients with insomnia.","subset":"pubmed_abstract"} +{"meta":{"pmid":28742195,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"The use of susceptibility-weighted imaging to detect cerebral microbleeds after lacunar infarction.\nTo study the value of susceptibility-weighted imaging (SWI) technology to detect cerebral microbleeds (CMBs) in senile cerebral lacunar infarction patients; and to evaluate the complicated cerebral hemorrhage risk after patients with CMBs took aspirin, an antiplatelet medication or received anticoagulant therapy. MRI scanning, using GRE-T2*WI, SWI and FSE sequences (T1WI, T2WI, and T2FLAIR), was performed on the three groups: (1) a cerebral lacunar infarction group; (2) cerebral lacunar infarction with cerebral microbleeds (CMBs) group; and (3) a healthy elderly group. A total of 60 cases were in each group (180 total patients). In addition, the lacunar infarction group and lacunar infarction with CMBs groups were both treated with formal antiplatelet or anticoagulant therapy, according to medical guidelines. Patients were followed for 12 months, during which time their cerebral hemorrhages and post-event effects were observed. The relativity of CMBs, antiplatelet therapy, anticoagulant therapy and cerebral hemorrhage transformation was analyzed and defined. The two groups of research patients with lacunar infarctions were scanned with relevant sequences. The SWI scanning sequence showed the highest positive rate of CMBs, followed by GRE-T2*WI and other conventional scanning sequences. T1WI, T2WI and T2FLAIR showed a relatively lower positive rate of CMBs. In the cerebral lacunar infarction group and healthy elderly group, 34 cases in the SWI sequence showed 84 positive sites; 18 cases in the GRE-T2*WI sequence showed 40 positive sites; 2 cases in the T1WI sequence showed 4 positive sites; and 6 cases in the T2WI sequence showed 11 positive sites. After a chi-squared test, the differences between the sequences were statistically significant (p < 0.05). In the lacunar infarction group, 26 cases (43.33%) exhibited microbleeding lesions, while the normal control group represented 8 cases (13.33%). The lacunar infarction group exhibited mild, moderate and severe cases, the three types of CMBs. The normal control group only showed mild hemorrhaging. The degree of lacunar infarction was significantly related to the severity of CMBs (p < 0.05). After patients with CMBs had received formal antiplatelet therapy and anticoagulation therapy, one case in the lacunar infarction with microbleeds group showed cerebral hemorrhaging, but this had no statistical significance (p > 0.05). The SWI scanning sequence is more sensitive than the GRE-T2*WI sequence. The GRE-T2*WI sequence is more sensitive than the conventional FSE sequence. SWI is highly sensitive and specific to the diagnosis of CMBs. It is an accurate and effective method for the analysis and diagnosis of CMBs. If patients with CMBs caused by lacunar infarction are treated with antiplatelet and anticoagulant therapy, the risk of cerebral hemorrhagic transformation is relatively smaller within 12 months. However, this needs to be observed further to define possible long-term risks.","subset":"pubmed_abstract"} +{"meta":{"pmid":26341331,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2022-49":1,"2022-40":2,"2022-33":2,"2022-21":1,"2022-05":1,"2021-49":1,"2023-40":1,"2024-10":3,"2024-26":1}}},"text":"Borrelia burgdorferi sensu stricto and Borrelia afzelii: Population structure and differential pathogenicity.\nMultiLocus sequence typing (MLST) is considered a powerful method to unveil relationships within bacterial populations and it constitutes an economical and fast alternative to whole genome sequencing. We used this method to understand whether there are differences in human pathogenicity within and between different Borrelia burgdorferi sensu lato species. Therefore, 136 strains from human patients or ticks from Europe were included in MLST analyses. The scheme employed used eight chromosomally located housekeeping genes (i.e. clpA, clpX, nifS, pepX, pyrG, recG, rplB and uvrA). We investigated Borrelia afzelii, one of the predominant species in Europe, and B. burgdorferi sensu stricto (s.s.), because it allowed comparative analysis to strains from the USA. We typed 113 patient isolates as well as 23 tick isolates. For further comparative purposes an additional 746 strains from Europe and the USA were included from the MLST website http:\/\/borrelia.mlst.net. We observed an overlap of the B. burgdorferi s.s. populations from Europe and the USA isolated from human patients while there was no overlap of the populations found in tick vectors. Further results indicate that B. afzelii was significantly less associated with disseminated infection than B. burgdorferi s.s. and that B. burgdorferi s.s. from Europe caused neuroborreliosis to a significantly greater extent than B. afzelii or B. burgdorferi s.s. in the USA. Our data suggest that there may be an evolutionary basis of differential interspecies pathogenicity in Borrelia. This was not evident within Borrelia species: we found the same sequence types in patients with disseminated or localized symptoms when the number of strains was sufficiently high. We hypothesize that the finding that B. burgdorferi s.s. in Europe is much more associated with neuroborreliosis than in the USA maybe linked to factor(s) related to the human host, the tick vector or the bacterium itself (e.g. plasmid content and structure).","subset":"pubmed_abstract"} +{"meta":{"pmid":20578566,"dup_signals":{"dup_doc_count":26,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":2,"2017-13":1,"unknown":11}}},"text":"Health savings accounts and health reimbursement arrangements: assets, account balances, and rollovers, 2006-2009.\nASSET LEVELS GROWING: In 2009, there was $7.1 billion in consumer-driven health plans (CDHPs), which include health savings accounts (or HSAs) and health reimbursement arrangements (or HRAs), spread across 5 million accounts. This is up from 2006, when there were 1.2 million accounts with $835.4 million in assets, and 2008, when 4.2 million accounts held $5.7 billion in assets. AVERAGE ACCOUNT BALANCE LEVELING OFF: Increases in average account balances appear to have leveled off. In 2006, account balances averaged $696. They increased to $1320 in 2007, a 90 percent increase. Account balances averaged $1356 in 2008 and $1419 in 2009, 3 percent and 5 percent increases, respectively. TYPICAL ENROLLEE: The typical CDHP enrollee was more likely than traditional plan enrollees to be young, unmarried, higher-income, educated, and exhibit healthy behavior. No differences were found between CDHPs enrollees and traditional plan enrollees with respect to gender, race, and presence of children. MORE ROLLOVERS: Overall, the number of people with a rollover, as well as the total level of assets being rolled over, have been increasing. The average rollover increased from $592 in 2006 to $1295 in 2009. DIFFERENCES IN ACCOUNT BALANCES: Men tend to have higher account balances than women, account balances increase with household income, education has a significant impact on account balances independent of income and other variables, and no statistically significant differences in account balances were found by smoking, obesity, or the presence of chronic health conditions. Individuals who developed a budget to manage their health care expenses had a higher account balance ($1726) than those who did not ($1428), but otherwise, no statistically significant differences in average account balances were found between individuals who exhibited various aspects of cost-conscious decision-making behaviors and those who did not. DIFFERENCES IN ROLLOVER AMOUNTS: Men rolled over more money than women, whites have higher rollover amounts than minorities, and the youngest adults and the oldest adults had the largest rollover amounts in 2009. Rollover amounts increase with household income and education, and individuals with single coverage rolled over a slightly higher average amount than those with family coverage. There was no statistically significant difference in rollover amounts by health status, although individuals who smokes ad higher rollover amounts than those who do not and obese individuals had lower average rollover amounts than nonobese individuals. Individuals who talked to their doctor about treatment options and costs, those who used an online cost-tracking tool provided by the health plan, and those who asked their doctor to recommend a less costly prescription drug had higher rollover amounts than those who did not take such actions.","subset":"pubmed_abstract"} +{"meta":{"pmid":27254810,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":10}}},"text":"Developing a Very Low Vision Orientation and Mobility Test Battery (O&M-VLV).\nThis study aimed to determine the feasibility of an assessment of vision-related orientation and mobility (O&M) tasks in persons with severe vision loss. These tasks may be used for future low vision rehabilitation clinical assessments or as outcome measures in vision restoration trials. Forty legally blind persons (mean visual acuity logMAR 2.3, or hand movements) with advanced retinitis pigmentosa participated in the Orientation & Mobility-Very Low Vision (O&M-VLV) subtests from the Low Vision Assessment of Daily Activities (LoVADA) protocol. Four categories of tasks were evaluated: route travel in three indoor hospital environments, a room orientation task (the \"cafe\"), a visual exploration task (the \"gallery\"), and a modified version of the Timed Up and Go (TUG) test, which assesses re-orientation and route travel. Spatial cognition was assessed using the Stuart Tactile Maps test. Visual acuity and visual fields were measured. A generalized linear regression model showed that a number of measures in the O&M-VLV tasks were related to residual visual function. The percentage of preferred walking speed without an aid on three travel routes was associated with visual field (p < 0.01 for all routes) whereas the number of contacts with obstacles during route travel was associated with acuity (p = 0.001). TUG-LV task time was associated with acuity (p = 0.003), as was the cafe time and distance traveled (p = 0.006 and p < 0.001, respectively). The gallery score was the only measure that was significantly associated with both residual acuity and fields (p < 0.001 and p = 0.001, respectively). The O&M-VLV was designed to capture key elements of O&M performance in persons with severe vision loss, which is a population not often studied previously. Performance on these tasks was associated with both binocular visual acuity and visual field. This new protocol includes assessments of orientation, which may be of benefit in vision restoration clinical trials.","subset":"pubmed_abstract"} +{"meta":{"pmid":18304276,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Comparing the performance of indicators of hand-washing practices in rural Indian households.\nTo compare the results obtained from 26 proxy indicators of domestic hand-washing practices with those obtained from direct, 'structured' observation of hand-washing in a sample of 387 households and to assess the potential of these indicators for use in the evaluation of hygiene promotion campaigns. Fieldwork in rural India between February 2005 and April 2006. Household-level data on hand-washing practices and the availability of soap and water were collected by structured observation, questionnaire survey, pocket voting, hand-wash demonstration and environmental check. Between them these techniques produced 27 binary indicators of hand-washing practices, each of which was used to classify households as 'hand-washing' or 'non-hand-washing. To assess the extent to which household classification based on each of 26 proxy indicators concurred with classification based on observation, we used the kappa statistic. The prevalence of households defined as 'hand-washing' according to each indicator was compared statistically with the prevalence according to structured observations by testing for a significant difference between two proportions. Agreement between all the proxy indicators and the observation data was poor and all but two of the indicators produced estimates of hand-washing prevalence that were significantly different from that resulting from observation. Although some interventions may be able to use proxy indicators as a guide to the magnitude and direction of their impact, these indicators do not provide an accurate guide to the actual practice or prevalence of hand-washing. Structured observation remains the best indicator of those tested.","subset":"pubmed_abstract"} +{"meta":{"pmid":7666247,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":5,"2020-50":2,"2020-40":4,"2019-35":2,"2019-22":2}}},"text":"Bioavailability of soybean isoflavones depends upon gut microflora in women.\nSoybean isoflavones have been proposed to be anticarcinogenic, but their effective doses have not been established. To study their bioavailability, seven women consumed 3.4, 6.9, or 10.3 mumol isoflavones\/kg body wt in soymilk in each of three meals of a liquid diet on one of three feeding days that were separated by 2-wk washout periods. Subjects were randomly assigned to doses in a cross-over design. Plasma, urine and fecal isoflavones were measured by reverse phase HPLC. In two subjects, fecal isoflavone recovery was 10-20 times that in the other five subjects. Average 48-h urinary recoveries of ingested daidzein and genistein were 16 +\/- 4 and 10 +\/- 4%, respectively, at all three doses among the five subjects excreting only small amounts of isoflavones in feces, whereas urinary recoveries of daidzein and genistein in the two subjects who excreted large amounts of fecal isoflavones were 32 +\/- 5 and 37 +\/- 6%, respectively. Urinary isoflavone excretion was nearly zero in all subjects at 48 h after dosing. Average plasma concentration of genistein at 24 h after the breakfast isoflavone dose in subjects excreting large amounts of fecal isoflavones was significantly greater by 2.5-fold than in subjects who excreted small amounts of fecal isoflavones (P < 0.05). In vitro anaerobic incubation of isoflavones with human feces showed that intestinal half-life of daidzein and genistein may be as little as 7.5 and 3.3 h, respectively. These data suggest that human isoflavone bioavailability depends upon the relative ability of gut microflora to degrade these compounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":26854742,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy.\nSleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence\/absence of nocturnal discharges or presence\/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record","subset":"pubmed_abstract"} +{"meta":{"pmid":24741137,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Surgical treatment of thoracic disc herniations using a modified transfacet approach.\nIdeal surgical treatment for thoracic disc herniation (TDH) is controversial due to variations in patient presentation, pathology, and possible surgical approach. Althougth discectomy may lead to improvements in neurologic function, it can be complicated by approach related morbidity. Various posterior surgical approaches have been developed to treate TDH, but the gold standard remains transthoracic decompression. Certain patients have comorbidities and herniation that are not optimally treated with an anterior approach. A transfacet pedicle approach was first described in 1995, but outcomes and complications have not been well described. The aim of this work was to evaluate the clinical effect and complications in a consecutive series of patients with symptomatic thoracic disc herniations undergoing thoracic discectomy using a modified transfacet approach. 33 patients with thoracic disc herniation were included in this study. Duration of the disease was from 12 days to 36 months, with less than 1 month in 13 patients. Of these, 15 patients were diagnosed with simple thoracic disc herniation, 6 were associated with ossified posterior longitudinal ligament, and 12 with ossified or hypertrophied yellow ligament. A total of 45 discs were involved. All the herniated discs and the ossified posterior longitudinal ligaments were excised using a modified transfacet approach. Laminectomy and replantation were performed for patients with ossified or hypertrophied yellow ligament. The screw-rod system was used on both sides in 14 patients and on one side in l9 patients. 29 patients were followed up for an average of 37 months (range 12-63 months) and 4 patients were lost to followup. Evaluation was based on Epstein and Schwall criteria.5 15 were classified as excellent and 10 as good, accounting for 86.21% (25\/29); 2 patients were classified as improved and 2 as poor. All the patients recovered neurologically after surgery. A total of 25 patients had significantly improved motor function from 3 to 6 months after surgery and 10 patients had slow recovery 6 months after surgery.. Of the three patients with postoperative complications, two had exacerbated preexisting defects and one had implant failure. Postoperative computed tomography or magnetic resonance imaging showed that all patients had well fused replanted lamina and completely decompressed canal. Thoracic discectomy using a modified transfacet approach can significantly improve the clinical outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19884499,"dup_signals":{"dup_doc_count":24,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":2,"2017-13":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":14}}},"text":"Learning by observation requires an early sleep window.\nNumerous studies have shown that sleep enhances memory for motor skills learned through practice. Motor skills can, however, also be learned through observation, a process possibly involving the mirror neuron system. We investigated whether motor skill enhancement through prior observation requires sleep to follow the observation, either immediately or after a delay, to consolidate the procedural memory. Sequence-specific fingertapping performance was tested in 64 healthy subjects in a balanced design. Electromyography verified absence of overt or subliminal hand muscle activations during observation. The results show that immediate sleep is necessary for the enhancement of a motor skill through prior observation. Immediate sleep improved the speed of subsequent performance by 22 +\/- 11% (mean +\/- SEM) (P = 0.04) and reduced the error rate by 42 +\/- 19% (P = 0.02). In contrast, no performance gains occurred if sleep was initiated more than 12 h after observation. A second study on 64 subjects ruled out explicit familiarity with the sequence or the spatiotemporal rhythm of the sequence to underlie performance improvements. The sleep-dependent observational motor learning enhancement is at least similar to that previously reported for implicit and declarative memory. The apparent prerequisite of observing real movements indicates that subjects transfer experience obtained through observation of movements to subsequent self-initiated movements, in the absence of practice. Moreover, the consolidation of this transfer requires an early sleep window. These findings could improve learning new motor skills in athletes and children, but also in patients having to remaster skills following stroke or injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":14982791,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"In vitro evaluation of double and triple combinations of antifungal drugs against Aspergillus fumigatus and Aspergillus terreus.\nMicrodilution broth checkerboard techniques based on the National Committee for Clinical Laboratory Standards methodology were used to study double and triple antifungal combinations against clinical isolates of Aspergillus fumigatus and A. terreus. The influences of the end-point definition (partial or complete inhibition) and the mode of reading (visually or spectrophotometrically) were determined. Interactions between antifungal drugs were also evaluated by agar diffusion tests. Combinations of caspofungin with either amphotericin B or voriconazole were additive for all the isolates, and antagonism was not observed. The interaction between caspofungin and flucytosine was synergistic for 62% of the isolates. In contrast, the interaction between voriconazole and flucytosine was never synergistic and antagonism was noted for 93% of the isolates. The triple combination of caspofungin with flucytosine and amphotericin B was synergistic for all the isolates tested. The triple combination of caspofungin with flucytosine and voriconazole was also mostly synergistic; but complex interactions were obtained for some isolates, with synergy or antagonism depending on the concentrations of caspofungin and voriconazole. Analysis of the influence of the reading technique on the results showed that spectrophotometric reading was a good alternative to the recommended visual reading. The results of these in vitro tests suggest that the activity of flucytosine as part of a double combination with caspofungin and as part of a triple combination with caspofungin and amphotericin B against Aspergillus spp. warrants further investigations. Animal studies are needed to evaluate the in vivo efficacies of these combinations.","subset":"pubmed_abstract"} +{"meta":{"pmid":28934226,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats.\nHeart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.","subset":"pubmed_abstract"} +{"meta":{"pmid":19091035,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":17}}},"text":"Malaria eradication: the economic, financial and institutional challenge.\nMalaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic development, the costs and consequences of the various tools and mixes of tools employed in control and eradication, issues concerning the extension of coverage of interventions and service delivery approaches, especially those that can reach the poorest, research on the processes of formulating and implementing malaria control and eradication policies, at both international and national levels, research on financing issues, at global and national levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":19876155,"dup_signals":{"dup_doc_count":17,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":2,"2015-48":1,"2015-40":1,"2015-32":3,"2015-27":1,"2015-22":2,"2015-18":1}}},"text":"Enhanced beam amplification in a photorefractive Bi(12)TiO(20) crystal by internal reflections.\nWe demonstrate experimentally that internal ref lections of a signal and (or) a pump beam allow one to increase beam amplification by two-beam coupling in a long Bi(12)TiO(20) crystal. When fanning is negligible, we achieve an enhancement of the amplification by adjustment of the spatial period of the transformation of the beam's polarization states with periodic reflections of the beams on the crystal boundaries. For the case of strong fanning the fanned beam is redirected by the reflections on the crystal surface, which allows one to use it as a pump beam, thus increasing net amplification gain.","subset":"pubmed_abstract"} +{"meta":{"pmid":25774740,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"Rational stabilization of complex proteins: a divide and combine approach.\nIncreasing the thermostability of proteins is often crucial for their successful use as analytic, synthetic or therapeutic tools. Most rational thermostabilization strategies were developed on small two-state proteins and, unsurprisingly, they tend to fail when applied to the much more abundant, larger, non-fully cooperative proteins. We show that the key to stabilize the latter is to know the regions of lower stability. To prove it, we have engineered apoflavodoxin, a non-fully cooperative protein on which previous thermostabilizing attempts had failed. We use a step-wise combination of structure-based, rationally-designed, stabilizing mutations confined to the less stable structural region, and obtain variants that, according to their van't Hoff to calorimetric enthalpy ratios, exhibit fully-cooperative thermal unfolding with a melting temperature of 75\u00b0C, 32 degrees above the lower melting temperature of the non-cooperative wild type protein. The ideas introduced here may also be useful for the thermostabilization of complex proteins through formulation or using specific stabilizing ligands (e.g. pharmacological chaperones).","subset":"pubmed_abstract"} +{"meta":{"pmid":24431204,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure.\ncAMP is a key mediator of connecting tubule and collecting duct (CD) Na(+) and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100% target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na(+) or K(+) excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na(+) channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3\/AC6 KO mice had similar arterial pressure and renal Na(+) and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na(+) and water excretion in general or vasopressin regulation of CD function in particular.","subset":"pubmed_abstract"} +{"meta":{"pmid":22747636,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Environmental stress increases selection against and dominance of deleterious mutations in inbred families of the Pacific oyster Crassostrea gigas.\nThe deleterious effects of inbreeding are well documented and of major concern in conservation biology. Stressful environments have generally been shown to increase inbreeding depression; however, little is known about the underlying genetic mechanisms of the inbreeding-by-stress interaction and to what extent the fitness of individual deleterious mutations is altered under stress. Using microsatellite marker segregation data and quantitative trait locus (QTL) mapping methods, I performed a genome scan for deleterious mutations affecting viability (viability or vQTL) in two inbred families of the Pacific oyster Crassostrea gigas, reared in a stressful, nutrient-poor diet and a favourable, nutrient-rich diet, which had significant effects on growth and survival. Twice as many vQTL were detected in the stressful diet compared with the favourable diet, resulting primarily from substantially greater mortality of homozygous genotypes. At vQTL, estimates of selection (s) and dominance (h) were greater in the stressful environment (= 0.86 vs. 0.54 and = 0.35 vs. 0.18, in stressful and nonstressful diets, respectively). There was no evidence of interaction between vQTL. Individual vQTL differed across diets in selection only, or in both selection and dominance, and some vQTL were not affected by diet. These results suggest that stress-associated increases in selection against individual deleterious alleles underlie greater inbreeding depression with stress. Furthermore, the finding that inbreeding-by-environment interaction appears, to some extent, to be locus specific, helps to explain previous observations of lineage-specific expression of inbreeding depression and environment-specific purging, which have important implications for conservation and evolutionary biology.","subset":"pubmed_abstract"} +{"meta":{"pmid":27036152,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":14}}},"text":"Adult Attachment Styles, Destructive Conflict Resolution, and the Experience of Intimate Partner Violence.\nAlthough there is ample evidence linking insecure attachment styles and intimate partner violence (IPV), little is known about the psychological processes underlying this association, especially from the victim's perspective. The present study examined how attachment styles relate to the experience of sexual and psychological abuse, directly or indirectly through destructive conflict resolution strategies, both self-reported and attributed to their opposite-sex romantic partner. In an online survey, 216 Spanish undergraduates completed measures of adult attachment style, engagement and withdrawal conflict resolution styles shown by self and partner, and victimization by an intimate partner in the form of sexual coercion and psychological abuse. As predicted, anxious and avoidant attachment styles were directly related to both forms of victimization. Also, an indirect path from anxious attachment to IPV victimization was detected via destructive conflict resolution strategies. Specifically, anxiously attached participants reported a higher use of conflict engagement by themselves and by their partners. In addition, engagement reported by the self and perceived in the partner was linked to an increased probability of experiencing sexual coercion and psychological abuse. Avoidant attachment was linked to higher withdrawal in conflict situations, but the paths from withdrawal to perceived partner engagement, sexual coercion, and psychological abuse were non-significant. No gender differences in the associations were found. The discussion highlights the role of anxious attachment in understanding escalating patterns of destructive conflict resolution strategies, which may increase the vulnerability to IPV victimization.","subset":"pubmed_abstract"} +{"meta":{"pmid":9126487,"dup_signals":{"dup_doc_count":23,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-14":3,"2023-06":1,"2022-40":1,"2022-27":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2023-40":1,"2024-22":3,"2024-18":1}}},"text":"Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21.\nBardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by retinitis pigmentosa, polydactyly, obesity, hypogenitalism, mental retardation, and renal anomalies. To detect linkage to BBS loci, 29 BBS families, of mixed but predominantly European ethnic origin, were typed with 37 microsatellite markers on chromosomes 2, 3, 11, 15, 16, and 17. The results show that an estimated 36-56% of the families are linked to the 11q13 chromosomal site (BBS1) previously described by M. Leppert et al. (1994, Nature Genet. 7, 108-112), with the gene order cen-D11S480-5 cM-BBS1-3 cM-D11S913\/D11S987-qter. A further 32-35% of the families are linked to the BBS4 locus, reported by R. Carmi et al. (1995, Hum. Mol. Genet. 4, 9-13) in chromosomal region 15q22.3-q23, with the gene order cen-D15S125-5 cM-BBS4-2 cM-D15S131\/D15S204-qter. Three consanguineous BBS families are homozygous for three adjacent chromosome 15 markers, consistent with identity by descent for this region. In one of these families haplotype analysis supports a localization for BBS4 between D15S131 and D15S114, a distance of about 2 cM. Weak evidence of linkage to the 16q21 (BBS2) region reported by A. E. Kwitek-Black et al. (1993, Nature Genet. 5, 392-396) was observed in 24-27% of families with the gene order cen-D16S408-2 cM-BBS2-5 cM-D16S400. A fourth group of families, estimated at 8%, are unlinked to all three of the above loci, showing that at least one other BBS locus remains to be found. No evidence of linkage was found to markers on chromosome 3, corresponding to the BBS3 locus, reported by V. C. Sheffield et al. (1994, Hum. Mol. Genet. 3, 1331-1335), or on chromosome 2 or 17, arguing against the involvement of a BBS locus in a patient with a t(2;17) translocation.","subset":"pubmed_abstract"} +{"meta":{"pmid":9109415,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2024-22":1}}},"text":"Direct physical interaction between the Caenorhabditis elegans 'death proteins' CED-3 and CED-4.\nThe two genes CED-4 and CED-3 (the nematode homologue of interleukin-1beta converting enzyme, ICE) of Caenorhabditis elegans are implicated in the control of cell death, but the mechanism by which this occurs is unknown. Here we provide evidence that CED-3 and CED-4 both contain sequences with homology to a domain present in RAIDD and the prodomain of certain ICE-like proteases (caspases). This domain is known to establish an interaction between RAIDD and these caspases. Similarly, CED-4 was found to interact with CED-3. Thus, the activity of the death protease CED-3 appears to be controlled by CED-4 through a direct physical interaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":29481447,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Photobiomodulation Therapy on Physiological and Performance Parameters During Running Tests: Dose-Response Effects.\nDellagrana, RA, Rossato, M, Sakugawa, RL, Baroni, BM, and Diefenthaeler, F. Photobiomodulation therapy on physiological and performance parameters during running tests: Dose-response effects. J Strength Cond Res 32(10): 2807-2815, 2018-This study was aimed at verifying effects of photobiomodulation therapy (PBMT) with different energy doses (15, 30, and 60 J per site) on physiological and performance parameters during running tests. Fifteen male recreational runners participated in a crossover, randomized, double-blind, and placebo-controlled trial. They performed testing protocol in 5 sessions with different treatments: control, placebo, and PBMT with 15, 30, or 60 J per site (14 sites in each lower limb). Physiological and performance variables were assessed during submaximal (at 8 and 9 km\u00b7h) and maximal running tests. Photobiomodulation therapy with 30 J significantly improved running economy (RE) at 8 and 9 km\u00b7h (3.01%, p=0.008 and 3.03%, p=0.009, respectively), rate of perceived exertion (RPE) at 8 km\/h21 (7.86%, p=0.033), velocity at V[Combining Dot Above]O2max (3.07%, p= 0.029), peak of velocity (PV) (1.49%, p=0.035), and total time to exhaustion (TTE) (3.41%, p=0.036) compared with placebo. Photobiomodulation therapy with 15 J improved running economy at 9 km\/h21 (2.98%, p=0.025), rate of perceived exertion at 8 km\/h21 (4.80%, p=0.010), PV (1.33%, p=0.008), total time to exhaustion (3.06%, p=0.008), and total distance (4.01%, p=0.011) compared with the placebo; whereas PBMT with 60 J only increased RE at 9 km\/h21 (3.87%, p=0.024) compared with placebo. All PBMT doses positively affected physiological and\/or performance parameters; however, magnitude-based inference reported that PBMT applied with 30 J led to more beneficial effects than 15 and 60 J.","subset":"pubmed_abstract"} +{"meta":{"pmid":21998422,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":11}}},"text":"Comparative performance of human papillomavirus DNA testing using novel sample collection methods.\nTo explore alternative cervical cancer screening approaches in an underserved population, we compared the performance of human papillomavirus (HPV) DNA assays in combination with different sample collection methods for primary cervical screening in the Mississippi Delta region. Three specimens were collected from women aged 26 to 65 years who were either routinely undergoing screening (n = 252) or not (n = 191): clinician-collected cervical specimens, clinician-collected cervicovaginal specimens, and self-collected cervicovaginal specimens taken at home. A novel collection device and medium were used for cervicovaginal sampling. Specimens were tested by three HPV DNA assays: hybrid capture 2 (HC2; Qiagen Corp., Gaithersburg, MD), Linear Array (LA; Roche Molecular Systems, Pleasanton, CA), and Amplicor (Roche Molecular Systems, Pleasanton, CA). Liquid-based cytology was performed on cervical specimens. We compared the overall positivity (a proxy for clinical specificity) for any carcinogenic HPV genotype and calculated the agreement across assay and specimen type using McNemar's test for differences in test positivity. Across all three assays there were no significant differences between clinician-collected and self-collected cervicovaginal specimens (P > 0.01 for all comparisons). For both cervicovaginal specimens (clinician collected and self-collected), fewer women tested positive by HC2 than by LA or Amplicor (P < 0.01 for all comparisons). HC2 had the best agreement between specimens for all assays. HC2 is likely more clinically specific, although possibly less sensitive, than either PCR test. Thus, use of HC2 on cervicovaginal specimens for screening could result in fewer referrals compared to LA and Amplicor.","subset":"pubmed_abstract"} +{"meta":{"pmid":34177913,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"PDCD1 Polymorphisms May Predict Response to Anti-PD-1 Blockade in Patients With Metastatic Melanoma.\nA significant number of patients (pts) with metastatic melanoma do not respond to anti-programmed cell death 1 (PD1) therapies. Identifying predictive biomarkers therefore remains an urgent need. We retrospectively analyzed plasma DNA of pts with advanced melanoma treated with PD-1 antibodies, nivolumab or pembrolizumab, for five PD-1 genotype single nucleotide polymorphisms (SNPs): PD1.1 (rs36084323, G>A), PD1.3 (rs11568821, G>A), PD1.5 (rs2227981, C>T) PD1.6 (rs10204225, G>A) and PD1.9 (rs2227982, C>T). Clinico-pathological and treatment parameters were collected, and presence of SNPs correlated with response, progression free survival (PFS) and overall survival (OS). 115 patients were identified with a median follow up of 18.7 months (range 0.26 - 52.0 months). All were Caucasian; 27% BRAF V600 mutation positive. At PD-1 antibody commencement, 36% were treatment-na\u00efve and 52% had prior ipilimumab. The overall response rate was 43%, 19% achieving a complete response. Overall median PFS was 11.0 months (95% CI 5.4 - 17.3) and median OS was 31.1 months (95% CI 23.2 - NA). Patients with the G\/G genotype had more complete responses than with A\/G genotype (16.5% vs. 2.6% respectively) and the G allele of PD1.3 rs11568821 was significantly associated with a longer median PFS than the AG allele, 14.1 vs. 7.0 months compared to the A allele (p=0.04; 95% CI 0.14 - 0.94). No significant association between the remaining SNPs and responses, PFS or OS were observed. Despite limitations in sample size, this is the first study to demonstrate an association of a germline PD-1 polymorphism and PFS in response to anti-PD-1 therapy in pts with metastatic melanoma. Extrinsic factors like host germline polymorphisms should be considered with tumor intrinsic factors as predictive biomarkers for immune checkpoint regulators.","subset":"pubmed_abstract"} +{"meta":{"pmid":27460368,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-04":1,"2020-45":1,"2020-10":1,"2023-40":1,"2024-18":1,"2024-30":1}}},"text":"DNA Extraction Protocols for Whole-Genome Sequencing in Marine Organisms.\nThe marine environment harbors a large proportion of the total biodiversity on this planet, including the majority of the earths' different phyla and classes. Studying the genomes of marine organisms can bring interesting insights into genome evolution. Today, almost all marine organismal groups are understudied with respect to their genomes. One potential reason is that extraction of high-quality DNA in sufficient amounts is challenging for many marine species. This is due to high polysaccharide content, polyphenols and other secondary metabolites that will inhibit downstream DNA library preparations. Consequently, protocols developed for vertebrates and plants do not always perform well for invertebrates and algae. In addition, many marine species have large population sizes and, as a consequence, highly variable genomes. Thus, to facilitate the sequence read assembly process during genome sequencing, it is desirable to obtain enough DNA from a single individual, which is a challenge in many species of invertebrates and algae. Here, we present DNA extraction protocols for seven marine species (four invertebrates, two algae, and a marine yeast), optimized to provide sufficient DNA quality and yield for de novo genome sequencing projects.","subset":"pubmed_abstract"} +{"meta":{"pmid":22952906,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":18}}},"text":"Dynamin- and Rab5-dependent endocytosis of a Ca2+ -activated K+ channel, KCa2.3.\nRegulation of the number of ion channels at the plasma membrane is a critical component of the physiological response. We recently demonstrated that the Ca(2+)-activated K(+) channel, KCa2.3 is rapidly endocytosed and enters a Rab35- and EPI64C-dependent recycling compartment. Herein, we addressed the early endocytic steps of KCa2.3 using a combination of fluorescence and biotinylation techniques. We demonstrate that KCa2.3 is localized to caveolin-rich domains of the plasma membrane using fluorescence co-localization, transmission electron microscopy and co-immunoprecipitation (co-IP). Further, in cells lacking caveolin-1, we observed an accumulation of KCa2.3 at the plasma membrane as well as a decreased rate of endocytosis, as assessed by biotinylation. We also demonstrate that KCa2.3 and dynamin II are co-localized following endocytosis as well as demonstrating they are associated by co-IP. Further, expression of K44A dynamin II resulted in a 2-fold increase in plasma membrane KCa2.3 as well as a 3-fold inhibition of endocytosis. Finally, we evaluated the role of Rab5 in the endocytosis of KCa2.3. We demonstrate that expression of a dominant active Rab5 (Q79L) results in the accumulation of newly endocytosed KCa2.3 on to the membrane of the Rab5-induced vacuoles. We confirmed this co-localization by co-IP; demonstrating that KCa2.3 and Rab5 are associated. As expected, if Rab5 is required for the endocytosis of KCa2.3, expression of a dominant negative Rab5 (S34N) resulted in an approximate 2-fold accumulation of KCa2.3 at the plasma membrane. This was confirmed by siRNA-mediated knockdown of Rab5. Expression of the dominant negative Rab5 also resulted in a decreased rate of KCa2.3 endocytosis. These results demonstrate that KCa2.3 is localized to a caveolin-rich domain within the plasma membrane and is endocytosed in a dynamin- and Rab5-dependent manner prior to entering the Rab35\/EPI64C recycling compartment and returning to the plasma membrane.","subset":"pubmed_abstract"} +{"meta":{"pmid":19886893,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2024-10":1,"unknown":9}}},"text":"Hierarchical modelling and estimation of abundance and population trends in metapopulation designs.\n1. Population assessment in changing environments is challenging because factors governing abundance may also affect detectability and thus bias observed counts. We describe a hierarchical modelling framework for estimating abundance corrected for detectability in metapopulation designs, where observations of 'individuals' (e.g. territories) are replicated in space and time. We consider two classes of models; first, we regard the data as independent binomial counts and model abundance and detectability based on a product-binomial likelihood. Secondly, we use the more complex detection-non-detection data for each territory to form encounter history frequencies, and analyse the resulting multinomial\/Poisson hierarchical model. Importantly, we extend both models to directly estimate population trends over multiple years. Our models correct for any time trends in detectability when assessing population trends in abundance. 2. We illustrate both models for a farmland and a woodland bird species, skylark Alauda arvensis and willow tit Parus montanus, by applying them to Swiss BBS data, where 268 1 km(2) quadrats were surveyed two to three times during 1999-2003. We fit binomial and multinomial mixture models where log(abundance) depended on year, elevation, forest cover and transect route length, and logit(detection) on year, season and search effort. 3. Parameter estimates were very similar between models with confidence intervals overlapping for most parameters. Trend estimates were similar for skylark (-0.074 +\/- 0.041 vs. -0.047 +\/- 0.019) and willow tit (0.044 +\/- 0.046 vs. 0.047 +\/- 0.018). As expected, the multinomial model gave more precise estimates, but also yielded lower abundance estimates for the skylark. This may be due to effects of territory misclassification (lumping error), which do not affect the binomial model. 4. Both models appear useful for estimating abundance and population trends free from distortions by detectability in metapopulation designs with temporally replicated observations. The ability to obtain estimates of abundance and population trends that are unbiased with respect to any time trends in detectability ought to be a strong motivation for the collection of replicate observation data.","subset":"pubmed_abstract"} +{"meta":{"pmid":23037041,"dup_signals":{"dup_doc_count":22,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2016-44":2,"2016-36":2,"2016-30":3,"2015-48":1,"2015-40":1,"2015-35":2,"2015-32":2,"2015-27":3,"2015-22":1,"2017-39":1}}},"text":"Stepwise fabrication of arbitrary fiber optic tapers.\nThis work reports a modified flame-brush technique to fabricate fiber tapers with arbitrary waist profiles. The flame-brush approach is used to produce small step reductions in the fiber diameter, or step-tapers, with a constant speed flame brush sweep, while the fiber is uniformly stretched. Arbitrary waist profiles in tapers are fabricated by approximating the taper diameter function to any monotonic function of the fiber length while combining a superposition of step-tapers. This method to produce the arbitrary profiles is described and a set of tapers with dissimilar transition regions are fabricated for its validation.","subset":"pubmed_abstract"} +{"meta":{"pmid":21624115,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":2,"unknown":8}}},"text":"Systematic quantitative characterization of cellular responses induced by multiple signals.\nCells constantly sense many internal and environmental signals and respond through their complex signaling network, leading to particular biological outcomes. However, a systematic characterization and optimization of multi-signal responses remains a pressing challenge to traditional experimental approaches due to the arising complexity associated with the increasing number of signals and their intensities. We established and validated a data-driven mathematical approach to systematically characterize signal-response relationships. Our results demonstrate how mathematical learning algorithms can enable systematic characterization of multi-signal induced biological activities. The proposed approach enables identification of input combinations that can result in desired biological responses. In retrospect, the results show that, unlike a single drug, a properly chosen combination of drugs can lead to a significant difference in the responses of different cell types, increasing the differential targeting of certain combinations. The successful validation of identified combinations demonstrates the power of this approach. Moreover, the approach enables examining the efficacy of all lower order mixtures of the tested signals. The approach also enables identification of system-level signaling interactions between the applied signals. Many of the signaling interactions identified were consistent with the literature, and other unknown interactions emerged. This approach can facilitate development of systems biology and optimal drug combination therapies for cancer and other diseases and for understanding key interactions within the cellular network upon treatment with multiple signals.","subset":"pubmed_abstract"} +{"meta":{"pmid":34096758,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"A reinforcer pathology approach to cannabis misuse: Evaluation of independent and interactive roles of cannabis demand and delay discounting in a sample of community adults.\nCannabis use is prevalent and concerns about cannabis misuse are increasing. A reinforcer pathology approach emphasizes the roles of drug reinforcing value (demand) and overvaluation of immediate rewards (delay discounting [DD]) in drug use but has been applied to a lesser extent to cannabis. The present study investigated the independent and interactive roles of these processes in relation to cannabis misuse in a community sample of adult cannabis users (N = 324; 44.8% female; Mage = 33.25). Participants completed a Marijuana Purchase Task (MPT), the Monetary Choice Questionnaire (MCQ), and the Cannabis Use Disorder Identification Test-Revised (CUDIT-R) to assess demand, DD, and cannabis misuse, respectively. Zero-order correlations revealed significant associations between CUDIT-R scores and both the demand indices (|rs | = .21-.56, p < .01-.001) and DD (r = .21, p < .01). In multivariate analyses, lower elasticity (i.e., price insensitivity) was robustly associated with higher CUDIT-R scores, while other demand indicators did not explain additional unique variance. However, as elasticity, intensity, and Omax exhibited robust zero-order intercorrelations, shared variance appeared to drive the association. An interactive relationship between elasticity and DD was not significant. These findings indicate that cannabis misuse is associated with both cannabis demand, particularly as measured by insensitivity to escalating costs, and immediate reward orientation, but the relationship was not synergistic. These results support a reinforcer pathology approach to cannabis misuse and, although causality cannot be inferred cross-sectionally, suggest that evaluating the longitudinal significance of these indicators is warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).","subset":"pubmed_abstract"} +{"meta":{"pmid":19896583,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":10}}},"text":"Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites.\nThe diagnosis of cognitive impairment and dementia must reflect an increasingly diverse and aging United States population. This study compared direct testing and informant reports of cognition with clinical diagnoses of cognitive impairment and dementia between African Americans and whites. Participants in the Aging, Demographics, and Memory Study completed in-person dementia evaluations, and were assigned clinical diagnoses (by a consensus panel of dementia experts) of normal; cognitive impairment, not demented (CIND); and dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used to assess cognitive performance and reported cognitive decline. A higher CERAD total score was associated with lower odds of CIND and dementia, at comparable ratios between African Americans and whites. Higher IQCODE scores were associated with increased odds of dementia in both African Americans and whites. Higher IQCODE scores were associated with increased odds of CIND among whites, but not among African Americans. Cultural differences may influence informant reports of prevalent CIND and dementia. Our findings also highlight the need for more comparative research to establish the cultural validity of measures used to diagnose these conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":24962578,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth.\nMany cancer cells rely more on aerobic glycolysis (the Warburg effect) than mitochondrial oxidative phosphorylation and catabolize glucose at a high rate. Such a metabolic switch is suggested to be due in part to functional attenuation of mitochondria in cancer cells. However, how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear. We previously reported that tyrosine phosphorylation activates and inhibits mitochondrial pyruvate dehydrogenase kinase (PDK) and phosphatase (PDP), respectively, leading to enhanced inhibitory serine phosphorylation of pyruvate dehydrogenase (PDH) and consequently inhibition of pyruvate dehydrogenase complex (PDC) in cancer cells. In particular, Tyr-381 phosphorylation of PDP1 dissociates deacetylase SIRT3 and recruits acetyltransferase ACAT1 to PDC, resulting in increased inhibitory lysine acetylation of PDHA1 and PDP1. Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. Moreover, expression of a phosphorylation-deficient PDP1 Y94F mutant in cancer cells resulted in increased oxidative phosphorylation, decreased cell proliferation under hypoxia, and reduced tumor growth in mice. Together, our findings suggest that phosphorylation at different tyrosine residues inhibits PDP1 through independent mechanisms, which act in concert to regulate PDC activity and promote the Warburg effect.","subset":"pubmed_abstract"} +{"meta":{"pmid":33713608,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":1,"2023-14":2,"2022-49":3,"2022-33":1,"2021-49":1,"2024-22":1,"2024-30":1}}},"text":"Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.\nAlthough many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD\/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained \u226420 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":11880245,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Locus of inhibition in the masked priming of response alternatives.\nMasked prime stimuli presented immediately before target stimuli in a choice reaction task give rise to behavioral costs when the primes and the target stimuli are mapped to the same response and result in benefits when they are mapped to opposite responses. Researchers assume that this negative compatibility effect reflects inhibitory processes in the control of perceptuomotor links. The authors investigated whether the inhibition operates at the level of abstract central codes or at effector-specific motor stages. In 2 experiments (N = 8 participants in each), left or right hand or foot responses were required to target stimuli that were preceded by masked arrow primes mapped to the same response side as the target stimuli in compatible trials and to the opposite response side in incompatible trials; the primes were irrelevant in neutral trials. In Experiment 1, when the masked primes determined both response side and modality, there was no transfer of negative compatibility effects across response modalities. That finding is inconsistent with a central abstract locus of inhibition and suggests that inhibition operates at effector-specific motor stages. In Experiment 2, primes conveyed only response side information but left response modality uncertain, and negative compatibility effects were elicited for both hand and foot responses, suggesting that partially informative masked primes can trigger a parallel activation and subsequent inhibition of response processes within separate effector systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":14763495,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Continuous venovenous hemofiltration without anticoagulation.\nWe conducted a prospective observational study to assess the efficacy of continuous venovenous hemofiltration (CVVH) with no anticoagulation. A standard anticoagulation protocol for CVVH, which prescribed no anticoagulation for patients at risk of bleeding, was applied to 48 critically ill patients treated with CVVH. Circuit life was prospectively observed, and the following data were obtained for each circuit: heparin use and dose, protamine use, daily prothrombin time-international normalized ratio, activated partial thromboplastin time, and platelet count. Out of 300 consecutive circuits, 143 (47.6%) received no anticoagulation, 31 (10.3%) received regional anticoagulation, and 126 received low dose heparin. No patients experienced bleeding complications secondary to CVVH. Platelet count was significantly lower in the no anticoagulation group (73 x 10(3)\/microl) compared with the low dose heparin group (119 x 10(3)\/microl) and the protamine group (104 x 10(3)\/microl) (p < 0.01 for both comparisons). There was no significant difference in mean circuit life among the three groups (heparin, 20.9 hours; no anticoagulation, 19.3 hours; protamine, 21.2 hours; not significant). In conclusion, for a group of patients deemed to be at risk of bleeding, CVVH without anticoagulation achieved an acceptable circuit life, which was similar to that obtained in other patients with low dose heparin anticoagulation or regional anticoagulation with heparin\/protamine.","subset":"pubmed_abstract"} +{"meta":{"pmid":9020075,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":2,"unknown":11}}},"text":"Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis.\nThe mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1beta (IL-1beta), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism.","subset":"pubmed_abstract"} +{"meta":{"pmid":17076510,"dup_signals":{"dup_doc_count":26,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2022-49":1,"2022-05":3,"2021-21":1,"2021-04":3,"2020-45":1,"2020-40":1,"2020-29":2,"2020-10":3,"2020-05":1,"2019-47":1,"2019-43":2,"2019-35":1,"2023-40":1,"2024-22":1}}},"text":"Direct nitric oxide detection in aqueous solution by copper(II) fluorescein complexes.\nA series of FL(n) (n = 1-5) ligands, where FL(n) is a fluorescein modified with a functionalized 8-aminoquinoline group as a copper-binding moiety, were synthesized, and the chemical and photophysical properties of the free ligands and their copper complexes were investigated. UV-visible spectroscopy revealed a 1:1 binding stoichiometry for the Cu(II) complexes of FL(1), FL(3), and FL(5) in pH 7.0 buffered aqueous solutions. The reactions of FL(2) or FL(4) with CuCl(2), however, appear to produce a mixture of 1:1 and 1:2 complexes, as suggested by Job's plots. These binding modes were modeled by the synthesis and X-ray crystal structure determination of Cu(II) complexes of 2-[(quinolin-8-ylamino)methyl]phenol (modL), employed as a surrogate of the FL(n) ligand family. Two kinds of crystals, [Cu(modL)(2)](BF(4))(2) and [Cu(2)(modL')(2)(CH(3)OH)](BF(4))(2) (modL' = 2-[(quinolin-8-ylamino)methyl]phenolate), were obtained. The structures suggest that one oxygen and two nitrogen atoms of the FL(n) ligands most likely bind to Cu(II). Introduction of nitric oxide (NO) to pH 7.0 buffered aqueous solutions of Cu(FL(n)) (1 microM CuCl(2) and 1 microM FL(n)) at 37 degrees C induces an increase in fluorescence. The fluorescence response of Cu(FL(n)) to NO is direct and specific, which is a significant improvement over commercially available small molecule-based probes that are capable of detecting NO only indirectly. The NO-triggered fluorescence increase of Cu(FL(5)) occurs by reduction of Cu(II) to Cu(I) with concomitant dissociation of the N-nitrosated fluorophore ligand from copper. Spectroscopic and product analyses of the reaction of the FL(5) copper complex with NO indicated that the N-nitrosated fluorescein ligand (FL(5)-NO) is the species responsible for fluorescence turn-on. Density functional theory (DFT) calculations of FL(5) versus FL(5)-NO reveal how N-nitrosation of the fluorophore ligand brings about the fluorescence increase. The copper-based probes described in the present work form the basis for real-time detection of nitric oxide production in living cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":30604177,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2022-27":1,"2022-05":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-24":2,"2020-16":1,"2020-10":1,"2019-47":1,"2022-49":1}}},"text":"Supplements with purported effects on muscle mass and strength.\nSeveral supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, \u03b2-Hydroxy-\u03b2-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or \u03b1-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, \u03b1-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":35150622,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":12}}},"text":"Urban landscape and street-design factors associated with road-traffic mortality in Latin America between 2010 and 2016 (SALURBAL): an ecological study.\nRoad-traffic injuries are a key cause of death and disability in low-income and middle-income countries, but the effect of city characteristics on road-traffic mortality is unknown in these countries. The aim of this study was to determine associations between city-level built environment factors and road-traffic mortality in large Latin American cities. We selected cities from Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Panama, and Peru; cities included in the analysis had a population of at least 100 000 people. We extracted data for road-traffic deaths that occurred between 2010 and 2016 from country vital registries. Deaths were grouped by 5-year age groups and sex. Road-traffic deaths were identified using ICD-10 codes, with adjustments for ill-defined codes and incomplete registration. City-level measures included population, urban development, street design, public transportation, and social environment. Associations were estimated using multilevel negative binomial models with robust variances. 366 cities were included in the analysis. There were 328 408 road-traffic deaths in nearly 3\u00b75 billion person-years across all countries, with an average crude rate of 17\u00b71 deaths per 100 000 person-years. Nearly half of the people who died were younger than 35 years. In multivariable models, road-traffic mortality was higher in cities where urban development was more isolated (rate ratio [RR] 1\u00b705 per 1 SD increase, 95% CI 1\u00b702-1\u00b709), but lower in cities with higher population density (0\u00b794, 0\u00b790-0\u00b798), higher gross domestic product per capita (0\u00b796, 0\u00b794-0\u00b798), and higher intersection density (0\u00b792, 0\u00b789-0\u00b795). Cities with mass transit had lower road mortality rates than did those without (0\u00b792, 0\u00b786-0\u00b799). Urban development policies that reduce isolated and disconnected urban development and that promote walkable street networks and public transport could be important strategies to reduce road-traffic deaths in Latin America and elsewhere. Wellcome Trust.","subset":"pubmed_abstract"} +{"meta":{"pmid":24786810,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Barriers to calling for urgent assistance despite a comprehensive pediatric rapid response system.\nRapid response systems (RRSs) aim to identify and rescue hospitalized patients whose condition is deteriorating before respiratory or cardiac arrest occurs. Previous studies of RRS implementation have shown variable effectiveness, which may be attributable in part to barriers preventing staff from activating the system. To proactively identify barriers to calling for urgent assistance that exist despite recent implementation of a comprehensive RRS in a children's hospital. Qualitative study using open-ended, semistructured interviews of 27 nurses and 30 physicians caring for patients in general medical and surgical care areas. The following themes emerged: (1) Self-efficacy in recognizing deteriorating conditions and activating the medical emergency team (MET) were considered strong determinants of whether care would be appropriately escalated for children in a deteriorating condition. (2) Intraprofessional and interprofessional hierarchies were sometimes challenging to navigate and led to delays in care for patients whose condition was deteriorating. (3) Expectations of adverse interpersonal or clinical outcomes from MET activations and intensive care unit transfers could strongly shape escalation-of-care behavior (eg, reluctance among subspecialty attending physicians to transfer patients to the intensive care unit for fear of inappropriate management). The results of this study provide an in-depth description of the barriers that may limit RRS effectiveness. By recognizing and addressing these barriers, hospital leaders may be able to improve the RRS safety culture and thus enhance the impact of the RRS on rates of cardiac arrest, respiratory arrest, and mortality outside the intensive care unit.","subset":"pubmed_abstract"} +{"meta":{"pmid":17554010,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Identifying injection drug users at risk of nonfatal overdose.\nDrug overdose is the second leading cause of accidental deaths among U.S. adults aged 15-64 years. Emergency physicians have a unique opportunity to provide overdose prevention interventions, because habitual drug users are in frequent need of medical care. The authors evaluated associations between individual-level risk factors and experiencing an overdose in the past six months to determine which characteristics and behaviors may be most predictive of overdose. The authors used data from a sample of street-recruited habitual drug users who participated in face-to-face interviews about overdose from November 2001 to February 2004. This analysis was restricted to 772 respondents who had been injecting for at least one year and who had injected heroin within the past two months. A total of 16.6% of participants had overdosed in the past six months. Characteristics and behaviors that were independently associated with an increased risk of a recent overdose were having had a prior overdose (odds ratio [OR], 28.58; 95% confidence interval [CI] = 14.10 to 57.96), using cocaine\/crack in the past six months (OR, 2.07; 95% CI = 1.25 to 3.45), using alcohol in the past six months (OR, 1.90; 95% CI = 1.01 to 3.57), experiencing serious withdrawal symptoms in the past two months (OR, 2.70; 95% CI = 1.58 to 4.61), and younger age. Drug users who have previously experienced a nonfatal overdose are at very high risk of experiencing future overdoses. Further longitudinal studies are needed to identify robust predictors of overdose risk over time in habitual drug users, but these data suggest that drug users who have overdosed warrant aggressive prevention efforts such as agonist maintenance treatment or provision of take-home naloxone.","subset":"pubmed_abstract"} +{"meta":{"pmid":28650820,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Terahertz Channel Model and Link Budget Analysis for Intrabody Nanoscale Communication.\nNanosized devices operating inside the human body open up new prospects in the healthcare domain. Invivo wireless nanosensor networks (iWNSNs) will result in a plethora of applications ranging from intrabody health-monitoring to drug-delivery systems. With the development of miniature plasmonic signal sources, antennas, and detectors, wireless communications among intrabody nanodevices will expectedly be enabled at both the terahertz band (0.1-10 THz) as well as optical frequencies (400-750 THz). This result motivates the analysis of the phenomena affecting the propagation of electromagnetic signals inside the human body. In this paper, a rigorous channel model for intrabody communication in iWNSNs is developed. The total path loss is computed by taking into account the combined effect of the spreading of the propagating wave, molecular absorption from human tissues, as well as scattering from both small and large body particles. The analytical results are validated by means of electromagnetic wave propagation simulations. Moreover, this paper provides the first framework necessitated for conducting link budget analysis between nanodevices operating within the human body. This analysis is performed by taking into account the transmitter power, medium path loss, and receiver sensitivity, where both the THz and photonic devices are considered. The overall attenuation model of intrabody THz and optical frequency propagation facilitates the accurate design and practical deployment of iWNSNs.","subset":"pubmed_abstract"} +{"meta":{"pmid":12097317,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions.\nTwo candidate human orthologs of Escherichia coli MutM\/Nei were recently identified in the human genome database, and one of these, NEH1, was characterized earlier (Hazra, T. K., Izumi, T., Boldogh, I., Imhoff, B., Kow, Y. W., Jaruga, P., and Dizdaroglu, M. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 3523-3528). Here we report characterization of the second protein, originally named NEH2 and now renamed NEIL2 (Nei-like). The 37-kDa wild-type NEIL2 expressed in and purified from E. coli has DNA glycosylase\/AP lyase activity, primarily for excising oxidative products of cytosine, with highest activity for 5-hydroxyuracil, one of the most abundant and mutagenic lesions induced by reactive oxygen species, and with lower activity for 5,6-dihydrouracil and 5-hydroxycytosine. It has negligible or undetectable activity with 8-oxoguanine, thymine glycol, 2-hydroxyadenine, hypoxanthine, and xanthine. NEIL2 is similar to NEIL1 in having N-terminal Pro as the active site. However, unlike NEIL1, its expression was independent of the cell cycle stage in fibroblasts, and its highest expression was observed in the testes and skeletal muscle. Despite the absence of a putative nuclear localization signal, NEIL2 was predominantly localized in the nucleus. These results suggest that NEIL2 is involved in global genome repair mainly for removing oxidative products of cytosine.","subset":"pubmed_abstract"} +{"meta":{"pmid":7978320,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Analysis of human cerebrospinal fluid by capillary electrophoresis with laser-induced fluorescence detection.\nCapillary electrophoresis with laser-induced fluorescence detection is used to analyze 10 microL samples of human cerebrospinal fluid. Primary amine-containing compounds in untreated cerebrospinal fluid are labeled with 3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde prior to analysis, producing fluorescent isoindoles. Electropherograms containing approximately 50 peaks are obtained in less than 35 min from cerebrospinal fluid samples. Ten peaks in the electropherograms have been identified and quantitated: arginine, glutamine, threonine, valine, gamma-amino-n-butyric acid, serine, alanine, glycine, glutamic acid, and aspartic acid. Detection limits for these 10 amino acids range from 0.29 nM for gamma-amino-n-butyric acid to 100 nM for threonine, and separation efficiencies as high as 190,000 theoretical plates are obtained for these analytes. Electropherograms of cerebrospinal fluid samples from patients with Alzheimer's disease and from children with different neurological disorders are compared to those of healthy controls. Differences in individual amino acid levels are observed between the patient groups, and these differences appear to be disease and age related. These results indicate that analysis of cerebrospinal fluid by capillary electrophoresis will be useful as a selective, rapid, and sensitive tool for both diagnosis of central nervous system disorders and for study of the mechanisms of these disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":26586794,"dup_signals":{"dup_doc_count":35,"dup_dump_count":3,"dup_details":{"curated_sources":4,"2018-39":5,"2018-34":11,"2018-26":15}}},"text":"The presence of the intron 3 16 bp duplication polymorphism of p53 (rs17878362) in breast cancer is associated with a low \u039440p53:p53 ratio and better outcome.\nBreast cancer is the most common female cancer, but it has relatively low rates of p53 mutations, suggesting other mechanisms are responsible for p53 inactivation. We have shown that the p53 isoform, \u039440p53, is highly expressed in breast cancer, where it may contribute to p53 inactivation. \u039440p53 can be produced by alternative splicing of p53 in intron 2 and this is regulated by the formation of G-quadruplex structures in p53 intron 3, from which the nucleotides forming these structures overlap with a common polymorphism, rs17878362. rs17878362 alters p53 splicing to decrease fully spliced p53 messenger RNA (mRNA) in vitro following ionizing radiation and this in turn alters \u039440p53:p53. Hence, the presence of rs17878362 may be important in regulating \u039440p53:p53 in breast cancer. This study aimed to determine if rs17878362 was associated with altered \u039440p53 and p53 expression and outcome in breast cancer. We sequenced p53 in breast tumours from 139 patients and compared this with \u039440p53 and p53 mRNA expression. We found that the ratio of \u039440p53:p53 was significantly lower in tumours homozygous for the polymorphic A2 allele compared with those who were wild-type (A1\/A1). Furthermore, there was a lower proportion of breast cancers carrying the A2 allele from patients who subsequently developed metastasis compared with those that did not. Finally, we show that patients whose tumours carried the polymorphic A2 allele had significantly better disease-free survival. These results show that rs17878362 is associated with a low \u039440p53:p53 ratio in breast cancer and that this is associated with better outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":18936372,"dup_signals":{"dup_doc_count":14}},"text":"Race and insurance status as risk factors for trauma mortality.\nTo determine the effect of race and insurance status on trauma mortality. Review of patients (aged 18-64 years; Injury Severity Score > or = 9) included in the National Trauma Data Bank (2001-2005). African American and Hispanic patients were each compared with white patients and insured patients were compared with uninsured patients. Multiple logistic regression analyses determined differences in survival rates after adjusting for demographics, injury severity (Injury Severity Score and revised Trauma Score), severity of head and\/or extremity injury, and injury mechanism. A total of 429 751 patients met inclusion criteria. African American (n = 72,249) and Hispanic (n = 41,770) patients were less likely to be insured and more likely to sustain penetrating trauma than white patients (n = 262,878). African American and Hispanic patients had higher unadjusted mortality rates (white, 5.7%; African American, 8.2%; Hispanic, 9.1%; P = .05 for African American and Hispanic patients) and an increased adjusted odds ratio (OR) of death compared with white patients (African American OR, 1.17; 95% confidence interval [CI], 1.10-1.23; Hispanic OR, 1.47; 95% CI, 1.39-1.57). Insured patients (47%) had lower crude mortality rates than uninsured patients (4.4% vs 8.6%; P = .05). Insured African American and Hispanic patients had increased mortality rates compared with insured white patients. This effect worsened for uninsured patients across groups (insured African American OR, 1.2; 95% CI, 1.08-1.33; insured Hispanic OR, 1.51; 95% CI, 1.36-1.64; uninsured white OR, 1.55; 95% CI, 1.46-1.64; uninsured African American OR, 1.78; 95% CI, 1.65-1.90; uninsured Hispanic OR, 2.30; 95% CI, 2.13-2.49). The reference group was insured white patients. Race and insurance status each independently predicts outcome disparities after trauma. African American, Hispanic, and uninsured patients have worse outcomes, but insurance status appears to have the stronger association with mortality after trauma.","subset":"pubmed_abstract"} +{"meta":{"pmid":9115020,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":10}}},"text":"Cancer mortality among man-made vitreous fiber production workers.\nWe have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock\/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock\/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock\/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock\/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock\/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.","subset":"pubmed_abstract"} +{"meta":{"pmid":20462317,"dup_signals":{"dup_doc_count":48,"dup_dump_count":41,"dup_details":{"curated_sources":3,"2022-21":1,"2021-10":1,"2020-24":1,"2020-10":1,"2019-47":1,"2019-43":1,"2019-30":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":2,"2016-40":2,"2016-36":2,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2022-27":1,"2024-10":2,"2015-18":1}}},"text":"Adaptation-induced blindness to sluggish stimuli.\nIt is well known that prolonged observation of a dynamic visual pattern raises the contrast threshold for a subsequently presented static pattern. We found that if the post-adaptation test was presented gradually, so that its onset transient was weak, the test pattern was undetectable even at high contrast. Although the smooth-onset patterns were invisible, they caused apparent shifts in the orientation and contrast of neighboring stimuli, indicating the implicit processing of the target features. However, this strong aftereffect was not obtained if the target grating drifted rapidly or was onset abruptly. These results suggest that when human observers become less sensitive to transients in stimuli due to dynamic adaptation, they cannot consciously perceive sluggish stimuli containing weak transients. This is consistent with the notion that the visual system cannot prompt a conscious awareness of a single stimulus unless triggered by enough transient or temporally salient signals.","subset":"pubmed_abstract"} +{"meta":{"pmid":7675648,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":11}}},"text":"[Imaging of metastases from thyroid carcinomas using 111In-pentetreotide scintigraphy].\nThere is little experience with imaging of thyroid carcinoma tissue by somatostatin receptor scintigraphy. Our case report describes an acromegalic patient, in whom 111In pentetreotide scintigraphy did not only demonstrate a receptor-positive pituitary tumor but also visualized metastases from a papillary thyroid carcinoma which had no correlate in radioiodine scintigraphy carried out under hypothyroid conditions. The possible role of this radiopharmaceutical in dedifferentiating thyroid carcinoma is discussed for its usefulness in tumor localisation and its predictive value for the outcome of an octreotide therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":32564056,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-21":1,"2021-10":2,"2020-50":2,"2020-40":1,"2023-50":1,"2024-18":1}}},"text":"Neonatal sevoflurane exposure induces impulsive behavioral deficit through disrupting excitatory neurons in the medial prefrontal cortex in mice.\nSevoflurane, in particular multiple exposures, has been reported to cause the abnormal neurological development including attention-deficit\/hyperactivity disorder (ADHD). This study is to investigate ADHD-like impulsivity in adult mice after repeated sevoflurane exposures at the neonatal stage. Six-day-old pups were exposed to 60% oxygen in the presence or absence of 3% sevoflurane for 2 h and the treatment was administrated once daily for three consecutive days. To assess the impulsivity, the cliff avoidance reaction (CAR) was carried out at the 8th week. Our results showed that repeated sevoflurane treatment increased the number of jumps and shortened the jumping latency in the CAR test. The cortices were harvested for immunostaining to detect c-Fos and calmodulin-dependent protein kinase II\u03b1 (CaMKII\u03b1) expression in the medial prefrontal cortex (mPFC). We found that mPFC neurons, especially excitatory neurons, were highly activated and related to impulsive behavior. The activation viruses (AAV-CaMKII\u03b1-hM3Dq) were injected to evaluate the effects of specific activation of mPFC excitatory neurons on impulsive behavior in the presence of clozapine-N-oxide (CNO). Likewise, the inhibitory viruses (AAV-CaMKII\u03b1-hM4Di) were injected in the sevoflurane group to explore whether the mPFC excitatory neuronal inhibition reduced the impulsivity. Our results revealed that chemogenetic activation of mPFC excitatory neurons induced impulsive behavior whereas inhibition of mPFC excitatory neurons partially rescued the deficit. These results indicate that repeated sevoflurane exposures at the critical time induce impulsive behavior accompanied with overactivation of mPFC excitatory neurons in adult stages. This work may further extend to understand the ADHD-like impulsive behavior of the anesthetic neurotoxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":27493774,"dup_signals":{"dup_doc_count":27,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":2,"unknown":21}}},"text":"Active and reactive behaviour in human mobility: the influence of attraction points on pedestrians.\nHuman mobility is becoming an accessible field of study, thanks to the progress and availability of tracking technologies as a common feature of smart phones. We describe an example of a scalable experiment exploiting these circumstances at a public, outdoor fair in Barcelona (Spain). Participants were tracked while wandering through an open space with activity stands attracting their attention. We develop a general modelling framework based on Langevin dynamics, which allows us to test the influence of two distinct types of ingredients on mobility: reactive or context-dependent factors, modelled by means of a force field generated by attraction points in a given spatial configuration and active or inherent factors, modelled from intrinsic movement patterns of the subjects. The additive and constructive framework model accounts for some observed features. Starting with the simplest model (purely random walkers) as a reference, we progressively introduce different ingredients such as persistence, memory and perceptual landscape, aiming to untangle active and reactive contributions and quantify their respective relevance. The proposed approach may help in anticipating the spatial distribution of citizens in alternative scenarios and in improving the design of public events based on a facts-based approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":28248401,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":4,"2024-26":1,"unknown":9}}},"text":"Multilateral spectral radiance factor scale comparison.\nThe field of spectral radiance factor (SRF) measurements has seen growing interest in recent years. Scale conformity has so far only been established between the national metrology institutes (NMIs) of Germany and the USA. This study aims at a bigger, multilateral scale comparison. For this purpose, a total of six NMIs participated in a scale comparison of goniospectrophotometers based on neutral and colored diffusely reflecting ceramics samples. In addition, two universities, providing a home-built gonioreflectometer and two widely used commercially available color measurement instruments, respectively, were involved. The wavelength range of the scale comparison covers the visible wavelength range from 380 nm to 780 nm. Results indicate systematic issues and that the uncertainty evaluation of the NMIs requires further work; although for the greatest part of the covered spectral range the agreement is good.","subset":"pubmed_abstract"} +{"meta":{"pmid":24960276,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Isotope-coded carbamidomethylation for quantification of N-glycoproteins with online microbore hollow fiber enzyme reactor-nanoflow liquid chromatography-tandem mass spectrometry.\nThis paper introduces a simple, inexpensive, and robust quantitative proteomic method for quantifying N-linked glycoproteins based on isotope-coded carbamidomethylation (iCCM) incorporated into an online microbore hollow fiber enzyme reactor and nanoflow liquid chromatography-tandem mass spectrometry (mHFER-nLC-MS\/MS). The iCCM quantitation uses carbamidomethylation (CM; a routine protection of thiol groups before proteolysis) of the Cys residue of proteins with iodoacetamide (IAA) or its isotope (IAA-(13)C2,D2: 4 Da difference). CM-\/iCCM-labeled proteome samples are mixed for proteolysis; then, online enrichment of N-glycopeptides using lectin affinity is carried out in an mHFER before nLC-MS\/MS for quantification using multiple reaction monitoring (MRM). Initial evaluation of the iCCM method varying the mixing ratio of CM-\/iCCM-labeled bovine serum albumin (BSA) standards yielded successful quantification of 18 peptides with less than 2% variation in the calculated ratio of light\/heavy-labeled peptides. The iCCM quantitation with mHFER-nLC-MS\/MS was evaluated with three standard glycoproteins (\u03b1-1-acid glycoproteins, fetuin and transferrin) and then applied to serum glycoproteins from liver cancer patients and controls, resulting in successful quantification of 73 N-glycopeptides (from 49 N-glycoproteins), among which 19 N-glycopeptides from 14 N-glycoproteins showed more than a 2.5-fold aberrant change in liver cancer patients' sera compared with the pooled control. Although iCCM quantitation with mHFER-nLC-MS\/MS applies only to glycopeptides with Cys residue, the method can offer several advantages over other labeling methods when applied to targeted glycoproteins: The iCCM method does not require an additional labeling reaction under special conditions nor complicated procedures to purify labeled products using additional columns. Isotope labeling at the protein level can minimize potential uncertainty originating from unequal efficiencies in protein digestion in separate vials and retrieval of each labeled peptide when labeling takes place at the peptide level. In addition, the labeling reagents for the iCCM method are readily obtained at a reasonable cost, which can make protein quantification easily accessible.","subset":"pubmed_abstract"} +{"meta":{"pmid":18208621,"dup_signals":{"dup_doc_count":22}},"text":"Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities.\nSubclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1\/2 in ovarian cancers. The mechanism of BRCA1\/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K\/AKT and p53 pathways.","subset":"pubmed_abstract"} +{"meta":{"pmid":21889617,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Quantification and molecular characterization of the feline leukemia virus A receptor.\nVirus receptors and their expression patterns on the cell surface determine the cell tropism of the virus, host susceptibility and the pathogenesis of the infection. Feline thiamine transport protein 1 (fTHTR1) has been identified as the receptor for feline leukemia virus (FeLV) A. The goal of the present study was to develop a quantitative, TaqMan real-time PCR assay to investigate fTHTR1 mRNA expression in tissues of uninfected and FeLV-infected cats, cats of different ages, in tumor tissues and leukocyte subsets. Moreover, the receptor was molecularly characterized in different feline species. fTHTR1 mRNA expression was detected in all 30 feline tissues investigated, oral mucosa scrapings and blood. Importantly, identification of significant differences in fTHTR1 expression relied on normalization with an appropriate reference gene. The lowest levels were found in the blood, whereas high levels were measured in the oral mucosa, salivary glands and the musculature. In the blood, T lymphocytes showed significantly higher fTHTR1 mRNA expression levels than neutrophil granulocytes. In vitro activation of peripheral blood mononuclear cells with concanavalin A alone or followed by interleukin-2 led to a transient increase of fTHTR1 mRNA expression. In the blood, but not in the examined tissues, FeLV-infected cats tended to have lower fTHTR1 mRNA levels than uninfected cats. The fTHTR1 mRNA levels were not significantly different between tissues with lymphomas and the corresponding non-neoplastic tissues. fTHTR1 was highly conserved among different feline species (Iberian lynx, Asiatic and Indian lion, European wildcat, jaguarundi, domestic cat). In conclusion, while ubiquitous fTHTR1 mRNA expression corresponded to the broad target tissue range of FeLV, particularly high fTHTR1 levels were found at sites of virus entry and shedding. The differential susceptibility of different species to FeLV could not be attributed to variations in the fTHTR1 sequence.","subset":"pubmed_abstract"} +{"meta":{"pmid":29160372,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-33":1,"2022-21":1,"2021-43":1,"2021-39":1,"2021-21":1,"2021-17":1,"2020-29":1,"2020-24":1,"2019-51":1,"2019-39":1,"2019-35":1,"2019-26":2,"2022-49":1}}},"text":"An experimental study of ascorbic acid effects in acute renal failure under general anesthesia.\nTo evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model. Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg\/kg) and high (300 mg\/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation. NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III. The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":11023816,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2022-49":1,"2022-21":1,"2021-39":1,"2021-10":1,"2020-45":1,"2020-34":1,"2020-10":1,"2019-39":1,"2019-22":1,"2019-13":1,"2023-50":1,"2024-22":1}}},"text":"Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.\nThe antiviral activity of several nucleoside analogues is often limited by their rapid degradation by pyrimidine nucleoside phosphorylases. In an attempt to avoid this degradation, several modified nucleosides have been synthesized. A series of 4'-thio-2'-deoxyuridines exhibits an anti-[herpes simplex virus (HSV)] activity significantly higher (20-600 times) than that shown by the corresponding 4'-oxy counterpart. We investigated the mode of action of these compounds and we found that: (i) several 4'-thio-2'-deoxyuridines are phosphorylated to the mono- and di-phosphates by HSV-1 thymidine kinase (TK) more efficiently than their corresponding 4'-oxy counterpart; (ii) both are inhibitors of cellular thymidylate synthase; (iii) 4'-thio-2'-deoxyuridines are resistant to phosphorolysis by human thymidine phosphorylase; (iv) both 4'-oxy- and 4'-thio-2'-deoxyuridines are phosphorylated to deoxyribonucleotide triphosphate in HSV-1-infected cells and are incorporated into viral DNA; (v) 4'-thio-2'-deoxyuridines are better inhibitors than their 4'-oxy counterparts of [(3)H]thymidine incorporation in HSV-1-infected cells; (vi) 4'-thio-2'-deoxyuridines are not recognized by HSV-1 and human uracil-DNA glycosylases. Our data suggest that 4'-thio-2'-deoxyuridines, resistant to pyrimidine phosphorylase, can be preferentially or selectively phosphorylated by viral TK in HSV-infected cells, where they are further converted into triphosphate by cellular nucleotide kinases. Once incorporated into viral DNA, they are better inhibitors of viral DNA synthesis than their corresponding 4'-oxy counterpart, either because they are not recognized, and thus not removed, by viral uracil-DNA glycosylase, or because they preferentially interfere with viral DNA polymerase.","subset":"pubmed_abstract"} +{"meta":{"pmid":29299964,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-18":1,"unknown":9}}},"text":"A Mainly Circum-Mediterranean Origin for West Eurasian and North African mtDNAs in Puerto Rico with Strong Contributions from the Canary Islands and West Africa.\nMaternal lineages of West Eurasian and North African origin account for 11.5% of total mitochondrial ancestry in Puerto Rico. Historical sources suggest that this ancestry arrived mostly from European migrations that took place during the four centuries of the Spanish colonization of Puerto Rico. This study analyzed 101 mitochondrial control region sequences and diagnostic coding region variants from a sample set randomly and systematically selected using a census-based sampling frame to be representative of the Puerto Rican population, with the goal of defining West Eurasian-North African maternal clades and estimating their possible geographical origin. Median-joining haplotype networks were constructed using hypervariable regions 1 and 2 sequences from various reference populations in search of shared haplotypes. A posterior probability analysis was performed to estimate the percentage of possible origins across wide geographic regions for the entire sample set and for the most common haplogroups on the island. Principal component analyses were conducted to place the Puerto Rican mtDNA set within the variation present among all reference populations. Our study shows that up to 38% of West Eurasian and North African mitochondrial ancestry in Puerto Rico most likely migrated from the Canary Islands. However, most of those haplotypes had previously migrated to the Canary Islands from elsewhere, and there are substantial contributions from various populations across the circum-Mediterranean region and from West African populations related to the modern Wolof and Serer peoples from Senegal and the nomad Fulani who extend up to Cameroon. In conclusion, the West Eurasian mitochondrial ancestry in Puerto Ricans is geographically diverse. However, haplotype diversity seems to be low, and frequencies have been shaped by population bottlenecks, migration waves, and random genetic drift. Consequently, approximately 47% of mtDNAs of West Eurasian and North African ancestry in Puerto Rico probably arrived early in its colonial history.","subset":"pubmed_abstract"} +{"meta":{"pmid":13568767,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"Basic research in Europe; different countries favor different systems for the support and organization of scientific work.\nEurope, traditionally the breeding ground for basic scientific research until the 1930's, is only now approaching full recovery from the devastating effects of the war. Great Britain has a more stimulating climate for research, a more progressive graduate-school program, and a more flexible professorship structure than any other country of Europe. Germany still has several years to go before the effects of the war will be obliterated. In most northern European countries, the organization and support of academic research ranges from good to excellent, and a stimulating intellectual atmosphere exists. Germany is rapidly contending for the lead in basic research along with England and Sweden, which are now in the forefront. The Netherlands is typified by superb organization, and most of the Scandinavian countries are high in quality if not always in quantity of research. France is characterized by brilliant individual contributions but over-all falls far short of her potential for scientific research. Switzerland, a highly industrialized country, is geared primarily for engineering and does not compete as highly on basic research as might otherwise be expected. Italian research is good in certain areas but is plagued by a number of difficulties that retard progress. Nevertheless, there are encouraging efforts being made in Italy to develop some good scientific programs. In the south of Europe the situation is generally discouraging and will continue to be so, except where a few dedicated, brilliant individuals are making good contributions with the meager resources available. Europe will continue to be a tremendous scientific manpower reserve for the United States, and, despite accusations of proselyting, the fact remains that in many European countries the employment possibilities are not commensurate with the production rate of scientists and engineers. If the universities of Europe would realign the professional structure of their departmental staffs and extend their graduate curricula they would give far more opportunity to young research scientists and make better use of their facilities. America can indeed be grateful to Europe for a great cultural and academic heritage, and one can sincerely hope that close cooperation in science will take place for many years to come.","subset":"pubmed_abstract"} +{"meta":{"pmid":30141709,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Encountering offenders in community palliative care settings: challenges for care provision.\nThere is very little research into the way that offender management strategies impinge on the practices and decision-making of palliative care personnel in community settings. To improve understanding of the challenges that community palliative care service providers encounter when caring for people who have been sentenced to custody and are under the supervision of the prison or probation services. This paper discusses one part of a larger multidisciplinary study on bereavement, loss and grief in the criminal justice system. It reports the findings from a focus group with 10 health professionals working within specialist community palliative care services. Thematic analysis was undertaken to identify and explicate the most significant themes arising from the transcript data. There were situations where the participants were able to identify that patients were under the jurisdiction of the criminal justice system or had relatives in custody. Three themes emerged that highlighted distinctive aspects of providing care to this patient group. These themes were: patients under prison, probation or police supervision altered the dynamics of care provision; prisoners were restricted from supporting or contacting their dying relatives in the community; and participants (professionals) were obstructed from supporting patients at home because of criminal or antisocial behaviour by relatives of the dying. Health professionals face multiple challenges that curtail them from fully realising the aims of palliative care for patients and relatives under criminal justice supervision, in ways that merit further consideration and research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22207590,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension.\nChronic hypoxia causes pulmonary hypertension with vascular remodeling, increase in vascular tone, and altered reactivity to agonists. These changes involve alterations in multiple Ca(2+) pathways in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that vanilloid (TRPV)- and melastatin-related transient receptor potential (TRPM) channels are expressed in pulmonary arteries (PAs). Here we found that TRPV4 was the only member of the TRPV and TRPM subfamilies upregulated in PAs of chronic hypoxic rats. The increase in TRPV4 expression occurred within 1 day of hypoxia exposure, indicative of an early hypoxic response. TRPV4 in PASMCs were found to be mechanosensitive. Osmo-mechanical stress imposed by hypotonic solution activated Ca(2+) transients; they were inhibited by TRPV4 specific short interfering RNA, the TRPV blocker ruthenium red, and the cytochrome P450 epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Consistent with TRPV4 upregulation, the Ca(2+) response induced by the TRPV4 agonist 4\u03b1-phorbol 12,13-didecanoate and hypotonicity was potentiated in hypoxic PASMCs. Moreover, a significant myogenic tone, sensitive to ruthenium red, was observed in pressurized endothelium denuded small PAs of hypoxic but not normoxic rats. The elevated basal intracellular Ca(2+) concentration in hypoxic PASMCs was also reduced by ruthenium red. In extension of these results, the development of pulmonary hypertension, right heart hypertrophy, and vascular remodeling was significantly delayed and suppressed in hypoxic trpv4(-\/-) mice. These results suggest the novel concept that TRPV4 serves as a signal pathway crucial for the development of hypoxia-induced pulmonary hypertension. Its upregulation may provide a pathogenic feed-forward mechanism that promotes pulmonary hypertension via facilitated Ca(2+) influx, subsequently enhanced myogenic tone and vascular remodeling.","subset":"pubmed_abstract"} +{"meta":{"pmid":16998485,"dup_signals":{"dup_doc_count":20,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2021-25":1,"2021-21":1,"2021-17":1,"2019-43":1,"2019-30":1,"2019-22":1,"2019-18":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2022-49":1,"2024-26":1}}},"text":"Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.\nImmunocompromised individuals are at high risk for life-threatening diseases, especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus. Conventional therapeutics are primarily active only against CMV, and resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this strategy can be extended to adenovirus, which comprises many serotypes. In addition, the preparation of a specific CTL line for each virus in every eligible individual would be impractical. Here we describe genetic modification of antigen-presenting cell lines to facilitate the production of CD4(+) and CD8(+) T lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a single cell culture. When administered to immunocompromised individuals, the single T lymphocyte line expands into multiple discrete virus-specific populations that supply clinically measurable antiviral activity. Monoculture-derived multispecific CTL infusion could provide a safe and efficient means to restore virus-specific immunity in the immunocompromised host.","subset":"pubmed_abstract"} +{"meta":{"pmid":29177542,"dup_signals":{"dup_doc_count":14,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2023-14":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-17":1,"2021-04":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2023-40":1}}},"text":"Adjustable transobturator sling for the treatment of primary stress urinary incontinence.\nThe purpose of the study was to evaluate the rate of postoperative voiding dysfunction after the insertion of an adjustable transobturator sling for the treatment of primary stress urinary incontinence (SUI). The secondary aim was to assess the objective and subjective cure rates and the impact of the surgery on quality of life. This prospective study included 171 patients with primary SUI who underwent insertion of an adjustable transobturator tape. A postoperative tension adjustment algorithm that included a cough stress test (CST), uroflowmetry and postvoid residual volume (PVR) measurement was applied in all patients the day after surgery. The baseline and control postoperative evaluations included vaginal examination, CST, Q-tip test, uroflowmetry and PVR measurement, 1-h pad test and administration questionnaires (UDI-6, IIQ-7, PISQ-12, ICIQ-SF). The day after surgery 65 patients (38.0%) required tape tension adjustment: an increase in tension in 53 patients (31.0%) and a decrease in 12 (7.0%). Continence was achieved in all patients. No patients showed voiding dysfunction after adjustment. Follow-up data for 12 months were available in 157 patients (91.8%). The objective and subjective cure rates were 96.2% and 97.5%, respectively. There was no statistically significant decrease in Qmax (p = 0.899) or increase in PVR (p = 0.187). According to the questionnaires scores, quality of life was improved in all patients. The adjustable transobturator sling minimizes the risk of postoperative voiding dysfunction and allows high objective and subjective cure rates to be achieved in patients with primary SUI. The technique also improves the patient's quality of life.","subset":"pubmed_abstract"} +{"meta":{"pmid":11303339,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":2,"2015-06":1,"2014-10":2,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":6}}},"text":"Behavioral momentum and the law of effect.\nIn the metaphor of behavioral momentum, the rate of a free operant in the presence of a discriminative stimulus is analogous to the velocity of a moving body, and resistance to change measures an aspect of behavior that is analogous to its inertial mass. An extension of the metaphor suggests that preference measures an analog to the gravitational mass of that body. The independent functions relating resistance to change and preference to the conditions of reinforcement may be construed as convergent measures of a single construct, analogous to physical mass, that represents the effects of a history of exposure to the signaled conditions of reinforcement and that unifies the traditionally separate notions of the strength of learning and the value of incentives. Research guided by the momentum metaphor encompasses the effects of reinforcement on response rate, resistance to change, and preference and has implications for clinical interventions, drug addiction, and self-control. In addition, its principles can be seen as a modern, quantitative version of Thorndike's (1911) Law of Effect, providing a new perspective on some of the challenges to his postulation of strengthening by reinforcement.","subset":"pubmed_abstract"} +{"meta":{"pmid":21315343,"dup_signals":{"dup_doc_count":31,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2023-14":1,"2022-21":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-45":2,"2020-40":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-40":1,"2024-18":3,"2024-10":1,"2017-13":1}}},"text":"A unique peri-prosthetic fracture pattern in well fixed femoral stems with polished, tapered, collarless design of total hip replacement.\nPeri-prosthetic fractures (PPF) are a recognised complication following hip arthroplasty. Prosthesis design and type influence PPF pattern. Surgeons rely on classification systems, such as the Vancouver, to aid treatment planning. This study highlights a specific fracture pattern that occurs with cemented well-fixed polished, tapered, collarless (PTC) stems. We reviewed a consecutive series of 21 PPF around well fixed PTC stems. The majority of the fractures were classified pre-operatively as Vancouver B2 (14\/21), but there were also B1 (6\/21) and A type fractures. The B2 fractures had common radiological and intra-operative findings: a spiral fracture with extensive fragmentation of bone and cement, debonding of cement from the implant, cement fracture, and a well-fixed cement-bone interface. Reconstruction of these fractures was more difficult than suggested by the radiographs. Two of the six patients who were considered to have a Vancouver B1 fracture underwent open reduction and internal fixation (ORIF), and had treatment-related complications. Retrospective review of the radiographs showed subtle features, such as subsidence of the stem into the centraliser, that are characteristic of a B2 fracture pattern. In summary, it is important to recognise this fracture pattern around secure PTC stems in order to prevent misinterpretation of the fracture as a Vancouver B1 rather than a B2, leading to failure of treatment, and to alert the surgeon that complex reconstruction will be required because of the extensive fragmentation.","subset":"pubmed_abstract"} +{"meta":{"pmid":15921344,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Patients' privacy of the person and human rights.\nThe UK Government published various circulars to indicate the importance of respecting the privacy and dignity of NHS patients following the implementation of the Human Rights Act, 1998. This research used an ethnographic method to determine the extent to which health professionals had in fact upheld the philosophy of these documents. Fieldwork using nonparticipant observation, and unstructured and semistructured interviews with patients and staff, took place over six months in three acute care wards in a large district NHS trust hospital. Applying the principles of phenomenology and grounded theory, the data were analysed and the contents organized into 11 key categories, leading to the formulation of a privacy model. The level of intrusion into patients' privacy by health professionals was measured against the benchmarking of the 'dignity and privacy' factors contained in the Department of Health's The essence of care document and Article 8(2) of the Human Rights Act. The findings established that patients had little privacy in the wards, and that the terms 'privacy of the person' and 'dignity' are interrelated.","subset":"pubmed_abstract"} +{"meta":{"pmid":14655948,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"A method for modifying the image quality parameters of digital radiographic images.\nA new computer simulation approach is presented that is capable of modeling several varieties of digital radiographic systems by their image quality characteristics. In this approach, the resolution and noise characteristics of ideal supersampled input images are modified according to input modulation transfer functions (MTFs) and noise power spectra (NPS). The modification process is separated into two routines-one for modification of the resolution and another for modification of the noise characteristics of the input image. The resolution modification routine blurs the input image by applying a frequency filter described by the input MTF. The resulting blurred image is then reduced to its final size to account for the sampling process of the digital system. The noise modification routine creates colored noise by filtering the frequency components of a white noise spectrum according to the input noise power. This noise is then applied to the image by a moving region of interest to account for variations in noise due to differences in attenuation. In order to evaluate the efficacy of the modification routines, additional routines were developed to assess the resolution and noise of digital images. The MTFs measured from the output images of the resolution modification routine were within 3% of the input MTF The NPS measured from the output images of the noise modification routine were within 2% of the input NPS. The findings indicate that the developed modification routines provide a good means of simulating the resolution and noise characteristics of digital radiographic systems for optimization or processing purposes.","subset":"pubmed_abstract"} +{"meta":{"pmid":23622420,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2014-10":1,"2015-18":1,"unknown":8}}},"text":"Changes in age distribution of hemorrhagic fever with renal syndrome: an implication of China's expanded program of immunization.\nVaccination against hemorrhagic fever with renal syndrome (HFRS) has been applied successfully for more than 20 years in China, and since 2008, the government has implemented the Expanded Program of Immunization (EPI) in regions with high incidence. In this study, we analyzed the EPI-related changes in age distribution in reported cases of HFRS and proposed new recommendations for prevention and control of the disease. Data relating to incidence of HFRS, geographical location and age distribution were collected through the China Information System for Disease Control and Prevention (CISDCP) from 2005 to 2010. Excel and SPSS 18.0 software, \u03c72 tests and descriptive methodology were used for analysis of the data. A total 75 434 HFRS cases were reported in 28 provinces in China between 2005 and 2010. The majority of HFRS cases occurred in adults aged 30 to 55 and this group accounted for 68.3% of the total. With the implementation of the immunization program, HFRS age distribution has clearly changed in recent years. The proportion of HFRS cases among individuals targeted by EPI (16-60 years of age) decreased from 86.9% in 2005 to 81.9% in 2010. However, the proportion of cases among the non-vaccinated group aged <16 and >60 had increased from 13.1% in 2005 to 18.1% in 2010. Notably, in the >60 age group the proportion rose from 8.8% in 2005 to 14.7% in 2010. These differences were statistically significant. HFRS vaccination has played an important role in HFRS control and prevention in China. However, since the proportion of HFRS cases over 60 years old has increased significantly since EPI was implemented, it is recommended that the age limit for vaccination be reconsidered. This finding may have practical implications for more effective HFRS vaccination in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":29230376,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-30":1,"unknown":16}}},"text":"Population structure and phenotypic variation of Sclerotinia sclerotiorum from dry bean (Phaseolus vulgaris) in the United States.\nThe ascomycete pathogen Sclerotinia sclerotiorum is a necrotrophic pathogen on over 400 known host plants, and is the causal agent of white mold on dry bean. Currently, there are no known cultivars of dry bean with complete resistance to white mold. For more than 20 years, bean breeders have been using white mold screening nurseries (wmn) with natural populations of S. sclerotiorum to screen new cultivars for resistance. It is thus important to know if the genetic diversity in populations of S. sclerotiorum within these nurseries (a) reflect the genetic diversity of the populations in the surrounding region and (b) are stable over time. Furthermore, previous studies have investigated the correlation between mycelial compatibility groups (MCG) and multilocus haplotypes (MLH), but none have formally tested these patterns. We genotyped 366 isolates of S. sclerotiorum from producer fields and wmn surveyed over 10 years in 2003-2012 representing 11 states in the United States of America, Australia, France, and Mexico at 11 microsatellite loci resulting in 165 MLHs. Populations were loosely structured over space and time based on analysis of molecular variance and discriminant analysis of principal components, but not by cultivar, aggressiveness, or field source. Of all the regions tested, only Mexico (n = 18) shared no MLHs with any other region. Using a bipartite network-based approach, we found no evidence that the MCGs accurately represent MLHs. Our study suggests that breeders should continue to test dry bean lines in several wmn across the United States to account for both the phenotypic and genotypic variation that exists across regions.","subset":"pubmed_abstract"} +{"meta":{"pmid":24195484,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2015-06":1,"2015-18":1,"unknown":12}}},"text":"The broccoli (Brassica oleracea) phloem tissue proteome.\nThe transport of sugars, hormones, amino acids, proteins, sugar alcohols, and other organic compounds from the sites of synthesis to the sites of use or storage occurs through the conducting cells of the phloem. To better understand these processes a comprehensive understanding of the proteins involved is required. While a considerable amount of data has been obtained from proteomic analyses of phloem sap, this has mainly served to identify the soluble proteins that are translocated through the phloem network. In order to obtain more comprehensive proteomic data from phloem tissue we developed a simple dissection procedure to isolate phloem tissue from Brassica oleracea. The presence of a high density of phloem sieve elements was confirmed using light microscopy and fluorescently labeled sieve element-specific antibodies. To increase the depth of the proteomic analysis for membrane bound and associated proteins, soluble proteins were extracted first and subsequent extractions were carried out using two different detergents (SDS and CHAPSO). Across all three extractions almost four hundred proteins were identified and each extraction method added to the analysis demonstrating the utility of an approach combining several extraction protocols. The phloem was found to be enriched in proteins associated with biotic and abiotic stress responses and structural proteins. Subsequent expression analysis identified a number of genes that appear to be expressed exclusively or at very high levels in phloem tissue, including genes that are known to express specifically in the phloem as well as novel phloem genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":30389806,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Evolutionary Quantitative Genetics of Genomic Imprinting.\nGenomic imprinting shapes the genotype-phenotype relationship by creating an asymmetry between the influences of paternally and maternally inherited gene copies. Consequently, imprinting can impact heritable and nonheritable variation, resemblance of relatives, and evolutionary dynamics. Although previous analyses have identified some of the quantitative genetic consequences of imprinting, we lack a framework that cleanly separates the influence of imprinting from other components of variation, particularly dominance. Here we apply a simple orthogonal genetic model to evaluate the roles of genetic (additive and dominance) and epigenetic (imprinting) effects. Imprinting increases the resemblance of relatives who share the expressed allele, and therefore increases variance among families of full or half-siblings. However, only part of this increased variance is heritable and contributes to selection responses. When selection is within, or among, families sharing only a single parent (half-siblings), which is common in selective breeding programs, imprinting can alter overall responses. Selection is more efficient when it acts among families sharing the expressed parent, or within families sharing the parent with lower expression. Imprinting also affects responses to sex-specific selection. When selection is on the sex whose gene copy has lower expression, the response is diminished or delayed the next generation, although the long-term response is unaffected. Our findings have significant implications for understanding patterns of variation, interpretation of short-term selection responses, and the efficacy of selective breeding programs, demonstrating the importance of considering the independent influence of genomic imprinting in quantitative genetics.","subset":"pubmed_abstract"} +{"meta":{"pmid":18929405,"dup_signals":{"dup_doc_count":31,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":2,"2022-49":2,"2022-40":1,"2022-33":1,"2022-27":1,"2022-21":3,"2022-05":1,"2021-43":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2020-40":1,"2020-34":1,"2020-24":2,"2020-10":1,"2019-43":1,"2023-50":1,"2024-18":1,"2024-26":1}}},"text":"Functional recovery after peripheral nerve injury and implantation of a collagen guide.\nAlthough surgery techniques improved over the years, the clinical results of peripheral nerve repair remain unsatisfactory. In the present study, we compare the results of a collagen nerve guide conduit to the standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves. We assessed behavioral and functional sensori-motor recovery in a rat model of peroneal nerve transection. A 1cm segment of the peroneal nerve innervating the Tibialis anterior muscle was removed and immediately replaced by a new biodegradable nerve guide fabricated from highly purified type I+III collagens derived from porcine skin. Four groups of animals were included: control animals (C, n=12), transected animals grafted with either an autologous nerve graft (Gold Standard; GS, n=12) or a collagen tube filled with an acellular skeletal muscle matrix (Tube-Muscle; TM, n=12) or an empty collagen tube (Collagen-Tube; CT, n=12). We observed that 1) the locomotor recovery pattern, analyzed with kinetic parameters and peroneal functional index, was superior in the GS and CT groups; 2) a muscle contraction was obtained in all groups after stimulation of the proximal nerve but the mechanical muscle properties (twitch and tetanus threshold) parameters indicated a fast to slow fiber transition in all operated groups; 3) the muscular atrophy was greater in animals from TM group; 4) the metabosensitive afferent responses to electrically induced fatigue and to two chemical agents (KCl and lactic acid) was altered in GS, CT and TM groups; 5) the empty collagen tube supported motor axonal regeneration. Altogether, these data indicate that motor axonal regeneration and locomotor recovery can be obtained with the insertion of the collagen tube RevolNerv. Future studies may include engineered conduits that mimic as closely as possible the internal organization of uninjured nerve.","subset":"pubmed_abstract"} +{"meta":{"pmid":21308768,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":2,"2022-49":1,"2022-33":1,"2021-49":1,"2021-31":2,"2021-21":1,"2021-10":1,"2021-04":2,"2020-40":1,"2020-34":1,"2020-29":1,"2020-24":1,"2020-16":1,"2017-30":1,"2023-14":1,"2013-48":1,"2014-10":1}}},"text":"Gene-environment interplay in common complex diseases: forging an integrative model\u2014recommendations from an NIH workshop.\nAlthough it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene-environment interaction remain a challenge and have had limited success to date. Given the current state-of-the-science, NIH sought input on ways to accelerate investigations of gene-environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene-environment interaction studies. Participants of the NIH Gene-Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene-environment interactions. Further, participants also emphasized the continued need for high-quality measures of environmental exposures and new genomic technologies in ongoing and new studies.","subset":"pubmed_abstract"} +{"meta":{"pmid":22355453,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":2,"unknown":9}}},"text":"The curious case of arenavirus entry, and its inhibition.\nArenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Jun\u00edn and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC. The virion is endocytosed on binding to a cell-surface receptor, and membrane fusion is initiated in response to physiological acidification of the endosome. As with other class I virus fusion proteins, GPC-mediated membrane fusion is promoted through a regulated sequence of conformational changes leading to formation of the classical postfusion trimer-of-hairpins structure. GPC is, however, unique among the class I fusion proteins in that the mature complex retains a stable signal peptide (SSP) as a third subunit, in addition to the canonical receptor-binding and fusion proteins. We will review the curious properties of the tripartite GPC complex and describe evidence that SSP interacts with the fusion subunit to modulate pH-induced activation of membrane fusion. This unusual solution to maintaining the metastable prefusion state of GPC on the virion and activating the class I fusion cascade at acidic pH provides novel targets for antiviral intervention.","subset":"pubmed_abstract"} +{"meta":{"pmid":16775354,"dup_signals":{"dup_doc_count":30,"dup_dump_count":26,"dup_details":{"curated_sources":4,"2022-21":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":1,"2020-29":1,"2020-16":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2023-06":1,"2015-18":1,"2013-48":1,"2013-20":1,"2024-18":1}}},"text":"Human papillomavirus E7 oncoprotein dysregulates steroid receptor coactivator 1 localization and function.\nHigh-risk human papillomaviruses (HPVs) are present in virtually all cervical carcinomas. However, the majority of women infected with high-risk HPVs do not develop cervical cancer. Therefore, cofactors must contribute to the development and progression of cervical cancer. Although numerous studies have implicated steroid hormones as cofactors in the initiation and progression of cervical neoplasia, the molecular mechanisms by which they contribute to cervical carcinogenesis are currently unknown. These observations led us to investigate a newly discovered association of the high-risk HPV type 16 (HPV16) E7 oncoprotein with steroid receptor coactivator 1 (SRC-1), an essential component of steroid hormone signaling. HPV16 E7 has been previously reported to interact with p300 and p300\/CBP-associated factor (PCAF), members of some SRC-1 transcriptional complexes. We demonstrate here that HPV16 E7 associates in vivo and in vitro with SRC-1 independently of p300 and PCAF. Luciferase reporter constructs under the control of either the interleukin-8 promoter or a promoter containing multimerized synthetic estrogen response elements were used to determine the effect of high- and low-risk HPV E7 expression on SRC-1-mediated transcription. In addition, histone acetyltransferase (HAT) assays were performed to determine the effect of HPV E7 on SRC-1-associated HAT activity. These experiments reveal that HPV16 E7 expression down-regulates SRC-1-mediated transcription and SRC-1-associated HAT activity. SRC-1 localization experiments show that SRC-1 is relocalized to the cytoplasm in the presence of high- and low-risk HPV E7 proteins. Our data suggest that HPV E7 proteins dysregulate hormone-dependent gene expression by association with and relocalization of SRC-1. Dysregulation of SRC-1 localization and function by HPV E7 may provide insight into the molecular mechanisms by which steroid hormones act as cofactors in the induction and progression of cervical neoplasia.","subset":"pubmed_abstract"} +{"meta":{"pmid":9012495,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"An activated form of type I serine\/threonine kinase receptor TARAM-A reveals a specific signalling pathway involved in fish head organiser formation.\nThe role of Transforming Growth Factor beta (TGF-beta)-related molecules in axis formation and mesoderm patterning in vertebrates has been extensively documented, but the identity and mechanisms of action of the endogenous molecules remained uncertain. In this study, we isolate a novel serine\/threonine kinase type I receptor, TARAM-A, expressed during early zebrafish embryogenesis first ubiquitously and then restricted to dorsal mesoderm during gastrulation. A constitutive form of the receptor is able to induce the most anterior dorsal mesoderm rapidly and to confer an anterior organizing activity. By contrast, the wild-type form is only able to induce a local expansion of the dorsal mesoderm. Thus an activated form of TARAM-A is sufficient to induce dorsoanterior structures and TARAM-A may be activated by dorsally localized signals. Our data suggest the existence in fish of a specific TGF-beta-related pathway for anterior dorsal mesoderm induction, possibly mediated by TARAM-A and activated at the late blastula stage by localized dorsal determinant.","subset":"pubmed_abstract"} +{"meta":{"pmid":28930531,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-49":1,"2022-27":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-24":1,"2023-14":1}}},"text":"Isolongifolene attenuates rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis.\nThe present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. Moreover, ILF attenuated rotenone induced toxicity by down-regulating Bax, caspases-3, 6, 8 and 9 expression and up-regulating of Bcl-2 expression. Furthermore regulation of p-P13K, p-AKT and p-GSK-3 beta expression by ILF, clearly confirmed its protective effects. Taken together, our results suggested that ILF attenuated rotenone-induced oxidative stress, mitochondrial dysfunction and apoptosis through the regulation of P13K\/AKT\/GSK-3 beta signaling pathways. However further pre-clinical studies are warranted in rodents to use ILF as a promising therapeutic agent for PD in future.","subset":"pubmed_abstract"} +{"meta":{"pmid":1308986,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage.\nAcutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.","subset":"pubmed_abstract"} +{"meta":{"pmid":11846740,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A logistic regression model for measuring gene-longevity associations.\nThe logistic regression model is a popular model for data analysis in epidemiological research. In this paper, we use this model to analyze genetic data collected from gene-longevity association studies. This new approach models the probability of observing one genotype as a function of the age of investigated individuals. Applying the model to genotype data on the TH and 3'ApoB-VNTR loci collected from an Italian centenarian study, we show how it can be used to model the different ways that genes affect survival, including sex- and age-specific influences. We highlight the advantages of this application over other available models. The application of the model to empirical data indicates that it is an efficient and easily applicable approach for determining the influences of genes on human longevity.","subset":"pubmed_abstract"} +{"meta":{"pmid":17240782,"dup_signals":{"dup_doc_count":25,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":2,"2013-48":2,"2013-20":1,"2024-18":1,"unknown":11}}},"text":"The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine.\nDifferent dietary proteins affect whole body protein anabolism and accretion and therefore, have the potential to influence results obtained from resistance training. This study examined the effects of supplementation with two proteins, hydrolyzed whey isolate (WI) and casein (C), on strength, body composition, and plasma glutamine levels during a 10 wk, supervised resistance training program. In a double-blind protocol, 13 male, recreational bodybuilders supplemented their normal diet with either WI or C (1.5 gm\/kg body wt\/d) for the duration of the program. Strength was assessed by 1-RM in three exercises (barbell bench press, squat, and cable pull-down). Body composition was assessed by dual energy X-ray absorptiometry. Plasma glutamine levels were determined by the enzymatic method with spectrophotometric detection. All assessments occurred in the week before and the week following 10 wk of training. Plasma glutamine levels did not change in either supplement group following the intervention. The WI group achieved a significantly greater gain (P < 0.01) in lean mass than the C group (5.0 +\/- 0.3 vs. 0.8 +\/- 0.4 kg for WI and C, respectively) and a significant (P < 0.05) change in fat mass (-1.5 +\/- 0.5 kg) compared to the C group (+0.2 +\/- 0.3 kg). The WI group also achieved significantly greater (P < 0.05) improvements in strength compared to the C group in each assessment of strength. When the strength changes were expressed relative to body weight, the WI group still achieved significantly greater (P < 0.05) improvements in strength compared to the C group.","subset":"pubmed_abstract"} +{"meta":{"pmid":30690158,"dup_signals":{"dup_doc_count":11}},"text":"Dynamic causal modelling of fluctuating connectivity in resting-state EEG.\nFunctional and effective connectivity are known to change systematically over time. These changes might be explained by several factors, including intrinsic fluctuations in activity-dependent neuronal coupling and contextual factors, like experimental condition and time. Furthermore, contextual effects may be subject-specific or conserved over subjects. To characterize fluctuations in effective connectivity, we used dynamic causal modelling (DCM) of cross spectral responses over 1- min of electroencephalogram (EEG) recordings during rest, divided into 1-sec windows. We focused on two intrinsic networks: the default mode and the saliency network. DCM was applied to estimate connectivity in each time-window for both networks. Fluctuations in DCM connectivity parameters were assessed using hierarchical parametric empirical Bayes (PEB). Within-subject, between-window effects were modelled with a second-level linear model with temporal basis functions as regressors. This procedure was conducted for every subject separately. Bayesian model reduction was then used to assess which (combination of) temporal basis functions best explain dynamic connectivity over windows. A third (between-subject) level model was used to infer which dynamic connectivity parameters are conserved over subjects. Our results indicate that connectivity fluctuations in the default mode network and to a lesser extent the saliency network comprised both subject-specific components and a common component. For both networks, connections to higher order regions appear to monotonically increase during the 1- min period. These results not only establish the predictive validity of dynamic connectivity estimates - in virtue of detecting systematic changes over subjects - they also suggest a network-specific dissociation in the relative contribution of fluctuations in connectivity that depend upon experimental context. We envisage these procedures could be useful for characterizing brain state transitions that may be explained by their cognitive or neuropathological underpinnings.","subset":"pubmed_abstract"} +{"meta":{"pmid":20855214,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":12}}},"text":"2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.\nAcetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC(50) value 6.6 \u03bcg\/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC(50) value 2-HDA 15.3 \u03bcg\/ml, control drug atovaquone 2.5 ng\/ml) and immunofluorescence analysis (IC(50) 2-HDA 4.88 \u03bcg\/ml, control drug atovaquone 0.37 ng\/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC(50) values of 0.38 and 0.58 \u03bcg\/ml (IC(50) control drugs 14 and 30 ng\/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC(50) values 3.7-31.7 \u03bcg\/ml), Trypanosoma cruzi (only 2-HDA, IC(50) 20.2 \u03bcg\/ml), and Leishmania donovani (IC(50) values 4.1-13.4 \u03bcg\/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to study the interaction of fatty acids with these key P. falciparum enzymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":8395015,"dup_signals":{"dup_doc_count":19,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2020-34":1,"2020-29":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-47":1,"2019-43":2,"2019-39":1,"2019-30":1,"2019-26":2,"2019-22":1,"2021-17":1}}},"text":"Genetic and biochemical characterization of a phosphatidylinositol-specific phospholipase C in Saccharomyces cerevisiae.\nHydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphatidylinositol-specific phospholipase C (PI-PLC) generates two second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. The polymerase chain reaction was used to isolate a Saccharomyces cerevisiae gene (PLC1) that encodes a protein of 869 amino acids (designated Plc1p) that bears greatest resemblance to the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain arrangement. Plc1p contains the conserved X and Y domains found in all higher eukaryotic PI-PLCs (51 and 29% identity, respectively, to the corresponding domains of rat delta 1 PI-PLC) and also contains a presumptive Ca(2+)-binding site (an E-F hand motif). Plc1p, modified by in-frame insertion of a His6 tract and a c-myc epitope near its amino terminus, was overexpressed from the GAL1 promoter, partially purified by nickel chelate affinity chromatography, and shown to be an active PLC enzyme in vitro with properties similar to those of its mammalian counterparts. Plc1p activity was strictly Ca2+ dependent: at a high Ca2+ concentration (0.1 mM), the enzyme hydrolyzed PIP2 at a faster rate than phosphatidylinositol, and at a low Ca2+ concentration (0.5 microM), it hydrolyzed PIP2 exclusively. Cells carrying either of two different deletion-insertion mutations (plc1 delta 1::HIS3 and plc1 delta 2::LEU2) were viable but displayed several distinctive phenotypes, including temperature-sensitive growth (inviable above 35 degrees C), osmotic sensitivity, and defects in the utilization of galactose, raffinose, and glycerol at permissive temperatures (23 to 30 degrees C). The findings reported here suggest that hydrolysis of PIP2 in S. cerevisiae is required for a number of nutritional and stress-related responses.","subset":"pubmed_abstract"} +{"meta":{"pmid":34931806,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-10":1,"unknown":9}}},"text":"4-Deoxy-4-fluoro-GalNAz (4FGalNAz) Is a Metabolic Chemical Reporter of O-GlcNAc Modifications, Highlighting the Notable Substrate Flexibility of O-GlcNAc Transferase.\nBio-orthogonal chemistries have revolutionized many fields. For example, metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain a bio-orthogonal functionality, such as azides or alkynes. MCRs are metabolically incorporated into glycoproteins by living systems, and bio-orthogonal reactions can be subsequently employed to install visualization and enrichment tags. Unfortunately, most MCRs are not selective for one class of glycosylation (e.g., N-linked vs O-linked), complicating the types of information that can be gleaned. We and others have successfully created MCRs that are selective for intracellular O-GlcNAc modification by altering the structure of the MCR and thus biasing it to certain metabolic pathways and\/or O-GlcNAc transferase (OGT). Here, we attempt to do the same for the core GalNAc residue of mucin O-linked glycosylation. The most widely applied MCR for mucin O-linked glycosylation, GalNAz, can be enzymatically epimerized at the 4-hydroxyl to give GlcNAz. This results in a mixture of cell-surface and O-GlcNAc labeling. We reasoned that replacing the 4-hydroxyl of GalNAz with a fluorine would lock the stereochemistry of this position in place, causing the MCR to be more selective. After synthesis, we found that 4FGalNAz labels a variety of proteins in mammalian cells and does not perturb endogenous glycosylation pathways unlike 4FGalNAc. However, through subsequent proteomic and biochemical characterization, we found that 4FGalNAz does not widely label cell-surface glycoproteins but instead is primarily a substrate for OGT. Although these results are somewhat unexpected, they once again highlight the large substrate flexibility of OGT, with interesting and important implications for intracellular protein modification by a potential range of abiotic and native monosaccharides.","subset":"pubmed_abstract"} +{"meta":{"pmid":24786708,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":1,"2023-14":1,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-40":1,"2024-22":1,"2024-26":1}}},"text":"Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes.\nThe incidence and prevalence of diabetes mellitus (DM) continue to grow markedly throughout the world, due primarily to the increase in type 2 DM (T2DM). Although improvements in DM and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease (CKD) and progress to end-stage renal disease (ESRD), the sheer increase in people developing DM will have a major impact on dialysis and transplant needs. This KDIGO conference addressed a number of controversial areas in the management of DM patients with CKD, including aspects of screening for CKD with measurements of albuminuria and estimated glomerular filtration rate (eGFR); defining treatment outcomes; glycemic management in both those developing CKD and those with ESRD; hypertension goals and management, including blockers of the renin-angiotensin-aldosterone system; and lipid management.","subset":"pubmed_abstract"} +{"meta":{"pmid":11290304,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2020-45":1,"2018-22":1,"2017-51":1,"2017-43":1,"2017-22":1,"2017-09":1,"2016-44":2,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2021-04":1}}},"text":"Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site.\nEvolutionarily conserved ovo loci encode developmentally regulated, sequence-specific, DNA-binding, C(2)H(2)-zinc-finger proteins required in the germline and epidermal cells of flies and mice. The direct targets of OVO activity are not known. Genetic experiments suggest that ovo acts in the same regulatory network as ovarian tumor (otu), but the relative position of these genes in the pathway is controversial. Three OVO-binding sites exist in a compact regulatory region that controls germline expression of the otu gene. Interestingly, the strongest OVO-binding site is very near the otu transcription start, where basal transcriptional complexes must function. Loss-of-function, gain-of-function and promoter swapping constructs demonstrate that OVO binding near the transcription start site is required for OVO-dependent otu transcription in vivo. These data unambiguously identify otu as a direct OVO target gene and raise the tantalizing possibility that an OVO site, at the location normally occupied by basal components, functions as part of a specialized core promoter.","subset":"pubmed_abstract"} +{"meta":{"pmid":17850662,"dup_signals":{"dup_doc_count":15,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":2,"2014-10":2,"2024-18":1,"unknown":7}}},"text":"One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors.\nUnstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization. In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling. After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference -1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]). Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization.","subset":"pubmed_abstract"} +{"meta":{"pmid":32262706,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Wound healing properties of hyaluronan derivatives bearing ferulate residues.\nHAFA macromolecules were designed as graft copolymers combining ferulic acid (FA) structure and the hyaluronic acid (HA) backbone linked through an ester bond. These materials were prepared by feruloylation of HA with bisimidazolide 3 [i.e. (E)-4-(3-(1H-imidazol-1-yl)-3-oxoprop-1-enyl)-2-methoxyphenyl 1H-imidazole-1-carboxylate] and obtained with different grafting degree (GD) values, which could be tuned by applying suitable reaction conditions. Among the numerous applications envisioned for HAFA graft copolymers on the basis of the physico-chemical, biological, and pharmacological properties of the starting natural products and the grafting-derived features such as physical cross-linking, potential wound healing properties have been evaluated in vitro and in vivo in preclinical models. In human keratinocyte (HaCaT) cells, our data showed the ability of HAFA-17 (GD = 7%) to ameliorate the in vitro scratch wound significantly with respect to the control HA and FA alone, and this effect was associated with the ability of HAFA-17 to also induce keratinocyte proliferation as determined by BrdU assay. In addition, experiments on wound healing in SKH1 mice confirmed the ability of HAFA-17 to improve the wound closure rate also in vivo. Overall, the data presented herein suggest HAFA-17 as a possible future drug for the therapeutic treatment of acute and chronic wounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":28580109,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":9}}},"text":"Photoswitchable interlocked thiodiglycolamide as a cocatalyst of a chalcogeno-Baylis-Hillman reaction.\nEn route to a photoswitchable interlocked catalyst we have proved the ability of thiodiglycolamide to act as a template in the formation of hydrogen-bonded [2]rotaxanes. X-ray diffraction studies reveal the shielding of the sulfide atom by the macrocycle. A series of molecular shuttles are described as having an isomerizable fumaramide and thiodiglycolamide binding sites for controlling the relative ring position at will. By employing these systems as photoregulated catalysts, the TiCl4-mediated chalcogeno-Morita-Baylis-Hillman reaction is tested. In the presence of the maleamide shuttle, in which the sulfide function is encapsulated by the macrocycle, a complete loss in control of the geometry of the produced aldol is observed. The E-aldol adduct is predominantly obtained when the photoisomerized fumaramide shuttle, in which the sulfide function is exposed, is used.","subset":"pubmed_abstract"} +{"meta":{"pmid":28750737,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":15}}},"text":"Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis.\nDespite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":15827195,"dup_signals":{"dup_doc_count":22,"dup_dump_count":16,"dup_details":{"curated_sources":4,"2023-23":2,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":2,"2021-49":1,"2021-31":1,"2021-17":1,"2020-50":1,"2018-22":1,"2018-05":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-22":1,"2024-26":1}}},"text":"Association of the influenza A virus RNA-dependent RNA polymerase with cellular RNA polymerase II.\nTranscription by the influenza virus RNA-dependent RNA polymerase is dependent on cellular RNA processing activities that are known to be associated with cellular RNA polymerase II (Pol II) transcription, namely, capping and splicing. Therefore, it had been hypothesized that transcription by the viral RNA polymerase and Pol II might be functionally linked. Here, we demonstrate for the first time that the influenza virus RNA polymerase complex interacts with the large subunit of Pol II via its C-terminal domain. The viral polymerase binds hyperphosphorylated forms of Pol II, indicating that it targets actively transcribing Pol II. In addition, immunofluorescence analysis is consistent with a new model showing that influenza virus polymerase accumulates at Pol II transcription sites. The present findings provide a framework for further studies to elucidate the mechanistic principles of transcription by a viral RNA polymerase and have implications for the regulation of Pol II activities in infected cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":15338453,"dup_signals":{"dup_doc_count":11}},"text":"Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome.\nThe SCN5A gene encodes the alpha subunit of the human cardiac voltage-gated sodium channel. Mutations in SCN5A are responsible for Brugada syndrome, an inherited cardiac disease that leads to idiopathic ventricular fibrillation (IVF) and sudden death. In this study, we screened nine individuals from a single family and 12 sporadic patients who were clinically diagnosed with Brugada syndrome. Using PCR-SSCP, DHPLC, and DNA sequencing analysis, we identified a novel single missense mutation associated with Brugada syndrome in the family and detected a C5607T polymorphism in Korean subjects. A single nucleotide substitution of G to A at nucleotide position 3934 changed the coding sense of exon 21 of the SCN5A from glycine to serine (G1262S) in segment 2 of domain III (DIII-S2). Four individuals in the family carried the identical mutation in the SCN5A gene, but none of the 12 sporadic patients did. This mutation was not found in 150 unrelated normal individuals. This finding is the first report of a novel mutation in SCN5A associated with Brugada syndrome in Koreans.","subset":"pubmed_abstract"} +{"meta":{"pmid":15339631,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":5}}},"text":"A genetic and spatial Bayesian analysis of mastitis resistance.\nA nationwide health card recording system for dairy cattle was introduced in Norway in 1975 (the Norwegian Cattle Health Services). The data base holds information on mastitis occurrences on an individual cow basis. A reduction in mastitis frequency across the population is desired, and for this purpose risk factors are investigated. In this paper a Bayesian proportional hazards model is used for modelling the time to first veterinary treatment of clinical mastitis, including both genetic and environmental covariates. Sire effects were modelled as shared random components, and veterinary district was included as an environmental effect with prior spatial smoothing. A non-informative smoothing prior was assumed for the baseline hazard, and Markov chain Monte Carlo methods (MCMC) were used for inference. We propose a new measure of quality for sires, in terms of their posterior probability of being among the, say 10% best sires. The probability is an easily interpretable measure that can be directly used to rank sires. Estimating these complex probabilities is straightforward in an MCMC setting. The results indicate considerable differences between sires with regards to their daughters disease resistance. A regional effect was also discovered with the lowest risk of disease in the south-eastern parts of Norway.","subset":"pubmed_abstract"} +{"meta":{"pmid":35866444,"dup_signals":{"dup_doc_count":20,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-30":2,"2024-22":1,"2024-18":3,"2024-10":1,"unknown":12}}},"text":"How should we interpret lactate in labour? A reference study.\nTo investigate maternal lactate concentrations in labour and the puerperium. Reference study. Tertiary obstetric unit. 1279 pregnant women with good perinatal outcomes at term. Electronic patient records were searched for women who had lactate measured on the day of delivery or in the following 24 hours, but who were subsequently found to have a very low likelihood of sepsis, based on their outcomes. The normative distribution of lactate and C-reactive protein (CRP), differences according to the mode of birth, and the proportion of results above the commonly used cut-offs (\u22652 and \u22654 mmol\/l). Lactate varied between 0.4-5.4 mmol\/l (median 1.8 mmol\/l, interquartile range [IQR] 1.3-2.5). It was higher in women who had vaginal deliveries than caesarean sections (median 1.9 vs. 1.6 mmol\/l, pdiff < 0.001), demonstrating the association with labour (particularly active pushing in the second stage). In contrast, CRP was more elevated in women who had caesarean sections (median 71.8 mg\/l) than those who had vaginal deliveries (33.4 mg\/l, pdiff < 0.001). In total, 40.8% had a lactate \u22652 mmol\/l, but 95.3% were <4 mmol\/l. Lactate in labour and the puerperium is commonly elevated above the levels expected in healthy pregnant or non-pregnant women. There is a paucity of evidence to support using lactate or CRP to make decisions about antibiotics around the time of delivery but, as lactate is rarely higher than 4 mmol\/l, this upper limit may still represent a useful severity marker for the investigation and management of sepsis in labour.","subset":"pubmed_abstract"} +{"meta":{"pmid":23856348,"dup_signals":{"dup_doc_count":28,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2020-24":1,"2018-30":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":1,"2021-10":1,"2015-11":1,"2014-10":1,"2013-48":1,"2015-18":1}}},"text":"On the study of the transmission networks of blood parasites from SW Spain: diversity of avian haemosporidians in the biting midge Culicoides circumscriptus and wild birds.\nBlood-sucking flying insects play a key role in the transmission of pathogens of vector-borne diseases. However, at least for the case of avian malaria parasites, the vast majority of studies focus on the interaction between parasites and vertebrate hosts, but there is a lack of information regarding the interaction between the parasites and the insect vectors. Here, we identified the presence of malaria and malaria-like parasite lineages harbored by the potential vector Culicoides circumscriptus (Kieffer). Also, we identified some nodes of the transmission network connecting parasite lineages, potential insect vectors and avian hosts by comparing Haemoproteus and Plasmodium lineages isolated from insects with those infecting wild birds in this and previous studies. Using a molecular approach, we analysed the presence of blood parasites in a total of 97 biting midges trapped in the Do\u00f1ana National Park (SW Spain) and surrounding areas. Also, 123 blood samples from 11 bird species were analyzed for the presence of blood parasite infections. Blood parasites Haemoproteus and Plasmodium were identified by amplification of a 478 bp fragment of the mitochondrial cytochrome b gen. Thirteen biting midges harboured blood parasites including six Haemoproteus and two Plasmodium lineages, supporting the potential role of these insects on parasite transmission. Moreover, ten (8.1%) birds carried blood parasites. Seven Plasmodium and one Haemoproteus lineages were isolated from birds. Overall, six new Haemoproteus lineages were described in this study. Also, we identified the transmission networks of some blood parasites. Two Haemoproteus lineages, hCIRCUM03 and GAGLA03, were identical to those isolated from Corvus monedula in southern Spain and Garrulus glandarius in Bulgaria, respectively. Furthermore, the new Haemoproteus lineage hCIRCUM05 showed a 99% similarity with a lineage found infecting captive penguins in Japan. The comparison of the parasite lineages isolated in this study with those previously found infecting birds allowed us to identify some potential nodes in the transmission network of avian blood parasite lineages. These results highlight the complexity of the transmission networks of blood parasites in the wild that may involve a high diversity of susceptible birds and insect vectors.","subset":"pubmed_abstract"} +{"meta":{"pmid":33758991,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":3,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Impact of population-based or targeted BMD interventions on fracture incidence.\nIn a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than -2.5. To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX\u00ae cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below -2.5 to be exactly -2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70-79-year age band and declined thereafter. Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK\/European anthropometric\/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":23573177,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":16}}},"text":"Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala: a novel methodology.\nKnowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons \u22655 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009-July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129-27,659 for children <5 years old (2.9-4.7 per 1,000 persons) and 6,882-7,836 for persons \u22655 years old (0.21-0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065-2,259 (0.5-1.0 per 1,000 persons) among children <5 years old and 779-2,252 cases (0.1-0.2 per 1,000 persons) for persons \u22655 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.","subset":"pubmed_abstract"} +{"meta":{"pmid":24794975,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":17}}},"text":"Transcriptional coregulators: fine-tuning metabolism.\nMetabolic homeostasis requires that cellular energy levels are adapted to environmental cues. This adaptation is largely regulated at the transcriptional level, through the interaction between transcription factors, coregulators, and the basal transcriptional machinery. Coregulators, which function as both metabolic sensors and transcriptional effectors, are ideally positioned to synchronize metabolic pathways to environmental stimuli. The balance between inhibitory actions of corepressors and stimulatory effects of coactivators enables the fine-tuning of metabolic processes. This tight regulation opens therapeutic opportunities to manage metabolic dysfunction by directing the activity of cofactors toward specific transcription factors, pathways, or cells\/tissues, thereby restoring whole-body metabolic homeostasis.","subset":"pubmed_abstract"} +{"meta":{"pmid":21892108,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2023-14":1,"2022-05":1,"2021-39":1,"2021-25":2,"2019-18":1,"2019-09":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2023-40":1,"2024-10":1,"2024-22":1}}},"text":"Survival benefits from follow-up of patients with lung cancer: a systematic review and meta-analysis.\nThe burden of lung cancer is high for patients and carers. Care after treatment may have the potential to impact on this. We reviewed the published literature on follow-up strategies intended to improve survival and quality of life. We systematically reviewed studies comparing follow-up regimes in lung cancer. Primary outcomes were overall survival (comparing more intensive versus less intensive follow-up) and survival comparing symptomatic with asymptomatic recurrence. Quality of life was identified as a secondary outcome measure. Hazard ratios (HRs) and 95% confidence intervals from eligible studies were synthesized. Nine studies that examined the role of more intensive follow-up for patients with lung cancer were included (eight observational studies and one randomized controlled trial). The studies of curative resection included patients with non-small cell lung cancer Stages I to III disease, and studies of palliative treatment follow-up included limited and extensive stage patients with small cell lung cancer. A total of 1669 patients were included in the studies. Follow-up programs were heterogeneous and multifaceted. A nonsignificant trend for intensive follow-up to improve survival was identified, for the curative intent treatment subgroup (HR: 0.83; 95% confidence interval: 0.66-1.05). Asymptomatic recurrence was associated with increased survival, which was statistically significant HR: 0.61 (0.50-0.74) (p < 0.01); quality of life was only assessed in one study. This meta-analysis must be interpreted with caution due to the potential for bias in the included studies: observed benefit may be due to systematic differences in outcomes rather than intervention effects. Some benefit was noted from intensive follow-up strategies. More robust data, in the form of randomized controlled trials, are needed to confirm these findings as the review is based primarily on observational studies. Future research should also include patient-centered outcomes to investigate the impact of follow-up regimes on living with lung cancer and psychosocial well-being.","subset":"pubmed_abstract"} +{"meta":{"pmid":22038679,"dup_signals":{"dup_doc_count":12}},"text":"A chronological history of the International Conference on Cryptococcus and Cryptococcosis (ICCC), an invaluable forum for growth of the cryptococcal research field and clinical practice.\nCryptococcologists meet every 3 years to present their new research data and discuss the current state of cryptococcosis therapy at the International Conference on Cryptococcus and Cryptococcosis (ICCC). The ICCC has served as a unique forum where mycologists could interact and share their research data in a setting exclusively devoted to the study of Cryptococcus and cryptococcosis. This article presents an historical perspective on the ICCC meetings, beginning with the first ICCC that was held in Jerusalem, Israel in 1989. Subsequent ICCC meetings have grown, in terms of attendance and submitted abstracts. The history of the ICCC serves as a testimony to the remarkable progress that has been made in our basic understanding of the molecular biology, biochemistry, ecology, and taxonomy of Cryptococcus as well as the epidemiology, immunology, clinical manifestations, and treatment for cryptococcosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":23316656,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"[Changes in subfoveal choroidal thickness of epiretinal membrane and macular hole before and after microincision vitrectomy surgery].\nTo evaluate the subfoveal choroidal thickness (SCT) of the epiretinal membrane (ERM) and macular hole (MH) both before and after microincision vitrectomy surgery. A total of 104 eyes of 104 subjects (64 ERM, 40 MH, mean age 68.9 years) were evaluated. All subjects underwent vitrectomy with internal limiting membrane peeling. SCT was measured before vitrectomy and 1 week, 1 month and 3 months postoperatively. SCT was measured by enhanced depth imaging OCT (EDI-OCT) using a Heiderberg Spectralis. The SCT of ERM was 202.6 microm before vitrectomy, and 201.8 microm at 1 week, 198.8 microm at 1 month, and 196.4 microm at 3 months postoperatively. There were no significant differences between the times of measurement. MH was 182.5 microm before vitrectomy, and 186.7 microm at 1 week, 189.4 microm at 1 month, and 187.4 microm at 3 months. There were also no significant differences between any other factors. The SCT between the ERM and MH was not significantly different at any time. We examined the correlation between the changes in SCT and the changes in age, refractive error and intraocular pressure (IOP), but found no significant correlation. The SCT hat not changed either before or after microincision vitrectomy surgery, and there was no siginificant correlation between SCT and any other factor.","subset":"pubmed_abstract"} +{"meta":{"pmid":21550032,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":10}}},"text":"The relationship between illegal behaviors and borderline personality symptoms among internal medicine outpatients.\nIn psychiatric dysfunction, illegal behaviors are frequently associated with the traditional prison personality antisocial personality disorder. However, some empirical data indicate that illegal behaviors may also be associated with borderline personality, which is the focus of the present study. Using a cross-sectional sample of consecutive internal medicine outpatients from a resident-provider clinic, we examined relationships between 27 illegal behaviors as delineated by the Federal Bureau of Investigation's crime-cataloguing schema and 2 measures of borderline personality disorder (BPD), the BPD scale of the Personality Diagnostic Questionnaire-4 and the Self-Harm Inventory. The overall correlations between BPD and the number of the 27 illegal behaviors endorsed were r = 0.32 (P < .001, n = 375) for the Personality Diagnostic Questionnaire-4 and r = 0.47 (P < .001, n = 372) for the Self-Harm Inventory. Six specific illegal behaviors were endorsed by at least 12 participants each, and analyses indicated associations for each of these illegal behaviors with BPD (ie, aggravated and simple assault, disorderly conduct, driving under the influence, drug abuse violations, public drunkenness\/intoxication). These 6 behaviors may be interrelated through alcohol\/substance use. Participants who were male and younger were more likely to report having engaged in a greater number of different illegal behaviors. There appear to be associations between illegal behaviors and BPD, particularly in relation to alcohol\/substance abuse and in young men.","subset":"pubmed_abstract"} +{"meta":{"pmid":24574030,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-10":1,"unknown":13}}},"text":"Chemically orthogonal three-patch microparticles.\nCompared to two-dimensional substrates, only a few methodologies exist for the spatially controlled decoration of three-dimensional objects, such as microparticles. Combining electrohydrodynamic co-jetting with synthetic polymer chemistry, we were able to create two- and three-patch microparticles displaying chemically orthogonal anchor groups on three distinct surface patches of the same particle. This approach takes advantage of a combination of novel chemically orthogonal polylactide-based polymers and their processing by electrohydrodynamic co-jetting to yield unprecedented multifunctional microparticles. Several micropatterned particles were fabricated displaying orthogonal click functionalities. Specifically, we demonstrate novel two- and three-patch particles. Multi-patch particles are highly sought after for their potential to present multiple distinct ligands in a directional manner. This work clearly establishes a viable route towards orthogonal reaction strategies on multivalent micropatterned particles.","subset":"pubmed_abstract"} +{"meta":{"pmid":20968201,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Angiogenesis in the degeneration of the lumbar intervertebral disc.\nThe goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre-surgery and post-surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF-2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post-operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking).","subset":"pubmed_abstract"} +{"meta":{"pmid":8982148,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive \"switching\" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.\nPainful crises in patients with sickle cell anemia are caused by vaso-occlusion and infarction. Occlusion of blood vessels depends on (at least) their diameter, the deformability of red cells, and the adhesion of blood cells to endothelium. Deoxygenated sickle cells are rigid because they contain linear polymers of hemoglobin S (Hb S); polymerization is highly concentration dependent, and dilution of Hb S by a nonsickling hemoglobin such as fetal hemoglobin (Hb F) would be expected to lead ultimately to a decrease in the frequency of painful crises. It might also be expected to decrease the severity of anemia, although the pathogenesis of anemia in sickle cell anemia (SS disease) is not clearly understood. Reversion to production of fetal rather than adult hemoglobin became practical with the discovery that HU was an orally effective and relatively safe \"switching agent.\" Preliminary dose-ranging studies led to a double-blind randomized controlled clinical trial, the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), designed to test whether patients treated with HU would have fewer crises than patients treated with placebo. The MSH was not designed to assess the mechanism(s) by which a beneficial effect might be achieved, but it was hoped that observations made during the study might illuminate that question. The 2 MSH treatment groups were similar to each other and were representative of African-American patients with relatively severe disease. The trial was closed earlier than expected, after demonstration that median crisis rate was reduced by almost 50% (2.5 versus 4.5 crises per year) in patients assigned to HU therapy. Hospitalizations, episodes of chest syndrome, and numbers of transfusions were also lower in patients treated with HU. Eight patients died during the trial, and treatment was stopped in 53. There were no instances of alarming toxicity. Patients varied widely in their maximum tolerated doses, but it was not clear that all were taking their prescribed treatments. When crisis frequency was compared with various clinical and laboratory measurements, pretreatment crisis rate and treatment with HU were clearly related to crisis rate during treatment. Pretreatment laboratory measurements were not associated with crisis rates during the study in either treatment group. It was not clear that clinical improvement was associated with an increase in Hb F. Crisis rates of the 2 treatment groups became different within 3 months. Mean corpuscular volumes (MCVs) and the proportion of Hb F containing red cells (F cells) rose, and neutrophil and reticulocyte counts fell, within 7 weeks. When patients were compared on the basis of 2-year crisis rates, those with lower crisis rates had higher F-cell counts and MCVs and lower neutrophil counts. Neutrophil, monocyte, reticulocyte, and platelet counts were directly associated, and F cells and MCV were inversely associated, with crisis rates in 3-month periods. In multivariable analyses, there was strong evidence of independent association of lower neutrophil counts with lower crisis rates. F-cell counts were associated with crisis rate only in the first 3 months of treatment; MCV showed an association over longer periods of time. Overall, the evidence that decreased neutrophil counts played a role in reducing crisis rates was strong. Increased F cells or MCV and evidence of cytoreduction by HU were also associated with decreased crisis rates, but no definitive statement can be made regarding the mechanism of action of HU because the study was not designed to address that question. Future studies should be designed to explore the mechanism of action of HU, to identify the optimal dosage regimen, and to study the effect of HU when combined with other antisickling agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":22926877,"dup_signals":{"dup_doc_count":22,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2020-24":3,"2020-16":2,"2020-10":1,"2020-05":2,"2019-51":1,"2019-43":3,"2019-39":1,"2019-35":1,"2018-47":1,"2018-26":1,"2018-22":1,"2018-05":1,"2017-51":1,"2017-30":1,"2016-44":1}}},"text":"Reconstructing the development of Baltic sea eutrophication 1850-2006.\nA comprehensive reconstruction of the Baltic Sea state from 1850 to 2006 is presented: driving forces are reconstructed and the evolution of the hydrography and biogeochemical cycles is simulated using the model BALTSEM. Driven by high resolution atmospheric forcing fields (HiResAFF), BALTSEM reproduces dynamics of salinity, temperature, and maximum ice extent. Nutrient loads have been increasing with a noteworthy acceleration from the 1950s until peak values around 1980 followed by a decrease continuing up to present. BALTSEM shows a delayed response to the massive load increase with most eutrophic conditions occurring only at the end of the simulation. This is accompanied by an intensification of the pelagic cycling driven by a shift from spring to summer primary production. The simulation indicates that no improvement in water quality of the Baltic Sea compared to its present state can be expected from the decrease in nutrient loads in recent decades.","subset":"pubmed_abstract"} +{"meta":{"pmid":12576321,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2019-51":1,"2015-18":1}}},"text":"Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1).\nHermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting 3 related organelles-melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least 15 nonallelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, that is, protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least 3 distinct protein complexes: the adaptor complex AP-3; the HPS1\/HPS4 complex; and BLOC-1 (biogenesis of lysosome-related organelles complex-1), consisting of the proteins encoded at 2 mouse HPS loci, pallid (pa) and muted (mu), and at least 3 other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno\/cno mice. The C-terminal 81 amino acids are replaced with 72 different amino acids in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of patients with HPS and failed to identify any CNO defects. Notably, although defects in components of the HPS1\/HPS4 and the AP-3 complexes are associated with HPS in humans, no defects in the known components of BLOC-1 have been identified in 142 patients with HPS screened to date, suggesting that BLOC-1 function may be critical in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":21995598,"dup_signals":{"dup_doc_count":28,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2015-48":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2020-50":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Canadian medical tourism companies that have exited the marketplace: Content analysis of websites used to market transnational medical travel.\nMedical tourism companies play an important role in promoting transnational medical travel for elective, out-of-pocket medical procedures. Though researchers are paying increasing attention to the global phenomenon of medical tourism, to date websites of medical tourism companies have received limited scrutiny. This article analyzes websites of Canadian medical tourism companies that advertised international healthcare but ultimately exited the marketplace. Using content analysis of company websites as an investigative tool, the article provides a detailed account of medical tourism companies that were based in Canada but no longer send clients to international health care facilities. Internet searches, Google Alerts, searches on Google News Canada and ProQuest Newsstand, and searches of an Industry Canada database were used to locate medical tourism companies located in Canada. Once medical tourism companies were identified, the social science research method of content analysis was used to extract relevant information from company websites. Company websites were analyzed to determine: 1) where these businesses were based; 2) the destination countries and medical facilities that they promoted; 3) the health services they advertised; 4) core marketing messages; and 5) whether businesses marketed air travel, hotel accommodations, and holiday excursions in addition to medical procedures. In total, 25 medical tourism companies that were based in Canada are now defunct. Given that an estimated 18 medical tourism companies and 7 regional, cross-border medical travel facilitators now operate in Canada, it appears that approximately half of all identifiable medical tourism companies in Canada are no longer in business. 13 of the previously operational companies were based in Ontario, 7 were located in British Columbia, 4 were situated in Quebec, and 1 was based in Alberta. 14 companies marketed medical procedures within a single country, 9 businesses marketed health care at 2 or more destination nations, and 2 companies did not specify particular health care destinations. 22 companies operated as \"generalist\" businesses marketing many different types of medical procedures. 3 medical tourism companies marketed \"specialist\" services restricted to dental procedures or organ transplants. In general, medical tourism companies marketed health services on the basis of access to affordable, timely, and high-quality care. 16 businesses offered to make travel arrangements, 20 companies offered to book hotel reservations, and 17 medical tourism companies advertised holiday excursions. This article provides a detailed empirical analysis of websites of medical tourism companies that were based in Canada but exited the marketplace and are now inoperative. The article identifies where these companies were located in Canada, what countries and health care facilities they selected as destination sites, the health services they advertised, how they marketed themselves in a competitive environment, and what travel-related services they promoted in addition to marketing health care. The paper reveals a fluid marketplace, with many medical tourism companies exiting this industry. In addition, by disclosing identities of companies, providing their websites, archiving these websites or print copies of websites for future studies, and analyzing content of medical tourism company websites, the article can serve as a useful resource for future studies. Citizens, health policy-makers, clinicians, and researchers can all benefit from increased insight into Canada's medical tourism industry.","subset":"pubmed_abstract"} +{"meta":{"pmid":26289203,"dup_signals":{"dup_doc_count":11}},"text":"Growing the gas-giant planets by the gradual accumulation of pebbles.\nIt is widely held that the first step in forming gas-giant planets, such as Jupiter and Saturn, was the production of solid 'cores' each with a mass roughly ten times that of the Earth. Getting the cores to form before the solar nebula dissipates (in about one to ten million years; ref. 3) has been a major challenge for planet formation models. Recently models have emerged in which 'pebbles' (centimetre-to-metre-sized objects) are first concentrated by aerodynamic drag and then gravitationally collapse to form objects 100 to 1,000 kilometres in size. These 'planetesimals' can then efficiently accrete left-over pebbles and directly form the cores of giant planets. This model is known as 'pebble accretion'; theoretically, it can produce cores of ten Earth masses in only a few thousand years. Unfortunately, full simulations of this process show that, rather than creating a few such cores, it produces a population of hundreds of Earth-mass objects that are inconsistent with the structure of the Solar System. Here we report that this difficulty can be overcome if pebbles form slowly enough to allow the planetesimals to gravitationally interact with one another. In this situation, the largest planetesimals have time to scatter their smaller siblings out of the disk of pebbles, thereby stifling their growth. Our models show that, for a large and physically reasonable region of parameter space, this typically leads to the formation of one to four gas giants between 5 and 15 astronomical units from the Sun, in agreement with the observed structure of the Solar System.","subset":"pubmed_abstract"} +{"meta":{"pmid":19877792,"dup_signals":{"dup_doc_count":20,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":3,"2013-20":1,"2024-18":1,"unknown":11}}},"text":"Efficacy of endovascular stenting in dural venous sinus stenosis for the treatment of idiopathic intracranial hypertension.\nMultiple pathophysiological mechanisms have been proposed for the increased intracranial pressure observed in idiopathic intracranial hypertension (IIH). The condition is well characterized, with intractable headaches, visual obscurations, and papilledema as dominant features, mainly affecting obese women. With the advent of MR venography and increased use of cerebral angiography, there has been recent emphasis on the significant number of patients with IIH found to have associated nonthrombotic dural venous sinus stenosis. This has led to a renewed interest in endovascular stenting as a treatment for IIH. However, the assumption that venous stenosis leads to a high pressure gradient that decreases CSF resorption through arachnoid villi requires further evidence. In this paper, the authors analyze the published results to date of dural venous sinus stenting in patients with IIH. They also present a case from their institution for illustration. The pathophysiological mechanism in IIH requires further elucidation, but venous sinus stenosis with subsequent intracranial hypertension appears to be an important mechanism in at least a subgroup of patients with IIH. Among these patients, 78% had complete relief or improvement of their main presenting symptoms after endovascular stenting. Resolution or improvement in papilledema was seen in 85.1% of patients. Endovascular stenting should be considered whenever venous sinus stenosis is diagnosed in patients with IIH.","subset":"pubmed_abstract"} +{"meta":{"pmid":29062247,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies.\nSusceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases. Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12\/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests. A diagnosis of mycobacterial infection was made clinically in a total of 25 patients including five (11.3%) of 45 patients who had severe combined immune deficiency, 12 (52.3%) of 21 patients who had chronic granulomatous disease, four patients (100%) who had interferon gamma receptor 2 partical deficiency, two patients (100%) who had interleukin 12 receptor beta 1 deficiency and one patient (100%) who had nuclear factor kapa-beta essential modulator deficiency. Mycobacterium strain could be typed in 14 (33%) of these 25 patients including Mycobacterium bovis, Mycobacterium chelonea, Mycobacterium elephantis, Mycobacterium fortuitum, and Mycobacterium tuberculosis. All patients were treated with anti-tuberculosis therapy. Thirty-six percent of these 25 patients underwent hematopoietic stem cell transplantation. Eight patients (five before, three after transplantation) died. Non-tuberculosis mycobacteria including mainly Mycobacterium bovis were observed with a higher rate compared to Mycobacterium tuberculosis in primary immunodeficiencies, especially in those affecting the interleukin 12\/interferon gamma pathway. Early diagnosis of primary immunodeficiencies with neonatal screening program and preventing administration of the Bacille Calmette-Guerin vaccine in these patients is important.","subset":"pubmed_abstract"} +{"meta":{"pmid":32857942,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2023-50":1,"2024-22":1}}},"text":"Approximate Target Pre-Cueing Reduces Programming Quiet Eye and Movement Preparation Time: Evidence for Parameter Pre-Programming?\nPurpose: We examined the effect of target pre-cues on quiet eye duration (QED). If quiet eye (QE) represents the initial and only period for the programming of movement parameters, then the precision of target pre-cues should not affect QED. In contrast, shorter QED after pre-cueing of targets implies some initial programming process to have occurred before QE. Method: Sixteen participants threw darts at targets projected onto a soft screen. We manipulated the precision of target pre-cues by highlighting an area within which the target would appear. These pre-cued areas were either the full screen (i.e., no cue), any half, quarter, or sixteenth of the screen. Participants threw eight times in each condition. Dependent measures included QED (programming and online segments), movement preparation time (MPT; from target presentation to initiation of movement), and radial error (cm). Results: Analysis revealed that programming QE was shorter when the target was pre-cued in the most precise sixteenth condition, compared to the no cue condition. Also, MPT was shorter when pre-cued in the sixteenth condition than in either the no cue or half screen conditions. Target pre-cueing conditions did not affect the other dependent variables. Conclusions: Shorter PQE following the most precise target pre-cueing implies that some pre-programming occurred before QE, perhaps through inhibition, but only when the pre-cue was specific enough to make pre-programming possible.","subset":"pubmed_abstract"} +{"meta":{"pmid":22339033,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":2,"2015-06":1,"unknown":7}}},"text":"Effect of low dosages of powdered activated carbon on membrane bioreactor performance.\nPrevious research has demonstrated that powdered activated carbon (PAC), when applied at very low dosages and long SRTs, reduces membrane fouling in membrane bioreactors (MBRs). This effect was related to the formation of stronger sludge flocs, which are less sensitive to shear. In this contribution the long-term effect of PAC addition was studied by running two parallel MBRs on sewage. To one of these, PAC was dosed and a lower fouling tendency of the sludge was verified, with a 70% longer sustainable filtration time. Low PAC dosages showed additional advantages with regard to oxygen transfer and dewaterability, which may provide savings on operational costs.","subset":"pubmed_abstract"} +{"meta":{"pmid":22021671,"dup_signals":{"dup_doc_count":59,"dup_dump_count":21,"dup_details":{"curated_sources":2,"2018-26":1,"2017-47":2,"2017-43":2,"2017-39":3,"2017-34":2,"2017-30":2,"2017-26":1,"2017-22":2,"2017-17":5,"2017-09":1,"2017-04":1,"2016-44":1,"2016-40":3,"2016-36":3,"2016-30":6,"2016-22":4,"2016-18":6,"2016-07":6,"2015-35":1,"2018-47":1,"2017-13":4}}},"text":"Wolbachia enhance Drosophila stem cell proliferation and target the germline stem cell niche.\nWolbachia are widespread maternally transmitted intracellular bacteria that infect most insect species and are able to alter the reproduction of innumerous hosts. The cellular bases of these alterations remain largely unknown. Here, we report that Drosophila mauritiana infected with a native Wolbachia wMau strain produces about four times more eggs than the noninfected counterpart. Wolbachia infection leads to an increase in the mitotic activity of germline stem cells (GSCs), as well as a decrease in programmed cell death in the germarium. Our results suggest that up-regulation of GSC division is mediated by a tropism of Wolbachia for the GSC niche, the cellular microenvironment that supports GSCs.","subset":"pubmed_abstract"} +{"meta":{"pmid":24195103,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":8}}},"text":"Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles.\nNanoparticle properties, such as small size relative to large highly modifiable surface area, offer great promise for neuro-therapeutics and nanodiagnostics. A fundamental understanding and control of how nanoparticles interact with the blood-brain barrier (BBB) could enable major developments in nanomedical treatment of previously intractable neurological disorders, and help ensure that nanoparticles not intended to reach the brain do not cause adverse effects. Nanosafety is of utmost importance to this field. However, a distinct lack of knowledge exists regarding nanoparticle accumulation within the BBB and the biological effects this may induce on neighbouring cells of the Central Nervous System (CNS), particularly in the long-term. This study focussed on the exposure of an in vitro BBB model to model carboxylated polystyrene nanoparticles (PS COOH NPs), as these nanoparticles are well characterised for in vitro experimentation and have been reported as non-toxic in many biological settings. TEM imaging showed accumulation but not degradation of 100 nm PS COOH NPs within the lysosomes of the in vitro BBB over time. Cytokine secretion analysis from the in vitro BBB post 24 h 100 nm PS COOH NP exposure showed a low level of pro-inflammatory RANTES protein secretion compared to control. In contrast, 24 h exposure of the in vitro BBB endothelium to 100 nm PS COOH NPs in the presence of underlying astrocytes caused a significant increase in pro-survival signalling. In conclusion, the tantalising possibilities of nanomedicine must be balanced by cautious studies into the possible long-term toxicity caused by accumulation of known 'toxic' and 'non-toxic' nanoparticles, as general toxicity assays may be disguising significant signalling regulation during long-term accumulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":18981805,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Diagnosis, treatment, and prevention of cerebral palsy.\nCerebral palsy is the most prevalent cause of persisting motor function impairment with a frequency of about 1\/500 births. In developed countries, the prevalence rose after introduction of neonatal intensive care, but in the past decade, this trend has reversed. A recent international workshop defined cerebral palsy as \"a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain.\" In a majority of cases, the predominant motor abnormality is spasticity; other forms of cerebral palsy include dyskinetic (dystonia or choreo-athetosis) and ataxic cerebral palsy. In preterm infants, about one-half of the cases have neuroimaging abnormalities, such as echolucency in the periventricular white matter or ventricular enlargement on cranial ultrasound. Among children born at or near term, about two-thirds have neuroimaging abnormalities, including focal infarction, brain malformations, and periventricular leukomalacia. In addition to the motor impairment, individuals with cerebral palsy may have sensory impairments, cognitive impairment, and epilepsy. Ambulation status, intelligence quotient, quality of speech, and hand function together are predictive of employment status. Mortality risk increases incrementally with increasing number of impairments, including intellectual, limb function, hearing, and vision. The care of individuals with cerebral palsy should include the provision of a primary care medical home for care coordination and support; diagnostic evaluations to identify brain abnormalities, severity of neurologic and functional abnormalities, and associated impairments; management of spasticity; and care for associated problems such as nutritional deficiencies, pain, dental care, bowel and bladder continence, and orthopedic complications. Current strategies to decrease the risk of cerebral palsy include interventions to prolong pregnancy (eg, 17alpha-progesterone), limiting the number of multiple gestations related to assisted reproductive technology, antenatal steroids for mothers expected to deliver prematurely, caffeine for extremely low birth weight neonates, and induced hypothermia for a subgroup of neonates diagnosed with hypoxic-ischemic encephalopathy.","subset":"pubmed_abstract"} +{"meta":{"pmid":12190897,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":12}}},"text":"Effects of rotary instruments and ultrasonic irrigation on debris and smear layer scores: a scanning electron microscopic study.\nThis study evaluated debris and smear layer scores after two types of instruments manufactured from different alloys were used to ultrasonically activate irrigants during canal preparation. The influence of two rotary preparation techniques on cleanliness of the shaped canals was also studied. Apical stops were prepared to size 45 in 42 single-canalled extracted premolars and canines, which were divided into six equal groups. Groups 1, 2 and 3 were prepared by ProFile.04 (PF) while groups 4, 5 and 6 were prepared by Lightspeed (LS). All groups were irrigated using 5.25% NaOCl and 17% EDTA. Irrigants in groups 2 and 5 were ultrasonically activated using a size 15 steel K-file and by a blunt flexible nickel-titanium wire in groups 3 and 6. Groups 1 and 4 served as negative controls. Roots were split and canal walls examined at 15x, 200x and 400x magnification in an SEM. Smear layer and debris scores were recorded at 3, 6 and 9 mm levels using a 5-step scoring scale and a 200- micro m grid. Means were tested for significance using nonparametric Mann-Whitney U and Kruskal-Wallis tests. Debris and smear layer scores for the six groups varied from 1.98 +\/- 1.04 to 3.47 +\/- 0.97 and from 1.37 +\/- 0.4 to 2.36 +\/- 0.99, respectively. Although all groups had significantly higher smear layer and debris scores at the 3 mm levels compared to the 9 mm levels (P < 0.05), no significant differences were recorded due to the ultrasonic energy transmitted by the two alloys. Ultrasonically activated irrigants did not reduce debris or smear layer scores. This finding was not influenced by the material nor by the design of the instrument used to transmit ultrasonic activation.","subset":"pubmed_abstract"} +{"meta":{"pmid":25492129,"dup_signals":{"dup_doc_count":11}},"text":"Management of a caseous lymphadenitis outbreak in a new Iberian ibex (Capra pyrenaica) stock reservoir.\nIn 2010, an Iberian ibex (Capra pyrenaica hispanica) stock reservoir was established for conservation purposes in north-eastern Spain. Eighteen ibexes were captured in the wild and housed in a 17 hectare enclosure. Once in captivity, a caseous lymphadenitis (CLA) outbreak occurred and ibex handlings were carried out at six-month intervals between 2010 and 2013 to perform health examinations and sampling. Treatment with a bacterin-based autovaccine and penicillin G benzatine was added during the third and subsequent handlings, when infection by Corynebacterium pseudotuberculosis was confirmed. Changes in lesion score, serum anti-C. pseudotuberculosis antibodies and haematological parameters were analyzed to assess captivity effects, disease emergence and treatment efficacy. Serum acute phase proteins (APP) Haptoglobin (Hp), Amyloid A (SAA) and Acid Soluble Glycoprotein (ASG) concentrations were also determined to evaluate their usefulness as indicators of clinical status. Once in captivity, 12 out of 14 ibexes (85.7%) seroconverted, preceding the emergence of clinical signs; moreover, TP, WBC, eosinophil and platelet cell counts increased while monocyte and basophil cell counts decreased. After treatment, casualties and fistulas disappeared and both packed cell volume (PCV) and haemoglobin concentration significantly increased. Hp, SAA and ASG values were under the limit of detection or showed no significant differences. A role for captivity in contagion rate is suggested by the increase in antibody levels against C. pseudotuberculosis and the emergence of clinical signs. Although boosted by captivity, this is the first report of an outbreak of caseous lymphadenitis displaying high morbidity and mortality in wild ungulates. Treatment consisting of both vaccination and antibiotic therapy seemed to prevent mortality and alleviate disease severity, but was not reflected in the humoural response. Haematology and APP were not useful indicators in our study, perhaps due to the sampling frequency. Presumably endemic and irrelevant in the wild, this common disease of domestic small ruminants is complicating conservation efforts for the Iberian ibex in north-eastern Spain.","subset":"pubmed_abstract"} +{"meta":{"pmid":31808828,"dup_signals":{"dup_doc_count":38,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2023-40":3,"2023-23":5,"2023-14":2,"2022-49":1,"2022-27":1,"2022-21":2,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":2,"2021-04":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-10":2,"2024-30":2,"2024-22":1,"2024-18":2,"2024-10":2}}},"text":"Patient blood management as the standard of care.\nBlood transfusion is one of the most common hospital procedures in developed countries. However, inappropriate use of blood transfusion is common, and this is of considerable concern because transfusion is known to be associated with adverse events and is costly. Reductions in blood use have resulted from recent evidence indicating that restrictive use of red blood cell transfusions is associated with similar patient outcomes to liberal strategies and from a focus on patient blood management (PBM), which recognizes the importance of conserving the patient's own blood alongside the judicious use of transfusion. A recent Consensus Conference in Frankfurt developed practice and research recommendations for PBM but also indicated that additional studies are needed to provide better evidence for PBM interventions, including for improved patient outcomes and lower hospital costs as well as for reductions in blood utilization. In the meanwhile, it is of utmost importance to translate PBM guidelines into practical day-to-day recommendations and encourage their use to make PBM \"the standard of care.\"","subset":"pubmed_abstract"} +{"meta":{"pmid":27192671,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Danazol Treatment for Telomere Diseases.\nGenetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).","subset":"pubmed_abstract"} +{"meta":{"pmid":15532695,"dup_signals":{"dup_doc_count":12,"dup_dump_count":11,"dup_details":{"curated_sources":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-34":1,"2018-22":1,"2018-09":1,"2020-24":1}}},"text":"Homeopathic proving symptoms: result of a local, non-local, or placebo process? A blinded, placebo-controlled pilot study.\nHomeopathic pathogenetic trials (HPTs) (provings) are the pillar of homeopathy. Symptoms experienced by healthy volunteers are used to find the correct medicine for therapy. It is unclear whether these symptoms are specific or due to placebo noise. Furthermore, it is uncertain whether proving effects, if present at all, are due to a local or non-local process To develop a test model which allows for testing if homeopathic proving symptoms are caused by placebo or causative mechanisms, and if these symptoms are due to local or non-local processes. Randomised, blinded, placebo-controlled, parallel-group study, with 1-week baseline and 2-weeks proving period. 11 healthy volunteers from two different homeopathic schools. PROVING SUBSTANCE: An homeopathic medicine (Cantharis 30c), blindly chosen from 12 potential medicines, compared to placebo. Number of symptoms typical for the medicine in the experimental and control group during baseline and proving period. During baseline there was no difference in the number of typical or atypical symptoms in either group. During the proving period, both more typical symptoms for Cantharis (P= 0.03) and more atypical symptoms (P= 0.02) were observed compared to baseline. Between-group differences were not significant. Effect sizes for the difference between the proving and control group for typical symptoms was d=0.4, and for atypical symptoms d=0.6. This proving model could be valuable in studying the validity of proving symptoms of homeopathic substances in healthy volunteers. Homeopathic proving symptoms appear to be specific to the medicine and do not seem to be due to a local process. Since this was a pilot study using a small number of provers, rival hypotheses cannot be ruled out and the study needs replication.","subset":"pubmed_abstract"} +{"meta":{"pmid":28990192,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Nonaqueous capillary electrophoresis mass spectrometry method for determining highly hydrophobic peptides.\nA nonaqueous capillary electrophoresis mass spectrometry (NACE-MS) method was developed to separate and determine highly hydrophobic temporin peptides. The nonaqueous background electrolyte solution was a mixture of 20% acetonitrile, 78% methanol and 2% formic acid, with 20 mM ammonium formate. The separation of six peptides was completed within 12 min. The CE system was connected to a triple quadrupole mass spectrometer operating in MRM mode using a chemical modifier solution of 2 mM ammonium formate in ethanol with the flow through microvial interface. The mass spectrometer offered a second dimension of separation for peptides having identical migration times but different structures. The new method represents the first system capable of reliably determining hydrophobic peptides without using reversed phase liquid chromatography mass spectrometry.","subset":"pubmed_abstract"} +{"meta":{"pmid":30986265,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":2,"unknown":7}}},"text":"Acute inflammation is associated with lower muscle strength, muscle mass and functional dependency in male hospitalised older patients.\nHospitalisation is associated with adverse health outcomes including loss of muscle strength, muscle mass and functional decline, which might be further aggravated by acute inflammation. This study aimed to determine whether acute inflammation, as denoted by C-reactive protein (CRP), is associated with muscle strength, muscle mass and functional dependency in hospitalised older patients. The observational, prospective EMPOWER study included 378 hospitalised patients aged 70 years and older. As part of the hospital assessment, 191 patients (50.5%) had CRP measured. Muscle strength and mass were measured using handheld dynamometry and bioelectrical impedance analysis respectively. Activities of Daily Living (ADL) were assessed using Katz score and Instrumental ADL (IADL) by Lawton and Brody score. Linear regression analyses and logistic regression analyses were performed stratified by sex and adjusted for age and comorbidities. Mean age was 79.7 years (SD 6.4) and 50.8% were males. On admission and discharge, males with elevated CRP had significantly lower handgrip strength and lower absolute muscle mass compared with males with normal CRP and those with no CRP measured. At three months post-discharge, males with elevated CRP were more likely to be ADL dependent than those with normal CRP and with no CRP measured. In females, no associations were found between CRP and muscle strength, muscle mass, ADL or IADL. Hospitalised older male patients with acute inflammation had lower muscle strength at admission and discharge and lower absolute muscle mass at admission and higher ADL dependency at three months post-discharge.","subset":"pubmed_abstract"} +{"meta":{"pmid":33106376,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":10}}},"text":"The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.\nThe three-orphan nuclear receptor 4A genes are induced by diverse stressors and stimuli, and there is increasing evidence that NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor1) play an important role in maintaining cellular homeostasis and in pathophysiology. In blood-derived tumors (leukemias and lymphomas), NR4A expression is low and NR4A1-\/-\/NR4A3-\/- double knockout mice rapidly develop acute myelocytic leukemia, suggesting that these receptors exhibit tumor suppressor activity. Treatment of leukemia and most lymphoma cells with drugs that induce expression of NR4A1and NR4A3 enhances apoptosis, and this represents a potential clinical application for treating this disease. In contrast, most solid tumor-derived cell lines express high levels of NR4A1 and NR4A2, and both receptors exhibit pro-oncogenic activities in solid tumors, whereas NR4A3 exhibits tumor-specific activities. Initial studies with retinoids and apoptosis-inducing agents demonstrated that their cytotoxic activity is NR4A1 dependent and involved drug-induced nuclear export of NR4A1 and formation of a mitochondrial proapoptotic NR4A1-bcl-2 complex. Drug-induced nuclear export of NR4A1 has been reported for many agents\/biologics and involves interactions with multiple mitochondrial and extramitochondrial factors to induce apoptosis. Synthetic ligands for NR4A1, NR4A2, and NR4A3 have been identified, and among these compounds, bis-indole derived (CDIM) NR4A1 ligands primarily act on nuclear NR4A1 to inhibit NR4A1-regulated pro-oncogenic pathways\/genes and similar results have been observed for CDIMs that bind NR4A2. Based on results of laboratory animal studies development of NR4A inducers (blood-derived cancers) and NR4A1\/NR4A2 antagonists (solid tumors) may be promising for cancer therapy and also for enhancing immune surveillance.","subset":"pubmed_abstract"} +{"meta":{"pmid":22336283,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":1,"2023-06":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":2,"2019-22":1,"2019-13":1,"2019-04":1,"2018-34":1,"2018-17":1,"2018-05":1,"2017-39":1,"2017-34":1,"2023-40":1}}},"text":"An exploratory study to assess the activity of the acarine growth inhibitor, fluazuron, against Sarcoptes scabei infestation in pigs.\nThe most common treatments for scabies in human and veterinary settings are topical 5% permethrin or systemic treatment with ivermectin. However, these treatments have very little activity against arthropod eggs, and therefore repeated treatment is frequently required. In-vitro, biochemical and molecular studies have demonstrated that human mites are becoming increasingly resistant to both acaricides. To identify alternate acaricides, we undertook a pilot study of the in vivo activity of the benzoylphenyl urea inhibitor of chitin synthesis, fluazuron, in pigs with sarcoptic mange. Pigs (n = 5) were infested with S. scabei var suis, and randomised to treatment at the start of peak infestation with fluazuron at a dose of 10 mg\/kg\/day per os for 7 days (n = 3) or no treatment (n = 2). Clinical scores, skin scrapings for mite counts and blood sampling for pharmacokinetic analysis were undertaken. Fluazuron was well absorbed in treated pigs with measureable blood levels up to 4 weeks post treatment. No adverse effects were observed. Modest acaricidal activity of the compound was observed, with a reduction in severity of skin lesions in treated pigs, as well as a reduction in number of scabies mite's early life stages. The moderate efficacy of fluazuron against scabies mites indicates a lead to the development of alternate treatments for scabies, such as combination therapies that maybe applicable for human use in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":7620873,"dup_signals":{"dup_doc_count":16,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2019-13":1,"2019-04":1,"2018-47":1,"2018-43":1,"2018-34":2,"2018-22":2,"2018-09":2,"2023-14":1,"2024-18":1}}},"text":"Comparative distribution of 2[125I]iodomelatonin binding in the brains of diurnal birds: outgroup analysis with turtles.\nThe roles that the pineal gland and its hormone melatonin play in the regulation of circadian rhythmicity and photoperiodism vary among vertebrate species. Recently, putative sites of melatonin action have been elucidated in several avian and mammalian species by application of in vitro binding of a radioiodinated melatonin agonist, 2[125I]iodomelatonin (IMEL) and autoradioradiography. These studies in mammals, birds and reptiles have indicated profound differences in the distribution of IMEL binding between these diverse groups, suggesting that these large differences in binding may reflect differences in melatonin function. The present study was performed to determine systematically whether the variance in IMEL binding among avian species corresponds to changes in circadian organization and\/or phylogenetic relationships. The distribution of specific IMEL binding was determined in the brains from birds belonging to 14 different species in 5 Orders (Psittaciformes, Passeriformes, Columbiformes, Galliformes and Anseriformes) using in vitro binding, autoradiography and computer-assisted image analysis. The distribution was compared to a similar study in 3 species of turtles as an outgroup. The data indicated IMEL binding in retinorecipient structures of the circadian, tectofugal, thalamofugal and accessory optic visual pathways in all avian species. Relay nuclei and integrative structures of the tectofugal, thalamofugal, accessory optic, and limbic systems, however, bound the hormone to varying degrees. In turtles, binding was observed in retinorecipient structures of the thalamofugal visual pathway and in retinorecipient and integrative areas of the tectofugal visual pathway. No binding was observed in the pineal gland, tuberal hypothalamus or adenohypophysis in any avian or testudine species. This distribution is drastically different from that observed in mammals, where binding predominates in the pars tuberalis of the adenohypophysis and in the suprachiasmatic nucleus, suggesting that the circadian system may influence a wide array of sensory and integrative functions in birds and reptiles through the circadian secretion of melatonin, but that this capacity has been lost in mammals.","subset":"pubmed_abstract"} +{"meta":{"pmid":28012663,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":15}}},"text":"Knemometry is more sensitive to systemic effects of inhaled corticosteroids in children with asthma than 24-hour urine cortisol excretion.\nPharmacodynamic assessment of the systemic effect of inhaled corticosteroids (ICSs) is often done by measuring 24-hour urine free cortisol (UFC) excretion. Knemometry assessing short-term lower-leg growth rate (LLGR) is a more rarely used alternative. The primary aim of this study was to compare the sensitivity of LLGR and 24-hour UFC excretion for evaluating systemic exposure to ICSs in prepubertal children with asthma. The secondary aim was to evaluate factors influencing the precision of LLGR calculated by the traditional 1 leg nonparametric method versus a new 2 leg parametric method. The study evaluated 60 children with mild asthma aged 5 to 12 years participating in a randomized controlled trial of ICSs with longitudinal concomitant assessments of LLGR and 24-hour UFC excretion. The sensitivity of the safety assessments was analyzed by comparing LLGR and 24-hour UFC in the placebo run-in period with values in the ICS treatment period by using paired t tests. Factors with a potential influence on LLGR were analyzed by means of ANOVA and the Levene test of homogeneity. The mean LLGR was significantly reduced during the ICS versus placebo run-in periods: 0.18 mm\/wk (SD, 0.55 mm\/wk) versus 0.45 mm\/wk (SD, 0.39 mm\/wk), with a mean difference of 0.27 mm\/wk (95% CI, 0.05-0.48 mm\/wk; P = .02). In contrast, there was no difference in 24-hour UFC excretion: 6.91 nmol\/mmol (SD, 4.67 nmol\/mmol) versus 7.58 nmol\/mmol (SD, 6.17 nmol\/mmol), with a mean difference of 0.67 nmol\/mmol (95% CI, -1.13 to 2.48 nmol\/mmol; P = .46). We observed no significant difference in parametric determined LLGR caused by the child's age or sex, investigator, or season of measurement, whereas some differences were observed for the nonparametric LLGR. These findings suggest that knemometry is a more sensitive pharmacodynamic measure of systemic effects of ICSs than 24-hour UFC excretion and that a parametric determination of LLGR increases the sensitivity of the method. These findings should be considered by legislative authorities in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":24129644,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"The development of highly active acyclic chiral hydrazides for asymmetric iminium ion organocatalysis.\nDouble asymmetric induction has been employed as a tool to optimise pyrazolidinone-derived organocatalysts for the asymmetric iminium ion catalysed Diels-Alder reaction. Mechanistic studies revealed a superior hydrazide catalyst deriving from methanolysis of the chiral pyrazolidinone precursor. This catalyst displays unusually high endo diastereoselectivity and good enantioselectivity with a range of \u03b2-arylenals and cyclic dienes at catalyst loadings as low as 1 mol%.","subset":"pubmed_abstract"} +{"meta":{"pmid":16847293,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-40":1,"2022-21":1,"2021-04":2,"2020-45":2,"2020-34":1,"2020-29":1,"2023-50":1,"2024-22":1}}},"text":"The association between quality of care and the intensity of diabetes disease management programs.\nAlthough disease management programs are widely implemented, little is known about their effectiveness. To determine whether disease management by physician groups is associated with diabetes care processes, control of intermediate outcomes, or the amount of medication used when intermediate outcomes are above target levels. Cross-sectional study. Patients were randomly sampled from 63 physician groups nested in 7 health plans sponsored by Translating Research into Action for Diabetes (87%) and from 4 health plans with individual physician contracts (13%). 8661 adults with diabetes who completed a survey (2000-2001) and had medical record data. Physician group and health plan directors described their organizations' use of physician reminders, performance feedback, and structured care management on a survey; their responses were used to determine measures of intensity of disease management. The current study measured 8 processes of care, including most recent hemoglobin A1c level, systolic blood pressure, serum low-density lipoprotein cholesterol level, and several measures of medication use. Increased use of any of 3 disease management strategies was significantly associated with higher adjusted rates of retinal screening, nephropathy screening, foot examinations, and measurement of hemoglobin A1c levels. Serum lipid level testing and influenza vaccine administration were associated with greater use of structured care management and performance feedback. Greater use of performance feedback correlated with an increased rate of foot examinations (difference, 5 percentage points [95% CI, 1 to 8 percentage points]), and greater use of physician reminders was associated with an increased rate of nephropathy screening (difference, 15 percentage points [CI, 6 to 23 percentage points]). No strategies were associated with intermediate outcome levels or level of medication management. Physician groups were not randomly sampled from population-based listings, and disease management strategies were not randomly allocated across groups. Disease management strategies were associated with better processes of diabetes care but not with improved intermediate outcomes or level of medication management. A greater focus on direct measurement, feedback, and reporting of intermediate outcome levels or of level of medication management may enhance the effectiveness of these programs.","subset":"pubmed_abstract"} +{"meta":{"pmid":19379012,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"Probing the structure and charge state of glutathione-capped Au25(SG)18 clusters by NMR and mass spectrometry.\nDespite the recent crystallographic determination of the crystal structure of Au(25)(SCH(2)CH(2)Ph)(18) clusters, the question--whether all thiolate-capped, 25-atom gold clusters adopt the same structure, regardless of the types of thiols (e.g., long-chain alkylthiols, aromatic thiols, or other functionalized ones)--still remains unanswered. To crystallize long-chain or bulky ligand (e.g., glutathione)-capped Au(25)(SR)(18) clusters has proven to be difficult due to the major amorphousness caused by such ligands; therefore, one needs to seek other strategies to probe the structural information of such gold clusters. Herein, we report a strategy to probe the Au(25) core structure and surface thiolate ligand distribution by means of NMR in combination with mass spectrometry. We use glutathione-capped Au(25)(SG)(18) clusters as an example to demonstrate the utility of this strategy. One-dimensional (1D) and two-dimensional (2D) correlation NMR spectroscopic investigation of Au(25)(SG)(18) reveals fine spectral features that explicitly indicate two types of surface binding modes of thiolates, which is consistent with the ligand distribution in the Au(25)(SCH(2)CH(2)Ph)(18) cluster. Laser desorption ionization (LDI) mass spectrometry analysis shows that Au(25)(SG)(18) exhibits an identical ionization and core fragmentation pattern with phenylethylthiolate-capped Au(25) clusters. The charge state of the native Au(25)(SG)(18) clusters was determined to be -1 by comparing their optical spectrum with those of [Au(25)(SCH(2)CH(2)Ph)(18)](q) of different charge states (q = -1, 0). Taken together, our results led to the conclusion that glutathione-capped Au(25)(SG)(18) clusters indeed adopt the same structure as that of Au(25)(SCH(2)CH(2)Ph)(18). This conclusion is also valid for other types of thiolate-capped Au(25) clusters, including hexyl- and dodecylthiolates. Interestingly, the chiral optical responses (e.g., circular dichroism (CD) signals in the visible wavelength region) from the Au(25)(SG)(18) clusters seem to be imparted by the chiral glutathione ligands because no similar CD signals were observed in Au(25)(SCH(2)CH(2)Ph)(18).","subset":"pubmed_abstract"} +{"meta":{"pmid":17262158,"dup_signals":{"dup_doc_count":20,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2013-20":2,"2017-13":1,"unknown":12}}},"text":"Head and neck reconstruction using infrahyoid myocutaneous flaps.\nThe use of pedicled myocutaneous flaps in head and neck reconstruction is widely accepted. Here we describe our experience with infrahyoid flaps (IHFs) employed to cover surgical defects in the oral cavity and oropharynx in patients with benign and malignant tumors. The aim was to evaluate the success rate for infrahyoid myocutaneous flap procedures performed at a single institution. Retrospective study, at the Head and Neck Surgery Service, Unicamp. Fourteen IHFs were used to reconstruct surgical defects in eleven men (78.5%) and three women (21.5%) with a mean age of 66.4 years. The anterior floor of the mouth was reconstructed in nine patients (64.2%), the base of tongue in three (21.4%), the lateral floor in one (7.1%), and the retromolar area (7.1%) in one. Thirteen patients (92.8%) had squamous cell carcinoma (SCC) and one (7.2%) ameloblastoma. The disease stage was T3 in eight (61.5%) of the SCC cases and T4 in five (38.5%). No patient presented total flap loss or fistula. The most common complication was epidermolysis, which delayed the beginning of oral ingestion. The patients with SCC received postoperative radiotherapy without major consequences to the flap. IHF is a safe and reliable procedure for reconstructing head and neck surgical defects. Due to its thinness and malleability, its use for oral cavity and oropharynx defects provides favorable cosmetic and functional outcomes. Complications, when present, are easy to manage.","subset":"pubmed_abstract"} +{"meta":{"pmid":16118602,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A cost-effectiveness analysis of interventions to increase repeat testing in patients treated for gonorrhea or chlamydia at public sexually transmitted disease clinics.\nPersons who have been infected with chlamydia or gonorrhea (CT\/GC) are at elevated risk for reinfection. The cost-effectiveness of interventions designed to encourage public sexually transmitted disease (STD) clinic patients to return for rescreening has not been well-evaluated. The goal of this study was to conduct a program- and societal-perspective cost-effectiveness analysis of five interventions designed to encourage public STD clinic patients infected with CT\/GC to return for rescreening 3 months after initial treatment. Researchers at two STD clinics collected cost data for the five interventions. These were combined with study data on return rates and CT\/GC positivity rates among returning patients to compare the cost-effectiveness of the interventions. The cost per patient counseled with a brief recommendation to return, followed by a telephone reminder after 3 months, was higher than two interventions: a brief recommendation to return with no reminder and a $20 incentive, received on return. However, the brief recommendation with a telephone reminder yielded the highest return rate (33%) and was the least costly in terms of cost per infection treated ($622 program, $813 societal). In-depth motivational counseling that helped clients identify risk factors and provided reasons for returning was more costly than a phone reminder alone and was not more effective. Phone reminders are more cost-effective than motivational counseling and improve return rates over a brief recommendation given at the time of initial treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":33094810,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":3,"2024-18":2,"2024-26":1,"unknown":7}}},"text":"Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study.\nChronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and\/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race\/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":33183357,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-23":2,"2023-14":1,"2023-06":2,"2022-40":1,"2022-21":1,"2022-05":2,"2021-49":1,"2021-39":1,"2021-25":1,"2024-22":2,"2024-18":1}}},"text":"Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study.\nPlasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE \u03b54 allele, comorbidities, brain amyloid-\u03b2 (A\u03b2) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE \u03b54 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of A\u03b2 deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.","subset":"pubmed_abstract"} +{"meta":{"pmid":28622419,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B.\nWhether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long-term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir\/tenofovir (ETV\/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10-center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV\/TDF for \u22651 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median, 6.8) years. HCCs have been diagnosed in 101\/1,951 (5.2%) patients within the first 5 years and 17\/1,205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV\/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness \u226512 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender-Hepatitis B score at baseline or year 5 developed HCC. The HCC risk decreases beyond year 5 of ETV\/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially \u226550 years), lower platelets, and liver stiffness \u226512 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444-1453).","subset":"pubmed_abstract"} +{"meta":{"pmid":16685844,"dup_signals":{"dup_doc_count":12}},"text":"A Hamilton-Jacobi-Bellman approach to high angular resolution diffusion tractography.\nThis paper describes a new framework for white matter tractography in high angular resolution diffusion data. A direction-dependent local cost is defined based on the diffusion data for every direction on the unit sphere. Minimum cost curves are determined by solving the Hamilton-Jacobi-Bellman using an efficient algorithm. Classical costs based on the diffusion tensor field can be seen as a special case. While the minimum cost (or equivalently the travel time of a particle moving along the curve) and the anisotropic front propagation frameworks are related, front speed is related to particle speed through a Legendre transformation which can severely impact anisotropy information for front propagation techniques. Implementation details and results on high angular diffusion data show that this method can successfully take advantage of the increased angular resolution in high b-value diffusion weighted data despite lower signal to noise ratio.","subset":"pubmed_abstract"} +{"meta":{"pmid":19052025,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Comparison of delayed enhancement patterns on multislice computed tomography immediately after coronary angiography and cardiac magnetic resonance imaging in acute myocardial infarction.\nRecent experimental and limited clinical studies have demonstrated the usefulness of delayed enhancement multislice computed tomography (MSCT) for assessing myocardial infarct size (IS) and transmurality. The aim of this study is to compare MSCT enhancement patterns immediately after coronary angiography (CAG) in an acute myocardial infarction (AMI) setting with cardiac magnetic resonance (CMR) enhancement during the second week follow-up. 26 patients admitted for an AMI were evaluated by MSCT immediately after CAG without iodine re-injection. All but three were reperfused. The same patients had delayed enhancement CMR imaging at 10 (SD 4)-day follow-up. Myocardial enhancement was considered transmural (non-viable) when involving >75% of myocardial thickness, subendocardial (1 - < or =75%) or normal (viable for the two latter). Two or more >75% enhanced segments were required to define transmurality on patient-level or culprit artery-level analysis. A semi-quantitative scale score was defined for the 17 left ventricular segments. IS was computed from these scores. On segment analysis, sensitivity, specificity, accuracy, positive and negative predictive values of MSCT for transmurality assessment were 84%, 96%, 94%, 85% and 96%, respectively, compared to CMR. On patient analysis, these respective values were 90%, 80%, 88%, 95% and 67%. IS assessed by the two methods were highly correlated (r = 0.94, p<0.0001) and the regression line did not statistically differ from the identity line. MSCT enhancement immediately following CAG without iodine re-injection for an AMI is a reliable method for evaluating transmurality and IS. This very early evaluation could be an interesting alternative to CMR.","subset":"pubmed_abstract"} +{"meta":{"pmid":26448759,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Correlative Light and Electron Microscopy Reveals the HAS3-Induced Dorsal Plasma Membrane Ruffles.\nHyaluronan is a linear sugar polymer synthesized by three isoforms of hyaluronan synthases (HAS1, 2, and 3) that forms a hydrated scaffold around cells and is an essential component of the extracellular matrix. The morphological changes of cells induced by active hyaluronan synthesis are well recognized but not studied in detail with high resolution before. We have previously found that overexpression of HAS3 induces growth of long plasma membrane protrusions that act as platforms for hyaluronan synthesis. The study of these thin and fragile protrusions is challenging, and they are difficult to preserve by fixation unless they are adherent to the substrate. Thus their structure and regulation are still partly unclear despite careful imaging with different microscopic methods in several cell types. In this study, correlative light and electron microscopy (CLEM) was utilized to correlate the GFP-HAS3 signal and the surface ultrastructure of cells in order to study in detail the morphological changes induced by HAS3 overexpression. Surprisingly, this method revealed that GFP-HAS3 not only localizes to ruffles but in fact induces dorsal ruffle formation. Dorsal ruffles regulate diverse cellular functions, such as motility, regulation of glucose metabolism, spreading, adhesion, and matrix degradation, the same functions driven by active hyaluronan synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":29021478,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":9}}},"text":"Rhabdomyolysis in a Patient with Polyarteritis Nodosa.\nPolyarteritis nodosa (PAN) is a medium vessel vasculitis affecting systemic organs. Muscle involvement of PAN usually lacks elevation of creatinine kinase (CK). We herein report a case of PAN with rhabdomyolysis. A 71-year-old man was hospitalized because of muscle weakness of the lower limbs that persisted for 1 month. On a physical examination, rapidly progressive lower proximal muscle weakness and bilateral drop foot were observed. His blood test showed an elevation in the C-reactive protein (19.5 mg\/dL) and CK (13,435 IU\/L) levels and negativity for anti-neutrophilic cytoplasmic antibody. Computed tomographic angiography showed stenosis of the left renal artery. Electromyogram indicated mono-neuritis multiplex pattern, and enhanced magnetic resonance imaging demonstrated discretely granular hyperintensities on T2 and slow tau inversion recovery in his femoral muscles. A femoral muscle-biopsy specimen showed fibrinoid necrosis of medium-sized vessels and disruption of the elastic lamina of the vessel wall in fascia. Furthermore, muscle necrosis was localized depending on the arterial distribution, suggesting ischemic changes in the muscles. Given these findings, he was diagnosed with PAN with rhabdomyolysis and treated with methyl-prednisolone pulse therapy followed by oral prednisolone at 50 mg\/day. He was additionally treated with monthly intravenous cyclophosphamide at 500 mg. Sustained remission has been obtained for two months since the treatment. Although rhabdomyolysis rarely manifests with PAN, it should be included in a differential diagnosis of febrile patients presenting with acute myalgia and weakness with CK elevation.","subset":"pubmed_abstract"} +{"meta":{"pmid":11851091,"dup_signals":{"dup_doc_count":15,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":3,"2013-48":2,"2013-20":1,"unknown":2}}},"text":"Reliability and validity of measures from the Behavioral Risk Factor Surveillance System (BRFSS).\nTo assess the reliability and validity of measures on the BRFSS, to assist users in evaluating the quality of BRFSS data, and to identify areas for further research. Review and summary of reliability and validity studies of measures on the BRFSS and studies of measures that were the same or similar to those on the BRFSS from other surveys. Measures determined to be of high reliability and high validity were current smoker, blood pressure screening, height, weight, and BMI, and several demographic characteristics. Measures of both moderate reliability and validity included when last mammography was received, clinical breast exam, sedentary lifestyle, intense leisure-time physical activity, and fruit and vegetable consumption. Few measures were of low validity and only one measure was determined to be of low reliability. Several other measures were of high or moderate reliability or validity, but not both. The reliability or validity could not be determined for some measures, primarily due to lack of research. Most questions on the core BRFSS instrument were at least moderately reliable and valid, and many were highly reliable and valid. Additional research is needed for some measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":28006927,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":11}}},"text":"The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors.\nMonoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC. Based on their mechanism of action, these agents can exert toxicities that are unlike conventional cytotoxic chemotherapy, whose nature is close to autoimmune diseases - immune related adverse events (irAEs). In this review we focus on the spectrum of irAEs associated with immune checkpoint antibodies, discussing the pharmacological treatment strategy and possible clinical impact.","subset":"pubmed_abstract"} +{"meta":{"pmid":18209115,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":7}}},"text":"Internet-delivered interventions aimed at adolescents: a Delphi study on dissemination and exposure.\nIt appears that in practice exposure to Internet-delivered behaviour change interventions, encouraging a healthy lifestyle for adolescents with regard to health risk behaviours, is quite low. There is, however, a lack of evidence-based insight into how to disseminate such interventions and how to reach optimal exposure. A more extensive exploration is therefore timely since this knowledge is crucial to improve the public health impact of such interventions. By means of a three-round Delphi study factors associated with dissemination of and exposure (first visit, stay long enough and revisit) to Internet-delivered interventions aimed at adolescents had been identified, as well as the extent to which experts agree on the importance of these factors. Results showed that there was a high rate of consensus among experts from several disciplines with regard to the importance of factors like word of mouth recommendation, the interface of the intervention and utilization of all features provided by the Internet. Experts do not agree, however, on a gold standard for successful dissemination. Overall, the results of this exploration serve as a handle for the formation of further research questions to be tested and answered in research among adolescents.","subset":"pubmed_abstract"} +{"meta":{"pmid":8625823,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2022-33":1,"2022-05":1,"2021-49":1,"2021-25":1,"2021-04":3,"2020-40":1,"2020-24":1,"2019-43":1,"2019-35":1,"2019-26":1,"2018-17":1,"2017-47":1,"2016-40":1,"2023-23":1,"2024-22":1}}},"text":"A group of genes required for maintenance of the amnioserosa tissue in Drosophila.\nThe amnioserosa is an extraembryonic, epithelial tissue that covers the dorsal side of the Drosophila embryo. The initial development of the amnioserosa is controlled by the dorsoventral patterning genes. Here we show that a group of genes, which we refer to as the U-shaped-group (ush-group), is required for maintenance of the amnioserosa tissue once it has differentiated. Using several molecular markers, we examined amnioserosa development in the ush-group mutants: u-shaped (ush), hindsight (hnt), serpent (srp) and tail-up (tup). Our results show that the amnioserosa in these mutants is specified correctly and begins to differentiate as in wild type. However, following germ-band extension, there is a premature loss of the amnioserosa. We demonstrate that this cell loss is a consequence of programmed cell death (apoptosis) in ush, hnt and srp, but not in tup. We discuss the role of the ush-group genes in maintaining the amnioserosa's viability. We also discuss a possible role for the amnioserosa in germ-band retraction in light of these mutants' unretracted phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":25568332,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Treatment of subclinical hyperthyroidism: effect on left ventricular mass and function of the heart using magnetic resonance imaging technique.\nThe aim of this study was to investigate structure and function of the heart in subclinical hyperthyroidism (SH) before and after obtaining euthyroidism by radioactive iodine treatment, using high precision and observer-independent magnetic resonance imaging (MRI) technology. Cardiac MRI was performed before and after euthyroidism was obtained by radioactive iodine treatment in 12 otherwise healthy patients (11 women and one man, mean age 59 years, range 44-71 years) with a nodular goiter and SH, and compared with eight healthy controls investigated at baseline. Cardiac data were expressed as an index, as per body surface area, except for heart rate (HR) and ejection fraction. Post-treatment cardiac MRI was performed in median 139 days after a normalized serum TSH value had been recorded. During treatment, serum TSH increased from (median (range)) 0.01 (0.01-0.09) to 0.88 (0.27-3.99) mU\/l. Patients with untreated SH had increased resting HR (P<0.01) as well as cardiac index (cardiac output as per body surface area) (P<0.01) compared with controls. Obtaining euthyroidism resulted in a significant decrease in left ventricular mass index (LVMI) of 2.7 g\/m(2) (P=0.034), in HR of 8 bpm (P=0.001), and in cardiac index of 0.24 l\/min per m(2) (P=0.017). Normalization of thyroid function by radioactive iodine treatment of SH resulted in significant reductions in clinically important heart parameters such as LVMI, HR, and cardiac index. SH should be regarded as a condition in which aggressive treatment should be considered to protect cardiac function.","subset":"pubmed_abstract"} +{"meta":{"pmid":30670444,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":12}}},"text":"The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes.\nIn cancer biology, tumor-promoting inflammation and an inflammatory microenvironment play a vital role in disease pathogenesis. In the past decade, aberrant innate immune activation and proinflammatory signaling within the malignant clone and the bone marrow (BM) microenvironment were identified as key pathogenic drivers of myelodysplastic syndromes (MDS). In particular, S100A9-mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation directs an inflammatory, lytic form of cell death termed pyroptosis that underlies many of the hallmark features of the disease. This circuit and accompanying release of other danger-associated molecular patterns expands BM myeloid-derived suppressor cells, creating a feed-forward process propagating inflammasome activation. Furthermore, somatic gene mutations of varied functional classes license the NLRP3 inflammasome to generate a common phenotype with excess reactive oxygen species generation, Wnt\/\u03b2-catenin-induced proliferation, cation flux-induced cell swelling, and caspase-1 activation. Recent investigations have shown that activation of the NLRP3 inflammasome complex has more broad-reaching importance, particularly as a possible disease-specific biomarker for MDS, and, mechanistically, as a driver of cardiovascular morbidity\/mortality in individuals with age-related, clonal hematopoiesis. Recognition of the mechanistic role of aberrant innate immune activation in MDS provides a new perspective for therapeutic development that could usher in a novel class of disease-modifying agents.","subset":"pubmed_abstract"} +{"meta":{"pmid":17947343,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":1,"2017-13":1,"2024-22":1,"unknown":8}}},"text":"The vascular system as a target of metal toxicity.\nVascular system function involves complex interactions among the vascular endothelium, smooth muscle, the immune system, and the nervous system. The toxic metals cadmium (Cd), arsenic (As), and lead (Pb) can target the vascular system in a variety of ways, ranging from hemorrhagic injury to subtle pathogenic remodeling and metabolic changes. Acute Cd exposure results in hemorrhagic injury to the testis, although some strains of animals are resistant to this effect. A comparison of Cd-sensitive with Cd-resistant mouse strains showed that expression of the Slc39a8 gene, encoding the ZIP8 transporter, in the testis vasculature endothelium is responsible for this difference. Endogenously, ZIP8 is a Mn(2+)\/HCO(3)(-)symporter that may also contribute to Cd damage in the kidney. Chronic Cd exposure is associated with various cardiovascular disorders such as hypertension and cardiomyopathy and it is reported to have both carcinogenic and anticarcinogenic activities. At noncytotoxic concentrations of 10-100nM, Cd can inhibit chemotaxis and tube formation of vascular endothelial cells. These angiostatic effects may be mediated through disruption of vascular endothelial cadherin, a Ca(2+)-dependent cell adhesion molecule. With regard to As, ingestion of water containing disease-promoting concentrations of As promotes capillarization of the liver sinusoidal endothelium. Because capillarization is a hallmark precursor for liver fibrosis and contributes to an imbalance of lipid metabolism, this As effect on hepatic endothelial cells may be a pathogenic mechanism underlying As-related vascular diseases. With regard to Pb, perinatal exposure may cause sustained elevations in adult blood pressure, and genetically susceptible animals may show enhanced sensitivity to this effect. Taken together, these data indicate that the vascular system is a critical target of metal toxicity and that actions of metals on the vascular system may play important roles in mediating the pathophysiologic effects of metals in specific target organs.","subset":"pubmed_abstract"} +{"meta":{"pmid":30463249,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"New Hope in Brain Glioma Surgery: The Role of Intraoperative Ultrasound. A Review.\nMaximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":23024621,"dup_signals":{"dup_doc_count":18,"dup_dump_count":7,"dup_details":{"curated_sources":1,"2015-18":2,"2015-11":2,"2015-06":2,"2014-10":3,"2013-48":2,"2013-20":1,"2017-13":1,"unknown":4}}},"text":"Locking and Non-locking Constructs Achieve Similar Radiographic and Clinical Outcomes for Internal Fixation of Intra-articular Distal Humerus Fractures.\nLocking plates have been used increasingly for the management of distal humerus fractures. Studies that compare patient-centered outcomes between locking and non-locking fixation for distal humerus fractures are lacking. The purposes of this study were to (1) determine whether locking plates offered superior fixation compared with non-locking plates for distal humerus fractures, (2) determine whether the use of locking plates was associated with fewer complications, and (3) determine whether locking plate use resulted in superior radiographic outcome compared with non-locking plates. Lastly, another aim was to determine the average cost difference associated with locking plate use versus non-locking plate use for distal humerus fracture fixation. Demographic, clinical, and radiographic data including loss of fixation, range of motion, rate of infection, nonunion and reoperation, as well as measures of fixation were collected retrospectively and compared on 96 patients with surgically treated AO type 13C distal humerus fractures (65 locking, 31 non-locking) at 6-week and 6-month follow-up. Average costs of locking and non-locking constructs were calculated and compared. Three in 96 (3.1%) of all cases experienced loss of fixation, with no difference between the two groups. There was no difference between locking and non-locking groups with regard to the rate of nonunion, infection, and reoperation at 6 weeks and 6 months. On average, locking plate constructs were 348% more expensive than non-locking constructs. While there are some significant differences in radiographic parameters and cost between locking and non-locking constructs for internal fixation of intra-articular distal humerus fractures, there were no statistically significant differences in clinical outcome.","subset":"pubmed_abstract"} +{"meta":{"pmid":24748851,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Molecular and Phenetic Characterization of the Bacterial Assemblage of Hot Lake, WA, an Environment with High Concentrations of Magnesium Sulfate, and Its Relevance to Mars.\nHot Lake (Oroville, WA) is an athalassohaline epsomite lake that can have precipitating concentrations of MgSO4 salts, mainly epsomite. Little biotic study has been done on epsomite lakes and it was unclear whether microbes isolated from epsomite lakes and their margins would fall within recognized halotolerant genera, common soil genera, or novel phyla. Our initial study cultivated and characterized epsotolerant bacteria from the lake and its margins. Approximately 100 aerobic heterotrophic microbial isolates were obtained by repetitive streak-plating in high-salt media including either 10% NaCl or 2 M MgSO4. The collected isolates were all bacteria, nearly evenly divided between Gram-positive and Gram-negative clades, the most abundant genera being Halomonas, Idiomarina, Marinobacter, Marinococcus, Nesterenkonia, Nocardiopsis, and Planococcus. Bacillus, Corynebacterium, Exiguobacterium, Kocuria, and Staphylococcus also were cultured. This initial study included culture-independent community analysis of direct DNA extracts of lake margin soil using PCR-based clone libraries and 16S rRNA gene phylogeny. Clones assigned Gram-positive bacterial clades (70% of total clones) were dominated by sequences related to uncultured actinobacteria. There were abundant Deltaproteobacteria clones related to bacterial sulfur metabolisms and clones of Legionella and Coxiella. These epsomite lake microbial communities seem to be divided between bacteria primarily associated with hyperhaline environments rich in NaCl and salinotolerant relatives of common soil organisms. Archaea appear to be in low abundance and none were isolated, despite near-saturated salinities. Growth of microbes at very high concentrations of magnesium and other sulfates has relevance to planetary protection and life-detection missions to Mars, where scant liquid water may form as deliquescent brines and appear as eutectic liquids.","subset":"pubmed_abstract"} +{"meta":{"pmid":27249836,"dup_signals":{"dup_doc_count":12}},"text":"An Insect Eye Inspired Miniaturized Multi-Camera System for Endoscopic Imaging.\nIn this work, we present a miniaturized high definition vision system inspired by insect eyes, with a distributed illumination method, which can work in dark environments for proximity imaging applications such as endoscopy. Our approach is based on modeling biological systems with off-the-shelf miniaturized cameras combined with digital circuit design for real time image processing. We built a 5 mm radius hemispherical compound eye, imaging a 180\u00b0\u00d7180\u00b0 degrees field of view while providing more than 1.1 megapixels (emulated ommatidias) as real-time video with an inter-ommatidial angle \u2206\u03d5 = 0.5\u00b0 at 18 mm radial distance. We made an FPGA implementation of the image processing system which is capable of generating 25 fps video with 1080 \u00d7 1080 pixel resolution at a 120 MHz processing clock frequency. When compared to similar size insect eye mimicking systems in literature, the system proposed in this paper features 1000 \u00d7 resolution increase. To the best of our knowledge, this is the first time that a compound eye with built-in illumination idea is reported. We are offering our miniaturized imaging system for endoscopic applications like colonoscopy or laparoscopic surgery where there is a need for large field of view high definition imagery. For that purpose we tested our system inside a human colon model. We also present the resulting images and videos from the human colon model in this paper.","subset":"pubmed_abstract"} +{"meta":{"pmid":29518339,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":7}}},"text":"High-Pressure Limit Rate Rules for \u03b1-H Isomerization of Hydroperoxyalkylperoxy Radicals.\nHydroperoxyalkylperoxy (OOQOOH) radical isomerization is an important low-temperature chain branching reaction within the mechanism of hydrocarbon oxidation. This isomerization may proceed via the migration of the \u03b1-hydrogen to the hydroperoxide group. In this work, a combination of high level composite methods-CBS-QB3, G3, and G4-is used to determine the high-pressure-limit rate parameters for the title reaction. Rate rules for H-migration reactions proceeding through 5-, 6-, 7-, and 8-membered ring transitions states are determined. Migrations from primary, secondary and tertiary carbon sites to the peroxy group are considered. Chirality is also investigated by considering two diastereomers for reactants and transition states with two chiral centers. This is important since chirality may influence the energy barrier of the reaction as well as the rotational energy barriers of hindered rotors in chemical species and transition states. The effect of chirality and hydrogen bonding interactions in the investigated energies and rate constants is studied. The results show that while the energy difference between two diastereomers ranges from 0.1-3.2 kcal\/mol, chirality hardly affects the kinetics, except at low temperatures (atmospheric conditions) or when two chiral centers are present in the reactant. Regarding the effect of the H-migration ring size, it is found that in most cases, the 1,5 and 1,6 H-migration reactions have similar rates at low temperatures (below \u223c830 K) since the 1,6 H-migration proceeds via a cyclohexane-like transition state similar to that of the 1,5 H-migration.","subset":"pubmed_abstract"} +{"meta":{"pmid":30241751,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.\nMeasurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%\/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%\/2 mm global analysis for institution 1, whilst for institution 2 it was 3%\/3 mm global analysis. The majority of errors (58\/59 for institution 1, 54\/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.","subset":"pubmed_abstract"} +{"meta":{"pmid":34371907,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Effect of Coffee and Cocoa-Based Confectionery Containing Coffee on Markers of DNA Damage and Lipid Peroxidation Products: Results from a Human Intervention Study.\nThe effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee\/day (1C), three cups of espresso coffee\/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2'-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":2826642,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A derivative of amiloride blocks both the light-regulated and cyclic GMP-regulated conductances in rod photoreceptors.\nVertebrate rod photoreceptors in the dark maintain an inward current across the outer segment membrane. The photoresponse results from a light-induced suppression of this dark current. The light-regulated current is not sensitive to either tetrodotoxin or amiloride, potent blockers of Na+ channels. Here, we report that a derivative of amiloride, 3',4'-dichlorobenzamil (DCPA), completely suppresses the dark current and light response recorded from rod photoreceptors. DCPA also blocks a cyclic GMP-activated current in excised patches of rod plasma membrane and a cGMP-induced Ca++ flux from rod disk membranes. These results are consistent with the notion that the Ca++ flux mechanism in the disk membrane and the light-regulated conductance in the plasma membrane are identical. DCPA also inhibits the Na\/Ca exchange mechanism in intact rods, but at a 5-10-fold-higher concentration than is required to block the cGMP-activated flux and current. The blocking action of DCPA in 10 nM Ca++ is different from that in 1 mM Ca++, which suggests either that the conductance state of the light-regulated channel may be modified in high and low concentrations of Ca++, or that there may be two ionic channels in the rod outer segment membrane.","subset":"pubmed_abstract"} +{"meta":{"pmid":30612490,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"2024-10":2,"unknown":8}}},"text":"CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation.\nMyocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1\/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 \u00b5g\/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1-treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1\/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF.","subset":"pubmed_abstract"} +{"meta":{"pmid":19593474,"dup_signals":{"dup_doc_count":33,"dup_dump_count":29,"dup_details":{"curated_sources":3,"2022-05":1,"2019-43":1,"2019-30":1,"2019-13":1,"2018-09":1,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":1,"2014-41":1,"2014-35":1,"2014-23":2,"2014-15":1,"2022-49":1}}},"text":"Strategies for efficient disruption of metabolism in Mycobacterium tuberculosis from network analysis.\nTuberculosis continues to be a major health challenge, warranting the need for newer strategies for therapeutic intervention and newer approaches to discover them. Here, we report the identification of efficient metabolism disruption strategies by analysis of a reactome network. Protein-protein dependencies at a genome scale are derived from the curated metabolic network, from which insights into the nature and extent of inter-protein and inter-pathway dependencies have been obtained. A functional distance matrix and a subsequent nearness index derived from this information, helps in understanding how the influence of a given protein can pervade to the metabolic network. Thus, the nearness index can be viewed as a metabolic disruptability index, which suggests possible strategies for achieving maximal metabolic disruption by inhibition of the least number of proteins. A greedy approach has been used to identify the most influential singleton, and its combination with the other most pervasive proteins to obtain highly influential pairs, triplets and quadruplets. The effect of deletion of these combinations on cellular metabolism has been studied by flux balance analysis. An obvious outcome of this study is a rational identification of drug targets, to efficiently bring down mycobacterial metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":9001744,"dup_signals":{"dup_doc_count":16,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-18":1,"2014-10":2,"2013-48":2,"2013-20":2,"2024-22":1,"unknown":6}}},"text":"Capacity to consent to voluntary hospitalization: searching for a satisfactory Zinermon screen.\nHalf a decade ago, the Zinermon court announced the need for clinicians to evaluate the competence of people with mental illness to consent to voluntary hospital admission, but the court did not specify the test of capacity that mental health professionals should use. As has occurred in other areas dealing with legal competence, there is a need for the field to develop standardized assessment procedures for evaluating capacity to consent to voluntary hospitalization. Both theoretical and practical considerations suggest that these procedures should be modeled after what S. K. Hoge has termed a \"weak\" model of consent. This and other studies of the ability of mentally ill persons to understand disclosed information suggest that their level of understanding may be assessed optimally with measures that utilize recognition rather than recall response elicitation formats.","subset":"pubmed_abstract"} +{"meta":{"pmid":26867270,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Knowledge and perception on tuberculosis transmission in Tanzania: Multinomial logistic regression analysis of secondary data.\nTuberculosis (TB) is one of the most important public health problems in Tanzania and was declared as a national public health emergency in 2006. Community and individual knowledge and perceptions are critical factors in the control of the disease. The objective of this study was to analyze the knowledge and perception on the transmission of TB in Tanzania. Multinomial Logistic Regression analysis was considered in order to quantify the impact of knowledge and perception on TB. The data used was adopted as secondary data from larger national survey 2007-08 Tanzania HIV\/AIDS and Malaria Indicator Survey. The findings across groups revealed that knowledge on TB transmission increased with an increase in age and level of education. People in rural areas had less knowledge regarding tuberculosis transmission compared to urban areas [OR = 0.7]. People with the access to radio [OR = 1.7] were more knowledgeable on tuberculosis transmission compared to those who did not have access to radio. People who did not have telephone [OR = 0.6] were less knowledgeable on tuberculosis route of transmission compared to those who had telephone. The findings showed that socio-demographic factors such as age, education, place of residence and owning telephone or radio varied systematically with knowledge on tuberculosis transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":29316908,"dup_signals":{"dup_doc_count":11}},"text":"Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study.\nThe aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed\u00ae) and its combination with boswellic acid extract from Indian frankincense root (Curamin\u00ae) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). The effects of CuraMed\u00ae 500-mg capsules (333 mg curcuminoids) and Curamin\u00ae 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients' global assessment of disease severity. Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin\u00ae compared to placebo was observed both in physical performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin\u00ae group. The treatments were well tolerated. Twelve-week use of curcumin complex or its combination with boswellic acid reduces pain-related symptoms in patients with OA. Curcumin in combination with boswellic acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin\u00ae increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and boswellic acid. This trial is registered at the database www.clinicaltrials.gov . https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02390349?term=EuroPharma&rank=1 . Study registration number: NCT02390349 .","subset":"pubmed_abstract"} +{"meta":{"pmid":29369813,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":3,"2024-10":1,"unknown":4}}},"text":"Yoga versus physical exercise for cardio-respiratory fitness in adolescent school children: a randomized controlled trial.\nBackground Yoga is very effective in improving health especially cardio-respiratory fitness and also overall performance in adolescents. There are no large numbers of randomized controlled studies conducted on comparing yoga with physical activity for cardio-respiratory fitness in adolescent school children with large sample size. Objective Aerobic training is known to improve physical and cardio-respiratory fitness in children. Cardio-respiratory fitness is an important indicator of health in children. In this study we evaluate the effects of yoga versus physical exercise training on cardio-respiratory fitness in adolescent school children. Subjects Eight hundred two school students from 10 schools across four districts were recruited for this study. Methods In this prospective two arm RCT around 802 students were randomized to receive daily one hour yoga training (n = 411) or physical exercise (n = 391) over a period of two months. VO2 max was estimated using 20 m shuttle run test. However, yoga (n = 377) and physical exercise (n = 371) students contributed data to the analyses. Data was analysed using students t test. Results There was a significant improvement in VO2 max using 20 m Shuttle run test in both yoga (p < 0.001) and exercise (p < 0.001) group following intervention. There was no significant change in VO2 max between yoga and physical exercise group following intervention. However, in the subgroup with an above median cut-off of VO2 max; there was a significant improvement in yoga group compared to control group following intervention (p = 0.03). Conclusion The results suggest yoga can improve cardio-respiratory fitness and aerobic capacity as physical exercise intervention in adolescent school children.","subset":"pubmed_abstract"} +{"meta":{"pmid":28817722,"dup_signals":{"dup_doc_count":25,"dup_dump_count":17,"dup_details":{"curated_sources":4,"2022-49":1,"2022-33":1,"2021-49":2,"2021-39":1,"2020-40":1,"2020-34":1,"2020-29":1,"2019-43":2,"2019-30":1,"2019-22":3,"2019-04":1,"2018-47":1,"2018-39":1,"2018-17":1,"2017-47":1,"2017-39":1,"2023-06":1}}},"text":"Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations.\nVitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD). Thus, this study aimed to investigate the potential of nicotinamide to promote the conversion of stem cells to mature CNS neurons. Nicotinamide was applied to differentiating mouse embryonic stem cells (mESC; Sox1GFP knock-in 46C cell line) during their conversion towards a neural fate. Cells were assessed for changes in their proliferation, differentiation and maturation; using immunocytochemistry and morphometric analysis methods. Results presented indicate that 10 mM nicotinamide, when added at the initial stages of differentiation, promoted accelerated progression of ESCs to a neural lineage in adherent monolayer cultures. By 14 days in vitro (DIV), early exposure to nicotinamide was shown to increase the numbers of differentiated \u03b2III-tubulin-positive neurons. Nicotinamide decreased the proportion of pluripotent stem cells, concomitantly increasing numbers of neural progenitors at 4 DIV. These progenitors then underwent rapid conversion to neurons, observed by a reduction in Sox 1 expression and decreased numbers of neural progenitors in the cultures at 14 DIV. Furthermore, GABAergic neurons generated in the presence of nicotinamide showed increased maturity and complexity of neurites at 14 DIV. Therefore, addition of nicotinamide alone caused an accelerated passage of pluripotent cells through lineage specification and further to non-dividing mature neurons. Our results show that, within an optimal dose range, nicotinamide is able to singly and selectively direct the conversion of embryonic stem cells to mature neurons, and therefore may be a critical factor for normal brain development, thus supporting previous evidence of the fundamental role of vitamins and their metabolites during early CNS development. In addition, nicotinamide may offer a simple effective supplement to enhance the conversion of stem cells to clinically relevant neurons.","subset":"pubmed_abstract"} +{"meta":{"pmid":20042178,"dup_signals":{"dup_doc_count":11}},"text":"Mycophenolate mofetil for ocular inflammation.\nTo evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases. Retrospective cohort study. Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each. Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation--sustained over consecutive visits spanning at least 28 days--was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy. Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.","subset":"pubmed_abstract"} +{"meta":{"pmid":28656534,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Relationship between subjective and actigraphy-measured sleep in 237 patients with metastatic colorectal cancer.\nPatients with cancers frequently experience sleep and circadian dysfunction. To date, only a few studies have used both a questionnaire and actigraphy for concomitant evaluation of sleep and circadian function in patients with cancer. We sought to evaluate objective sleep and circadian parameters in metastatic colon cancer (MCC) patients and their associations with symptoms and quality of life (QOL). Patients reported subjective sleep problems on the EORTC QLQ-C30. Sleep and circadian parameters were calculated using a wrist-actigraph that patients wore for 72 h. 237 Patients with MCC (mean age: 60.4 years; range: 20.7-77.6; Male\/Female ratio: 1.66) participated in this cross-sectional study. Subjective sleep problems were reported by 63.4% of patients (S+). No differences in any sleep parameters (sleep efficiency, sleep latency, total sleep time, total time in bed, wake after sleep onset, activity bathyphase) were observed between S+ and S- patients. However, S+ patients displayed a significantly worse circadian function than S- patients (96.4 vs 98.1%; p = 0.005). The presence of poor subjective sleep and objective circadian dysfunction negatively affected symptoms and QOL domains (p = 0.038). Subjective report of sleep problems was not associated with worse objectively measured sleep parameters in patients with MCC although it was associated with disrupted circadian rest-activity rhythm and poorer QOL. These findings coincide with prior research in cancer patients in that an inconsistent relationship exists between subjective and objective sleep measurements on some sleep domains. This study supports the value of coupled evaluation of self-reported and objective measures of sleep and circadian function in cancer patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":19668273,"dup_signals":{"dup_doc_count":26,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2017-39":1,"2016-44":3,"2016-36":4,"2016-30":3,"2015-48":3,"2015-35":2,"2015-22":2,"2023-23":1,"2024-18":2,"2024-22":1}}},"text":"Robust three-dimensional best-path phase-unwrapping algorithm that avoids singularity loops.\nIn this paper we propose a novel hybrid three-dimensional phase-unwrapping algorithm, which we refer to here as the three-dimensional best-path avoiding singularity loops (3DBPASL) algorithm. This algorithm combines the advantages and avoids the drawbacks of two well-known 3D phase-unwrapping algorithms, namely, the 3D phase-unwrapping noise-immune technique and the 3D phase-unwrapping best-path technique. The hybrid technique presented here is more robust than its predecessors since it not only follows a discrete unwrapping path depending on a 3D quality map, but it also avoids any singularity loops that may occur in the unwrapping path. Simulation and experimental results have shown that the proposed algorithm outperforms its parent techniques in terms of reliability and robustness.","subset":"pubmed_abstract"} +{"meta":{"pmid":22258115,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Questionnaire study of the association between patient numbers and regular visiting by general practitioners in care homes.\nregular visiting in care homes enables proactive care. Surveys of managers found variation in medical care yet little is known about factors influencing general practitioners (GPs) visiting patterns. We examined whether practice factors including numbers of registered patients are associated with regular visiting. postal questionnaires sent to 73 care homes of European Care Group and separate questionnaires to visiting practices. information on regularity of visiting was requested from homes and practices. Practices were asked for numbers of doctors and training status. As data were not normally distributed, non-parametric tests were used to compare practices regularly visiting with those visiting only on request in terms of numbers of registered care home patients. forty-seven (64%) of homes responded, with care provided for 1,867 patients by 162 practices. Practices visiting regularly had significantly more patients than practices that did not [median (IQR) 32 (28) versus 3 (5), P < 0.001]. Ninety-five (31%) of practices responded showing a similar association of registrations with regular visiting [median (IQR) 20 (37) versus 4 (4), P < 0.001]. There was no association between numbers of doctors or training status on regular visiting. the number of registered patients is strongly associated with regular care home visiting. Aligning practices with care homes thereby increasing registered patients per practice could encourage proactive care.","subset":"pubmed_abstract"} +{"meta":{"pmid":28681744,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":14}}},"text":"Levodopa dose maintenance or reduction in patients with Parkinson's disease transitioning to levodopa\/carbidopa\/entacapone.\nLevodopa bioavailability is enhanced by adding entacapone. However, the optimal dose of levodopa while transitioning to levodopa\/carbidopa\/entacapone (LCE) in Parkinson's disease (PD) during the wearing-off period is unclear. The relative therapeutic efficacy and safety of different doses of levodopa were assessed when transitioning to the LCE combination for optimizing combined levodopa therapy. A randomized, multicenter, double-arm, open-label study was conducted in Korea. The patients were randomly assigned to either a maintained levodopa dose (Group 1, n = 66) or a reduced levodopa dose by 15-25% (Group 2, n = 41). Treatment efficacy, safety, and tolerability were assessed during an 8-week treatment period. Eighty of the 107 (74.8%) participants completed the study (Group 1, n = 50; Group 2, n = 30). The patients' global impression of a change in scores indicated significant benefits of maintaining the levodopa dose (Group 1) compared to reducing the dose (Group 2). Although changes in the unified Parkinson's disease rating scale (UPDRS) scores, Hoehn and Yahr (H and Y) stages, and duration of ON, OFF and dyskinesia were not statistically different between the groups, an increased ON time and a reduced OFF time occurred in both the groups after LCE administration. Twenty-four participants (26.7%) experienced adverse events and 15 of them did not complete the study in the safety population (Group 1, n = 57; Group 2, n = 38). Significant drug-related withdrawal caused troublesome dyskinesia and aggravation of Parkinsonism in both Group 1 and Group 2, respectively. Direct transitioning to LCE, without levodopa dose reduction, is recommended in Asian patients with PD and wearing-off.","subset":"pubmed_abstract"} +{"meta":{"pmid":30846214,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":13}}},"text":"Blood Pressure Control and Cardiovascular Outcomes in Patients With Atrial Fibrillation (From the ORBIT-AF Registry).\nSystolic blood pressure (SBP) and its association with clinical outcomes in atrial fibrillation (AF) patients in community practice are poorly characterized. In patients with AF, we sought to (1) examine the prevalence of baseline uncontrolled hypertension and the overall change in SBP control, (2) identify predictors of uncontrolled SBP over 2 years of follow-up, and (3) determine the relation between SBP and clinical outcomes. We analyzed 10,132 patients with AF at 176 clinics in the ORBIT-AF registry between 2010 and 2014, classified as: (1) no history of hypertension; (2) controlled hypertension (baseline SBP <140 mm Hg); (3) and uncontrolled hypertension (baseline SBP >140 mm Hg). Predictors of SBP >140 mm Hg at baseline or in follow-up were identified with pooled logistic regression. Random effects Cox regression models were used to compare cardiovascular outcomes and major bleeding as a function of continuous, time-dependent SBP. Overall 8,383 (83%) of patients with AF had hypertension. Of these, 24.2% (n = 2032) had uncontrolled baseline SBP, with little change over 2 years. Predictors of elevated follow-up SBP included uncontrolled baseline SBP, females, previous percutaneous coronary intervention, and diabetes. For every 5 mm Hg increase in follow-up SBP, the adjusted risk of stroke or systemic embolism or transient ischemic attack (adjusted hazard ratio [aHR] 1.05, 95% confidence interval [CI] 1.01 to 1.08, p = 0.01), myocardial infarction (aHR 1.05, 95% CI 1.00 to 1.11, p = 0.04), and major bleeding (aHR 1.03, 95% CI 1.00 to 1.06, p = 0.04) increased modestly. In conclusion, in patients with AF, higher SBP was associated with increasing adverse events; therefore, more rigorous blood pressure control should be emphasized.","subset":"pubmed_abstract"} +{"meta":{"pmid":10934026,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development.\nMutation of sucker (suc) disrupts development of the lower jaw and other ventral cartilages in pharyngeal segments of the zebrafish head. Our sequencing, cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et-1). Like mouse and chick Et-1, suc\/et-1 is expressed in a central core of arch paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal endoderm, but not in skeletogenic neural crest. Long before chondrogenesis, suc\/et-1 mutant embryos have severe defects in ventral arch neural crest expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches. Dorsal expression patterns are unaffected. Later in development, suc\/et-1 mutant embryos display defects in mesodermal and endodermal tissues of the pharynx. Ventral premyogenic condensations fail to express myoD, which correlates with a ventral muscle defect. Further, expression of shh in endoderm of the first pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic analyses to show that suc\/et-1 functions nonautonomously in neural crest cells, and is thus required in the environment of postmigratory neural crest cells to specify ventral arch fates. Our mosaic analyses further show that suc\/et-1 nonautonomously functions in mesendoderm for ventral arch muscle formation. Collectively our results support a model for dorsoventral patterning of the gnathostome pharyngeal arches in which Et-1 in the environment of the postmigratory cranial neural crest specifies the lower jaw and other ventral arch fates.","subset":"pubmed_abstract"} +{"meta":{"pmid":11389679,"dup_signals":{"dup_doc_count":25,"dup_dump_count":21,"dup_details":{"curated_sources":3,"2020-45":1,"2019-43":1,"2018-17":1,"2018-05":2,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-35":1,"2023-14":1,"2017-13":1,"2024-22":1}}},"text":"Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta.\nThe feto-placental unit relies on a maternal supply of indispensable amino acids and iodothyronines for early development and normal growth. We examined the role of the System L transporter in placental uptake of these substances, using the human placental choriocarcinoma cell line BeWo as a model experimental system. BeWo cells express both heavy (4F2hc) and light (LAT1, LAT2) chains of the System L holotransporter. Saturable transport of both L-[(3)H]tryptophan and [(125)I]tri-iodo-L-thyronine in BeWo cells includes components sensitive to inhibition by the System-L-specific substrate 2-endoamino-bicycloheptane-2-carboxylic acid; kinetic properties of these components indicate that the 4F2hc-LAT1 transporter isoform is likely to predominate for the carriage of both substances at physiologically relevant concentrations. Both 4F2hc and LAT1 proteins are also expressed in human placental membranes and LAT1 at least is localized largely to the syncytiotrophoblast layer of the term human placenta. The 4F2hc-LAT1 transporter might therefore serve a vital role in supplying the developing fetus and the placenta with both thyroid hormones and indispensable amino acids from the maternal circulation.","subset":"pubmed_abstract"} +{"meta":{"pmid":27558943,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Estimating the cost-effectiveness of brief interventions for heavy drinking in primary health care across Europe.\nScreening and Brief Interventions for alcohol are an effective public health measure to tackle alcohol-related harm, however relatively few countries across the European Union (EU) have implemented them widely. This may be due to a lack of understanding of the specific financial implications of such policies within each country. A novel 'meta-modelling' approach was developed based on previous SBI cost-effectiveness models for four EU countries. Data were collected on the key factors which drive cost-effectiveness for all 28 EU countries (mean per capita alcohol consumption, proportion of the population to be screened over a 10-year SBI programme; per capita alcohol-attributable mortality; per capita alcohol-attributable morbidity; mean cost of an alcohol-related hospitalisation and mean SBI-delivery staff cost). Regression analysis was used to fit two meta-models estimating net programme costs and Quality-Adjusted Life Years (QALYs) gained, to calculate cost-effectiveness estimates specific to each EU country. Costs are dependent upon the proportion of the population covered by the screening programme, the country-specific per capita mortality and morbidity rate and the country-specific costs of GP care and hospitalisation. QALYs depend on the proportion of the population screened and per capita alcohol consumption. Despite large inter-country variability in factor values, SBI programmes are likely to be cost-effective in 24 out of 28 EU countries and cost-saving in 50% of countries. Implementing national programmes of SBI in primary health care would be a cost-effective means of reducing alcohol-attributable morbidity and deaths in almost all countries of the EU.","subset":"pubmed_abstract"} +{"meta":{"pmid":28413946,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":2,"unknown":21}}},"text":"Kinetics of Ligand Binding Through Advanced Computational Approaches: A Review.\nLigand residence times and binding rates have been found to be useful quantities to consider during drug design. The underlying structural and dynamic determinants of these kinetic quantities are difficult to discern. Driven by developments in computational hardware and simulation methodologies, molecular dynamics (MD) studies on full binding and unbinding pathways have emerged recently, showing these structural and dynamic determinants in atomic detail. However, the long timescales related to drug binding and release are still prohibitive to conventional MD simulation. Here we discuss a suite of enhanced sampling methods that have been applied to the study of full ligand binding or unbinding pathways, and reveal the kinetics of drug binding and\/or release. We divide these sampling methods into three families (trajectory parallelization, metadynamics, and temperature- based methods), and discuss recent applications of each, as well as their basic theoretical underpinnings including how kinetic information is extracted. We then present an outlook for how the field could evolve, and how the rich variety of sampling methods discussed here can be leveraged in the future for computationally driven drug design.","subset":"pubmed_abstract"} +{"meta":{"pmid":32613998,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Predicting coated-nanoparticle drug release systems with perturbation-theory machine learning (PTML) models.\nNanoparticles (NPs) decorated with coating agents (polymers, gels, proteins, etc.) form Nanoparticle Drug Delivery Systems (DDNS), which are of high interest in nanotechnology and biomaterials science. There have been increasing reports of experimental data sets of biological activity, toxicity, and delivery properties of DDNS. However, these data sets are still dispersed and not as large as the datasets of DDNS components (NP and drugs). This has prompted researchers to train Machine Learning (ML) algorithms that are able to design new DDNS based on the properties of their components. However, most ML models reported up to date predictions of the specific activities of NP or drugs over a determined target or cell line. In this paper, we combine Perturbation Theory and Machine Learning (PTML algorithm) to train a model that is able to predict the best components (NP, coating agent, and drug) for DDNS design. In so doing, we downloaded a dataset of >30 000 preclinical assays of drugs from ChEMBL. We also downloaded an NP data set formed by preclinical assays of coated Metal Oxide Nanoparticles (MONPs) from public sources. Both the drugs and NP datasets of preclinical assays cover multiple conditions of assays that can be listed as two arrays, namely, cjdrug and cjNP. The cjdrug array includes >504 biological activity parameters (c0drug), >340 target proteins (c1drug), >650 types of cells (c2drug), >120 assay organisms (c3drug), and >60 assay strains (c4drug). On the other hand, the cjNP array includes 3 biological activity parameters (c0NP), 40 types of proteins (c1NP), 10 shapes of nanoparticles (c2NP), 6 assay media (c3NP), and 12 coating agents (c4NP). After downloading, we pre-processed both the data sets by separate calculation PT operators that are able to account for changes (perturbations) in the drug, coating agents, and NP chemical structure and\/or physicochemical properties as well as for the assay conditions. Next, we carry out an information fusion process to form a final dataset of above 500 000 DDNS (drug + MONP pairs). We also trained other linear and non-linear PTML models using R studio scripts for comparative purposes. To the best of our knowledge, this is the first multi-label PTML model that is useful for the selection of drugs, coating agents, and metal or metal-oxide nanoparticles to be assembled in order to design new DDNS with optimal activity\/toxicity profiles.","subset":"pubmed_abstract"} +{"meta":{"pmid":29157924,"dup_signals":{"dup_doc_count":25,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-14":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-34":1,"2020-29":3,"2020-24":1,"2019-43":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2023-50":1,"2024-10":3,"2024-22":1}}},"text":"Instrumental variable methods for a binary outcome were used to informatively address noncompliance in a randomized trial in surgery.\nRandomization can be used as an instrumental variable (IV) to account for unmeasured confounding when seeking to assess the impact of noncompliance with treatment allocation in a randomized trial. We present and compare different methods to calculate the treatment effect on a binary outcome as a rate ratio in a randomized surgical trial. The effectiveness of peeling versus not peeling the internal limiting membrane of the retina as part of the surgery for a full thickness macular hole. We compared the IV-based estimates (nonparametric causal bound and two-stage residual inclusion approach [2SRI]) with standard treatment effect measures (intention to treat, per protocol and treatment received [TR]). Compliance was defined in two ways (initial and up to the time point of interest). Poisson regression was used for the model-based approaches with robust standard errors to calculate the risk ratio (RR) with 95% confidence intervals. Results were similar for 1-month macular hole status across methods. For 3- and 6-month macular hole status, nonparametric causal bounds provided a narrower range of uncertainty than other methods, though still had substantial imprecision. For 3-month macular hole status, the TR estimate was substantially different from the other point estimates. Nonparametric causal bound approaches are a useful addition to an IV estimation approach, which tend to have large levels of uncertainty. Methods which allow RRs to be calculated when addressing noncompliance in randomized trials exist and may be superior to standard estimates. Further research is needed to explore the properties of different IV methods in a broad range of randomized controlled trial scenarios.","subset":"pubmed_abstract"} +{"meta":{"pmid":21884984,"dup_signals":{"dup_doc_count":41,"dup_dump_count":28,"dup_details":{"curated_sources":2,"2023-40":2,"2023-14":1,"2023-06":1,"2022-40":3,"2022-33":2,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":2,"2021-17":3,"2021-10":1,"2021-04":1,"2020-45":2,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-13":1,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2015-18":1,"2024-18":1}}},"text":"Cross-regulation between an alternative splicing activator and a transcription repressor controls neurogenesis.\nNeurogenesis requires the concerted action of numerous genes that are regulated at multiple levels. However, how different layers of gene regulation are coordinated to promote neurogenesis is not well understood. We show that the neural-specific Ser\/Arg repeat-related protein of 100 kDa (nSR100\/SRRM4) negatively regulates REST (NRSF), a transcriptional repressor of genes required for neurogenesis. nSR100 directly promotes alternative splicing of REST transcripts to produce a REST isoform (REST4) with greatly reduced repressive activity, thereby activating expression of REST targets in neural cells. Conversely, REST directly represses nSR100 in nonneural cells to prevent the activation of neural-specific splicing events. Consistent with a critical role for nSR100 in the inhibition of REST activity, blocking nSR100 expression in the developing mouse brain impairs neurogenesis. Our results thus reveal a fundamental role for direct regulatory interactions between a splicing activator and transcription repressor in the control of the multilayered regulatory programs required for neurogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":27244483,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"A Method for Continuous (239)Pu Determinations in Arctic and Antarctic Ice Cores.\nAtmospheric nuclear weapons testing (NWT) resulted in the injection of plutonium (Pu) into the atmosphere and subsequent global deposition. We present a new method for continuous semiquantitative measurement of (239)Pu in ice cores, which was used to develop annual records of fallout from NWT in ten ice cores from Greenland and Antarctica. The (239)Pu was measured directly using an inductively coupled plasma-sector field mass spectrometer, thereby reducing analysis time and increasing depth-resolution with respect to previous methods. To validate this method, we compared our one year averaged results to published (239)Pu records and other records of NWT. The (239)Pu profiles from the Arctic ice cores reflected global trends in NWT and were in agreement with discrete Pu profiles from lower latitude ice cores. The (239)Pu measurements in the Antarctic ice cores tracked low latitude NWT, consistent with previously published discrete records from Antarctica. Advantages of the continuous (239)Pu measurement method are (1) reduced sample preparation and analysis time; (2) no requirement for additional ice samples for NWT fallout determinations; (3) measurements are exactly coregistered with all other chemical, elemental, isotopic, and gas measurements from the continuous analytical system; and (4) the long half-life means the (239)Pu record is stable through time.","subset":"pubmed_abstract"} +{"meta":{"pmid":26022304,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The Gut Microbiome of Wild Lemurs: A Comparison of Sympatric Lemur catta and Propithecus verreauxi.\nMammalian gut microbes are invaluable to the host's metabolism, but few researchers have examined gut microbial dynamics under natural conditions in wild mammals. This study aims to help fill this knowledge gap with a survey of the natural variation of the gut microbiome in 2 wild lemur species, Lemur catta and Propithecus verreauxi. The wild L. catta were also compared to a captive population to discern the effect of habitat within a species. Gut microbial DNA was extracted from fecal samples collected in Madagascar and the Vienna Zoo and sequenced. The wild and captive L. catta had distinct microbial communities, likely due to differences in diet and development between their populations. The wild L. catta and P. verreauxi also had distinct gut microbiomes, due to a change in microbial abundance, not composition. Within each lemur species, there was abundant variation between individuals and from the dry to the wet season. The intraspecific and temporal microbial variation requires more investigation, with changes in diet a likely contributor.","subset":"pubmed_abstract"} +{"meta":{"pmid":12463512,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Improved blood compatibility and decreased VSMC proliferation of surface-modified metal grafted with sulfonated PEG or heparin.\nAlthough the technique of coronary stenting has remarkably improved long-term results in recent years, (sub)acute thrombosis and late restenosis still remain problems to be solved. Metallic surfaces were regarded as thrombogenic, due to their positive surface charges, and stenosis resulted from the activation and proliferation of vascular smooth muscle cells (VSMCs). In this study, a unique surface modification method for metallic surfaces was studied using a self-assembled monolayer (SAM) technique. The method included the deposition of thin gold layers, the chemisorption of disulfides containing functional groups, and the subsequent coupling of PEG derivatives or heparin utilizing the functional groups of the disulfides. All the reactions were confirmed by ATR-FTIR and XPS. The surface modified with sulfonated PEG (Au-S-PEG-SO3) or heparinized PEG (Au-S-PEG-Hep) exhibited decreased static contact angles and therefore increased hydrophilicity to a great extent, which resulted from the coupling of PEG and the ionic groups attached. In vitro fibrinogen adsorption and platelet adhesion onto the Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces decreased to a great extent, indicating enhanced blood compatibility. This decreased interaction of the modified surfaces should be attributed to the non-adhesive property of PEG and the synergistic effect of sulfonated PEG. The effect of the surface modification on the adhesion and proliferation of VSMCs was also investigated. The modified Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces also exhibited decreased adhesion of VSMCs, while the deposited gold layer itself was effective. The enhanced blood compatibility and the decreased adhesion of VSMCs on the modified metallic surfaces may help to decrease thrombus formation and suppress restenosis. It would therefore be very useful to apply these modified surfaces to stents for improved functions. A long-term in vivo study using animal models is currently under way.","subset":"pubmed_abstract"} +{"meta":{"pmid":678046,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":3,"unknown":14}}},"text":"Primary affective disorder, aggression, and criminality. A review and clinical study.\nAggressive and criminal behavior among patients with manic and depressive conditions has been in need of greater delineation, particularly since the advent of current pharmacotherapies. This report reviews the literature on aggression and criminality among bipolar and unipolar patients and the nature and occurrence of these conditions among criminal and unprosecuted offender populations, and presents a study of 100 consecutive prisoners (89 women, 11 men) referred for psychiatric evaluation. It is hypothesized that manic and depressive states are underdiagnosed in prison populations, particularly among female prisoners. A comparatively high incidence (10%) of primary affective disorder was found in this study; possible causes of the hypothesized underdiagnosis are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":17855124,"dup_signals":{"dup_doc_count":11}},"text":"Markov random field based automatic image alignment for electron tomography.\nWe present a method for automatic full-precision alignment of the images in a tomographic tilt series. Full-precision automatic alignment of cryo electron microscopy images has remained a difficult challenge to date, due to the limited electron dose and low image contrast. These facts lead to poor signal to noise ratio (SNR) in the images, which causes automatic feature trackers to generate errors, even with high contrast gold particles as fiducial features. To enable fully automatic alignment for full-precision reconstructions, we frame the problem probabilistically as finding the most likely particle tracks given a set of noisy images, using contextual information to make the solution more robust to the noise in each image. To solve this maximum likelihood problem, we use Markov Random Fields (MRF) to establish the correspondence of features in alignment and robust optimization for projection model estimation. The resulting algorithm, called Robust Alignment and Projection Estimation for Tomographic Reconstruction, or RAPTOR, has not needed any manual intervention for the difficult datasets we have tried, and has provided sub-pixel alignment that is as good as the manual approach by an expert user. We are able to automatically map complete and partial marker trajectories and thus obtain highly accurate image alignment. Our method has been applied to challenging cryo electron tomographic datasets with low SNR from intact bacterial cells, as well as several plastic section and X-ray datasets.","subset":"pubmed_abstract"} +{"meta":{"pmid":24833689,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Longitudinal cohort survey of women's smoking behaviour and attitudes in pregnancy: study methods and baseline data.\nTo report the methods used to assemble a contemporary pregnancy cohort for investigating influences on smoking behaviour before, during and after pregnancy and to report characteristics of women recruited. Longitudinal cohort survey. Two maternity hospitals, Nottingham, England. 3265 women who attended antenatal ultrasound scan clinics were offered cohort enrolment; those who were 8-26 weeks pregnant and were currently smoking or had recently stopped smoking were eligible. Cohort enrollment took place between August 2011 and August 2012. Prevalence of smoking at cohort entry and at two follow-up time points (34-36 weeks gestation and 3 months postnatally); response rate, participants' sociodemographic characteristics. 1101 (33.7%, 95% CI 32.1% to 35.4%) women were eligible for inclusion in the cohort, and of these 850 (77.2%, 95% CI 74.6% to 79.6%) were recruited. Within the cohort, 57.4% (N=488, 95% CI 54.1% to 60.7%) reported to be current smokers. Current smokers were significantly younger than ex-smokers (p<0.05), more likely to have no formal qualifications and to not be in current paid employment compared to recent ex-smokers (p<0.001). This contemporary cohort, which seeks very detailed information on smoking in pregnancy and its determinants, includes women with comparable sociodemographic characteristics to those in other UK cross-sectional studies and cohorts. This suggests that future analyses using this cohort and aimed at understanding smoking behaviour in pregnancy may produce findings that are broadly generalisable.","subset":"pubmed_abstract"} +{"meta":{"pmid":32024428,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Melatonin in Mitochondria: Mitigating Clear and Present Dangers.\nIn cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol. By allowing the conversion of pyruvate to acetyl-CoA in mitochondria, melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype. Acetyl-CoA in the mitochondria also serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":29038047,"dup_signals":{"dup_doc_count":26,"dup_dump_count":17,"dup_details":{"curated_sources":1,"2023-06":2,"2021-39":1,"2021-31":1,"2021-25":2,"2021-21":3,"2021-10":1,"2021-04":1,"2020-16":2,"2020-10":2,"2019-51":1,"2019-35":1,"2019-30":3,"2019-26":1,"2019-13":1,"2018-47":1,"2018-39":1,"2023-40":1}}},"text":"Joint groupwise registration and ADC estimation in the liver using a B-value weighted metric.\nThe purpose of this work is to develop a groupwise elastic multimodal registration algorithm for robust ADC estimation in the liver on multiple breath hold diffusion weighted images. We introduce a joint formulation to simultaneously solve both the registration and the estimation problems. In order to avoid non-reliable transformations and undesirable noise amplification, we have included appropriate smoothness constraints for both problems. Our metric incorporates the ADC estimation residuals, which are inversely weighted according to the signal content in each diffusion weighted image. Results show that the joint formulation provides a statistically significant improvement in the accuracy of the ADC estimates. Reproducibility has also been measured on real data in terms of the distribution of ADC differences obtained from different b-values subsets. The proposed algorithm is able to effectively deal with both the presence of motion and the geometric distortions, increasing accuracy and reproducibility in diffusion parameters estimation.","subset":"pubmed_abstract"} +{"meta":{"pmid":10964332,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Positron emission tomography scanning in malignant melanoma.\nSeveral recent studies have demonstrated the low yield of anatomically based computed tomography scans in evaluating Stage III (American Joint Committee on Cancer) patients with malignant melanoma. The purpose of this study was to investigate the efficacy and clinical utility of functionally based positron emission tomography (PET) scans in the same patient population. A prospective evaluation of 106 whole body PET scans obtained after injection of 2-fluorine-18, 2-fluoro-2-deoxy-D-glucose (FDG) was performed in 95 patients with clinically evident Stage III lymph node and\/or in-transit melanoma. Areas of abnormality on FDG PET scanning were identified visually as foci of increased metabolic activity compared with background, and all positive foci were assessed pathologically. In this patient population, there were 234 areas that were evaluated pathologically of which 165 were confirmed histologically to be melanoma. PET scanning identified 144 of the 165 areas of melanoma for a sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10 microscopic foci, 9 foci less than 1 cm, and 2 foci greater than 1 cm. There were 39 areas of increased PET activity that were not associated with malignancy for a 78.6% predictive value of a positive test. Of the 39 false-positive areas (false-positive rate of 56.5%), 13 could be attributed to recent surgery, 3 to arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus, and 1 to a colonic polyp. Pathologic evaluation of the remaining false-positive areas failed to reveal a definitive etiology for their increased activity on PET scan. With the application of pertinent clinical information, the predictive value of a positive PET scan could be improved to 90. 6%. The specificity of PET scanning in this study was only 43.5% because very few prophylactic lymph node dissections were performed. Thirty-six of the total 183 abnormal areas (19.7%) on PET scanning proved to be unsuspected areas of metastatic disease. These findings led to a change in the planned clinical management in patients after 16 of the 106 PET scans (15.1%). FDG PET scanning can be helpful in managing patients with Stage III melanoma in whom further surgery is contemplated. Although false-positive areas are not uncommon, PET scans did change the management of patients 15% of the time. PET's inability to identify microscopic disease suggests that it is of limited use in evaluating patients with Stage I-II disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":28665745,"dup_signals":{"dup_doc_count":18,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2021-21":1,"2021-04":1,"2020-40":1,"2019-35":1,"2019-22":1,"2018-43":1,"2018-34":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2024-26":1,"2024-30":1}}},"text":"Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro.\nPrion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system protein misfolding cyclic amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes\/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":21206703,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":11}}},"text":"Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population.\nDistribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.","subset":"pubmed_abstract"} +{"meta":{"pmid":23974724,"dup_signals":{"dup_doc_count":24,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2023-50":3,"2023-40":2,"2023-14":2,"2022-49":1,"2022-27":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":2,"2021-31":2,"2021-17":2,"2021-04":1,"2020-50":1,"2020-45":1,"2024-22":1}}},"text":"Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.\nChildren with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p \u2264 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p \u2264 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":29168486,"dup_signals":{"dup_doc_count":36,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-10":2,"2024-30":1,"unknown":31}}},"text":"Infrared spectrum and structure of the homochiral serine octamer-dichloride complex.\nThe amino acid serine is known to form a very stable octamer that has properties that set it apart from serine complexes of different sizes or from complexes composed of other amino acids. For example, both singly protonated serine octamers and anionic octamers complexed with two halogen ions strongly prefer homochirality, even when assembled from racemic D,L mixtures. Consequently, the structures of these complexes are of great interest, but no acceptable candidates have so far been identified. Here, we investigate anionic serine octamers coordinated with two chloride ions using a novel technique coupling ion mobility spectrometry-mass spectrometry with infrared spectroscopy, in combination with theoretical calculations. The results allow the identification of a unique structure for (Ser8Cl2)2- that is highly symmetric, very stable and homochiral and whose calculated properties match those observed in experiments.","subset":"pubmed_abstract"} +{"meta":{"pmid":23382420,"dup_signals":{"dup_doc_count":58,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2023-50":2,"2023-40":5,"2023-23":4,"2023-06":3,"2022-49":2,"2022-40":3,"2022-27":1,"2022-21":3,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":3,"2021-31":4,"2021-25":2,"2021-21":1,"2021-17":1,"2021-10":3,"2021-04":1,"2020-50":2,"2020-45":3,"2020-40":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2024-18":1,"2024-10":1,"2024-26":1}}},"text":"Simultaneously reconstructing viral cross-species transmission history and identifying the underlying constraints.\nThe factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. Here, we describe a flexible Bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors of cross-species transmission. Specifically, we use a generalized linear model extension of phylogenetic diffusion to perform Bayesian model averaging over candidate predictors. By further extending this model with branch partitioning, we allow for distinct host transition processes on external and internal branches, thus discriminating between recent cross-species transmissions, many of which are likely to result in dead-end infections, and host shifts that reflect successful onwards transmission in the new host species. Our approach corroborates genetic distance between hosts as a key determinant of both host shifts and cross-species transmissions of rabies virus in North American bats. Furthermore, our results indicate that geographical range overlap is a modest predictor for cross-species transmission, but not for host shifts. Although our evolutionary framework focused on the multi-host reservoir dynamics of bat rabies virus, it is applicable to other pathogens and to other discrete state transition processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":2330923,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions.\nEight patients with transfusion-dependent thalassemia major were given continuous intravenous infusions of the chelator, deferoxamine mesylate, to reduce iron overload. Within 5 to 9 days of starting the infusions, four patients developed a pulmonary syndrome of moderate to life-threatening severity characterized by tachypnea, hypoxemia, and a diffuse interstitial pattern on chest roentgenogram. Pulmonary function studies showed restrictive dysfunction. Lung biopsy showed diffuse abnormalities with alveolar damage, interstitial fibrosis, and inflammation. The inflammatory infiltrate comprised lymphocytes, eosinophils, and mast cells. Exposure of the biopsy specimen to fluorescein-conjugated anti-IgE antibody showed fixation of IgE to the mast cell surface, suggesting a hypersensitivity reaction. Detailed studies failed to identify an infectious agent. The temporal relationship between drug administration and lung disease, and the clinical similarities in the four affected patients, strongly suggested a cause and effect relationship. We recommend that therapy with continuous intravenous infusions of deferoxamine be monitored carefully with respect to pulmonary status.","subset":"pubmed_abstract"} +{"meta":{"pmid":33637304,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes.\nThe etiology of frontotemporal dementia (FTD) is poorly understood. To identify genes with predicted expression levels associated with FTD, we integrated summary statistics with external reference gene expression data using a transcriptome-wide association study approach. FUSION software was used to leverage FTD summary statistics (all FTD: n = 2154 cases, n = 4308 controls; behavioral variant FTD: n = 1337 cases, n = 2754 controls; semantic dementia: n = 308 cases, n = 616 controls; progressive nonfluent aphasia: n = 269 cases, n = 538 controls; FTD with motor neuron disease: n = 200 cases, n = 400 controls) from the International FTD-Genomics Consortium with 53 expression quantitative loci tissue type panels (n = 12,205; 5 consortia). Significance was assessed using a 5% false discovery rate threshold. We identified 73 significant gene-tissue associations for FTD, representing 44 unique genes in 34 tissue types. Most significant findings were derived from dorsolateral prefrontal cortex splicing data (n = 19 genes, 26%). The 17q21.31 inversion locus contained 23 significant associations, representing 6 unique genes. Other top hits included SEC22B (a gene involved in vesicle trafficking), TRGV5, and ZNF302. A single gene finding (RAB38) was observed for behavioral variant FTD. For other clinical subtypes, no significant associations were observed. We identified novel candidate genes (e.g., SEC22B) and previously reported risk regions (e.g., 17q21.31) for FTD. Most significant associations were observed in dorsolateral prefrontal cortex splicing data despite the modest sample size of this reference panel. This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.","subset":"pubmed_abstract"} +{"meta":{"pmid":28795746,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Pt-dipyridyl tetrazine metal-organic network on the Au(100) surface: insights from first principles calculations.\nMetal-organic coordination networks with active metal centers are a promising class of materials for next-generation catalysts. Motivated by experimental observations of the formation of a Pt-Dipyridyl Tetrazine (DT) metal-organic network on the Au(100) surface [D. Skomski et al., J. Am. Chem. Soc., 2014, 136, 9862], we carried out density functional theory based calculations on the same system. In this discussion, we demonstrate that the strong interaction between DT ligands and Pt metal centers makes the network stable and that the Pt centers become positively charged by donating their electrons to the DT ligands, resulting in +2 oxidation states for the Pt centers. We further show that the Au substrate withdraws electrons from and hybridizes with the dz2 orbital of the Pt centers, altering their electronic structure and related properties. Furthermore, we find that the Pt centers can absorb SO2via donor-acceptor interactions, leading to the formation of \u03c3-bonds in which Pt dz2 orbitals act as electron donors, and that the strength of the resultant \u03c3-bond depends on the registry of the Pt centers with the Au(100) surface. Finally, we identify factors, such as the specificity of the ligands and the substrate, and the fullness of the outer shell of the metal centers, that may affect the chemical properties of the metal centers. We suggest modifications (and replacement) of these factors as one of the ways to tune and design metal-organic coordination networks for next-generation catalysts.","subset":"pubmed_abstract"} +{"meta":{"pmid":12706204,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease.\nDerivatives of the muscarinic antagonist 3-quinuclidinyl-4-iodobenzilate (QNB), particularly [123I]-(R,R)-I-QNB, are currently being assessed as in vivo ligands to monitor muscarinic receptors in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), relating changes to disease symptoms and to treatment response with cholinergic medication. To assist in the evaluation of in vivo binding, muscarinic receptor density in post-mortem human brain was measured by autoradiography with [125I]-(R,R)-I-QNB and [125I]-(R,S)-I-QNB and compared to M1 ([3H]pirenzepine) and M2 and M4 ([3H]AF-DX 384) receptor binding. Binding was calculated in tissue containing striatum, globus pallidus (GPe), claustrum, and cingulate and insula cortex, in cases of AD, DLB, Parkinson's disease (PD) and normal elderly controls. Pirenzepine, AF-DX 384 and (R,S)-I-QNB binding in the striatum correlated positively with increased Alzheimer-type pathology, and AF-DX 384 and (R,R)-I-QNB cortical binding correlated positively with increased Lewy body (LB) pathology; however, striatal pirenzepine binding correlated negatively with cortical LB pathology. M1 receptors were significantly reduced in striatum in DLB compared to AD, PD, and controls and there was a significant correlation between M1 and dopamine D2 receptor densities. [3H]AF-DX 384 binding was higher in the striatum and GPe in AD. Binding of [125I]-(R,R)-I-QNB, which may reflect increased muscarinic M4 receptors, was higher in cortex and claustrum in DLB and AD. [125I]-(R,S)-I-QNB binding was higher in the GPe in AD. Low M1 and D2 receptors in DLB imply altered regulation of the striatal projection neurons which express these receptors. Low density of striatal M1 receptors may relate to the extent of movement disorder in DLB, and to a reduced risk of parkinsonism with acetylcholinesterase inhibition.","subset":"pubmed_abstract"} +{"meta":{"pmid":30708941,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Modeling of Disordered Protein Structures Using Monte Carlo Simulations and Knowledge-Based Statistical Force Fields.\nThe description of protein disordered states is important for understanding protein folding mechanisms and their functions. In this short review, we briefly describe a simulation approach to modeling protein interactions, which involve disordered peptide partners or intrinsically disordered protein regions, and unfolded states of globular proteins. It is based on the CABS coarse-grained protein model that uses a Monte Carlo (MC) sampling scheme and a knowledge-based statistical force field. We review several case studies showing that description of protein disordered states resulting from CABS simulations is consistent with experimental data. The case studies comprise investigations of protein\u207bpeptide binding and protein folding processes. The CABS model has been recently made available as the simulation engine of multiscale modeling tools enabling studies of protein\u207bpeptide docking and protein flexibility. Those tools offer customization of the modeling process, driving the conformational search using distance restraints, reconstruction of selected models to all-atom resolution, and simulation of large protein systems in a reasonable computational time. Therefore, CABS can be combined in integrative modeling pipelines incorporating experimental data and other modeling tools of various resolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":26462197,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-18":2,"2024-10":1,"unknown":6}}},"text":"Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.\nThe segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":27557994,"dup_signals":{"dup_doc_count":19,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-24":1,"2019-47":1,"2019-39":1,"2019-30":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"The Societal Cost of Schizophrenia: A Systematic Review.\nCost-of-illness (COI) studies provide useful information on the economic burden that schizophrenia imposes on a society. This study aims to give a general overview of COI studies for schizophrenia and to compare the societal cost of schizophrenia across countries. It also aims to identify the main cost components of schizophrenia and factors associated with higher societal cost to improve the quality and reporting of COI studies for schizophrenia. We performed an electronic search on multiple databases (MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Health Management Information Consortium [HMIC] and the System for Information on Grey Literature [openSIGLE]) to identify COI studies of schizophrenia published between 1996 and 2016. The primary outcome of this review was societal cost per schizophrenia patient, by cost component. All costs were converted to $US, year 2015 values. We included 19 studies in this review. The annual societal cost per patient varied from $US5818 in Thailand to $US94,587 in Norway; whereas the lifetime societal cost per patient was estimated to be $US988,264 in Australia (all year 2015 values). The main cost drivers were direct healthcare costs and productivity losses. Factors associated with higher individual costs included patient demographics, severity of disease and methods used to calculate the costs of productivity losses and comorbidities. This review highlights the large economic burden of schizophrenia. The magnitude of the cost estimates differs considerably across countries, which might be caused by different economic conditions and healthcare systems and widespread methodological heterogeneity among COI studies. Proposed recommendations based on this review can be used to improve the consistency and comparability of COI studies for schizophrenia.","subset":"pubmed_abstract"} +{"meta":{"pmid":30984393,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Ethnic Differences in the Effects of Naloxone on Sustained Evoked Pain: A Preliminary Study.\nEthnic differences in pain response have been well documented, with non-Hispanic Black (NHB) participants reporting enhanced clinical pain and greater laboratory-evoked pain sensitivity to a variety of quantitative sensory testing (QST) methods compared to non-Hispanic Whites (NHW). One potential mechanism that may contribute to these disparities is differential functioning of endogenous pain-regulatory systems. To evaluate endogenous opioid (EO) mechanisms in pain responses, we examined group differences in response to tonic capsaicin pain following double-blinded crossover administration of saline and the opioid antagonist, naloxone. Ten percent topical capsaicin cream and a thermode were applied to the dorsum of the non-dominant hand, maintaining a constant temperature of 40\u00b0C for 90 min. Naloxone (0.1 mg\/kg) or saline placebo was administered at the 25 min mark and post-drug pain intensity ratings were obtained every 5 min thereafter. As an index of EO function, blockade effects were derived for each participant, reflecting the difference between mean post-drug pain intensity ratings under the saline versus naloxone conditions, with higher positive scores reflecting greater EO inhibition of pain. Thirty-nine healthy, young individuals (19 non-Hispanic Black [NHB], 20 non-Hispanic White [NHW]) participated. Group difference in EO function were identified, with NHB participants displaying lower EO function scores (mean=-10.8, SD=10.1) as compared to NHW participants (mean=-0.89, SD=11.5; p=0.038). NHB participants experienced significant paradoxical analgesia with naloxone. Thirty five percent of the NHW participants showed a positive blockade effect indicating EO analgesia (i.e., an increase in pain with naloxone), while only 10% of the NHB participants exhibited evidence of EO analgesia. These findings suggest differential functioning of the endogenous opioid pain regulatory system between NHB and NHW participants. Future research is warranted to examine whether these differences contribute to the disparities observed in clinical pain between groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":21632380,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Bryophyte diaspore bank: a genetic memory? Genetic structure and genetic diversity of surface populations and diaspore bank in the liverwort Mannia fragrans (Aytoniaceae).\nPropagule banks are assumed to be able to store considerable genetic variability. Bryophyte populations are expected to rely more heavily on stored propagules than those of seed plants due to the vulnerability of the haploid gametophyte. This reliance has important implications for the genetic structure and evolutionary potential of surface populations. A liverwort, Mannia fragrans, was used to test whether the bryophyte diaspore bank functions as a \"genetic memory.\" If a diaspore bank is capable of conserving genetic variability over generations, the levels of genetic diversity in the soil are expected to be similar or higher than at the surface. Surface and diaspore bank constituents of two populations of M. fragrans were investigated. Genetic structure and diversity measured as unbiased heterozygosity were analyzed using three ISSR markers. Similar genetic diversities were found in the soil (H(s) = 0.067) and at the surface (H(s)= 0.082). However, more haplotypes and specific haplotype lineages were present in soil samples. The results suggest that the bryophyte diaspore bank has an important role in accumulating genetic variability over generations and seasons. It is postulated that the role of the diaspore bank as a \"genetic memory\" is especially important in species of temporarily available habitats that have long-lived spores and genetically variable populations.","subset":"pubmed_abstract"} +{"meta":{"pmid":29763967,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Machine learning algorithms for outcome prediction in (chemo)radiotherapy: An empirical comparison of classifiers.\nMachine learning classification algorithms (classifiers) for prediction of treatment response are becoming more popular in radiotherapy literature. General Machine learning literature provides evidence in favor of some classifier families (random forest, support vector machine, gradient boosting) in terms of classification performance. The purpose of this study is to compare such classifiers specifically for (chemo)radiotherapy datasets and to estimate their average discriminative performance for radiation treatment outcome prediction. We collected 12 datasets (3496 patients) from prior studies on post-(chemo)radiotherapy toxicity, survival, or tumor control with clinical, dosimetric, or blood biomarker features from multiple institutions and for different tumor sites, that is, (non-)small-cell lung cancer, head and neck cancer, and meningioma. Six common classification algorithms with built-in feature selection (decision tree, random forest, neural network, support vector machine, elastic net logistic regression, LogitBoost) were applied on each dataset using the popular open-source R package caret. The R code and documentation for the analysis are available online (https:\/\/github.com\/timodeist\/classifier_selection_code). All classifiers were run on each dataset in a 100-repeated nested fivefold cross-validation with hyperparameter tuning. Performance metrics (AUC, calibration slope and intercept, accuracy, Cohen's kappa, and Brier score) were computed. We ranked classifiers by AUC to determine which classifier is likely to also perform well in future studies. We simulated the benefit for potential investigators to select a certain classifier for a new dataset based on our study (pre-selection based on other datasets) or estimating the best classifier for a dataset (set-specific selection based on information from the new dataset) compared with uninformed classifier selection (random selection). Random forest (best in 6\/12 datasets) and elastic net logistic regression (best in 4\/12 datasets) showed the overall best discrimination, but there was no single best classifier across datasets. Both classifiers had a median AUC rank of 2. Preselection and set-specific selection yielded a significant average AUC improvement of 0.02 and 0.02 over random selection with an average AUC rank improvement of 0.42 and 0.66, respectively. Random forest and elastic net logistic regression yield higher discriminative performance in (chemo)radiotherapy outcome and toxicity prediction than other studied classifiers. Thus, one of these two classifiers should be the first choice for investigators when building classification models or to benchmark one's own modeling results against. Our results also show that an informed preselection of classifiers based on existing datasets can improve discrimination over random selection.","subset":"pubmed_abstract"} +{"meta":{"pmid":21531244,"dup_signals":{"dup_doc_count":23,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-14":1,"2023-06":2,"2022-49":2,"2022-27":1,"2022-21":1,"2022-05":2,"2021-43":1,"2021-39":1,"2021-21":1,"2020-45":1,"2020-40":1,"2020-05":1,"2019-51":1,"2019-39":1,"2023-40":1,"2024-10":1,"2013-20":1,"2024-18":1}}},"text":"Cognition and daytime functioning in sleep-related breathing disorders.\nSleep-related breathing disorders encompass a range of disorders in which abnormal ventilation occurs during sleep as a result of partial or complete obstruction of the upper airway, altered respiratory drive, abnormal chest wall movement, or respiratory muscle function. The most common of these is obstructive sleep apnea (OSA), occurring in both adults and children, and causing significant cognitive and daytime dysfunction and reduced quality of life. OSA patients experience repetitive brief cessation of breathing throughout the night, which causes intermittent hypoxemia (reductions in hemoglobin oxygen levels) and fragmented sleep patterns. These nocturnal events result in excessive daytime sleepiness, and changes in mood and cognition. Chronic excessive sleepiness during the day is a common symptom of sleep-related breathing disorders, which is assessed in sleep clinics both subjectively (questionnaire) and objectively (sleep latency tests). Mood changes are often reported by patients, including irritability, fatigue, depression, and anxiety. A wide range of cognitive deficits have been identified in untreated OSA patients, from attentional and vigilance, to memory and executive functions, and more complex tasks such as simulated driving. These changes are reflected in patient reports of difficulty in concentrating, increased forgetfulness, an inability to make decisions, and falling asleep at the wheel of a motor vehicle. These cognitive changes can also have significant downstream effects on daily functioning. Moderate to severe cases of the disorder are at a higher risk of having a motor vehicle accident, and may also have difficulties at work or school. A number of comorbidities may also influence the cognitive changes in OSA patients, including hypertension, diabetes, and stroke. These diseases can cause changes to neural vasculature and result in neural damage, leading to cognitive impairments. Examination of OSA patients using neuroimaging techniques such as structural magnetic resonance imaging and proton magnetic resonance spectroscopy has observed significant changes to brain structure and metabolism. The downstream effects of neural, cognitive, and daytime functional impairments can be significant if left untreated. A better understanding of the cognitive effects of these disorders, and development of more effective assessment tools for diagnosis, will aid early intervention and improve quality of life of the patient.","subset":"pubmed_abstract"} +{"meta":{"pmid":19893468,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Halitosis: a stomatological and psychological issue.\nIt can be stated that halitosis is located on the ridge connecting dentistry, oral medicine, parodontology and psychology. It represents, at the same time, the manifestation of an organic malfunctioning of the oral apparatus, and a problematic element for the individual and his\/her relational life. A smelly emanation comes into conflict with the wish to attract, to please, to seduce. The attitudes towards the possibility to suffer from bad breath have two typical opposite expressions, which share the common characteristic that many are bad judges of one's own breath. The dentist, in fact, is frequently involved in the management of patients who believe they have bad breath problems, which in reality are non-existent (pseudo-halitosis), and, more often, of patients who are not aware they have an halitosis condition, and who are not inclined to accept it (denied halitosis). Generally, the most adequate and suitable option is that of communicating to the unaware patient the existence and the nature of the problem. What is said, and especially the way of saying it, may play an important role in patient's acceptance of the information without producing, or reducing to a minimum, the undesirable side effects on the patient-professional relationship, and on the personal dynamics of the patient him\/herself. A useful procedure is provided by employing a pre-visit questionnaire, that may suitably ask many different questions about relevant dental and mucosal aspects, for instance, dental complaints, the frequency of toothbrushing and flossing, gum bleeding, and about psychological aspects, such as dental anxiety, and degree of satisfaction as regards one's oral condition, in order to solve or alleviate the patient's problem, avoiding unnecessary personal discomfort and, at the same time, providing competent and effective professional help. Strategies for communicating in an effective way, in order to properly face both the somatic and the psychological aspects, are proposed. A questionnaire (Halitosis Questionnaire - HQ) is also provided, to facilitate the assessment and the management of the halitosis issue.","subset":"pubmed_abstract"} +{"meta":{"pmid":24863701,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"A high-density linkage map enables a second-generation collared flycatcher genome assembly and reveals the patterns of avian recombination rate variation and chromosomal evolution.\nDetailed linkage and recombination rate maps are necessary to use the full potential of genome sequencing and population genomic analyses. We used a custom collared flycatcher 50 K SNP array to develop a high-density linkage map with 37 262 markers assigned to 34 linkage groups in 33 autosomes and the Z chromosome. The best-order map contained 4215 markers, with a total distance of 3132 cM and a mean genetic distance between markers of 0.12 cM. Facilitated by the array being designed to include markers from most scaffolds, we obtained a second-generation assembly of the flycatcher genome that approaches full chromosome sequences (N50 super-scaffold size 20.2 Mb and with 1.042 Gb (of 1.116 Gb) anchored to and mostly ordered and oriented along chromosomes). We found that flycatcher and zebra finch chromosomes are entirely syntenic but that inversions at mean rates of 1.5-2.0 event (6.6-7.5 Mb) per My have changed the organization within chromosomes, rates high enough for inversions to potentially have been involved with many speciation events during avian evolution. The mean recombination rate was 3.1 cM\/Mb and correlated closely with chromosome size, from 2 cM\/Mb for chromosomes >100 Mb to >10 cM\/Mb for chromosomes <10 Mb. This size dependence seemed entirely due to an obligate recombination event per chromosome; if 50 cM was subtracted from the genetic lengths of chromosomes, the rate per physical unit DNA was constant across chromosomes. Flycatcher recombination rate showed similar variation along chromosomes as chicken but lacked the large interior recombination deserts characteristic of zebra finch chromosomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":19114615,"dup_signals":{"dup_doc_count":25,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2023-40":1,"2023-14":1,"2023-06":2,"2022-49":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort.\nThe purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C >or=6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%. This was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40-79 years recruited from U.K. general practices attended a health examination (1993-1998) and were followed for CVD events\/death until April 2007. CVD risk estimates were calculated for 10,137 individuals. Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly. Both the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":19399136,"dup_signals":{"dup_doc_count":62,"dup_dump_count":33,"dup_details":{"curated_sources":4,"2021-39":1,"2021-17":1,"2020-45":1,"2020-29":1,"2019-35":1,"2019-30":1,"2018-43":2,"2018-22":2,"2018-13":2,"2018-05":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":4,"2017-04":2,"2016-44":2,"2016-36":3,"2016-30":1,"2016-22":2,"2016-18":2,"2016-07":2,"2015-48":3,"2015-40":2,"2015-35":2,"2015-32":3,"2015-27":3,"2015-22":4,"2022-05":1,"2017-13":2}}},"text":"A three-dimensional multispectral fluorescence optical tomography imaging system for small animals based on a conical mirror design.\nWe have developed a three dimensional (3D) multispectral fluorescence optical tomography small animal imaging system with an innovative geometry using a truncated conical mirror, allowing simultaneous viewing of the entire surface of the animal by an EMCCD camera. A conical mirror collects photons approximately three times more efficiently than a flat mirror. An x-y mirror scanning system makes it possible to scan a collimated excitation laser beam to any location on the mouse surface. A pattern of structured light incident on the small animal surface is used to extract the surface geometry for reconstruction. A finite element based algorithm is applied to model photon propagation in the turbid media and a preconditioned conjugate gradient (PCG) method is used to solve the large linear system matrix. The reconstruction algorithm and the system feasibility are evaluated by phantom experiments. These experiments show that multispectral measurements improve the spatial resolution of reconstructed images. Finally, an in vivo imaging study of a xenograft tumor in a mouse shows good correlation of the reconstructed image with the location of the fluorescence probe as determined by subsequent optical imaging of cryosections of the mouse.","subset":"pubmed_abstract"} +{"meta":{"pmid":27495819,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":2,"unknown":9}}},"text":"Visual Fixation in the ICU: A Strong Predictor of Long-Term Recovery After Moderate-to-Severe Traumatic Brain Injury.\nPosttraumatic amnesia is superior to the initial Glasgow Coma Scale score for predicting traumatic brain injury recovery, but it takes days\/weeks to assess. Here, we examined whether return of visual fixation-a potential marker of higher cognitive function-within 24 hours of ICU admission could be used as an early predictor of traumatic brain injury recovery. Two-phase cohort study. Level-I trauma ICU. Moderate-to-severe traumatic brain injury discharged alive between 2010 and 2013. None. Return of visual fixation was assessed through standard behavioral assessments in 181 traumatic brain injury patients who had lost the ability to fixate at ICU admission (phase 1) and compared with posttraumatic amnesia duration and the initial Glasgow Coma Scale score to predict performance on the Glasgow Outcome Scale-Extended 10-40 months after injury (n = 144; phase 2a). A subgroup also completed a visual attention task (n = 35; phase 2b) and a brain MRI after traumatic brain injury (n = 23; phase 2c). With an area under the curve equal to 0.85, presence\/absence of visual fixation at 24 hours of ICU admission was found as performant as posttraumatic amnesia (area under the curve, 0.81; difference between area under the curve, 0.04; p = 0.28) for predicting patients' Glasgow Outcome Scale-Extended score. Conversely, the initial Glasgow Coma Scale score was not (area under the curve, 0.63). Even when controlling for age\/medication\/CT scan findings, fixation remained a significant predictor of Glasgow Outcome Scale-Extended scores (\u03b2, -0.29; p < 0.05). Poorer attention performances and greater regional brain volume deficits were also observed in patients who could not fixate at 24 hours of ICU admission versus those who could. Visual fixation within 24 hours of ICU admission could be as performant as posttraumatic amnesia for predicting traumatic brain injury recovery, introducing a new variable of interest in traumatic brain injury outcome research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22363782,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Is there a valence-specific pattern in emotional conflict in major depressive disorder? An exploratory psychological study.\nPatients with major depressive disorder (MDD) clinically exhibit a deficit in positive emotional processing and are often distracted by especially negative emotional stimuli. Such emotional-cognitive interference in turn hampers the cognitive abilities of patients in their ongoing task. While the psychological correlates of such emotional conflict have been well identified in healthy subjects, possible alterations of emotional conflict in depressed patients remain to be investigated. We conducted an exploratory psychological study to investigate emotional conflict in MDD. We also distinguished depression-related stimuli from negative stimuli in order to check whether the depression-related distractors will induce enhanced conflict in MDD. A typical word-face Stroop paradigm was adopted. In order to account for valence-specificities in MDD, we included positive and general negative as well as depression-related words in the study. MDD patients demonstrated a specific pattern of emotional conflict clearly distinguishable from the healthy control group. In MDD, the positive distractor words did not significantly interrupt the processing of the negative target faces, while they did in healthy subjects. On the other hand, the depression-related distractor words induced significant emotional conflict to the positive target faces in MDD patients but not in the healthy control group. Our findings demonstrated for the first time an altered valence-specific pattern in emotional conflict in MDD patients. The study sheds a novel and specific light on the affective mechanisms underlying the abnormal emotional-cognitive interference in MDD. Such emotional conflict bears important clinical relevance since it may trigger the widespread cognitive dysfunctions frequently observed in MDD. The present findings may have important clinical implications in both prediction and psychotherapy of MDD.","subset":"pubmed_abstract"} +{"meta":{"pmid":26457417,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"The Male-female Birth Ratio in California and the 1992 April Riots in Los Angeles.\nMale live births slightly exceed female live births. This is usually expressed as M\/F, the ratio of male to total live births. A multitude of external influences have been shown to reduce this ratio, including stress provoked through witnessing violent events; M\/F dips occur three to four months later. The April 1992 Los Angeles riots constituted six days of extreme civil unrest in the city of Los Angeles. This study was carried out in order to ascertain whether M\/F dipped in California following this event. Monthly male and female live births for California were obtained from the Centers for Disease Control and Prevention for the State of California for 1992 and for January 1993. This study analysed 649 073 live births; M\/F was lowest in August 1992 (0.5085). This was significantly lower than for the period after (September 1992 to January 1993, p = 0.044). The ratio of male to total live births was higher in January to July 1992 than in August 1992, but this difference was not statistically significant. Stress has been shown to reduce M\/F through an excess of male fetal loss during gestation and\/or from gender-biased conception favouring females. Only the former mechanism is supported by these findings. This is the first time that violent events at state level have been shown to have potentially influenced M\/F.","subset":"pubmed_abstract"} +{"meta":{"pmid":26588288,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA.\nTerminal base pairs of DNA and RNA molecules in solution are known to undergo frequent transient opening events (fraying). Accurate modeling of this process is important because of its involvement in nucleic acid end recognition and enzymatic catalysis. In this article, we describe fraying in molecular dynamics simulations with the ff99bsc0, ff99bsc0\u03c7OL3, and ff99bsc0\u03c7OL4 force fields, both for DNA and RNA molecules. Comparison with the experiment showed that while some features of fraying are consistent with the available data, others indicate potential problems with the force field description. In particular, multiple noncanonical structures are formed at the ends of the DNA and RNA duplexes. Among them are tWC\/sugar edge pair, C-H edge\/Watson-Crick pair, and stacked geometries, in which the terminal bases are stacked above each other. These structures usually appear within the first tens to hundreds of nanoseconds and substantially limit the usefulness of the remaining part of the simulation due to geometry distortions that are transferred to several neighboring base pairs (\"end effects\"). We show that stability of the noncanonical structures in ff99bsc0 may be partly linked to inaccurate glycosidic (\u03c7) torsion potentials that overstabilize the syn region and allow for rapid anti to syn transitions. The RNA refined glycosidic torsion potential \u03c7OL3 provides an improved description and substantially more stable MD simulations of RNA molecules. In the case of DNA, the \u03c7OL4 correction gives only partial improvement. None of the tested force fields provide a satisfactory description of the terminal regions, indicating that further improvement is needed to achieve realistic modeling of fraying in DNA and RNA molecules.","subset":"pubmed_abstract"} +{"meta":{"pmid":18997784,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":11}}},"text":"Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin.\nGerodermia osteodysplastica is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that gerodermia osteodysplastica is caused by loss-of-function mutations in SCYL1BP1, which is highly expressed in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues.","subset":"pubmed_abstract"} +{"meta":{"pmid":16669182,"dup_signals":{"dup_doc_count":65,"dup_dump_count":44,"dup_details":{"curated_sources":4,"2023-40":2,"2023-14":2,"2023-06":1,"2022-49":1,"2022-27":2,"2022-21":2,"2021-49":1,"2021-43":1,"2021-31":3,"2021-25":1,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":3,"2020-50":3,"2020-45":1,"2020-40":2,"2020-34":1,"2020-29":1,"2020-24":1,"2020-05":1,"2019-51":1,"2019-47":2,"2019-43":1,"2019-39":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2014-15":2,"2024-30":3,"2024-26":1,"2024-18":1,"2024-10":1,"2014-10":1,"2013-48":1,"2013-20":1}}},"text":"Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound.\nUltrasound is an established modality for quantification of vascular function in clinical studies of cardiovascular disease. We determined whether cardiovascular magnetic resonance imaging (CMR) can provide a comparable assessment of vascular function. In seventeen control subjects, we used CMR to quantify endothelium-dependent (flow mediated dilatation, FMD) and endothelium-independent dilatation of the brachial artery, brachial and carotid distensibility, aortic compliance, and pulse wave velocity. These were compared to brachial and carotid measurements obtained by established ultrasound protocols. Twelve of the volunteers then underwent repeated measurements with both modalities. There was good agreement between imaging modalities for measures of endothelial function and arterial structure in the same subjects (difference between CMR and ultrasound for FMD = 0.14 +\/- 6.8%, and brachial artery area = - 0.7 +\/- 2.2 mm2, correlation between modalities for FMD = 0.62, p = 0.01 and for area = 0.87, p = < 0.0001). Inter-study reproducibility was also similar (coefficient of variation (CV) for FMD: CMR = 0.3, ultrasound = 0.3, CV for brachial artery area: CMR = 0.1, ultrasound = 0.1). Comparability and reproducibility were not as strong for functional measures if repeated studies were several days apart (CV for FMD by ultrasound on the same day = 0.1 and several days apart = 0.4). CMR and ultrasound show good agreement for quantitative measures of vascular structure and function with good reproducibility for both modalities. The major advantage of CMR is that it allows one-stop integrated assessment of both peripheral and central measures of vascular function.","subset":"pubmed_abstract"} +{"meta":{"pmid":9729487,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-40":1,"2020-10":1,"2020-05":2,"2019-51":1,"2019-30":1,"2019-13":1,"2018-30":2,"2017-51":1,"2016-44":1,"2023-50":1}}},"text":"The Arabidopsis thaliana gametophytic mutation gemini pollen1 disrupts microspore polarity, division asymmetry and pollen cell fate.\nPollen development and male gametogenesis are critically dependent upon cell polarization leading to a highly asymmetric cell division termed pollen mitosis I. A mutational approach was adopted in Arabidopsis thaliana to identify genes involved these processes. Four independent gemini pollen mutants were isolated which produce divided or twin-celled pollen. The gemini pollen1 mutant was characterized in detail and shown to act gametophytically resulting in reduced transmission through both sexes. gemini pollen1 showed an incompletely penetrant phenotype resulting in equal, unequal and partial divisions at pollen mitosis I. The division planes in gemini pollen1 were shown to be aligned with the polar axis (as in wild type) and evidence was obtained for incomplete nuclear migration, which could account for altered division symmetry. gemini pollen1 also showed division phenotypes consistent with spatial uncoupling of karyokinesis and cytokinesis suggesting that GEMINI POLLEN1 may be required for the localization of phragmoplast activity. Cell fate studies showed that in both equal and unequal divisions a vegetative cell marker gene was activated in both daughter cells. Daughter cells with a range of intermediate or hybrid vegetative\/generative cell fates suggests that cell fate is quantitatively related to cell size. The potential mode of action of GEMINI POLLEN1 and its effects on cell fate are discussed in relation to proposed models of microspore polarity and cell fate determination.","subset":"pubmed_abstract"} +{"meta":{"pmid":30225683,"dup_signals":{"dup_doc_count":13,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2022-21":1,"2021-31":1,"2021-21":1,"2021-04":2,"2020-50":1,"2019-43":1,"2019-22":2,"2019-09":2,"2023-23":1}}},"text":"Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction.\nInterstitial fibrosis after acute myocardial infarction (MI) leads to cardiac structural remodeling and dysfunction. The peroxisome proliferator-activated receptor-gamma (PPAR-\u03b3) agonist chrysin has been shown to protect injured myocardium through suppression of oxidative stress and inflammation. This study was designed to investigate the effect and mechanism of chrysin on myocardial fibrosis. A rat MI model was created by ligating the left coronary artery. The rats with MI were treated with chrysin (40 mg\/kg\/day) or 0.5% carboxymethylcellulose sodium by intragastric administration for 4 weeks after operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed in vitro. Echocardiography showed that cardiac function was significantly improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up-regulated PPAR-\u03b3 and inhibited the nuclear factor-kappa B (NF-\u03baB) pathway by suppressing inhibitor kappa B kinase \u03b2 phosphorylation. Immunohistochemistry analysis and PCR detected downregulated expression of AP-1 after chrysin treatment. Chrysin also markedly reduced the increased \u03b1-SMA, typeland type III collagen expression of CFs mediated by AngII in vitro. In conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct peripheral zone after MI. The underlined mechanism may be the up-regulation of PPAR-\u03b3 and inhibition of the NF-\u03baB and AP1 pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":32264164,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Injectable MnSr-doped brushite bone cements with improved biological performance.\nGood mechanical properties and high injectability are the major requirements to ensure widespread application of calcium phosphate cements (CPCs) as bone substitutes in minimally invasive surgeries. However, obtaining CPCs that exhibit a good compromise between these two properties as well as good biological performance is still a great challenge. This study presents novel solutions to improve these properties, which include (i) co-doping \u03b2-tricalcium phosphate (\u03b2-TCP) powder with Sr and Mn, and (ii) adding small amounts of saccharides (sucrose or fructose) to the setting-liquid solution. The combination of these two strategies enabled full injectability and significantly increased the wet compressive strength of CPCs in comparison to undoped or solely Sr-doped CPCs. Furthermore, the proliferative response of human MG63 osteoblastic cells, their rate of collagen-I secretion, and particularly their growth behaviour on the cement surfaces were also enhanced. The overall improved relevant properties of Mn\/Sr co-doped CPCs with added sucrose, including in vitro biological performance, renders them very promising materials for bone regeneration and tissue engineering.","subset":"pubmed_abstract"} +{"meta":{"pmid":30380048,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Differential self-report error by socioeconomic status in hypertension and hypercholesterolemia: INSEF 2015 study.\nThis study aimed to compare self-reported and examination-based prevalence of hypertension and hypercholesterolemia in Portugal in 2015 and to identify factors associated with the measurement error in self-reports. We used data from the Portuguese National Health Examination Survey (n = 4911), that combines personal interview, blood collection and, physical examination. Sensitivity and specificity of self-reported hypertension and hypercholesterolemia were calculated. Poisson regression was used to estimate prevalence ratios (PRs) of underreport of hypertension and hypercholesterolemia according to sex, age, socioeconomic status (education and income) and general practitioner (GP) consultation in the past year. Sensitivity of self-reports was 69.8% for hypertension and 38.2% for hypercholesterolemia. Underreport of hypertension was associated with male gender (PR = 1.54), lack of GP consultation (PR = 1.70) and being 25-44 years old (PR = 2.45) or 45-54 years old (PR = 2.37). Underreport of hypercholesterolemia was associated with lack of GP consultation (PR = 1.15), younger age (PR = 1.83 for 25-44 age group and PR = 1.52 for 45-54 age group), secondary (PR = 1.30) and higher (PR = 1.27) education. Self-reported data underestimate prevalence of hypertension and hypercholesterolemia. Magnitude of measurement error in self-reports varies by health conditions and population characteristics. Adding objective measurements to self-reported questionnaires improve data accuracy allowing better understanding of socioeconomic inequalities in health.","subset":"pubmed_abstract"} +{"meta":{"pmid":27605015,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":1,"2021-49":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-16":1,"2020-10":2,"2019-47":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-26":1,"2022-05":1}}},"text":"Strong coupling of Asian Monsoon and Antarctic climates on sub-orbital timescales.\nThere is increasing evidence that millennial-scale climate variability played an active role on orbital-scale climate changes, but the mechanism for this remains unclear. A (230)Th-dated stalagmite \u03b4(18)O record between 88 and 22 thousand years (ka) ago from Yongxing Cave in central China characterizes changes in Asian monsoon (AM) strength. After removing the 65\u00b0N insolation signal from our record, the \u03b4(18)O residue is strongly anti-phased with Antarctic temperature variability on sub-orbital timescales during the Marine Isotope Stage (MIS) 3. Furthermore, once the ice volume signal from Antarctic ice core records were removed and extrapolated back to the last two glacial-interglacial cycles, we observe a linear relationship for both short- and long-duration events between Asian and Antarctic climate changes. This provides the robust evidence of a link between northern and southern hemisphere climates that operates through changes in atmospheric circulation. We find that the weakest monsoon closely associated with the warmest Antarctic event always occurred during the Terminations. This finding, along with similar shifts in the opal flux record, suggests that millennial-scale events play a key role in driving the deglaciation through positive feedbacks associated with enhanced upwelling and increasing CO2.","subset":"pubmed_abstract"} +{"meta":{"pmid":26596258,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Cytoplasmic polyadenylation in mammalian oocyte maturation.\nOocyte developmental competence is the ability of the mature oocyte to be fertilized and subsequently drive early embryo development. Developmental competence is acquired by completion of oocyte maturation, a process that includes nuclear (meiotic) and cytoplasmic (molecular) changes. Given that maturing oocytes are transcriptionally quiescent (as are early embryos), they depend on post-transcriptional regulation of stored transcripts for protein synthesis, which is largely mediated by translational repression and deadenylation of transcripts within the cytoplasm, followed by recruitment of specific transcripts in a spatiotemporal manner for translation during oocyte maturation and early development. Motifs within the 3' untranslated region (UTR) of messenger RNA (mRNA) are thought to mediate repression and downstream activation by their association with binding partners that form dynamic protein complexes that elicit differing effects on translation depending on cell stage and interacting proteins. The cytoplasmic polyadenylation (CP) element, Pumilio binding element, and hexanucleotide polyadenylation signal are among the best understood motifs involved in CP, and translational regulation of stored transcripts as their binding partners have been relatively well-characterized. Knowledge of CP in mammalian oocytes is discussed as well as novel approaches that can be used to enhance our understanding of the functional and contributing features to transcript CP and translational regulation during mammalian oocyte maturation. WIREs RNA 2016, 7:71-89. doi: 10.1002\/wrna.1316 For further resources related to this article, please visit the WIREs website.","subset":"pubmed_abstract"} +{"meta":{"pmid":29773743,"dup_signals":{"dup_doc_count":26,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2023-40":1,"2022-49":1,"2022-27":1,"2022-21":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":1,"2020-50":1,"2020-10":1,"2020-05":1,"2019-51":1,"2019-43":2,"2019-30":1,"2018-51":1,"2023-50":1,"2024-22":1,"2024-10":2,"2024-26":1}}},"text":"Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens.\nWhole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.","subset":"pubmed_abstract"} +{"meta":{"pmid":7806560,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Structurally divergent histone H1 variants in chromosomes containing highly condensed interphase chromatin.\nCondensed and late-replicating interphase chromatin in the Dipertan insect Chironomus contains a divergent type of histone H1 with an inserted KAP-KAP repeat that is conserved in single H1 variants of Caenorhabditis elegans and Volvox carteri. H1 peptides comprising the insertion interact specifically with DNA. The Chironomid Glyptotendipes exhibits a corresponding correlation between the presence of condensed chromosome sections and the appearance of a divergent H1 subtype. The centromere regions and other sections of Glyptotendipes barbipes chromosomes are inaccessible to immunodecoration by anti-H2B and anti-H1 antibodies one of which is known to recognize nine different epitopes in all domains of the H1 molecule. Microelectrophoresis of the histones from manually isolated unfixed centromeres revealed the presence of H1 and core histones. H1 genes of G. barpipes were sequenced and found to belong to two groups. H1 II and H1 III are rather similar but differ remarkably from H1 I. About 30% of the deduced amino acid residues were found to be unique to H1 I. Most conspicuous is the insertion, SPAKSPGR, in H1 I that is lacking in H1 II and H1 III and at its position gives rise to the sequence repeat SPAKSPAKSPGR. The homologous H1 I gene in Glyptotendipes salinus encodes the very similar repeat TPAKSPAKSPGR. Both sequences are structurally related to the KAPKAP repeat in H1 I-1 specific for condensed chromosome sites in Chironomus and to the SPKKSPKK repeat in sea urchin sperm H1, lie at almost the same distance from the central globular domain, and could interact with linker DNA in packaging condensed chromatin.","subset":"pubmed_abstract"} +{"meta":{"pmid":16448579,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Effects of acute topiramate dosing on methamphetamine-induced subjective mood.\nClinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramate's therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamine's reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.","subset":"pubmed_abstract"} +{"meta":{"pmid":12580336,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2023-14":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-25":1,"2021-10":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-50":1}}},"text":"Cytokines: powerful regulators of glial cell activation.\nIt is now clear that cytokines function as powerful regulators of glial cell function in the central nervous system (CNS), either inhibiting or promoting their contribution to CNS pathology. Although these interactions are complex, the availability of animals with targeted deletions of these genes and\/or their receptors, as well as transgenic mice in which cytokine expression has been targeted to specific cell types, and the availability of purified populations of glia that can be studied in vitro, has provided a wealth of interesting and frequently surprising data relevant to this activity. A particular feature of many of these studies is that it is the nature of the receptor that is expressed, rather than the cytokine itself, that regulates the functional properties of these cytokines. Because cytokine receptors are themselves modulated by cytokines, it becomes evident that the effects of these cytokines may change dramatically depending upon the cytokine milieu present in the immediate environment. An additional exciting aspect of these studies is the previously underappreciated role of these factors in repair to the CNS. In this review, we focus on current information that has helped to define the role of cytokines in regulating glial cell function as it relates to the properties of microglia and astrocytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":29513301,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Changing Trends in Gastric Polyps.\nThe prevalence of gastric polyps varies around the world reflecting regional associations. We describe demographic features of patients with gastric polyp diagnosis treated between 1980 and 2016 at a referral center in Mexico City and analyzed trends of polyp subtype. We conducted a blind review of archival slides of gastric biopsies with polyp diagnosis from the years 1980, 1990, 2000, 2010, and 2016. Initial diagnosis; patient's gender, age and symptoms; and number and location of lesions were recorded. Blind slide review and trend analysis were performed. In 3887 gastric biopsies, 192 patients (4.93%) with epithelial polyps were identified. The median age of patients was 58 years; 73% were female. Polyps were single in 143\/192 cases (74.4%), almost 67% in the oxyntic mucosa, and 85% were associated with dyspepsia. The prevalence was 0.5%, 1.6%, 1.9%, 4.6%, and 9.6% for the years 1980, 1990, 2000, 2010, and 2016, respectively, resulting in a rising trend in the prevalence of epithelial polyps of 380% in 46 years. Fundic gland polyps (FGPs) had a global frequency of 66.6% (128\/192). They were identified for the first time in the third period of the study, with a frequency of 28.6% (6\/21), 66.6% (35\/53), and 78.3% (87\/111) for the years 2000, 2010, and 2016, respectively. Contrary, hyperplastic polyps (HPs) decreased 20%. A relative prevalence of 3.29%, 0.97%, and 0.15% was observed for FGP, HP, and gastric adenoma, respectively. The 1400% change of FGP explains the increased prevalence of gastric polyps. Chronic treatment with proton pump inhibitors and Helicobacter pylori eradication are possible explanations.","subset":"pubmed_abstract"} +{"meta":{"pmid":29799046,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":10}}},"text":"Nano-designed semiconductors for electro- and photoelectro-catalytic conversion of carbon dioxide.\nDevelopment of novel catalysts with high efficiency for CO2 conversion is of great research interest, because of the climate hazards caused by the gradual increase in CO2 concentration. Among various types of catalysts, semiconductors have been widely used as effective candidates for both electro- and photoelectro-CO2 conversion. Very recently, with the emerging nanotechnology and advanced characterization techniques, tremendous achievements have been made in highly efficient and clean CO2 conversion based on semiconductor catalysts. This review gives a systematic overview of this field, including the rational design of semiconductor catalysts for electro- and photoelectro-chemical CO2 conversion. Recent advances in the development of mechanism understandings on reaction pathways of CO2 and the feasibility for industrial production are discussed. Furthermore, the challenges and future perspectives of electro- and photoelectro-catalytic CO2 conversion are outlined.","subset":"pubmed_abstract"} +{"meta":{"pmid":30400285,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-26":1,"unknown":12}}},"text":"Substitution of Fish for Red Meat or Poultry and Risk of Ischemic Stroke.\nWe investigated the risk of ischemic stroke and its subtypes when red meat or poultry was substituted with fish. A total of 57,053 participants aged 50\u207b65 years at baseline were included in the Danish Diet, Cancer and Health study. All participants filled in a food-frequency questionnaire at recruitment. Potential ischemic stroke cases were identified by linkage to the Danish National Patient Register, and all cases were validated and subclassified. Substitutions were investigated as 150 g\/week of fish for 150 g\/week of red meat or of poultry using multivariable Cox proportional hazard regression models. During 13.5 years of follow-up, 1879 participants developed an ischemic stroke. Replacing red meat or poultry with fish was not associated with the rate of total ischemic stroke, but there was a statistically significant lower rate of large artery atherosclerosis when fish replaced processed (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.67; 0.90) and unprocessed (HR: 0.87; 95% CI: 0.75; 0.99) red meat. A statistically significant higher rate of cardioembolism was found when poultry was replaced by total fish (HR: 1.42; 95% CI: 1.04; 1.93). When fatty fish replaced unprocessed red meat, a statistically significant lower rate of small-vessel occlusion was found (HR: 0.88; 95% CI: 0.77; 0.99). In conclusion, replacing red meat with fish was not associated with risk of total ischemic stroke but was associated with a lower risk of subtypes of ischemic stroke.","subset":"pubmed_abstract"} +{"meta":{"pmid":19797656,"dup_signals":{"dup_doc_count":11,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2015-18":1,"unknown":3}}},"text":"Preferential growth of single-walled carbon nanotubes with metallic conductivity.\nSingle-walled carbon nanotubes can be classified as either metallic or semiconducting, depending on their conductivity, which is determined by their chirality. Existing synthesis methods cannot controllably grow nanotubes with a specific type of conductivity. By varying the noble gas ambient during thermal annealing of the catalyst, and in combination with oxidative and reductive species, we altered the fraction of tubes with metallic conductivity from one-third of the population to a maximum of 91%. In situ transmission electron microscopy studies reveal that this variation leads to differences in both morphology and coarsening behavior of the nanoparticles that we used to nucleate nanotubes. These catalyst rearrangements demonstrate that there are correlations between catalyst morphology and resulting nanotube electronic structure and indicate that chiral-selective growth may be possible.","subset":"pubmed_abstract"} +{"meta":{"pmid":28639650,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":3,"2022-05":1,"2021-49":1,"2020-50":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":2,"2022-49":1,"2024-18":1}}},"text":"Mechanisms of H and CO loss from the uracil nucleobase following low energy electron irradiation.\nIonising radiation in cells generates secondary low energy electrons (LEEs) which can induce biomolecular damage when incident upon a particular biomolecule. Notable biomolecules include those contained within double-stranded DNA and RNA helices, which upon exposure to LEEs, may form reactive intermediate products that show detriment to their specific structures and functions. Such damaging processes are understood to proceed via dissociative electron attachment (DEA). Using anion resonance stabilisation methods, coupled to state-of-the-art electronic structure methods, and reaction path mapping, the work presented herein highlights the detailed mechanisms associated with molecular elimination of CO and H from the uracil nucleobase following LEE irradiation - providing a rationale for earlier experiments. The results highlight a subset of resonances that show a labile route for forming CO + anionic 1,3-dihydroimidazole (1,3-DHIM-). The nascent 1,3-DHIM anion is itself unstable with respect to N-H bond fission - ultimately forming anionic 1-imidazole (1-IM-) + H products. This hitherto unknown mechanism sheds light on the possible lesion processes that may be encountered by biomolecular constituents when exposed to electron energies analogous to those present in medicinal X-ray diagnostics, aviation and interstellar space. The work also offers some insight into the reactive processes that may have occurred in prebiotic earth.","subset":"pubmed_abstract"} +{"meta":{"pmid":29062608,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"MGST2 and WNT2 are candidate genes for comitant strabismus susceptibility in Japanese patients.\nStrabismus is a common condition with misalignment between two eyes that may lead to decrease of visual acuity, lack of binocularity, and diplopia. It is caused by heterogeneous environmental and genetic risk factors. Our previous research has identified new chromosomal susceptibility loci in 4q28.3 and 7q31.2 regions for comitant strabismus in Japanese families. We conducted a verification study by linkage analysis to narrow the chromosomal loci down to a single gene. From Japanese and U.S. databases, 24 rsSNPs and 233 rsSNPs were chosen from the 4q28.3 and 7q31.2 region, respectively, and were typed in 108 affected subjects and 96 unaffected subjects of 58 families with primary and non-syndromic comitant strabismus. Three major analytical methods were used: transmission disequilibrium test (TDT), TDT allowing for errors (TDTae), and linkage analysis under dominant and recessive inheritance. The SNPs with significant P values in TDT and TDTae were located solely at the gene, microsomal glutathione S-transferase 2 (MGST2), on chromosome 4q28.3 locus. In contrast, significant SNPs were dispersed in a few genes, containing wingless-type MMTV integration site family member 2 (WNT2), on chromosome 7q31.2 locus. The distribution of significant SNPs on the 7q31.2 locus showed that only the ST7 to WNT2 region in the same big haplotype block contained significant SNPs for all three methods of linkage analysis. This study suggests that MGST2 and WNT2 are potential candidates for comitant strabismus in Japanese population.","subset":"pubmed_abstract"} +{"meta":{"pmid":19576203,"dup_signals":{"dup_doc_count":35,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":1,"2020-45":1,"2020-34":1,"2020-29":4,"2020-24":1,"2020-16":1,"2020-10":4,"2020-05":6,"2019-51":1,"2019-47":2,"2019-43":6,"2019-30":1,"2021-25":1}}},"text":"Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors.\nIdentification of multipotent cardiac progenitors has provided important insights into the mechanisms of myocardial lineage specification, yet has done little to clarify the origin of the endocardium. Despite its essential role in heart development, characterization of the endocardial lineage has been limited by the lack of specific markers of this early vascular subpopulation. To distinguish endocardium from other vasculature, we generated an NFATc1-nuc-LacZ BAC transgenic mouse line capable of labeling this specific endothelial subpopulation at the earliest stages of cardiac development. To further characterize endocardiogenesis, embryonic stem cells (ESCs) derived from NFATc1-nuc-LacZ blastocysts were utilized to demonstrate that endocardial differentiation in vitro recapitulates the close temporal-spatial relationship observed between myocardium and endocardium seen in vivo. Endocardium is specified as a cardiac cell lineage, independent from other vascular populations, responding to BMP and Wnt signals that enhance cardiomyocyte differentiation. Furthermore, a population of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors, represents a mesodermal precursor of the endocardial endothelium, as well as other cardiovascular lineages. Taken together, these studies emphasize that the endocardium is a unique cardiac lineage and provides further evidence that endocardium and myocardium are derived from a common precursor.","subset":"pubmed_abstract"} +{"meta":{"pmid":11992153,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Araucnephia iberaensis n. sp., a neotropical black fly with a peculiar distribution (Diptera-Simuliidae).\nAraucnephia Wygodzinsky & Coscar\u00f3n is a Neotropical black fly genus in which only one species from Central Chile is known. Another species has now been found in Corrientes province on the eastern side of the Iber\u00e1 tropical swamps of Argentina, on the western border of the mountainous region of southern Brazil. This new species, A. iberaensis, is herein described and illustrated and information on its bionomics is recorded. It is an interesting species because previous to its discovery no black fly genus or subgenus from Central Chile region has been found in tropical areas, because these two regions are separated by the Monte and Pampas realms. Similarly, no Brazilian genus or subgenus has crossed the Andes mountains to Chile. A comparison with other Neotropical, Nearctic, Ethiopian (Afrotropical) and Australian Prosimuliini (sensu Crosskey & Howard) showed Araucnephia to be a valid taxon most closely related to Araucnephioides (sympatric in Chile). Araucnephia also shows great affinities with Lutzsimulium from Southeast Brazil and Argentina and Paracnephia from South Africa.","subset":"pubmed_abstract"} +{"meta":{"pmid":27558419,"dup_signals":{"dup_doc_count":30,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2018-09":1,"2018-05":1,"2017-39":2,"2017-34":2,"2017-30":2,"2017-26":2,"2017-22":2,"2017-17":2,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":1,"2018-13":1,"2017-13":2}}},"text":"Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human Tissue Ex Vivo.\nUnprotected sexual intercourse with HIV-infected men is the major cause of new infections. HIV virions are released into semen by various cells of the male genital tract, as well as by infected monocytes and lymphocytes present in semen. Some of these virions may attach to the surfaces of cells, infected or uninfected. We investigated whether cells carrying attached HIV on their surfaces can transmit infection. We addressed this question in a model system of human tissue exposed ex vivo to monocytes and lymphocytes carrying HIV on their surfaces. We gamma irradiated the cells to prevent their productive infection. In spite of comparable amounts of HIV attached to monocytes and lymphocytes, only monocytes were capable of transmitting infection and triggering productive infection in tissue. This HIV-1 transmission was mediated by cell-cell contacts. Our experiments suggest that in vivo, HIV attached to infected or uninfected monocytes, which far outnumber lymphocytes in HIV-infected semen, may contribute to sexual transmission of HIV from men to their partners. The vast majority of new HIV infections occur through sexual transmission, in which HIV is transferred from the semen of an infected male to an uninfected partner. In semen, HIV-1 particles may exist as free-floating virions; inside infected cells; or attached to the surfaces of cells, whether they are infected or not. Here, we investigated whether HIV attached to the surfaces of monocytes or lymphocytes could transmit infection to human tissue. Incubation of human tissue with monocyte-attached HIV resulted in productive tissue infection. In contrast, there was no infection of tissues when they were incubated with lymphocyte-attached HIV-1. Our results highlight the important role that seminal monocytes may play in HIV transmission in vivo, especially since monocytes far outnumber lymphocytes in the semen of HIV-infected individuals.","subset":"pubmed_abstract"} +{"meta":{"pmid":25880152,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":2,"2024-26":1,"unknown":10}}},"text":"Changing physician behavior: what works?\nThere are various interventions for guideline implementation in clinical practice, but the effects of these interventions are generally unclear. We conducted a systematic review to identify effective methods of implementing clinical research findings and clinical guidelines to change physician practice patterns, in surgical and general practice. Systematic review of reviews. We searched electronic databases (MEDLINE, EMBASE, and PubMed) for systematic reviews published in English that evaluated the effectiveness of different implementation methods. Two reviewers independently assessed eligibility for inclusion and methodological quality, and extracted relevant data. Fourteen reviews covering a wide range of interventions were identified. The intervention methods used include: audit and feedback, computerized decision support systems, continuing medical education, financial incentives, local opinion leaders, marketing, passive dissemination of information, patient-mediated interventions, reminders, and multifaceted interventions. Active approaches, such as academic detailing, led to greater effects than traditional passive approaches. According to the findings of 3 reviews, 71% of studies included in these reviews showed positive change in physician behavior when exposed to active educational methods and multifaceted interventions. Active forms of continuing medical education and multifaceted interventions were found to be the most effective methods for implementing guidelines into general practice. Additionally, active approaches to changing physician performance were shown to improve practice to a greater extent than traditional passive methods. Further primary research is necessary to evaluate the effectiveness of these methods in a surgical setting.","subset":"pubmed_abstract"} +{"meta":{"pmid":23376480,"dup_signals":{"dup_doc_count":25,"dup_dump_count":23,"dup_details":{"curated_sources":2,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2019-13":1,"2015-18":1,"2017-13":1}}},"text":"Using the Q10 model to simulate E. coli survival in cowpats on grazing lands.\nMicrobiological quality of surface waters can be affected by microbial load in runoff from grazing lands. This effect, with other factors, depends on the survival of microorganisms in animal waste deposited on pastures. Since temperature is a leading environmental parameter affecting survival, it indirectly impacts water microbial quality. The Q10 model is widely used to predict the effect of temperature on rates of biological processes, including survival. Objectives of this work were to (i) evaluate the applicability of the Q10 model to Escherichia coli inactivation in bovine manure deposited on grazing land (i.e., cowpats) and (ii) identify explanatory variables for the previously reported E. coli survival dynamics in cowpats. Data utilized in this study include published results on E. coli concentrations in natural and repacked cowpats from research conducted the U.S. (Virginia and Maryland), New Zealand, and the United Kingdom. Inspection of the datasets led to conceptualizing E. coli survival (in cowpats) as a two-stage process, in which the initial stage was due to growth, inactivation or stationary state of the population and the second stage was the approximately first-order inactivation. Applying the Q10 model to these datasets showed a remarkable similarity in inactivation rates, using the thermal time. The reference inactivation rate constant of 0.042 (thermal days)(-1) at 20 \u00b0C gave a good approximation (R(2)=0.88) of all inactivation stage data with Q10=1.48. The reference inactivation rate constants in individual studies were no different from the one obtained by pooling all data (P<0.05). The rate of logarithm of the E. coli concentration change during the first stage depended on temperature. Duration of the first stage, prior to the first-order inactivation stage and the initial concentration of E. coli in cowpats, could not be predicted from available data. Diet and age are probable factors affecting these two parameters however, until their environmental and management predictors are known, microbial water quality modeling must treat them as a stochastic source of uncertainty in simulation results.","subset":"pubmed_abstract"} +{"meta":{"pmid":24576264,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Preface for buccal drug delivery theme issue.\nDuring the past years, buccal drug delivery has attracted the attention of researchers looking for alternative delivery routes of administration. As an alternative to oral drug delivery, the buccal mucosal route avoids the passage through the acidic gastric environment, intestinal and bacterial enzymatic activity, absorption issues associated with the intestinal epithelium (e.g. P-glycoprotein efflux), and the first pass metabolism of the liver. Therefore, the buccal route could be a good delivery route for macromolecules and other drugs not compatible with the gastrointestinal tract environment. This \"Buccal Drug Delivery\" special edition of Drug Development and Industrial Pharmacy aims to bring together a range of different aspects relevant to the growing field of buccal drug delivery. The special edition includes thorough reviews of the literature, as well as original research articles touching on most prominent features related to buccal drug delivery systems, such as the move toward the use of nanotechnology in different ways to facilitate buccal drug delivery with the potential to prompt future product developments.","subset":"pubmed_abstract"} +{"meta":{"pmid":22346599,"dup_signals":{"dup_doc_count":15,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2013-48":1,"2013-20":1,"2024-26":1,"unknown":6}}},"text":"CAROLS: a new airborne L-band radiometer for ocean surface and land observations.\nThe \"Cooperative Airborne Radiometer for Ocean and Land Studies\" (CAROLS) L-Band radiometer was designed and built as a copy of the EMIRAD II radiometer constructed by the Technical University of Denmark team. It is a fully polarimetric and direct sampling correlation radiometer. It is installed on board a dedicated French ATR42 research aircraft, in conjunction with other airborne instruments (C-Band scatterometer-STORM, the GOLD-RTR GPS system, the infrared CIMEL radiometer and a visible wavelength camera). Following initial laboratory qualifications, three airborne campaigns involving 21 flights were carried out over South West France, the Valencia site and the Bay of Biscay (Atlantic Ocean) in 2007, 2008 and 2009, in coordination with in situ field campaigns. In order to validate the CAROLS data, various aircraft flight patterns and maneuvers were implemented, including straight horizontal flights, circular flights, wing and nose wags over the ocean. Analysis of the first two campaigns in 2007 and 2008 leads us to improve the CAROLS radiometer regarding isolation between channels and filter bandwidth. After implementation of these improvements, results show that the instrument is conforming to specification and is a useful tool for Soil Moisture and Ocean Salinity (SMOS) satellite validation as well as for specific studies on surface soil moisture or ocean salinity.","subset":"pubmed_abstract"} +{"meta":{"pmid":20194151,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":8}}},"text":"Clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma.\nTo identify and assess the clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma (MM). From a prospectively maintained database, we identified 47 patients seen between January 1, 1990, and August 31, 2008, with a diagnosis of AL amyloidosis that was made at least 6 months after MM diagnosis; these patients form the study group. Among the 47 patients, 36 developed typical features, 3 had atypical features, and 8 had an incidental finding of amyloidosis. Amyloid deposits were demonstrated in bone marrow, subcutaneous fat aspirate, or organ biopsy in 24, 19, and 12 patients, respectively. One organ was involved in 29 patients (62%), whereas 11 patients (23%) had involvement in more than one organ. At diagnosis of AL amyloidosis, treatment was changed or started in 22 patients, whereas the same treatment was continued in 21 patients, and no treatment data were available for the rest. The best hematologic response included partial response or better in 11 patients (23%) and stable disease in 18 patients (38%). Improvement in an organ was seen in 3 of the 21 evaluable patients. The median overall survival from diagnosis of AL amyloidosis was 9.1 months (95% confidence interval, 4-14). Of the 6 patients still alive, 2 underwent peripheral blood stem cell transplant, and none had cardiac involvement or involvement in more than one organ. Delayed onset of AL amyloidosis is rarely seen in patients with MM and requires a high index of suspicion for prompt diagnosis. Outcome of these patients is poor, especially in the presence of cardiac involvement.","subset":"pubmed_abstract"} +{"meta":{"pmid":22961293,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":16}}},"text":"Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis.\nAvailable literature suggests that both vitamin D and calcium may be associated with a wide range of non-skeletal outcomes. However, epidemiological evidence supporting their individual associations with incident cerebrovascular disease is scarce. We conducted a systematic review and meta-analysis of prospective cohort studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases, and reported cerebrovascular disease (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke, cerebrovascular accident or transient ischemic attack) by circulating vitamin D (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two independent investigators abstracted information on 25(OH)D and calcium, cerebrovascular outcomes and other characteristics from selected studies. Relative risks (RRs) were pooled by both random and fixed effects meta-analyses and were further examined under different study-level characteristics. Publication bias was assessed with funnel plots and Egger's asymmetry test. From 5,778 initial references, nine unique prospective cohort studies met our inclusion criteria. Seven studies (involving 47,809 participants and 926 cerebrovascular events) focused on circulating 25(OH)D and 3 reported on circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a comparison of individuals in the top third versus those in the bottom third at baseline, the combined RR for cerebrovascular disease, adjusted for several conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in the prospective studies that reported on baseline circulating calcium levels for cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent evidence of heterogeneity or publication bias among included studies. Available data indicate that higher circulating level of vitamin D is associated with a decreased risk of cerebrovascular disease. Conversely, higher circulating calcium concentration is associated with an increased risk of cerebrovascular disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":26033457,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Male burying beetles extend, not reduce, parental care duration when reproductive competition is high.\nMale parents spend less time caring than females in many species with biparental care. The traditional explanation for this pattern is that males have lower confidence of parentage, so they desert earlier in favour of pursuing other mating opportunities. However, one recent alternative hypothesis is that prolonged male parental care might also evolve if staying to care actively improves paternity. If this is the case, an increase in reproductive competition should be associated with increased paternal care. To test this prediction, we manipulated the level of reproductive competition experienced by burying beetles, Nicrophorus vespilloides (Herbst, 1783). We found that caregiving males stayed for longer and mated more frequently with their partner when reproductive competition was greater. Reproductive productivity did not increase when males extended care. Our findings provide support for the increased paternity hypothesis. Extended duration of parental care may be a male tactic both protecting investment (in the current brood) and maximizing paternity (in subsequent brood(s) via female stored sperm) even if this fails to maximize current reproductive productivity and creates conflict of interest with their mate via costs associated with increased mating frequency.","subset":"pubmed_abstract"} +{"meta":{"pmid":16983407,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"Statistical adaptive sensing by detectors with spectrally overlapping bands.\nIt has recently been reported that by using a spectral-tuning algorithm, the photocurrents of multiple detectors with spectrally overlapping responsivities can be optimally combined to synthesize, within certain limits, the response of a detector with an arbitrary responsivity. However, it is known that the presence of noise in the photocurrent can degrade the performance of this algorithm significantly, depending on the choice of the responsivity spectrum to be synthesized. We generalize this algorithm to accommodate noise. The results are applied to quantum-dot mid-infrared detectors with bias-dependent spectral responses. Simulation and experiment are used to show the ability of the algorithm to reduce the adverse effect of noise on its spectral-tuning capability.","subset":"pubmed_abstract"} +{"meta":{"pmid":20181225,"dup_signals":{"dup_doc_count":12,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2019-04":1,"2018-43":1,"2018-34":2,"2018-22":1,"2018-13":1,"2017-51":2,"2017-43":2,"2019-30":1}}},"text":"Exploring the promises of intersectionality for advancing women's health research.\nWomen's health research strives to make change. It seeks to produce knowledge that promotes action on the variety of factors that affect women's lives and their health. As part of this general movement, important strides have been made to raise awareness of the health effects of sex and gender. The resultant base of knowledge has been used to inform health research, policy, and practice. Increasingly, however, the need to pay better attention to the inequities among women that are caused by racism, colonialism, ethnocentrism, heterosexism, and able-bodism, is confronting feminist health researchers and activists. Researchers are seeking new conceptual frameworks that can transform the design of research to produce knowledge that captures how systems of discrimination or subordination overlap and \"articulate\" with one another. An emerging paradigm for women's health research is intersectionality. Intersectionality places an explicit focus on differences among groups and seeks to illuminate various interacting social factors that affect human lives, including social locations, health status, and quality of life. This paper will draw on recently emerging intersectionality research in the Canadian women's health context in order to explore the promises and practical challenges of the processes involved in applying an intersectionality paradigm. We begin with a brief overview of why the need for an intersectionality approach has emerged within the context of women's health research and introduce current thinking about how intersectionality can inform and transform health research more broadly. We then highlight novel Canadian research that is grappling with the challenges in addressing issues of difference and diversity. In the analysis of these examples, we focus on a largely uninvestigated aspect of intersectionality research - the challenges involved in the process of initiating and developing such projects and, in particular, the meaning and significance of social locations for researchers and participants who utilize an intersectionality approach. The examples highlighted in the paper represent important shifts in the health field, demonstrating the potential of intersectionality for examining the social context of women's lives, as well as developing methods which elucidate power, create new knowledge, and have the potential to inform appropriate action to bring about positive social change.","subset":"pubmed_abstract"} +{"meta":{"pmid":23748955,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Genome Maps, a new generation genome browser.\nGenome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https:\/\/github.com\/compbio-bigdata-viz\/genome-maps). Genome Maps is available at: http:\/\/www.genomemaps.org.","subset":"pubmed_abstract"} +{"meta":{"pmid":14978251,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor.\nDehydroepiandrosterone sulfotransferase (SULT2A1) is a cytosolic enzyme that mediates sulfo-conjugation of endogenous hydroxysteroids (dehydroepiandrosterone, testosterone, bile acids), and diverse xenobiotic compounds. Upon sulfonation, SULT2A1 substrates become polar and water-soluble and thus suitable for rapid excretion. SULT2A1 is abundantly expressed in the liver and intestine. Recent evidence has shown that the ligand-activated vitamin D receptor (VDR) can transcriptionally induce the xenobiotic-metabolizing cytochrome P450 enzymes. Herein, we report that VDR also targets SULT2A1 for transcriptional activation. Vitamin D stimulated endogenous SULT2A1 expression and induced transfected human, mouse, and rat SULT2A1 promoters in liver and intestinal cells upon cotransfection with VDR. An inverted repeat DNA element (IR0), located within -191 to -168 positions of mouse and rat Sult2A1, mediates VDR induction of Sult2A1. DNase1 footprinting, competition EMSA, and antibody supershift assay showed that the IR0 is a binding site for the RXR-alpha\/VDR heterodimer. Point mutations within the IR0 prevented RXR\/VDR binding and abolished VDR-mediated Sult2A1 induction. The IR0 element conferred VDR responsiveness on a thymidine kinase promoter. Thus, VDR-mediated nuclear signaling may be important in the phase II metabolism involving Sult2A1. The rodent Sult2A1 gene is also induced by the farnesoid X receptor (FXR) and pregnane X receptor (PXR) through the same IR0. In competition transfections, FXR or PXR inhibited VDR induction of the IR0. Competitive functional interactions among VDR, PXR, and FXR suggest that the intracellular hormonal and metabolic milieu may determine the extent to which a specific nuclear receptor pathway would influence steroid\/xenobiotic metabolism using dehydroepiandrosterone sulfotransferase.","subset":"pubmed_abstract"} +{"meta":{"pmid":22749353,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":1,"2024-22":1,"2024-30":1,"unknown":8}}},"text":"GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells.\nGM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103(+) DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103(+) and CD11b(+) DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8(+) T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8(+) T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":29321231,"dup_signals":{"dup_doc_count":11}},"text":"Chronic traumatic encephalopathy in an epilepsy surgery cohort: Clinical and pathologic findings.\nTo determine the occurrence of chronic traumatic encephalopathy (CTE) in young adult patients undergoing epilepsy surgery. Ten patients who underwent epilepsy surgery were randomly selected for this retrospective study. The patients were 18-45 years of age, had preoperative neuropsychological evaluation, and had 1 year postoperative follow-up. Microscopic sections from resections were evaluated for the presence of CTE with standard stains and antibodies to tau (clone AT8). The median age at resection was 32.5 years (range 23-43) and the median duration of seizures was 23.5 years (range 3-28). Eight had a history of head injury. Preoperative neuropsychological testing showed mild to moderate cognitive impairment in 8 patients (80%). Pathologic examination in one patient showed focal sparse tau-immunoreactive lesions along descending rami and cortical gyral depths of the resected frontal lobe. Nine patients had no evidence of CTE. All focal cortical resections showed variable subpial and subcortical gliosis commonly identified in patients with chronic seizure disorders. The present small retrospective observational study suggests that CTE may occur, but appears uncommon, in young adult patients undergoing surgical treatment for drug-resistant focal epilepsy. The significance of these findings requires further investigation to define the relative importance of tau accumulation in younger adult patients with drug-resistant focal epilepsy and cognitive decline.","subset":"pubmed_abstract"} +{"meta":{"pmid":17251132,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the US, UK and the Netherlands.\nAn increasing number of avian flu cases in humans, arising primarily from direct contact with poultry, in several regions of the world have prompted the urgency to develop pandemic preparedness plans worldwide. Leading recommendations in these plans include basic public health control measures for minimizing transmission in hospitals and communities, the use of antiviral drugs and vaccination. This paper presents a mathematical model for the evaluation of the pandemic flu preparedness plans of the United States (US), the United Kingdom (UK) and the Netherlands. The model is used to assess single and combined interventions. Using data from the US, we show that hospital and community transmission control measures alone can be highly effective in reducing the impact of a potential flu pandemic. We further show that while the use of antivirals alone could lead to very significant reductions in the burden of a pandemic, the combination of transmission control measures, antivirals and vaccine gives the most 'optimal' result. However, implementing such an optimal strategy at the onset of a pandemic may not be realistic. Thus, it is important to consider other plausible alternatives. An optimal preparedness plan is largely dependent on the availability of resources; hence, it is country-specific. We show that countries with limited antiviral stockpiles should emphasize their use therapeutically (rather than prophylactically). However, countries with large antiviral stockpiles can achieve greater reductions in disease burden by implementing them both prophylactically and therapeutically. This study promotes alternative strategies that may be feasible and attainable for the US, UK and the Netherlands. It emphasizes the role of hospital and community transmission control measures in addition to the timely administration of antiviral treatment in reducing the burden of a flu pandemic. The latter is consistent with the preparedness plans of the UK and the Netherlands. Our results indicate that for low efficacy and coverage levels of antivirals and vaccine, the use of a vaccine leads to the greatest reduction in morbidity and mortality compared with the singular use of antivirals. However, as these efficacy and coverage levels are increased, the use of antivirals is more effective.","subset":"pubmed_abstract"} +{"meta":{"pmid":33693684,"dup_signals":{"dup_doc_count":94,"dup_dump_count":22,"dup_details":{"curated_sources":2,"2023-50":7,"2023-40":5,"2023-23":4,"2023-14":5,"2023-06":10,"2022-49":7,"2022-40":2,"2022-33":2,"2022-27":6,"2022-21":2,"2022-05":6,"2021-49":1,"2021-43":4,"2021-39":7,"2021-31":4,"2021-21":4,"2021-17":4,"2024-26":1,"2024-22":3,"2024-18":5,"2024-10":2,"2024-30":1}}},"text":"A Biomarker-based Biological Age in UK Biobank: Composition and Prediction of Mortality and Hospital Admissions.\nChronological age is the strongest risk factor for most chronic diseases. Developing a biomarker-based age and understanding its most important contributing biomarkers may shed light on the effects of age on later-life health and inform opportunities for disease prevention. A subpopulation of 141 254 individuals healthy at baseline were studied, from among 480 019 UK Biobank participants aged 40-70 recruited in 2006-2010, and followed up for 6-12 years via linked death and secondary care records. Principal components of 72 biomarkers measured at baseline were characterized and used to construct sex-specific composite biomarker ages using the Klemera Doubal method, which derived a weighted sum of biomarker principal components based on their linear associations with chronological age. Biomarker importance in the biomarker ages was assessed by the proportion of the variation in the biomarker ages that each explained. The proportions of the overall biomarker and chronological age effects on mortality and age-related hospital admissions explained by the biomarker ages were compared using likelihoods in Cox proportional hazard models. Reduced lung function, kidney function, reaction time, insulin-like growth factor 1, hand grip strength, and higher blood pressure were key contributors to the derived biomarker age in both men and women. The biomarker ages accounted for >65% and >84% of the apparent effect of age on mortality and hospital admissions for the healthy and whole populations, respectively, and significantly improved prediction of mortality (p < .001) and hospital admissions (p < 1 \u00d7 10-10) over chronological age alone. This study suggests that a broader, multisystem approach to research and prevention of diseases of aging warrants consideration.","subset":"pubmed_abstract"} +{"meta":{"pmid":20946689,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":11}}},"text":"Changing malaria intervention coverage, transmission and hospitalization in Kenya.\nReports of declining incidence of malaria disease burden across several countries in Africa suggest that the epidemiology of malaria across the continent is in transition. Whether this transition is directly related to the scaling of intervention coverage remains a moot point. Paediatric admission data from eight Kenyan hospitals and their catchments have been assembled across two three-year time periods: September 2003 to August 2006 (pre-scaled intervention) and September 2006 to August 2009 (post-scaled intervention). Interrupted time series (ITS) models were developed adjusting for variations in rainfall and hospital use by surrounding communities to show changes in malaria hospitalization over the two periods. The temporal changes in factors that might explain changes in disease incidence were examined sequentially for each hospital setting, compared between hospital settings and ranked according to plausible explanatory factors. In six out of eight sites there was a decline in Malaria admission rates with declines between 18% and 69%. At two sites malaria admissions rates increased by 55% and 35%. Results from the ITS models indicate that before scaled intervention in September 2006, there was a significant month-to-month decline in the mean malaria admission rates at four hospitals (trend P < 0.05). At the point of scaled intervention, the estimated mean admission rates for malaria was significantly less at four sites compared to the pre-scaled period baseline. Following scaled intervention there was a significant change in the month-to-month trend in the mean malaria admission rates in some but not all of the sites. Plausibility assessment of possible drivers of change pre- versus post-scaled intervention showed inconsistent patterns however, allowing for the increase in rainfall in the second period, there is a suggestion that starting transmission intensity and the scale of change in ITN coverage might explain some but not all of the variation in effect size. At most sites where declines between observation periods were documented admission rates were changing before free mass ITN distribution and prior to the implementation of ACT across Kenya. This study provides evidence of significant within and between location heterogeneity in temporal trends of malaria disease burden. Plausible drivers for changing disease incidence suggest a complex combination of mechanisms, not easily measured retrospectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":17651192,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Heterozygosity-fitness correlations in a bottlenecked island species: a case study on the Seychelles warbler.\nWe used capture-mark-recapture models to investigate the effects of both individual and parental heterozygosity, measured at microsatellite loci on the survival of Seychelles warblers (Acrocephalus sechellensis), an endemic island species which went through a severe population bottleneck in the middle of the last century. We found that an individual's survival was not correlated with multilocus heterozygosity, or with heterozygosity at any specific locus. However, maternal, but not paternal, multilocus heterozygosity was positively associated with offspring survival, but only in years with low survival probabilities. A nestling cross-fostering experiment showed that this was a direct maternal effect as there was an effect of the genetic mother's, but not of the social mother's, heterozygosity. Heterozygosity-fitness correlations at microsatellite markers were generally assumed to reflect genome-wide effects. Although this might be true in partially inbred populations, such correlations may also arise as a result of local effects with specific markers being closely linked to genes which determine fitness. However, heterozygosity at the individual microsatellite loci was not correlated and therefore does not seem to reflect genome-wide heterozygosity. This suggests that even in a small bottlenecked population, heterozygosity-fitness correlations may not be caused by genome-wide effects. Support for the local effects hypothesis was also equivocal; although three specific loci were associated with offspring survival, including all single-locus heterozygosities as independent predictors for the variation in survival was not supported by the data. Furthermore, in contrast to the local effects hypothesis, the loci which contributed most to the heterozygosity-survival relationship were not more polymorphic than the other loci. This study highlights the difficulties in distinguishing between the two hypotheses.","subset":"pubmed_abstract"} +{"meta":{"pmid":18473668,"dup_signals":{"dup_doc_count":23,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":2,"2017-13":1,"2015-18":3,"2015-11":1,"2014-10":1,"2024-30":1,"unknown":11}}},"text":"Bullying perspectives among rural youth: a mixed methods approach.\nFew studies have examined violence among rural youth even though it is recognized as a societal concern. A mixed method, descriptive study was conducted to examine violence among rural youth including their perceptions and experiences of it. This article focuses specifically on the perceptions and experiences of bullying among rural youth that were generated from the Qualitative Phase One interviews and Quantitative Phase Two responses. A mixed method study was conducted in two separate phases. The information generated from the Qualitative Phase One (n = 52) was used to develop a survey instrument employed in the subsequent Quantitative Phase Two (n = 180). The youth who were involved in each phase lived in different geographic areas of a Western Canadian province. The qualitative phase generated a number of comments about the experience of being bullied or how it felt to be a bully. In the survey instrument, specific questions related to bullying were embedded within it. Demographic information was collected in both phases of the study. Research assistants were used to collect the data in each phase. The transcripts from the qualitative phase were analyzed for categories and themes. The survey instrument included demographic questions and seventy questions that included a four-point Likert scale. The data were analyzed using SPSS v14 (SPSS Inc; Chicago, IL, USA). For this article, the survey questions that focused on bullying were considered alongside the qualitative comments in order to more fully understand the perceptions and viewpoints of rural youth regarding this particular aspect of violence. Conducting a mixed method study provides a more in-depth understanding of bullying among youth in the rural context. The pain and humiliation of being bullied provided a personalized understanding of the survey responses that indicated which youth are targets of bullying. For example, comments were made about being picked on because of personal characteristics such as being overweight or dressing in an unacceptable manner. In addition, bullies openly talked about the power they gained from their role. The frequency responses to the questions in the survey confirmed that bullies obtain power from their behavior and that youth who are different are bullied. The participants also noted that something needed to be done to address bullying but remarked that they would not seek professionals' help. The findings negate the myth that rural places are ideal places to raise children. Although the youth did not identify that they would access professionals, it is important for members of rural communities to acknowledge bullying, its impacts and how they can prevent it. Working from the social structure of rural communities is a first step in this process. Rural communities will benefit as a whole if bullying, an important societal concern, is addressed. Building on the social structure of rural communities is important, However, listening to rural youth themselves is the key if true change is to be implemented.","subset":"pubmed_abstract"} +{"meta":{"pmid":8031500,"dup_signals":{"dup_doc_count":51,"dup_dump_count":42,"dup_details":{"curated_sources":2,"2023-40":1,"2023-23":3,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-21":2,"2022-05":1,"2021-49":1,"2021-43":2,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-40":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":2,"2018-17":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2024-18":3,"2024-10":1,"2017-13":1,"2024-22":1}}},"text":"The nucleus accumbens in monkeys (Macaca fascicularis): I. The organization of behaviour.\nA behavioural comparison was made between six unoperated control monkeys and six monkeys which received bilateral ibotenic acid lesions of the nucleus accumbens. Two of the control monkeys were subsequently given bilateral lesions of the anterior cingulate and medial frontal cortex (areas 24, 25 and 32) and were retested on the behavioural tasks. The NA lesioned monkeys, but not the anterior cingulate lesioned monkeys, were significantly impaired on a hoarding task in which they were required to remove 18 peanuts from their shells and store them in their cheek pouches. These same monkeys were not impaired when the nuts were presented without shells. Evidence is provided which suggests that this deficit is not motivational or due to gross motor impairments. A second task in which the animals were required to search through four boxes to retrieve food revealed a decrease in the tendency for the NA and cingulate lesioned animals to use an organized pattern of searching. Both groups were found to return to a previously opened box more often than controls. However, neither group showed signs of perseverative behaviour. Data from a ten-box version of this task suggest that these return errors were not due to a decrease in working memory. Together these studies suggest that both the NA and the anterior cingulate cortex contribute to the ability to organize behaviour temporally and spatially.","subset":"pubmed_abstract"} +{"meta":{"pmid":29510423,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth.\nTo evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death\/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci.","subset":"pubmed_abstract"} +{"meta":{"pmid":23020813,"dup_signals":{"dup_doc_count":26,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":1,"2015-35":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":3,"2015-18":1}}},"text":"Global trends in exclusive breastfeeding.\nInfant and young child feeding is critical for child health and survival. Proportion of infants 0-5 months who are fed exclusively with breast milk is a common indicator used for monitoring and evaluating infant and young child feeding in a given country and region. Despite progress made since 1990, a previous review in 2006 of global and regional trends found improvement to be modest. The current study provides an update in global and regional trends in exclusive breastfeeding from 1995 to 2010, taking advantage of the wealth of data from recent household surveys. Using the global database of infant and young child feeding maintained by the United Nations Children's Fund, the authors examined estimates from 440 household surveys in 140 countries over the period between 1995 and 2010 and calculated global and regional averages of the rate of exclusive breastfeeding among infants 0-5 months for the two time points to assess the trends. Trend data suggest the prevalence of exclusive breastfeeding among infants younger than six months in developing countries increased from 33% in 1995 to 39% in 2010. The prevalence increased in almost all regions in the developing world, with the biggest improvement seen in West and Central Africa. In spite of the well-recognized importance of exclusive breastfeeding, the practice is not widespread in the developing world and increase on the global level is still very modest with much room for improvement. Child nutrition programmes worldwide continue to require investments and commitments to improve infant feeding practices in order to have maximum impact on children's lives.","subset":"pubmed_abstract"} +{"meta":{"pmid":18369258,"dup_signals":{"dup_doc_count":25,"dup_dump_count":20,"dup_details":{"curated_sources":2,"2016-30":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":2,"2014-42":2,"2014-41":2,"2016-36":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1}}},"text":"Modeling, clustering, and segmenting video with mixtures of dynamic textures.\nA dynamic texture is a spatio-temporal generative model for video, which represents video sequences as observations from a linear dynamical system. This work studies the mixture of dynamic textures, a statistical model for an ensemble of video sequences that is sampled from a finite collection of visual processes, each of which is a dynamic texture. An expectationmaximization (EM) algorithm is derived for learning the parameters of the model, and the model is related to previous works in linear systems, machine learning, time-series clustering, control theory, and computer vision. Through experimentation, it is shown that the mixture of dynamic textures is a suitable representation for both the appearance and dynamics of a variety of visual processes that have traditionally been challenging for computer vision (e.g. fire, steam, water, vehicle and pedestrian traffic, etc.). When compared with state-of-the-art methods in motion segmentation, including both temporal texture methods and traditional representations (e.g. optical flow or other localized motion representations), the mixture of dynamic textures achieves superior performance in the problems of clustering and segmenting video of such processes.","subset":"pubmed_abstract"} +{"meta":{"pmid":16763113,"dup_signals":{"dup_doc_count":22,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2024-22":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2024-30":1,"unknown":14}}},"text":"The importance of demographic niches to tree diversity.\nMost ecological hypotheses about species coexistence hinge on species differences, but quantifying trait differences across species in diverse communities is often unfeasible. We examined the variation of demographic traits using a global tropical forest data set covering 4500 species in 10 large-scale tree inventories. With a hierarchical Bayesian approach, we quantified the distribution of mortality and growth rates of all tree species at each site. This allowed us to test the prediction that demographic differences facilitate species richness, as suggested by the theory that a tradeoff between high growth and high survival allows species to coexist. Contrary to the prediction, the most diverse forests had the least demographic variation. Although demographic differences may foster coexistence, they do not explain any of the 16-fold variation in tree species richness observed across the tropics.","subset":"pubmed_abstract"} +{"meta":{"pmid":19014428,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":11}}},"text":"GOLPH2 expression in renal cell cancer.\nRenal cell carcinomas (RCC) are among the most common and most lethal genitourinary malignancies. GOLPH2 (golgi phosphoprotein 2, GOLM1) has recently been proposed as a biomarker for hepatocellular and prostate cancer. In this study we analysed the expression patterns and the prognostic and diagnostic value of GOLPH2 in RCC. GOLPH2 protein expression was analysed by immunohistochemistry in 104 clinically well characterized RCC cases in comparison with matched normal kidney tissue and in association with clinico-pathological parameters. Statistical analyses including Kaplan Meier analyses were performed with SPSS version 15.0. GOLPH2 was highly expressed in normal renal tubules and in almost half of RCC with a statistically significant predominance in the papillary and chromophobe histological subtypes. No other associations with clinico-pathological parameters were detectable. The Kaplan-Meier curves showed a weak trend for unfavourable prognosis of tumours with high GOLPH2 expression, but failed significance. GOLPH2 protein is expressed in normal renal tissue (especially in distal tubular epithelia) and is down-regulated in the majority of clear cell RCC. In papillary and chromophobe RCC GOLPH2 expression is consistently present. In contrast to its diagnostic value in hepatocellular and prostatic carcinomas, a prognostic or diagnostic value of GOLPH2 in RCC appears to be unlikely.","subset":"pubmed_abstract"} +{"meta":{"pmid":30479355,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2022-40":1,"2022-33":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-40":1,"2019-47":1,"2019-43":2,"2019-35":1,"2019-26":1,"2023-50":1}}},"text":"Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis.\nRecently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":27535970,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":3,"unknown":15}}},"text":"Regulation of HIF1\u03b1 under Hypoxia by APE1\/Ref-1 Impacts CA9 Expression: Dual Targeting in Patient-Derived 3D Pancreatic Cancer Models.\nPancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States. Aggressive treatment regimens have not changed the disease course, and the median survival has just recently reached a year. Several mechanisms are proposed to play a role in PDAC therapeutic resistance, including hypoxia, which creates a more aggressive phenotype with increased metastatic potential and impaired therapeutic efficacy. AP Endonuclease-1\/Redox Effector Factor 1 (APE1\/Ref-1) is a multifunctional protein possessing a DNA repair function in base excision repair and the ability to reduce oxidized transcription factors, enabling them to bind to their DNA target sequences. APE1\/Ref-1 regulates several transcription factors involved in survival mechanisms, tumor growth, and hypoxia signaling. Here, we explore the mechanisms underlying PDAC cell responses to hypoxia and modulation of APE1\/Ref-1 redox signaling activity, which regulates the transcriptional activation of hypoxia-inducible factor 1 alpha (HIF1\u03b1). Carbonic anhydrase IX (CA9) is regulated by HIF1\u03b1 and functions as a part of the cellular response to hypoxia to regulate intracellular pH, thereby promoting cell survival. We hypothesized that modulating APE1\/Ref-1 function will block activation of downstream transcription factors, STAT3 and HIF1\u03b1, interfering with the hypoxia-induced gene expression. We demonstrate APE1\/Ref-1 inhibition in patient-derived and established PDAC cells results in decreased HIF1\u03b1-mediated induction of CA9. Furthermore, an ex vivo three-dimensional tumor coculture model demonstrates dramatic enhancement of APE1\/Ref-1-induced cell killing upon dual targeting of APE1\/Ref-1 and CA9. Both APE1\/Ref-1 and CA9 are under clinical development; therefore, these studies have the potential to direct novel PDAC therapeutic treatment. Mol Cancer Ther; 15(11); 2722-32. \u00a92016 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":12324610,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Arabidopsis Mutants Lacking Blue Light-Dependent Inhibition of Hypocotyl Elongation.\nWe have isolated a new class of photomorphogenic mutants in Arabidopsis. Hypocotyl elongation is not inhibited in the mutant seedlings by continuous blue light but is inhibited by far red light, indicating that these mutations are phenotypically different from the previously isolated long hypocotyl (hy) mutants. Complementation analysis indicated that recessive nuclear mutations at three genetic loci, designated blu1, blu2, and blu3, can result in the blu mutant phenotype and that these mutants are genetically distinct from other long hypocotyl mutants. The BLU genes appear to be important only during seedling development because the blu mutations have little effect on mature plants, whereas hypocotyl elongation and cotyledon expansion are altered in seedlings. The genetic separation of the blue and far red sensitivities of light-induced hypocotyl inhibition in the blu and hy mutants demonstrates that two photosensory systems function in this response.","subset":"pubmed_abstract"} +{"meta":{"pmid":19675008,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Whether depositing fat or losing weight, fish maintain a balance.\nIn fish, the relative amount of tissues of different densities changes significantly over short periods throughout the year, depending on the availability of food, nutrition and their developmental status, such as sexual maturation. If a land-living animal accumulates fat it influences not only its general state of health, but also markedly increases its energy expenditure for locomotion owing to the force of gravity. On a body submerged in water, this force, which acts on the centre of gravity (COG), is counterbalanced by a lifting force that is negligible in air and which acts on the centre of buoyancy (COB). Any difference in the longitudinal positions of the two centres will therefore result in pitching moments that must be counteracted by body or fin movements. The displacement of the COG away from the COB is a result of tissues of different density (e.g. bones and fat) not being distributed homogeneously along the body axis. Moreover, the proportions of tissues of different densities change significantly with feeding status. It is still unknown whether these changes produce a displacement of the COG and thus affect the hydrostatic stability of fish. Analysis of computed tomography and magnetic resonance imaging images of Atlantic herring, Atlantic salmon and Atlantic mackerel reveals that the COG is fairly constant in each species, although we recorded major interspecies differences in the relative amount of fat, muscle and bone. We conclude that the distribution of different tissues along the body axis is very closely adjusted to the swimming mode of the fish by keeping the COG constant, independent of the body fat status, and that fish can cope with large variations in energy intake without jeopardizing their COG and thus their swimming performance.","subset":"pubmed_abstract"} +{"meta":{"pmid":17989160,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"The relationship between the components of pulmonary artery pressure remains constant under all conditions in both health and disease.\nThe relationships among systolic pulmonary artery pressure (SPAP), diastolic pulmonary artery pressure (DPAP), and mean pulmonary artery pressure (MPAP) have been found to be constant in humans breathing air, at rest, while supine. It would be important for those studying the pulmonary circulation if this relationship were maintained under other circumstances, such as change in posture, during exercise, or after pharmacologic manipulation. In particular, it would be useful if the relationship were maintained when treating pulmonary hypertension because this would allow different methods of measurement to be compared, such as SPAP from echocardiography and MPAP from right heart catheterization. Data were reviewed from both healthy subjects and those with pulmonary hypertension (n = 65) who had a micromanometer-tipped, high-fidelity pulmonary artery catheter inserted for between 6 and 36 h in the Scottish Pulmonary Vascular Unit between 1997 and 2003. The 5-min averages, while the patient was supine at rest, were analyzed by linear regression to compare the response of SPAP and DPAP with MPAP. There were linear relationships (measured in millimeters of mercury) of SPAP with MPAP (SPAP = 1.50 MPAP + 0.46), and DPAP with MPAP (DPAP = 0.71 MPAP - 0.66). These were maintained with a high degree of accuracy following changes in posture and activity. SPAP, MPAP, and DPAP were strongly related, and these relationships were maintained under varying conditions. This finding will allow comparison between invasive and noninvasive descriptions of pulmonary hemodynamics found in the literature.","subset":"pubmed_abstract"} +{"meta":{"pmid":26061961,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Animal personality in a foundation species drives community divergence and collapse in the wild.\nDespite thousands of papers on the topic, precious few of the studies on animal personality have considered the role of personality in shaping community-level processes. Here, we test the effect of individual variation on the long-term trajectories of biological communities, from initiation to their demise. The spider Anelosimus studiosus builds webs that serve as habitat for >50 species of spider, which together construct a species-rich silken reef. This species also exhibits a temporally consistent behavioural polymorphism where females exhibit either an aggressive or docile phenotype (personality). In this study, we established incipient colonies of either two docile or two aggressive females and then tracked community succession and persistence over 7 years in the field. In particular, we noted the community compositions associated with colony extinction\/collapse events, which are common in this species. The community composition of webs founded by different phenotypes diverged rapidly in their early successional stages. However, this period of divergence was ephemeral and all communities eventually converged on a similar composition; communities founded by aggressive females merely took longer to reach it. This secondary stage of community convergence was itself short-lived and independent of founders' personality; all communities collapsed within a year of achieving it. Experimentally imposing this fatal climax composition on colonies caused 80% of communities to collapse within a year, suggesting that this climax composition actually causes the collapse of the community. Community collapse was characterized by a complete die-off of the foundation species and the dispersal of all other spiders. Thus, the behavioural traits of the founding, foundational individuals of these communities dictate their path of succession and longevity in the wild.","subset":"pubmed_abstract"} +{"meta":{"pmid":23426511,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Excess nicotinamide increases plasma serotonin and histamine levels.\nMethylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).","subset":"pubmed_abstract"} +{"meta":{"pmid":35341240,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Confronting the Challenging Asymmetric Carbonyl 1,2-Addition Using Vinyl Heteroarene Pronucleophiles: Ligand-Controlled Regiodivergent Processes through a Dearomatized Allyl-Cu Species.\nThe selective reductive coupling of vinyl heteroarenes with aldehydes and ketones represents a versatile approach for the rapid construction of enantiomerically enriched secondary and tertiary alcohols, respectively. Herein, we demonstrate a CuH-catalyzed regiodivergent coupling of vinyl heteroarenes with carbonyl-containing electrophiles, in which the selectivity is controlled by the ancillary ligand. This approach leverages an in situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either the dearomatized or exocyclic addition products, respectively. The method exhibits excellent regio-, diastereo-, and enantioselectivity and tolerates a range of common functional groups and heterocycles. The dearomative pathway allows direct access to a variety of functionalized saturated heterocyclic structures. The reaction mechanism was probed using a combination of experimental and computational approach. Density functional theory studies suggest that the ligand-controlled regioselectivity results from the C-H\/\u03c0 interaction and steric repulsion in transition states, leading to the major and minor regioisomers, respectively. Hydrocupration of vinyl heteroarene pronucleophile is the enantiodetermining step, whereas the diastereoselectivity is enforced by steric interactions between the benzylic or allyl-Cu intermediate and carbonyl-containing substrates in a six-membered cyclic transition state.","subset":"pubmed_abstract"} +{"meta":{"pmid":2995611,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Topography of cytochrome oxidase activity in owl monkey cortex.\nIn primate cortical tissue which has been stained for the mitochondrial enzyme cytochrome oxidase, a topographical pattern of regularly spaced blobs has been demonstrated in primary visual cortex (Hendrickson, A. E., S. P. Hunt, and J. -Y. Wu (1981) Nature 292: 605-607; Horton, J. C., and D. H. Hubel (1981) Nature 292: 762-764), and a pattern of stripes has been shown in secondary visual cortex (V2) as well (Livingstone, M. S., and D. H. Hubel (1982) Proc. Natl. Acad. Sci. U. S. A. 79: 6098-6101; Tootell, R. B. H., M. S. Silverman, E. Switkes, and R. L. De Valois (1982) Soc. Neurosci. Abstr. 8: 707). These regular cytoarchitectonic landmarks have proven extremely useful in parsing the functional and anatomical architecture of these two cortical areas. In order to look for similar landmarks in other cortical areas of a primate, we completely unfolded the cortical gray matter in the owl monkey (Aotus trivirgatus), sectioned it parallel with the flattened cortical surface, and stained the tissue for cytochrome oxidase. Distinctive cytochrome oxidase topographies were found in about seven different cortical areas. As in other primates, area V1 is characterized by blobs and area V2 is characterized by strips. In the owl monkey, area MT is characterized by an elaborate topography of dark staining in layers 1 to 4, interspersed with light blob-shaped regions, and partially surrounded by a dark ring. Many of these topographic inhomogeneities are also reflected in the lower layer myelination topography in MT. Visual area(s) VP\/VA is characterized by an irregular or strip-like topography. In some animals, a distinctive topography can be seen in area DX, which is presumably equivalent to either area DM or DI. Primary auditory cortex stains very darkly, but the overall shape of area A is quite variable and the borders are indistinct. Somatosensory area 3B stains quite darkly with sharp borders, but again the overall shape of area 3B is different from that previously described.","subset":"pubmed_abstract"} +{"meta":{"pmid":33167476,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"The Influence of Aerobic Fitness on Heart Rate Responses of Custody Assistant Recruits during Circuit Training Sessions.\nThis study captured heart rate (HR) responses of custody assistant (CA) recruits undertaking circuit training sessions. Data from 10 male and 12 female CA recruits were analyzed. Based on YMCA step test recovery HR, recruits were divided into higher fitness (HF; top 25%), lower fitness (LF; bottom 25%), and moderate fitness (MF; remaining recruits) groups. HR was measured during two circuit training sessions featuring calisthenics and running. HR zones were defined as: very light (<57% of age-predicted maximum heart-rate [HRmax]); light (57-63% HRmax); moderate (64-76% HRmax); vigorous (77-95% HRmax); and very vigorous (>95% HRmax). A one-way ANOVA, with Bonferroni post hoc, calculated between-group differences in time spent, and percentage of total time, in the HR zones. In session one, the LF group spent less time in the light training zone compared to the MF group, and more time in the very vigorous zone compared to the HF group (p = 0.027-0.047). In session two, the LF group spent more time in the moderate zone compared to both groups, and a greater percentage of time in the very vigorous zone compared to the MF group (p = 0.002-0.004). LF recruits generally worked harder during circuit training than their fitter counterparts, which supported recommendations for ability-based modifications.","subset":"pubmed_abstract"} +{"meta":{"pmid":18007776,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-22":1,"2016-44":1}}},"text":"Two-photon spectroscopy and analysis with a white-light continuum probe.\nWe present a powerful experimental tool and analysis for characterization of two-photon absorption (2PA) spectra. We demonstrate this method with ZnS and then apply it to organic dyes in solution. We also compare the results with those from other methods such as two-photon fluorescence spectroscopy. This femtosecond pump-probe method uses a white-light continuum (WLC) as the probe to produce a nondegenerate 2PA spectrum. The extreme chirp of the WLC requires that transmittance data be collected over a range of temporal delays between pump and probe pulses. These data then need to be corrected for the effects of this chirp as well as for the temporal walk-off of the pulses in the sample that result from the frequency nondegenerate nature of the experiment. We present a simple analytic solution for the transmitted fluence through the sample, which is applicable for most practical cases.","subset":"pubmed_abstract"} +{"meta":{"pmid":19090249,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Comparison of antioxidant and free radical scavenging activities of the essential oils from flowers and fruits of Otostegia persica Boiss.\nThe aerial parts of the endemic plant of Otostegia persica Boiss. in two different stages of flowering and fruiting were hydro-distilled to extract oils in the yields of 0.3 and 0.15% (v\/w), respectively. The oils were analyzed by GC and GC\/MS. Twenty-eight and thirty-one components were identified, representing 97.59 and 94.61% of the oils, respectively. The main compounds of the essential oil flowers (EOFL) were alpha-pinene (17.21%), 1-octen,3-ol (13.44%) and cubenol (7.27%), whereas diisooctyl phthalate (45%) and hexadecanoic acid (11.07%) were the major constituents of the essential oil of the fruits (EOFR). The oils were screened for their possible antioxidant activities by two complementary test systems, namely DPPH free radical-scavenging and ammonium thiocyanate. In both tested systems, EOFL exerted greater antioxidant and radical scavenging activity. In the first case, EOFL exerted antioxidant activity with an IC50 19.8 +\/- 1.8 microg mL(-1) almost similar to BHA and ascorbic acid (15.2 +\/- 1.1 and 17.4 +\/- 1.3), respectively. In the ammonium thiocyanate system, the inhibition rate of oxidation of linoleic acid for EOFL was estimated 93.5 +\/- 2.8. The higher activity of this oil in comparison to EOFR may be attributed to its high content of monoterpenes, especially oxygenated ones in the oil of the flowers.","subset":"pubmed_abstract"} +{"meta":{"pmid":29302358,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-25":1,"2021-04":1,"2020-40":1,"2019-18":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-47":1,"2017-39":1,"2023-40":1,"2024-22":2,"2024-26":1}}},"text":"Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges.\nSignificant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions.","subset":"pubmed_abstract"} +{"meta":{"pmid":23807104,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Mastery learning for health professionals using technology-enhanced simulation: a systematic review and meta-analysis.\nCompetency-based education requires individualization of instruction. Mastery learning, an instructional approach requiring learners to achieve a defined proficiency before proceeding to the next instructional objective, offers one approach to individualization. The authors sought to summarize the quantitative outcomes of mastery learning simulation-based medical education (SBME) in comparison with no intervention and nonmastery instruction, and to determine what features of mastery SBME make it effective. The authors searched MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, Scopus, key journals, and previous review bibliographies through May 2011. They included original research in any language evaluating mastery SBME, in comparison with any intervention or no intervention, for practicing and student physicians, nurses, and other health professionals. Working in duplicate, they abstracted information on trainees, instructional design (interactivity, feedback, repetitions, and learning time), study design, and outcomes. They identified 82 studies evaluating mastery SBME. In comparison with no intervention, mastery SBME was associated with large effects on skills (41 studies; effect size [ES] 1.29 [95% confidence interval, 1.08-1.50]) and moderate effects on patient outcomes (11 studies; ES 0.73 [95% CI, 0.36-1.10]). In comparison with nonmastery SBME instruction, mastery learning was associated with large benefit in skills (3 studies; effect size 1.17 [95% CI, 0.29-2.05]) but required more time. Pretraining and additional practice improved outcomes but, again, took longer. Studies exploring enhanced feedback and self-regulated learning in the mastery model showed mixed results. Limited evidence suggests that mastery learning SBME is superior to nonmastery instruction but takes more time.","subset":"pubmed_abstract"} +{"meta":{"pmid":23743944,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2021-39":1,"2021-25":1,"2019-35":1,"2019-26":1,"2019-18":1,"2018-51":1,"2018-34":1,"2018-26":1,"2018-05":1,"2017-51":1,"2017-30":1,"2017-17":1,"2023-23":1,"2017-13":1,"2024-22":1}}},"text":"Reliability in patient-centered observations of family physicians.\nPatient-centered communication is an important component of primary care and related to improved patient health outcomes and satisfaction. The Patient-Centered Observation Form (PCOF) was developed as an educational assessment tool to improve resident physician-patient communication. However, reliability of the tool has not been tested. Residents and patients were observed in routine medical encounters in a Midwestern family medicine residency center as part of a prospective, quasi-experimental study. Four independent observers (two faculty clinicians and two social scientists) used the PCOF to rate videorecorded patient encounters in the areas of establishing rapport, maintaining relationships, agenda setting, efficiency, information gathering, assessing patient perspectives, effective and open use of the electronic medical record (EMR), sharing information, discussion of behavior changes, co-creating a plan, and shared decision making. A total of 13 physician-patient encounters were observed. Mean overall reliability for the PCOF was 0.67 using four raters, 0.45 for clinicians only, and 0.62 for social scientists. Adequate reliability (>0.7) was found for behavior change discussion (0.89) in clinician ratings but not with social scientists (0.62). Social scientists had adequate reliability in assessing patients' perspectives on health (0.86) and shared decision making (0.78), but these were not considered reliable among clinicians (0.46 and 0.00, respectively). Reliability of the PCOF for assessing patient-centered competence is dependent on the content of communication being scored and the training history of the evaluator. These results challenge researchers and physicians to develop more reliable scoring instructions and tools for assessing patient-centered competence.","subset":"pubmed_abstract"} +{"meta":{"pmid":19386966,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Relationship between heterosexual anal sex, injection drug use and HIV infection among black men and women.\nUS blacks carry a disproportionate risk of heterosexually transmitted HIV. This study aimed to evaluate the association between self-reported heterosexual anal intercourse and HIV. Using respondent-driven sampling (RDS), we recruited and interviewed 909 blacks from areas of high poverty and HIV prevalence in Houston, Texas, and who reported heterosexual sex in the last year. All individuals were tested for HIV. Weighted prevalence values were calculated to account for non-random recruitment associated with RDS. The weighted population prevalence of HIV infection was 2.4% and 2.5% among men and women, respectively. Education, employment status, income and crack cocaine use were not associated with HIV infection. Lifetime injection drug use (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.33%) and heterosexual anal intercourse (OR 2.41, 95% CI 1.02-5.73%) were associated with HIV infection. Individuals who reported both injection drug use and heterosexual anal intercourse had 6.21 increased odds of HIV (95% CI 2.47-15.61%). Our results suggest that heterosexual anal sex may be a vector for HIV transmission, especially in the context of injection drug use. Prevention strategies directed at curbing the HIV epidemic among black heterosexuals require that we correctly identify the risks so that appropriate interventions can be developed.","subset":"pubmed_abstract"} +{"meta":{"pmid":27197066,"dup_signals":{"dup_doc_count":11}},"text":"Immunogenic Subtypes of Breast Cancer Delineated by Gene Classifiers of Immune Responsiveness.\nThe abundance and functional orientation of tumor-infiltrating lymphocytes in breast cancer is associated with distant metastasis-free survival, yet how this association is influenced by tumor phenotypic heterogeneity is poorly understood. Here, a bioinformatics approach defined tumor biologic attributes that influence this association and delineated tumor subtypes that may differ in their ability to sustain durable antitumor immune responses. A large database of breast tumor expression profiles and associated clinical data was compiled, from which the ability of phenotypic markers to significantly influence the prognostic performance of a classification model that incorporates immune cell-specific gene signatures was ascertained. Markers of cell proliferation and intrinsic molecular subtype reproducibly distinguished two breast cancer subtypes that we refer to as immune benefit-enabled (IBE) and immune benefit-disabled (IBD). The IBE tumors, comprised mostly of highly proliferative tumors of the basal-like, HER2-enriched, and luminal B subtypes, could be stratified by the immune classifier into significantly different prognostic groups, while IBD tumors could not, indicating the potential for productive engagement of metastasis-protective immunity in IBE tumors, but not in IBD tumors. The prognostic stratification in IBE was independent of conventional variables. Gene network analysis predicted the activation of TNF\u03b1\/IFN\u03b3 signaling pathways in IBE tumors and the activation of the transforming growth factor-\u03b2 pathway in IBD tumors. This prediction supports a model in which breast tumors can be distinguished on the basis of their potential for metastasis-protective immune responsiveness. Whether IBE and IBD represent clinically relevant contexts for evaluating sensitivity to immunotherapeutic agents warrants further investigation. Cancer Immunol Res; 4(7); 600-10. \u00a92016 AACR.","subset":"pubmed_abstract"} +{"meta":{"pmid":31416407,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":9}}},"text":"Cognitive Training in Young Patients With Traumatic Brain Injury: A Fixel-Based Analysis.\nBackground. Traumatic brain injury (TBI) is associated with altered white matter organization and impaired cognitive functioning. Objective. We aimed to investigate changes in white matter and cognitive functioning following computerized cognitive training. Methods. Sixteen adolescents with moderate-to-severe TBI (age 15.6 \u00b1 1.8 years, 1.2-4.6 years postinjury) completed the 8-week BrainGames program and diffusion weighted imaging (DWI) and cognitive assessment at time point 1 (before training) and time point 2 (after training). Sixteen healthy controls (HC) (age 15.6 \u00b1 1.8 years) completed DWI assessment at time point 1 and cognitive assessment at time point 1 and 2. Fixel-based analyses were used to examine fractional anisotropy (FA), mean diffusivity (MD), and fiber cross-section (FC) on a whole brain level and in tracts of interest. Results. Patients with TBI showed cognitive impairments and extensive areas with decreased FA and increased MD together with an increase in FC in the body of the corpus callosum and left superior longitudinal fasciculus (SLF) at time point 1. Patients improved significantly on the inhibition measure at time point 2, whereas the HC group remained unchanged. No training-induced changes were observed on the group level in diffusion metrics. Exploratory correlations were found between improvements on verbal working memory and reduced MD of the left SLF and between increased performance on an information processing speed task and increased FA of the right precentral gyrus. Conclusions. Results are indicative of positive effects of BrainGames on cognitive functioning and provide preliminary evidence for neuroplasticity associated with cognitive improvements following cognitive intervention in TBI.","subset":"pubmed_abstract"} +{"meta":{"pmid":26967332,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation.\nDihydrodipicolinate synthase (DHDPS) catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions.","subset":"pubmed_abstract"} +{"meta":{"pmid":28399482,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Functionalized polymer-iron oxide hybrid nanofibers: Electrospun filtration devices for metal oxyanion removal.\nVia a single-pot electrospinning synthesis, we developed a functionalized polymer-metal oxide nanofiber filter for point of use (POU) water treatment of metal oxyanions (e.g., arsenate and chromate). Polyacrylonitrile (PAN) functionalization was accomplished by inclusion of surface-active, quaternary ammonium salts (QAS) [cetyltrimethylammonium bromide (CTAB) or tetrabutylammonium bromide (TBAB)] that provide strong base ion exchange sites. Embedded iron oxide [ferrihydrite (Fh)] nanoparticles were used for their established role as metal sorbents. We examined the influence of QAS and Fh loading on composite properties, including nanofiber morphology, surface area, surface chemical composition, and the accessibility of embedded nanoparticles to solution. Composite performance was then evaluated using kinetic, isotherm, and pH-edge sorption experiments with arsenate and chromate, and benchmarked to unmodified PAN nanofibers and freely dispersed Fh nanoparticles. We also assessed the long-term stability of QAS in the composite matrix. For composites containing QAS or Fh nanoparticles, increasing QAS\/Fh nanoparticle loading generally yielded increasing metal oxyanion uptake. The optimized composite (PAN 7 wt%, Fh 3 wt%, TBAB 1 wt%) exhibited two distinct sites for simultaneous, non-competitive metal binding (i.e., iron oxide sites for arsenate removal via sorption and well-retained QAS sites for chromate removal via ion exchange). Moreover, surface-segregating QAS enriched Fh abundance at the nanofiber surface, allowing immobilized nanoparticles to exhibit reactivity comparable to that of unsupported (i.e., suspended or freely dispersed) nanoparticles. To simulate POU application, the optimized composite was tested in a dead-end, flow-through filtration system for arsenate and chromate removal at environmentally relevant concentrations (e.g., \u03bcg\/L) in both idealized and simulated tap water matrices. Performance trends indicate that dual mechanisms for uptake are maintained in kinetically limited regimes. Although chromate removal via ion exchange is more susceptible to interfering counter-ions, arsenate removal in simulated tap water indicates that \u223c130 g of the composite could produce an individual's annual supply of drinking water (assuming an influent contaminated with 100 \u03bcg As\/L, which is 10 times the current MCL).","subset":"pubmed_abstract"} +{"meta":{"pmid":2565532,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"The poly(A)-poly(A)-binding protein complex is a major determinant of mRNA stability in vitro.\nUsing an in vitro mRNA decay system, we investigated how poly(A) and its associated poly(A)-binding protein (PABP) affect mRNA stability. Cell extracts used in the decay reactions were depleted of functional PABP either by adding excess poly(A) competitor or by passing the extracts over a poly(A)-Sepharose column. Polyadenylated mRNAs for beta-globin, chloramphenicol acetyltransferase, and simian virus 40 virion proteins were degraded 3 to 10 times faster in reactions lacking PABP than in those containing excess PABP. The addition of purified Saccharomyces cerevisiae or human cytoplasmic PABP to PABP-depleted reactions stabilized the polyadenylated mRNAs. In contrast, the decay rates of nonpolyadenylated mRNAs were unaffected by PABP, indicating that both the poly(A) and its binding protein were required for maintaining mRNA stability. A nonspecific single-stranded binding protein from Escherichia coli did not restore stability to polyadenylated mRNA, and the stabilizing effect of PABP was inhibited by anti-PABP antibody. The poly(A) tract was the first mRNA segment to be degraded in PABP-depleted reactions, confirming that the poly(A)-PABP complex was protecting the 3' region from nucleolytic attack. These results indicate that an important function of poly(A), in conjunction with its binding protein, is to protect polyadenylated mRNAs from indiscriminate destruction by cellular nucleases. A model is proposed to explain how the stability of an mRNA could be affected by the stability of its poly(A)-PABP complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":30036218,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Undifferentiated Endometrial Carcinomas: Clinicopathologic Characteristics and Treatment Outcomes.\nUndifferentiated endometrial carcinoma (UEC) represents a recently recognized and rare diagnosis that is commonly misclassified on histopathologic evaluation. These cancers account for less than 10% of carefully reviewed series of endometrial cancers from academic medical centers. We reviewed a single-institutional experience with the management of UEC focusing on clinicopathologic characteristics and treatment outcomes. The medical records of all patients treated for histologically proven endometrial carcinoma between 2007 through 2016 were reviewed. Analysis was limited to 24 consecutive patients with histologically proven endometrial carcinomas that had at least a component of undifferentiated carcinoma on central pathology review. All patients were initially treated by definitive surgical resection. Grade 3 endometrioid carcinomas treated over the same period were used as a control group. The Kaplan-Meier method was used to estimate survival outcomes. The median age at diagnosis was 66 years (range, 37-74 years). Ten patients presented with locally advanced or metastatic disease (42%). Fifteen patients (63%) received adjuvant chemotherapy with carboplatin and paclitaxel, 12 patients (50%) received adjuvant pelvic external beam radiation, and 10 patients (42%) received adjuvant vaginal cuff brachytherapy. With a median follow-up of 14 months (range, 0.5-115 months), 4 patients (21%) had developed disease recurrence and\/or progression, 2 patients (11%) had died of disease, and 1 patient died of treatment complications. Twelve patients (63%) were alive with no evidence of disease at last contact. Outcomes were comparable to those with grade 3 endometrioid carcinoma. Our data are consistent with prior studies demonstrating that UEC represents a rare clinical entity characterized by high rates of locally advanced disease at presentation. However, survival outcomes appear to be comparable to other high-grade endometrial cancers. Further studies investigating optimal adjuvant therapy in these patients are warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":31265459,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Kawasaki disease and 13-valent pneumococcal conjugate vaccination among young children: A self-controlled risk interval and cohort study with null results.\nKawasaki disease is an acute vasculitis that primarily affects children younger than 5 years of age. Its etiology is unknown. The United States Vaccine Safety Datalink conducted postlicensure safety surveillance for 13-valent pneumococcal conjugate vaccine (PCV13), comparing the risk of Kawasaki disease within 28 days of PCV13 vaccination with the historical risk after 7-valent PCV (PCV7) vaccination and using chart-validation. A relative risk (RR) of 2.38 (95% CI 0.92-6.38) was found. Concurrently, the Food and Drug Administration (FDA) conducted a postlicensure safety review that identified cases of Kawasaki disease through adverse event reporting. The FDA decided to initiate a larger study of Kawasaki disease risk following PCV13 vaccination in the claims-based Sentinel\/Postlicensure Rapid Immunization Safety Monitoring (PRISM) surveillance system. The objective of this study was to determine the existence and magnitude of any increased risk of Kawasaki disease in the 28 days following PCV13 vaccination. The study population included mostly commercially insured children from birth to <24 months of age in 2010 to 2015 from across the US. Using claims data of participating Sentinel\/PRISM data-providing organizations, PCV13 vaccinations were identified by means of current procedural terminology (CPT), Healthcare Common Procedure Coding System (HCPCS), and National Drug Code (NDC) codes. Potential cases of Kawasaki disease were identified by first-in-365-days International Classification of Diseases 9th revision (ICD-9) code 446.1 or International Classification of Diseases 10th revision (ICD-10) code M30.3 in the inpatient setting. Medical records were sought for potential cases and adjudicated by board-certified pediatricians. The primary analysis used chart-confirmed cases with adjudicated symptom onset in a self-controlled risk interval (SCRI) design, which controls for time-invariant potential confounders. The prespecified risk interval was Days 1-28 after vaccination; a 28-day-long control interval followed this risk interval. A secondary analytic approach used a cohort design, with alternative potential risk intervals of Days 1-28 and Days 1-42. The varying background risk of Kawasaki disease by age was adjusted for in both designs. In the primary analysis, there were 43 confirmed cases of Kawasaki disease in the risk interval and 44 in the control interval. The age-adjusted risk estimate was 1.07 (95% CI 0.70-1.63; p = 0.76). In the secondary, cohort analyses, which included roughly 700 potential cases and more than 3 million person-years, the risk estimates of potential Kawasaki disease in the risk interval versus in unexposed person-time were 0.84 (95% CI 0.65-1.08; p = 0.18) for the Days 1-28 risk interval and 0.97 (95% CI 0.79-1.19; p = 0.80) for the Days 1-42 risk interval. The main limitation of the study was that we lacked the resources to conduct medical record review for all the potential cases of Kawasaki disease. As a result, potential cases rather than chart-confirmed cases were used in the cohort analyses. With more than 6 million doses of PCV13 administered, no evidence was found of an association between PCV13 vaccination and Kawasaki disease onset in the 4 weeks after vaccination nor of an elevated risk extending or concentrated somewhat beyond 4 weeks. These null results were consistent across alternative designs, age-adjustment methods, control intervals, and categories of Kawasaki disease case included.","subset":"pubmed_abstract"} +{"meta":{"pmid":29227053,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":1,"unknown":16}}},"text":"Quantifying the funding gap for management of traumatic brain injury at a major trauma centre in South Africa.\nTrauma is an eminently preventable disease. However, prevention programs divert resources away from other priorities. Costing trauma related diseases helps policy makers to make decisions on re-source allocation. We used data from a prospective digital trauma registry to cost Traumatic Brain Injury (TBI) at our institution over a two-year period and to estimate the funding gap that exists in the care of TBI. All patients who were admitted to the Pietermaritzburg Metropolitan Trauma Service (PMTS) with TBI were identified from the Hybrid Electronic Medical Registry (HMER). A micro-costing model was utilised to generate costs for TBI. Costs were generated for two scenarios in which all moderate and severe TBI were admitted to ICU. The actual cost was then sub-tracted from the scenario costs to establish the funding gap. During the period January 2012 to December 2014, a total of 3 301 patients were treated for TBI in PMB. The mean age was 30 years (SD 50). There were 2 632 (80%) males and 564 (20%) females. The racial breakdown was overwhelmingly African (96%), followed by Asian (2%), Caucasian (1%) and mixed race (1%). There were 2 540 mild (GCS 13-15), 326 moderate (9-12), and 329 severe (GCS \u22648) TBI admissions during the period under review. A total of 139 patients died (4.2%). A total of 242 (7.3%) patients were admitted to ICU. Of these 137 (57%) had a GCS of 9 or less. A total of 2 383 CT scans were performed. The total cost of TBI over the two-year period was ZAR 62 million. If all 326 patients with moderate TBI had been admitted to ICU there would have been a further 281 ICU admissions. This was labelled Scenario 1. If all patients with severe as well as moderate TBI had been admitted there would have been a further 500 ICU admissions. This was labelled Scenario 2. Based on Scenario 1 and Scenario 2 the total cost would have been ZAR 73 272 250 and ZAR 82 032 250 respectively. The funding gaps for Scenario 1 and Scenario 2 were ZAR 11 240 000 and ZAR 20 000 000 respectively. There is a significant burden of TBI managed by the PMTS. The cost of managing TBI each year is in the order of sixty million ZAR. A significant funding gap exists in our environment. This data does not include any data on the broader social costs of TBI. Investing in programs to reduce and prevent TBI is justified by the potential for significant savings.","subset":"pubmed_abstract"} +{"meta":{"pmid":22039412,"dup_signals":{"dup_doc_count":15,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-22":1,"2024-18":2,"2024-10":4,"unknown":3}}},"text":"Direct ex-vivo evaluation of pneumococcal specific T-cells in healthy adults.\nStreptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine\/threonine kinase (StkP). We were able to detect direct ex-vivo StkP(446-60)-tetramer binding in HLA-DRB1*1501 adults. These StkP(446-60)-tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP(446-60)-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We found that ex-vivo pneumococcal-specific T cells were detectable in healthy adults and that they were enriched with cell surface markers associated with recent antigen exposure and later stages of antigen-driven differentiation. It is likely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynx and it is possible that they may be preventing subsequent colonisation and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":24368578,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Exercise, energy expenditure, and body composition in people with spinal cord injury.\nThe objective of this study was to verify the long-term effects of exercise on energy expenditure and body composition in individuals with spinal cord injury (SCI), as very little information is available on this population under free-living conditions. Free-living energy expenditure and body composition using doubly labeled water (DLW) was measured in 13 individuals with SCI, subdivided in 2 groups: (1) sedentary (SED; N = 7) and (2) regularly engaged in any exercise program, for at least 150 min\u00b7wk(-1) (EXE; N = 6). The total daily energy expenditure (TDEE) was significantly higher in the EXE group (33 \u00b1 4.5 kcal\u00b7kg(-1)\u00b7day(-1)) if compared with SED group (27 \u00b1 4.3 kcal\u00b7kg(-1)\u00b7day(-1)). The percentage of body fat was significantly higher in SED group than in EXE group (38 \u00b1 6% and 28 \u00b1 9%). Our findings revealed that, despite the severity of SCI, the actual ACSM's guidelines for weight management for healthy adults exercise could significantly increase TDEE and BMR and improve body composition in individuals who regularly perform exercise. However, the EXE group still showed a high percentage of body fat, suggesting that a more specific approach might be considered (ie, increased intensity or volume, or combining with a diet program).","subset":"pubmed_abstract"} +{"meta":{"pmid":30297656,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":2,"2024-22":1,"unknown":8}}},"text":"Salmon Fillet Intake Led to Higher Serum Triacylglycerol in Obese Zucker Fa\/Fa Rats But Not in Normolipidemic Long-Evans Rats.\nThe triacylglycerol lowering effect of fatty fish and fish oils is well recognized, however we recently showed that salmon intake resulted in higher serum triacylglycerol concentration in obese Zucker fa\/fa rats. Since effects of salmon fillet have never before been studied in rats, the objective of this study was to compare effects of salmon intake on serum lipids in hyperlipidemic obese rats with normolipidemic lean rats. Zucker fa\/fa rats and Long-Evans rats were fed diets with 25% protein from baked salmon fillet and 75% protein from casein, or casein as sole protein source (control group) for four weeks. Serum triacylglycerol concentration was higher, and cholesterol and apolipoproteinB-100 concentrations were lower in Zucker fa\/fa rats fed Baked Salmon Diet compared to Zucker fa\/fa rats fed Control Diet, with no differences in serum triacylglycerol, cholesterol and apolipoproteinB-100 between Long-Evans rats fed Baked Salmon Diet or Control Diet. Serum triacylglycerol fatty acid composition showed greater similarities to dietary fatty acids in Zucker fa\/fa rats than in Long-Evans rats. To conclude, intake of baked salmon fillet resulted in higher serum triacylglycerol concentration and lower serum cholesterol concentration in hyperlipidemic obese Zucker fa\/fa rats but did not affect serum lipids in normolipidemic lean Long-Evans rats.","subset":"pubmed_abstract"} +{"meta":{"pmid":18823235,"dup_signals":{"dup_doc_count":72,"dup_dump_count":45,"dup_details":{"curated_sources":4,"2023-40":4,"2023-23":2,"2023-14":1,"2023-06":2,"2022-40":2,"2022-33":1,"2022-27":1,"2022-21":4,"2022-05":1,"2021-49":2,"2021-43":4,"2021-39":1,"2021-31":1,"2021-25":2,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":1,"2019-43":1,"2019-26":1,"2018-43":1,"2018-30":2,"2018-17":1,"2018-09":2,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-26":3,"2024-22":2,"2024-18":1,"2024-10":3,"2017-13":2,"2015-18":1,"2015-11":1,"2015-06":1,"2013-48":1,"2013-20":2}}},"text":"Optimizing functional accuracy of TMS in cognitive studies: a comparison of methods.\nTranscranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure-function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4. We discuss these graded effect size differences in light of the revealed interindividual variances in the actual target stimulation site within and between approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":27009986,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Porphyra (Bangiophyceae) Transcriptomes Provide Insights Into Red Algal Development And Metabolism.\nThe red seaweed Porphyra (Bangiophyceae) and related Bangiales have global economic importance. Here, we report the analysis of a comprehensive transcriptome comprising ca. 4.7 million expressed sequence tag (EST) reads from P. umbilicalis (L.) J. Agardh and P. purpurea (Roth) C. Agardh (ca. 980 Mbp of data generated using 454 FLX pyrosequencing). These ESTs were isolated from the haploid gametophyte (blades from both species) and diploid conchocelis stage (from P. purpurea). In a bioinformatic analysis, only 20% of the contigs were found to encode proteins of known biological function. Comparative analysis of predicted protein functions in mesophilic (including Porphyra) and extremophilic red algae suggest that the former has more putative functions related to signaling, membrane transport processes, and establishment of protein complexes. These enhanced functions may reflect general mesophilic adaptations. A near-complete repertoire of genes encoding histones and ribosomal proteins was identified, with some differentially regulated between the blade and conchocelis stage in P. purpurea. This finding may reflect specific regulatory processes associated with these distinct phases of the life history. Fatty acid desaturation patterns, in combination with gene expression profiles, demonstrate differences from seed plants with respect to the transport of fatty acid\/lipid among subcellular compartments and the molecular machinery of lipid assembly. We also recovered a near-complete gene repertoire for enzymes involved in the formation of sterols and carotenoids, including candidate genes for the biosynthesis of lutein. Our findings provide key insights into the evolution, development, and biology of Porphyra, an important lineage of red algae.","subset":"pubmed_abstract"} +{"meta":{"pmid":29358336,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":11}}},"text":"Screening and Genomic Characterization of Filamentous Hemagglutinin-Deficient Bordetella pertussis.\nDespite high vaccine coverage, pertussis cases in the United States have increased over the last decade. Growing evidence suggests that disease resurgence results, in part, from genetic divergence of circulating strain populations away from vaccine references. The United States employs acellular vaccines exclusively, and current Bordetella pertussis isolates are predominantly deficient in at least one immunogen, pertactin (Prn). First detected in the United States retrospectively in a 1994 isolate, the rapid spread of Prn deficiency is likely vaccine driven, raising concerns about whether other acellular vaccine immunogens experience similar pressures, as further antigenic changes could potentially threaten vaccine efficacy. We developed an electrochemiluminescent antibody capture assay to monitor the production of the acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 U.S. surveillance isolates collected from 2010 to 2016 identified two that were both Prn and Fha deficient. Three additional Fha-deficient laboratory strains were also identified from a historic collection of 65 isolates dating back to 1935. Whole-genome sequencing of deficient isolates revealed putative, underlying genetic changes. Only four isolates harbored mutations to known genes involved in Fha production, highlighting the complexity of its regulation. The chromosomes of two Fha-deficient isolates included unexpected structural variation that did not appear to influence Fha production. Furthermore, insertion sequence disruption of fhaB was also detected in a previously identified pertussis toxin-deficient isolate that still produced normal levels of Fha. These results demonstrate the genetic potential for additional vaccine immunogen deficiency and underscore the importance of continued surveillance of circulating B. pertussis evolution in response to vaccine pressure.","subset":"pubmed_abstract"} +{"meta":{"pmid":32802822,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-40":1,"2021-31":1,"2021-25":2,"2021-21":1,"2021-10":1,"2020-50":1,"2020-45":1,"2020-34":1,"2023-06":1,"2024-10":1,"2024-30":1}}},"text":"Acidification in the U.S. Southeast: Causes, Potential Consequences and the Role of the Southeast Ocean and Coastal Acidification Network.\nCoastal acidification in southeastern U.S. estuaries and coastal waters is influenced by biological activity, run-off from the land, and increasing carbon dioxide in the atmosphere. Acidification can negatively impact coastal resources such as shellfish, finfish, and coral reefs, and the communities that rely on them. Organismal responses for species located in the U.S. Southeast document large negative impacts of acidification, especially in larval stages. For example, the toxicity of pesticides increases under acidified conditions and the combination of acidification and low oxygen has profoundly negative influences on genes regulating oxygen consumption. In corals, the rate of calcification decreases with acidification and processes such as wound recovery, reproduction, and recruitment are negatively impacted. Minimizing the changes in global ocean chemistry will ultimately depend on the reduction of carbon dioxide emissions, but adaptation to these changes and mitigation of the local stressors that exacerbate global acidification can be addressed locally. The evolution of our knowledge of acidification, from basic understanding of the problem to the emergence of applied research and monitoring, has been facilitated by the development of regional Coastal Acidification Networks (CANs) across the United States. This synthesis is a product of the Southeast Coastal and Ocean Acidification Network (SOCAN). SOCAN was established to better understand acidification in the coastal waters of the U.S. Southeast and to foster communication among scientists, resource managers, businesses, and governments in the region. Here we review acidification issues in the U.S. Southeast, including the regional mechanisms of acidification and their potential impacts on biological resources and coastal communities. We recommend research and monitoring priorities and discuss the role SOCAN has in advancing acidification research and mitigation of and adaptation to these changes.","subset":"pubmed_abstract"} +{"meta":{"pmid":2060432,"dup_signals":{"dup_doc_count":14,"dup_dump_count":6,"dup_details":{"curated_sources":4,"2021-39":4,"2021-31":1,"2020-40":1,"2020-10":1,"2020-05":2,"2019-51":1}}},"text":"Major role for arterial disease in morbidity and mortality after kidney transplantation in diabetic recipients.\nTo identify clinical characteristics of diabetic end-stage renal disease patients that place individual transplant candidates at high risk for arterial morbidity and mortality after transplantation. We studied the course of 101 sequential renal allograft recipients with insulin-dependent diabetes mellitus, transplanted between 10 November 1980 and 1 April 1986. Arterial disorders were tabulated from medical records and interviews with individual patients, their families, and their private physicians. Documentation of discrete arterial events included recorded physical examinations, radiographic studies, laboratory data, electrocardiograms, peripheral vascular flow studies, and operative reports. The prevalence of preoperative arterial disease was compared with the occurrence of new arterial events after kidney transplantation. Within a mean follow-up period of 47 mo, a 30% absolute mortality rate was observed. Of these deaths, 57% resulted from arterial disorders. Clinical manifestations of arterial disease were recognized in 41% of recipients before transplantation, and 78% of these patients suffered new vascular events after transplantation. Of the entire sample, 57% developed at least one new complication of arterial disease after transplantation, whereas only 34% had no vascular diagnosis before or after transplantation. Cerebral, coronary, and peripheral arterial complications after transplantation occurred in 14, 28, and 36% of the patients, respectively. The corresponding incidences of stroke, myocardial infarction, and amputation were 12, 14, and 25%. Pretransplant coronary artery disease predisposed to new coronary events after transplantation, but only peripheral arterial complications occurred more often after transplantation compared with the preoperative period. The probability of arterial complications or death correlated with patient age at first transplant and duration of diabetes but not with sex or smoking history. Intrinsic arterial disease in diabetic renal allograft recipients contributes heavily to the long-term morbidity and mortality after transplantation and poses the major threat to survival. Diabetic transplant candidates greater than 35 yr of age or with clinical evidence of arterial disease should undergo an extensive vascular assessment, including stress thallium myocardial imaging and\/or coronary arteriography. Such recipients should receive careful preoperative counseling about their excess risk for subsequent arterial disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":22240152,"dup_signals":{"dup_doc_count":24,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-18":1,"unknown":21}}},"text":"Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards.\nAccumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In this study, we developed a method for the analysis of structurally related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally related (-)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (-)-epicatechin-3'-\u03b2-D-glucuronide, (-)-epicatechin-3'-sulfate, and a 3'-O-methyl-(-)-epicatechin-5\/7-sulfate are the predominant SREM in humans and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting, to a significant extent, of interlaboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.","subset":"pubmed_abstract"} +{"meta":{"pmid":23594577,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Automated mortality monitoring in Scotland from 2009.\nMortality monitoring systems are important for gauging the effect of influenza and other wide ranging health threats. We present the daily all-cause mortality monitoring system routinely used in Scotland, which differs from others by using two different statistical models for calculating expected mortality. The first model is an extended Serfling model, which captures annual seasonality in mortality using sine and cosine terms, and is frequently seen in other systems. Serfling models fit to summer seasonality well, but not to the winter peak. Thus, during the winter, there are frequent 'excesses', higher than expected mortality, making it harder to directly judge if winter mortality is higher than in previous years. The second model, a Generalised Additive Model, resolves this by allowing a more flexible seasonal pattern that includes the winter peak. Thus, excesses under the second model directly indicate if winter mortality is higher than in previous years, useful, for example, in judging if a new strain of seasonal influenza is more likely to produce death than previous ones. As common in all-cause mortality monitoring systems, the Scottish system uses a reporting delay correction: we discuss the difficulties of interpretation when such a correction is used and possible avenues for future work that may address these difficulties.","subset":"pubmed_abstract"} +{"meta":{"pmid":8317812,"dup_signals":{"dup_doc_count":17,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":14}}},"text":"Occupational dust exposure and chronic obstructive pulmonary disease. A systematic overview of the evidence.\nThe object of this study was to assess the relationship between occupational dust exposure and chronic obstructive pulmonary disease (COPD). Studies were identified using MEDLINE (January 1966 to July 1991), SCISEARCH, manual review of reference lists, and personal contact with more than 30 international experts. Studies of COPD, lung function, emphysema, chronic bronchitis, or mortality in workers exposed to nonorganic dust were retrieved. Studies were included if dust exposure was measured quantitatively, and a quantitative relationship between dust exposure and one of the outcomes of interest was calculated while controlling at least for smoking and age. Methodological rigor was assessed, and data regarding the study populations, prognostic factors, and outcomes were extracted independently by two reviewers. Thirteen reports derived from four cohorts of workers met our inclusion criteria. Three of the cohorts were of coal miners and one was of gold miners. All of the studies found a statistically significant association between loss of lung function and cumulative respirable dust exposure. It was estimated that 80 (95% CI, 34 to 137) of 1,000 nonsmoking coal miners with a cumulative respirable dust exposure of 122.5 gh\/m3 (considered equivalent to 35 years of work with a mean respirable dust level of 2 mg\/m3) could be expected to develop a clinically important (> 20%) loss of FEV1 attributable to dust. Among 1,000 smoking miners the comparable estimate was 66 (95% CI, 49 to 84). The risk of a clinically important loss of lung function attributable to dust among nonsmoking gold miners was estimated to be three times as large as for coal miners at less than one fifth of the cumulative respirable dust exposure (21.3 gh\/m3), the maximal exposure observed among the cohort of gold miners. We conclude that occupational dust is an important cause of COPD, and the risk appears to be greater for gold miners than for coal miners. One possible explanation of the greater risk among gold miners is the higher silica content in gold mine dust.","subset":"pubmed_abstract"} +{"meta":{"pmid":7672579,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":10}}},"text":"Characterization of the major transcripts encoded by the regulatory MuDR transposable element of maize.\nThe MuDR element controls the transposition of the Mutator transposable element family in maize. Previous studies reported the presence of two major MuDR-homologous transcripts that correlate with Mutator activity. In this study, we describe the structure and processing of these two major transcripts. The transcripts are convergent, initiating from opposite ends of the element within the 220-bp terminal inverted repeats. The convergent transcripts do not overlap, and only 200 bp of internal MuDR sequences are not transcribed. Cloning and sequencing of multiple MuDR cDNAs revealed unusual intron\/exon junctions, differential splicing, and multiple polyadenylation sites. RNase protection experiments indicated that some splicing failure occurs in young seedlings, and that a low level of antisense RNA exists for both transcripts. On a whole plant level, the presence of the major MuDR transcripts strictly correlates with Mutator activity in that no MuDR transcripts are observed in non-Mutator or inactive Mutator stocks. Examination of various tissues from active Mutator stocks indicates that the two transcripts are present in all organs and tissues tested, including those with no apparent transposition activity. This suggests that Mutator activity is not simply controlled by the level of the major MuDR transcripts.","subset":"pubmed_abstract"} +{"meta":{"pmid":13563805,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"The freezing point depression of mammalian tissues after sudden heating in boiling distilled water.\nThe calculated freezing point depression of freshly excised boiled mammalian tissue is approximately the same as that of plasma. The boiling procedure was chosen to eliminate the influence of metabolism on the level of the freezing point depression. Problems created by the boiling, such as equilibrium between tissue and diluent, change in activity coefficient by dilution, and loss of CO(2) content, are discussed. A frozen crushed tissue homogenate is hypertonic to plasma. Boiling and dilution of such hypertonic homogenate exposed to room temperature for 5 to 15 minutes did not produce significant or unexplicable decreases in its osmotic activity. Moreover, freezing and crushing of a boiled diluted tissue did not produce any increase of the isoosmotic level of freezing point depression. It is possible to explain these data either with the hypothesis of hypertonic cell fluid or with that of isotonic cell fluid. In the case of an assumed isotonic cell fluid, data can be explained with one assumption, experimentally backed. In the case of an assumed hypertonic theory data can be explained only with the help of at least three ad hoc postulates. The data support the validity of the classical concept which holds that cell fluid is isotonic to extracellular fluid.","subset":"pubmed_abstract"} +{"meta":{"pmid":26819473,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"BioCircos.js: an interactive Circos JavaScript library for biological data visualization on web applications.\nWe here present BioCircos.js, an interactive and lightweight JavaScript library especially for biological data interactive visualization. BioCircos.js facilitates the development of web-based applications for circular visualization of various biological data, such as genomic features, genetic variations, gene expression and biomolecular interactions. BioCircos.js and its manual are freely available online at http:\/\/bioinfo.ibp.ac.cn\/biocircos\/ firstname.lastname@example.com Supplementary data are available at Bioinformatics online.","subset":"pubmed_abstract"} +{"meta":{"pmid":29065010,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"INTRARETINAL HYPERREFLECTIVE FOCI IN BEST VITELLIFORM MACULAR DYSTROPHY.\nTo report on the presence of hyperreflective foci (HF) on spectral domain optical coherence tomography in patients with Best vitelliform macular dystrophy (BVMD), and to describe the relationship between HF and stages of the disease. Consecutive patients diagnosed with BVMD were enrolled in a prospective cross-sectional study. All patients and control subjects underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. identification of HF in BVMD. Secondary outcome: assessment of the HF in each stage and correlation with best-corrected visual acuity. Overall, 75 eyes of 39 patients were included in the study (Stage 1: 13%, Stage 2: 43%, Stage 3: 15%, Stage 4: 21%, and Stage 5: 8%). On spectral domain optical coherence tomography assessment, intraretinal HF were present in 83% of all eyes, in 91% of eyes affected by clinical BVMD (Stages 2-5) and in 100% of patients in Stages 4 and 5. In 46% of clinically diseased eyes, HF were localized in the fovea and in correspondence with the BVMD lesions at the level of the outer nuclear layer and outer plexiform layer. Hyperreflective foci were present in 16% of control eyes. Mean number of HF in eyes affected by clinical BVMD stood at 7.67 \u00b1 7.35. These were predominantly small HF (6.23 \u00b1 6.14, P < 0.001) localized in the outer nuclear layer (5.19 \u00b1 5.38, P = 0.001) and presented largely in the extrafoveal, rather than the foveal area (5.21 \u00b1 5.57 vs 2.46 \u00b1 2.73, P = 0.001). Analysis of HF distribution revealed that the control group and Stage 1 eyes had the fewest HF; Stage 4 displayed a significant increase in the number of HF compared with Stages 2 and 3; Stage 5 also showed an increased number of HF, although this difference was statistically significant only with Stage 3 eyes. The best-corrected visual acuity was negatively related to the number of HF, with best-corrected visual acuity deteriorating as the number of HF increased in Stages 2 to 5 (P < 0.001). This study describes the presence of HF in BVMD using spectral domain optical coherence tomography. Our data suggest that HF identification is correlated with the progression of the disease and could represent a useful biomarker of BVMD.","subset":"pubmed_abstract"} +{"meta":{"pmid":29166913,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":11}}},"text":"Socioeconomic disadvantage, fetal environment and child development: linked Scottish administrative records based study.\nCognitive development in childhood is negatively affected by socioeconomic disadvantage. This study examined whether differences in fetal environment might mediate the association between family socioeconomic position and child development. Data were linked from the Scottish Longitudinal Study, maternity inpatient records and the Child Health Surveillance Programme - Pre School for 32,238 children. The outcome variables were based on health visitor assessment of gross motor, hearing and language, vision and fine motor, and social development. Socioeconomic position was measured using parental social class and highest qualification attained. Random-effects logistic regression models were estimated to account for multiple reviews and familial clustering. Mediation analysis was conducted using the Karlson-Holm-Breen method. Hearing and language, vision and fine motor, and social development were associated with lower parental social class and lower parental educational qualifications after adjustment for fetal environment. Fetal environment partially mediated the estimated effect of having parents without educational qualifications for hearing and language (\u03b2 = 0\u00b715; 95% confidence interval (CI) = 0\u00b707, 0\u00b723), vision and fine motor (\u03b2 = 0\u00b719; CI = 0\u00b710, 0\u00b728) and social development (\u03b2 = 0\u00b714; CI = 0\u00b703 to 0\u00b725). Socioeconomic position predicted hearing and language, vision and fine motor, and social development but not gross motor development. For children of parents without educational qualifications, fetal environment appears to contribute to a part of the socioeconomic gradient in child development abnormalities but post-natal environment appears to still explain the majority of the gradient and for other children most of it.","subset":"pubmed_abstract"} +{"meta":{"pmid":29183875,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Navigating chronic pain: how taking a few wrong turns can miss sinister pathology.\nBone sarcomas are rare in childhood, and their presentation can often mimic more benign complaints or chronic musculoskeletal pain. Ewing sarcomas in particular are often diagnosed after a significant delay from the onset of symptoms. At a population level, a long diagnostic delay is not necessarily associated with worse survival , as tumours that display slow growth also tend to be less aggressive. For any specific individual however, a delayed diagnosis can result in a larger tumour that is more difficult to treat. We explore a case of Ewing sarcoma and discuss how the presenting features, approach to imaging and the role of clinician cognitive bias may have led to diagnostic delay.Ewing sarcoma is treated with chemotherapy and surgery and\/or radiotherapy based on the initial site of disease, size of tumour and response to initial treatment. With current UK treatments, overall survival is approximately 70% for localised tumours and up to 20% in those with metastatic disease. Bone sarcomas usually present with deep-seated mechanical bone pain akin to toothache. The pain can be intermittent over the course of days or weeks, but pain occurring at night should be considered a red flag. Swelling may also present. On plain X-ray, bone sarcomas can demonstrate areas of bone destruction, new bone formation, periosteal inflammation and soft tissue swelling, but in some cases the changes are very subtle. Persistent unexplained symptoms require MRI to exclude tumours and detect potential benign causes that are amenable to treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":33093230,"dup_signals":{"dup_doc_count":26,"dup_dump_count":16,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":3,"2023-14":1,"2023-06":1,"2022-49":1,"2022-33":2,"2022-27":2,"2022-05":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-10":1,"2020-50":1,"2023-50":1,"2024-22":3,"2024-18":2}}},"text":"The single flagellum of Leishmania has a fixed polarisation of its asymmetric beat.\nEukaryotic flagella undertake different beat types as necessary for different functions; for example, the Leishmania parasite flagellum undergoes a symmetric tip-to-base beat for forward swimming and an asymmetric base-to-tip beat to rotate the cell. In multi-ciliated tissues or organisms, the asymmetric beats are coordinated, leading to movement of the cell, organism or surrounding fluid. This coordination involves a polarisation of power stroke direction. Here, we asked whether the asymmetric beat of the single Leishmania flagellum also has a fixed polarisation. We developed high frame rate dual-colour fluorescence microscopy to visualise flagellar-associated structures in live swimming cells. This showed that the asymmetric Leishmania beat is polarised, with power strokes only occurring in one direction relative to the asymmetric flagellar machinery. Polarisation of bending was retained in deletion mutants whose flagella cannot beat but have a static bend. Furthermore, deletion mutants for proteins required for asymmetric extra-axonemal and rootlet-like flagellum-associated structures also retained normal polarisation. Leishmania beat polarisation therefore likely arises from either the nine-fold rotational symmetry of the axoneme structure or is due to differences between the outer doublet decorations.","subset":"pubmed_abstract"} +{"meta":{"pmid":25886403,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Acute febrile illness is associated with Rickettsia spp infection in dogs.\nRickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. Dogs from southern Italy with acute fever (n = 99) were compared with case-control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum\/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank\u00ae, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and\/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and\/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR.","subset":"pubmed_abstract"} +{"meta":{"pmid":20299157,"dup_signals":{"dup_doc_count":16,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2020-50":1,"2019-47":1,"2019-09":1,"2018-34":1,"2018-13":1,"2017-51":1,"2017-39":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2022-21":1,"2017-13":1,"2024-10":1}}},"text":"Neuroticism and conscientiousness are associated with cortisol diurnal profiles in adults--role of positive and negative affect.\nA substantial body of research on the pathophysiology of negative health outcomes has focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Maladaptive and adaptive personality features have been discussed to be associated with health outcomes. In the current study, we investigated the association of neuroticism (N) and conscientiousness (C) with diurnal cortisol levels in 102 working parents (M age=37 years; 50% female). Further, we examined the impact of daily positive and negative affect on this association. During a 6-day time-sampling phase, cortisol was measured at awakening and after that within intervals of 3h. We found a positive association of N with cortisol levels throughout the measurement period, but no association of C with daily cortisol. When accounting for daily positive and negative affect, individuals with high scores on C displayed reductions in daily cortisol concentrations that were driven by positive affect compared to individuals with low C scores. No such association emerged for N. Our findings might further elucidate the role of personality in HPA axis regulation and improve our understanding of the association of endocrine states and health outcomes.","subset":"pubmed_abstract"} +{"meta":{"pmid":27391588,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Use of the Electronic Medical Record to Assess Pancreas Size in Type 1 Diabetes.\nThis study harnessed the electronic medical record to assess pancreas volume in patients with type 1 diabetes (T1D) and matched controls to determine whether pancreas volume is altered in T1D and identify covariates that influence pancreas volume. This study included 25 patients with T1D and 25 age-, sex-, and weight-matched controls from the Vanderbilt University Medical Center enterprise data warehouse. Measurements of pancreas volume were made from medical imaging studies using magnetic resonance imaging (MRI) or computed tomography (CT). Patients with T1D had a pancreas volume 47% smaller than matched controls (41.16 ml vs. 77.77 ml, P < 0.0001) as well as pancreas volume normalized by subject body weight, body mass index, or body surface area (all P < 0.0001). Pancreatic volume was smaller with a longer duration of T1D across the patient population (N = 25, P = 0.04). Additionally, four individual patients receiving multiple imaging scans displayed progressive declines in pancreas volume over time (~ 6% of volume\/year), whereas five controls scanned a year apart did not exhibit a decline in pancreas size (P = 0.03). The pancreas was uniformly smaller on the right and left side of the abdomen. Pancreas volume declines with disease duration in patients with T1D, suggesting a protracted pathological process that may include the exocrine pancreas.","subset":"pubmed_abstract"} +{"meta":{"pmid":30610162,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":13}}},"text":"Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.\nApoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Loss of Fas and Bim function in Bcl2l11-\/-Faslpr\/lpr mice inhibited apoptosis of T cells and prevented the early T cell attrition resulting from lymphocytic choriomeningitis virus infection. Bcl2l11-\/-Faslpr\/lpr mice were also resistant to prolonged allograft survival induced by CoB targeting the CD40-CD154 pathway. These results demonstrate that both extrinsic and intrinsic apoptosis pathways function concurrently to regulate T cell homeostasis during the early stages of immune responses and allograft survival during CoB.","subset":"pubmed_abstract"} +{"meta":{"pmid":31727059,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-10":2,"2021-04":1,"2020-40":1,"2023-50":1,"2024-22":1}}},"text":"Economic evaluation studies in the field of HIV\/AIDS: bibliometric analysis on research development and scopes (GAPRESEARCH).\nThe rapid decrease in international funding for HIV\/AIDS has been challenging for many nations to effectively mobilize and allocate their limited resources for HIV\/AIDS programs. Economic evaluations can help inform decisions and strategic planning. This study aims to examine the trends and patterns in economic evaluation studies in the field of HIV\/AIDS and determine their research landscapes. Using the Web of Science databases, we synthesized the number of papers and citations on HIV\/AIDS and economic evaluation from 1990 to 2017. Collaborations between authors and countries, networks of keywords and research topics were visualized using frequency of co-occurrence and Jaccards' similarity index. A Latent Dirichlet Allocation (LDA) analysis to categorize papers into different topics\/themes. A total of 372 economic evaluation papers were selected, including 351 cost-effectiveness analyses (CEA), 11 cost-utility analyses (CUA), 12 cost-benefit analyses (CBA). The growth of publications, their citations and usages have increased remarkably over the years. Major research topics in economic evaluation studies consisted of antiretroviral therapy (ART) initiation and treatment; drug use prevention interventions and prevention of mother-to-child transmission interventions. Moreover, lack of contextualized evidence was found in specific settings with high burden HIV epidemics, as well as emerging most-at-risk populations such as trans-genders or migrants. This study highlights the knowledge and geographical discrepancies in HIV\/AIDS economic evaluation literature. Future research directions are also informed for advancing economic evaluation in HIV\/AIDS research.","subset":"pubmed_abstract"} +{"meta":{"pmid":15833931,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Disposition and metabolism of [2-14C]quercetin-4'-glucoside in rats.\nQuercetin-4'-glucoside is a major flavonol in onions, and this study investigated the absorption and fate of radiolabeled quercetin-4'-glucoside in rats. Rats ingested [2-(14)C]quercetin-4'-glucoside and the distribution of radioactivity throughout the body was determined after 0.5, 1, 2, and 5 h. The gastrointestinal tract, liver, kidney, and plasma were extracted, and radiolabeled components were identified and quantified using high-performance liquid chromatography with on-line radioactivity detection and tandem mass spectrometry. Two hours after dosing, all the [2-(14)C]quercetin-4'-glucoside had been metabolized. More than 85% of the ingested radioactivity was present in the gastrointestinal tract at all time points with approximately 6% being absorbed and present in blood and internal organs, primarily the liver and kidneys. More than 95% of the absorbed radioactivity was in the form of >20 different methylated glucuronated and\/or sulfated quercetin conjugates. Five hours after ingestion, the main radiolabeled metabolites were quercetin diglucuronides in the gut, liver, and kidneys and glucuronyl sulfates of methylated quercetin in plasma. The main site of quercetin metabolism seemed to be the gastrointestinal tract. Quercetin metabolites may have a major influence on the gut mucosal epithelium and on colonic disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":21346618,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Brain volume changes after withdrawal of atypical antipsychotics in patients with first-episode schizophrenia.\nThe influence of antipsychotic medication on brain morphology in schizophrenia may confound interpretation of brain changes over time. We aimed to assess the effect of discontinuation of atypical antipsychotic medication on change in brain volume in patients. Sixteen remitted, stable patients with first-episode schizophrenia, schizoaffective or schizophreniform disorder and 20 healthy controls were included. Two magnetic resonance imaging brain scans were obtained from all subjects with a 1-year interval. The patients either discontinued (n = 8) their atypical antipsychotic medication (olanzapine, risperidone, or quetiapine) or did not (n = 8) discontinue during the follow-up period. Intracranial volume and volumes of total brain, cerebral gray and white matter, cerebellum, third and lateral ventricle, nucleus caudatus, nucleus accumbens, and putamen were obtained. Multiple linear regression analyses were used to assess main effects for group (patient-control) and discontinuation (yes-no) for brain volume (change) while correcting for age, sex, and intracranial volume. Decrease in cerebral gray matter and caudate nucleus volume over time was significantly more pronounced in patients relative to controls. Our data suggest decreases in the nucleus accumbens and putamen volumes during the interval in patients who discontinued antipsychotic medication, whereas increases were found in patients who continued their antipsychotics. We confirmed earlier findings of excessive gray matter volume decrements in patients with schizophrenia compared with normal controls. We found evidence suggestive of decreasing volumes of the putamen and nucleus accumbens over time after discontinuation of medication. This might suggest that discontinuation reverses effects of atypical medication.","subset":"pubmed_abstract"} +{"meta":{"pmid":4554365,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-23":1,"2022-40":2,"2022-33":1,"2022-27":1,"2021-25":1,"2021-10":1,"2020-29":2,"2020-10":1,"2023-50":1,"2024-10":2,"2024-18":1}}},"text":"A fine-structural analysis of the fusion of myogenic cells.\nThe fusion of myogenic cells has been examined on the fine-structural level in muscle cell cultures of embryonic Japanese Coturnix quail. Cells, selected by light microscopy, were serially sectioned normal to their long axis. In this plane, oblique sections of cell membranes are rare and plasmalemmal profiles are more easily traced between adjacent cells. In seven cases, pairs of cells, apparently fixed in the process of fusion, are joined by a single cytoplasmic bridge. Since obliquely sectioned membranes often suggest cytoplasmic confluence, tilting stage analysis was employed to resolve cell membranes in suspect cases. In contrast to such artifacts of superposition, however, the observed intercommunicating pores are contained within a pair of culs-de-sac formed by the fused membranes of both cells. These blind pouches can be traced back between the cells to the external space. The confluent regions are clearly demarcated and they are not simply areas between vesicular profiles. The results of this analysis suggest that (a) at no time is there any loss of integrity of the cellular envelope, and (b) fusion is most probably initiated at single sites between pairs of cells, the pore enlarging, leaving first vestiges and eventually no trace of the original intervening membranes.","subset":"pubmed_abstract"} +{"meta":{"pmid":22249328,"dup_signals":{"dup_doc_count":33,"dup_dump_count":31,"dup_details":{"curated_sources":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2014-52":1,"2014-49":1,"2014-41":1,"2014-35":2,"2014-23":1,"2014-15":1,"2018-26":1}}},"text":"An audit to assess awareness and knowledge of nutrition in a UK spinal cord injuries centre.\nA single centre survey. To test: (i) awareness of nutrition screening tools and related care plans and; (ii) nutrition knowledge of doctors, nurses and dietitians working in spinal cord injuries (SCI) centres. The 14-item questionnaire was sent to 102 nurses, 17 doctors and 15 dietitians working in UK SCI centres during January-March 2010. Sixty-two (46.5%) questionnaires were completed and returned for analysis. The present audit demonstrated that awareness of the need for nutritional screening is good: 83% of staff reported that they are aware there is a nutrition screening tool. This audit also demonstrated areas of poor knowledge, such as calorie content of intravenous fluids, indicators of malnutrition, and choice of nutritional support in malnourished patients. All doctors, but only 38% of nurses, knew how to calculate body mass index. Surprisingly, nearly half (49%) of the participants thought that at least 20% weight loss was required to indicate malnutrition. This high-perceived cut-off point suggests that malnutrition is likely to continue to be undetected and unmanaged. The overall scores (median) showed clear differences in nutritional knowledge between groups (median: dietitians 92.8%; doctors 53.5%; nurses 35.7; P<0.01). This suggests that dietitians could have an important role in training healthcare professionals about nutrition. This study highlights the need for further education in SCI medicine in order to improve the efficacy of feeding and nutrition therapy for SCI patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":9824578,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Intestinal permeability and inflammation in patients on NSAIDs.\nThe frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain. To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs. Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar). Two hundred and eighty six patients on 12 different NSAIDs underwent indium-111 white cell faecal excretion studies to assess the prevalence and severity of intestinal inflammation. The iso- and hyperosmolar tests showed significant malabsorption of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Intestinal permeability changes were significantly more pronounced and frequent with the hypo- and hyperosmolar as opposed to the iso-osmolar test. Sequential studies showed that four and nine patients (of 13) developed inflammation after three and six months treatment with NSAIDs, respectively. There was no significant difference (p>0.1) in the prevalence (54-72%) or severity of intestinal inflammation in the 286 patients taking the various NSAIDs apart from those on aspirin and nabumetone, these having no evidence of intestinal inflammation. There was no significant correlation between the inflammatory changes and age, sex, dose of NSAID, length of disease, or NSAID ingestion. Intestinal permeability test dose composition is an important factor when assessing the effects of NSAIDs on intestinal integrity. All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.","subset":"pubmed_abstract"} +{"meta":{"pmid":28580466,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Optical sensing of mechanical pressure based on diffusion measurement in polyacrylamide cell-like barometers.\nDiffusion and transport of small molecules within hydrogel networks are of high interest for biomedical and pharmaceutical research. Herein, using fluorescence correlation spectroscopy (FCS), we experimentally showed that the diffusion time in the hydrogel was directly related to the mechanical state (compression or swelling) and thus to the volume fraction of the gel. Following this observation, we developed cell-like barometers in the form of PAA microbeads, which when incorporated between cells and combined with a diffusion-based optical readout could serve as the first biosensors to measure the local pressure inside the growing biological tissues. To illustrate the potential of the present method, we used multicellular spheroids (MCS) as a tissue model, and it was observed that the growth-associated tissue stress was lower than 1 kPa, but significantly increased when an external compressive stress was applied.","subset":"pubmed_abstract"} +{"meta":{"pmid":11184218,"dup_signals":{"dup_doc_count":39,"dup_dump_count":32,"dup_details":{"curated_sources":4,"2023-23":1,"2023-14":1,"2021-39":1,"2021-21":1,"2020-10":1,"2020-05":1,"2019-43":1,"2019-39":1,"2019-26":1,"2019-18":1,"2019-04":1,"2018-47":2,"2018-39":1,"2018-30":1,"2018-09":1,"2017-39":1,"2017-30":2,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2023-50":1,"2024-26":2,"2024-30":1}}},"text":"School health education and gender: an interactive effect?\nPost-primary school students (n = 2407) and young adults (n = 477) participated in a cross-sectional evaluation of a health education programme for schools. The Lifeskills programme is based on a philosophy of student empowerment, and aims to teach knowledge and skills relevant to health promoting behaviour. School students were recruited in schools, while young adults were opportunistically recruited in workplaces, training centres and on public transport. Those who attended schools where Lifeskills had been taught and who remembered such lessons were conservatively classified as the intervention group, while those who attended other schools and did not remember such lessons were classified as the comparison group. Participants completed questionnaires designed to collect data on health-related behaviours, indicators, knowledge and psychological health. School-level factors were employed as covariates in subsequent analyses of covariance. Amongst younger pupils, females reported more positive health behaviours but lower levels of psychological well-being and more symptoms. The impact of the programme became evident at ages 13-15. Those involved drank less and reported more positive adjustment to school. However, sex differences remained, with females reporting more health-promoting behaviour and more symptoms, and lagging behind males in self-esteem and general well-being. An interaction between gender and the intervention was identified among senior pupils. Exposure was especially beneficial for females. However, as young adults, the two main effects of gender and programme participation re-emerged as the most important independent variables, and the interaction between them was not significant. This pattern has implications for the interpretation of evaluations conducted on short-term interventions as well as for short-term impact evaluations.","subset":"pubmed_abstract"} +{"meta":{"pmid":2513368,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Tissue-selective acute effects of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase on cholesterol biosynthesis in lens.\nInhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme that regulates cholesterol synthesis, lower serum cholesterol by increasing the activity of low density lipoprotein (LDL) receptors in the liver. In rat liver slices, the dose-response curves for inhibition of [14C]acetate incorporation into cholesterol were similar for the active acid forms of lovastatin, simvastatin, and pravastatin. The calculated IC50 values were approximately 20-50 nM for all three drugs. Interest in possible extrahepatic effects of reductase inhibitors is based on recent findings that some inhibitors of HMG-CoA reductase, lovastatin and simvastatin, can cause cataracts in dogs at high doses. To evaluate the effects of these drugs on cholesterol synthesis in the lens, we developed a facile, reproducible ex vivo assay using lenses from weanling rats explanted to tissue culture medium. [14C]Acetate incorporation into cholesterol was proportional to time and to the number of lenses in the incubation and was completely eliminated by high concentrations of inhibitors of HMG-CoA reductase. At the same time, incorporation into free fatty acids was not inhibited. In marked contrast to the liver, the dose-response curve for pravastatin in lens was shifted two orders of magnitude to the right of the curves for lovastatin acid and simvastatin acid. The calculated IC50 values were 4.5 +\/- 0.7 nM, 5.2 +\/- 1.5 nM, and 469 +\/- 42 nM for lovastatin acid, simvastatin acid, and pravastatin, respectively. Thus, while equally active in the liver, pravastatin was 100-fold less inhibitory in the lens compared to lovastatin and simvastatin. Similar selectivity was observed with rabbit lens. Following oral dosing, ex vivo inhibition of [14C]acetate incorporation into cholesterol in rat liver was similar for lovastatin and pravastatin, but cholesterol synthesis in lens was inhibited by lovastatin by as much as 70%. This inhibition was dose-dependent and no inhibition in lens was observed with pravastatin even at very high doses. This tissue-selective inhibition of sterol synthesis by pravastatin was likely due to the inability of pravastatin to enter the intact lens since pravastatin and lovastatin acid were equally effective inhibitors of HMG-CoA reductase enzyme activity in whole lens homogenates. We conclude that pravastatin is tissue-selective with respect to lens and liver in its ability to inhibit cholesterol synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":27515047,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Single oxygen vacancies of (TiO2)35 as a prototype reduced nanoparticle: implication for photocatalytic activity.\nTitanium dioxide (TiO2), as a semiconductor metal oxide, has been one of the most popular materials studied in the field of photocatalysis. In the present study, the properties of single oxygen vacancies of (TiO2)35, a prototype of an anatase nanoparticle, were investigated by DFT calculations. (TiO2)35 is the minimum sized model (\u223c2 nm) for a bipyramidal nanoparticle with anatase phase and eight {101} facets. All the available oxygen vacancies at various sites according to position, coordination number, and distance from the center atom were examined. The geometric, energetic and electronic properties of the reduced TiO2 clusters were analyzed by hybrid DFT functionals with different Hartree-Fock exchange ratios (0, 12.5 and 25%). It was found that the structure of pristine (TiO2)35 is somewhat different from the bulk lattice, with a relatively high surface to volume ratio. Moreover, the particular highly (three)-coordinated oxygen atom is energetically the most favorable for oxygen vacancy formation from the nanoparticle mainly due to its substantially high relaxation energy. TiO2 nanoparticles have low oxygen vacancy formation energy and narrow band gap because of their defect states, and can be utilized as an efficient photocatalyst material.","subset":"pubmed_abstract"} +{"meta":{"pmid":27462314,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Evaluation of the Antioxidant Activity of Aqueous and Methanol Extracts of Pleurotus ostreatus in Different Growth Stages.\nTotal polyphenols and flavonoids contents, as well as ferric reducing antioxidant power (FRAP), metal ions chelating activity, reducing power assay and scavenging activity of DPPH and ABTS radicals in aqueous and methanolic extracts obtained from mycelium, primordium, and fruiting body of Pleurotus ostreatus in both fresh as dry, were evaluated. The total polyphenol content of dried samples was higher in aqueous extracts obtained both in room temperature and boiling. The total polyphenol content of the fresh samples obtained at room temperature and boiling was higher in aqueous extract of mycelium and in the methanolic extract of the fruiting body. In general, flavonoids represented a very small percentage of the total polyphenol content. The antioxidant activity measured by the FRAP method of extracts from fresh samples were higher with respect to the dried samples. The results of the metal ion chelating activity indicate that all extracts tested had acted. The reducing power of all samples was concentration dependent. In general, the extracts of dried samples showed higher reducing power than the extracts of fresh samples and tend to show greater reducing power by aqueous than methanolic extracts. It was observed that the DPPH and ABTS radical scavenging activities were positively correlated to the concentration of the extract. The results suggested that antioxidant activity could be due to polyphenols, but mainly by different molecules or substances present in the extracts. Overall, the fruiting body of P. ostreatus showed the best results and the possibility of continuing to investigate its functional properties of this fungus is opened. This is the first report where the antioxidant activity of P. ostreatus in different growth stage was reported.","subset":"pubmed_abstract"} +{"meta":{"pmid":2842437,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Restriction mapping of Lymantria dispar nuclear polyhedrosis virus DNA: localization of the polyhedrin gene and identification of four homologous regions.\nThe genome of the multiple-embedded nuclear polyhedrosis virus (MNPV) of Lymantria dispar (LdMNPV) was partially characterized by restriction endonuclease analysis and a physical map was constructed using cosmid cloning and Southern cross blot hybridization. Using BamHI, BglII, EcoRI and HindIII, the size of the genome was estimated to be 88.5 x 10(6) Mr or 134.04 kbp. LdMNPV DNA was also analysed using methylation-sensitive restriction enzymes. The resulting restriction profiles suggested that extensive methylation did not occur at the nucleotide sequence recognized by HpaII and MspI. A BamHI restriction map was constructed by comparing overlapping BamHI fragments between cosmid clones containing partial digests of viral DNA. The positions of the BglII, EcoRI and HindIII sites were determined by Southern cross blot hybridizations and aligned to the BamHI restriction map. At least four homologous regions were identified by cross blot hybridizations of BglII-digested LdMNPV DNA and such regions were found to be interspersed along the genome in a fashion similar to that reported for other baculoviruses. Using recombinant plasmids containing the HindIII-V fragment of Autographa californica MNPV to probe Southern blots of LdMNPV DNA, the restriction fragment(s) that contain the polyhedrin gene were identified. Based on these findings the map was oriented with the polyhedrin gene of LdMNPV as the zero point.","subset":"pubmed_abstract"} +{"meta":{"pmid":1751104,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":8}}},"text":"Effect of erythropoietin on neutrophil chemiluminescence in hemodialyzed patients.\nErythropoietin (EPO) has been used widely for correcting anemia in hemodialyzed (HD) patients. Enhancement of phagocytic function during EPO treatment of HD patients has been studied, but no data have been available on the effect of EPO on neutrophil chemiluminescence (CL) after challenge with phorbol myristate acetate (PMA). CL was measured in prehemodialysis whole blood samples from 15 stabilized patients and 15 normal healthy control subjects (C) after challenge with PMA. Before EPO treatment, CL was noted to be significantly higher in HD patients than in C, which changed significantly after 5 weeks of treatment (Rx) and continued for 13 weeks of Rx. There was a significant increase in hematocrit in these HD patients after 5 weeks that persisted until the 13th week. It was concluded that there is a significant decrease in whole blood CL in response to challenge with PMA during correction of anemia in HD patients treated with EPO. This study demonstrated that EPO could decrease enhanced PMA-activated reactive oxygen metabolite production and suggested that this decrease may protect against tissue damage, including red blood cell hemolysis in the uremic milieu.","subset":"pubmed_abstract"} +{"meta":{"pmid":37066020,"dup_signals":{"dup_doc_count":12,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-22":3,"2024-18":2,"2024-10":1,"2024-26":1,"unknown":4}}},"text":"Genomic epidemiology of human adenovirus F40 and F41 in coastal Kenya: A retrospective hospital-based surveillance study (2013-2022).\nHuman enteric adenovirus species F (HAdV-F) is a leading cause of childhood diarrhoeal deaths. The genomic analysis would be key to understanding transmission dynamics, potential drivers of disease severity, and vaccine development. However, currently, there are limited HAdV-F genomic data globally. Here, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in coastal Kenya from children <13 years of age who reported a history of three or more loose stools in the previous 24 hours. The genomes were analysed together with the data from the rest of the world by phylogenetic analysis and mutational profiling. Types and lineages were assigned based on phylogenetic clustering consistent with the previously described criteria and nomenclature. Participant clinical and demographic data were linked to genotypic data. Of ninety-one cases identified using real-time Polymerase Chain Reaction, eighty-eight near-complete genomes were assembled, and these were classified into HAdV-F40 (n = 41) and HAdV-F41 (n = 47). These types co-circulated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineages 1-3) and HAdV-F41 (Lineages 1, 2A, 3A, 3C, and 3D). Types F40 and F41 coinfections were observed in five samples and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe diseases as defined using the Vesikari Scoring System, respectively. Intratypic recombination was found in four HAdV-F40 sequences occurring between Lineages 1 and 3. None of the HAdV-F41 cases had jaundice. This study provides evidence of extensive genetic diversity, coinfections, and recombination within HAdV-F40 in a rural coastal Kenya that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.","subset":"pubmed_abstract"} +{"meta":{"pmid":25891694,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":11}}},"text":"Initial experience with a tailor-made simulation and navigation program using a 3-D printer model of kidney transplantation surgery.\nThree-dimensional (3-D) printing systems allow for the creation of surgical models mimicking real tissue. We developed a kidney graft and pelvic cavity replica as a patient-specific 3-D model using a 3-D printing system with simultaneous jetting of different materials and subsequently evaluated the usefulness of surgical simulation and navigation of living kidney transplantation. After generating a stereolithographic file of the organ surface based on multidetector computed tomographic data, we created a 3-D organ model using an inkjet 3-D printer and manufactured a pelvic cavity replica using patient-specific data. The patients' individual 3-D printed models were used to plan and guide the surgical procedures for laparoscopic donor nephrectomy and recipient transplantation surgery. The 3-D organ replicas obtained using transparent materials allowed for the creation of models that showed the visceral organs, blood vessels, and other details, thereby overcoming the limitations of conventional image-guided navigation. Our pelvic replicas can be made according to each patient's specific anatomical data, thus representing personalized surgical procedures. This level of detail of the anatomy enables the surgeons and trainees to virtually treat various pelvic conditions before they perform the surgical procedure. The use of these replicas may also reduce the length of the operation and provide better anatomical reference tools for tailor-made simulation and navigation of kidney transplantation surgery, consequently helping to improve training for the operating room staff, students, and trainees. We believe that our sophisticated personalized donor graft and pelvic replications obtained using a 3-D printing system are advantageous for kidney transplantation surgery.","subset":"pubmed_abstract"} +{"meta":{"pmid":16150694,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Truncation and activation of calcineurin A by calpain I in Alzheimer disease brain.\nA disturbance of calcium homeostasis is believed to play an important role in the neurodegeneration of the brains of Alzheimer disease (AD) patients, but the molecular pathways by which it contributes to the disease are not well understood. Here we studied the activation of two major Ca(2+)-regulated brain proteins, calpain and calcineurin, in AD brain. We found that calpain I is activated, which in turn cleaves and activates calcineurin in AD brain. Mass spectrometric analysis indicated that the cleavage of calcineurin by calpain I is at lysine 501, a position C-terminal to the autoinhibitory domain, which produces a 57-kDa truncated form. The 57-kDa calcineurin maintains its Ca(2+)\/calmodulin dependence of the phosphatase activity, but the phosphatase activity is remarkably activated upon truncation. The cleavage and activation of calcineurin correlate to the number of neurofibrillary tangles in human brains. These findings suggest that the overactivation of calpain I and calcineurin may mediate the role of calcium homeostatic disturbance in the neurodegeneration of AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":32264123,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Hydrogen bonded capsules by layer-by-layer assembly of tannic acid and poly(2-n-propyl-2-oxazoline) for encapsulation and release of macromolecules.\nWe report hydrogen bonded capsules with the built-in ability to release loaded bioactive molecules at a physiological temperature of 37 \u00b0C. The use of neutral and non-toxic building blocks such as tannic acid (TA) and poly(2-n-propyl-2-oxazoline)s (PnPropOx) as hydrogen bonding donor and acceptor results in stable hollow capsules. The temperature induced morphological changes of the shell were investigated using a scanning electron microscope and an optical microscope and revealed pore formation in the shell when the temperature (T) increases beyond the cloud point temperature (TCP) of PnPropOx. Furthermore, confocal laser scanning microscopic investigation of the hollow capsules loaded with different probes of varying hydrodynamic diameters revealed that the open and closed state of the capsules could be effectively manipulated by varying the incubation time and hydrodynamic radius of the probes. Such hydrogen bonded capsules have high potential for use in temperature responsive sustained drug delivery applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":24196516,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2015-18":1,"unknown":7}}},"text":"Ants learn to rely on more informative attributes during decision-making.\nEvolutionary theory predicts that animals act to maximize their fitness when choosing among a set of options, such as what to eat or where to live. Making the best choice is challenging when options vary in multiple attributes, and animals have evolved a variety of heuristics to simplify the task. Many of these involve ranking or weighting attributes according to their importance. Because the importance of attributes can vary across time and place, animals might benefit by adjusting weights accordingly. Here, we show that colonies of the ant Temnothorax rugatulus use their experience during nest site selection to increase weights on more informative nest attributes. These ants choose their rock crevice nests on the basis of multiple features. After exposure to an environment where only one attribute differentiated options, colonies increased their reliance on this attribute relative to a second attribute. Although many species show experience-based changes in selectivity based on a single feature, this is the first evidence in animals for adaptive changes in the weighting of multiple attributes. These results show that animal collectives, like individuals, change decision-making strategies according to experience. We discuss how these colony-level changes might emerge from individual behaviour.","subset":"pubmed_abstract"} +{"meta":{"pmid":12657070,"dup_signals":{"dup_doc_count":11}},"text":"Depression treatment in a sample of 1,801 depressed older adults in primary care.\nTo examine rates and predictors of lifetime and recent depression treatment in a sample of 1,801 depressed older primary care patients Cross sectional survey data collected from 1999 to 2001 as part of a treatment effectiveness trial. Eighteen primary care clinics belonging to eight organizations in five states. One thousand eight hundred one clinic users aged 60 and older who met diagnostic criteria for major depression or dysthymia. Lifetime depression treatment was defined as ever having received a prescription medication, counseling, or psychotherapy for depression. Potentially effective recent depression treatment was defined as 2 or more months of antidepressant medications or four or more sessions of counseling or psychotherapy for depression in the past 3 months. The mean age +\/- standard deviation was 71.2 +\/- 7.5; 65% of subjects were women. Twenty-three percent of the sample came from ethnic minority groups (12% were African American, 8% were Latino, and 3% belonged to other ethnic minorities). The median household income was $23,000. Most study participants (83%) reported depressive symptoms for 2 or more years, and most (71%) reported two or more prior depressive episodes. About 65% reported any lifetime depression treatment, and 46% reported some depression treatment in the past 3 months, although only 29% reported potentially effective recent depression treatment. Most of the treatment provided consisted of antidepressant medications, with newer antidepressants such as selective serotonin reuptake inhibitors constituting the majority (78%) of antidepressants used. Most participants indicated a preference for counseling or psychotherapy over antidepressant medications, but only 8% had received such treatment in the past 3 months, and only 1% reported four or more sessions of counseling. Men, African Americans, Latinos, those without two or more prior episodes of depression, and those who preferred counseling to antidepressant medications reported significantly lower rates of depression care. The findings suggest that there is considerable opportunity to improve care for older adults with depression. Particular efforts should be focused on improving access to depression care for older men, African Americans, Latinos, and patients who prefer treatments other than antidepressants.","subset":"pubmed_abstract"} +{"meta":{"pmid":37884331,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":7,"unknown":7}}},"text":"Increased Metabolic Activity of the Thymus and Lymph Nodes in Pediatric Oncology Patients After Coronavirus Disease 2019 Vaccination.\nWe hypothesized that 18F-FDG PET\/MRI would reveal thymus activation in children after coronavirus disease 2019 (COVID-19) vaccination. Methods: We retrospectively analyzed the 18F-FDG PET\/MRI scans of 6 children with extrathoracic cancer before and after COVID-19 vaccination. We compared pre- and postvaccination SUVmax, mean apparent diffusion coefficient, and size of the thymus and axillary lymph nodes using a paired t test. Results: All 6 patients showed increased 18F-FDG uptake in the axillary lymph nodes after vaccination (P = 0.03). In addition, these patients demonstrated increased 18F-FDG uptake in the thymus. When compared with baseline, the postvaccination scans of these patients demonstrated an increased mean thymic SUV (P = 0.02), increased thymic size (P = 0.13), and decreased thymic mean apparent diffusion coefficient (P = 0.08). Conclusion: 18F-FDG PET\/MRI can reveal thymus activation in addition to local lymph node reactions in children after COVID-19 vaccination.","subset":"pubmed_abstract"} +{"meta":{"pmid":23429762,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"No Association between the Response to the Addition of an Atypical Antipsychotic Drug to an SSRI or SNRI and the BDNF (Val66Met) Polymorphism in Refractory Major Depressive Disorder in Japanese Patients.\nThis study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression. The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores \u226515 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean\u00b1SD, 48\u00b113 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay. No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year. These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.","subset":"pubmed_abstract"} +{"meta":{"pmid":31804964,"dup_signals":{"dup_doc_count":17,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-49":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-21":3,"2021-17":1,"2021-04":1,"2020-45":1,"2020-10":1,"2023-40":1}}},"text":"Habitual physical activity is associated with lower fasting and greater glucose-induced GLP-1 response in men.\nThe hormone glucagon-like peptide-1 (GLP-1) decreases blood glucose and appetite. Greater physical activity (PA) is associated with lower incidence of type 2 diabetes. While acute exercise may increase glucose-induced response of GLP-1, it is unknown how habitual PA affects GLP-1 secretion. We hypothesised that habitual PA associates with greater glucose-induced GLP-1 responses in overweight individuals. Cross-sectional analysis of habitual PA levels and GLP-1 concentrations in 1326 individuals (mean (s.d.) age 66 (7) years, BMI 27.1 (4.5) kg\/m2) from the ADDITION-PRO cohort. Fasting and oral glucose-stimulated GLP-1 responses were measured using validated radioimmunoassay. PA was measured using 7-day combined accelerometry and heart rate monitoring. From this, energy expenditure (PAEE; kJ\/kg\/day) and fractions of time spent in activity intensities (h\/day) were calculated. Cardiorespiratory fitness (CRF; mL O2\/kg\/min) was calculated using step tests. Age-, BMI- and insulin sensitivity-adjusted associations between PA and GLP-1, stratified by sex, were evaluated by linear regression analysis. In 703 men, fasting GLP-1 concentrations were 20% lower (95% CI: -33; -3%, P = 0.02) for every hour of moderate-intensity PA performed. Higher CRF and PAEE were associated with 1-2% lower fasting GLP-1 (P = 0.01). For every hour of moderate-intensity PA, the glucose-stimulated GLP-1 response was 16% greater at peak 30 min (1; 33%, P rAUC0-30 = 0.04) and 20% greater at full response (3; 40%, P rAUC0-120 = 0.02). No associations were found in women who performed PA 22 min\/day vs 32 min\/day for men. Moderate-intensity PA is associated with lower fasting and greater glucose-induced GLP-1 responses in overweight men, possibly contributing to improved glucose and appetite regulation with increased habitual PA.","subset":"pubmed_abstract"} +{"meta":{"pmid":22206730,"dup_signals":{"dup_doc_count":11}},"text":"Increased adenosine concentration in bronchoalveolar lavage fluid of horses with lower airway inflammation.\nSeveral reports have suggested a role for adenosine in the pathogenesis of chronic airway conditions and this has led to new therapeutic strategies to limit airway inflammation. In this study, detectable levels of adenosine in bronchoalveolar lavage (BAL) samples from 11 horses with non-infectious lower-airway inflammation and 14 healthy controls are reported, with significantly higher values in horses with airway inflammation. Although these increased levels did not correlate with changes in neutrophil percentage in BAL, a positive association between adenosine levels and signs of lower airway inflammation (clinical score) was observed. These novel findings support the hypothesis that adenosine may contribute to bronchoconstriction and also act as a pro-inflammatory mediator in the bronchoalveolar milieu of horses with airway inflammation. Further investigation of this axis could lead to new approaches for the treatment of highly prevalent lower airway inflammatory conditions in the horse.","subset":"pubmed_abstract"} +{"meta":{"pmid":25643352,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"CXCL9 contributes to antimicrobial protection of the gut during citrobacter rodentium infection independent of chemokine-receptor signaling.\nChemokines have been shown to be effective bactericidal molecules against a variety of bacteria and fungi in vitro. These direct antimicrobial effects are independent of their chemotactic activities involving immunological receptors. However, the direct biological role that these proteins may play in host defense, particularly against intestinal pathogens, is poorly understood. Here, we show that CXCL9, an ELR- chemokine, exhibits direct antimicrobial activity against Citrobacter rodentium, an attaching\/effacing pathogen that infects the gut mucosa. Inhibition of this antimicrobial activity in vivo using anti-CXCL9 antibodies increases host susceptibility to C. rodentium infection with pronounced bacterial penetration into crypts, increased bacterial load, and worsened tissue pathology. Using Rag1(-\/-) mice and CXCR3(-\/-) mice, we demonstrate that the role for CXCL9 in protecting the gut mucosa is independent of an adaptive response or its immunological receptor, CXCR3. Finally, we provide evidence that phagocytes function in tandem with NK cells for robust CXCL9 responses to C. rodentium. These findings identify a novel role for the immune cell-derived CXCL9 chemokine in directing a protective antimicrobial response in the intestinal mucosa.","subset":"pubmed_abstract"} +{"meta":{"pmid":11884946,"dup_signals":{"dup_doc_count":24,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2014-10":2,"2013-48":2,"unknown":18}}},"text":"Epstein-Barr virus infection is associated with endothelial Bcl-2 expression in transplant liver allografts.\nIn liver transplant recipients with Epstein-Barr virus (EBV) disease, we reported a low rate of acute rejection after stopping or markedly lowering immunosuppression. This observation led to the hypothesis that EBV, as a means of viral persistence, induces expression of antiapoptotic factors and these factors, in turn, confer protection to the transplanted organ. Bcl-2, an antiapoptotic factor induced by EBV in various host cells, is not normally expressed in the liver. We questioned whether bcl-2 is expressed in the transplanted liver and whether its expression is modified by EBV. Retrospective liver biopsy specimen from liver transplant patients diagnosed with EBV (n=12) were examined for the presence of bcl-2 by immunohistochemistry and compared with EBV (-) transplant (n=15), and nontransplant (n=13) livers. The most significant finding was the presence of endothelial bcl-2 expression in the majority of EBV (+) transplant samples examined (67%) and its relative absence in the other two groups (P<0.005). There was also bcl-2 expression in the hepatocytes and lymphocytes of the majority of transplant liver samples, irrespective of EBV status. We have identified a strong association between EBV infection and endothelial bcl-2 expression in transplant livers. We also found that transplantation, in itself, was associated with bcl-2 expression in the hepatocytes and lymphocytes of liver allografts.","subset":"pubmed_abstract"} +{"meta":{"pmid":23820783,"dup_signals":{"dup_doc_count":16,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-33":2,"2022-27":1,"2022-05":1,"2021-25":1,"2019-35":1,"2019-18":1,"2019-09":1,"2018-39":1,"2018-22":1,"2018-05":1,"2017-39":1}}},"text":"Effects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndrome.\nDiet is important in triggering the symptoms of irritable bowel syndrome (IBS). This study investigated the impact of dietary guidance on the symptoms, quality of life and habitual diet of patients with IBS. Forty-six patients who fulfilled the Rome III criteria for the diagnosis of IBS were included. Of these patients, 17 completed the entire study. Each patient attended three sessions (~45 min in duration) and received individual guidance on their dietary management. The patients were asked to complete the following questionnaires prior to receiving the dietary guidance, and at least 3 months subsequently: The Birmingham IBS symptom score questionnaire, the IBS Quality of Life (IBS-QOL) questionnaire, the Short-Form Nepean and Dyspepsia Index (SF\u2011NDI) and the MoBa Food Frequency Questionnaire (MoBa FFQ). The time at which patients completed the questionnaires following dietary guidance ranged from 3-9 months (median, 4 months). The total IBS symptom scores were reduced once the patients had received dietary guidance (P=0.001). The total score for the quality of life, as assessed by the IBS\u2011QOL and the SF-NDI, increased significantly following the dietary guidance sessions (P=0.003 and P=0.002, respectively). There were no statistical differences in the intake of calories, carbohydrate, fiber, protein, fat or alcohol in the patients with IBS following dietary guidance. There were increases in the consumption of dairy products, \u03b2-carotene, retinol equivalents, riboflavin, vitamin B12 and calcium, although only the increase in vitamin B12 consumption was statistically significant. There was a significant reduction in the consumption of certain fruits and vegetables that were rich in highly fermentable short-chain carbohydrates, disaccharides, monosaccharides and polyols, as well as insoluble fibers. In conclusion, three 45-min dietary guidance sessions, administered by a nurse, reduced the symptoms and improved the quality of life of patients with IBS, and resulted in an adequate intake of vitamins and minerals. Individual dietary guidance is a cost-effective option for the management of IBS.","subset":"pubmed_abstract"} +{"meta":{"pmid":27134057,"dup_signals":{"dup_doc_count":11}},"text":"Meta-Analysis of the Duration of Dual Antiplatelet Therapy in Patients Treated With Second-Generation Drug-Eluting Stents.\nThe purpose of the study was to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention, especially in the era of second-generation drug-eluting stents (DES). The work was conducted from November 2014 to April 2015. All randomized controlled trials comparing short (<12 months) versus long (\u226512 months) DAPT in patients treated with second-generation DES were analyzed. Sensitivity analyses were performed for length of DAPT and type of DES. All-cause death was the primary end point, whereas cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), and major bleeding were secondary end points. Results were pooled and compared with random-effect models and meta-regression analysis. Eight randomized controlled trials with 18,810 randomized patients were included. The studies compared 3 versus 12 months of DAPT (2 trials), 6 versus 12 months (3 trials), 6 versus 24 months (1 trial), 12 versus 24 months (1 trial), and 12 versus 30 months (1 trial). Comparing short versus long DAPT, there were no significant differences in all-cause death (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.66 to 1.44), cardiovascular death (OR 0.95; 95% CI 0.65 to 1.37), and ST (OR 1.20; 95% CI 0.79 to 1.83), and no differences were present when considering everolimus-eluting and fast-release zotarolimus-eluting stents separately. Shorter DAPT was inferior to longer DAPT in preventing MI (OR 1.35; 95% CI 1.03 to 1.77). Conversely, major bleeding was reduced by shorter DAPT (OR 0.60; 95% CI 0.42 to 0.96). Baseline features did not influence these results in meta-regression analysis. In conclusion, DAPT for \u22646 months is reasonable for patients treated with everolimus-eluting and fast-release zotarolimus-eluting stents, with the benefit of less major bleeding at the cost of increased MI, with similar survival and ST rates. An individualized patient approach to DAPT duration should take into account the competing risks of bleeding and ischemic complications after present-generation DES.","subset":"pubmed_abstract"} +{"meta":{"pmid":22540973,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2022-27":1,"2022-21":1,"2021-39":1,"2021-10":1,"2020-40":1,"2020-16":1,"2018-30":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-23":1}}},"text":"Differential Plasmodium falciparum infection of Anopheles gambiae s.s. molecular and chromosomal forms in Mali.\nAnopheles gambiae sensu stricto (s.s.) is a primary vector of Plasmodium falciparum in sub-Saharan Africa. Although some physiological differences among molecular and chromosomal forms of this species have been demonstrated, the relative susceptibility to malaria parasite infection among them has not been unequivocally shown. The objective of this study was to investigate P. falciparum circumsporozoite protein infection (CSP) positivity among An. gambiae s.s. chromosomal and molecular forms. Wild An. gambiae from two sites Kela (n=464) and Sidarebougou (n=266) in Mali were screened for the presence of P. falciparum CSP using an enzyme-linked immunosorbent assay (ELISA). Samples were then identified to molecular form using multiple PCR diagnostics (n=713) and chromosomal form using chromosomal karyotyping (n=419). Of 730 An. gambiae sensu lato (s.l.) mosquitoes, 89 (12.2%) were CSP ELISA positive. The percentage of positive mosquitoes varied by site: 52 (11.2%) in Kela and 37 (13.9%) in Sidarebougou. Eighty-seven of the positive mosquitoes were identified to molecular form and they consisted of nine Anopheles arabiensis (21.4%), 46 S (10.9%), 31 M (12.8%), and one MS hybrid (14.3%). Sixty of the positive mosquitoes were identified to chromosomal form and they consisted of five An. arabiensis (20.0%), 21 Savanna (15.1%), 21 Mopti (30.4%), 11 Bamako (9.2%), and two hybrids (20.0%). In this collection, the prevalence of P. falciparum infection in the M form was equivalent to infection in the S form (no molecular form differential infection). There was a significant differential infection by chromosomal form such that, P. falciparum infection was more prevalent in the Mopti chromosomal forms than in the Bamako or Savanna forms; the Mopti form was also the most underrepresented in the collection. Continued research on the differential P. falciparum infection of An. gambiae s.s. chromosomal and molecular forms may suggest that Plasmodium - An. gambiae interactions play a role in malaria transmission.","subset":"pubmed_abstract"} +{"meta":{"pmid":32598315,"dup_signals":{"dup_doc_count":26,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":19}}},"text":"The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE).\nThis paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic biology. The COMBINE initiative coordinates the development of various community standards and formats for computational models in the life sciences. Over the past 10 years, COMBINE has brought together standard communities that have further developed and harmonized their standards for better interoperability of models and data. COMBINE 2019 was co-located with a stakeholder workshop of the European EU-STANDS4PM initiative that aims at harmonized data and model standardization for in silico models in the field of personalized medicine, as well as with the FAIRDOM PALs meeting to discuss findable, accessible, interoperable and reusable (FAIR) data sharing. This report briefly describes the work discussed in invited and contributed talks as well as during breakout sessions. It also highlights recent advancements in data, model, and annotation standardization efforts. Finally, this report concludes with some challenges and opportunities that this community will face during the next 10 years.","subset":"pubmed_abstract"} +{"meta":{"pmid":23746838,"dup_signals":{"dup_doc_count":26,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2023-40":2,"2023-23":1,"2022-49":1,"2022-33":1,"2022-05":1,"2021-39":1,"2020-45":1,"2020-40":1,"2020-34":1,"2020-24":1,"2020-16":2,"2020-10":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-30":1,"2019-26":1,"2023-50":1,"2024-22":2}}},"text":"The hallmarks of aging.\nAging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":23526627,"dup_signals":{"dup_doc_count":17,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-49":2,"2021-49":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-05":2,"2017-34":2,"2023-23":1,"2024-10":1}}},"text":"The child's body without fluid: mother's knowledge and practices about hydration and rehydration in Salvador, Bahia, Brazil.\nThe aim of this article was to anthropologically analyse knowledge and practices about hydration and rehydration in a specific ethnographic context, where diverse therapies are combined to treat and take care of child diarrhoea as part of a wider social process that circumscribes transactions between self-care and biomedicine. Ethnographic data from a qualitative study in the neighbourhood of Nova Constituinte (Salvador, Bahia) which was part of an interdisciplinary project aimed at epidemiologically evaluating an environmental sanitation programme. These data results from a series of in-depth interviews of 29 interviewees and field observations collected over two stages (1997\/1998-2003\/2004). Knowledge about hydration and rehydration is practical knowledge that demonstrates some of the cultural limits of dehydration in terms of the normality or pathology criteria related to child diarrhoea. This knowledge belongs to local interpretations, treatment experiences and the care that mothers provide in relation to their child's diarrhoea. We observed a process of medicalisation in the discourse about hydration and self-care. Unlike rehydration, hydration is structural to self-care processes. While the former constitutes a way of alleviating diarrhoea, the latter is a type of care centred on healing. The difference between these practices does not lie in the type of remedies used but in the meaning attributed to them and the way they are combined.","subset":"pubmed_abstract"} +{"meta":{"pmid":24477207,"dup_signals":{"dup_doc_count":58,"dup_dump_count":36,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-14":1,"2022-49":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-10":1,"2020-45":1,"2020-29":1,"2019-51":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":2,"2018-17":2,"2018-09":4,"2017-51":2,"2017-43":2,"2017-39":2,"2017-34":2,"2017-30":1,"2017-26":2,"2017-22":2,"2017-17":2,"2017-09":2,"2017-04":2,"2016-50":2,"2016-44":2,"2016-40":2,"2017-13":2,"2024-22":1}}},"text":"IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?\nIncomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances.","subset":"pubmed_abstract"} +{"meta":{"pmid":31803381,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"In vitro comparison of marginal and internal fit between stainless steel crowns and esthetic crowns of primary molars using different luting cements.\nThis study was to assess and compare the marginal and internal fit of stainless steel crowns (SSCs) with those of preveneered SSCs and zirconia crowns using different luting cements. In this in vitro study, 36 primary first molars were divided into three groups (n = 12) each prepared to receive different crowns (SSCs, preveneered SSCs, or zirconia crowns). Each group was further subgrouped (n = 4) according to the luting cement (resin cement, glass ionomer cement [GIC], or resin-modified GIC [RMGIC]). After cementation, the teeth were sectioned in the buccolingual direction to assess the marginal and internal fit. The results were analyzed using ANOVA and Bonferroni statistical tests. The level of significance was set at P < 0.05. Zirconia crowns, especially those cemented with resin cement, were associated with the lowest marginal and internal gap width. Regardless of the luting cement, no significant difference was observed between all three crowns tested in terms of marginal gap (P > 0.05); however, zirconia crowns cemented with resin cement had significantly lower internal gap than preveneered SSCs and SSCs cemented with resin cement. In addition, those cemented with RMGIC had significantly lower internal gap than preveneered SSCs cemented with that cement (P < 0.05). Zirconia crowns cemented with resin cement were the most accurately fitted internally, while marginally, they were not significantly different from the rest of crown-luting cement combinations tested.","subset":"pubmed_abstract"} +{"meta":{"pmid":31363728,"dup_signals":{"dup_doc_count":15,"dup_dump_count":8,"dup_details":{"curated_sources":4,"2022-05":1,"2021-49":3,"2021-39":1,"2021-25":1,"2021-21":2,"2020-50":1,"2020-45":1,"2022-33":1}}},"text":"Starch and \u03b2-glucan in a whole-grain-like structural form improve hepatic insulin sensitivity in diet-induced obese mice.\nWhole-grain food (WGF) is well known for its anti-diabetic effect, and alleviation of obesity-induced insulin resistance (IR) might be one of the underlying mechanisms. In the current study, the effects of starch, as the main component in WGF, and \u03b2-glucan in a whole-grain-like structural form (WGLSF) on hepatic IR and glucose homeostasis were investigated using high-fat (HF)-induced obese C57BL\/6J mice. After treatment for 8 weeks, the body weight gain and IR of the mice were significantly reduced. The hepatic Akt, the key component in insulin signaling, was activated, and the hepatic expression and protein levels of glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate carboxykinase (PEPCK) were reduced. Moreover, WGLSF effectively reduced the hepatic levels of free fatty acids and the pro-inflammatory cytokines TNF-\u03b1, IL-6, and NF-\u03baB. Additionally, the reduced level of the phosphorylated c-Jun-N-terminal kinases (JNK) indicated that WGLSF treatment might inactivate the JNK signaling, leading to improved hepatic IR. These results demonstrated that starch and \u03b2-glucan in a whole grain-like structural form have the potential as a dietary strategy to combat obesity-induced hepatic IR for improved health.","subset":"pubmed_abstract"} +{"meta":{"pmid":32619977,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"Language network reorganization before and after temporal lobe epilepsy surgery.\nEpilepsy surgery is the recommended treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). This method offers a good chance of seizure freedom but carries a considerable risk of postoperative language impairment. The extremely variable neurocognitive profiles in surgical epilepsy patients cannot be fully explained by extent of resection, fiber integrity, or current task-based functional MRI (fMRI). In this study, the authors aimed to investigate pathology- and surgery-triggered language organization in TLE by using fMRI activation and network analysis as well as considering structural and neuropsychological measures. Twenty-eight patients with unilateral TLE (16 right, 12 left) underwent T1-weighted imaging, diffusion tensor imaging, and task-based language fMRI pre- and postoperatively (n = 15 anterior temporal lobectomy, n = 11 selective amygdalohippocampectomy, n = 2 focal resection). Twenty-two healthy subjects served as the control cohort. Functional connectivity, activation maps, and laterality indices for language dominance were analyzed from fMRI data. Postoperative fractional anisotropy values of 7 major tracts were calculated. Naming, semantic, and phonematic verbal fluency scores before and after surgery were correlated with imaging parameters. fMRI network analysis revealed widespread, bihemispheric alterations in language architecture that were not captured by activation analysis. These network changes were found preoperatively and proceeded after surgery with characteristic patterns in the left and right TLEs. Ipsilesional fronto-temporal connectivity decreased in both left and right TLE. In left TLE specifically, preoperative atypical language dominance predicted better postoperative verbal fluency and naming function. In right TLE, left frontal language dominance correlated with good semantic verbal fluency before and after surgery, and left fronto-temporal language laterality predicted good naming outcome. Ongoing seizures after surgery (Engel classes ID-IV) were associated with naming deterioration irrespective of seizure side. Functional findings were not explained by the extent of resection or integrity of major white matter tracts. Functional connectivity analysis contributes unique insight into bihemispheric remodeling processes of language networks after epilepsy surgery, with characteristic findings in left and right TLE. Presurgical contralateral language recruitment is associated with better postsurgical language outcome in left and right TLE.","subset":"pubmed_abstract"} +{"meta":{"pmid":16150143,"dup_signals":{"dup_doc_count":28,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2013-48":1,"2017-13":1,"unknown":25}}},"text":"The \"lipid accumulation product\" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison.\nBody mass index (BMI, kg\/m2) may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC) and fasting triglycerides (TG) concentration to describe lipid overaccumulation. The WC (estimated population minimum 65 cm for men and 58 cm for women) and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults) were used to compute a \"lipid accumulation product\" [LAP = (WC-65) x TG for men and (WC-58) x TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex) the former had more adverse risk levels than the latter (p < 0.002) for seven lipid variables, uric acid concentration, heart rate, systolic and diastolic blood pressure. Further adjustment for age did not materially alter these comparisons except for blood pressures (p > 0.1). As continuous variables, LAP provided a consistently more adverse beta coefficient (slope) than BMI for nine cardiovascular risk variables (p < 0.01), but not for blood pressures (p > 0.2). LAP (describing lipid overaccumulation) performed better than BMI (describing weight overaccumulation) for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing.","subset":"pubmed_abstract"} +{"meta":{"pmid":18301775,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"Are there multiple visual short-term memory stores?\nClassic work on visual short-term memory (VSTM) suggests that people store a limited amount of items for subsequent report. However, when human observers are cued to shift attention to one item in VSTM during retention, it seems as if there is a much larger representation, which keeps additional items in a more fragile VSTM store. Thus far, it is not clear whether the capacity of this fragile VSTM store indeed exceeds the traditional capacity limits of VSTM. The current experiments address this issue and explore the capacity, stability, and duration of fragile VSTM representations. We presented cues in a change-detection task either just after off-set of the memory array (iconic-cue), 1,000 ms after off-set of the memory array (retro-cue) or after on-set of the probe array (post-cue). We observed three stages in visual information processing 1) iconic memory with unlimited capacity, 2) a four seconds lasting fragile VSTM store with a capacity that is at least a factor of two higher than 3) the robust and capacity-limited form of VSTM. Iconic memory seemed to depend on the strength of the positive after-image resulting from the memory display and was virtually absent under conditions of isoluminance or when intervening light masks were presented. This suggests that iconic memory is driven by prolonged retinal activation beyond stimulus duration. Fragile VSTM representations were not affected by light masks, but were completely overwritten by irrelevant pattern masks that spatially overlapped the memory array. We find that immediately after a stimulus has disappeared from view, subjects can still access information from iconic memory because they can see an after-image of the display. After that period, human observers can still access a substantial, but somewhat more limited amount of information from a high-capacity, but fragile VSTM that is overwritten when new items are presented to the eyes. What is left after that is the traditional VSTM store, with a limit of about four objects. We conclude that human observers store more sustained representations than is evident from standard change detection tasks and that these representations can be accessed at will.","subset":"pubmed_abstract"} +{"meta":{"pmid":34177297,"dup_signals":{"dup_doc_count":18,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2023-40":2,"2023-23":1,"2022-49":1,"2022-40":1,"2022-33":2,"2022-27":1,"2022-05":1,"2021-39":2,"2021-25":1,"2024-10":1,"2024-22":1}}},"text":"What Has Changed in the Treatment of Psoriatic Arthritis After COVID-19?\nCoronavirus disease 2019 is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. Coronavirus disease 2019 leads to the rapid activation of innate immune cells, particularly in patients with severe disease. Psoriatic arthritis is a heterogeneous chronic inflammatory disease characterized by the association of psoriasis and arthritis. Similar to those with other viruses, patients with psoriatic arthritis are at a significant risk of infection with severe acute respiratory syndrome coronavirus 2. Patients with psoriatic arthritis are immunosuppressed owing to immune dysregulation during the active disease period or owing to immunosuppressive drugs administered during remission, and they are prone to infections. The severe acute respiratory syndrome coronavirus 2 is a threat to millions of people globally owing to the decline in immunity and because a significant number of people develop severe illness. In the period of coronavirus disease 2019 pandemic, we briefly present recommendations for the treatment of psoriatic arthritis. In this review, we briefly address the management options and treatment recommendations for patients with psoriatic arthritis during and after the coronavirus disease 2019 pandemic in light of recent scientific publications.","subset":"pubmed_abstract"} +{"meta":{"pmid":8853359,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":12}}},"text":"Differences between cytokine effects in the microcirculation of the rat.\nWe studied by in vivo microscopy in rat cremaster muscle the acute and delayed effects of short exposure to tumor necrosis factor (TNF), interleukin (IL)-1 beta, and IL-6 on basal tone and vascular reactivity of second- to fourth-order arterioles (A2-A4). A 20-min exposure to recombinant human (rh) TNF (0.1-10 ng\/ml) induced a significant arteriolar vasodilation, but no significant changes in basal tone were found after exposure to the same doses of IL-1 beta. In contrast, the same exposure to IL-6 (0.1-10 ng\/ml) induced a significant dose-dependent vasoconstriction (i.e., 8, 15, and 21% at 10 ng\/ml in A2-A4 arterioles, respectively). This vasoconstriction was inhibited by the thromboxane A2 receptor antagonist SQ-29548. We did not find any significant effect of rhTNF or IL-6 on vascular reactivity to norepinephrine immediately after exposure to these two cytokines or 100 min after the end of the exposure. Contrastingly, a large dose-dependent decrease in reactivity to norepinephrine was found immediately after exposure to IL-1 beta and still persisted 100 min after the end of the exposure. Such a decrease was not found for the vasoconstriction in response to KCl. We conclude that, at the microvascular level, large differences exist between the three cytokines generally considered to mediate the harmful cardiovascular effects in sepsis. 1) TNF but not IL-1 beta is responsible for a vasodilatory effect, whereas the effect of IL-6 is a thromboxane A2-mediated vasoconstriction. 2) Short exposure to IL-1 beta but not to rhTNF or IL-6 diminishes the response of the arterioles to norepinephrine but not to KCl.","subset":"pubmed_abstract"} +{"meta":{"pmid":25255945,"dup_signals":{"dup_doc_count":24,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-14":1,"2022-49":1,"2022-27":1,"2022-05":2,"2021-49":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-09":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-22":3,"2024-18":1}}},"text":"3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI.\nGamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders. Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher-GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (\u22653T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time. To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times. Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate+Gluatmine), by providing 1.66 times larger signal for the 3.02ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging. Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":19297248,"dup_signals":{"dup_doc_count":17,"dup_dump_count":9,"dup_details":{"curated_sources":1,"2024-26":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":7}}},"text":"The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial.\nHigh body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 degrees C and 39 degrees C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1.20, 95% CI 0.96-1.50). In a post-hoc analysis of patients with baseline body temperature 37-39 degrees C, treatment with paracetamol was associated with improved outcome (1.43, 1.02-1.97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37-39 degrees C, but this post-hoc finding needs further study. Netherlands Heart Foundation.","subset":"pubmed_abstract"} +{"meta":{"pmid":31602448,"dup_signals":{"dup_doc_count":29,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-43":1,"2021-31":2,"2020-40":2,"2020-29":4,"2020-16":3,"2020-10":1,"2020-05":1,"2019-51":2,"2019-47":1,"2019-43":4,"2023-23":1,"2024-26":2,"2024-30":1}}},"text":"Versatility of bilayer metal oxide coatings on silver nanowire networks for enhanced stability with minimal transparency loss.\nSilver nanowire (AgNW) networks have been lately much investigated thanks to their physical properties and are therefore foreseen to play a key role in many industrial devices as transparent electrodes, but their stability can be an issue. Although it has been shown that thin metal oxide coatings enhance the stability of AgNW networks, such stabilization is achieved at the expense of transparency. We demonstrate that by depositing a second oxide coating, which acts as an antireflective layer, it is possible to obtain highly stable and transparent composite electrodes. AgNW networks were deposited by the airbrush method, and zinc oxide (ZnO) and aluminum oxide (Al2O3) coatings were deposited, by Atmospheric Pressure Spatial Atomic Layer Deposition (AP-SALD), using both glass and plastic substrates; therefore, the proposed fabrication method is low-cost and compatible with high-throughput scalable fabrication. The mechanical stability of bare, ZnO and ZnO\/Al2O3-coated AgNWs upon bending is also presented. The obtained nanocomposites exhibit highly homogeneous and conformal oxide coatings with average thicknesses of a few tens of nanometers. Samples with bilayer coatings of 70 nm ZnO\/70 nm Al2O3 still exhibit very good stability after annealing in air up to 450 \u00b0C for 6 repetitive cycles.","subset":"pubmed_abstract"} +{"meta":{"pmid":27199900,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":8}}},"text":"A Novel MSCRAMM Subfamily in Coagulase Negative Staphylococcal Species.\nCoagulase negative staphylococci (CoNS) are important opportunistic pathogens. Staphylococcus epidermidis, a coagulase negative staphylococcus, is the third leading cause of nosocomial infections in the US. Surface proteins like Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are major virulence factors of pathogenic gram positive bacteria. Here, we identified a new chimeric protein in S. epidermidis, that we call SesJ. SesJ represents a prototype of a new subfamily of MSCRAMMs. Structural predictions show that SesJ has structural features characteristic of a MSCRAMM along with a N-terminal repeat region and an aspartic acid containing C-terminal repeat region, features that have not been previously observed in staphylococcal MSCRAMMs but have been found in other surface proteins from gram positive bacteria. We identified and analyzed structural homologs of SesJ in three other CoNS. These homologs of SesJ have an identical structural organization but varying sequence identities within the domains. Using flow cytometry, we also show that SesJ is expressed constitutively on the surface of a representative S. epidermidis strain, from early exponential to stationary growth phase. Thus, SesJ is positioned to interact with protein targets in the environment and plays a role in S. epidermidis virulence.","subset":"pubmed_abstract"} +{"meta":{"pmid":21219130,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Characterization of a synergistic interaction between two cucurbit-infecting begomoviruses: Squash leaf curl virus and Watermelon chlorotic stunt virus.\nSquash leaf curl virus (SLCV) and Watermelon chlorotic stunt virus (WmCSV) are cucurbit-infecting bipartite begomoviruses. Both viruses are found in the eastern Mediterranean basin but the effects of dual infection of both viruses on melon (Cucumis melo L.) have not been described. 'Arava' melon plants were inoculated in the greenhouse, using whiteflies, with either SLCV, WmCSV, or both. Control plants were exposed to nonviruliferous whiteflies or not exposed at all. Following inoculation, plants were transplanted to a 50-mesh insect-proof nethouse and grown until fruit maturity. The experiment was performed in two melon-growing seasons: spring, transplant in May and harvest in July; and summer, transplant in August and harvest in October. Following inoculation, SLCV-infected melon plants showed mild symptoms that disappeared with time, and there was no effect on plant height. WmCSV-infected plants developed disease symptoms that became more obvious with time, and plants were somewhat shorter than control plants in the spring but not in the summer. SLCV had no effect on yield, regardless of season. WmCSV had no statistically significant effect on yield in the spring but, in the summer, reduced yield by 22%, on average. Dual-inoculated plants showed a synergistic interaction between the two viruses. They developed disease symptoms that were more pronounced than WmCSV alone, with plants being shorter than control plants by 20 to 25% regardless of season. Moreover, the yield of dual-inoculated plants was reduced on average by 21% in the spring and 54% in the summer, and fruit appearance was adversely affected. Dual inoculation did not affect WmCSV DNA level but SLCV DNA level was increased several-fold by the presence of WmCSV.","subset":"pubmed_abstract"} +{"meta":{"pmid":27279775,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Homogenized boundary conditions and resonance effects in Faraday cages.\nWe present a mathematical study of two-dimensional electrostatic and electromagnetic shielding by a cage of conducting wires (the so-called 'Faraday cage effect'). Taking the limit as the number of wires in the cage tends to infinity, we use the asymptotic method of multiple scales to derive continuum models for the shielding, involving homogenized boundary conditions on an effective cage boundary. We show how the resulting models depend on key cage parameters such as the size and shape of the wires, and, in the electromagnetic case, on the frequency and polarization of the incident field. In the electromagnetic case, there are resonance effects, whereby at frequencies close to the natural frequencies of the equivalent solid shell, the presence of the cage actually amplifies the incident field, rather than shielding it. By appropriately modifying the continuum model, we calculate the modified resonant frequencies, and their associated peak amplitudes. We discuss applications to radiation containment in microwave ovens and acoustic scattering by perforated shells.","subset":"pubmed_abstract"} +{"meta":{"pmid":24998973,"dup_signals":{"dup_doc_count":18}},"text":"Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice.\nMethamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5mg\/kg-bw\/ip\/day\/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis-vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43-57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5mg\/kg\/day\/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5mg\/kg\/day\/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg\/kg\/day\/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5mg\/kg\/day\/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation.","subset":"pubmed_abstract"} +{"meta":{"pmid":25895888,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"A Functional Group Approach for Prediction of APPI Response of Organic Synthetic Targets.\nAtmospheric pressure photoionization (APPI) is a technique of choice for ionization of non-polar molecules in mass spectrometry (MS). Reported APPI-based studies tend to focus on a selected compound class, which may contain a variety of functional groups. These studies demonstrate that APPI response frequently differs substantially, indicating a certain dependence on the functional group present. Although this dependence could be employed for APPI response prediction, its systematic use is currently absent. Here, we apply APPI MS to a judiciously-compiled set of 63 compounds containing a number of diverse functional groups commonly utilized in synthesis, reactive functional groups, as well as those containing boron and silicon. Based on the outcome of APPI MS of these compounds, we propose and evaluate a simple guideline to estimate the APPI response for a novel compound, the key properties of which have not been characterized in the gas phase. Briefly, we first identify key functional groups in the compound and gather knowledge on the known ionization energies from the smallest analogues containing said functional groups. We then consider local inductive and resonance effects on said ionization energies for the compounds of interest to estimate the APPI response. Finally, application of APPI MS to compounds of interest considered herein demonstrated extended upper mass ionization limit of 3.5 kDa for non-polymeric compounds.","subset":"pubmed_abstract"} +{"meta":{"pmid":9641491,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Anthropometric and hormone effects of an eight-week exercise-diet intervention in breast cancer patients: results of a pilot study.\nTo assess the feasibility of an exercise-diet intervention in sedentary, overweight breast cancer patients, we conducted a pilot 8-week intervention. Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast cancer patients, ages 25-75 years, who were identified through two Seattle breast surgery practices and the University of Washington Breast Clinic. Ten patients were eligible and interested and were enrolled in the intervention, which consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20% of calories from fat) diet. Nine patients completed the program; all adhered well to the intervention and data collection protocol. The patients, ages 40-74 years, lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6 cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67 diastolic blood pressure points, and 4.0 pulse beats\/min, and they gained an average of 2.3% lean mass. Slight, nonsignificant decreases were observed in serum concentration of total and free estradiol, estrone sulfate, total testosterone, androstenedione, and dehydroepiandrosterone. These pilot data indicate that breast cancer patients are highly motivated to join and adhere to an intense exercise-diet intervention and can experience significant measurable changes in anthropometric and fat mass measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":22661492,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818.\nThe process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals. To use a new systems approach to provide an overview of host metabolism and the developing immune system in response to nutritional intervention around the weaning period. Piglets (n=14) were weaned onto either an egg-based or soya-based diet at 3 weeks until 7 weeks, when all piglets were switched onto a fish-based diet. Half the animals on each weaning diet received Bifidobacterium lactis NCC2818 supplementation from weaning onwards. Immunoglobulin production from immunologically relevant intestinal sites was quantified and the urinary (1)H NMR metabolic profile was obtained from each animal at post mortem (11 weeks). Different weaning diets induced divergent and sustained shifts in the metabolic phenotype, which resulted in the alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary standardisation. B lactis NCC2818 supplementation affected the systemic metabolism of the different weaning diet groups over and above the effects of diet. Additionally, production of gut mucosa-associated IgA and IgM was found to depend upon the weaning diet and on B lactis NCC2818 supplementation. The correlation of urinary (1)H NMR metabolic profile with mucosal immunoglobulin production was demonstrated, thus confirming the value of this multi-platform approach in uncovering non-invasive biomarkers of immunity. This has clear potential for translation into human healthcare with the development of urine testing as a means of assessing mucosal immune status. This might lead to early diagnosis of intestinal dysbiosis and with subsequent intervention, arrest disease development. This system enhances our overall understanding of pathologies under supra-organismal control.","subset":"pubmed_abstract"} +{"meta":{"pmid":31479425,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":14,"unknown":7}}},"text":"Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity.\nPolyunsaturated fatty acids such as docosahexaenoic acid (DHA) positively affect the outcome of retinopathy of prematurity (ROP). Given that DHA metabolism by cytochrome P450 and soluble epoxide hydrolase (sEH) enzymes affects retinal angiogenesis and vascular stability, we investigated the role of sEH in a mouse model of ROP. In WT mice, hyperoxia elicited tyrosine nitration and inhibition of sEH and decreased generation of the DHA-derived diol 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP). Correspondingly, in a murine model of ROP, sEH-\/- mice developed a larger central avascular zone and peripheral pathological vascular tuft formation than did their WT littermates. Astrocytes were the cells most affected by sEH deletion, and hyperoxia increased astrocyte apoptosis. In rescue experiments, 19,20-DHDP prevented astrocyte loss by targeting the mitochondrial membrane to prevent the hyperoxia-induced dissociation of presenilin-1 and presenilin-1-associated protein to attenuate poly ADP-ribose polymerase activation and mitochondrial DNA damage. Therapeutic intravitreal administration of 19,20-DHDP not only suppressed astrocyte loss, but also reduced pathological vascular tuft formation in sEH-\/- mice. Our data indicate that sEH activity is required for mitochondrial integrity and retinal astrocyte survival in ROP. Moreover, 19,20-DHDP may be more effective than DHA as a nutritional supplement for preventing retinopathy in preterm infants.","subset":"pubmed_abstract"} +{"meta":{"pmid":24831757,"dup_signals":{"dup_doc_count":26,"dup_dump_count":23,"dup_details":{"curated_sources":1,"2021-25":1,"2021-04":1,"2019-51":1,"2019-35":1,"2019-26":1,"2019-22":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":2,"2018-34":1,"2018-30":1,"2018-22":2,"2018-13":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2022-49":1}}},"text":"Reliability and concurrent validity of a Smartphone, bubble inclinometer and motion analysis system for measurement of hip joint range of motion.\nTraditional methods of assessing joint range of motion (ROM) involve specialized tools that may not be widely available to clinicians. This study assesses the reliability and validity of a custom Smartphone application for assessing hip joint range of motion. Intra-tester reliability with concurrent validity. Passive hip joint range of motion was recorded for seven different movements in 20 males on two separate occasions. Data from a Smartphone, bubble inclinometer and a three dimensional motion analysis (3DMA) system were collected simultaneously. Intraclass correlation coefficients (ICCs), coefficients of variation (CV) and standard error of measurement (SEM) were used to assess reliability. To assess validity of the Smartphone application and the bubble inclinometer against the three dimensional motion analysis system, intraclass correlation coefficients and fixed and proportional biases were used. The Smartphone demonstrated good to excellent reliability (ICCs>0.75) for four out of the seven movements, and moderate to good reliability for the remaining three movements (ICC=0.63-0.68). Additionally, the Smartphone application displayed comparable reliability to the bubble inclinometer. The Smartphone application displayed excellent validity when compared to the three dimensional motion analysis system for all movements (ICCs>0.88) except one, which displayed moderate to good validity (ICC=0.71). Smartphones are portable and widely available tools that are mostly reliable and valid for assessing passive hip range of motion, with potential for large-scale use when a bubble inclinometer is not available. However, caution must be taken in its implementation as some movement axes demonstrated only moderate reliability.","subset":"pubmed_abstract"} +{"meta":{"pmid":37789703,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":4,"2024-30":2,"2024-26":1,"2024-10":2,"unknown":4}}},"text":"\"We adjusted for race\" now what: A systematic review of utilization and reporting of race in AJE and Epidemiology, 2020-2021.\nRace is a social construct, commonly used in epidemiologic research to adjust for confounding. However, adjustment of race may mask racial disparities thereby perpetuating structural racism. We conducted a systematic review of articles published in Epidemiology and American Journal of Epidemiology between 2020 and 2021 to 1) understand how race, ethnicity, and similar social constructs were operationalized, utilized, and reported and 2) characterize good and poor practices of utilization and reporting of race data based on the extent to which they reveal or mask systemic racism. Original research articles were considered for full review and data extraction if race data were used in the study analysis. We extracted how race was categorized; utilized - as descriptor, confounder, or for effect measure modification (EMM); and reported - if the authors discussed racial disparities and systemic bias-related mechanisms responsible for perpetuating the disparities. Of the 561 articles, 299 had race data available and 192 (34.2%) used race data in analyses. Among the 160 United States-based studies, 81 different racial categorizations were used. Race was most often utilized as a confounder (52%), followed by effect measure modifier (33%), and descriptive variable (12%). Fewer than one in four articles (22.9%) exhibited good practices (EMM along with discussing disparities and mechanisms), 63.5% of the articles exhibited poor practices (confounding only or not discussing mechanisms), and 13.5% were considered neither poor nor good practices. We discuss implications and provide 13 recommendations for operationalization, utilization, and reporting of race in epidemiologic and public health research.","subset":"pubmed_abstract"} +{"meta":{"pmid":22003404,"dup_signals":{"dup_doc_count":23,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2013-48":1,"2017-13":1,"unknown":16}}},"text":"Predictors for adolescent visits to practitioners of complementary and alternative medicine in a total population (the Young-HUNT Studies).\nTo investigate the factors predicting adolescent visits to practitioners of complementary and alternative medicine (CAM). A longitudinal cohort study conducted in an adolescent total population in Central Norway (The Nord-Tr\u00f8ndelag Health Studies (HUNT)). In Young-HUNT 1, all inhabitants aged 13 to 19 years (N = 8944, 89% response rate) were invited to participate, and the youngest group (13 to 15 year olds) was surveyed again 4 years later (Young-HUNT 2, N = 2429, 82% response rate). The participants completed a comprehensive questionnaire on health and life style which included a question regarding visits to a CAM practitioner in the last 12 months. One in eleven (8.7%, 95%CI 7.6-9.8%) had visited a CAM practitioner, an increase of 26% in 4 years (1.8% points). The final multivariable analysis predicted increased odds of an adolescent becoming a CAM visitor four years later (p<0.05) if she or he had previously visited a CAM practitioner (adjOR 3.4), had musculoskeletal pain (adjOR 1.5), had migraine (adjOR 2.3), used asthma medicines (adjOR 1.8) or suffered from another disease lasting more than three months (adjOR 2.1). Being male predicted reduced odds of visiting a CAM practitioner in the future (adjOR 0.6). We can conclude from this study that future visits to a CAM practitioner are predicted by both predisposing factors (being female, having visited a CAM practitioner previously) and medical need factors (having had musculoskeletal pain, migraine, used asthma medicines or experienced another disease lasting more than three months). None of the specific variables associated with CAM visits were predictive for CAM visits four years later.","subset":"pubmed_abstract"} +{"meta":{"pmid":22562956,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":3,"unknown":8}}},"text":"Repression of malignant tumor progression upon pharmacologic IGF1R blockade in a mouse model of insulinoma.\nNVP-AEW541, a specific ATP-competitive inhibitor of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase, has been reported to interfere with tumor growth in various tumor transplantation models. We have assessed the efficacy of NVP-AEW541 in repressing tumor growth and tumor progression in the Rip1Tag2 transgenic mouse model of pancreatic \u03b2-cell carcinogenesis. In addition, we have tested NVP-AEW541 in Rip1Tag2;RipIGF1R double-transgenic mice which show accelerated tumor growth and increased tumor malignancy compared with Rip1Tag2 single-transgenic mice. Previously, we have shown that high levels of IGF-2, a high-affinity ligand for IGF1R, are required for Rip1Tag2 tumor cell survival and tumor growth. Unexpectedly, treatment of Rip1Tag2 mice with NVP-AEW541 in prevention and intervention trials neither did affect tumor growth nor tumor cell proliferation and apoptosis. Yet, it significantly repressed progression to tumor malignancy, that is, the rate of the transition from differentiated adenoma to invasive carcinoma. Treatment of Rip1Tag2;RipIGF1R double-transgenic mice resulted in moderately reduced tumor volumes and increased rates of tumor cell apoptosis. Sustained expression of IGF-2 and of the IGF-2-binding form of insulin receptor (IR-A) in tumor cells suggests a compensatory role of IR-A upon IGF1R blockade. The results indicate that inhibition of IGF1R alone is not sufficient to efficiently block insulinoma growth and imply an overlapping role of IGF1R and insulin receptor in executing mitogenic and survival stimuli elicited by IGF-2. The reduction of tumor invasion upon IGF1R blockade on the other hand indicates a critical function of IGF1R signaling for the acquisition of a malignant phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":18937576,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":14}}},"text":"A reliable diagnosis of human rabies based on analysis of skin biopsy specimens.\nThe number of human deaths due to rabies is currently underestimated to be 55,000 deaths per year. Biological diagnostic methods for confirmation of rabies remain limited, because testing on postmortem cerebral samples is the reference method, and in many countries, sampling brain tissue is rarely practiced. There is a need for a reliable method based on a simple collection of nonneural specimens. A new reverse-transcription, heminested polymerase chain reaction (RT-hnPCR) protocol was standardized at 3 participating centers in Cambodia, Madagascar, and France. Fifty-one patients from Cambodia, Madagascar, Senegal, and France were prospectively enrolled in the study; 43 (84%) were ultimately confirmed as having rabies. A total of 425 samples were collected from these patients during hospitalization. We studied the accuracy of the diagnosis by comparing the results obtained with use of biological fluid specimens (saliva and urine) and skin biopsy specimens with the results obtained with use of the standard rabies diagnostic procedure performed with a postmortem brain biopsy specimen. The data obtained indicate a high specificity (100%) of RT-hnPCR and a higher sensitivity (>\/=98%) when the RT-hnPCR was performed with skin biopsy specimens than when the test was performed with fluid specimens, irrespective of the time of collection (i.e., 1 day after the onset of symptoms or just after death). Also, a sensitivity of 100% was obtained with the saliva sample when we analyzed at least 3 successive samples per patient. Skin biopsy specimens should be systematically collected in cases of encephalitis of unknown origin. These samples should be tested by RT-hnPCR immediately to confirm rabies; if the technique is not readily available locally, the samples should be tested retrospectively for epidemiological purposes.","subset":"pubmed_abstract"} +{"meta":{"pmid":24358443,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-27":1,"2022-05":1,"2021-31":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-34":1,"2020-29":1,"2020-16":1,"2022-40":1,"2024-18":1}}},"text":"Elevated plasma norepinephrine inhibits insulin secretion, but adrenergic blockade reveals enhanced \u03b2-cell responsiveness in an ovine model of placental insufficiency at 0.7 of gestation.\nIn pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced \u03b2-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory \u03b2-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 \u00b1 211 v. 292 \u00b1 65 pg\/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 \u00b1 0.03 v. 1.08 \u00b1 0.06 ng\/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 \u00b1 0.11 ng\/ml; P < 0.05) but decreased GSIS in controls (0.86 \u00b1 0.02 ng\/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory \u03b2-cell stimulus-secretion responsiveness is present before IUGR.","subset":"pubmed_abstract"} +{"meta":{"pmid":11988573,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2017-13":1,"2024-30":1,"unknown":10}}},"text":"Mammal population losses and the extinction crisis.\nThe disappearance of populations is a prelude to species extinction. No geographically explicit estimates have been made of current population losses of major indicator taxa. Here we compare historic and present distributions of 173 declining mammal species from six continents. These species have collectively lost over 50% of their historic range area, mostly where human activities are intensive. This implies a serious loss of ecosystem services and goods. It also signals a substantial threat to species diversity.","subset":"pubmed_abstract"} +{"meta":{"pmid":30135819,"dup_signals":{"dup_doc_count":46,"dup_dump_count":38,"dup_details":{"curated_sources":2,"2022-49":2,"2022-27":1,"2021-49":1,"2021-21":1,"2021-10":1,"2020-24":1,"2020-16":4,"2020-10":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-09":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-39":2,"2017-30":2,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2023-23":1,"2024-18":1,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"Features and functionality of the Iterapi platform for internet-based psychological treatment.\nThe purpose of this article is to describe an internet-based platform for improving symptoms and quality of life for people with psychological and behavioural health problems such as depression, anxiety, phobia, psychological trauma, hearing loss and tinnitus. The online platform, called Iterapi, was developed at the Department of Behavioural Sciences and Learning at Link\u00f6ping University, Sweden and has been running for nearly two decades and used in many randomized controlled trials and outpatient treatments. The intention of this article is to share our experience with developing such a treatment solution and the process flow and elements of running internet-based psychological interventions. This will likely be of use to developers building similar services, therapists considering integrating such approaches in their practices and institutions, as well as researchers curious about the functions included on the platform and methodology used for running studies. We describe the security aspects of the platform, central concepts underlying its development, how the platform can be used in a study or treatment and the main features and functions the platform offers. We comment on practical considerations regarding blending of methods within the platform, such as self-help treatments with asynchronous communication and real-time text chat and video conversations. We also point out the advantages of using Internet-assisted treatments, the challenges that we have faced and future planned upgrades. Due to continuous development of the platform, its user-friendliness, accessibility across devices and numerous features, many research colleagues from Sweden as well as other countries such as Germany, United Kingdom, Romania and Israel have chosen to implement their own studies on the platform.","subset":"pubmed_abstract"} +{"meta":{"pmid":17325158,"dup_signals":{"dup_doc_count":29,"dup_dump_count":20,"dup_details":{"curated_sources":3,"2021-10":1,"2019-39":2,"2019-04":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2017-43":2,"2017-22":2,"2017-09":2,"2016-44":1,"2016-40":2,"2016-36":1,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2022-21":1}}},"text":"Risk of falls and motor vehicle collisions in glaucoma.\nTo investigate the risk of falls and motor vehicle collisions (MVCs) in patients with glaucoma. The sample comprised 48 patients with glaucoma (mean visual field mean deviation [MD] in the better eye = -3.9 dB; 5.1 dB SD) and 47 age-matched normal control subjects, who were recruited from a university-based hospital eye care clinic and are enrolled in an ongoing prospective study of risk factors for falls, risk factors for MVCs, and on-road driving performance in glaucoma. Main outcome measures at baseline were previous self-reported falls and MVCs, and police-reported MVCs. Demographic and medical data were obtained. In addition, functional independence in daily living, physical activity level and balance were assessed. Clinical vision measures included visual acuity, contrast sensitivity, standard automated perimetry, useful field of view (UFOV), and stereopsis. Analyses of falls and MVCs were adjusted to account for the possible confounding effects of demographic characteristics, medications, and visual field impairment. MVC analyses were also adjusted for kilometers driven per week. There were no significant differences between patients with glaucoma and control subjects with respect to number of systemic medical conditions, body mass index, functional independence, and physical activity level (P > 0.10). At baseline, 40 (83%) patients with glaucoma and 44 (94%) control subjects were driving. Compared with control subjects, patients with glaucoma were over three times more likely to have fallen in the previous year (odds ratio [OR](adjusted) = 3.71; 95% CI, 1.14-12.05), over six times more likely to have been involved in one or more MVCs in the previous 5 years (OR(adjusted) = 6.62; 95% CI, 1.40-31.23), and more likely to have been at fault (OR(adjusted) = 12.44; 95% CI, 1.08-143.99). The strongest risk factor for MVCs in patients with glaucoma was impaired UFOV selective attention (OR(adjusted) = 10.29; 95% CI, 1.10-96.62; for selective attention >350 ms compared with <\/=350 ms). There is an increased risk of falls and MVCs in patients with glaucoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":28723907,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2021-39":1,"2021-31":1,"2019-47":1,"2019-39":1,"2019-13":1,"2019-09":1,"2018-51":1,"2018-26":1,"2018-17":1,"2018-09":1,"2023-23":1,"2024-10":1,"2024-26":1}}},"text":"Auditory and visual distractors disrupt multisensory temporal acuity in the crossmodal temporal order judgment task.\nThe ability to synthesize information across multiple senses is known as multisensory integration and is essential to our understanding of the world around us. Sensory stimuli that occur close in time are likely to be integrated, and the accuracy of this integration is dependent on our ability to precisely discriminate the relative timing of unisensory stimuli (crossmodal temporal acuity). Previous research has shown that multisensory integration is modulated by both bottom-up stimulus features, such as the temporal structure of unisensory stimuli, and top-down processes such as attention. However, it is currently uncertain how attention alters crossmodal temporal acuity. The present study investigated whether increasing attentional load would decrease crossmodal temporal acuity by utilizing a dual-task paradigm. In this study, participants were asked to judge the temporal order of a flash and beep presented at various temporal offsets (crossmodal temporal order judgment (CTOJ) task) while also directing their attention to a secondary distractor task in which they detected a target stimulus within a stream visual or auditory distractors. We found decreased performance on the CTOJ task as well as increases in both the positive and negative just noticeable difference with increasing load for both the auditory and visual distractor tasks. This strongly suggests that attention promotes greater crossmodal temporal acuity and that reducing the attentional capacity to process multisensory stimuli results in detriments to multisensory temporal processing. Our study is the first to demonstrate changes in multisensory temporal processing with decreased attentional capacity using a dual task paradigm and has strong implications for developmental disorders such as autism spectrum disorders and developmental dyslexia which are associated with alterations in both multisensory temporal processing and attention.","subset":"pubmed_abstract"} +{"meta":{"pmid":22214353,"dup_signals":{"dup_doc_count":24,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":1,"2017-13":1,"2024-26":1,"unknown":19}}},"text":"Non-invasive ventilation and gastrostomy may not impact overall quality of life in patients with ALS.\nNon-invasive positive pressure ventilation (NIPPV) may improve health-related quality of life (HRQoL) in patients with ALS. The effect of percutaneous endoscopic gastrostomy (PEG) on HRQoL is not known. Instruments measuring QoL more broadly have not been used to assess effects of these interventions. This study was undertaken to do so via the ALS-Specific Quality of Life Instrument-revised (ALSSQOL-R). A retrospective review was carried out of ALS patients who had undergone one QoL assessment prior to NIPPV or PEG initiation and two assessments following one of these interventions. Random coefficients models were developed. Twenty-two patients met criteria for inclusion: six NIPPV, 11 PEG, and five NIPPV + PEG. The ALSSQoL-R did not change significantly following NIPPV or PEG or both. Function declined in all three groups over the same time-period. In conclusion, overall QoL in ALS does not appear to change after NIPPV or PEG. This may reflect the impact of non-health-related factors or may be due to a response shift. QoL instruments that include domains outside of health status may not be sensitive to changes from single interventions. Larger, prospective studies are needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":2208707,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Effect of blood collection and processing on radioimmunoassay results for apolipoprotein B in plasma.\nWe studied the effects of different blood collection and processing procedures on quantification of apolipoprotein (apo) B by radioimmunoassay. High-density lipoprotein subfractions HDL3 and HDL2 and isolated apoA-I did not cross-react in the assay. Analytical recovery of apoB at different doses of very-low- and low-density lipoproteins were complete. Inter- and intra-assay coefficients of variation (CVs) averaged 7.4% and 6.0%, respectively. Blood from 20 subjects was collected into tubes containing EDTA alone or EDTA with antiproteolytic and antioxidant agents; one half of each plasma was separated immediately, half after 3 h at 4 degrees C. Regardless of the addition of protective agents or the time difference in separating plasma from other blood elements, freezing plasma at -70 degrees C decreased apoB content a similar amount, an average of 6.8%. This loss of apoB immunoreactivity was not related to apoB content in fresh plasma. Analysis of variance showed no differential effect on apoB content by the various additions to whole blood or plasma. No additional apoB content was lost in once-frozen aliquots of three human plasma pools during storage at -70 degrees C for up to 18 months. We conclude that concentrations of apoB in human plasma can be measured reliably after long-term storage, although the absolute value may decrease slightly as a result of freezing.","subset":"pubmed_abstract"} +{"meta":{"pmid":1734525,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Aromatase enzyme activity and sex determination in chickens.\nDuring development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens.","subset":"pubmed_abstract"} +{"meta":{"pmid":33822811,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":9}}},"text":"Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma.\nT cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been described as a transmembrane protein, expressed on the surface of various T cells as well as different cells of innate immunity. It has since been associated with Th1 mediated autoimmune diseases and transplantation tolerance studies, thereby indicating a possible role of this receptor in counter-regulation of Th2 immune responses. In the present study we therefore directly examined the role of Tim-3 in allergic inflammation and respiratory tolerance. First, Tim-3-\/- mice and wild type controls were immunized and challenged with the model allergen ovalbumin (OVA) to induce an asthma-like phenotype. Analysis of cell numbers and distribution in the bronchoalveolar lavage (BAL) fluid as well as lung histology in H&E stained lung sections demonstrated a comparable degree of eosinophilic inflammation in both mouse strains. Th2 cytokine production in restimulated cell culture supernatants and serum IgE and IgG levels were equally increased in both genotypes. In addition, cell proliferation and the distribution of different T cell subsets were comparable. Moreover, analysis of both mouse strains in our respiratory tolerance model, where mucosal application of the model allergen before immunization, prevents the development of an asthma-like phenotype, revealed no differences in any of the parameters mentioned above. The current study demonstrates that Tim-3 is dispensable not only for the development of allergic inflammation but also for induction of respiratory tolerance in mice in an OVA-based model.","subset":"pubmed_abstract"} +{"meta":{"pmid":31225839,"dup_signals":{"dup_doc_count":18,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-10":1,"2024-26":1,"unknown":13}}},"text":"Building Family Caregiver Skills Using a Simulation-Based Intervention: A Randomized Pilot Trial.\nTo evaluate the feasibility, acceptability, safety, and fidelity of a psychoeducational intervention to improve family caregiver technical and communication skills using structured simulations. 18 family caregivers of adult patients receiving radiation therapy for head and neck cancer at University Hospitals Seidman Cancer Center in Cleveland, Ohio. A two-group, randomized pilot trial design was used. The intervention consisted of four one-on-one sessions between the caregiver and nurse interventionist during the patient's first, second, fourth, and sixth week of radiation treatment. Participants completed measures of self-efficacy for caregiving, anxiety, depression, and health-related quality of life at baseline, during the fifth week of radiation therapy, and four weeks after radiation therapy. 4 of the 9 caregiver participants completed the intervention. Improvements in scores for the intervention group were noted for self-efficacy, global mental health, anxiety, and depression. Refinement of the intervention is needed to improve feasibility. Although a caregiver intervention that incorporates simulation for skills training is acceptable and safe, flexibility in protocol is needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":19712436,"dup_signals":{"dup_doc_count":11}},"text":"Colonisation of poplar trees by gfp expressing bacterial endophytes.\nWith the exception of nitrogen fixing bacteria, there is little known about the colonisation patterns or population sizes of bacterial endophytes in deciduous trees. This study describes the isolation, identification, construction and re-colonisation patterns of three green fluorescent protein(gfp):kanamycin(R) labelled bacterial endophytes when re-introduced into poplar trees, their original host plant. Two of these endophytes showed considerable colonisation in the roots and stems of inoculated plants. gfp expressing cells of all three strains were observed to colonise the xylem tissue of the root. All three strains proved to be efficient rhizosphere colonisers, supporting the theory that the rhizosphere can serve as a source of bacterial endophytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":14751951,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Effect of physiotherapy attendance on outcome after anterior cruciate ligament reconstruction: a pilot study.\nIn many centres patients are routinely referred for physiotherapy after anterior cruciate ligament (ACL) reconstruction. However, to date the role and amount of supervised physiotherapy required has not been clearly established. To establish whether there was any difference in outcome between a group of patients who attended physiotherapy regularly after ACL reconstruction and a group who attended only infrequently. Ten patients who had attended physiotherapy infrequently (mean 1.9 visits) during the first six months after ACL reconstructive surgery were matched for age, sex, graft type, and activity level and occupation before injury with 10 patients who had attended physiotherapy regularly (mean 26.5 visits). Outcome was assessed at 12 months using the Cincinnati knee rating system and the IKDC form. Compared with the regular physiotherapy group, patients in the minimal physiotherapy group had fewer symptoms (mean Cincinnati symptom score 46.2 v 43.4, p = 0.045). There was also a trend towards higher overall Cincinnati knee scores in the minimal physiotherapy group (mean 93.7 v 87.3, p = 0.06) but no difference in IKDC ratings. These preliminary results indicate that some patients who choose to attend physiotherapy on a very limited basis after ACL reconstruction can achieve satisfactory, if not better, outcomes than patients who attend physiotherapy regularly.","subset":"pubmed_abstract"} +{"meta":{"pmid":28970926,"dup_signals":{"dup_doc_count":21,"dup_dump_count":19,"dup_details":{"curated_sources":2,"2023-06":1,"2021-43":1,"2019-09":1,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-26":1,"2018-22":1,"2018-13":1,"2018-09":1,"2017-51":1,"2017-47":1,"2017-43":1,"2017-34":1,"2017-26":1,"2023-23":1,"2024-10":1,"2024-30":1}}},"text":"Structure and spin state of nonheme FeIVO complexes depending on temperature: predictive insights from DFT calculations and experiments.\nThe spin states (S = 1 and S = 2) of nonheme FeIVO intermediates are believed to play an important role in determining their chemical properties in enzymatic and biomimetic reactions. However, it is almost impossible to investigate the spin state effect of nonheme FeIVO species experimentally, since FeIVO models having the S = 1 and S = 2 spin states at the same time neither exist nor can be synthesized. However, recent synthesis of an FeIVO complex with an S = 1 spin state (triplet), [(Me3NTB)FeIVO]2+ (1), and a structurally similar FeIVO complex but with an S = 2 spin state (quintet), [(TQA)FeIVO]2+ (2), has allowed us to compare their reactivities at 233 K. In the present study, we show that structural variants control the spin-state selectivity and reactivity of nonheme FeIVO complexes. While 1 and 2 were proposed to be in an octahedral geometry based on DFT calculations and spectroscopic characterization done at 4 K, further DFT calculations show that these species may well assume a trigonal bipyramidal structure by losing one coordinated solvent ligand at 233 K. Thus, the present study demonstrates that the structure and spin state of nonheme FeIVO complexes can be different at different temperatures; therefore, the structural and\/or spin state information obtained at 4 K should be carefully used at a higher temperature (e.g., 233 K). In addition to 1 and 2, [(TPA)FeIVO]2+ (3) with an S = 1 spin state, whose spin state was determined spectroscopically and theoretically at 233 K, is included in this study to compare the chemical properties of S = 1 and S = 2 FeIVO complexes. The present results add another dimension to the discussion of the reactivites of nonheme FeIVO species, in which the structural preference and spin state of nonheme FeIVO species can vary depending on temperature.","subset":"pubmed_abstract"} +{"meta":{"pmid":14747002,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":11}}},"text":"Genetics of multiple sclerosis.\nMultiple sclerosis (MS) is probably aetiologically heterogeneous. Systematic genetic epidemiological and molecular genetic studies have provided important insights. Both genetic and non-genetic (environment, stochastic) factors may be involved in susceptibility as well as outcome, but we have yet to understand their relative roles. Any environmental factor is likely to be ubiquitous and act on a population-basis rather than within the family microenvironment. Taken together, the results of genome screening studies provide strong evidence for exclusion of a major locus in MS. There are, however, many genes that seem to be associated with MS. These include, but are in no way limited to, HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A. The future of MS genetics, as for most common complex disorders, will be dependent on the resources available, ranging from biological samples and comprehensive databases of clinical and epidemiological information to the development of new technologies and statistical methods.","subset":"pubmed_abstract"} +{"meta":{"pmid":28003936,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":3,"unknown":15}}},"text":"Towards quantitative viromics for both double-stranded and single-stranded DNA viruses.\nViruses strongly influence microbial population dynamics and ecosystem functions. However, our ability to quantitatively evaluate those viral impacts is limited to the few cultivated viruses and double-stranded DNA (dsDNA) viral genomes captured in quantitative viral metagenomes (viromes). This leaves the ecology of non-dsDNA viruses nearly unknown, including single-stranded DNA (ssDNA) viruses that have been frequently observed in viromes, but not quantified due to amplification biases in sequencing library preparations (Multiple Displacement Amplification, Linker Amplification or Tagmentation). Here we designed mock viral communities including both ssDNA and dsDNA viruses to evaluate the capability of a sequencing library preparation approach including an Adaptase step prior to Linker Amplification for quantitative amplification of both dsDNA and ssDNA templates. We then surveyed aquatic samples to provide first estimates of the abundance of ssDNA viruses. Mock community experiments confirmed the biased nature of existing library preparation methods for ssDNA templates (either largely enriched or selected against) and showed that the protocol using Adaptase plus Linker Amplification yielded viromes that were \u00b11.8-fold quantitative for ssDNA and dsDNA viruses. Application of this protocol to community virus DNA from three freshwater and three marine samples revealed that ssDNA viruses as a whole represent only a minor fraction (<5%) of DNA virus communities, though individual ssDNA genomes, both eukaryote-infecting Circular Rep-Encoding Single-Stranded DNA (CRESS-DNA) viruses and bacteriophages from the Microviridae family, can be among the most abundant viral genomes in a sample. Together these findings provide empirical data for a new virome library preparation protocol, and a first estimate of ssDNA virus abundance in aquatic systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":18218093,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2013-20":1,"unknown":11}}},"text":"Where to deliver? Analysis of choice of delivery location from a national survey in India.\nIn order to reduce maternal mortality, the Indian government has increased its commitment to institutional deliveries. We assess the determinants of home, private and public sector utilization for a delivery in a Western state. Cross sectional analyses of the National Family Health Survey - 2 dataset. Maharashtra state. The dataset had a sample size of 5391 ever-married females between the ages of 15 to 49 years. Data were abstracted for the most recent birth (n = 1510) and these were used in the analyses. Conceptual framework was the Andersen Behavioral Model. Multinomial logistic regression analyses was conducted to assess the association of predisposing, enabling and need factors on use of home, public or private sector for delivery. A majority delivered at home (n = 559, 37%); with private and public facility deliveries accounting for 32% (n = 493) and 31% (n = 454) respectively. For the choice set of home delivery versus public facility, women with higher birth order and those living in rural areas had greater odds of delivering at home, while increasing maternal age, greater media exposure, and more then three antenatal visits were associated with greater odds of delivery in a public facility. Maternal and paternal education, scheduled caste\/tribe status, and media exposure were statistically significant predictors of the choice of public versus private facility delivery. As India's economy continues to grow, the private sector will continue to expand. Given the high household expenditures on health, the government needs to facilitate insurance schemes or provide grants to prevent impoverishment. It also needs to strengthen the public sector so that it can return to its mission of being the safety net.","subset":"pubmed_abstract"} +{"meta":{"pmid":20843885,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-26":2,"2024-18":2,"2024-10":2,"2024-30":1,"unknown":9}}},"text":"Ethics of health research in communities: perspectives from the southwestern United States.\nThe increasing attention paid to community-based research highlights the question of whether human research protections focused on the individual are adequate to safeguard communities. We conducted a study to explore how community members perceive low-risk health research, the adequacy of human research protection processes, and the ethical conduct of community-based research. Eighteen focus groups were conducted among rural and urban Hispanic and Native American communities in New Mexico using a semistructured guide. Group transcriptions were analyzed using iterative readings and coding, with review of the analytic summary by group members. Although participants recognized the value of health research, many also identified several adverse effects of research in their communities, including social (community and individual labeling, stigmatization, and discrimination) and economic (community job losses, increased insurance rates, and loss of community income). A lack of community beneficence was emphasized by participants who spoke of researchers who fail to communicate results adequately or assist with follow-through. Many group members did not believe current human research and data privacy processes were adequate to protect or assist communities. Ethical review of community-based health research should apply the Belmont principles to communities. Researchers should adopt additional approaches to community-based research by engaging communities as active partners throughout the research process, focusing on community priorities, and taking extra precautions to assure individual and community privacy. Plans for meaningful dissemination of results to communities should be part of the research design.","subset":"pubmed_abstract"} +{"meta":{"pmid":28971890,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":3,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-25":1,"2020-40":1,"2020-29":1,"2019-47":1,"2019-35":1,"2019-22":1,"2019-09":1,"2018-47":1,"2018-34":1,"2018-22":1,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway.\nMain goal of this study is to detect the possible alterations in microRNA (miRNA) expression and the pathway targeted in plasma at the time of embryo transfer and pregnancy testing dependent on the assisted reproductive treatment (ART) outcome after ovarian hyperstimulation for in vitro fertilization. Changes in miRNA expression in plasma of women, who became pregnant (n = 6) vs women who failed implantation (n = 6) following day 5 embryo transfer (ET), were investigated at the day of ET and pregnancy testing (PT). Protein expression to validate the finding was performed with a sample size of n = 20 (10 per group) using enzyme-linked immunosorbent assay. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DIANA-miRPath, v3.0 software based on predicted targets by DIANA-microT-CDS. 4 miRNAs could be identified as possible biomarkers for implantation success. The 11 miRNAs showing the highest significant alterations were all associated with the regulation of WNT3 and WNT7a. While WNT7a presented with a significant decrease between ET and PT in case of ongoing pregnancy, women with implantation failure showed unaltered concentrations. WNT3 presented with a significant decrease in both groups. However, the loss of WNT3 between ET and PT was significantly higher in patients who became pregnant. Main limitation of this prospective study is its small sample size, defining it as a pilot analysis. To conclude, we could demonstrate a significant change in miRNA profile dependent on the ART outcome affecting Wnt pathway. Our findings indicate a possible prospective use of miRNA as biomarkers for implantation success.","subset":"pubmed_abstract"} +{"meta":{"pmid":23317943,"dup_signals":{"dup_doc_count":16,"dup_dump_count":15,"dup_details":{"curated_sources":1,"2022-33":1,"2021-39":1,"2021-31":1,"2021-21":1,"2019-26":1,"2019-18":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-30":1,"2023-23":1}}},"text":"Effect of intensive care unit environment on in-hospital delirium after cardiac surgery.\nThe etiology of postcardiac surgery delirium is complex. Our primary objective was to determine the effect of the postoperative environment on the prevalence of delirium by examining the in-hospital delirium rates in 2 postoperative intensive care units with differing physical infrastructure. We further sought to identify other risk factors associated with in-hospital delirium. The rates of postoperative delirium were retrospectively examined in consecutive cardiac surgery patients during 2 separate 6-month periods. Environment 1 was characterized by a lack of physical barriers between bed spaces and was windowless, and environment 2 consisted of private rooms with physical barriers for each patient and with wall-to-wall exterior windows. Univariate and multivariate analyses to determine the risk factors associated with in-hospital delirium, including the effect of environment, were undertaken. Of the 1010 patients studied, 148 (14.7%) experienced in-hospital delirium after cardiac surgery. The prevalence of delirium was not significantly different between environments 1 and 2 (16.1% vs 13.5%; P = .25). However, in patients younger than 65 years, the proportion of intensive care unit days on which delirium occurred was greater in environment 1 than in environment 2 (5.4% vs 1.7%; P = .006). Postoperative stroke or transient ischemic attack, mechanical ventilation longer than 24 hours, age 65 years or older, concomitant coronary artery bypass grafting and valve surgery, prehospital admission benzodiazepine use, a requirement for any postoperative blood product transfusion, and postoperative renal insufficiency were identified as risk factors. The intensive care unit environment did not have a significant effect on the overall prevalence of delirium. However, that does not preclude the possibility that the intensive care unit environment might interact with other factors, such as age, in a complex manner. Attempts to reduce delirium by adjusting the intensive care unit environment alone will likely not be sufficient, and instead will require a more comprehensive multimodal approach.","subset":"pubmed_abstract"} +{"meta":{"pmid":20949428,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Pilot immunization of mice infected with an equine strain of Corynebacterium pseudotuberculosis.\nThis pilot study evaluated protection of an equine autogenous bacterin-toxoid vaccine against Corynebacterium pseudotuberculosis infection. Twenty-four BALB\/c mice were inoculated with two doses of bacterin-toxoid vaccine or two injections of a placebo. Clinical, microbiologic, and pathologic outcomes were assessed after intradermal infection with one of two equine-origin C. pseudotuberculosis strains. Mice receiving bacterin-toxoid from fast-growing C. pseudotuberculosis showed significant protection from challenge infection, as evidenced by a higher survival rate, fewer gross and histopathologic lesions, and lower bacterial levels on culture. Successful protection via a vaccine against equine internal abscesses might provide supplementary management options against an important, potentially fatal disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":30481762,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"On the Enigma of the Human Neurenteric Canal.\nExistence and biomedical relevance of the neurenteric canal, a transient midline structure during early neurulation in the human embryo, have been controversially discussed for more than a century by embryologists and clinicians alike. In this study, the authors address the long-standing enigma by high-resolution histology and three-dimensional reconstruction using new and historic histological sections of 5 human 17- to 21-day-old embryos and of 2 marmoset monkey embryos of the species Callithrix jacchus at corresponding stages. The neurenteric canal presents itself as the classical vertical connection between the amniotic cavity and the yolk sac cavity and is lined (a) craniolaterally by a horseshoe-shaped \"hinge of involuting notochordal cells\" within Hensen's node and (b) caudally by the receding primitive streak epiblast dorsally and by notochordal plate epithelium ventrally, the latter of which covered the (longitudinal) notochordal canal on its ventral side at the preceding stage. Furthermore, asymmetric parachordal nodal expression in Callithrix and morphological asymmetries within the nodes of the other specimens suggest an early non-cilium-dependent left-right symmetry breaking mode previously postulated for other mammals. We conclude that structure and position of the mammalian neurenteric canal support the notion of its homology with the reptilian blastopore as a whole and with a dorsal segment of the blastopore in amphibia. These new features of the neurenteric canal may further clarify the aetiology of foetal malformations such as junctional neurulation defects, neuroendodermal cysts, and the split notochord syndrome.","subset":"pubmed_abstract"} +{"meta":{"pmid":34767449,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"Speckle-free holography with partially coherent light sources and camera-in-the-loop calibration.\nComputer-generated holography (CGH) holds transformative potential for a wide range of applications, including direct-view, virtual and augmented reality, and automotive display systems. While research on holographic displays has recently made impressive progress, image quality and eye safety of holographic displays are fundamentally limited by the speckle introduced by coherent light sources. Here, we develop an approach to CGH using partially coherent sources. For this purpose, we devise a wave propagation model for partially coherent light that is demonstrated in conjunction with a camera-in-the-loop calibration strategy. We evaluate this algorithm using light-emitting diodes (LEDs) and superluminescent LEDs (SLEDs) and demonstrate improved speckle characteristics of the resulting holograms compared with coherent lasers. SLEDs in particular are demonstrated to be promising light sources for holographic display applications, because of their potential to generate sharp and high-contrast two-dimensional (2D) and 3D images that are bright, eye safe, and almost free of speckle.","subset":"pubmed_abstract"} +{"meta":{"pmid":22710735,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":10}}},"text":"Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients.\nPulmonary hypertension and secondary cardiac dysfunction are important contributors of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor, may be useful in this setting for its combined actions as a pulmonary vasodilator and to improve systolic and diastolic function. This study aimed to assess the effects of milrinone on cardiac function and pulmonary artery pressure in infants with CDH. A retrospective review of echocardiograms performed on infants with CDH who received milrinone was performed. Tissue Doppler imaging velocities were used to assess systolic and diastolic function. Pulmonary artery pressure was assessed from the pattern and velocity of ductal shunting. Six infants with CDH and severe pulmonary hypertension were identified. Systolic and diastolic myocardial velocities were reduced in the right ventricle (RV) and interventricular septum (IVS) at baseline. In the 72 h after commencement of milrinone, there was a significant increase in early diastolic myocardial velocities in the RV, accompanied by increasing systolic velocities in the RV and IVS. Oxygenation index was significantly reduced, blood pressure unchanged, and ductal shunt velocity minimally altered over the same time period. Milrinone use was associated with an improvement in systolic and diastolic function in the RV, corresponding to an improvement in clinical status.","subset":"pubmed_abstract"} +{"meta":{"pmid":17005606,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":8}}},"text":"M(1) and M(2) muscarinic acetylcholine receptor subtypes mediate Ca(2+) channel current inhibition in rat sympathetic stellate ganglion neurons.\nMuscarinic acetylcholine receptors (mAChRs) are known to mediate the acetylcholine inhibition of Ca(2+) channels in central and peripheral neurons. Stellate ganglion (SG) neurons provide the main sympathetic input to the heart and contribute to the regulation of heart rate and myocardial contractility. Little information is available regarding mAChR regulation of Ca(2+) channels in SG neurons. The purpose of this study was to identify the mAChR subtypes that modulate Ca(2+) channel currents in rat SG neurons innervating heart muscle. Accordingly, the modulation of Ca(2+) channel currents by the muscarinic cholinergic agonist, oxotremorine-methiodide (Oxo-M), and mAChR blockers was examined. Oxo-M-mediated mAChR stimulation led to inhibition of Ca(2+) currents through voltage-dependent (VD) and voltage-independent (VI) pathways. Pre-exposure of SG neurons to the M(1) receptor blocker, M(1)-toxin, resulted in VD inhibition of Ca(2+) currents after Oxo-M application. On the other hand, VI modulation of Ca(2+) currents was observed after pretreatment of cells with methoctramine (M(2) mAChR blocker). The Oxo-M-mediated inhibition was nearly eliminated in the presence of both M(1) and M(2) mAChR blockers but was unaltered when SG neurons were exposed to the M(4) mAChR toxin, M(4)-toxin. Finally, the results from single-cell RT-PCR and immunofluorescence assays indicated that M(1) and M(2) receptors are expressed and located on the surface of SG neurons. Overall, the results indicate that SG neurons that innervate cardiac muscle express M(1) and M(2) mAChR, and activation of these receptors leads to inhibition of Ca(2+) channel currents through VI and VD pathways, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":22019635,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"A functional cutin matrix is required for plant protection against water loss.\nThe plant cuticle, a cutin matrix embedded with and covered by wax, seals the aerial organ's surface to protect the plant against uncontrolled water loss. The cutin matrix is essential for the cuticle to function as a barrier to water loss. Recently, we identified from wild barley a drought supersensitive mutant, eibi1, which is caused by a defective cutin matrix as the result of the loss of function of HvABCG31, an ABCG full transporter. Here, we report that eibi1 epidermal cells contain lipid-like droplets, which are supposed to consist of cutin monomers that have not been transported out of the cells. The eibi1 cuticle is fragile due to a defective cutin matrix. The rice ortholog of the EIBI1 gene has a similar pattern of expression, young shoot but not flag leaf blade, as the barley gene. The model of the function of Eibi1 is discussed. The HvABCG31 full transporter functions in the export of cutin components and contributed to land plant colonization, hence also to terrestrial life evolution.","subset":"pubmed_abstract"} +{"meta":{"pmid":8038715,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Active DNA topoisomerase II with minimum molecular mass from regenerating rat liver.\nWe have purified the type II DNA topoisomerase from regenerating rat liver. The purified topoisomerase II migrated as two bands with molecular masses of 70 kDa and 55 kDa on SDS-PAGE. Immunoblotting analysis using antiserum against rat topoisomerase II gene product expressed in Escherichia coli suggested that the two bands on SDS-gel are proteolytic products of the intact 173 kDa form. However, these products retained the enzyme activities such as catenation and relaxation of supercoiled circular duplex monomer DNA and unknotting of knotted phage P4 DNA. These results suggest that DNA topoisomerase II consists of different functional domains and that the whole enzyme is not required for its activity. The activities of the purified enzyme were completely inhibited by 1 mM novobiocin, a bacterial gyrase inhibitor. However, no inhibitory effect was observed when another gyrase inhibitor, nalidixic acid was used.","subset":"pubmed_abstract"} +{"meta":{"pmid":19042469,"dup_signals":{"dup_doc_count":25,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2022-49":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-21":1,"2021-17":1,"2020-40":1,"2020-29":1,"2020-05":1,"2019-30":1,"2019-26":1,"2019-09":1,"2018-51":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-26":1,"2018-17":2,"2023-14":1,"2024-22":1}}},"text":"Men's work: men's voices and actions against sexism and violence.\nThis short article details the initial findings from a 3-month conversation between 21 male activists who work to prevent violence against women. Using Participatory Action Research methodology, this research project investigates what men who do this work would like to learn from other men who do this work. To date, no research has been done that examines what it is that motivates and sustains men who work, as their primary effort, to prevent men's violence against women. This article examines some of the initial findings from this research, and examines the implications for engaging and mobilizing other men to prevent men's violence against women. This article begins with a description of the research project, followed by an overview of the findings, continues with a discussion of the implications from these initial findings for preventing men's violence against women, and ends with some lessons learned from the process of this research project and a brief overview of the next step of this conversation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28303193,"dup_signals":{"dup_doc_count":21,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":18}}},"text":"Biodiversity in agricultural landscapes: The effect of apple cultivar on epiphyte diversity.\nIn natural systems, extended phenotypes of trees can be important in determining the species composition and diversity of associated communities. Orchards are productive systems where trees dominate, and can be highly biodiverse, but few studies have considered the importance of tree genetic background in promoting associated biodiversity. We tested the effect of apple cultivar (plant genetic background) on the diversity and composition of the associated epiphytic bryophyte community across a total of seven cultivars in five productive East Anglian orchards where each orchard contained two cultivars. Data were collected from 617 individual trees, over 5 years. Species richness and community composition were significantly influenced by both orchard and cultivar. Differences among orchards explained 16% of the variation in bryophyte community data, while cultivar explained 4%. For 13 of the 41 bryophyte species recorded, apple cultivar was an important factor in explaining their distribution. While the effects of cultivar were small, we were able to detect them at multiple levels of analysis. We provide evidence that extended phenotypes act in productive as well as natural systems. With issues of food security ranking high on the international agenda, it is important to understand the impact of production regimes on associated biodiversity. Our results can inform mitigation of this potential conflict.","subset":"pubmed_abstract"} +{"meta":{"pmid":29068996,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules: A systematic review and meta-analysis.\nReal-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules.","subset":"pubmed_abstract"} +{"meta":{"pmid":23859042,"dup_signals":{"dup_doc_count":17,"dup_details":{"curated_sources":2,"unknown":15}}},"text":"Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol production and ER\/PR expression in breast cancer and trophoblast tumor cells.\nPhytoestrogens have a controversial effect on hormone-dependent tumours. Herein, we investigated the effect of the pumpkin seed extract (PSE) on estradiol production and estrogen receptor (ER)-\u03b1\/ER-\u03b2\/progesterone receptor (PR) status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various concentrations of PSE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the PSE on ER-\u03b1\/ER-\u03b2\/PR expression was assessed by immunocytochemistry. The PSE was found to contain both lignans and flavones. Estradiol production was elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In MCF7 cells, a significant ER-\u03b1 downregulation and a significant PR upregulation were observed. The above results after properly designed animal studies could highlight a potential role of pumpkin seed's lignans in breast cancer prevention and\/or treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":26741801,"dup_signals":{"dup_doc_count":53,"dup_dump_count":36,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":2,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":2,"2022-21":2,"2021-43":3,"2021-31":2,"2021-21":2,"2021-17":2,"2021-10":2,"2020-50":2,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":2,"2017-51":1,"2017-47":1,"2017-43":1,"2017-39":1,"2017-34":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-18":1,"2017-13":1,"2024-30":1}}},"text":"Near-optimal Integration of Magnitude in the Human Parietal Cortex.\nHumans are often observed to make optimal sensorimotor decisions but to be poor judges of situations involving explicit estimation of magnitudes or numerical quantities. For example, when drawing conclusions from data, humans tend to neglect the size of the sample from which it was collected. Here, we asked whether this sample size neglect is a general property of human decisions and investigated its neural implementation. Participants viewed eight discrete visual arrays (samples) depicting variable numbers of blue and pink balls. They then judged whether the samples were being drawn from an urn in which blue or pink predominated. A participant who neglects the sample size will integrate the ratio of balls on each array, giving equal weight to each sample. However, we found that human behavior resembled that of an optimal observer, giving more credence to larger sample sizes. Recording scalp EEG signals while participants performed the task allowed us to assess the decision information that was computed during integration. We found that neural signals over the posterior cortex after each sample correlated first with the sample size and then with the difference in the number of balls in either category. Moreover, lateralized beta-band activity over motor cortex was predicted by the cumulative difference in number of balls in each category. Together, these findings suggest that humans achieve statistically near-optimal decisions by adding up the difference in evidence on each sample, and imply that sample size neglect may not be a general feature of human decision-making.","subset":"pubmed_abstract"} +{"meta":{"pmid":19027948,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":17}}},"text":"Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability.\nThe extracellular matrix (ECM) exerts powerful control over many cellular phenomena, including stem cell differentiation. As such, design and modulation of ECM analogs to ligate specific integrin is a promising approach to control cellular processes in vitro and in vivo for regenerative medicine strategies. Although fibronectin (FN), a crucial ECM protein in tissue development and repair, and its RGD peptide are widely used for cell adhesion, the promiscuity with which they engage integrins leads to difficulty in control of receptor-specific interactions. Recent simulations of force-mediated unfolding of FN domains and sequences analysis of human versus mouse FN suggest that the structural stability of the FN's central cell-binding domains (FN III9-10) affects its integrin specificity. Through production of FN III9-10 variants with variable stabilities, we obtained ligands that present different specificities for the integrin alpha(5)beta(1) and that can be covalently linked into fibrin matrices. Here, we demonstrate the capacity of alpha(5)beta(1) integrin-specific engagement to influence human mesenchymal stem cell (MSC) behavior in 2D and 3D environments. Our data indicate that alpha(5)beta(1) has an important role in the control of MSC osteogenic differentiation. FN fragments with increased specificity for alpha(5)beta(1) versus alpha(v)beta(3) results in significantly enhanced osteogenic differentiation of MSCs in 2D and in a clinically relevant 3D fibrin matrix system, although attachment\/spreading and proliferation were comparable with that on full-length FN. This work shows how integrin-dependant cellular interactions with the ECM can be engineered to control stem cell fate, within a system appropriate for both 3D cell culture and tissue engineering.","subset":"pubmed_abstract"} +{"meta":{"pmid":29499107,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":10}}},"text":"Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering.\nHepatic differentiation of human-induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels comparable with hPCLS indicating excellent future perspectives for the development of a bioartificial liver system for toxicity testing or as liver support device for patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":29042426,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General Population?\nTranscatheter aortic valve implantation (TAVI) is indicated for patients with aortic stenosis who are intermediate-high surgical risk. Although all-cause mortality rates after TAVI are established, survival attributable to the procedure is unclear because of competing causes of mortality. The aim was to report relative survival (RS) after TAVI, which accounts for background mortality risks in a matched general population. National cohort data (n=6420) from the 2007 to 2014 UK TAVI registry were matched by age, sex, and year to mortality rates for England and Wales (population, 57.9 million). The Ederer II method related observed patient survival to that expected from the matched general population. We modelled RS using a flexible parametric approach that modelled the log cumulative hazard using restricted cubic splines. RS of the TAVI cohort was 95.4%, 90.2%, and 83.8% at 30 days, 1 year, and 3 years, respectively. By 1-year follow-up, mortality hazards in the >85 years age group were not significantly different from those of the matched general population; by 3 years, survival rates were comparable. The flexible parametric RS model indicated that increasing age was associated with significantly lower excess hazards after the procedure; for example, by 2 years, a 5-year increase in age was associated with 20% lower excess mortality over the general population. RS after TAVI was high, and survival rates in those aged >85 years approximated those of a matched general population within 3 years. High rates of RS indicate that patients selected for TAVI tolerate the risks of the procedure well.","subset":"pubmed_abstract"} +{"meta":{"pmid":28744180,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":2,"2024-18":2,"unknown":12}}},"text":"Mutant selection in the self-incompatible plant radish (Raphanus sativus L. var. sativus) using two-step TILLING.\nRadish (Raphanus sativus L. var. sativus), a widely cultivated root vegetable crop, possesses a large sink organ (the root), implying that photosynthetic activity in radish can be enhanced by altering both the source and sink capacity of the plant. However, since radish is a self-incompatible plant, improved mutation-breeding strategies are needed for this crop. TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful method used for reverse genetics. In this study, we developed a new TILLING strategy involving a two-step mutant selection process for mutagenized radish plants: the first selection is performed to identify a BC1M1 line, that is, progenies of M1 plants crossed with wild-type, and the second step is performed to identify BC1M1 individuals with mutations. We focused on Rubisco as a target, since Rubisco is the most abundant plant protein and a key photosynthetic enzyme. We found that the radish genome contains six RBCS genes and one pseudogene encoding small Rubisco subunits. We screened 955 EMS-induced BC1M1 lines using our newly developed TILLING strategy and obtained six mutant lines for the six RsRBCS genes, encoding proteins with four different types of amino acid substitutions. Finally, we selected a homozygous mutant and subjected it to physiological measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":9371013,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"New oral therapies for type 2 diabetes.\nOver the past few years, several oral agents for the treatment of type 2 diabetes have become available in the United States. Metformin, a biguanide that has been used for decades in other countries throughout the world, improves glycemic control without exacerbating hyperinsulinemia or promoting weight gain. This agent has recently been reintroduced in the United States. Acarbose is an alpha-glucosidase inhibitor that improves glycemic control by decreasing the intestinal absorption of glucose, thereby decreasing postprandial glucose elevations. The use of metformin and acarbose may be limited by their side effects and potential risks, especially the risk of lactic acidosis with metformin. The third newly available agent, troglitazone, has been shown to improve insulin sensitivity. Combinations of metformin, acarbose and troglitazone may facilitate improved glycemic control without the use of insulin, or they may allow sulfonylurea or insulin dosages to be reduced, in this way minimizing the adverse effects of hyperinsulinemia. Unfortunately, current oral therapies do not prevent the inevitable decline in glycemic control that occurs during the natural history of type 2 diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":31539484,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Confidence Can Be Used to Discriminate Between Accurate and Inaccurate Lie Decisions.\nThere is a long-standing belief that confidence is not useful at discriminating between accurate and inaccurate deception decisions. Historically, this position made sense because people showed little ability to discriminate lie-tellers from truth-tellers. But, it is now widely accepted that, under certain conditions, people can discriminate between lie-tellers and truth-tellers. Nevertheless, belief that confidence does not discriminate between accurate and inaccurate responses persists. This belief is somewhat paradoxical because, to the extent that people can discriminate between lie-tellers and truth-tellers, signal detection theory naturally predicts a positive relationship between confidence and accuracy. In line with our signal-detection-based predictions, we show that, among decisions about whether someone is lying, those made with high confidence are more accurate than those made with low confidence. This important relationship has gone unnoticed in past work because of a reliance on inappropriate measures. Past research examining the confidence-accuracy relationship in deception research relied on correlating average confidence with proportion of correctly identified lies. These correlations provide information on whether more confident judges tend to be more accurate but remain silent on the arguably more important question of whether higher confidence decisions are more accurate than lower confidence decisions. We show that confidence-accuracy characteristic analyses are uniquely suited to measuring the confidence-accuracy relationship in deception research.","subset":"pubmed_abstract"} +{"meta":{"pmid":20573643,"dup_signals":{"dup_doc_count":24,"dup_dump_count":19,"dup_details":{"curated_sources":4,"2023-14":1,"2022-21":1,"2021-49":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-45":2,"2020-40":1,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Chart documentation quality and its relationship to the validity of administrative data discharge records.\nThe validity of administrative data may be vulnerable to how well physicians document medical charts. The objective of this study is to determine the relationship between chart documentation quality and the validity of administrative data. The charts for patients who underwent carotid endarterectomy were re-abstracted and rated for the quality of documentation. Poorly and well-documented charts were compared by patient, physician, and hospital variables, as well as on agreement between the administrative and re-abstracted data. Of the 2061 charts reviewed, 42.6 per cent were rated well documented. The proportion of charts well documented varied from 14.6 to 87.5 per cent across 17 hospitals, but did not vary significantly by patient characteristics. The kappa statistic was generally higher for well-documented charts than for poorly documented charts, but varied across comorbidities. In conclusion, poorly documented hospital charts tend to be translated into invalid administrative data, which reduces the communication of clinical information among healthcare providers.","subset":"pubmed_abstract"} +{"meta":{"pmid":24182358,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"A comparison of cone beam computed tomography and periapical radiography for the detection of vertical root fractures in nonendodontically treated teeth.\nTo compare in an ex vivo model, the diagnostic accuracy of periapical radiography and cone beam computed tomography (CBCT) for the detection of artificially induced incomplete and complete vertical root fractures (VRFs), and to determine whether the width of the VRFs had an impact on the diagnostic accuracy of the imaging systems. Incomplete VRFs were induced in 30 nonendodontically treated human mandibular premolar and molar teeth. VRF widths were measured using optical coherence tomography. Complete VRFs were induced in 15 of these teeth. 3D Accuitomo and i-CAT CBCT scans and periapical radiographs were taken prior to and after fracture induction. Receiver operating characteristic (ROC) analysis was carried for each imaging technique. In addition, values for sensitivity, specificity, positive and negative predictive values, inter- and intra-examiner agreement were calculated. In the ROC analysis, both CBCT scanners were significantly more accurate than periapical radiography for the detection of incomplete VRFs (P < 0.05). The overall area under the ROC curve (AUC) values for 3D Accuitomo, i-CAT and periapical radiography were 0.687, 0.659 and 0.540, respectively. The sensitivity of 3D Accuitomo, i-CAT and periapical radiography was 27%, 28% and 3% respectively. Interexaminer agreement for the detection of incomplete fractures with periapical radiographs, 3D Accuitomo and i-CAT was 0.020, 0.229 and 0.333, respectively. Both CBCT scanners were significantly more accurate (P < 0.01) in detecting VRFs of \u226550 \u03bcm compared with VRFs of <50 \u03bcm. 3D Accuitomo was significantly better than i-CAT in detecting VRFs of <50 \u03bcm (P < 0.05). For complete fractures, the AUC values for 3D Accuitomo (0.999) and i-CAT (0.998) were significantly higher (P < 0.05) than for periapical radiography (0.724). Under the conditions of this ex vivo study, periapical radiographs and CBCT were unreliable for the detection of simulated incomplete VRFs. The widths of the fractures appeared to have an impact on the diagnostic accuracy of CBCT as the detection of VRFs of \u226550 \u03bcm was significantly higher than those of <50 \u03bcm. The detection of complete fractures was significantly higher for all systems than that of incomplete fractures.","subset":"pubmed_abstract"} +{"meta":{"pmid":22682578,"dup_signals":{"dup_doc_count":21,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":3,"2015-11":2,"2015-06":3,"2014-10":3,"2013-48":3,"2013-20":3,"unknown":3}}},"text":"Unusual primary osseous Hodgkin lymphoma in rib with associated soft tissue mass: a case report and review of literature.\nHodgkin lymphoma (HL) typically presents as nodal lesion and may involve extranodal sites during the progression of the disease. Primary osseous HL without any lymph node association is extremely rare and only a few such cases have been described in the literature. We present a case of unusual primary HL in rib occurring in a middle-aged female patient. Computed tomography (CT) scan revealed an osteolytic lesion was located at the right second rib and was associated with a large soft tissue mass. There was no regional lymph node involvement. CT scan of neck and abdomen was performed and showed no pathologic findings, particularly no lymphadenopathy and organomegaly could be observed. Histologically, typical binucleated Reed-Sternberg (RS) cells and lacunar cells were scattered in the background of reactive inflammation with infiltration of lymphocytes, histiocytes and eosinophilic granulocytes. By immunohistochemistry, RS cells and lacunar cells were positive for CD15 and CD30 with typical membrane and paranuclear dot-like staining pattern. However, these cells were negative for Epstein-Barr virus detection by in situ hybridization. A diagnosis of primary osseous HL was made. The patient received systemic chemotherapy and local radiotherapy, and was on regular follow-up for 24 months. There was no sign of recurrence of tumor and lymph node or bone marrow involvement. Because there is a possibility of secondary bone involvement by systemic HL, strict histological analysis and thorough radiographic examination are suggested to be necessary for accurately diagnosing this tumor when it presents as a solitary bone lesion.","subset":"pubmed_abstract"} +{"meta":{"pmid":22963326,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Effects of prior short multiple-sprint exercises with different intersprint recoveries on the slow component of oxygen uptake during high-intensity exercise.\nThis study compares the effects of two short multiple-sprint exercise (MSE) (6 \u00d7 6 s) sessions with two different recovery durations (30 s or 180 s) on the slow component of oxygen uptake ([Formula: see text]O(2)) during subsequent high-intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of the difference between the gas exchange threshold and [Formula: see text]O(2peak) (\u039450). Then, the subjects performed two MSEs of 6 \u00d7 6 s separated by two intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min later by the \u039450 (\u039450(30) and \u039450(180), respectively). Electromyography (EMG) activities of the vastus medialis and lateralis were measured throughout each exercise bout. During MSE(30), muscle activity (root mean square) increased significantly (p \u2264 0.04), with a significant leftward-shifted median frequency of the power density spectrum (MDF; p \u2264 0.01), whereas MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean [Formula: see text]O(2) value was significantly higher in MSE(30) than in MSE(180) (p < 0.001). During \u039450(30), [Formula: see text]O(2) and the deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%, p = 0.02, and -34%, p = 0.003, respectively) compared with \u039450. There were no significant modifications of the [Formula: see text]O(2) slow component in \u039450(180) compared with \u039450 (p = 0.32). The neuromuscular and metabolic adaptations during MSE(30) (preferential activation of type I muscle fibers evidenced by decreased MDF and a greater aerobic metabolism contribution to the required energy demands), but not during MSE(180), may lead to reduced [Formula: see text]O(2) and [HHb] slow components, suggesting an alteration in motor units recruitment profile (i.e., change in the type of muscle fibers recruited) and (or) an improved muscle O(2) delivery during subsequent exercise.","subset":"pubmed_abstract"} +{"meta":{"pmid":7377790,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":3,"unknown":9}}},"text":"Hereditary acrodermatitis enteropathica in an adult.\nThe condition of a 33-year-old woman who had a history of blisters following trauma on the hands, knees, and feet since 1 year of age previously had been diagnosed as epidermolysis bullosa. She also had psoriasiform plaques, a pustular crusted periorificial eruption, paronychia, alopecia, and photophobia. She had had minimal history of diarrhea. A markedly decreased serum zinc level was found, and treatment with zinc sulfate was instituted, resulting in clearing of all clinical manifestations. Since patients with hereditary acrodermatitis enteropathica may have minimal or no diarrhea and the correct diagnosis may be long delayed, the condition should not be considered strictly a disease of children.","subset":"pubmed_abstract"} +{"meta":{"pmid":8118036,"dup_signals":{"dup_doc_count":19,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2023-14":1,"2022-49":1,"2022-21":1,"2021-49":2,"2021-43":1,"2021-31":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":1,"2023-40":1,"2024-18":1}}},"text":"DNA rearrangements proximal to the EVI1 locus associated with the 3q21q26 syndrome.\nSpecific rearrangements involving 3q21 and 3q26 are well documented in acute myeloid leukemia (AML). Aberrant expression of the Ecotropic virus integration-1 (EVI1) gene, located at 3q26, has been reported in individuals with AML and translocations or inversions of chromosome 3 long arm. We have studied six individuals with AML and inv(3)(q21q26) for disruptions to the EVI1 locus by in situ hybridization and long-range mapping. EVI1 transcripts have been detected in the blast cells of the two individuals available for expression studies. We derived a YAC containing the EVI1 gene and showed that it crossed the 3q26 inversion breakpoints in three of four cases examined. Pulsed field analysis detected aberrant fragments 3' of the EVI1 gene in all six patients. The orientation of the gene was established and the locations of the breakpoints were refined by in situ hybridization using phage clones from this region.","subset":"pubmed_abstract"} +{"meta":{"pmid":8584116,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Expression of candidate pro-GnRH processing enzymes in rat hypothalamus and an immortalized hypothalamic neuronal cell line.\nSince gonadotropin-releasing hormone (GnRH, also referred to as LHRH) is a major hormone regulating mammalian reproduction, identification of the processing steps involved in the conversion of the pro-LHRH to LHRH is fundamental to our understanding of its physiology. Extracts from immortalized LHRH neurons (GT1) were used to isolate the pro-LHRH intermediate products and to identify the enzymes which may participate in these conversions. The GT1 cells contain and secrete a pro-LHRH species that elutes at approximately 10,000-12,000 molecular weight. The pro-LHRH is metabolized to various N- and C-terminally modified LHRH products and to gonadotropin-releasing hormone-associated peptide (GAP). Analyses of these intermediates suggests that, at least, four different enzymatic steps are involved in pro-LHRH processing. Northern blot analyses reveal that prohormone convertase 2 (PC2), carboxypeptidase E, glutaminyl cyclase, and peptidyl-glycine alpha-amidating monooxygenase are expressed in the GT1 cells and rat hypothalamus. PC2 immunoreactivity is localized to the perikarya and beaded axon-like processes of these cells. SDS-PAGE analyses indicate that PC2 is biosynthesized, processed and secreted by the immortalized LHRH neurons. Our results indicate that the GT1 cell line may serve as a useful model to study the regulation of pro-LHRH processing and that it may also represent an important tool for dissecting the molecular and cellular basis of mammalian reproduction.","subset":"pubmed_abstract"} +{"meta":{"pmid":14983524,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Interaction of Cep135 with a p50 dynactin subunit in mammalian centrosomes.\nCep135 is a 135-kDa, coiled-coil centrosome protein important for microtubule organization in mammalian cells [Ohta et al., 2002: J. Cell Biol. 156:87-99]. To identify Cep135-interacting molecules, we screened yeast two-hybrid libraries. One clone encoded dynamitin, a p50 dynactin subunit, which localized at the centrosome and has been shown to be involved in anchoring microtubules to centrosomes. The central domain of p50 binds to the C-terminal sequence of Cep135; this was further confirmed by immunoprecipitation and immunostaining of CHO cells co-expressing the binding domains for Cep135 and p50. Exogenous p50 lacking the Cep 135-binding domain failed to locate at the centrosome, suggesting that Cep135 is required for initial targeting of the centrosome. Altered levels of Cep135 and p50 by RNAi and protein overexpression caused the release of endogenous partner molecules from centrosomes. This also resulted in dislocation of other centrosomal molecules, such as gamma-tubulin and pericentrin, ultimately leading to disorganization of microtubule patterns. These results suggest that Cep135 and p50 play an important role in assembly and maintenance of functional microtubule-organizing centers.","subset":"pubmed_abstract"} +{"meta":{"pmid":17974028,"dup_signals":{"dup_doc_count":13,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-44":1,"2016-40":1,"2016-36":1,"2018-51":1}}},"text":"TreeViewJ: An application for viewing and analyzing phylogenetic trees.\nPhylogenetic trees are widely used to visualize evolutionary relationships between different organisms or samples of the same organism. There exists a variety of both free and commercial tree visualization software available, but limitations in these programs often require researchers to use multiple programs for analysis, annotation, and the production of publication-ready images. We present TreeViewJ, a Java tool for visualizing, editing and analyzing phylogenetic trees. The software allows researchers to color and change the width of branches that they wish to highlight, and add names to nodes. If collection dates are available for taxa, the software can map them onto a timeline, and sort the tree in ascending or descending date order. TreeViewJ is a tool for researchers to visualize, edit, \"decorate,\" and produce publication-ready images of phylogenetic trees. It is open-source, and released under an GPL license, and available at http:\/\/treeviewj.sourceforge.net.","subset":"pubmed_abstract"} +{"meta":{"pmid":2085059,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":14}}},"text":"[High dosage vitamin E therapy in patients with activated arthrosis].\nThe known antiphlogistic in vitro effect of vitamin E was tested in a double-blind randomized study in patients with osteoarthritis. Fifty-three in-patients with osteoarthritis of the hip (n = 34) or the knee (n = 19) were treated for 3 weeks with 400 mg vitamin E (d-alpha-tocopherolacetate, V, n = 26) or 50 mg Diclofenac (D, n = 27) three times daily. A standardized therapeutic exercise program was performed; local therapy was not permitted. There were no significant differences in the efficacy of the two drugs, although one patient of the V-group refused further treatment after 8 days because of inefficacy. V reduced or abolished the pain at rest in 77% (D in 85%), the pain on pressure in 67% (D in 50%), and the pain on movement in 62% (D in 63%). Both treatments appeared to be equally effective in reducing the circumference of the knee joints (p = 0.001) and the walking time (p less than 0.001) and in increasing the joint mobility (p less than 0.002). Patients (n = 11) with a plasma-alpha-tocopherol increase higher than two standard deviations of the mean value at onset (greater than 25.2 mg\/l) seemed to have a more pronounced reduction of pain (eight out of 11 patients) compared with four out of 11 patients with a moderate increase of vitamin E. Side effects occurred in two out of 26 patients with V (7.7%), and in 25.9% during D-treatment. One patient with D therefore stopped the therapy after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":24840192,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":9}}},"text":"Bone enhancing effect of titanium-binding proteins isolated from bovine bone and implanted into rat calvaria with titanium scaffold.\nBased on our previous finding that a chromatography with titanium beads selectively binds phosphoproteins, including caseins, phosvitin and dentin phosphoproteins, we investigated whether bone phosphoproteins also bind to titanium. Bovine bone matrix proteins were extracted with 2 M urea\/PBS after demineralization. The 2 M urea extract was directly applied to the titanium chromatography column as reported. The chromatogram showed an initial large peak at breakthrough position (non-binding fraction) and a smaller second peak eluted later (titanium-binding fraction). Both peaks were analyzed by SDS polyacrylamide gel electrophoresis. Stains-all staining which preferentially identifies phospho-proteins revealed that the first peak contained no positively stained band, while the second peak showed 4 or 5 distinctive bands indicative of bone phosphoproteins. To investigate the biological functions of the titanium-binding bone proteins (TiBP), we implanted them into calvaria of rats, combined with titanium web (TW), a highly porous titanium scaffold of thin titanium-fibers. Bone TiBP induced significantly enhanced bone formation, and new bone appeared connected directly to titanium fibers, accompanied by active blood vessel formations. Control TW alone did not induce bone formation within the titanium framework. These results demonstrate that the bone titanium-binding proteins include phosphoproteins which enhance bone formation when implanted into bone with titanium.","subset":"pubmed_abstract"} +{"meta":{"pmid":34264150,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-22":1,"unknown":11}}},"text":"A Signal Detection Approach to Understanding the Identification of Fake News.\nResearchers across many disciplines seek to understand how misinformation spreads with a view toward limiting its impact. One important question in this research is how people determine whether a given piece of news is real or fake. In the current article, we discuss the value of signal detection theory (SDT) in disentangling two distinct aspects in the identification of fake news: (a) ability to accurately distinguish between real news and fake news and (b) response biases to judge news as real or fake regardless of news veracity. The value of SDT for understanding the determinants of fake-news beliefs is illustrated with reanalyses of existing data sets, providing more nuanced insights into how partisan bias, cognitive reflection, and prior exposure influence the identification of fake news. Implications of SDT for the use of source-related information in the identification of fake news, interventions to improve people's skills in detecting fake news, and the debunking of misinformation are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":24820110,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Self-Checking Cell-Based Assays for GPCR Desensitization and Resensitization.\nG protein-coupled receptors (GPCRs) play stimulatory or modulatory roles in numerous physiological states and processes, including growth and development, vision, taste and olfaction, behavior and learning, emotion and mood, inflammation, and autonomic functions such as blood pressure, heart rate, and digestion. GPCRs constitute the largest protein superfamily in the human and are the largest target class for prescription drugs, yet most are poorly characterized, and of the more than 350 nonolfactory human GPCRs, over 100 are orphans for which no endogenous ligand has yet been convincingly identified. We here describe new live-cell assays that use recombinant GPCRs to quantify two general features of GPCR cell biology-receptor desensitization and resensitization. The assays employ a fluorogen-activating protein (FAP) reporter that reversibly complexes with either of two soluble organic molecules (fluorogens) whose fluorescence is strongly enhanced when complexed with the FAP. Both assays require no wash or cleanup steps and are readily performed in microwell plates, making them adaptable to high-throughput drug discovery applications.","subset":"pubmed_abstract"} +{"meta":{"pmid":29045651,"dup_signals":{"dup_doc_count":32,"dup_dump_count":29,"dup_details":{"curated_sources":3,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-49":1,"2021-39":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2023-50":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Clinical decision support alert malfunctions: analysis and empirically derived taxonomy.\nTo develop an empirically derived taxonomy of clinical decision support (CDS) alert malfunctions. We identified CDS alert malfunctions using a mix of qualitative and quantitative methods: (1) site visits with interviews of chief medical informatics officers, CDS developers, clinical leaders, and CDS end users; (2) surveys of chief medical informatics officers; (3) analysis of CDS firing rates; and (4) analysis of CDS overrides. We used a multi-round, manual, iterative card sort to develop a multi-axial, empirically derived taxonomy of CDS malfunctions. We analyzed 68 CDS alert malfunction cases from 14 sites across the United States with diverse electronic health record systems. Four primary axes emerged: the cause of the malfunction, its mode of discovery, when it began, and how it affected rule firing. Build errors, conceptualization errors, and the introduction of new concepts or terms were the most frequent causes. User reports were the predominant mode of discovery. Many malfunctions within our database caused rules to fire for patients for whom they should not have (false positives), but the reverse (false negatives) was also common. Across organizations and electronic health record systems, similar malfunction patterns recurred. Challenges included updates to code sets and values, software issues at the time of system upgrades, difficulties with migration of CDS content between computing environments, and the challenge of correctly conceptualizing and building CDS. CDS alert malfunctions are frequent. The empirically derived taxonomy formalizes the common recurring issues that cause these malfunctions, helping CDS developers anticipate and prevent CDS malfunctions before they occur or detect and resolve them expediently.","subset":"pubmed_abstract"} +{"meta":{"pmid":29039327,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Formulation of lyophilized single vial kit of N-N-Ethylene-L-Dicysteine (EC) for labeling with 99mTc. II: Radiochemical and clinical evaluation as a renal tubular agent in comparison with 99mTc-MAG3.\nA Technetium 99mTc labeled lyophilized single component kit of N-N-ethylene-I-dicysteine (EC) is developed to replace multiple step kit developed by others. The aim of study is to formulate a radionuclide that is easy to prepare, has rapid plasma clearance, produce high quality images and is an affective alternative to radioiodine labeled orthoiodohippurate, which has been remained the physiological 'gold standard' since long time. To achieve this goal, the systematically varied key parameters such as pH, the use of reducing agents, stabilizers and additives are optimized to obtain maximum radiochemical purity and optimum biodistribution in non human and human primates. Various pH levels of EC showed equally good results in animal experiments but only pH 10 was suitable for human use. Dynamic and renal Scintigraphic studies are carried out with 99mTc-EC at pH 8 in 12 volunteers and at pH 10 in 18 volunteers and compared with 99mTc-MAG3, Background ratios, renograms, relative renal function and semi quantitative parameters are available in all studies. The background ratios (mean \u00b1 SD) at 30th minute are 0229\u00b10.024 and 0.236\u00b10.018 for 99mTc-EC at pH 10 and 99mTc-MAG3 respectively. The mean \u00b1 standard error of mean (SEM) values of TMAX and time to half activity (T12) for 99mTc-EC (pH10) are 3.7\u00b10.6 and 7.3\u00b11.0 respectively while for 99mTc-MAG3, they are 4.0\u00b10.8 and 7.9\u00b11.4 with p values 0.001 and 0.049 respectively. The values of relative renal function (RRF) for 99mTc-EC and 99mTc-MAG3 are 50.8\u00b13.11 and 51.2\u00b13.4 respectively with p value of 0.822. The residual activity at 25th minute (A25 \/ A MAX) and renal uptake are 0. 209\u00b112.67\u00b12.80 for 99mTc-EC and 0.218\u00b10.035 and 1053\u00b12.98 for 99mTc-MAG3 (p=0.031 an 0.0003) respectively. The correlation coefficient (R2) for TMAX, T1\/2, A25\/AMAX and renal uptake are 0.96, 0.69, 0.93 and 0.85 respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":24866019,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"A PLC\u03b31-dependent, force-sensitive signaling network in the myogenic constriction of cerebral arteries.\nMaintaining constant blood flow in the face of fluctuations in blood pressure is a critical autoregulatory feature of cerebral arteries. An increase in pressure within the artery lumen causes the vessel to constrict through depolarization and contraction of the encircling smooth muscle cells. This pressure-sensing mechanism involves activation of two types of transient receptor potential (TRP) channels: TRPC6 and TRPM4. We provide evidence that the activation of the \u03b31 isoform of phospholipase C (PLC\u03b31) is critical for pressure sensing in cerebral arteries. Inositol 1,4,5-trisphosphate (IP3), generated by PLC\u03b31 in response to pressure, sensitized IP3 receptors (IP3Rs) to Ca(2+) influx mediated by the mechanosensitive TRPC6 channel, synergistically increasing IP3R-mediated Ca(2+) release to activate TRPM4 currents, leading to smooth muscle depolarization and constriction of isolated cerebral arteries. Proximity ligation assays demonstrated colocalization of PLC\u03b31 and TRPC6 with TRPM4, suggesting the presence of a force-sensitive, local signaling network comprising PLC\u03b31, TRPC6, TRPM4, and IP3Rs. Src tyrosine kinase activity was necessary for stretch-induced TRPM4 activation and myogenic constriction, consistent with the ability of Src to activate PLC\u03b3 isoforms. We conclude that contraction of cerebral artery smooth muscle cells requires the integration of pressure-sensing signaling pathways and their convergence on IP3Rs, which mediate localized Ca(2+)-dependent depolarization through the activation of TRPM4.","subset":"pubmed_abstract"} +{"meta":{"pmid":33758673,"dup_signals":{"dup_doc_count":13,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":6,"2024-30":1,"unknown":4}}},"text":"Emission Ratios for Ammonia and Formic Acid and Observations of Peroxy Acetyl Nitrate (PAN) and Ethylene in Biomass Burning Smoke as Seen by the Tropospheric Emission Spectrometer (TES).\nWe use the Tropospheric Emission Spectrometer (TES) aboard the NASA Aura satellite to determine the concentrations of the trace gases ammonia (NH3) and formic acid (HCOOH) within boreal biomass burning plumes, and present the first detection of peroxy acetyl nitrate (PAN) and ethylene (C2H4) by TES. We focus on two fresh Canadian plumes observed by TES in the summer of 2008 as part of the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS-B) campaign. We use TES retrievals of NH3 and HCOOH within the smoke plumes to calculate their emission ratios (1.0% \u00b1 0.5% and 0.31% \u00b1 0.21%, respectively) relative to CO for these Canadian fires. The TES derived emission ratios for these gases agree well with previous aircraft and satellite estimates, and can complement ground-based studies that have greater surface sensitivity. We find that TES observes PAN mixing ratios of ~2 ppb within these mid-tropospheric boreal biomass burning plumes when the average cloud optical depth is low (<0.1) and that TES can detect C2H4 mixing ratios of ~2 ppb in fresh biomass burning smoke plumes.","subset":"pubmed_abstract"} +{"meta":{"pmid":16842846,"dup_signals":{"dup_doc_count":13}},"text":"In vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS.\nA novel in vitro model of glial scarring was developed by adapting a primary cell-based system previously used for studying neuroinflammatory processes in neurodegenerative disease. Midbrains from embryonic day 14 Fischer 344 rats were mechanically dissociated and grown on poly-D-lysine coated 24 well plates to a confluent layer of neurons, astrocytes, and microglia. The culture was injured with either a mechanical scrape or foreign-body placement (segments of 50 microm diameter stainless steel microwire), fixed at time points from 6 h to 10 days, and assessed by immunocytochemistry. Microglia invaded the scraped wound area at early time points and hypertrophied activated astrocytes repopulated the wound after 7 days. The chronic presence of microwire resulted in a glial scar forming at 10 days, with microglia forming an inner layer of cells coating the microwire, while astrocytes surrounded the microglial core with a network of cellular processes containing upregulated GFAP. Vimentin expressing cells and processes were present in the scrape at early times and within the astrocyte processes forming the glial scar. Neurons within the culture did not repopulate the scrape wound and did not respond to the microwire, although they were determined to be electrically active through patch clamp recording. The time course and relative positions of the glia in response to the different injury paradigms correlated well with stereotypical in vivo responses and warrant further work in the development of a functional in vitro test bed.","subset":"pubmed_abstract"} +{"meta":{"pmid":10458915,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":11}}},"text":"Identification, chromosomal assignment, and expression analysis of the human homeodomain-containing gene Orthopedia (OTP).\nHomeodomain (HD) genes are helix-turn-helix transcription factors that play key roles in the specification of cell fates. In the central nervous system (CNS), HD genes not only position cells along an axis, but also specify cell migration patterns and may influence axonal connectivity. In an effort to identify novel HD genes involved in the development of the human CNS, we have cloned, characterized, and mapped the human homologue of the murine HD gene Orthopedia (Otp), whose product is found in multiple cell groups within the mouse hypothalamus, amygdala, and brain stem. Human cDNA and genomic libraries were screened with probes derived from mouse Otp sequences to find the human homologue, OTP. The deduced amino acid sequence of the open reading frame of the human cDNA is 99% homologous to mouse Otp and demonstrates a high degree of conservation when compared to sea urchin and Drosophila. OTP was mapped to human chromosome 5q13.3 using radiation hybrid panel mapping and fluorescence in situ hybridization. Flanking markers were identified from YAC clones containing OTP. A single putative OTP gene product was found in 17-week human fetal brain tissue by Western blot analysis using a novel polyclonal antibody raised against a conserved 13-amino-acid sequence at the C-terminus of the OTP protein. Expression in the developing human hypothalamus was confirmed by immunohistochemistry.","subset":"pubmed_abstract"} +{"meta":{"pmid":30864374,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":4,"unknown":7}}},"text":"Sodium-glucose cotransporters: new targets of cancer therapy?\nGlucose, the key source of metabolic energy, is imported into cells by two categories of transporters: 1) facilitative glucose transporters (GLUTs) and 2) secondary active sodium-glucose cotransporters (SGLTs). Cancer cells have an increased demand for glucose uptake and utilisation compared to normal cells. Previous studies have demonstrated the overexpression of GLUTs, mainly GLUT1, in many cancer types. As the current standard positron emission tomography (PET) tracer 2-deoxy-2-(18F)fluoro-D-glucose (2-FDG) for imaging tumour cells via GLUT1 lacks in sensitivity and specificity, it may soon be replaced by the newly designed, highly sensitive and specific SGLT tracer \u03b1-methyl-4-(F-18)fluoro-4-deoxy-Dglucopyranoside (Me-4FDG) in clinical detection and tumour staging. This tracer has recently demonstrated the functional activity of SGLT in pancreatic, prostate, and brain cancers. The mRNA and protein expression of SGLTs have also been reported in colon\/colorectal, lung, ovarian, head, neck, and oral squamous carcinomas. So far, SGLTs have been poorly investigated in cancer, and their protein expression and localisation are often controversial due to a lack of specific SGLT antibodies. In this review, we describe current knowledge concerning SGLT1 and SGLT2 (over)expression in various cancer types. The findings of SGLTs in malignant cells may help in developing novel cancer therapies with SGLT2 or SGLT1\/SGLT2 inhibitors already used in diabetes mellitus treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":26944133,"dup_signals":{"dup_doc_count":11}},"text":"Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib.\nChemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL\/6J, DBA\/2J, BALB\/cJ, and C3H\/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL\/6J and Balb\/cJ DRG-NOG was more sensitive to cisplatin than DBA\/2J and C3H\/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA\/2J and C3H\/H3J mice. C57BL\/6J DRG-NOG was most sensitive and Balb\/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN.","subset":"pubmed_abstract"} +{"meta":{"pmid":26991631,"dup_signals":{"dup_doc_count":23,"dup_details":{"curated_sources":2,"unknown":21}}},"text":"Patient-related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS-CAN prospective study.\nLittle is known about the effects of frailty, disability and physical functioning on the clinical outcomes for myelodysplastic syndromes (MDS). We investigated the predictive value of these factors on overall survival (OS) in 445 consecutive patients with MDS and chronic monomyelocytic leukaemia (CMML) enrolled in a multi-centre prospective national registry. Frailty, comorbidity, instrumental activities of daily living, disability, quality of life, fatigue and physical performance measures were evaluated at baseline and were added as covariates to conventional MDS-related factors as predictors of OS in Cox proportional hazards models. The median age was 73 years, and 79% had revised International Prognostic Scoring System (IPSS-R) risk scores of intermediate or lower. Frailty correlated only modestly with comorbidity. OS was significantly shorter for patients with higher frailty and comorbidity scores, any disability, impaired grip strength and timed chair stand tests. By multivariate analysis, the age-adjusted IPSS-R, frailty (Hazard ratio 2\u00b77 (95% confidence interval [CI] 1\u00b77-4\u00b72), P < 0\u00b70001) and Charlson comorbidity score (Hazard ratio 1\u00b78 (95% CI 1\u00b71-2\u00b78), P = 0\u00b701) were independently prognostic of OS. Incorporation of frailty and comorbidity scores improved risk stratification of the IPSS-R by 30% and 5%, respectively. These data demonstrate for the first time, the importance of considering frailty in prognostic models and a potential target for therapeutic intervention in optimizing clinical outcomes in older MDS patients. ClinicalTrials.gov Identifier: NCT02537990.","subset":"pubmed_abstract"} +{"meta":{"pmid":21871072,"dup_signals":{"dup_doc_count":20,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2013-48":3,"2013-20":1,"2024-26":1,"unknown":14}}},"text":"A multicenter randomized controlled trial evaluating the effect of small stitches on the incidence of incisional hernia in midline incisions.\nThe median laparotomy is frequently used by abdominal surgeons to gain rapid and wide access to the abdominal cavity with minimal damage to nerves, vascular structures and muscles of the abdominal wall. However, incisional hernia remains the most common complication after median laparotomy, with reported incidences varying between 2-20%. Recent clinical and experimental data showed a continuous suture technique with many small tissue bites in the aponeurosis only, is possibly more effective in the prevention of incisional hernia when compared to the common used large bite technique or mass closure. The STITCH trial is a double-blinded multicenter randomized controlled trial designed to compare a standardized large bite technique with a standardized small bites technique. The main objective is to compare both suture techniques for incidence of incisional hernia after one year. Secondary outcomes will include postoperative complications, direct costs, indirect costs and quality of life. A total of 576 patients will be randomized between a standardized small bites or large bites technique. At least 10 departments of general surgery and two departments of oncological gynaecology will participate in this trial. Both techniques have a standardized amount of stitches per cm wound length and suture length wound length ratio's are calculated in each patient. Follow up will be at 1 month for wound infection and 1 year for incisional hernia. Ultrasound examinations will be performed at both time points to measure the distance between the rectus muscles (at 3 points) and to objectify presence or absence of incisional hernia. Patients, investigators and radiologists will be blinded during follow up, although the surgeon can not be blinded during the surgical procedure. The STITCH trial will provide level 1b evidence to support the preference for either a continuous suture technique with many small tissue bites in the aponeurosis only or for the commonly used large bites technique.","subset":"pubmed_abstract"} +{"meta":{"pmid":24131868,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":4,"2024-18":1,"unknown":2}}},"text":"Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.\nNeural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in the neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown. We ablated ILK specifically in the neural crest using the Wnt1-Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of neural cell adhesion molecule (NCAM) and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis\/innervation were observed in ILK mutant outflow tract that may partly be due to reduced transforming growth factor \u03b22 (TGF\u03b22) but increased bone morphogenetic protein (BMP) signaling. Consistent with these observations, microarray analysis of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis. Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.","subset":"pubmed_abstract"} +{"meta":{"pmid":17604511,"dup_signals":{"dup_doc_count":22,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":19}}},"text":"Sleeping sickness in Uganda: revisiting current and historical distributions.\nSleeping sickness is a parasitic, vector-borne disease, carried by the tsetse fly and prevalent in sub-Saharan Africa. The disease continues to pose a public health burden in Uganda, which experienced a widespread outbreak in 1900-1920, and a more recent outbreak in 1976-1989. The disease continues to spread to uninfected districts. This paper compares the spatial distributions of sleeping in Uganda for the 1900-1920 outbreak period with current disease foci, and discusses information gaps and implications arising for future research, prevention and control. Population census records for 1911 and sleeping sickness records from Medical and Sanitary Reports of the Ugandan Protectorate for 1905-1936 were extracted from the Uganda Archives. Current sleeping sickness distribution data were provided by the Ministry of Health, Uganda. These were used to develop sleeping sickness distribution maps for comparison between the early 1900s and the early 2000s. The distribution of sleeping sickness from 1905-1920 shows notable differences compared to the current distribution of disease. In particular, archival cases were recorded in south-west and central Uganda, areas currently free of disease. The disease focus has moved from lakeshore Buganda (1905-1920) to the Busoga and south-east districts. Archival sleeping sickness distributions indicate the potential for a much wider area of disease risk than indicated by current disease foci. This is compounded by an absence of tsetse distribution data, continued political instability in north-central Uganda, continued spread of disease into new districts, and evidence of the role of livestock movements in spreading the parasite. These results support concerns as to the potential mergence of the two disease foci in the south-east and north-west of the country.","subset":"pubmed_abstract"} +{"meta":{"pmid":8950679,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Loss of heterozygosity in tuberous sclerosis hamartomas.\nWe have previously described in tuberous sclerosis (TSC) hamartomas the phenomenon of loss of heterozygosity (LOH) for DNA markers in the region of both the TSC2 gene on chromosome 16p13.3 and the TSC1 gene on 9q34. We now describe the spectrum of LOH in 51 TSC hamartomas from 34 cases of TSC. DNA was extracted from leucocytes or normal paraffin embedded tissue, and from frozen paraffin embedded hamartoma tissue from the same patient. The samples were analysed for 11 markers spanning the TSC1 locus and nine markers spanning the TSC2 locus. Twenty-one of 51 hamartomas showed LOH (41%). There was significantly more LOH on 16p13.3, with 16 hamartomas showing LOH around TSC2, and five in the vicinity of TSC1. No hamartoma showed LOH for markers around both loci. All the areas of LOH on chromosome 9 were large, but the smallest region of overlap lay between the markers D9S149 and D9S114, providing independent evidence for the localisation of the TSC1 gene. These data show that LOH is a common finding in a wide range of hamartomas, affecting the same TSC locus in different lesions from the same patient but not affecting both loci. These data support the hypothesis that both the TSC genes act as tumour suppressors and that the manifestations of TSC in patients with germline TSC mutations rise from \"second hit\" somatic mutations inactivating the remaining normal copy of the TSC gene.","subset":"pubmed_abstract"} +{"meta":{"pmid":32370964,"dup_signals":{"dup_doc_count":13}},"text":"ACR Appropriateness Criteria\u00ae Acute Trauma to the Foot.\nAcute injuries to the foot are frequently encountered in the emergency room and in general practice settings. This publication defines best practices for imaging evaluations for several variants of patients presenting with acute foot trauma. The variants include scenarios when the Ottawa rules can be evaluated, when there are exclusionary criteria, and when suspected pathology is in anatomic areas not addressed by the Ottawa rules. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND\/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.","subset":"pubmed_abstract"} +{"meta":{"pmid":22294467,"dup_signals":{"dup_doc_count":13}},"text":"Improved dynamic response assessment for intra-articular injected iron oxide nanoparticles.\nThe emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear\/nonproportional intensity to concentration profile due to the competing effects of T\u2081 and T\u2082 relaxation. A concentration calibration phantom and an in vivo study of intra-articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference-ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations.","subset":"pubmed_abstract"} +{"meta":{"pmid":18462574,"dup_signals":{"dup_doc_count":18,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-48":1,"2014-10":1,"unknown":14}}},"text":"The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation.\nTo evaluate three technologies for the management of advanced colorectal cancer: (1) first-line irinotecan combination [with 5-fluorouracil (5-FU)] or second-line monotherapy; (2) first- or second-line oxaliplatin combination (again, with 5-FU); and (3) raltitrexed, where 5-FU is inappropriate. To examine the role of irinotecan and oxaliplatin in reducing the extent of incurable disease before curative surgery (downstaging). Ten electronic bibliographic databases covering the period up to August 2004. Searches identified existing studies of the effectiveness and economics of the technologies and any studies that evaluated any of the indications outlined above were included. Data were extracted and assessed generic components of methodological quality. Survival outcomes were meta-analysed. Seventeen trials were found, of varying methodological quality. Compared with 5-FU, first-line irinotecan improved overall survival (OS) by 2-4 months (p=0.0007), progression-free survival (PFS) by 2-3 months (p<0.00001) and response rates (p<0.001). It offered a different toxicity profile and no quality of life (QoL) advantage. However, second-line irinotecan compared with 5-FU improved OS by 2 months (p=0.035) and PFS by 1 month (p=0.03), and provided a better partial response rate, but with more toxicities and no QoL advantage. Compared with second-line best supportive care, irinotecan improved OS by 2 months (p=0.0001), had a different toxicity profile and maintained baseline QoL longer, but with no overall difference. The addition of oxaliplatin to second-line 5-FU is associated with a borderline significant improvement in overall survival (p<0.07); a significantly higher response rate (<0.0001); and more serious toxicities. There is no evidence for a significant difference in QoL. Schedules with treatment breaks may not reduce clinical effectiveness but reduce toxicity. The addition of oxaliplatin to second-line 5-FU also saw no improvement in OS (p<0.07), better PFS (by 2.1 months, p=0.0001), an 8.9% higher response rate (p<0.0001), more toxicities and no QoL advantage. There was no significant difference in OS or PFS between first-line irinotecan and oxaliplatin combinations except when 5-FU was delivered by bolus injection, when oxaliplatin provided better OS (p=0.032) and response rates (p=0.032), but not PFS (p=0.169). The regimens had different toxicity profiles and neither conferred a QoL advantage. When compared to 5-FU, raltitrexed is associated with no significant difference in overall or progression-free survival; no significant difference in response rates; more vomiting and nausea, but less diarrhoea and mucositis; no significant difference in, or worse QoL. Raltitrexed treatment was cut short in two out of four included trials due to excess toxic deaths. 5-FU followed by irinotecan was inferior to any other sequence. First-line irinotecan\/5-FU combination improved OS and PFS, although further unplanned therapy exaggerated the OS effect size. Staged combination therapy (combination oxaliplatin followed by combination irinotecan or vice versa) provided the best OS and PFS, although there was no head-to-head comparison against other treatment plans. In the only trial to use three active chemotherapies in any staged combination, median OS was over 20 months. In another study, the longest median OS from a treatment plan using two active agents was 16.2 months. Where irinotecan or oxaliplatin were used with 5-FU to downstage people with unresectable liver metastases, studies consistently showed response rates of around 50%. Resection rates ranged from 9 to 35% with irinotecan and from 7 to 51% with oxaliplatin. In the one study that compared the regimens, oxaliplatin enabled more resections (p=0.02). Five-year OS rates of 5-26% and disease-free survival rates of 3-11% were reported in studies using oxaliplatin. Alone or in combination, 5-FU was more effective and less toxic when delivered by continuous infusion. Existing economic models were weak because of the use of unplanned second-line therapies in their trial data: the survival benefits in patients on such trials cannot be uniquely attributed to the allocated therapy. Consequently, the economic analyses are either limited to the use of PES (at best, a surrogate outcome) or are subject to confounding. Weaknesses in cost components, the absence of direct in-trial utility estimates and the limited use of sensitivity analysis were identified. Improvements to the methodologies used in existing economic studies are presented. Using data from two trials that planned treatment sequences, an independent economic evaluation of six plans compared with first-line 5-FU followed on progression by second-line irinotecan monotherapy (NHS standard treatment) is presented. 5-FU followed on progression by irinotecan combination cost 13,174 pounds per life-year gained (LYG) and 10,338 pounds per quality-adjusted life-year (QALY) gained. Irinotecan combination followed on progression by additional second-line therapies was estimated to cost 12,418 pounds per LYG and 13,630 pounds per QALY gained. 5-FU followed on progression by oxaliplatin combination was estimated to cost 23,786 pounds per LYG and 31,556 pounds per QALY gained. Oxaliplatin combination followed on progression by additional second-line therapies was estimated to cost 43,531 pounds per LYG and 67,662 pounds per QALY gained. Evaluations presented in this paragraph should be interpreted with caution owing to missing information on the costs of salvage therapies in the trial from which data were drawn. Irinotecan combination followed on progression by oxaliplatin combination cost 12,761 pounds per LYG and 16,663 pounds per QALY gained. Oxaliplatin combination followed on progression by irinotecan combination cost 16,776 pounds per LYG and 21,845 pounds per QALY gained. The evaluation suggests that these two sequences have a cost-effectiveness profile that is favourable in comparison to other therapies currently funded by the NHS. However, the differences in OS observed between the two trials from which data were taken may be a result of heterogeneous patient populations, unbalanced protocol-driven intensity biases or other differences between underlying health service delivery systems. Treatment with three active therapies appears most clinically effective and cost-effective. NHS routine data could be used to validate downstaging findings and a meta-analysis using individual patient-level data is suggested to validate the optimal treatment sequence.","subset":"pubmed_abstract"} +{"meta":{"pmid":17601083,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2020-24":1,"2019-22":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-09":1,"2017-51":1,"2017-43":1,"2021-04":1}}},"text":"Modernization and medicinal plant knowledge in a Caribbean horticultural village.\nHerbal medicine is the first response to illness in rural Dominica. Every adult knows several \"bush\" medicines, and knowledge varies from person to person. Anthropological convention suggests that modernization generally weakens traditional knowledge. We examine the effects of commercial occupation, consumerism, education, parenthood, age, and gender on the number of medicinal plants freelisted by individuals. All six predictors are associated with bush medical knowledge in bivariate analyses. Contrary to predictions, commercial occupation and consumerism are positively associated with herbal knowledge. Gender, age, occupation, and education are significant predictors in multivariate analysis. Women tend to recall more plants than do men. Education is negatively associated with plants listed; age positively associates with number of species listed. There are significant interactions among commercial occupation, education, age, and parenthood, suggesting that modernization has complex effects on knowledge of traditional medicine in Dominica.","subset":"pubmed_abstract"} +{"meta":{"pmid":24873211,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Embedded correlated wavefunction schemes: theory and applications.\nConspectus Ab initio modeling of matter has become a pillar of chemical research: with ever-increasing computational power, simulations can be used to accurately predict, for example, chemical reaction rates, electronic and mechanical properties of materials, and dynamical properties of liquids. Many competing quantum mechanical methods have been developed over the years that vary in computational cost, accuracy, and scalability: density functional theory (DFT), the workhorse of solid-state electronic structure calculations, features a good compromise between accuracy and speed. However, approximate exchange-correlation functionals limit DFT's ability to treat certain phenomena or states of matter, such as charge-transfer processes or strongly correlated materials. Furthermore, conventional DFT is purely a ground-state theory: electronic excitations are beyond its scope. Excitations in molecules are routinely calculated using time-dependent DFT linear response; however applications to condensed matter are still limited. By contrast, many-electron wavefunction methods aim for a very accurate treatment of electronic exchange and correlation. Unfortunately, the associated computational cost renders treatment of more than a handful of heavy atoms challenging. On the other side of the accuracy spectrum, parametrized approaches like tight-binding can treat millions of atoms. In view of the different (dis-)advantages of each method, the simulation of complex systems seems to force a compromise: one is limited to the most accurate method that can still handle the problem size. For many interesting problems, however, compromise proves insufficient. A possible solution is to break up the system into manageable subsystems that may be treated by different computational methods. The interaction between subsystems may be handled by an embedding formalism. In this Account, we review embedded correlated wavefunction (CW) approaches and some applications. We first discuss our density functional embedding theory, which is formally exact. We show how to determine the embedding potential, which replaces the interaction between subsystems, at the DFT level. CW calculations are performed using a fixed embedding potential, that is, a non-self-consistent embedding scheme. We demonstrate this embedding theory for two challenging electron transfer phenomena: (1) initial oxidation of an aluminum surface and (2) hot-electron-mediated dissociation of hydrogen molecules on a gold surface. In both cases, the interaction between gas molecules and metal surfaces were treated by sophisticated CW techniques, with the remainder of the extended metal surface being treated by DFT. Our embedding approach overcomes the limitations of conventional Kohn-Sham DFT in describing charge transfer, multiconfigurational character, and excited states. From these embedding simulations, we gained important insights into fundamental processes that are crucial aspects of fuel cell catalysis (i.e., O2 reduction at metal surfaces) and plasmon-mediated photocatalysis by metal nanoparticles. Moreover, our findings agree very well with experimental observations, while offering new views into the chemistry. We finally discuss our recently formulated potential-functional embedding theory that provides a seamless, first-principles way to include back-action onto the environment from the embedded region.","subset":"pubmed_abstract"} +{"meta":{"pmid":14972655,"dup_signals":{"dup_doc_count":11}},"text":"Effects of estradiol on immediate early gene expression associated with ovulation in lactating rats: role of nutritional status.\nIn rats, food restriction during lactation extends lactational infertility, an effect that is in part due to attenuated luteinizing hormone (LH) responses to the positive feedback effects of estradiol (E2). In cycling rats, rising endogenous E2 levels not only induce a surge in LH release, but also increase the expression of the immediate early gene Fos in the anteroventral preoptic area (AVPV) and within gonadotropin releasing hormone (GnRH) neurons. This experiment examined whether the induction of Fos expression in the AVPV and within GnRH neurons after E2 treatment varied with stage of lactation and nutritional status. Brains of estrogen-treated ad lib fed and food-restricted lactating rats were processed for Fos or Fos\/GnRH immunocytochemistry on days 15, 20, or 25 postpartum (pp). Cell counts from both labeling studies showed that on day 15 pp, neuronal activation in the AVPV and within GnRH neurons was low and did not differ between ad lib fed and food-restricted dams. On day 20 pp, levels of Fos-like immunoreactivity (FOS-IR) in the AVPV remained low in all dams but were significantly higher in ad lib fed dams. By day 25 pp, the ability of E2 to induce FOS-IR in the AVPV of food-restricted dams remained compromised. The proportion of GnRH cells expressing FOS-IR following E2 stimulation was restored to baseline levels by day 20 pp regardless of the nutritional status of the dam. These results show that the effects of E2 on neuronal events that correlate with the LH surge, are attenuated during lactation. Furthermore, food restriction during lactation selectively alters neuronal activation in the AVPV suggesting that this area integrates nutritional information to regulate LH release.","subset":"pubmed_abstract"} +{"meta":{"pmid":32841919,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-26":2,"2024-30":1,"unknown":13}}},"text":"COVID-19 versus HIT hypercoagulability.\nA striking feature of COVID-19 is the high frequency of thrombosis, particularly in patients who require admission to intensive care unit because of respiratory complications (pneumonia\/adult respiratory distress syndrome). The spectrum of thrombotic events is wide, including in situ pulmonary thrombosis, deep-vein thrombosis and associated pulmonary embolism, as well as arterial thrombotic events (stroke, myocardial infarction, limb artery thrombosis). Unusual thrombotic events have also been reported, e.g., cerebral venous sinus thrombosis, mesenteric artery and vein thrombosis. Several hematology abnormalities have been observed in COVID-19 patients, including lymphopenia, neutrophilia, thrombocytopenia (usually mild), thrombocytosis, elevated prothrombin time and partial thromboplastin times (the latter abnormality often indicating lupus anticoagulant phenomenon), hyperfibrinogenemia, elevated von Willebrand factor levels, and elevated fibrin d-dimer. Many of these abnormal hematologic parameters-even as early as the time of initial hospital admission-indicate adverse prognosis, including greater frequency of progression to severe respiratory illness and death. Progression to overt disseminated intravascular coagulation in fatal COVID-19 has been reported in some studies, but not observed in others. We compare and contrast COVID-19 hypercoagulability, and associated increased risk of venous and arterial thrombosis, from the perspective of heparin-induced thrombocytopenia (HIT), including the dilemma of providing thromboprophylaxis and treatment recommendations when available data are limited to observational studies. The frequent use of heparin-both low-molecular-weight and unfractionated-in preventing and treating COVID-19 thrombosis, means that vigilance for HIT occurrence is required in this patient population.","subset":"pubmed_abstract"} +{"meta":{"pmid":17090304,"dup_signals":{"dup_doc_count":28,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":3,"2015-11":3,"2015-06":4,"2014-10":3,"2013-48":3,"2013-20":4,"unknown":7}}},"text":"BCR and its mutants, the reciprocal t(9;22)-associated ABL\/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility.\nThe reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome--Ph+) the derivative 9+ encodes either the p40(ABL\/BCR) fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL\/BCR) fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL\/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL\/BCR proteins with that of wild-type BCR. We investigated the effects of BCR and ABL\/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1alpha gradient. Here we show that both ABL\/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL\/BCR fusion proteins in comparison to their physiological counterpart BCR.","subset":"pubmed_abstract"} +{"meta":{"pmid":32606494,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Processing and Reporting of Cytology Specimens from Mediastinal Lymph Nodes Collected using Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A State-of-the-Art Review.\nEndobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is presently the preferred modality for sampling mediastinal lymph nodes. There is an unmet need for standardization of processing and reporting of cytology specimens obtained by EBUS-TBNA. The manuscript is a state-of-the-art review on the technical aspects of processing and reporting of EBUS-TBNA specimens. A literature search was conducted using the PubMed database, and the available evidence was discussed among the authors. The evidence suggests that at least one air-dried and one alcohol-fixed slide should be prepared from each lymph node pass. The remaining material should be utilized for microbiological analysis (in saline) and cell block preparation (10% formalin or other solutions). Wherever available, rapid-onsite evaluation should be performed to assess the adequacy of the sample and guide the need for additional material. The lymph node aspirate should also be collected in Roswell Park Memorial Institute solution in cases where lymphoma is under consideration. The use of liquid-based cytology provides good quality specimens that are free from blood and air-drying artifacts and can be used wherever available. Sample adequacy and the diagnostic category should be furnished separately in the cytology report.","subset":"pubmed_abstract"} +{"meta":{"pmid":23083782,"dup_signals":{"dup_doc_count":11}},"text":"Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol.\nThe purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. Electrocardiographic and clinical parameters of 382 LQT1\/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Patients (56% female, 27% symptomatic, heart rate 76 \u00b1 16 beats\/min, QTc 472 \u00b1 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol\/nadolol. Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":9361775,"dup_signals":{"dup_doc_count":27,"dup_dump_count":25,"dup_details":{"curated_sources":2,"2022-21":1,"2021-49":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-16":1,"2020-05":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2023-50":1,"2024-22":1,"2024-18":1,"2024-30":1}}},"text":"Fetal and perinatal influence of xenoestrogens on testis gene expression.\nThe incidence of reproductive abnormalities in the male has been reported to have increased during the past 50 years. It has been suggested that these changes may be attributable to the presence of chemicals with oestrogenic activity in our environment. The aim of the experiments described in this chapter was to investigate the effects of acute exposure to high levels of xenoestrogens either indirectly during fetal life, or directly during neonatal life, on gene expression in the testis and pituitary. Fetal treatment involved administration of diethylstilbestrol (DES), 4-octylphenol (OP) or vehicle (oil, control) to pregnant rats on days 11.5 and 15.5 post coitum; fetuses were recovered on day 17.5. There was no difference between fetuses from control and treated mothers in either the overall histology of the testes or numbers of Leydig cells as determined by immunohistochemistry with an antibody directed against 3 beta-HSD. However there was a consistent and striking reduction in the amount of P450 17-a hydroxylase C17, 20 lyase (P450c17) and steroidogenic factor 1 (SF-1) detected by immunocytochemistry in testes from treatment groups given the higher doses of OP and DES. Oestrogen receptors (ER alpha) were present in the fetal leydig cells of all animals. Neonatal treatment involved direct injection of oil (control), DES, OP or Bisphenol A (Bis A) on days 2, 4, 6, 8, 10 and 12; pituitaries and testes were recovered on day 18. Testis weights and seminiferous tubule diameters were significantly reduced in animals treated with DES. In these same animals immunocytochemical localisation revealed that the amounts of FSH beta subunit and inhibin alpha subunit were reduced in their pituitaries and testes respectively. OP did not appear to have an acute, measurable effect on testis gene expression but a reduction in testis weight was noted in adult animals given the same treatment regime. The effects observed are consistent with negative feedback by oestrogens on pituitary production of FSH resulting in retarded maturation of seminiferous tubules and reduced Sertoli cell numbers. These studies have demonstrated that administration of high levels of oestrogens can affect gene expression in the testis early in life. However, the relevance of these findings to observations in man await a) a greater understanding of the physiological role(s) of oestrogens in normal males, b) an evaluation of the sources, routes of exposure, concentrations in vivo and bioavailability of xenoestrogens.","subset":"pubmed_abstract"} +{"meta":{"pmid":2480100,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The wound is a possible source of posttraumatic immunosuppression.\nWound fluid from 10-day-old healing wounds in rats inhibits lymphocyte immune responses. Since severe injury is frequently complicated by immunosuppression as manifested by sepsis, we hypothesized that the wound may be a source of factors that impair host immune responses. Therefore, we studied the effect of systemic wound fluid administration on the survival of rats subjected to an acute peritonitis model. Male Sprague-Dawley rats, fitted with internal jugular catheters 48 hours previously, underwent cecal ligation and puncture with a 23-gauge needle. Immediately after the operation, rats were treated intravenously every 12 hours with either wound fluid obtained from 10-day-old healing wounds and adjusted to 10 mg of protein per milliliter or rat serum. In vitro testing of the wound fluid showed it to be highly inhibitory of thymic lymphocyte mitogenesis. Rats treated with wound fluid had significantly higher mortality after peritonitis than did control rats. The data show that the wound contains factors that can impair host immune responses to sepsis. This suggests that the wound may be the source of posttraumatic host immunosuppression.","subset":"pubmed_abstract"} +{"meta":{"pmid":15544372,"dup_signals":{"dup_doc_count":25,"dup_dump_count":14,"dup_details":{"curated_sources":4,"2020-24":2,"2020-16":2,"2020-10":2,"2019-47":2,"2019-43":2,"2019-39":2,"2019-35":2,"2019-18":1,"2018-47":1,"2018-26":1,"2018-05":1,"2017-51":1,"2017-34":1,"2016-44":1}}},"text":"Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane: a surface force study.\nThe purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 A (30 A per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to a specific recognition between the hydrophobic adamantane groups on the PEO-Ad polymer and the hydrophobic cavity in the beta-cyclodextrin molecules. Furthermore, the attractive force observed on separation has increased significantly, which is a further indication of a specific interaction between the beta-cyclodextrin polymer and the adamantane groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":21330947,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Burn and smoke injury activates poly(ADP-ribose)polymerase in circulating leukocytes.\nThe nuclear enzyme poly(ADP-ribose)polymerase (PARP) plays a significant role in the pathogenesis of various forms of critical illness. DNA strand breaks induced by oxidative and nitrative stress trigger the activation of PARP, and PARP, in turn, mediates cell death and promotes proinflammatory responses. Until recently, most studies focused on the role of PARP in solid organs such as heart, liver, and kidney. We investigated the effect of burn and smoke inhalation on the levels of poly(ADP-ribosylated) proteins in circulating sheep leukocytes ex vivo. Adult female merino sheep were subjected to burn injury (2\u00d7 20% each flank, 3 degrees) and smoke inhalation injury (insufflated with a total of 48 breaths of cotton smoke) under deep anesthesia. Arterial and venous blood was collected at baseline, immediately after the injury and 1 to 24 h after the injury. Leukocytes were isolated with the Histopaque method. The levels of poly(ADP-ribosyl)ated proteins were determined by Western blotting. The amount of reactive oxygen species was quantified by the OxyBlot method. To examine whether PARP activation continues to increase ex vivo in the leukocytes, blood samples were incubated at room temperature or at 37\u00b0C for 3 h with or without the PARP inhibitor PJ34. To investigate whether the plasma of burn\/smoke animals may trigger PARP activation, burn\/smoke plasma was incubated with control leukocytes in vitro. The results show that burn and smoke injury induced a marked PARP activation in circulating leukocytes. The activity was the highest immediately after injury and at 1 h and decreased gradually over time. Incubation of whole blood at 37\u00b0C for 3 h significantly increased poly(ADP-ribose) levels, indicative of the presence of an ongoing cell activation process. In conclusion, PARP activity is elevated in leukocytes after burn and smoke inhalation injury, and the response parallels the time course of reactive oxygen species generation in these cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":21990275,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder.\nThe designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2\u00bd years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I.","subset":"pubmed_abstract"} +{"meta":{"pmid":17671637,"dup_signals":{"dup_doc_count":16,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2024-26":1,"unknown":12}}},"text":"Treatment for chronic myelogenous leukemia: the long road to imatinib.\nThe scientists of today have become accustomed to the extremely rapid pace of progress in the biomedical sciences spurred on by the discovery of recombinant DNA and the advent of automated DNA sequencing and PCR, with progress usually being measured in months or years at most. What is often forgotten, however, are the many prior advances that were needed to reach our present state of knowledge. Here I illustrate this by discussing the scientific discoveries made over the course of the past century and a half that ultimately led to the recent successful development of drugs, particularly imatinib mesylate, to treat chronic myelogenous leukemia.","subset":"pubmed_abstract"} +{"meta":{"pmid":25896576,"dup_signals":{"dup_doc_count":13,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2018-26":1,"2018-09":2,"2017-47":2,"2017-39":2,"2017-30":2,"2017-22":1,"2017-17":1,"2018-30":1}}},"text":"Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.\nThe present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia\/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus\/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.","subset":"pubmed_abstract"} +{"meta":{"pmid":15148168,"dup_signals":{"dup_doc_count":20,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":14}}},"text":"An animal model for cochlear implants.\nTo test the feasibility of using the deaf white cat model of early-onset deafness. We studied the neuronal effects of prosthetic intervention with a clinical, \"off-the-shelf\" multichannel cochlear implant. We placed cochlear implants in 5 deaf white kittens at age 12 and 24 weeks. The devices were activated and stimulated in the laboratory using a clinical speech processor programmed with a high-resolution continuous interleaved sampling (CIS) strategy for 8 to 24 weeks. Stimulus parameters were guided by electrically evoked brainstem responses and intracochlear-evoked potentials. Kittens were assessed with respect to their tolerance and general behavior in response to speech, music, and environmental sounds. Surgical complications were minimal, and kittens tolerated the experimental procedures well. Subjects were able to detect and respond to a specific sound played from a computer speaker. Electrophysiologic responses were reliably attainable and showed consistency with observed behavioral responses to sound. This experimental paradigm, using clinical devices, can be used in a practical research setting in cats. Deafness and other variations in neural activity result in many distinct changes to the central auditory pathways. Animal models will facilitate assessment of the reversibility of deafness-associated changes at the level of the neuron and its connections. Our observations of the feasibility of using clinical devices in animal models will enable us to simulate clinical conditions in addressing questions about the effects of \"replacement\" activity on the structure and function within the central auditory pathways in deafness.","subset":"pubmed_abstract"} +{"meta":{"pmid":21504619,"dup_signals":{"dup_doc_count":21,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-18":3,"2015-11":3,"2015-06":2,"2014-10":3,"2013-48":3,"2013-20":3,"unknown":3}}},"text":"Poor nutritional status of schoolchildren in urban and peri-urban areas of Ouagadougou (Burkina Faso).\nMalnutrition is still highly prevalent in developing countries. Schoolchildren may also be at high nutritional risk, not only under-five children. However, their nutritional status is poorly documented, particularly in urban areas. The paucity of information hinders the development of relevant nutrition programs for schoolchildren. The aim of this study carried out in Ouagadougou was to assess the nutritional status of schoolchildren attending public and private schools. The study was carried out to provide baseline data for the implementation and evaluation of the Nutrition Friendly School Initiative of WHO. Six intervention schools and six matched control schools were selected and a sample of 649 schoolchildren (48% boys) aged 7-14 years old from 8 public and 4 private schools were studied. Anthropometric and haemoglobin measurements, along with thyroid palpation, were performed. Serum retinol was measured in a random sub-sample of children (N = 173). WHO criteria were used to assess nutritional status. Chi square and independent t-test were used for proportions and mean comparisons between groups. Mean age of the children (48% boys) was 11.5 \u00b1 1.2 years. Micronutrient malnutrition was highly prevalent, with 38.7% low serum retinol and 40.4% anaemia. The prevalence of stunting was 8.8% and that of thinness, 13.7%. The prevalence of anaemia (p = 0.001) and vitamin A deficiency (p < 0.001) was significantly higher in public than private schools. Goitre was not detected. Overweight\/obesity was low (2.3%) and affected significantly more children in private schools (p = 0.009) and younger children (7-9 y) (p < 0.05). Thinness and stunting were significantly higher in peri-urban compared to urban schools (p < 0.05 and p = 0.004 respectively). Almost 15% of the children presented at least two nutritional deficiencies. This study shows that malnutrition and micronutrient deficiencies are also widely prevalent in schoolchildren in cities, and it underlines the need for nutrition interventions to target them.","subset":"pubmed_abstract"} +{"meta":{"pmid":9701266,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Successful renal transplantation in American Indians.\nThe incidence of end-stage renal disease is rapidly growing among American Indians, but there have been no detailed reports of outcomes after renal transplantation in this population. We compared the effects of race on risks and outcomes for renal transplants performed at a single center. There were 68 transplants in American Indians, 55 in African-Americans, 32 in Asians, 33 in other races, and 1253 in Caucasians (total = 1441 transplants). American Indian transplant recipients had a high prevalence of risk factors. American Indians were more likely to be diabetic (45.6%) compared with African-Americans (21.8%), Asians (9.4%), other races (15.2%), and Caucasians (25.9%); overall P<0.001. American Indian transplant recipients were more likely to be obese (25.0% had body mass index >30 kg\/m2) compared with African-Americans (12.7%), Asians (3.1%), other races (6.1%), and Caucasians (9.7%); overall P<0.01. The percent of patients with peak panel-reactive antibody >50% was higher for American Indian recipients (32.4%) compared with African-Americans (16.4%), Asians (21.9%), other races (27.3%) and Caucasians (15.6%); P<0.01. Despite these differences in risk, there were no statistically significant differences in the incidence of acute rejection, patient survival, or graft survival between American Indians and other racial groups in univariate survival analysis. In a Cox proportional hazards model that adjusted for multiple risk factors, graft survival was not different for American Indians (P=0.71), African-Americans (P=0.60), or other races (P=0.34) compared with Caucasians, whereas Asians were only 44% as likely to have graft failure (P=0.07). Patient survival was not different among races. Outcomes for renal transplantation are excellent for American Indians, despite a high prevalence of risk factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":12714738,"dup_signals":{"dup_doc_count":11}},"text":"Micellar nanocontainers distribute to defined cytoplasmic organelles.\nBlock copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. An understanding of their cellular distribution is essential to achieving selective delivery of drugs at the subcellular level. Triple-labeling confocal microscopy in live cells revealed the localization of micelles in several cytoplasmic organelles, including mitochondria, but not in the nucleus. Moreover, micelles change the cellular distribution of and increase the amount of the agent delivered to the cells. These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets.","subset":"pubmed_abstract"} +{"meta":{"pmid":24800688,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"Electroconvulsive therapy, hypertensive surge, blood-brain barrier breach, and amnesia: exploring the evidence for a connection.\nPreclinical and clinical evidence show that electroconvulsive therapy (ECT)-induced intraictal surge in blood pressure may result in a small, transient breach in the blood-brain barrier, leading to mild cerebral edema and a possible leach of noxious substances from blood into brain tissues. These changes may impair neuronal functioning and contribute to the mechanisms underlying ECT-induced cognitive deficits. Some but not all clinical data on the subject suggest that blood pressure changes during ECT correlate with indices of cognitive impairment. In animal models, pharmacological manipulations of blood pressure during electroconvulsive shocks attenuate electroconvulsive shock-induced amnestic changes; however, the evidence suggests that antihypertensive mechanisms may not necessarily be involved. Clinical studies involving pre-ECT administration of antihypertensive medications do not provide convincing evidence of benefits. It is concluded that there is insufficient support, at present, for the hypothesis that the hypertensive surge during ECT and the resultant blood-brain barrier breach contribute meaningfully to ECT-induced cognitive deficits. Future research should address the subset of patients who experience pronounced hypertensive changes during ECT, and clinically relevant outcome measures, such as autobiographical memory impairment, should be examined.","subset":"pubmed_abstract"} +{"meta":{"pmid":22328496,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Snakeskin, a membrane protein associated with smooth septate junctions, is required for intestinal barrier function in Drosophila.\nSeptate junctions (SJs) are the membrane specializations observed between epithelial cells in invertebrates. SJs play a crucial role in epithelial barrier function by restricting the free diffusion of solutes through the intercellular space. In arthropod species, two morphologically different types of SJs have been described: pleated septate junctions (pSJs) and smooth septate junctions (sSJs), which are specific to ectodermal and endodermal epithelia, respectively. In contrast to the recent identification of pSJ-related proteins, the molecular constituents of sSJs are mostly unknown. Here, we report the discovery of a new sSJ-specific membrane protein, designated 'Snakeskin' (Ssk). Ssk is highly concentrated in sSJs in the Drosophila midgut and Malpighian tubules. Lack of Ssk expression is embryonically lethal in Drosophila and results in defective sSJ formation accompanied by abnormal morphology of midgut epithelial cells. We also show that the barrier function of the midgut to a fluorescent tracer is impaired in ssk-knockdown larvae. These results suggest that Ssk is required for the intestinal barrier function in Drosophila.","subset":"pubmed_abstract"} +{"meta":{"pmid":11080823,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"In vitro and in vivo functional analysis of human T cell lymphotropic virus type 1 pX open reading frames I and II.\nHuman T lymphotropic virus type 1 (HTLV-1) is a complex retrovirus containing regulatory and accessory genes encoded in four open reading frames (ORF I-IV) of the pX region. It is not clear what role pX ORFs I and II-encoded proteins have in the pathogenesis of the lymphoproliferative diseases associated with HTLV-1 infection. The conserved ORF I encodes for a hydrophobic 12-kDa protein, p12, (I) that contains four SH3 binding motifs (PXXP) that localizes to cellular endomembranes when overexpressed in cultured cells. Differential splicing of pX ORF II results in the production of two nuclear proteins, p13(II) and p30(II). p13(II) also localizes to mitochondria. p30(II) shares homology with the POU family of transcription factors. We have identified functional roles of pX ORF I and ORF II in establishment and maintenance of infection in a rabbit model. To functionally study p12(I) we have tested a proviral clone with selective ablation of ORF I (ACH.p12(I)) for its ability to infect quiescent peripheral blood mononuclear cells (PBMC). Our data indicate that T cells infected with the wild-type clone of HTLV-1 (ACH) are more efficient than ACH.p12(I) in infecting quiescent PBMC. These findings parallel our animal model data and suggest a role for p12(I) in the activation of quiescent lymphocytes, a prerequisite for effective viral replication in vivo. To test the ability of p30(II) to function as a transcription factor we have constructed p30(II) as a Gal4-fusion protein. When transfected with Gal4-driven luciferase reporter genes, the p30(II)-Gal4-fusion protein induces transcriptional activity up to 50-fold in both 293 and HeLa-Tat cells. These systems will be useful to identify molecular mechanisms that explain the functional role of pX ORF I and ORF II-encoded proteins in HTLV-1 replication.","subset":"pubmed_abstract"} +{"meta":{"pmid":26832787,"dup_signals":{"dup_doc_count":15}},"text":"Evaluation of synthetic coumarins for antiausterity cytotoxicity against pancreatic cancers.\nA series of functionalized coumarins were synthesized and evaluated for their capacity to inhibit the resistance to starvation of pancreatic cancer cells. This form of cytotoxicity, termed 'antiausterity' activity, was evaluated using a preferential cytotoxicity assay that compared cell survival in nutrient poor and nutrient rich conditions. Six of the seventeen compounds showed weak antiausterity activity against PANC-1. Compound 34 was active against PANC-1, MIA PaCa-2, and Capan-1 cancer cell lines. All of the compounds tested were simplified structural analogs of previously reported natural product leads. Six of the compounds, including 34, contain functionalized triazoles as novel potential bioisosteres of the side chain of the natural product angelmarin. Overall, the analogs were found to have low antiausterity activity relative to the corresponding natural products.","subset":"pubmed_abstract"} +{"meta":{"pmid":28680674,"dup_signals":{"dup_doc_count":14,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":10}}},"text":"Palaeoecological implications of the preservation potential of soft-bodied organisms in sediment-density flows: testing turbulent waters.\nInterpreting how far organisms within fossil assemblages may have been transported and if they all originated from the same location is fundamental to understanding whether they represent true palaeocommunities. In a three-factorial experimental design, we used an annular flume to generate actualistic sandy sediment-density flows that were fast (2 ms-1) and fully turbulent in order to test the effects of flow duration, sediment concentration, and grain angularity on the states of bodily damage experienced by the freshly euthanized polychaete Alitta virens. Results identified statistically significant effects of flow duration and grain angularity. Increasing sediment concentration had a statistically significant effect with angular sediment but not with rounded sediment. Our experiments demonstrate that if soft-bodied organisms such as polychaetes were alive and then killed by a flow then they would have been capable of enduring prolonged transport in fast and turbulent flows with little damage. Dependent upon sediment concentration and grain angularity, specimens were capable of remaining intact over flow durations of between 5 and 180 min, equating to transport distances up to 21.6 km. This result has significant palaeoecological implications for fossil lagerst\u00e4tten preserved in deposits of sediment-density flows because the organisms present may have been transported over substantial distances and therefore may not represent true palaeocommunities.","subset":"pubmed_abstract"} +{"meta":{"pmid":24882163,"dup_signals":{"dup_doc_count":13}},"text":"Stress enhances reconsolidation of declarative memory.\nRetrieval of negative emotional memories is often accompanied by the experience of stress. Upon retrieval, a memory trace can temporarily return into a labile state, where it is vulnerable to change. An unresolved question is whether post-retrieval stress may affect the strength of declarative memory in humans by modulating the reconsolidation process. Here, we tested in two experiments whether post-reactivation stress may affect the strength of declarative memory in humans. In both experiments, participants were instructed to learn neutral, positive and negative words. Approximately 24h later, participants received a reminder of the word list followed by exposure to the social evaluative cold pressor task (reactivation\/stress group, nexp1=20; nexp2=18) or control task (reactivation\/no-stress group, nexp1=23; nexp2=18). An additional control group was solely exposed to the stress task, without memory reactivation (no-reactivation\/stress group, nexp1=23; nexp2=21). The next day, memory performance was tested using a free recall and a recognition task. In the first experiment we showed that participants in the reactivation\/stress group recalled more words than participants in the reactivation\/no-stress and no-reactivation\/stress group, irrespective of valence of the word stimuli. Furthermore, participants in the reactivation\/stress group made more false recognition errors. In the second experiment we replicated our observations on the free recall task for a new set of word stimuli, but we did not find any differences in false recognition. The current findings indicate that post-reactivation stress can improve declarative memory performance by modulating the process of reconsolidation. This finding contributes to our understanding why some memories are more persistent than others.","subset":"pubmed_abstract"} +{"meta":{"pmid":28639634,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":3,"2022-05":2,"2021-49":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":2}}},"text":"Copper(ii) catalyzed iodine-promoted oxidative cyclization of 2-amino-1,3,5-triazines and chalcones: synthesis of aroylimidazo[1,2-a][1,3,5]triazines.\nAn efficient copper(ii) catalyzed iodine-promoted synthesis of aroylimidazo[1,2-a][1,3,5]triazines from 2-amino-1,3,5-triazines and chalcones under mild conditions has been developed. The reaction occurred with good yields and excellent regioselectivities, and tolerated chalcone containing functionalities such as ethers, halogens, and nitro groups. The successful application of this methodology for a gram-scale reaction indicates its potential for bulk synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":15811984,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Association between compensation status and outcome after surgery: a meta-analysis.\nCompensation, whether through workers' compensation or through litigation, has been associated with poor outcome after surgery; however, this association has not been examined by meta-analysis. To investigate the association between compensation status and outcome after surgery. We searched MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL, the Cochrane Controlled Trials Register, and reference lists of retrieved articles and textbooks, and we contacted experts in the field. The review included any trial of surgical intervention in which compensation status was reported and results were compared according to that status. No restrictions were placed on study design, language, or publication date. Studies were selected by 2 unblinded independent reviewers. Two reviewers independently extracted data on study type, study quality, surgical procedure, outcome, country of origin, length and completeness of follow-up, and compensation type. Two hundred eleven studies satisfied the inclusion criteria. Of these, 175 stated that the presence of compensation (workers' compensation with or without litigation) was associated with a worse outcome, 35 found no difference or did not describe a difference, and 1 described a benefit associated with compensation. A meta-analysis of 129 studies with available data (n = 20,498 patients) revealed the summary odds ratio for an unsatisfactory outcome in compensated patients to be 3.79 (95% confidence interval, 3.28-4.37 by random-effects model). Grouping studies by country, procedure, length of follow-up, completeness of follow-up, study type, and type of compensation showed the association to be consistent for all subgroups. Compensation status is associated with poor outcome after surgery. This effect is significant, clinically important, and consistent. Because data were obtained from observational studies and were not homogeneous, the summary effect should be interpreted with caution. Compensation status should be considered a potential confounder in all studies of surgical intervention. Determination of the mechanism for this association requires further study.","subset":"pubmed_abstract"} +{"meta":{"pmid":19697129,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":11}}},"text":"Clinical and histological features of nonalcoholic fatty liver disease in children.\nNonalcoholic fatty liver disease (NAFLD) is becoming more frequently diagnosed as the prevalence of obesity in children increases rapidly. The aim of this study was to investigate the correlation of clinical findings with histopathologic features in children with NAFLD. We reviewed the clinical data and liver histology results of children with biopsy-proven NAFLD at Seoul National University Hospital. NAFLD was classified as simple steatosis, type 1 nonalcoholic steatohepatitis (NASH), characterized by ballooning degeneration and perisinusoidal fibrosis, or type 2 NASH, characterized by portal inflammation and portal fibrosis. Among 80 total patients, 84% were male. All patients were obese or overweight. Insulin resistance was present in 96% of children. Perisinusoidal fibrosis was noted in 45% of children and portal fibrosis was noted in 77%. Simple steatosis was present in 22% of children, type 1 NASH in 34%, and type 2 NASH in 44%. No differences were found among NAFLD subtypes or NAFLD activity score with regard to sex, blood pressure, or levels of aminotransferase, fasting lipid, or insulin. Children with NASH were older and had higher body mass index than those with simple steatosis. Patients with type 2 NASH had higher body mass index and advanced fibrosis compared with patients with type 1 NASH. Obesity and older age are associated with development of NASH. Type 2 NASH is the most common form and associated with a greater severity of obesity and advanced fibrosis.","subset":"pubmed_abstract"} +{"meta":{"pmid":35025000,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"A critical review on microbial degradation of petroleum-based plastics: quantitatively effects of chemical addition in cultivation media on biodegradation efficiency.\nPetroleum-based plastics (PBP) with different properties have been developed to suit various needs of modern lives. Nevertheless, these well-developed properties also present the double-edged sword effect that significantly threatens the sustainability of the environment. This work focuses on the impact of microbial cultivating conditions (the elementary compositions and temperature) to provide insightful information for the process optimization of microbial degradation. The major elementary compositions in cultivation media and temperature from the literature were radically reviewed and assessed using the constructed supervised machine learning algorithm. Fifty-two literatures were collected as a training dataset to investigate the impact of major chemical elements and cultivation temperature upon PBP biodegradation. Among six singular parameters (NH4+, K+, PO43-, Mg2+, Ca2+, and temperature) and thirty corresponding binary parameters, four singular (NH4+, K+, PO43-, and Mg2+) and six binary parameters (NH4+\/K+, NH4+\/PO43-, NH4+\/Ca2+, K+\/PO43-, PO43-\/Mg2+, Mg2+\/Temp) were identified as statistically significant towards microbial degradation through analysis of variance (ANOVA). The binary effect (PO43-\/Mg2+) is found to be the most statistically significant towards the microbial degradation of PBP. The concentration range, which locates at 0.1-0.6 g\/L for Mg2+ and 0-2.8 g\/L for PO43-, was identified to contribute to the maximum PBP biodegradation. Among all the investigated elements, Mg2+ is the only element that is statistically and significantly associated with the variations of cultivation temperature. The optimal preparation conditions within \u00b1 20% uncertainties based upon the range of collected literature reports are recommended. Five representative cultivation elementary compositions (NH4+, K+, PO43-, Mg2+, and Ca2+) and temperature were reviewed from fifty two different literature reports to investigate their impacts on the microbial degradation of PBP using supervised machine learning algorithm. The optimal cultivation conditions based upon collected literature reports to achieve biodegradation over 80% were identified.","subset":"pubmed_abstract"} +{"meta":{"pmid":29480919,"dup_signals":{"dup_doc_count":23,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":20}}},"text":"Increasing Self-Awareness of Medical Students Through the Use of Ultrasonography.\nSelf-awareness is vital for the health and development of medical students, but few reported modalities successfully increase medical student self-awareness. To assess the effect of ultrasonography on medical student self-awareness and health status. In 2016, first- and second-year osteopathic medical students completed a 9-item survey, created specifically for the current study, which included questions about the use of ultrasonography, health status, and self-awareness after completing at least 1 ultrasonography course. Differences between student responses by class were analyzed using \u03c72 analysis for items assessing experience with ultrasonography and t tests for items assessing self-awareness. Of the 329 students surveyed, 192 (58.4%) reported using ultrasonography to explore or monitor their own health or body. Forty-nine students (14.9%) found out something about their health that they did not know before their exposure to ultrasonography. Significant differences were found in the use of ultrasonography between first-year and second-year students; more second-year students reported using ultrasonography outside of laboratory hours (P<.05) and discovering incidental findings (P<.05). The largest portions of students reported average health status for exercise (106 of 325 [32.6%]), stress management (174 of 324 [53.7%]), and sleep (137 of 326 [42.0%]). The largest portions of students reported very good health status for tobacco use (282 of 322 [87.6%]), alcohol use (138 of 323 [42.7%]), and healthy relationships (118 of 326 [36.2%]). Statistically significant differences existed in responses between first- and second-year students regarding exercise (P=.007) and alcohol use (P=.001). The majority of students agreed or strongly agreed (182 of 326 [55.8%]) that access to ultrasonography equipment and ultrasonography training during the first and second years of medical school increased their self-awareness. The results suggest that the incorporation of ultrasonography into medical education could potentially increase medical student health status and self-awareness.","subset":"pubmed_abstract"} +{"meta":{"pmid":24363805,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":12}}},"text":"Coral growth and bioerosion of Porites lutea in response to large amplitude internal waves.\nThe Similan Islands (Thailand) in the Andaman Sea are exposed to large amplitude internal waves (LAIW), as evidenced by i.a. abrupt fluctuations in temperature of up to 10\u00b0C at supertidal frequencies. Although LAIW have been shown to affect coral composition and framework development in shallow waters, the role of LAIW on coral growth is so far unknown. We carried out a long-term transplant experiment with live nubbins and skeleton slabs of the dominating coral Porites lutea to assess the net growth and bioerosion in LAIW-exposed and LAIW-protected waters. Depth-related, seasonal and interannual differences in LAIW-intensities on the exposed western sides of the islands allowed us to separate the effect of LAIW from other possible factors (e.g. monsoon) affecting the corals. Coral growth and bioerosion were inversely related to LAIW intensity, and positively related to coral framework development. Accretion rates of calcareous fouling organisms on the slabs were negligible compared to bioerosion, reflecting the lack of a true carbonate framework on the exposed W faces of the Similan Islands. Our findings show that LAIW may play an important, yet so far overlooked, role in controlling coral growth in tropical waters.","subset":"pubmed_abstract"} +{"meta":{"pmid":21214892,"dup_signals":{"dup_doc_count":28,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":3,"2024-26":2,"2024-18":1,"unknown":21}}},"text":"Changes in health workers' malaria diagnosis and treatment practices in Kenya.\nChange of Kenyan treatment policy for uncomplicated malaria from sulphadoxine-pyrimethamine to artemether-lumefantrine (AL) was accompanied by revised recommendations promoting presumptive malaria diagnosis in young children and, wherever possible, parasitological diagnosis and adherence to test results in older children and adults. Three years after the policy implementation, health workers' adherence to malaria diagnosis and treatment recommendations was evaluated. A national cross-sectional, cluster sample survey was undertaken at public health facilities. Data were collected using quality-of-care assessment methods. Analysis was restricted to facilities with AL in stock. Main outcomes were diagnosis and treatment practices for febrile outpatients stratified by age, availability of diagnostics, use of malaria diagnostic tests, and test result. The analysis included 1,096 febrile patients (567 aged <5 years and 529 aged \u22655 years) at 88 facilities with malaria diagnostics, and 880 febrile patients (407 aged <5 years and 473 aged \u22655 years) at 71 facilities without malaria diagnostic capacity. At all facilities, 19.8% of young children and 28.7% of patients aged \u22655 years were tested, while at facilities with diagnostics, 33.5% and 53.7% were respectively tested in each age group. Overall, AL was prescribed for 63.6% of children aged <5 years and for 65.0% of patients aged \u22655 years, while amodiaquine or sulphadoxine-pyrimethamine monotherapies were prescribed for only 2.0% of children and 3.9% of older children and adults. In children aged <5 years, AL was prescribed for 74.7% of test positive, 40.4% of test negative and 60.7% of patients without test performed. In patients aged \u22655 years, AL was prescribed for 86.7% of test positive, 32.8% of test negative and 58.0% of patients without test performed. At least one anti-malarial treatment was prescribed for 56.6% of children and 50.4% of patients aged \u22655 years with a negative test result. Overall, malaria testing rates were low and, despite different age-specific recommendations, only moderate differences in testing rates between the two age groups were observed at facilities with available diagnostics. In both age groups, AL use prevailed, and prior ineffective anti-malarial treatments were nearly non-existent. The large majority of test positive patients were treated with recommended AL; however, anti-malarial treatments for test negative patients were widespread, with AL being the dominant choice. Recent change of diagnostic policy to universal testing in Kenya is an opportunity to improve upon the quality of malaria case management. This will be, however, dependent upon the delivery of a comprehensive case management package including large scale deployment of diagnostics, good quality of training, post-training follow-up, structured supervisory visits, and more intense monitoring.","subset":"pubmed_abstract"} +{"meta":{"pmid":21849545,"dup_signals":{"dup_doc_count":27,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2017-13":1,"2024-26":1,"unknown":22}}},"text":"Determination of transmembrane water fluxes in neurons elicited by glutamate ionotropic receptors and by the cotransporters KCC2 and NKCC1: a digital holographic microscopy study.\nDigital holographic microscopy (DHM) is a noninvasive optical imaging technique that provides quantitative phase images of living cells. In a recent study, we showed that the quantitative monitoring of the phase signal by DHM was a simple label-free method to study the effects of glutamate on neuronal optical responses (Pavillon et al., 2010). Here, we refine these observations and show that glutamate produces the following three distinct optical responses in mouse primary cortical neurons in culture, predominantly mediated by NMDA receptors: biphasic, reversible decrease (RD) and irreversible decrease (ID) responses. The shape and amplitude of the optical signal were not associated with a particular cellular phenotype but reflected the physiopathological status of neurons linked to the degree of NMDA activity. Thus, the biphasic, RD, and ID responses indicated, respectively, a low-level, a high-level, and an \"excitotoxic\" level of NMDA activation. Moreover, furosemide and bumetanide, two inhibitors of sodium-coupled and\/or potassium-coupled chloride movement strongly modified the phase shift, suggesting an involvement of two neuronal cotransporters, NKCC1 (Na-K-Cl) and KCC2 (K-Cl) in the genesis of the optical signal. This observation is of particular interest since it shows that DHM is the first imaging technique able to monitor dynamically and in situ the activity of these cotransporters during physiological and\/or pathological neuronal conditions.","subset":"pubmed_abstract"} +{"meta":{"pmid":30460204,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":16}}},"text":"pYR4 From a Norwegian Isolate of Yersinia ruckeri Is a Putative Virulence Plasmid Encoding Both a Type IV Pilus and a Type IV Secretion System.\nEnteric redmouth disease caused by the pathogen Yersinia ruckeri is a significant problem for fish farming around the world. Despite its importance, only a few virulence factors of Y. ruckeri have been identified and studied in detail. Here, we report and analyze the complete DNA sequence of pYR4, a plasmid from a highly pathogenic Norwegian Y. ruckeri isolate, sequenced using PacBio SMRT technology. Like the well-known pYV plasmid of human pathogenic Yersiniae, pYR4 is a member of the IncFII family. Thirty-one percent of the pYR4 sequence is unique compared to other Y. ruckeri plasmids. The unique regions contain, among others genes, a large number of mobile genetic elements and two partitioning systems. The G+C content of pYR4 is higher than that of the Y. ruckeri NVH_3758 genome, indicating its relatively recent horizontal acquisition. pYR4, as well as the related plasmid pYR3, comprises operons that encode for type IV pili and for a conjugation system (tra). In contrast to other Yersinia plasmids, pYR4 cannot be cured at elevated temperatures. Our study highlights the power of PacBio sequencing technology for identifying mis-assembled segments of genomic sequences. Comparative analysis of pYR4 and other Y. ruckeri plasmids and genomes, which were sequenced by second and the third generation sequencing technologies, showed errors in second generation sequencing assemblies. Specifically, in the Y. ruckeri 150 and Y. ruckeri ATCC29473 genome assemblies, we mapped the entire pYR3 plasmid sequence. Placing plasmid sequences on the chromosome can result in erroneous biological conclusions. Thus, PacBio sequencing or similar long-read methods should always be preferred for de novo genome sequencing. As the tra operons of pYR3, although misplaced on the chromosome during the genome assembly process, were demonstrated to have an effect on virulence, and type IV pili are virulence factors in many bacteria, we suggest that pYR4 directly contributes to Y. ruckeri virulence.","subset":"pubmed_abstract"} +{"meta":{"pmid":24011419,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":12}}},"text":"Elution strategies for reversed-phase high-performance liquid chromatography analysis of sucrose alkanoate regioisomers with charged aerosol detection.\nA broad range of elution strategies for RP-HPLC analysis of sucrose alkanoate regioisomers with CAD was systematically evaluated. The HPLC analyses were investigated using design-of-experiments methodology and analysed by analysis of variance (ANOVA) and regression modelling. Isocratic elutions, isocratic elutions with increased flow, and gradient elutions with step-down profiles and step-up profiles were performed and the chromatographic parameters of the different elution strategies were described by suitable variables. Based on peak resolutions general resolution deviation for multiple peaks (RDm) was developed for sample-independent evaluation of separation of any number of peaks in chromatographic analysis. Isocratic elutions of sucrose alkanoates showed similar relationships between eluent acetonitrile concentration and retention time for all regioisomers of sucrose caprate and sucrose laurate, as confirmed by evaluation of the curvatures using approximate second derivatives and Kendall rank correlation coefficients. Regression modelling and statistical analysis showed that acetonitrile concentration and flow rate were highly significant for both average adjusted retention time and RDm for sucrose laurate. For both responses the effect of changes in acetonitrile concentration was larger than the effect of changes in flow rate, over the ranges studied. Regression modelling of the step-down gradient profiles for the sucrose alkanoates showed that the eluent acetonitrile concentrations were the overall most significant variables for retention time and separation. The models for average adjusted retention time of sucrose caprate and sucrose laurate showed only a few differences in the significance levels of terms, while the models for RDm showed larger differences between the sucrose alkanoates, in both the number of terms and their significance. Efficiency evaluation of elution strategies, in terms of RDm and analysis time, showed that the best results were offered by step-down gradient elution for sucrose caprate and isocratic elution with increased flow for sucrose laurate. Step-down gradient elution of sucrose caprate offered improvements in separation at similar analysis time compared to isocratic elution, with the most efficient elutions achieved with elution profile acetonitrile concentrations at 32.5% and 25%, resulting in reduction of RDm by 13-38% and reduction of analysis time by 3-9%. For sucrose laurate, isocratic elution with increased flow showed improvements in separation and reductions in analysis time compared to isocratic elution, such as elution at 37% with flow 2.0mL\/min resulting in reduction of analysis time by 34% and equal RDm, while elution at 35% with flow 2.0mL\/min reduced RDm by 29% and analysis time by 6%, compared to isocratic elution at 38% acetonitrile with standard flow (1.0mL\/min).","subset":"pubmed_abstract"} +{"meta":{"pmid":24070809,"dup_signals":{"dup_doc_count":26,"dup_dump_count":20,"dup_details":{"curated_sources":4,"2023-14":3,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-10":1,"2024-26":1}}},"text":"Pharmacogenetic associations with vascular endothelial growth factor inhibition in participants with neovascular age-related macular degeneration in the IVAN Study.\nTo determine if prespecified genetic polymorphisms influence responsiveness to vascular endothelial growth factor (VEGF) inhibition in neovascular age-related macular degeneration (nAMD). The objectives were to replicate 3 reported pharmacogenetic associations of response in nAMD and to test for novel associations. Cohort study, combining information about patients' genotypes with information from a randomized controlled trial about responsiveness to anti-VEGF therapy for nAMD. Five hundred nine participants with nAMD, enrolled in the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial. Participants were classified as responders or nonresponders to VEGF inhibition based on the optical coherence tomography (OCT) metric of total retinal thickness (TRT). We computed the change in TRT from baseline to the latest time point for which OCT data were available (3, 6, 9, or 12 months). Eyes with changes in TRT greater than or equal to the 75th percentile or more were classified as responders, and those with changes less than or equal to the 25th percentile or lower were classified as non-responders. Three previously reported associations of response to VEGF inhibition in nAMD involving single nucleotide polymorphisms (SNPs) at the CFH, FZD4, and HTRA1\/ARMS2 loci were tested for replication. An additional 482 SNPs also were tested using a candidate gene approach. Associations were estimated as odds ratios (ORs) with confidence intervals (CIs). The primary outcome was evidence of a genetic association with response to VEGF inhibition as measured by change in TRT. One hundred twenty-six participants were classified as responders and 128 were classified as nonresponders. The SNP rs10490924 in HTRA1\/ARMS2 showed a borderline association with responsiveness after Bonferroni correction (OR, 1.53; CI, 0.99-2.36; P = 0.055, Bonferroni correction). None of the other 484 additional SNPs tested for association was significant after Bonferroni correction for multiple testing. The smallest corrected P value was 0.84 (P = 0.002, uncorrected) for rs9679290 in the EPAS1 (HIF2A) gene on chromosome 2. Four of the 10 most significant results were in this gene. We estimated pharmacogenetic associations using high-quality phenotype data from a randomized controlled clinical trial of nAMD. No significant association or replication of previous associations were observed. Further investigation of the EPAS1 (HIF2A) gene, however, may, be merited.","subset":"pubmed_abstract"} +{"meta":{"pmid":10896821,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-30":1,"unknown":7}}},"text":"Renal amino acid metabolism during endotoxemia in the rat.\nThe kidney has an important function in the exchange of nitrogenous metabolites. Glutamine is the most important substrate for renal ammoniagenesis and thus plays a crucial role in acid-base homeostasis. Furthermore, the kidney is the main endogenous source for de novo arginine production from citrulline, which in turn is derived from intestinal glutamine metabolism. Sepsis is a condition in which glutamine availability is reduced, whereas the need for arginine biosynthesis may be increased. Limited bioavailability of glutamine may affect arginine synthesis, which may have consequences for nitric oxide (NO) synthesis. Therefore, we studied renal glutamine and arginine metabolism in a rat model of endotoxemia and related this to NO metabolism. Rats were subject to double hit endotoxemia, and control rats received 0.9% NaCl. Renal blood flow was measured using para-aminohippuric acid. Concentrations of plasma amino acids and nitrate were measured in the aorta and renal vein to calculate net renal uptake or release of amino acids and address NO production. The arterial concentrations of glutamine and ammonia were not changed in endotoxemic rats. Although renal glutamine uptake was reduced, total renal ammonia production was not changed during endotoxemia. The arterial concentration of citrulline and renal citrulline uptake was not altered in endotoxin-treated rats, but renal arginine production was increased. However, no effect was observed on nitric oxide production. Although the kidney has very important functions in the excretion of waste products and in interorgan metabolism, this study suggests that the kidney has a limited role in glutamine, arginine, and NO metabolism during late endotoxemia in rats.","subset":"pubmed_abstract"} +{"meta":{"pmid":24949778,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Diffusion on demand to control precipitation aging: application to Al-Mg-Si alloys.\nWe demonstrate experimentally that a part-per-million addition of Sn solutes in Al-Mg-Si alloys can inhibit natural aging and enhance artificial aging. The mechanism controlling the aging is argued to be vacancy diffusion, with solutes trapping vacancies at low temperature and releasing them at elevated temperature, which is supported by a thermodynamic model and first-principles computations of Sn-vacancy binding. This \"diffusion on demand\" solves the long-standing problem of detrimental natural aging in Al-Mg-Si alloys, which is of great scientific and industrial importance. Moreover, the mechanism of controlled buffering and release of excess vacancies is generally applicable to modulate diffusion in other metallic systems.","subset":"pubmed_abstract"} +{"meta":{"pmid":31796574,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2024-18":1,"2024-30":1,"unknown":7}}},"text":"Implementation of clinical decision support to manage acute kidney injury in secondary care: an ethnographic study.\nOver the past decade, acute kidney injury (AKI) has become a global priority for improving patient safety and health outcomes. In the UK, a confidential inquiry into AKI led to the publication of clinical guidance and a range of policy initiatives. National patient safety directives have focused on the mandatory establishment of clinical decision support systems (CDSSs) within all acute National Health Service (NHS) trusts to improve the detection, alerting and response to AKI. We studied the organisational work of implementing AKI CDSSs within routine hospital care. An ethnographic study comprising non-participant observation and interviews was conducted in two NHS hospitals, delivering AKI quality improvement programmes, located in one region of England. Three researchers conducted a total of 49 interviews and 150 hours of observation over an 18-month period. Analysis was conducted collaboratively and iteratively around emergent themes, relating to the organisational work of technology adoption. The two hospitals developed and implemented AKI CDSSs using very different approaches. Nevertheless, both resulted in adaptive work and trade-offs relating to the technology, the users, the organisation and the wider system of care. A common tension was associated with attempts to maximise benefit while minimise additional burden. In both hospitals, resource pressures exacerbated the tensions of translating AKI recommendations into routine practice. Our analysis highlights a conflicted relationship between external context (policy and resources), and organisational structure and culture (eg, digital capability, attitudes to quality improvement). Greater consideration is required to the long-term effectiveness of the approaches taken, particularly in light of the ongoing need for adaptation to incorporate new practices into routine work.","subset":"pubmed_abstract"} +{"meta":{"pmid":19912172,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-18":1,"unknown":3}}},"text":"Semi-Markov models with phase-type sojourn distributions.\nContinuous-time multistate models are widely used for categorical response data, particularly in the modeling of chronic diseases. However, inference is difficult when the process is only observed at discrete time points, with no information about the times or types of events between observation times, unless a Markov assumption is made. This assumption can be limiting as rates of transition between disease states might instead depend on the time since entry into the current state. Such a formulation results in a semi-Markov model. We show that the computational problems associated with fitting semi-Markov models to panel-observed data can be alleviated by considering a class of semi-Markov models with phase-type sojourn distributions. This allows methods for hidden Markov models to be applied. In addition, extensions to models where observed states are subject to classification error are given. The methodology is demonstrated on a dataset relating to development of bronchiolitis obliterans syndrome in post-lung-transplantation patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":28930709,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Responding to Moral Distress and Ethical Concerns at the Intersection of Medical Illness and Unmet Mental Health Needs.\nSome of the most difficult clinical ethics consultations involve patients who have both medical and mental health needs, as these cases can result in considerable moral distress on the part of the bedside staff. In this article we examine the issues that such consults raise through the illustrative example of a particular case: several years ago our ethics consultation service received a request from a critical care attending physician who was considering a rarely performed psychosurgical intervention to address intractable and life-threatening agitation and aggression in an adolescent patient for whom standard treatments had proven unsuccessful. We consider strategies that may be useful in addressing not only the ethical dilemmas or the clinical problems, but also the emotional, social, and moral distress that arise in delivering care in such complex cases, in which standard routine practices of care have been exhausted. In addition, we explore the processes that led to this situation and suggest ways to promote early recognition and intervention for similar cases in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":29185708,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":10}}},"text":"The Autophagy-Related Beclin-1 Protein Requires the Coiled-Coil and BARA Domains To Form a Homodimer with Submicromolar Affinity.\nBeclin-1 (BECN1) is an essential component of macroautophagy. This process is a highly conserved survival mechanism that recycles damaged cellular components or pathogens by encasing them in a bilayer vesicle that fuses with a lysosome to allow degradation of the vesicular contents. Mutations or altered expression profiles of BECN1 have been linked to various cancers and neurodegenerative diseases. Viruses, including HIV and herpes simplex virus 1 (HSV-1), are also known to specifically target BECN1 as a means of evading host defense mechanisms. Autophagy is regulated by the interaction between BECN1 and Bcl-2, a pro-survival protein in the apoptotic pathway that stabilizes the BECN1 homodimer. Disruption of the homodimer by phosphorylation or competitive binding promotes autophagy through an unknown mechanism. We report here the first recombinant synthesis (3-5 mg\/L in an Escherichia coli culture) and characterization of full-length, human BECN1. Our analysis reveals that full-length BECN1 exists as a soluble homodimer (KD \u223c 0.45 \u03bcM) that interacts with Bcl-2 (KD = 4.3 \u00b1 1.2 \u03bcM) and binds to lipid membranes. Dimerization is proposed to be mediated by a coiled-coil region of BECN1. A construct lacking the C-terminal BARA domain but including the coiled-coil region exhibits a homodimer KD 3.5-fold weaker than that of full-length BECN1, indicating that both the BARA domain and the coiled-coil region of BECN1 contribute to dimer formation. Using site-directed mutagenesis, we show that residues at the C-terminus of the coiled-coil region previously shown to interact with the BARA domain play a key role in dimerization and mutations weaken the interface by \u223c5-fold.","subset":"pubmed_abstract"} +{"meta":{"pmid":9639537,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"GPI anchor biosynthesis in yeast: phosphoethanolamine is attached to the alpha1,4-linked mannose of the complete precursor glycophospholipid.\nCells synthesize the GPI anchor carbohydrate core by successively adding N-acetylglucosamine, three mannoses, and phosphoethanolamine (EtN-P) onto phosphatidylinositol, thus forming the complete GPI precursor lipid which is then added to proteins. Previously, we isolated a GPI deficient yeast mutant accumulating a GPI intermediate containing only two mannoses, suggesting that it has difficulty in adding the third, alpha1,2-linked Man of GPI anchors. The mutant thus displays a similar phenotype as the mammalian mutant cell line S1A-b having a mutation in the PIG-B gene. The yeast mutant, herein named gpi10-1 , contains a mutation in YGL142C, a yeast homolog of the human PIG-B. YGL142C predicts a highly hydrophobic integral membrane protein which by sequence is related to ALG9, a yeast gene required for adding Man in alpha1,2 linkage to N-glycans. Whereas gpi10-1 cells grow at a normal rate and make normal amounts of GPI proteins, the microsomes of gpi10-1 are completely unable to add the third Man in an in vitro assay. Further analysis of the GPI intermediate accumulating in gpi10 shows it to have the structure Manalpha1-6(EtN-P-)Manalpha1-4GlcNalpha1-6(acyl) Inositol-P-lipid. The presence of EtN-P on the alpha1,4-linked Man of GPI anchors is typical of mammalian and a few other organisms but had not been observed in yeast GPI proteins. This additional EtN-P is not only found in the abnormal GPI intermediate of gpi10-1 but is equally present on the complete GPI precursor lipid of wild type cells. Thus, GPI biosynthesis in yeast and mammals proceeds similarly and differs from the pathway described for Trypanosoma brucei in several aspects.","subset":"pubmed_abstract"} +{"meta":{"pmid":21857368,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Relationship of blood pressure and cardiovascular disease risk factors in normotensive middle-aged men.\nWe conducted this study to investigate whether subjects with high-normal systolic blood pressure (SBP) have an increased risk of cardiovascular disease (CVD) and\/or diabetes compared to subjects with low-normal SBP, using metabolic syndrome (MetS) as a risk factor for future CVD\/diabetes.The study included 6133 apparently healthy Taiwanese men aged 40-65 years. All subjects were normotensive, and none took medication for any abnormal MetS component. To avoid the effect of age on blood pressure, we stratified patients first by age then by SBP (that is, low, middle, and high SBP). We pooled all the low, middle, and high SBP groups from the different age strata to create 3 larger groups (Group 1, Group 2, and Group 3, respectively). The MetS components in subjects with the lowest SBP (Group 1) were compared with those in the other 2 groups. All of the MetS components, except for high-density lipoprotein cholesterol (HDL-C), were significantly lower in Group 1. Thus, it was not surprising that Group 2 and Group 3 had significantly higher odds ratios for abnormal body mass index, fasting plasma glucose, low-density lipoprotein-cholesterol (LDL-C), and triglycerides than Group 1 (but not for HDL-C). Specifically, Group 3 had a 1.7-fold higher odds ratio (p < 0.001) for having MetS than Group 1. Age, body mass index, fasting plasma glucose, LDL-C, and log triglycerides correlated significantly with SBP. In multivariate linear regression analysis, we found that only body mass index, fasting plasma glucose, and log triglycerides remained significantly related to SBP. Among them, body mass index had the highest \u03b2 value.In conclusion, the level of SBP was highly correlated with body mass index, fasting plasma glucose, and triglycerides in subjects with normotension. Although there is not a cause-and-effect relationship, the risk of CVD and diabetes was significantly associated with an elevation of SBP, even when the SBP remained within the normal range. Further studies are needed to determine whether normotensive subjects would benefit from medical management.","subset":"pubmed_abstract"} +{"meta":{"pmid":24366501,"dup_signals":{"dup_doc_count":20,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":16}}},"text":"An overview of the clinical use of filter paper in the diagnosis of tropical diseases.\nTropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed.","subset":"pubmed_abstract"} +{"meta":{"pmid":11723510,"dup_signals":{"dup_doc_count":16,"dup_dump_count":6,"dup_details":{"curated_sources":5,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":5}}},"text":"[Assessment of the promotion of breastfeeding in public and private maternities of S\u00e3o Paulo city, Brazil].\nThe World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) carried out a study to compare and evaluate the practices of protecting, promoting and supporting breastfeeding in public and private hospitals using the \"ten steps\" of the Hospital Initiative (BFHI) as a reference parameter. Forty-five hospitals of the municipality of S\u00e3o Paulo participated in the study. Data on the practices of infant feeding were collected by interviewing nurseries' supervisors of all public hospitals (26), and from a random sample of private hospitals (19), corresponding to a third of the total, during the years 1996-1997. More than a quarter of the public hospitals and more than one third of the private hospitals did not comply with any of the BFHI steps. Seven of the \"ten steps\" were observed in only two public hospitals. In general, practices of protection, promotion, and support of breastfeeding were seen at a higher frequency in public hospitals. The present study shows that practices considered detrimental to the onset and progressing of breastfeeding - unnecessary separation of the mother and her newborn, restrictions regarding the length of time and frequency of breastfeeding, use of pre-lacteal foods and supplements - are still quite frequently observed in public and private hospitals within the city of S\u00e3o Paulo. Given the benefits of breastfeeding for both the mother's and their children's health, and the important role maternities play for an early and successful onset of breastfeeding, it is paramount that the BFHI patterns be adopted by hospitals within the municipality of S\u00e3o Paulo.","subset":"pubmed_abstract"} +{"meta":{"pmid":29194072,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":8}}},"text":"Prenatal thrombosis of renal veins and the inferior vena cava in a newborn with double heterozygosity for the factor V Leiden and prothrombin gene G20210A mutations: a case report.\n: Renal vein thrombosis in a neonate is a rare but well recognized condition with low mortality but high morbidity. The cause has not been explained clearly yet but is probably a multifactorial process that includes inherited prothrombotic abnormalities. Antenatal onset of renal vein thrombosis is important due to the increased risk for permanent organ damage. We report a case of prenatal thrombosis of the renal veins and the inferior vena cava in a newborn with double heterozygosity for factor V Leiden and prothrombin gene mutations who had persistently impaired renal function requiring chronic peritoneal dialysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":16717192,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity.\nA key goal of regenerative medicine is an understanding of the genetic factors that define the properties of stem cells. However, stem cell research in mammalian tissue has been hampered by a paucity of stem cell-specific markers. Although increasing evidence suggests that members of the Musashi (Msi) family of RNA-binding proteins play important functions in progenitor cells, it remains unclear whether there is a stem cell-autonomous requirement for Msi because of an inability to distinguish stem cells from early-lineage cells in mammalian tissues. Here, using the Drosophila testis as a model system for the study of stem cell regulation, we show specific evidence for a cell-autonomous requirement for Msi family proteins in regulating stem cell differentiation, leading to the identification of an RNA-binding protein required for spermatogonial stem cell maintenance. We found that loss of Msi function disrupts the balance between germ-line stem cell renewal and differentiation, resulting in the premature differentiation of germ-line stem cells. Moreover, we found that, although Msi is expressed in both somatic and germ cells, Msi function is required intrinsically in stem cells for maintenance of stem cell identity. We also discovered a requirement for Msi function in male meiosis, revealing that Msi has distinct roles at different stages of germ cell differentiation. We describe the complementary expression patterns of the murine Msi paralogues Msi1 and Msi2 during spermatogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi.","subset":"pubmed_abstract"} +{"meta":{"pmid":23855907,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2019-09":1,"2018-51":2,"2018-39":1,"2018-26":1,"2018-09":1,"2017-47":1,"2017-26":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-18":1,"2017-13":1}}},"text":"EMG-based pattern recognition approach in post stroke robot-aided rehabilitation: a feasibility study.\nSeveral studies investigating the use of electromyographic (EMG) signals in robot-based stroke neuro-rehabilitation to enhance functional recovery. Here we explored whether a classical EMG-based patterns recognition approach could be employed to predict patients' intentions while attempting to generate goal-directed movements in the horizontal plane. Nine right-handed healthy subjects and seven right-handed stroke survivors performed reaching movements in the horizontal plane. EMG signals were recorded and used to identify the intended motion direction of the subjects. To this aim, a standard pattern recognition algorithm (i.e., Support Vector Machine, SVM) was used. Different tests were carried out to understand the role of the inter- and intra-subjects' variability in affecting classifier accuracy. Abnormal muscular spatial patterns generating misclassification were evaluated by means of an assessment index calculated from the results achieved with the PCA, i.e., the so-called Coefficient of Expressiveness (CoE). Processing the EMG signals of the healthy subjects, in most of the cases we were able to build a static functional map of the EMG activation patterns for point-to-point reaching movements on the horizontal plane. On the contrary, when processing the EMG signals of the pathological subjects a good classification was not possible. In particular, patients' aimed movement direction was not predictable with sufficient accuracy either when using the general map extracted from data of normal subjects and when tuning the classifier on the EMG signals recorded from each patient. The experimental findings herein reported show that the use of EMG patterns recognition approach might not be practical to decode movement intention in subjects with neurological injury such as stroke. Rather than estimate motion from EMGs, future scenarios should encourage the utilization of these signals to detect and interpret the normal and abnormal muscle patterns and provide feedback on their correct recruitment.","subset":"pubmed_abstract"} +{"meta":{"pmid":24760005,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Specific activation of K-RasG12D allele in the bladder urothelium results in lung alveolar and vascular defects.\nK-ras is essential for embryogenesis and its mutations are involved in human developmental syndromes and cancer. To determine the consequences of K-ras activation in urothelium, we used uroplakin-II (UPK II) promoter driven Cre recombinase mice and generated mice with mutated KrasG12D allele in the urothelium (UPK II-Cre;LSL-K-rasG12D). The UPK II-Cre;LSL-K-rasG12D mice died neonatally due to lung morphogenesis defects consisting of simplification with enlargement of terminal air spaces and dysmorphic pulmonary vasculature. A significant alteration in epithelial and vascular basement membranes, together with fragmentation of laminin, points to extracellular matrix degradation as the causative mechanism of alveolar and vascular defects. Our data also suggest that altered protease activity in amniotic fluid might be associated with matrix defects in lung of UPK II-Cre;LSL-K-rasG12. These defects resemble those observed in early stage human neonatal bronchopulmonary dysplasia (BPD), although the relevance of this new mouse model for BPD study needs further investigation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22661953,"dup_signals":{"dup_doc_count":12,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":2,"2024-26":1,"2024-10":2,"unknown":5}}},"text":"Why Do We have to Move Fluid to be Able to Breathe?\nThe ability to breathe air represents a fundamental step in vertebrate evolution that was accompanied by several anatomical and physiological adaptations. The morphology of the air-blood barrier is highly conserved within air-breathing vertebrates. It is formed by three different plies, which are represented by the alveolar epithelium, the basal lamina, and the endothelial layer. Besides these conserved morphological elements, another common feature of vertebrate lungs is that they contain a certain amount of fluid that covers the alveolar epithelium. The volume and composition of the alveolar fluid is regulated by transepithelial ion transport mechanisms expressed in alveolar epithelial cells. These transport mechanisms have been reviewed extensively. Therefore, the present review focuses on the properties and functional significance of the alveolar fluid. How does the fluid enter the alveoli? What is the fate of the fluid in the alveoli? What is the function of the alveolar fluid in the lungs? The review highlights the importance of the alveolar fluid, its volume and its composition. Maintenance of the fluid volume and composition within certain limits is critical to facilitate gas exchange. We propose that the alveolar fluid is an essential element of the air-blood barrier. Therefore, it is appropriate to refer to this barrier as being formed by four plies, namely (1) the thin fluid layer covering the apical membrane of the epithelial cells, (2) the epithelial cell layer, (3) the basal membrane, and (4) the endothelial cells.","subset":"pubmed_abstract"} +{"meta":{"pmid":27502591,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-18":1,"2024-22":1,"unknown":12}}},"text":"Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline.\nTo provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. The Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org\/NACT-ovarian-guideline and www.asco.org\/guidelineswiki.","subset":"pubmed_abstract"} +{"meta":{"pmid":30498822,"dup_signals":{"dup_doc_count":12}},"text":"Normative Values of Muscle Power using Force Plate Jump Tests in Men Aged 77-101 Years: The Osteoporotic Fractures in Men (MrOS) Study.\nTo determine normative values for weight-bearing, countermovement leg extension (\"jump\") tests in the oldest men and characteristics of those not completing vs. completing tests. 2014-16 cross-sectional exam. Six U.S. sites from the Osteoporotic Fractures in Men (MrOS) Study. Community-dwelling men (N=1,841) aged 84.5\u00b14.2 (range: 77-101) years. N\/A. Jump tests on a force plate measured lower-extremity muscle peak power\/kg, velocity and force\/kg at peak power, with normative values for 5-year age groups and by limitations in moderate-intensity activities of daily living (ADLs) and climbing several flights of stairs. Jump completion was 68.9% (N=1,268\/1,841) and 98% (1,242\/1,268) had \u22651 analyzable trial\/participant. Exclusions primarily were due to poor mobility and\/or balance: 24.8% (456\/1,841) prior to and 6.4% (N=117\/1,841) after attempting testing. Peak power was 20.8\u00b15.3 W\/kg, with 1.2\u00b10.3 m\/s for velocity, and 16.7\u00b11.9 N\/kg for force at peak power. Each 5-year age group >80 years had subsequently 10% lower power\/kg, with 30% lower power\/kg at >90 vs. \u226480 years (all p<0.05). Velocity and force\/kg at peak power were 24% and 9% lower respectively, at >90 vs. \u226480 years (all p<0.05). Limitations in both moderate ADLs and climbing several flights of stairs were associated with 16% lower age-adjusted power\/kg, equivalent to 5-10 years of aging, with 11% and 6% lower age-adjusted velocity and force\/kg respectively, vs. those without limitation (all p<0.05). Men not completing vs. completing jumps had older age, higher BMI, lower physical activity, more comorbidities, worse cognition, more IADLs\/ADLs and more falls in the past year (all p<0.05). Post-jump pain occurred in 4.6% (58\/1,268), with 2 participants stopping testing due to pain. Only 24\/1,242 (2%) had all trials\/participant without flight (i.e., inability to lift feet), with 323\/1,242 having \u22651 trial\/participant without flight (total of 28%). No serious adverse safety events (e.g., injury) occurred. A multicenter cohort of oldest men with a range of function had higher declines in jump power\/kg and velocity vs. force\/kg across each 5-year age group >80 years. Future research should examine age- and functional-related declines in jump measures related to physical performance decline, falls, fractures, and disability.","subset":"pubmed_abstract"} +{"meta":{"pmid":12206576,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":14}}},"text":"Subjective quality of life in severely mentally ill patients: a comparison of two instruments.\nAlthough many quality of life (QOL) scales have been developed, comparison of specific QOL instruments is lacking. We compared the psychometric properties of two QOL measures in parallel samples of mentally disturbed and non-patient subjects. We simultaneously administered the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and self-report items of the Lancashire Quality of Life Profile (LQOLP) to 199 patients with severe mental disorders and 175 non-patients. The patients were evaluated with psychiatric rating scales. We identified five concordant domains, and five instrument-specific domains for the LQOLP and four for the Q-LES-Q. The Q-LES-Q provides better psychometric properties than the LQOLP in both samples. Both instruments show a good capacity to evaluate QOL and discriminate between the patients and non-patient controls. Within the patient sample, both QOL measures showed similarly negative correlations with severity of depression, but not mania, positive, negative, and general symptomatology. Both instruments proved to be mental health related, but neither was mental-disorder specific. Despite the acceptable psychometric properties and correlation of general QOL indices, similar QOL domains proved to be instrument specific and not sufficiently compatible. These discrepancies should be considered when comparing evaluations from similar domains in these QOL scales.","subset":"pubmed_abstract"} +{"meta":{"pmid":31541130,"dup_signals":{"dup_doc_count":11}},"text":"Evaluating FAIR maturity through a scalable, automated, community-governed framework.\nTransparent evaluations of FAIRness are increasingly required by a wide range of stakeholders, from scientists to publishers, funding agencies and policy makers. We propose a scalable, automatable framework to evaluate digital resources that encompasses measurable indicators, open source tools, and participation guidelines, which come together to accommodate domain relevant community-defined FAIR assessments. The components of the framework are: (1) Maturity Indicators - community-authored specifications that delimit a specific automatically-measurable FAIR behavior; (2) Compliance Tests - small Web apps that test digital resources against individual Maturity Indicators; and (3) the Evaluator, a Web application that registers, assembles, and applies community-relevant sets of Compliance Tests against a digital resource, and provides a detailed report about what a machine \"sees\" when it visits that resource. We discuss the technical and social considerations of FAIR assessments, and how this translates to our community-driven infrastructure. We then illustrate how the output of the Evaluator tool can serve as a roadmap to assist data stewards to incrementally and realistically improve the FAIRness of their resources.","subset":"pubmed_abstract"} +{"meta":{"pmid":1430602,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Depressed patients with dysfunctional families: description and course of illness.\nSixty-eight depressed patients were subdivided according to their family's level of family functioning into functional and dysfunctional groups. Patients from dysfunctional families did not differ from those from functional families on measures of severity of depression, chronicity of depression, depression subtypes, other nonaffective psychiatric diagnoses, history of depression, or neuroendocrine functioning. Patients from dysfunctional families did have significantly higher levels of neuroticism. A 12-month follow-up of these patients indicated that depressed patients with dysfunctional families had a significantly poorer course of illness, as manifested by higher levels of depression, lower levels of overall adjustment, and a lower proportion of recovered patients. Thus, impaired family functioning appears to be an important prognostic factor in major depression.","subset":"pubmed_abstract"} +{"meta":{"pmid":6634414,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-18":1,"2024-26":1,"unknown":7}}},"text":"The elongation of mismatched primers by DNA polymerase alpha from calf thymus.\nThe ability of the 9S and 5.7S DNA polymerase alpha subspecies from calf thymus in elongating a mismatched primer terminus has been investigated. With poly(dA) as template, the elongation rate for (dT)8dG, (dT)8dC and (dT)10dGdT is 20-fold lower for the 9S enzyme and 5-fold lower for the 5.7S enzyme as compared to (dT)10. The presence of a second mismatch at the primer terminus reduces the elongation rate further by a factor of two. Exonucleolytic excision of the mismatches can be excluded. With (dT)8dG (dT)n as primer we show, that at least five T-residues have to follow the mismatch in order to establish the elongation rate of a perfectly paired primer. The KM value for (dT)10 dG as primer is 400 nM as compared to 10 nM for (dT)10. Addition of Mn2+ increases the relative efficiency of elongation of the mismatched primers.","subset":"pubmed_abstract"} +{"meta":{"pmid":27008880,"dup_signals":{"dup_doc_count":60,"dup_dump_count":30,"dup_details":{"curated_sources":4,"2023-50":3,"2023-40":3,"2023-23":1,"2023-14":3,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":1,"2022-21":2,"2022-05":3,"2021-39":4,"2021-31":2,"2021-25":1,"2021-21":1,"2021-17":2,"2021-10":1,"2021-04":2,"2020-50":2,"2020-45":1,"2020-40":4,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":3,"2019-51":1,"2019-04":1,"2024-30":4,"2024-26":2,"2024-18":1,"2024-10":1}}},"text":"Optimal Cutoff and Accuracy of an IgM Enzyme-Linked Immunosorbent Assay for Diagnosis of Acute Scrub Typhus in Northern Thailand: an Alternative Reference Method to the IgM Immunofluorescence Assay.\nThe enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus.","subset":"pubmed_abstract"} +{"meta":{"pmid":25258728,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"EEG-based emotion recognition using deep learning network with principal component based covariate shift adaptation.\nAutomatic emotion recognition is one of the most challenging tasks. To detect emotion from nonstationary EEG signals, a sophisticated learning algorithm that can represent high-level abstraction is required. This study proposes the utilization of a deep learning network (DLN) to discover unknown feature correlation between input signals that is crucial for the learning task. The DLN is implemented with a stacked autoencoder (SAE) using hierarchical feature learning approach. Input features of the network are power spectral densities of 32-channel EEG signals from 32 subjects. To alleviate overfitting problem, principal component analysis (PCA) is applied to extract the most important components of initial input features. Furthermore, covariate shift adaptation of the principal components is implemented to minimize the nonstationary effect of EEG signals. Experimental results show that the DLN is capable of classifying three different levels of valence and arousal with accuracy of 49.52% and 46.03%, respectively. Principal component based covariate shift adaptation enhances the respective classification accuracy by 5.55% and 6.53%. Moreover, DLN provides better performance compared to SVM and naive Bayes classifiers.","subset":"pubmed_abstract"} +{"meta":{"pmid":29152458,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Lysosomal storage diseases.\nLysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively.","subset":"pubmed_abstract"} +{"meta":{"pmid":22666229,"dup_signals":{"dup_doc_count":26,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":19}}},"text":"Global Gene Expression Profiling in PPAR-\u03b3 Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease.\nKidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-\u03b3 agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":19477262,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Hemolytic and genotoxic evaluation of organochalcogens in human blood cells in vitro.\nThis study investigated the hemolytic and genotoxic effect of different organoselenium and organotellurium compounds in human blood cells, as simple tests for screening the toxicity of organochalcogenides. For osmotic fragility (OF) test, samples of total blood were incubated with the organochalcogens at 4, 8, 50, 75 and 100 microM or vehicle (DMSO) for 90 min at 37 degrees C. The EC(50) values for hemolysis were significantly increased in erythrocytes exposed to diphenyl selenide (II), diphenyl diselenide (III), diphenyl telluride (IV), diphenyl ditelluride (V), (S)-2-amino-1-diselenide-3-methylpropanyl (IX), butyl(styryl)telluride (XIII) and 2-(butyltellurium)furan (XIV) at higher concentrations tested. The exposure of erythrocytes to organochalcogens diphenyl diselenide (II) and butyl(styryl)telluride (XIII), which had greater hemolytic effect, did not modify catalase activity, reactive oxygen species (ROS) production and -SH content. On the other hand, Na(+)\/K(+) ATPase activity of erythrocyte ghosts was significantly inhibited by the compounds diphenyl diselenide (II) and butyl(styryl)telluride (XIII) (P<0.05) in a concentration-dependent manner. The inhibition of Na(+)\/K(+) ATPase activity was completely reversed by dithiothreitol (DTT); indicating reaction of these organochalcogens with thiol groups of the enzyme. The thiol oxidase activity of the compounds II and XIII was supported by the fact that the rate of DTT oxidation was increased significantly by both chalcogens. In the higher concentrations, the compounds (II) and (XIII) were strongly genotoxic and cytotoxic to human leukocytes cells, as verified by the DNA damage and cell viability evaluation. Our results suggest that at relatively high concentration organochalcogenides exhibit hemolytic and genotoxic action in human blood cells, which are probably linked to their thiol oxidase activity and preferential interaction with sulfhydryl groups critical to enzymes.","subset":"pubmed_abstract"} +{"meta":{"pmid":24998696,"dup_signals":{"dup_doc_count":14}},"text":"Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.\nHepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":1838611,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-14":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2023-40":1,"2024-18":1}}},"text":"Pace-maker activity in the myometrium of the oestrous rat: in vivo studies using video-laparoscopy.\nFemale rats had one oviduct, or the cranial tip of one or both uterine horns, lesioned by coagulation, or separated from the remainder of the uterus. After recovery and return to oestrous cycles, myometrial activity at oestrus was analysed by video-laparoscopy. Lesioning the oviduct had no effect on myometrial activity. Coagulating the cranial tip of one horn initially reduced the frequency of ipsilateral longitudinal contractions propagating caudally, but this returned to normal after 14 days. Separating the cranial tip of the uterus had permanent effects on myometrial activity. Separation of one tip reduced the frequency of ipsilateral longitudinal contractions propagating caudally, had no effect on ipsilateral contractions propagating cranially, but reduced the frequency of contralateral contractions propagating cranially. The effect of a lesion near one uterotubal junction on contractions originating contralaterally near the cervix results from communication between uterine horns at the cervical junction; arrival of a caudally propagating contraction in one horn frequently generates a cranially propagating contraction in the other. Separating both uterine tips reduced the frequency of longitudinal contractions propagating in both directions. We conclude that, at oestrus, most spontaneous myometrial contractions are generated by pace-makers in the cranial tip of each uterine horn. The pace-makers are close to the uterotubal junction and regenerate after destruction by coagulation. When their influence is permanently removed, new pace-makers do not develop in myometrium caudal to the lesion. We conclude that most myometrial cells do not exhibit spontaneous pace-maker activity in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":37066411,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":7,"2024-30":1,"unknown":7}}},"text":"Genome-wide association study in 404,302 individuals identifies 7 significant loci for reaction time variability.\nReaction time variability (RTV), reflecting fluctuations in response time on cognitive tasks, has been proposed as an endophenotype for many neuropsychiatric disorders. There have been no large-scale genome wide association studies (GWAS) of RTV and little is known about its genetic underpinnings. Here, we used data from the UK Biobank to conduct a GWAS of RTV in participants of white British ancestry (n = 404,302) as well as a trans-ancestry GWAS meta-analysis (n = 44,873) to assess replication. We found 161 genome-wide significant single nucleotide polymorphisms (SNPs) distributed across 7 genomic loci in our discovery GWAS. Functional annotation of the variants implicated genes involved in synaptic function and neural development. The SNP-based heritability (h2SNP) estimate for RTV was 3%. We investigated genetic correlations between RTV and selected neuropsychological traits using linkage disequilibrium score regression, and found significant correlations with several traits, including a positive correlation with schizophrenia. We assessed the predictive ability of a polygenic score (PGS) for RTV, calculated using PRSice and PRS-CS, and found that the RTV-PGS significantly predicted RTV in independent cohorts, but that the generalizability to other ancestry groups was poor. These results identify genetic underpinnings of RTV, and support the use of RTV as an endophenotype for neurological and psychiatric disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":14983869,"dup_signals":{"dup_doc_count":15,"dup_dump_count":11,"dup_details":{"curated_sources":4,"2022-21":1,"2021-43":1,"2019-18":1,"2019-09":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2022-40":1}}},"text":"Genetic enhancement technologies and the new society.\nSo long as procreation continues to remain a central driving force in a marital relationship, and the family the very core of progressive society, efforts will be undertaken to expand the period of fecundity and combat infertility. Genetic planning and eugenic programming are more rational and humane alternatives to population regulation than death by famine and war. Genetic enhancement technologies and the scientific research undertaken to advance them should be viewed as not only aiding (or, sometimes resolving) the tragedy of infertility in family planning, but as a tool for enhancing the health of a Nation's citizens by engineering man's genetic weaknesses out of the line of inheritance. Put simply, healthier and genetically sound individuals have a much better opportunity for pursuing and achieving the \"good life\" and making a significant contribution to society's greater well being.","subset":"pubmed_abstract"} +{"meta":{"pmid":27793178,"dup_signals":{"dup_doc_count":13}},"text":"Urinary incontinence among pregnant women, following antenatal care at University of Gondar Hospital, North West Ethiopia.\nUrinary incontinence is defined as a complaint of any involuntary leakage of urine. During pregnancy, the prevalence of urinary incontinence ranges from 32 to 64 %. Different factors like demographic factors, obstetric factors, and other external factors affect urinary incontinence. In Ethiopia, there is no study conducted so far on the magnitude of urinary incontinence and factors associated among pregnant women. The objective of this study was to determine the prevalence of urinary incontinence and associated factors among pregnant women following antenatal care at the University of Gondar Hospital. Institution based cross- sectional study was conducted among 422 pregnant women following antenatal care at the University of Gondar Hospital. Data was collected using a structured questionnaire and analyzed using SPSS version 20. Descriptive, bivariate, and multivariate analyses were performed. The results were considered significant at p-value < 0.05. The overall prevalence of urinary incontinence among the participants was 11.4 % [48]. After adjustment episiotomy, constipation, obese women, chronic cough\/sneezing, asthma\/allergies\/sinusitis was associated with urinary incontinence. In this study, a lower prevalence was found than that of previous studies. There was a significant association of urinary incontinence with a previous history of episiotomy, constipation, maternal BMI, and respiratory problems.","subset":"pubmed_abstract"} +{"meta":{"pmid":29531801,"dup_signals":{"dup_doc_count":17,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-18":1,"2024-10":1,"2024-30":1,"unknown":13}}},"text":"Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis.\nAlzheimer's disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-\u03b2 (A\u03b2) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. A\u03b2 peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently A\u03b2 in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":18155257,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":2,"2023-23":1,"2022-40":1,"2022-27":1,"2022-05":1,"2021-43":1,"2021-31":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2023-50":1,"2024-22":1}}},"text":"Pharmacotherapeutic targeting of the endocannabinoid signaling system: drugs for obesity and the metabolic syndrome.\nEndogenous signaling lipids (\"endocannabinoids\") functionally related to Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (Cannabis), are important biomediators and metabolic regulators critical to mammalian (patho)physiology. The growing family of endocannabinoids, along with endocannabinoid biosynthetic and inactivating enzymes, transporters, and at least two membrane-bound, G-protein coupled receptors, comprise collectively the mammalian endocannabinoid signaling system. The ubiquitous and diverse regulatory actions of the endocannabinoid system in health and disease have supported the regulatory approval of natural products and synthetic agents as drugs that alter endocannabinoid-system activity. More recent data support the concept that the endocananbinoid system may be modulated for therapeutic gain at discrete pharmacological targets with safety and efficacy. Potential medications based on the endocannabinoid system have thus become a central focus of contemporary translational research for varied indications with important unmet medical needs. One such indication, obesity, is a global pandemic whose etiology has a pathogenic component of endocannabinoid-system hyperactivity and for which current pharmacological treatment is severely limited. Application of high-affinity, selective CB1 cannabinoid receptor ligands to attenuate endocannabinoid signaling represents a state-of-the-art approach for improving obesity pharmacotherapy. To this intent, several selective CB1 receptor antagonists with varied chemical structures are currently in advanced preclinical or clinical trials, and one (rimonabant) has been approved as a weight-management drug in some markets. Emerging preclinical data suggest that CB1 receptor neutral antagonists may represent breakthrough medications superior to antagonists\/inverse agonists such as rimonabant for therapeutic attenuation of CB1 receptor transmission. Since obesity is a predisposing condition for the cluster of cardiovascular and metabolic derangements collectively known as the metabolic syndrome, effective endocannabinoid-modulatory anti-obesity therapeutics would also help redress other major health problems including type-2 diabetes, atherothrombosis, inflammation, and immune disorders. Pressing worldwide healthcare needs and increasing appreciation of endocannabinoid biology make the rational design and refinement of targeted CB1 receptor modulators a promising route to future medications with significant therapeutic impact against overweight, obesity, obesity-related cardiometabolic dysregulation, and, more generally, maladies having a reward-supported appetitive component.","subset":"pubmed_abstract"} +{"meta":{"pmid":22736897,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":3,"unknown":6}}},"text":"Effects of Lagenaria sicessaria fruit juice on lipid profile and glycoprotein contents in cardiotoxicity induced by isoproterenol in rats.\nThis study investigated antihyperlipidemic effects of Lagenaria siceraria fruit juice (LSFJ) in isoproterenol (ISO)induced cardiotoxicity in rats. Rats treated with ISO (200 mg\/kg, s.c.) showed a significant increase in the levels of triglycerides, cholesterol, and free fatty acids, in both serum and heart tissue. An increase in the levels of phospholipids, low-density lipoprotein, and very low-density lipoprotein-cholesterol, and decrease in high-density lipoprotein-cholesterol in serum and phospholipid levels in the heart were observed. ISO intoxicated rats also showed a significant decrease in the activities of lecithin: cholesterol acyl transferase, whereas lipoprotein lipase was found to be increased. Administration of LSFJ (400 mg\/kg, p.o.) for 30 consecutive days and challenged with ISO on day 29th and 30th significantly attenuated these alterations and restored the levels of serum and heart lipids along with lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the protective effect of LSFJ during ISO-induced cardiotoxicity in rats.","subset":"pubmed_abstract"} +{"meta":{"pmid":28725287,"dup_signals":{"dup_doc_count":11}},"text":"How to Recover from a Brain Disease: Is Addiction a Disease, or Is there a Disease-like Stage in Addiction?\nPeople struggling with addiction are neither powerless over their addiction, nor are they fully in control. Lewis vigorously objects to the brain disease model of addiction (BDMA), because it makes people lose belief in their self-efficacy, and hence hinders their recovery. Although he acknowledges that there is a compulsive state in addiction, he objects to the claim that this compulsion is carved in stone. Lewis argues that the BDMA underestimates the agency of addicted people, and hence hinder their recovery. Lewis's work offers us a very much to be welcomed neurobiology of recovery. It offers addicted people a hopeful and respectful narrative for their recovery that treats them as agents rather than as damaged brains. However, I argue that overestimating people's agency can also result in people losing belief in their self-efficacy. Lewis's strong focus on the agency of addicted people might not match their experiences of struggle, hence reinforcing their feelings of guilt when they fail to control their use. I propose to replace the notion of addiction as a disease with a notion of a disease-like stage in addiction. I call this stage the duress stage in addiction, in which the addictive behaviour is largely impervious to the agent's values and to available techniques of self-control. However, the agent can overcome this stage by developing new techniques of self-control, by building on their self-concept and belief in self-efficacy, by changing their environments and habits, and by engaging in projects that are meaningful to the agent.","subset":"pubmed_abstract"} +{"meta":{"pmid":29147495,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.\nMetastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the \u0394\u0394ct method. Migration assay was used to evaluate cancer metastasis. Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls. C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":19068048,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":2,"unknown":7}}},"text":"Physiotherapists' accounts of their clients in geriatric inpatient rehabilitation.\nThis article aims to describe how physiotherapists working with frail older people talk about their clients. Semi-structured qualitative interviews with physiotherapists (n = 11) were audio recorded, transcribed and analysed using discourse analysis. Two accounts were identified: (i) older adults as recipients of a treatment intervention at the rehabilitation centre, with the dimensions 'a focus on physical impairments' and 'a focus on social needs' and (ii) older adults as partners in an exercise intervention to support their everyday living at home. Older adults' everyday living context was not considered in the approach where, in an isolated and objectified manner, the physiotherapists focused on physical impairments. Placing great emphasis on the clients' social needs in turn implied passive treatments. In both instances the physiotherapists' activities were focused on the present, that is, the time of the clients' stay at the rehabilitation facility, rather than on their everyday challenges at home. These aspects were taken into accounts to a greater extent when older adults were positioned as partners and functional limitations were contemplated in relation to domestic daily living.","subset":"pubmed_abstract"} +{"meta":{"pmid":12462267,"dup_signals":{"dup_doc_count":85,"dup_dump_count":26,"dup_details":{"curated_sources":3,"2023-50":6,"2023-40":7,"2023-23":6,"2023-14":6,"2023-06":5,"2022-49":2,"2022-40":3,"2022-33":2,"2022-27":1,"2022-21":2,"2022-05":4,"2021-49":2,"2021-43":7,"2021-39":3,"2021-31":4,"2021-25":2,"2021-21":4,"2021-17":4,"2021-10":2,"2021-04":2,"2020-50":2,"2020-45":2,"2020-40":1,"2020-34":1,"2020-24":1,"2020-16":1}}},"text":"Influence of rumen protein degradability and supplementation frequency on steers consuming low-quality forage: II. Ruminal fermentation characteristics.\nSeven ruminally and duodenally cannulated steers (264 +\/- 8 kg BW) consuming low-quality forage (5% CP; 61% NDF; 31% ADF) were used to determine the influence of CP degradability and supplementation frequency (SF) on ruminal fermentation characteristics. Treatments included an unsupplemented control and degradable intake protein (DIP) or undegradable intake protein (UIP) provided daily, every 3 d, or every 6 d. The DIP treatments (18% UIP) were calculated to provide 100% of the DIP requirement, while the UIP treatments (60% UIP) were provided on an isonitrogenous basis compared with DIP. Ruminal NH3-N was increased on the day all supplements were provided with supplemental CP (P = 0.04) and for DIP compared with UIP (P < 0.01). Also, because ruminal NH3-N increased at a greater rate with DIP compared with UIP as SF decreased, a linear effect of SF x CP degradability interaction (P = 0.02) was observed. In addition, NH3-N was greater on the day only daily supplements were provided for supplemented treatments (P = 0.04), and decreased linearly (P < 0.01) as SF decreased. Concentration of total VFA increased linearly (P = 0.02) as SF decreased on the day all supplements were provided, whereas on the day only daily supplements were provided, total VFA were greater for UIP compared with DIP (P = 0.01), and decreased linearly (P < 0.01) as SF decreased. An interaction concerning the linear effect of SF and CP degradability (P = 0.02) was observed for ruminal liquid volume on the day all supplements were provided. This was the result of an increase in liquid volume with DIP as SF decreased compared with a minimal effect with UIP. In contrast, there was no influence of supplementation on liquid volume the day only daily supplements were provided. Ruminal liquid dilution rate was greater (P = 0.02) with CP supplementation on the day all supplements were provided. We did observe a quadratic effect of SF x CP degradability interaction (P = 0.01) for dilution rate because of a quadratic response with DIP (greatest value with the every-third-day treatment) compared with a decrease as SF decreased for UIP. On the day only daily supplements were provided, ruminal liquid dilution rate decreased linearly (P = 0.02) as SF decreased. These results suggest that DIP and UIP elicit different effects on ruminal fermentation when supplemented infrequently to ruminants consuming low-quality forage while not adversely affecting nutrient intake and digestibility.","subset":"pubmed_abstract"} +{"meta":{"pmid":23793683,"dup_signals":{"dup_doc_count":12}},"text":"A brief intervention for drug use, sexual risk behaviours and violence prevention with vulnerable women in South Africa: a randomised trial of the Women's Health CoOp.\nTo assess the impact of the Women's Health CoOp (WHC) on drug abstinence among vulnerable women having HIV counselling and testing (HCT). Randomised trial conducted with multiple follow-ups. 15 communities in Cape Town, South Africa. 720 drug-using women aged 18-33, randomised to an intervention (360) or one of two control arms (181 and 179) with 91.9% retained at follow-up. The WHC brief peer-facilitated intervention consisted of four modules (two sessions), 2 h addressing knowledge and skills to reduce drug use, sex risk and violence; and included role-playing and rehearsal, an equal attention nutrition intervention, and an HCT-only control. Biologically confirmed drug abstinence measured at 12-month follow-up, sober at last sex act, condom use with main and casual sex partners, and intimate partner violence. At the 12-month endpoint, 26.9% (n=83\/309) of the women in the WHC arm were abstinent from drugs, compared with 16.9% (n=27\/160) in the Nutrition arm and 20% (n=31\/155) in the HCT-only control arm. In the random effects model, this translated to an effect size on the log odds scale with an OR of 1.54 (95% CI 1.07 to 2.22) comparing the WHC arm with the combined control arms. Other 12-month comparison measures between arms were non-significant for sex risk and victimisation outcomes. At 6-month follow-up, women in the WHC arm (65.9%, 197\/299) were more likely to be sober at the last sex act (OR1.32 (95% CI 1.02 to 1.84)) than women in the Nutrition arm (54.3%, n=82\/152). This is the first trial among drug-using women in South Africa showing that a brief intervention added to HCT results in greater abstinence from drug use at 12 months and a larger percentage of sexual activity not under the influence of substances. NCT00729391 ClinicalTrials.gov.","subset":"pubmed_abstract"} +{"meta":{"pmid":28631794,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"An efficient target-intermediate recycling amplification strategy for ultrasensitive fluorescence assay of intracellular lead ions.\nAn ultrasensitive fluorescence assay for intracellular Pb2+ determination was proposed through target-intermediate recycling amplification based on metal-assisted DNAzyme catalysis and strand displacement reactions. Compared with only target recycling-based fluorescence assay with an M amplification ratio, the proposed assay could achieve an M \u00d7 N amplification ratio to obtain an improved sensitivity by more than 10 times, in which M and N are the amplification ratios of target recycling and intermediate recycling, respectively. Remarkably, this proposed ultrasensitive fluorescence assay could be applied to the determination of various analytes with the well-designed detection probe, especially in intracellular assay, providing a promising tool for clinical diagnosis and biomedical detection.","subset":"pubmed_abstract"} +{"meta":{"pmid":34254824,"dup_signals":{"dup_doc_count":20,"dup_details":{"curated_sources":2,"unknown":18}}},"text":"Targeting Bacterial Gyrase with Cystobactamid, Fluoroquinolone, and Aminocoumarin Antibiotics Induces Distinct Molecular Signatures in Pseudomonas aeruginosa.\nThe design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to different sites of the same target can be differentiated by their transcriptome or metabolome signatures. The effects of three fluoroquinolones, two aminocoumarins, and two cystobactamids, all inhibiting bacterial gyrase, on Pseudomonas aeruginosa at subinhibitory concentrations could be distinguished clearly by RNA sequencing as well as metabolomics. We observed a strong (2.8- to 212-fold) induction of autolysis-triggering pyocins in all gyrase inhibitors, which correlated with extracellular DNA (eDNA) release. Gyrase B-binding aminocoumarins induced the most pronounced changes, including a strong downregulation of phenazine and rhamnolipid virulence factors. Cystobactamids led to a downregulation of a glucose catabolism pathway. The study implies that clustering cellular mechanisms of action according to the primary target needs to take class-dependent variances into account. IMPORTANCE Novel antibiotics are urgently needed to tackle the growing worldwide problem of antimicrobial resistance. Bacterial pathogens possess few privileged targets for a successful therapy: the majority of existing antibiotics as well as current candidates in development target the complex bacterial machinery for cell wall synthesis, protein synthesis, or DNA replication. An important mechanistic question addressed by this study is whether inhibiting such a complex target at different sites with different compounds has similar or differentiated cellular consequences. Using transcriptomics and metabolomics, we demonstrate that three different classes of gyrase inhibitors can be distinguished by their molecular signatures in P. aeruginosa. We describe the cellular effects of a promising, recently identified gyrase inhibitor class, the cystobactamids, in comparison to those of the established gyrase A-binding fluoroquinolones and the gyrase B-binding aminocoumarins. The study results have implications for mode-of-action discovery approaches based on target-specific reference compounds, as they highlight the intraclass variability of cellular compound effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":25583040,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-22":1,"unknown":7}}},"text":"Charlson index scores from administrative data and case-note review compared favourably in a renal disease cohort.\nThe Charlson index is a widely used measure of comorbidity. The objective was to compare Charlson index scores calculated using administrative data to those calculated using case-note review (CNR) in relation to all-cause mortality and initiation of renal replacement therapy (RRT) in the Grampian Laboratory Outcomes Mortality and Morbidity Study (GLOMMS-1) chronic kidney disease cohort. Modified Charlson index scores were calculated using both data sources in the GLOMMS-1 cohort. Agreement between scores was assessed using the weighted Kappa. The association with outcomes was assessed using Poisson regression, and the performance of each was compared using net reclassification improvement. Of 3382 individuals, median age 78.5 years, 56% female, there was moderate agreement between scores derived from the two data sources (weighted kappa 0.41). Both scores were associated with mortality independent of a number of confounding factors. Administrative data Charlson scores were more strongly associated with death than CNR scores using net reclassification improvement. Neither score was associated with commencing RRT. Despite only moderate agreement, modified Charlson index scores from both data sources were associated with mortality. Neither was associated with commencing RRT. Administrative data compared favourably and may be superior to CNR when used in the Charlson index to predict mortality.","subset":"pubmed_abstract"} +{"meta":{"pmid":20463747,"dup_signals":{"dup_doc_count":42,"dup_dump_count":26,"dup_details":{"curated_sources":2,"2023-23":6,"2023-14":2,"2022-40":1,"2022-21":3,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-10":1,"2021-04":2,"2020-50":2,"2020-40":2,"2019-04":1,"2018-43":1,"2018-34":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2017-34":1,"2023-40":1,"2024-30":2,"2024-26":2,"2024-10":2}}},"text":"Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene.\nAnkylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B*27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P approximately 0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P=0.0004, odds ratio (OR)=1.2, 95% confidence interval (CI)=1.1-1.4; rs3812571 P=0.0003, OR=1.2, 95% CI=1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P=0.000005, OR=1.2, 95% CI=1.1-1.3 and rs3812571 P=0.000006, OR=1.2, 95% CI=1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.","subset":"pubmed_abstract"} +{"meta":{"pmid":1959476,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis.\nAbnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":3989913,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-48":1,"unknown":11}}},"text":"Retrovirus D\/New England and its relation to Mason-Pfizer monkey virus.\nSeventeen isolates of retrovirus D\/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was prepared from Hirt supernatants of cells infected with one of these isolates (D\/New England 398). By restriction endonuclease analysis, cloned pD398 DNA represented full-length viral DNA with one long terminal repeat. A detailed restriction endonuclease map of pD398 was derived and compared with a map of the cloned Mason-Pfizer monkey virus genome. Forty-six percent (13 of 28) of restriction endonuclease sites were found to be conserved when these related viruses were compared. Five of the D\/New England isolates, including those from three different macaque species, were examined for strain variability by restriction endonuclease typing. Comparison of over 30 restriction endonuclease sites has not distinguished any of these D\/New England isolates. It thus appears that a single strain of type D retrovirus is infecting three different species of macaques in the New England colony. Markedly reduced cross-hybridization was observed between cloned pD398 and Mason-Pfizer monkey virus DNAs at high stringency; this reduced cross-hybridization was localized to the pol-env regions of the genome. Only very weak hybridization of D\/New England DNA to cloned squirrel monkey type D retrovirus DNA could be detected even at low-stringency conditions. What role type D retrovirus plays in the immunodeficiency syndrome of macaques remains to be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":34827569,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Extraction and Chemical Characterization of Functional Phenols and Proteins from Coffee (Coffea arabica) By-Products.\nNot all the coffee produced goes to the roasting stage, because non-compliant green coffee beans are usually discarded by roasters and the silverskin of the coffee is usually removed and discarded. In the present work, non-compliant green coffee beans and coffee silverskins were fully characterized from a chemical point of view. In addition, enzyme-assisted extraction was applied to recover a fraction rich in proteins and polyphenols, tested for antimicrobial, antityrosinase, and antioxidant activities. Non-compliant green coffee beans showed higher amounts of polyphenols, flavanols, flavonoids, and caffeine than coffee silverskins (which were richer in tannins). The enzymatic extraction of non-compliant coffee green beans produced extracts with a good protein content and with a consistent quantity of polyphenols. The extract showed antioxidant, antityrosinase, and antimicrobial activity, thus representing a promising strategy to recover defective green coffee beans. The antioxidant and antimicrobial activity of coffee silver skins is lower than that of non-compliant coffee green beans extracts, while the antityrosinase activity is comparable.","subset":"pubmed_abstract"} +{"meta":{"pmid":11959773,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"Humoral and cell mediated immune response to cow's milk proteins in Beh\u00e7et's disease.\nTo investigate the humoral and cellular immune response against cow's milk proteins in Beh\u00e7et's disease and to distinguish any behaviour during active or inactive disease. Peripheral blood mononuclear cells from 16 patients and from eight normal controls were cultured in the presence of phytohaemagglutinin (PHA), beta-casein, beta-lactoglobulin, or chicken egg albumin. Interferon gamma (IFNgamma) and interleukin 4 (IL4) were measured in the culture supernatants by enzyme linked immunosorbent assay (ELISA). Serum samples from 46 patients with Beh\u00e7et's disease and from 37 healthy subjects were also studied for antibody detection. Antibodies to beta-casein, beta-lactoglobulin, and chicken egg albumin were determined by ELISA. High IFNgamma but not IL4 levels were found in the supernatants of lymphocytes from patients with active disease cultured in the presence of cow's milk proteins. Levels were comparable with those obtained in cultures stimulated with PHA. A significantly higher level of anti-beta-casein and anti-beta-lactoglobulin IgG and IgA antibodies was found in patients with active Beh\u00e7et's disease. No relation was found between their occurrence and the age of the patients, the duration of disease, or the presence of gastrointestinal abnormalities. Antibodies to chicken albumin were detected at low levels and with a prevalence similar to that of healthy subjects. The results indicate that an active immune response occurs in Beh\u00e7et's disease. This response involves an increased frequency of antibodies to cow's milk protein and a strong Th1 polarisation after exposure to these antigens. The occurrence of these abnormalities supports a putative role for cow's milk proteins immune response in the pathogenesis of Beh\u00e7et's disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":7891179,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat.\nSerotonergic brainstem projections to hippocampus are thought to preferentially target and increase, via 5-HT3 receptors, the excitability of a distinct subpopulation of interneurons that primarily regulate GABAB-mediated inhibition in the dendritic region of pyramidal cells. Hippocampal slice work suggests that the between-burst hyperpolarization caused by slow (GABAB) IPSPs plays a significant role in controlling the strength of LTP induced with theta burst stimulation. According to the above observations it was assumed that blockade of hippocampal 5-HT3 receptors should reduce the hyperpolarization and thereby enhance both the frequency of the naturally occurring theta rhythm and the induction of LTP; moreover, if LTP-like mechanisms provide the substrate for certain forms of memory, such treatment was expected to facilitate learning. Each of the above predictions was tested and confirmed in the present set of experiments. The effects of ondansetron, a potent and selective antagonist of the 5-HT3 receptor, were examined on (1) frequency of the hippocampal theta rhythm, (2) induction of LTP in field CA1 of freely moving rats, and (3) retention of olfactory and spatial memory in tasks known to depend on an intact hippocampus. When injected intraperitoneally into freely moving rats, the drug reliably and significantly increased the frequency of the hippocampal theta rhythm in a dose-dependent manner. Second, at concentrations that facilitate theta frequency (100 micrograms\/kg and 500 micrograms\/kg), an injection of the drug 30 min prior to delivering electrical stimulation bursts significantly increased the magnitude and duration of LTP compared to that obtained in the same animals after vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":20451868,"dup_signals":{"dup_doc_count":35,"dup_dump_count":32,"dup_details":{"curated_sources":3,"2021-17":1,"2021-04":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-15":1,"2022-05":1,"2015-18":1,"2015-11":1,"2014-10":1,"2013-48":1,"2017-13":1}}},"text":"The Alzheimer's disease neuroimaging initiative: progress report and future plans.\nThe Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)\/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid beta (Abeta) and species of tau, with clinical\/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Abeta and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA\/LONI\/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD.","subset":"pubmed_abstract"} +{"meta":{"pmid":16753236,"dup_signals":{"dup_doc_count":16,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2023-23":1,"2021-31":1,"2021-17":1,"2019-09":1,"2018-51":1,"2018-34":1,"2018-13":2,"2017-51":1,"2017-43":1,"2017-34":1,"2023-50":1,"2013-20":1,"2024-26":1}}},"text":"Comparison of propidium monoazide with ethidium monoazide for differentiation of live vs. dead bacteria by selective removal of DNA from dead cells.\nThe differentiation between live and dead bacterial cells presents an important challenge in many microbiological applications. Due to the persistence of DNA in the environment after cells have lost viability, DNA-based detection methods cannot differentiate whether positive signals originate from live or dead bacterial targets. We present here a novel chemical, propidium monoazide (PMA), that (like propidium iodide) is highly selective in penetrating only into 'dead' bacterial cells with compromised membrane integrity but not into live cells with intact cell membranes\/cell walls. Upon intercalation in the DNA of dead cells, the photo-inducible azide group allows PMA to be covalently cross-linked by exposure to bright light. This process renders the DNA insoluble and results in its loss during subsequent genomic DNA extraction. Subjecting a bacterial population comprised of both live and dead cells to PMA treatment thus results in selective removal of DNA from dead cells. We provide evidence that this chemical can be applied to a wide range of species across the bacterial kingdom presenting a major advantage over ethidium monoazide (EMA). The general application of EMA is hampered by the fact that the chemical can also penetrate live cells of some bacterial species. Transport pumps actively export EMA out of metabolically active cells, but the remaining EMA level can lead to substantial loss of DNA. The higher charge of PMA might be the reason for the higher impermeability through intact cell membranes, thus avoiding DNA loss.","subset":"pubmed_abstract"} +{"meta":{"pmid":31413283,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-22":1,"unknown":9}}},"text":"Rumen bacterial community responses to DPA, EPA and DHA in cattle and sheep: A comparative in vitro study.\nThe role of marine lipids as modulators of ruminal biohydrogenation of dietary unsaturated fatty acids may be explained by the effects of their n-3 polyunsaturated fatty acids (PUFA) on the bacterial community. However, the impact of individual PUFA has barely been examined, and it is uncertain which bacteria are truly involved in biohydrogenation. In addition, despite interspecies differences in rumen bacterial composition, we are not aware of any direct comparison of bovine and ovine responses to dietary PUFA. Therefore, rumen fluid from cannulated cattle and sheep were used as inocula to examine in vitro the effect of 20:5n-3 (EPA), 22:5n-3 (DPA), and 22:6n-3 (DHA) on the bacterial community. Amplicon 16 S rRNA sequencing suggested that EPA and DHA had a greater contribution to the action of marine lipids than DPA both in cattle and sheep. Certain effects were exclusive to each ruminant species, which underlines the complexity of rumen microbial responses to dietary fatty acids. Based on changes in bacterial abundance, Barnesiella, Prevotella, Paraprevotella, Hallela, Anaerovorax, Succiniclasticum, Ruminococcus and Ruminobacter may be involved in the ruminal response in biohydrogenation to the addition of marine lipids, but further research is necessary to confirm their actual role in ruminal lipid metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":34693230,"dup_signals":{"dup_doc_count":28,"dup_dump_count":5,"dup_details":{"curated_sources":1,"2024-26":2,"2024-22":4,"2024-18":6,"2024-10":2,"2024-30":1,"unknown":12}}},"text":"Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19.\nThe longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Fifty-eight patients and thirty matched controls (single visit), recruited between 14th March - 25th May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV\u0307O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4\u00b73 mls\/m2, P=0\u00b7005) decreased and RV ejection fraction (+3\u00b72%, P=0\u00b70003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V\u0307O2, although better, were abnormal in patients versus controls. 31% had reduced pV\u0307O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. The authors' work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE\/18\/3\/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care\/National Institute for Health Research Grant (MR\/V027859\/1) ISRCTN number 10980107.","subset":"pubmed_abstract"} +{"meta":{"pmid":14655704,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Virus inactivation in aluminum and polyaluminum coagulation.\nInorganic aluminum salts, such as aluminum sulfate, are coagulants that cause small particles, such as bacteria and viruses as well as inorganic particles, to destabilize and combine into larger aggregates. In this investigation, batch coagulation treatments of water samples spiked with Qbeta, MS2, T4, and P1 viruses were conducted with four different aluminum coagulants. The total infectious virus concentration in the suspension of floc particles that eventually formed by dosing with coagulant was measured after the floc particles were dissolved by raising the pH with an alkaline beef extract solution. The virus concentrations were extremely reduced after the water samples were dosed with aluminum coagulants. Viruses mixed with and adsorbed onto preformed aluminum hydroxide floc were, however, completely recovered after the floc dissolution. These results indicated that the aluminum coagulation process inactivates viruses. Virucidal activity was most prominent with the prehydrolyzed aluminum salt coagulant, polyaluminum chloride (PACl). Virucidal activity was lower in river water than in ultrapure water--natural organic matter in the river water depressed the virucidal activity. Mechanisms and kinetics of the virus inactivation were discussed. Our results suggest that intermediate polymers formed during hydrolysis of the aluminum coagulants sorbed strongly to viruses, either rendering them inactive or preventing infectivity.","subset":"pubmed_abstract"} +{"meta":{"pmid":22919916,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":16}}},"text":"Disentangling trophic relationships in a High Arctic tundra ecosystem through food web modeling.\nDetermining the manner in which food webs will respond to environmental changes is difficult because the relative importance of top-down vs. bottom-up forces in controlling ecosystems is still debated. This is especially true in the Arctic tundra where, despite relatively simple food webs, it is still unclear which forces dominate in this ecosystem. Our primary goal was to assess the extent to which a tundra food web was dominated by plant-herbivore or predator-prey interactions. Based on a 17-year (1993-2009) study of terrestrial wildlife on Bylot Island, Nunavut, Canada, we developed trophic mass balance models to address this question. Snow Geese were the dominant herbivores in this ecosystem, followed by two sympatric lemming species (brown and collared lemmings). Arctic foxes, weasels, and several species of birds of prey were the dominant predators. Results of our trophic models encompassing 19 functional groups showed that <10% of the annual primary production was consumed by herbivores in most years despite the presence of a large Snow Goose colony, but that 20-100% of the annual herbivore production was consumed by predators. The impact of herbivores on vegetation has also weakened over time, probably due to an increase in primary production. The impact of predators was highest on lemmings, intermediate on passerines, and lowest on geese and shorebirds, but it varied with lemming abundance. Predation of collared lemmings exceeded production in most years and may explain why this species remained at low density. In contrast, the predation rate on brown lemmings varied with prey density and may have contributed to the high-amplitude, periodic fluctuations in the abundance of this species. Our analysis provided little evidence that herbivores are limited by primary production on Bylot Island. In contrast, we measured strong predator-prey interactions, which supports the hypothesis that this food web is primarily controlled by top-down forces. The presence of allochthonous resources subsidizing top predators and the absence of large herbivores may partly explain the predominant role of predation in this low-productivity ecosystem.","subset":"pubmed_abstract"} +{"meta":{"pmid":19387496,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Isolation, biology and chemistry of the disorazoles: new anti-cancer macrodiolides.\nCovering: 1994 to 2008. The disorazoles comprise a family of 29 closely related macrocyclic polyketides isolated in 1994 from the fermentation broth of the gliding myxobacterium Sorangium cellulosum. Disorazoles A1, E and C1 have shown exceptional biological activites toward inhibiting the proliferation of human cancer cell lines in picomolar and nanomolar concentrations through the disruption of microtubule polymerization. This review gives a brief introduction describing the biosynthesis and the significance of the disorazoles as a new class of microtubulin disruptors. Another portion of the review focuses on the biology of the disorazoles, specifically disorazole A1 and C1, and their antiproliferative efficacy against animal and human tumor cell lines, as well as the available SAR data. The majority of the discussion addresses synthetic efforts, including partial syntheses of various disorazoles and a summary of the total synthesis of disorazole C1.","subset":"pubmed_abstract"} +{"meta":{"pmid":24923554,"dup_signals":{"dup_doc_count":26,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2023-23":2,"2023-14":1,"2022-33":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-10":1,"2020-50":2,"2020-40":1,"2020-29":1,"2020-24":1,"2020-16":2,"2020-10":1,"2020-05":1,"2019-51":1,"2019-35":1,"2024-18":2}}},"text":"SOS, the formidable strategy of bacteria against aggressions.\nThe presence of an abnormal amount of single-stranded DNA in the bacterial cell constitutes a genotoxic alarm signal that induces the SOS response, a broad regulatory network found in most bacterial species to address DNA damage. The aim of this review was to point out that beyond being a repair process, SOS induction leads to a very strong but transient response to genotoxic stress, during which bacteria can rearrange and mutate their genome, induce several phenotypic changes through differential regulation of genes, and sometimes acquire characteristics that potentiate bacterial survival and adaptation to changing environments. We review here the causes and consequences of SOS induction, but also how this response can be modulated under various circumstances and how it is connected to the network of other important stress responses. In the first section, we review articles describing the induction of the SOS response at the molecular level. The second section discusses consequences of this induction in terms of DNA repair, changes in the genome and gene expression, and sharing of genomic information, with their effects on the bacteria's life and evolution. The third section is about the fine tuning of this response to fit with the bacteria's 'needs'. Finally, we discuss recent findings linking the SOS response to other stress responses. Under these perspectives, SOS can be perceived as a powerful bacterial strategy against aggressions.","subset":"pubmed_abstract"} +{"meta":{"pmid":18362190,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Host cells participate in the in vitro effects of novel diamidine analogues against tachyzoites of the intracellular apicomplexan parasites Neospora caninum and Toxoplasma gondii.\nThe in vitro effects of 19 dicationic diamidine derivatives against the proliferative tachyzoite stages of the apicomplexan parasites Neospora caninum and Toxoplasma gondii were investigated. Four compounds (DB811, DB786, DB750, and DB766) with similar structural properties exhibited profound inhibition of tachyzoite proliferation. The lowest 50% inhibitory concentrations were found for DB786 (0.21 microM against Neospora and 0.22 microM against Toxoplasma) and DB750 (0.23 microM against Neospora and 0.16 microM against Toxoplasma), with complete proliferation inhibition at 1.7 microM for both drugs against both species. DB750 and DB786 were chosen for further studies. Electron microscopy of N. caninum-infected human foreskin fibroblast (HFF) cultures revealed distinct alterations and damage of parasite ultrastructure upon drug treatment, while host cells remained unaffected. For true parasiticidal efficacy against N. caninum, a treatment duration of 3 h at 1.7 microM was sufficient for DB750, while a longer treatment period (24 h) was necessary for DB786. Pretreatment of tachyzoites for 1 h prior to host cell exposure had no effect on infectivity. However, pretreatment of uninfected host cells had a significant adverse effect on N. caninum proliferation: exposure of HFFs to 1.7 microM DB750 for 6, 12, or 24 h, followed by infection with N. caninum tachyzoites and subsequent culture in the absence of DB750, resulted in significantly delayed parasite proliferation. This suggests that either (i) these compounds or their respective active metabolites were still present after the removal of the drugs or (ii) the drug treatments reversibly impaired some functional activities in HFFs that were essential for parasite proliferation and\/or survival.","subset":"pubmed_abstract"} +{"meta":{"pmid":23574389,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Indoor aerosols: from personal exposure to risk assessment.\nMotivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic\/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure\/risk assessment methods are still needed, together with a serious focus on exposure control.","subset":"pubmed_abstract"} +{"meta":{"pmid":34938438,"dup_signals":{"dup_doc_count":14,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-22":3,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":6}}},"text":"Comparative biomechanics of the Pan and Macaca mandibles during mastication: finite element modelling of loading, deformation and strain regimes.\nThe mechanical behaviour of the mandibles of Pan and Macaca during mastication was compared using finite element modelling. Muscle forces were calculated using species-specific measures of physiological cross-sectional area and scaled using electromyographic estimates of muscle recruitment in Macaca. Loading regimes were compared using moments acting on the mandible and strain regimes were qualitatively compared using maps of principal, shear and axial strains. The enlarged and more vertically oriented temporalis and superficial masseter muscles of Pan result in larger sagittal and transverse bending moments on both working and balancing sides, and larger anteroposterior twisting moments on the working side. The mandible of Pan experiences higher principal strain magnitudes in the ramus and mandibular prominence, higher transverse shear strains in the top of the symphyseal region and working-side corpus, and a predominance of sagittal bending-related strains in the balancing-side mandible. This study lays the foundation for a broader comparative study of Hominidae mandibular mechanics in extant and fossil hominids using finite element modelling. Pan's larger and more vertical masseter and temporalis may make it a more suitable model for hominid mandibular biomechanics than Macaca.","subset":"pubmed_abstract"} +{"meta":{"pmid":1545116,"dup_signals":{"dup_doc_count":16,"dup_details":{"curated_sources":2,"unknown":14}}},"text":"Cytokine- and Ig-producing T cells in mucosal effector tissues: analysis of IL-5- and IFN-gamma-producing T cells, T cell receptor expression, and IgA plasma cells from mouse salivary gland-associated tissues.\nThe present study has focused on the analysis of cytokine- and Ig-producing mononuclear cells (MC) that reside in the salivary glands and their associated tissues (SGAT) in the oral region. The SGAT are located under the mandibular area and consist of submandibular glands, periglandular lymph nodes, and cervical lymph nodes. MC were isolated from individual SGAT and examined for T cell subsets and TCR expression, in comparison with T cells obtained from other mucosa-associated and systemic tissues. Forty to fifty percent of MC in submandibular glands were CD3+ T cells, equally divided into CD4+ CD8- and CD4- CD8+ T cell subsets. On the other hand, the intestinal lamina propria and Peyer's patches possessed a approximately 2 to 3:1 ratio of CD4+ CD8- to CD4- T cells. A high frequency of CD4- CD8- (double negative) (DN) T cells (approximately 6 to 10%) was also isolated from submandibular glands. In contrast, approximately 70 to 90% of MC in periglandular lymph nodes and cervical lymph nodes were CD3+ T cells and like the peripheral lymph nodes consisted of fivefold higher numbers of CD4+ CD8- than CD4- CD8+ T cells, with low numbers of DN cells (less than 5%). When expression of gamma\/delta and alpha\/beta TCR was examined in individual T cell subsets of submandibular glands, the CD4- CD8+ and DN T cell fractions contained 25% and 100% gamma\/delta TCR+ cells, respectively. On the other hand, essentially all CD4+ CD8- T cells in SGAT as well as CD4- CD8+ cells in periglandular lymph nodes and cervical lymph nodes were alpha\/beta TCR+ T cells. When cytokine production was examined by using IFN-gamma- and IL-5-specific enzyme-linked immunospot assays, the CD3+ CD4+ CD8- T cells in submandibular glands contained T cells spontaneously producing IFN-gamma and IL-5. Further, IL-5 spot-forming cells (SFC) were two- to threefold greater in number, compared with IFN-gamma SFC. The periglandular lymph node T cells contained cytokine producing cells with a ratio of 2:1 for IL-5 and IFN-gamma SFC cells, whereas cervical lymph node T cells did not produce cytokines unless stimulated with T cell mitogens. When the isotype distribution of Ig-producing cells was examined among SGAT, submandibular glands contained large numbers of IgA-producing cells, with few IgM- and IgG-producing cells, a pattern similar to that of the lamina propria. Further, elevated numbers of IgA-secreting cells were also seen in periglandular lymph nodes but not in cervical lymph nodes.(ABSTRACT TRUNCATED AT 400 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":11075619,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2013-20":1,"2017-13":1,"unknown":11}}},"text":"Thyroid hormones and lipid metabolism in a group of patients over seventy.\nNumerous studies have suggested a marked correlation between thyroid functionality indices and lipid metabolism. In this trial we assessed the functional parameters of 165 individuals over 70, 87 women and 78 men, correlating the serum values of T3, T4, FT4, TSH with cholesterol, triglycerides, HDL, Apo-A and Apo-B levels. The correlation was performed over the whole population studied and subsequently, after dividing the population by sex and age (3 age groups: A, 70-75; B, 76-80; C, over 80) in the individual groups. In the population as a whole, we have observed a statistically significant correlation between T4\/cholesterol (P=0.0001); T3\/cholesterol (P=0.06); T4\/triglycerides (P=0.0001); T3\/triglycerides (P=0.09); T4\/HDL (P=0.0001); T4\/Apo-A (P= 0.02); T3\/Apo-A (P=0.008); T4\/Apo-B (P=0.0001). Analysis by gender shows a statistically significance between the female and male sexes in the correlation between T3\/cholesterol (P=0.001); T3\/triglycerides (P=0.06); T4\/cholesterol (P=0.0001) and T4\/triglycerides (P=0.0001). When the data were analyzed by age, in Group A (75-80) there was no statistically significant correlation, whereas in Group B (76-80) there has been an increase in significance in the correlation between T3\/cholesterol (P=0.006); T3\/triglycerides (P=0.001); T3\/Hdl (P=0.08); T3\/Apo-A (P=0.0001); T3\/Apo-B (P=0.08); T4\/cholesterol (P=0.00001) and ); T4\/Apo-A (P=0.0001). On the other hand in the Group C age group (over 80) this significance is considerably lower. Maybe this decrease of correlations should be attributed to a global savings of the older organisms, or to a process of natural selection.","subset":"pubmed_abstract"} +{"meta":{"pmid":10882109,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2014-10":2,"2013-48":2,"2013-20":6,"unknown":5}}},"text":"Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.\nUV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic DNA and from the nontranscribed strand of an expressed gene. Expression of p48 suppressed UV-induced mutations arising from the nontranscribed strand, but had no effect on cellular UV sensitivity. These results define the role of p48 in DNA repair, demonstrate the importance of CPDs in mutagenesis, and suggest how rodent models can be improved to better reflect cancer susceptibility in humans.","subset":"pubmed_abstract"} +{"meta":{"pmid":36925414,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":1,"2024-18":1,"unknown":6}}},"text":"Connectome-wide Mega-analysis Reveals Robust Patterns of Atypical Functional Connectivity in Autism.\nNeuroimaging studies of functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide pattern, and whether these are age and\/or sex dependent. The study included resting-state functional magnetic resonance imaging and clinical data from the EU-AIMS LEAP (European Autism Interventions Longitudinal European Autism Project) and the ABIDE (Autism Brain Imaging Data Exchange) 1 and 2 initiatives of 1824 (796 with autism) participants with an age range of 5-58 years. Between-group differences in FC were assessed, and associations between FC and clinical symptom ratings were investigated through canonical correlation analysis. Autism was associated with a brainwide pattern of hypo- and hyperconnectivity. Hypoconnectivity predominantly affected sensory and higher-order attentional networks and correlated with social impairments, restrictive and repetitive behavior, and sensory processing. Hyperconnectivity was observed primarily between the default mode network and the rest of the brain and between cortical and subcortical systems. This pattern was strongly associated with social impairments and sensory processing. Interactions between diagnosis and age or sex were not statistically significant. The FC alterations observed, which primarily involve hypoconnectivity of primary sensory and attention networks and hyperconnectivity of the default mode network and subcortex with the rest of the brain, do not appear to be age or sex dependent and correlate with clinical dimensions of social difficulties, restrictive and repetitive behaviors, and alterations in sensory processing. These findings suggest that the observed connectivity alterations are stable, trait-like features of autism that are related to the main symptom domains of the condition.","subset":"pubmed_abstract"} +{"meta":{"pmid":27521160,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":9}}},"text":"On the contribution of Angola to the initial spread of HIV-1.\nAngola borders and has long-term links with Democratic Republic of Congo (DRC) as well as high levels of Human Immunodeficiency Virus (HIV) genetic diversity, indicating a potential role in the initial spread of the HIV-1 pandemic. Herein, we analyze 564 C2V3 and 354 pol publicly available sequences from DRC, Republic of Congo (RC) and Angola to better understand the initial spread of the virus in this region. Phylogeographic analyses were performed with the BEAST software. While our results pinpoint the origin of the pandemic to Kinshasa (DRC) around 1906, the introduction of HIV-1 to Angola could have occurred early between the 1910s and 1940s. Furthermore, most of the HIV-1 migrations out of Kinshasa were directed not only to Lubumbashi and Mbuji-Mayi (DRC), but also to Luanda and Brazzaville. Kinshasa census records corroborate these findings, indicating that the early exportation of the virus to Angola might be related to the high number of Angolans in Kinshasa at that time, originated mostly from the North of Angola. In summary, our results place Angola at the epicenter of the early HIV dissemination, together with DRC and RC.","subset":"pubmed_abstract"} +{"meta":{"pmid":38158162,"dup_signals":{"dup_doc_count":13,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-30":7,"2024-26":1,"2024-22":2,"2024-18":2}}},"text":"Investigation of iso-propylchaetominine anticancer activity on apoptosis, cell cycle and Wnt signaling pathway in different cancer models.\nDysregulation of the Wnt signaling pathway contributes to the development of many cancer types. Natural compounds produced with biotechnological systems have been the focus of research for being a new drug candidate both with unlimited resources and cost-effective production. In this study, it was aimed to reveal the effects of isopropylchaetominine on cytotoxic, cytostatic, apoptotic and Wnt signaling pathways in brain, pancreatic and prostate cancer. The IC50 values of isopropylchaetominine in U-87 MG, PANC1, PC3 and LNCaP cells were calculated as 91.94 \u03bcM, 41.68 \u03bcM, 54.54 \u03bcM and 7.86 \u03bcM in 72nd h, respectively. The metabolite arrests the cell cycle in G0\/G1 phase in each cancer cells. Iso-propylchaetominine induced a 4.3-fold and 1.9-fold increase in apoptosis in PC3 and PANC1 cells, respectively. The toxicity of isopropylchaetominine in healthy fibroblast cells was assessed using the annexin V method, and no significant apoptotic activity was observed between the groups treated with the active substance and untreated. In U-87 MG, PANC1, PC3, and LNCaP cells under treatment with isopropylchaetominin, the expression levels of DKK3, TLE1, AES, DKK1, FRZB, DAB2, AXIN1\/2, PPARD, SFRP4, APC and SOX17 tumor suppressor genes increased significantly. Decreases in expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5, Wnt6, Wnt10, Wnt11, FRZ2, FRZ3, FRZ7, TCF7L1, BCL9, PYGO, CCND2, c-MYC, WISP1 and CTNNB1 oncogenic genes were detected. All these result shows that isopropylchaetominine can present promising new treatment strategy in different cancer types.","subset":"pubmed_abstract"} +{"meta":{"pmid":31242404,"dup_signals":{"dup_doc_count":21,"dup_dump_count":13,"dup_details":{"curated_sources":3,"2021-31":1,"2021-17":1,"2021-04":1,"2020-40":3,"2020-29":1,"2020-16":2,"2020-10":2,"2019-47":1,"2019-39":2,"2019-30":1,"2021-43":1,"2024-10":1,"2024-22":1}}},"text":"Integrin beta 4 (ITGB4) and its tyrosine-1510 phosphorylation promote pancreatic tumorigenesis and regulate the MEK1-ERK1\/2 signaling pathway.\nPancreatic cancer is the fourth leading cause of cancer death, with a 5-year survival rate of only 1-4%. Integrin-mediated cell adhesion is critical for the initiation, progression, and metastasis of cancer. In this study we investigated the role of integrin b4 (ITGB4) and its phosphorylation at tyrosine Y1510 (p-ITGB4-Y1510) in the tumorigenesis of pancreatic cancer. We analyzed the expression of ITGB4 and p-ITGB4-Y1510 in pancreatic cancer tissue and cell lines using immunohistochemistry, Western blot, or semi-quantitative reverse transcription PCR. ITGB4 and p-ITGB4-Y1510 were highly expressed in pancreatic cancer (n = 176) compared with normal pancreatic tissue (n = 171). High p-ITGB4-Y1510 expression correlated with local invasion and distant metastasis of pancreatic cancer, and high ITGB4 was significantly associated with poor survival of patients. Inhibition of ITGB4 by siRNA significantly reduced migration and invasion of PC-1.0 and AsPC-1 cells. Overexpression of the mutant ITGB4-Y1510A (a mutation of tyrosine to alanine at 1510 position) in PC-1.0 and AsPC-1 cells not only blocked the ITGB4 phosphorylation at Y1510 but also suppressed the expression of ITGB4 (p < 0.05 vs. wild-type ITGB4). The transfection of PC-1.0 and AsPC-1 cells with ITGB4-Y1510A significantly decreased the level of p-mitogen-activated protein kinase kinase (MEK)1 (T292) and p-extracellular signal-regulated kinase (ERK)1\/2 but did not affect the level of p-MEK1 (T386) and p-MEK2 (T394). Overall, our study showed that ITGB4 and its phosphorylated form promote cell migration and invasion in pancreatic cancer and that p-ITGB4-Y1510 regulates the downstream MEK1-ERK1\/2 signaling cascades. Targeting ITGB4 or its phosphorylation at Y1510 may be a novel therapeutic option for pancreatic cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":7032812,"dup_signals":{"dup_doc_count":17,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":13}}},"text":"Role of dopamine in the regulation of blood pressure and the renin--angiotensin--aldosterone system in conscious rats.\n1. In conscious rats, intracerebroventricular injection of dopamine resulted in a decrease in blood pressure, whereas injection of metoclopramide, the dopamine antagonist, produced an increase in blood pressure. The central depressor effect of dopamine was attenuated by a subpressor pretreatment with intraventricular metoclopramide, but not by phentolamine. 2. Intravenous administration of dopamine increase blood pressure. This increase in blood pressure was almost completely abolished by intravenous phentolamine. Metoclopramide, when injected intravenously, did not reduce any change in blood pressure. 3. Plasma renin activity and plasma aldosterone concentration were decreased by intraventricular injection of dopamine, and increased by that of metoclopramide. In contrast, intravenous administration of metoclopramide increased plasma aldosterone concentration without changing plasma renin activity. Plasma concentrations of potassium, sodium and corticosterone were not affected by these treatments. 4. These results suggest that the dopaminergic system in the brain, but not in the systemic circulation, is involved in the regulation of blood pressure. It is also suggested that the central dopaminergic system participates in the regulation of aldosterone secretion by changes in the renin--angiotensin axis, whereas the peripheral dopaminergic modulation of aldosterone secretion appears to occur independently of the renin--angiotensin system.","subset":"pubmed_abstract"} +{"meta":{"pmid":20212861,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Gain model for microchannel plates.\nIt is shown that microchannel plates (MCPs) tend to act as if they were discrete stage electron multipliers with a fixed number of stages or dynodes if a plausible assumption is made regarding the behavior of the secondary electrons emitted from the semiconducting sidewalls of tubular channel electron multipliers under the grazing incidence conditions predominantly encountered in these multipliers. The shape of the resultant predicted gain-voltage transfer characteristic for the MCP fits well with experimental data, confirming the assumption made and permitting the use of curve matching techniques to determine such important MCP parameters as the average number of active dynodes, the gain per stage, the crossover potential for the MCP wall material, the transit time through the multiplier, etc.","subset":"pubmed_abstract"} +{"meta":{"pmid":11952483,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Evaluation of the new Ocuton S tonometer.\nTo evaluate the intra- and interobserver variability of the Ocuton S tonometer, its correlation with Goldmann tonometry, the reliability of self-tonometry and the safety of the instrument. Thirty-five healthy subjects and 45 patients with primary open-angle glaucoma (POAG), aged from 38 to 80 years (mean age: 64.6 +\/- 12.2 years), underwent tonometry with the Ocuton S tonometer in one eye chosen at random. The intra- and interobserver variability between two operators (kappa coefficient), the Ocuton S\/Goldmann correlation and the reliability of self-tonometry were evaluated by performing two tonometries on each patient in subgroups. Each tonometry was considered as the mean of three consecutive measurements. Central ultrasonic pachymetry, keratometry and corneal biomicroscopy were also evaluated. The intra- and interobserver variability ranged from 0.38 to 0.66. The difference between the means of intraocular pressure (IOP) with the Ocuton S (24.4 +\/- 4.7 mmHg) and the Goldmann tonometer (18.1 +\/- 4.7 mmHg) was statistically significant (p < 0.0001). Linear regression analysis revealed a good Ocuton S\/Goldmann correspondence (r = 0.88, p = 0.0001). However, IOP values detected with the Ocuton were consistently overestimated, compared to those detected with the Goldmann tonometer. The correlation between corneal thickness and IOP was statistically significant both for the Goldmann (r = 0.510, p = 0.021) and for the Ocuton S tonometer (r = 0.520, p = 0.019). No correlation was found between keratometry and IOP. The mean measurement obtained by self-tonometry (21.9 +\/- 3.6 mmHg) showed no statistically significant difference when compared to the mean measurement obtained by an expert operator (21.3 +\/- 3.4 mmHg). The Ocuton S tonometer is a safe instrument that can be used easily by the patient. However, in comparison to the Goldmann tonometer, it overestimates IOP and requires further technical and methodological refinements in order to ensure greater reliability.","subset":"pubmed_abstract"} +{"meta":{"pmid":21453005,"dup_signals":{"dup_doc_count":21,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2019-39":2,"2018-47":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2023-50":1,"2024-18":2}}},"text":"Obesity, hypertension, and migration: a meta-analysis of populations of the South Asian diaspora.\nThe effects of migration on human health have been a topic of interest for demographers and human biologists. Even if migrants to a new region achieve a higher standard of living in their new place of residence, their improved living conditions may not be associated with better health. Part of the difficulty of understanding the health consequences of migration is the complications in trying to control for variables that may affect health, such as gender, age, and urban or rural environment of migrants and nonmigrants. In this paper we report results of a meta-analysis of the body mass index (BMI) and blood pressure (BP) of people of South Asian descent, by comparing nonmigrants who inhabit the subcontinent, with migrants who moved to various places around the globe. Our results indicate that BMI almost always increases to a significant level upon migration and that an increase in BMI is most pronounced in female migrants. Our results also show that BP does not always increase in migrant communities and that it is actually lower in some migrant samples than it is in comparable nonmigrant groups. Therefore, our results show that BP and the BMI do not behave in the same manner following a migration event. We propose that the BMI changes experienced by migrants are likely to reflect different activity levels and diet in the new homeland. However, the BP changes experienced by migrants are likely to reflect stress broadly defined. Such stress may be increased or decreased, depending on the specific migration experience. We propose that the BMI and BP measure two different dimensions of the migration experience.","subset":"pubmed_abstract"} +{"meta":{"pmid":33356869,"dup_signals":{"dup_doc_count":40,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-40":3,"2023-23":1,"2023-14":4,"2023-06":2,"2022-49":2,"2022-40":2,"2022-27":1,"2022-21":2,"2022-05":1,"2021-49":1,"2021-43":2,"2021-39":1,"2021-31":3,"2021-21":4,"2021-17":3,"2024-26":2,"2024-18":1,"2024-10":3}}},"text":"Diverse roles for the posteromedial thalamus in sensory-evoked cortical plasticity.\nThe posteromedial thalamus (POm) has extensive recurrent connectivity with the whisker-related primary somatosensory cortex (wS1) of rodents. However, its functional contribution to somatosensory processing in wS1 remains unclear. This article reviews several recent findings, which begin to elucidate the role of POm in sensory-evoked plasticity and discusses their implications for somatosensory processing.","subset":"pubmed_abstract"} +{"meta":{"pmid":24723263,"dup_signals":{"dup_doc_count":13}},"text":"Somatodendritic ion channel expression in substantia nigra pars compacta dopaminergic neurons across postnatal development.\nDopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in the control of movement, sleep, reward, learning, and nervous system disorders and disease. To date, a thorough characterization of the ion channel phenotype of this important neuronal population is lacking. Using immunohistochemistry, we analyzed the somatodendritic expression of voltage-gated ion channel subunits that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-, and 40-day-old rats. Our results demonstrate that the same complement of somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to P40. The major developmental changes were an increase in the dendritic range of the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK channels. Our study sheds light on the ion channel subunits that contribute to the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium currents, IH (mainly HCN2, HCN4), and the L- (Cav1.2, Cav1.3) and T-type (mainly Cav3.1, Cav3.3) calcium currents in SNc dopaminergic neurons. Finally, no robust differences in voltage-gated ion channel immunolabeling were observed across the population of SNc dopaminergic neurons for each age examined, suggesting that differing levels of individual ion channels are unlikely to distinguish between specific subpopulations of SNc dopaminergic neurons. This is significant in light of previous studies suggesting that age- or region-associated variations in the expression profile of voltage-gated ion channels in SNc dopaminergic neurons may underlie their vulnerability to dysfunction and disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":27457369,"dup_signals":{"dup_doc_count":34,"dup_dump_count":32,"dup_details":{"curated_sources":2,"2023-23":1,"2023-06":1,"2022-40":1,"2022-21":1,"2021-43":1,"2021-31":1,"2021-17":1,"2021-04":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-26":1,"2018-13":1,"2017-47":1,"2017-39":1,"2017-30":1,"2017-22":1,"2017-09":1,"2023-50":1,"2017-13":1,"2024-22":1}}},"text":"Evaluation of the effects of the low-level laser therapy on swelling, pain, and trismus after removal of impacted lower third molar.\nIn current study we aimed to examine the effect of a low-level laser therapy on the pain, mouth opening and swelling of patients whose impacted 3rd molar tooth was extracted in addition measurement volumetrically to the edema with 3dMD face system. It was surveyed 15 patients who had bilateral symmetric lower 3rd molars. Surgical sides of patients were randomly separated into two groups: the study group and the control group. It was applied extra oral low-level laser therapy (LLLT, 0.3 W, 40 s, 4 J\/cm(2)) to the study group (n = 15) after the surgical operation and on the 2nd day. Only routine postoperative recommendation (ice application) was made in the control (n = 15) group. The maximum mouth opening, pain level and facial swelling evaluated. 3dMD Face\u00ae (3dMD, Atlanta, GA) Photogrammetric System was used to evaluate volumetric changes of the swelling. There was no statistically significant difference in the edema and interincisal opening between the groups and the pain level in the laser group was significantly lower than in the control group on the 7(th) postoperative day. Although there were decreasing trismus, swelling, and pain level, with this LLLT, there was significant difference only in the 7th day pain level in the laser group compared with the control group.","subset":"pubmed_abstract"} +{"meta":{"pmid":33714056,"dup_signals":{"dup_doc_count":12}},"text":"12-Month peak alpha frequency is a correlate but not a longitudinal predictor of non-verbal cognitive abilities in infants at low and high risk for autism spectrum disorder.\nAlthough studies of PAF in individuals with autism spectrum disorder (ASD) report group differences and associations with non-verbal cognitive ability, it is not known how PAF relates to familial risk for ASD, and whether similar associations with cognition in are present in infancy. Using a large multi-site prospective longitudinal dataset of infants with low and high familial risk for ASD, metrics of PAF at 12 months were extracted and growth curves estimated for cognitive development between 12-36 months. Analyses tested whether PAF 1) differs between low and high risk infants, 2) is associated with concurrent non-verbal\/verbal cognitive ability and 3) predicts developmental change in non-verbal\/verbal ability. Moderation of associations between PAF and cognitive ability by familial risk status was also tested. No differences in 12-month PAF were found between low and high risk infants. PAF was associated with concurrent non-verbal cognitive ability, but did not predict change in non-verbal cognitive over development. No associations were found between PAF and verbal ability, along with no evidence of moderation. PAF is not related to familial risk for ASD, and is a neural marker of concurrent non-verbal cognitive ability, but not verbal ability, in young infants at low and high risk for ASD.","subset":"pubmed_abstract"} +{"meta":{"pmid":24752022,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Improving nurses' knowledge of continuous ST-segment monitoring.\nContinuous ST-segment monitoring can result in detection of myocardial ischemia, but in clinical practice, continuous ST-segment monitoring is conducted incorrectly and underused by many registered nurses (RNs). Many RNs are unable to correctly institute ST-segment monitoring guidelines because of a lack of education. To evaluate whether an educational intervention, provided to 32 RNs, increases knowledge and correct clinical decision making (CDM) for the use of continuous ST-segment monitoring. At a single institution, an ST-segment monitoring class was provided to RNs in 2 cardiovascular units. Knowledge and correct CDM instruments were used for a baseline pretest and subsequent posttest after ST-segment monitoring education. Statistical significance between pretest and posttest scores for knowledge and correct CDM practice was noted with dependent t tests (P = .0001). Many RNs responsible for electrocardiographic monitoring are not aware of evidence-based ST-segment monitoring practice guidelines and cannot properly place precordial leads needed for ST-segment monitoring. Knowledge and correct CDM with ST-segment monitoring can be improved with focused education.","subset":"pubmed_abstract"} +{"meta":{"pmid":25577661,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":2,"2024-10":2,"unknown":11}}},"text":"Immunological effect of administration of sequential doses of Haemophilus influenzae type b and pneumococcal conjugate vaccines in the same versus alternating limbs in the routine infant immunisation schedule: an open-label randomised controlled trial.\nThe use of different limbs for the administration of sequential doses of an intradermal rabies vaccine was shown to result in reduced vaccine immunogenicity. We aimed to assess whether this phenomenon also occurs with routine infant vaccines. In this open-label, randomised, controlled study, eligible healthy infants 6-12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb. Infants in the consistent limb group received the diphtheria-tetanus-acellular pertussis-inactived polio-Haemophilus influenzae type b combined vaccine (DTaP-IPV-Hib) at 2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2, 4, and 12 months, all administered to the right leg. Infants in the alternating limb group received DTaP-IPV-Hib in the left leg at 2 months and in the right leg at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4 months, and in the left arm at 12 months. All infants in both groups received the combined H influenzae type b and capsular group C Neisseria meningitidis tetanus toxoid conjugate vaccine (Hib-MenC-TT), administered in the left leg at 12 months. Randomisation was achieved by randomly generated codes, with permuted block size of 30, and was stratified by study site. Group allocation was not masked from study staff and parents of participants after enrolment, but group allocation was masked from laboratory staff assessing blood samples. The current study was a prespecified secondary objective of a parent phase 4 trial that assessed the induction of immunity following varying schedules of vaccination with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in infancy. The objective of the current study was to compare the immunogenicity and reactogenicity of vaccines delivered in either consistent or alternating limbs. Immunogenicity was assessed by comparing serum IgG geometric mean concentrations at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01129518. Between July 5, 2010, and Aug 1, 2013, we enrolled 509 infants and randomly allocated them to the consistent limb group (n=254) or the alternating limb group (n=255). Anti-H influenzae type b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower in the consistent limb group than in the alternating limb group at 5 months (consistent limb 0\u00b741 \u03bcg\/mL [95% CI 0\u00b731-0\u00b754] vs alternating limb 0\u00b761 \u03bcg\/mL [0\u00b745-0\u00b782]; p=0\u00b70268) and at 12 months (0\u00b735 \u03bcg\/mL [0\u00b728-0\u00b743] vs 0\u00b750 \u03bcg\/mL [0\u00b740-0\u00b762]; p=0\u00b70136). Anti-tetanus toxoid antibody IgG geometric mean concentrations were lower in the consistent limb group (1\u00b763 IU\/mL [95% CI 1\u00b740-1\u00b790]) than in the alternating limb group (2\u00b730 IU\/mL [1\u00b797-2\u00b768]) at 13 months (p=0\u00b70008) and at 24 months (0\u00b744 IU\/mL [0\u00b737-0\u00b752] vs 0\u00b761 IU\/mL [0\u00b751-0\u00b773]; p=0\u00b70074). Anti-pneumococcal IgG geometric mean concentrations were similar between both groups at all timepoints. The proportions of participants who had adverse events did not differ between the two groups. Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research. NIHR Oxford Biomedical Research Centre and GlaxoSmithKline Biologicals.","subset":"pubmed_abstract"} +{"meta":{"pmid":30306961,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":10}}},"text":"Clinician Perspectives of an Avatar-Directed Scheduling and Memory App.\nEffective strategies are needed to address the need for scheduling support in the unique setting of a home rehabilitation service, providing home based therapy, as well as telerehabilitation. One approach is an electronic avatar-directed scheduling and memory aid in the form of an app. The aim of this study is to investigate clinician perspectives on the use of this type of technology. In this mixed method study a total of sixteen clinicians from various disciplines based at a metropolitan hospital in Adelaide (SA, Australia) participated in 2 semi-structured focus groups aimed to explore experiences and attitudes towards scheduling support in the form of an avatar-directed app, perceptions on the usefulness of the app, as well as acceptability. Thematic analysis was undertaken on focus groups' transcripts. Self-reported technology proficiency, perceived usefulness (PU), and perceived ease of use (PEOU) were assessed quantitatively. Summary statistics were used to analyse the quantitative data and Spearman's correlation was used to explore the relationship between participant characteristics and individual and mean scores for PU and PEOU. Four themes emerged from the focus groups: effectiveness versus efficiency, patient empowerment, practicality and ease of use, and likability of the avatar. Clinicians experienced time constraints, and welcomed technology that could assist with reliable scheduling of appointments and therapy sessions. They liked the concept of the avatar and found the app interesting, novel and fun. However, although the app was reasonably easy to use, the setting up was problematic and time consuming. Clinicians did not see the app as beneficial to their patients, and felt that the technology did not add value to the delivery of care. The older, more experienced, clinicians found the app more difficult to use, but neither the level of technological competency, nor gender, was found to be associated with PU or PEOU. Although clinicians appreciated the concept of an avatar-directed scheduling and memory app, they did not see it as a useful tool in the provision of scheduling assistance in this particular setting providing short-term rehabilitation services. Clinicians felt time-poor and emphasized the importance of a time-efficient solution. Perceived lack of usefulness in this context and poor likeability of the avatar highlight the need for clinician involvement in the design process before an app can be successfully implemented in a clinical setting.","subset":"pubmed_abstract"} +{"meta":{"pmid":21438171,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2017-13":1,"unknown":10}}},"text":"Higher tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis.\nPoor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI\u00ae, 300 mg at 60 mg\/ml) inhaled from the PARI LC PLUS\u00ae nebulizer requires about 20 min. This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg\/ml tobramycin solution delivered by an investigational eFlow\u00ae nebulizer. Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1) > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS\u00ae delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 \u00b1 2.5 min (mean \u00b1 SD) with serum levels of 1,089 \u00b1 388 \u00b5g\/L. The investigational eFlow\u00ae delivered 46.3(40.3-51.7) mg in 4.0 \u00b1 1.0 min with blood levels of 909 \u00b1 458 \u00b5g\/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients. These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow\u00ae, a very efficient electronic nebulizer.","subset":"pubmed_abstract"} +{"meta":{"pmid":27792174,"dup_signals":{"dup_doc_count":12}},"text":"\"A Vegetarian vs. Conventional Hypocaloric Diet: The Effect on Physical Fitness in Response to Aerobic Exercise in Patients with Type 2 Diabetes.\" A Parallel Randomized Study.\nIt has been shown that it is possible to modify macronutrient oxidation, physical fitness and resting energy expenditure (REE) by changes in diet composition. Furthermore, mitochondrial oxidation can be significantly increased by a diet with a low glycemic index. The purpose of our trial was to compare the effects of a vegetarian (V) and conventional diet (C) with the same caloric restriction (-500 kcal\/day) on physical fitness and REE after 12 weeks of diet plus aerobic exercise in 74 patients with type 2 diabetes (T2D). An open, parallel, randomized study design was used. All meals were provided for the whole study duration. An individualized exercise program was prescribed to the participants and was conducted under supervision. Physical fitness was measured by spiroergometry and indirect calorimetry was performed at the start and after 12 weeks Repeated-measures ANOVA (Analysis of variance) models with between-subject (group) and within-subject (time) factors and interactions were used for evaluation of the relationships between continuous variables and factors. Maximal oxygen consumption (VO2max) increased by 12% in vegetarian group (V) (F = 13.1, p < 0.001, partial \u03b7\u00b2 = 0.171), whereas no significant change was observed in C (F = 0.7, p = 0.667; group \u00d7 time F = 9.3, p = 0.004, partial \u03b7\u00b2 = 0.209). Maximal performance (Watt max) increased by 21% in V (F = 8.3, p < 0.001, partial \u03b7\u00b2 = 0.192), whereas it did not change in C (F = 1.0, p = 0.334; group \u00d7 time F = 4.2, p = 0.048, partial \u03b7\u00b2 = 0.116). Our results indicate that V leads more effectively to improvement in physical fitness than C after aerobic exercise program.","subset":"pubmed_abstract"} +{"meta":{"pmid":8846025,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Identification of an 80kD protein associated with the alpha 3 beta 1 integrin as a proteolytic fragment of the alpha 3 subunit: studies with human keratinocytes.\nWe have characterised a protein of approximately 80kD previously observed to co-immunoprecipitate with the alpha 3 beta 1 integrin in lysates of surface labelled human epidermalkeratinocytes. The 80kD protein only appeared when keratinocytes were harvested with trypsin\/EDTA prior to lysis and a protein of similar molecular mass could be immunoprecipitated from human dermal fibroblasts following treatment of the cells with trypsin\/EDTA. N terminal sequencing established that the 80kD protein had homology with the alpha 3 integrin subunit. Peptide-mass fingerprinting was used to confirm that the protein comprised the amino terminus of alpha 3 and established that the site of cleavage was after amino acid 629. The 80kD fragment could be coimmunoprecipitated with alpha 3 beta 1 using an antibody to the cytoplasmic domain of the alpha 3 subunit, showing that the fragment remained complexed with intact alpha 3 beta 1. When antibodies to the cytoplasmic and extracellular domains of alpha 3 were used to label human epidermis by immunofluorescence, the staining patterns were indistinguishable and there is therefore no evidence that proteolysis of alpha 3 plays a role in keratinocyte detachment from the basement membrane during terminal differentiation. Whether the 80kD fragment has any effects, positive or negative, on alpha 3 beta 1-mediated adhesion remains to be determined.","subset":"pubmed_abstract"} +{"meta":{"pmid":26322380,"dup_signals":{"dup_doc_count":19,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-40":2,"2023-14":1,"2022-27":1,"2022-05":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":1,"2021-04":1,"2020-34":1,"2020-29":2,"2024-10":1,"2024-26":1}}},"text":"Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.\nTo decrease the mortality of lung cancer, better screening and diagnostic tools as well as treatment options are needed. Protein glycosylation is one of the major post-translational modifications that is altered in cancer, but it is not exactly clear which glycan structures are affected. A better understanding of the glycan structures that are differentially regulated in lung tumor tissue is highly desirable and will allow us to gain greater insight into the underlying biological mechanisms of aberrant glycosylation in lung cancer. Here, we assess differential glycosylation patterns of lung tumor tissue and nonmalignant tissue at the level of individual glycan structures using nLC-chip-TOF-MS. Using tissue samples from 42 lung adenocarcinoma patients, 29 differentially expressed (FDR < 0.05) glycan structures were identified. The levels of several oligomannose type glycans were upregulated in tumor tissue. Furthermore, levels of fully galactosylated glycans, some of which were of the hybrid type and mostly without fucose, were decreased in cancerous tissue, whereas levels of non- or low-galactosylated glycans mostly with fucose were increased. To further assess the regulation of the altered glycosylation, the glycomics data was compared to publicly available gene expression data from lung adenocarcinoma tissue compared to nonmalignant lung tissue. The results are consistent with the possibility that the observed N-glycan changes have their origin in differentially expressed glycosyltransferases. These results will be used as a starting point for the further development of clinical glycan applications in the fields of imaging, drug targeting, and biomarkers for lung cancer.","subset":"pubmed_abstract"} +{"meta":{"pmid":18053273,"dup_signals":{"dup_doc_count":19,"dup_dump_count":6,"dup_details":{"curated_sources":3,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":3,"2013-48":1,"2017-13":1,"unknown":8}}},"text":"The elimination of Chagas' disease from Brazil.\nOn 9 June 2006 the Pan American Health Organization (PAHO) presented the Minister of Health of Brazil with the International Elimination of Transmission of Chagas' Disease Certificate. This act was the culmination of an intensive process that began in 1991 with the Southern Cone Initiative, a joint agreement between the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and Peru, to control Chagas' disease by the elimination of the main vector, Triatoma infestans. This initiative has been highly successful and the prevalence area of the vector diminished rapidly in the last years. As a consequence, the current seroprevalence in children aged between 0 and 5 years is of the order of 10(-5), a clear indication that transmission, if it is occurring, is only accidental. In this review I calculate the basic reproduction number, R0, for Chagas' disease and demonstrate that its relatively low value (1.25) explains why vectorial transmission was interrupted relatively easily. In addition, I used a mathematical model to forecast how long the remaining cases of the disease, as well as the additional vertically transmitted cases will last.","subset":"pubmed_abstract"} +{"meta":{"pmid":10790389,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":8}}},"text":"The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain.\nThe Drosophila gene female-lethal(2)d [fl(2)d] interacts genetically with the master regulatory gene for sex determination, Sex-lethal. Both genes are required for the activation of female-specific patterns of alternative splicing on transformer and Sex-lethal pre-mRNAs. We have used P-element-mediated mutagenesis to identify the fl(2)d gene. The fl(2)d transcription unit generates two alternatively spliced mRNAs that can encode two protein isoforms differing at their amino terminus. The larger isoform contains a domain rich in histidine and glutamine but has no significant homology to proteins in databases. Several lines of evidence indicate that this protein is responsible for fl(2)d function. First, the P-element insertion that inactivates fl(2)d interrupts this ORF. Second, amino acid changes within this ORF have been identified in fl(2)d mutants, and the nature of the changes correlates with the severity of the mutations. Third, all of the phenotypes associated with fl(2)d mutations can be rescued by expression of this cDNA in transgenic flies. Fl(2)d protein can be detected in extracts from Drosophila cell lines, embryos, larvae, and adult animals, without apparent differences between sexes, as well as in adult ovaries. Consistent with a possible function in posttranscriptional regulation, Fl(2)d protein has nuclear localization and is enriched in nuclear extracts.","subset":"pubmed_abstract"} +{"meta":{"pmid":29467136,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":10}}},"text":"Attitudes and perceptions of health professionals towards management of hypothyroidism in general practice: a qualitative interview study.\nTo explore the attitudes and perceptions of health professionals towards management of hypothyroidism that contributes to the suboptimal treatment of hypothyroidism in general practice. A qualitative interview study using semistructured interviews. Sixteen participants were interviewed between March and August 2016 comprising nine general practitioners (GPs), four pharmacists, two practice nurses and one nurse practitioner. General practice and community pharmacies in the counties of Northumberland, Tyne and Wear, Stockton-on-Tees and North Cumbria, North of England, UK. A grounded-theory approach was used to generate themes from interviews, which were underpinned by the theory of planned behaviour to give explanation to the data. Although health professionals felt that hypothyroidism was easy to manage, GPs and nurses generally revealed inadequate knowledge of medication interactions and levothyroxine pharmacokinetics. Pharmacists felt limited in the advice that they provide to patients due to lack of access to patient records. Most GPs and nurses followed local guidelines, and relied on blood tests over clinical symptoms to adjust levothyroxine dose. The information exchanged between professional and patient was usually restricted by time and often centred on symptoms rather than patient education. Health professionals felt that incorrect levothyroxine adherence was the main reason behind suboptimal treatment, although other factors such as comorbidity and concomitant medication were mentioned. Enablers perceived by health professionals to improve the management of hypothyroidism included continuity of care, blood test reminders, system alerts for interfering medications and prescription renewal, and accessible blood tests and levothyroxine prescriptions for patients. There is a significant health professional behavioural component to the management of hypothyroidism. Addressing the differences in patient and professional knowledge and perceptions could reduce the barriers to optimal treatment, while continuity of care and increased involvement of pharmacists and practice nurses would help to promote optimal thyroid replacement.","subset":"pubmed_abstract"} +{"meta":{"pmid":25651245,"dup_signals":{"dup_doc_count":30,"dup_details":{"curated_sources":2,"unknown":28}}},"text":"Tenofovir-based preexposure prophylaxis for HIV infection among African women.\nReproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).","subset":"pubmed_abstract"} +{"meta":{"pmid":12093987,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Relationship of adherence to pediatric asthma morbidity among inner-city children.\nMorbidity from asthma among children is one of the most important US health concerns. This study examines the relationship of baseline nonadherence to subsequent asthma morbidity among inner-city children. A multisite, prospective, longitudinal panel study was conducted of 1199 children who were aged 4 to 9 years and had asthma and their caregivers, most of whom were parents, in emergency departments and clinics at 8 research centers in 7 US metropolitan inner-city areas. Nine morbidity indicators were collected at 3, 6, and 9 months after baseline, including hospitalizations, unscheduled visits, days of wheeze\/cough, and days of reduced activities. Children whose caregivers scored high on a new measure, Admitted Nonadherence, experienced significantly worse morbidity on 8 of the 9 measures. Children who scored high on a new Risk for Nonadherence measure experienced significantly worse morbidity on all 9 morbidity measures. Multiple and logistic regressions found that the adherence measures had independent significant effects on morbidity. Combining the measures improved estimates of morbidity: children whose caregivers were poor on either adherence measure had worse morbidity than those with good adherence on both, eg, rate of hospitalization was twice as high, they missed more than twice as much school, had poorer overall functioning, and experienced more days of wheezing and more restricted days of activity. Risk for Nonadherence and Admitted Nonadherence independently and jointly predicted subsequent asthma morbidity. Targeting risks for nonadherence may be an effective intervention strategy. Most risks can be controlled by physicians through reducing the complexity of asthma regimens, communicating effectively with caregivers about medication use, and correcting family misconceptions about asthma medication side effects.","subset":"pubmed_abstract"} +{"meta":{"pmid":28979574,"dup_signals":{"dup_doc_count":20,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2020-10":1,"2019-35":1,"2019-13":1,"2019-04":1,"2018-47":1,"2018-26":1,"2018-09":1,"2018-05":1,"2017-47":1,"2017-39":2,"2020-34":1,"2024-18":2,"2024-10":2}}},"text":"Comparison of Composition and Anticaries Effect of Galla Chinensis Extracts with Different Isolation Methods.\nGalla chinensis water extract (GCE) has been demonstrated to inhibit dental caries by favorably shifting the demineralization\/remineralization balance of enamel and inhibiting the biomass and acid formation of dental biofilm. The present study focused on the comparison of composition and anticaries effect of Galla chinensis extracts with different isolation methods, aiming to improve the efficacy of caries prevention. The composition of water extract (GCE), ethanol extract (eGCE) and commercial tannic acid was compared. High performance liquid chromatography coupled to electrospray ionization-time of flight-mass spectrometry (HPLC-ESI-TOF-MS) analysis was used to analyze the main ingredients. In vitro pH-cycling regime and polymicrobial biofilms model were used to assess the ability of different Galla chinensis extracts to inhibit enamel demineralization, acid formation and biofilm formation. All the GCE, eGCE and tannic acid contained a high level of total phenolics. HPLC-ESI-TOF-MS analysis showed that the main ingredients of GCE were gallic acid (GA), while eGCE mainly contained 4-7 galloylglucopyranoses (GGs) and tannic acid mainly contained 5-10 GGs. Furthermore, eGCE and tannic acid showed a better effect on inhibiting enamel demineralization, acid formation and biofilm formation compared to GCE. Galla chinensis extracts with higher tannin content were suggested to have higher potential to prevent dental caries.","subset":"pubmed_abstract"} +{"meta":{"pmid":19660220,"dup_signals":{"dup_doc_count":42,"dup_dump_count":33,"dup_details":{"curated_sources":3,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-26":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-27":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":4,"2014-41":2,"2014-35":1,"2014-23":2,"2014-15":2,"2017-34":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2017-13":1}}},"text":"Creation of a neovagina by the Vecchietti procedure in a patient with corrected high imperforate anus.\nVaginal atresia is often associated with high imperforate anus. Because the commonly used methods of surgical vaginal creation (eg, McIndoe, intestinal segment interposition) may adversely affect urinary and fecal continence, the less-invasive Vecchietti procedure was selected for a young adult with a successfully corrected high imperforate anus. A 21-year-old was born with a high imperforate anus, vaginal atresia, right hemi-uterus, and left renal agenesis. A colostomy was done at birth, a pull-through procedure at 9 months, and a stoma closure 3 months later. At age 13, an obstructed and dilated right hemiuterus and fallopian tube were resected. A laparoscopic version of the Vecchietti procedure was used for creation of a neovagina. After the patient had been in the hospital for 2 days, traction was gradually advanced every other day in the office. At 2 weeks postoperatively, the bead was removed revealing a 7-cm vagina. Further elongation was achieved using the Frank method, while continence remained intact. The Vecchietti procedure is an attractive, minimally invasive alternative for creation of a neovagina in patients at risk for compromise to their vesico-anorectal continence.","subset":"pubmed_abstract"} +{"meta":{"pmid":24779546,"dup_signals":{"dup_doc_count":20,"dup_dump_count":16,"dup_details":{"curated_sources":3,"2020-50":1,"2020-40":1,"2020-24":1,"2019-47":1,"2019-30":1,"2018-39":1,"2018-26":1,"2018-17":1,"2017-51":1,"2017-43":2,"2017-30":1,"2017-17":1,"2017-04":1,"2016-50":1,"2016-44":1,"2022-49":1}}},"text":"Evaluation of three different methods of distance learning for postgraduate diagnostic imaging education: A pilot study.\nObjective : The purpose of this study was to evaluate the perceived effectiveness and learning potential of 3 Web-based educational methods in a postgraduate radiology setting. Methods : Three chiropractic radiology faculty from diverse geographic locations led mini-courses using asynchronous discussion boards, synchronous Web conferencing, and asynchronous voice-over case presentations formatted for Web viewing. At the conclusion of each course, participants filled out a 14-question survey (using a 5-point Likert scale) designed to evaluate the effectiveness of each method in achieving specified course objectives and goals and their satisfaction when considering the learning potential of each method. The mean, standard deviation, and percentage agreements were tabulated. Results : Twenty, 15, and 10 participants completed the discussion board, Web conferencing, and case presentation surveys, respectively. All educational methods demonstrated a high level of agreement regarding the course objective (total mean rating >4.1). The case presentations had the highest overall rating for achieving the course goals; however, all but one method still had total mean ratings >4.0 and overall agreement levels of 70%-100%. The strongest potential for interactive learning was found with Web conferencing and discussion boards, while case presentations rated very low in this regard. Conclusions : The perceived effectiveness in achieving the course objective and goals was high for each method. Residency-based distance education may be a beneficial adjunct to current methods of training, allowing for international collaboration. When considering all aspects tested, there does not appear to be a clear advantage to any one method. Utilizing various methods may be most appropriate.","subset":"pubmed_abstract"} +{"meta":{"pmid":30675626,"dup_signals":{"dup_doc_count":12}},"text":"Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes.\nIn type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven. Moreover, viruses have rarely been isolated from the pancreas of individuals with type 1 diabetes, mainly (but not solely) due to the inaccessibility of the organ. Here, we review past and recent literature to evaluate the proposals that chronic, recurrent and, possibly, persistent enteroviral infections occur in pancreatic beta cells in type 1 diabetes. We also explore whether these infections may be sustained by different virus strains over time and whether multiple viral hits can occur during the natural history of type 1 diabetes. We emphasise that only a minority of beta cells appear to be infected at any given time and that enteroviruses may become replication defective, which could explain why they have been isolated from the pancreas only rarely. We argue that enteroviral infection of beta cells largely depends on the host innate and adaptive immune responses, including innate responses mounted by beta cells. Thus, we propose that viruses could play a role in type 1 diabetes on multiple levels, including in the triggering and chronic stimulation of autoimmunity and in the generation of inflammation and the promotion of beta cell dysfunction and stress, each of which might then contribute to autoimmunity, as part of a vicious circle. We conclude that studies into the effects of vaccinations and\/or antiviral drugs (some of which are currently on-going) is the only means by which the role of viruses in type 1 diabetes can be finally proven or disproven.","subset":"pubmed_abstract"} +{"meta":{"pmid":24202787,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation.\nDYTCA is a syndrome that is characterized by predominant dystonia and mild cerebellar ataxia. We examined two affected siblings with healthy, consanguineous, Turkish parents. Both patients presented with a combination of childhood-onset cerebellar ataxia, dystonia, and sensory axonal neuropathy. In the brother, dystonic features were most pronounced in the legs, while his sister developed torticollis. Routine diagnostic investigations excluded known genetic causes. Biochemical analyses revealed a mitochondrial respiratory chain complex IV and a coenzyme Q10 deficiency in a muscle biopsy. By exome sequencing, we identified a homozygous missense mutation (c.154A >C; p.Thr52Pro) in both patients in exon 2 of the COX20 (FAM36A) gene, which encodes a complex IV assembly factor. This variant was confirmed by Sanger sequencing, was heterozygous in both parents, and was absent from 427 healthy controls. The exact same mutation was recently reported in a patient with ataxia and muscle hypotonia. Among 128 early-onset dystonia and\/or ataxia patients, we did not detect any other patient with a COX20 mutation. cDNA sequencing and semi-quantitative analysis were performed in fibroblasts from one of our homozygous mutation carriers and six controls. In addition to the exchange of an amino acid, the mutation led to a shift in splicing. In conclusion, we extend the phenotypic spectrum of a recently identified mutation in COX20 to a recessively inherited, early-onset dystonia-ataxia syndrome that is characterized by reduced complex IV activity. Further, we confirm a pathogenic role of this mutation in cerebellar ataxia, but this mutation seems to be a rather rare cause.","subset":"pubmed_abstract"} +{"meta":{"pmid":25560559,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Choice of resolution by functional trait or taxonomy affects allometric scaling in soil food webs.\nBelowground organisms often display a shift in their mass-abundance scaling relationships due to environmental factors such as soil chemistry and atmospheric deposition. Here we present new empirical data that show strong differences in allometric scaling according to whether the resolution at the local scale is based on a taxonomic or a functional classification, while only slight differences arise according to soil environmental conditions. For the first time, isometry (an inverse 1:1 proportion) is recognized in mass-abundance relationships, providing a functional signal for constant biomass distribution in soil biota regardless of discrete trophic levels. Our findings are in contrast to those from aquatic ecosystems, in that higher trophic levels in soil biota are not a direct function of increasing body mass.","subset":"pubmed_abstract"} +{"meta":{"pmid":29039274,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"Different Escherichia coli B2-ST131 clades (B and C) producing extended-spectrum \u03b2-lactamases (ESBL) colonizing residents of Portuguese nursing homes.\nESBL-producing Enterobacteriaceae and particularly Escherichia coli ST131 isolates producing CTX-M enzymes are commonly found colonizing the intestine of nursing home (NH) residents, but ST131 subclonal structure has been scarcely explored in this vulnerable population. Our goal was to perform a pilot study to assess the faecal carriage rate and epidemiological features of ESBL- and\/or carbapenemase-producing Enterobacteriaceae (ESBL-E and CPE, respectively) among NH residents. For this purpose, faecal samples from residents at 4 different NHs in the North of Portugal (representing 9\u00b75% of the residents' population, July 2014) were screened for ESBL-E and\/or CPE by phenotypic and genotypic methods. Clonal structure and plasmid typing of ESBL-producing E. coli (ESBL-Ec) was performed by PCR and sequencing. Four ESBL-Ec isolates (2 CTX-M-15\/2 CTX-M-14) were found in 20% of the samples, all belonging to the pandemic clonal lineage B2-ST131-O25b:H4. Two different clades were identified, the C2\/H30-Rx-virotype C producing CTX-M-15 and an atypical B\/H22-like-virotype D5 (producing CTX-M-14 and fluoroquinolone-resistant), firstly described in Portugal. This pilot study highlights the role of NH residents as a source of different ST131 clades, besides emphasizing the importance of E. coli B2-ST131 subtyping in different clinical settings, and understanding the transmission dynamics of the different variants.","subset":"pubmed_abstract"} +{"meta":{"pmid":15855029,"dup_signals":{"dup_doc_count":23,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-26":1,"unknown":20}}},"text":"Dependence of the DPOAE amplitude pattern on acoustical biasing of the cochlear partition.\nDistortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs in response to simultaneous increases in the levels of high frequency primary tones in the presence of a low frequency biasing tone of 30 Hz at 120 dB SPL. The DPOAE amplitudes plotted as functions of the biasing tone phase angle show distinctive repeatable minima, which are identical to the amplitude notches observed for the distortion products at the output of a single saturating non-linearity. The number of the amplitude minima grows with increasing order of the DPOAE, a feature that is also reproduced by the model. The model of DPOAE generation due to a single saturating non-linearity does not explain the experimentally observed asymmetry of the response of the DPOAEs to rising and falling half cycles of the biasing tone. This asymmetry is attributed to a hypothetical mechanism, which adjusts the operating point of the outer hair cell's mechanoelectrical transducer. Experimental data were consistent with a hypothesis that, for the parameters of stimulation used in this study, both lower and upper sideband DPOAEs are dominated by emission generated from a single and spatially localized place in the cochlea.","subset":"pubmed_abstract"} +{"meta":{"pmid":28588266,"dup_signals":{"dup_doc_count":28,"dup_dump_count":16,"dup_details":{"curated_sources":1,"2022-40":2,"2022-33":2,"2020-45":2,"2020-40":2,"2019-39":2,"2019-26":2,"2019-22":1,"2019-09":2,"2019-04":2,"2018-30":2,"2018-17":2,"2018-09":2,"2017-51":1,"2017-47":1,"2017-39":1,"2017-30":1}}},"text":"Rumen Fluid Metabolomics Analysis Associated with Feed Efficiency on Crossbred Steers.\nThe rumen has a central role in the efficiency of digestion in ruminants. To identify potential differences in rumen function that lead to differences in average daily gain (ADG), rumen fluid metabolomic analysis by LC-MS and multivariate\/univariate statistical analysis were used to identify differences in rumen metabolites. Individual feed intake and body-weight was measured on 144 steers during 105 d on a high concentrate ration. Eight steers with the greatest ADG and 8 steers with the least-ADG with dry matter intake near the population average were selected. Blood and rumen fluid was collected from the 16 steers 26 d before slaughter and at slaughter, respectively. As a result of the metabolomics analysis of rumen fluid, 33 metabolites differed between the ADG groups based on t-test, fold changes and partial least square discriminant analysis. These metabolites were primarily involved in linoleic and alpha-linolenic metabolism (impact-value 1.0 and 0.75, respectively; P < 0.05); both pathways were down-regulated in the greatest-ADG compared with least-ADG group. Ruminal biohydrogenation might be associated with the overall animal production. The fatty acids were quantified in rumen and plasma using targeted MS to validate and evaluate the simple combination of metabolites that effectively predict ADG.","subset":"pubmed_abstract"} +{"meta":{"pmid":23572295,"dup_signals":{"dup_doc_count":18,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2024-30":2,"2024-26":1,"2024-22":1,"2024-18":1,"2024-10":1,"2017-13":1,"unknown":10}}},"text":"Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.\nEvidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid\/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.","subset":"pubmed_abstract"} +{"meta":{"pmid":17730790,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Changes in atmospheric carbon-14 attributed to a variable sun.\nThe (14)C production rate in the upper atmosphere changes with time because the galactic cosmic-ray flux responsible for (14)C production is modulated by the changes in solar wind magnetic properties. The resulting changes in the atmospheric (14)C level are recorded in tree rings and are used to calculate past (14)C production rates from a carbon reservoir model that describes terrestrial carbon exchange between the atmosphere, ocean, and biosphere. These past (14)C production rate changes are compared with (14)C production rates determined from 20th-century neutron flux measurements, and a theory relating (14)C production and solar variability, as given by geomagnetic Aa indices and sunspot numbers, is developed. This theory takes into account long-term solar changes that were previously neglected. The 860-year (14)C record indicates three episodes when sunspots apparently were absent: A.D. 1654 to 1714 (Maunder minimum), 1416 to 1534 (Sp\u00f6rer minimum), and 1282 to 1342 (Wolf minimum). A less precisely defined minimum occurred near A.D. 1040. The part of this record after A.D. 1645 correlates well with the basic features of the historical record of sunspot numbers. The magnitude of the calculated (14)C production rates points to a further increase in cosmic-ray flux when sunspots are absent. This flux was greatest during the Sp\u00f6rer minimum. A record of approximate sunspot numbers and Aa indices for the current millennium is also presented.","subset":"pubmed_abstract"} +{"meta":{"pmid":11032916,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells.\nAntitumor effect of the stem bark of Acanthopanax senticosus HARMS (ASH) from Hokkaido (Japanese name: Ezoukogi) on human stomach cancer KATO III cells was investigated. The extract of the stem bark of ASH prepared with hot water was dissolved in distilled water and used for the assay of antitumor effect on the KATO III cells. The exposure of KATO III cells to ASH led to both growth inhibition and induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with ASH. The fragmentation by ASH of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. We have investigated which component in ASH is effective on the induction of apoptosis. Among chlorogenic acid, syringaresinol di-o-beta-D glucoside, syringin, and sesamin, components of the n-butanol extract prepared from ASH, sesamin suppressed the growth and induced apoptosis in the cells. These findings suggest that growth inhibition by ASH results from the apoptosis induced by sesamin, a component of ASH.","subset":"pubmed_abstract"} +{"meta":{"pmid":25558481,"dup_signals":{"dup_doc_count":17,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2022-27":1,"2021-31":1,"2021-25":1,"2021-21":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-29":1,"2019-13":1,"2019-04":1,"2018-43":1,"2023-14":1,"2024-10":1}}},"text":"Red luminescence and ferromagnetism in europium oxynitridosilicates with a \u03b2-K2SO4 structure.\nThe new compounds LaSrSiO3N and LaBaSiO3N activated with Eu(2+) are orange-red light-emitting luminescent materials under excitation in the UV-blue range. They represent the first examples of stoichiometric alkaline earth oxynitridosilicates with a \u03b2-K2SO4 structure. The isostructural compound LaEuSiO3N is ferromagnetic with a Curie temperature of 3 K and also shows red luminescence (\u03bbmax = 705 nm) under excitation at 405 nm.","subset":"pubmed_abstract"} +{"meta":{"pmid":7063861,"dup_signals":{"dup_doc_count":24,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-22":1,"2017-13":1,"2024-26":1,"unknown":19}}},"text":"The origin of man: a chromosomal pictorial legacy.\nMan, gorilla, and chimpanzee likely shared an ancestor in whom the fine genetic organization of chromosomes was similar to that of present man. A comparative analysis of high-resolution chromosomes from orangutan, gorilla, chimpanzee, and man suggests that 18 or 23 pairs of chromosomes of modern man are virtually identical to those of our \"common hominoid ancestor\", with the remaining pairs slightly different. From this lineage, gorilla separated fist, and three major chromosomal rearrangements presumably occurred in a progenitor of chimpanzee and man before the final divergence of these tow species. A precursor of the hominoid ancestor and orangutan is also assumed.","subset":"pubmed_abstract"} +{"meta":{"pmid":11408655,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":12}}},"text":"G protein regulation of ion channels and abscisic acid signaling in Arabidopsis guard cells.\nThe phytohormone abscisic acid (ABA) promotes plant water conservation by decreasing the apertures of stomatal pores in the epidermis through which water loss occurs. We found that Arabidopsis thaliana plants harboring transferred DNA insertional mutations in the sole prototypical heterotrimeric GTP-binding (G) protein alpha subunit gene, GPA1, lack both ABA inhibition of guard cell inward K(+) channels and pH-independent ABA activation of anion channels. Stomatal opening in gpa1 plants is insensitive to inhibition by ABA, and the rate of water loss from gpa1 mutants is greater than that from wild-type plants. Manipulation of G protein status in guard cells may provide a mechanism for controlling plant water balance.","subset":"pubmed_abstract"} +{"meta":{"pmid":18937623,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Topical diclofenac: clinical effectiveness and current uses in osteoarthritis of the knee and soft tissue injuries.\nDiclofenac is a commonly used non-steroidal anti-inflammatory drug (NSAID) for symptom control in osteoarthritis (OA) of the knee and soft tissue injuries. Although treatment with oral diclofenac is associated with serious adverse effects involving both the gastrointestinal and renal systems, these adverse effects are thought to be limited with topical diclofenac formulations without loss of efficacy. The aim of this review is to explore the available evidence in relation to the pharmacokinetics, efficacy and reported adverse effects of the topical diclofenac formulations available. In the majority of studies examined, topical diclofenac formulations with sodium lotion, lecithin or epolamine gel, patch or plaster were either superior or equivalent to oral diclofenac formulations or placebo. Topical diclofenac significantly reduced pain and morning stiffness and improved physical function and patient global assessment without major adverse effects reported in patients with OA of the knee; and provided significant pain relief in patients with sports and soft tissue injuries involving the ankle, knee or shoulder. In the majority of studies, the predominant adverse effect involved pruritus or rash at the site of application, or nausea. The principle outcome of these studies is that topical diclofenac is a safe and practical alternative as a method of treatment in OA of the knee or as an alternative treatment for sports and soft tissue injury.","subset":"pubmed_abstract"} +{"meta":{"pmid":15821191,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Lung volume reduction surgery vs medical treatment: for patients with advanced emphysema.\nTo contribute to the knowledge on the therapeutic value of lung volume reduction surgery (LVRS). Two similar, independently conceived and conducted, multicenter, randomized clinical trials. The Canadian Lung Volume Reduction (CLVR) study and the Overholt-Blue Cross Emphysema Surgery Trial (OBEST). Using a fixed-effects meta-analysis, the 6-month results produced by the addition of LVRS to optimal medical therapy were compared to those obtained from optimal medical therapy alone. Patients were required to have severe emphysema, marked airflow limitation (ie, FEV(1), 15 to 40% predicted), hyperinflation (total lung capacity [TLC], > 120% predicted), CO(2), < 55 mm Hg, and measurable dyspnea (chronic respiratory disease questionnaire [CRDQ] scores <\/= 4 for the CLVR study, or Medical Research Council dyspnea scale >\/= 1 for the OBEST). Optimal medical therapy included pulmonary rehabilitation in both arms of both studies. The CLVR study randomized 58 patients and the OBEST randomized 35 patients for a total of 93 patients. Of these, 54 patients were randomized to undergo surgery, and 39 patients were randomized to receive medical treatment. The 6-month mortality rate (including operative mortality) in the surgical and medical cohorts was similar (5.6% vs 5.1%, respectively). A comparison of the medical and surgical arms of the combined CLVR study\/OBEST population showed that LVRS was associated with a higher FEV(1) (167 mL or 24% predicted; 95% confidence interval [CI], 29 to 304; p = 0.017), lower residual volume (-1,342 mL or 24.5% predicted; 95% CI, -1,844 to -840; p < 0.001), lower TLC (-1,044 mL or 13% predicted; 95% CI, -1483 to -605; p < 0.001), and higher 6-min walk distance (148.8 feet; 95% CI, 24.3 to 273.2; p = 0.019). Each domain of the CRDQ showed statistically significant improvement in the surgical arm of the study, but not in the medical arm. The summary physical component scale of the Medical Outcomes Study 36-item short form (SF-36) was also more favorable in the LVRS cohort (6.9; 95% CI, 2.86 to 10.90; p < 0.001). The summary mental component scale of the SF-36 did not show a statistically significant difference between the two groups. Six months after randomization, LVRS produced better palliation than optimal medical therapy in patients with advanced emphysema.","subset":"pubmed_abstract"} +{"meta":{"pmid":30158947,"dup_signals":{"dup_doc_count":21,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":1,"2024-30":1,"unknown":17}}},"text":"Overexpression of a High-Affinity Nitrate Transporter OsNRT2.1 Increases Yield and Manganese Accumulation in Rice Under Alternating Wet and Dry Condition.\nNitrate and manganese (Mn) are necessary elements for the growth and development of rice in paddy soil. Under physiological conditions, we previously reported that the uptake of Mn in roots can be improved by the addition of external nitrate but not ammonium. To investigate the mechanism(s) of this phenotype, we produced plant lines overexpressing OsNRT2.1 and assessed Mn uptake under alternating wet and dry (AWD) and waterlogged (WL) conditions. Under AWD condition, we observed a 31% reduction in grain yields of wild type (WT) plants compared to WL condition. Interestingly, the overexpression of OsNRT2.1 could recover this loss, as OsNRT2.1 transgenic lines displayed higher grain yields than WT plants. We also observed 60% higher grain Mn in the transgenic lines in AWD condition and approximately 30% higher Mn in the grain of transgenic lines in WL condition. We further found that the overexpression of OsNRT2.1 did not alter Mg and Fe in the seeds in either growth condition. The reasons for the increased Mn content in OsNRT2.1 transgenic seeds in AWD condition could be explained by the elevated expression of OsNRAMP family genes including OsNRAMP3, OsNRAMP5, and OsNRAMP6 in node I, the panicle-neck, and the flag leaves. The mechanism(s) underpinning the upregulation of these genes requires further investigation. Taken together, our results provide a new function of OsNRT2.1 in improving rice yields and grain Mn accumulation during water-saving cultivation patterns. This represents a new strategy for maintaining yield and improving food quality in a sustainable agricultural system.","subset":"pubmed_abstract"} +{"meta":{"pmid":31817189,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-30":1,"unknown":7}}},"text":"Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?\nThe prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (\u22652\u00d7 upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4-5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.","subset":"pubmed_abstract"} +{"meta":{"pmid":27520794,"dup_signals":{"dup_doc_count":11}},"text":"Adolescent fiber intake and mammographic breast density in premenopausal women.\nTo date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent fiber intake with mammographic density in premenopausal women. This study included 743 cancer-free premenopausal women (mean age, 44.9 years) within the Nurses' Health Study II cohort. Percent breast density, absolute dense and non-dense areas were measured from digitized film mammograms using a computer-assisted thresholding technique. Adolescent and adult diet were assessed with a food frequency questionnaire; energy-adjusted nutrient intakes were estimated for each food item. Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations between quartiles of adolescent fiber intake and each of the breast density measures, adjusted for potential confounders. Associations were examined separately for total fiber intake; fiber from fruits, vegetables, legumes, and cereal; and food sources of fiber (fruits, vegetables, and nuts). In multivariable analyses, total fiber intake during adolescence was not associated with percent breast density (p for trend = 0.64), absolute dense area (p for trend = 0.80), or non-dense area (p for trend = 0.75). Similarly, neither consumption of fiber from fruits, vegetables, legumes, or cereal nor specific sources of fiber intake (fruits, vegetables, or nuts) during adolescence were associated with any of the mammographic density phenotypes. Our findings do not support the hypothesis that adolescent fiber intake is associated with premenopausal mammographic breast density.","subset":"pubmed_abstract"} +{"meta":{"pmid":33584383,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-26":1,"2024-10":1,"2024-30":1,"unknown":6}}},"text":"Mental Health Consequences for Healthcare Workers During the COVID-19 Pandemic: A Scoping Review to Draw Lessons for LMICs.\nBackground: The COVID-19 pandemic has had a significant impact on the mental health of healthcare workers (HCWs) particularly in low and middle-income countries (LMICs). This scoping review provides a summary of current evidence on the mental health consequences of COVID on HCWs. Methods: A scoping review was conducted searching PubMed and Embase for articles relevant to mental health conditions among HCWs during COVID-19. Relevant articles were screened and extracted to summarize key outcomes and findings. Results: A total of fifty-one studies were included in this review. Depressive symptoms, anxiety symptoms, psychological trauma, insomnia and sleep quality, workplace burnout and fatigue, and distress were the main outcomes reviewed. Most studies found a high number of symptoms endorsed for depression, anxiety, and other conditions. We found differences in symptoms by sex, age, and HCW role, with female, younger-aged, frontline workers, and non-physician workers being affected more than other subgroups. Conclusion: This review highlights the existing burden of mental health conditions reported by HCWs during COVID-19. It also demonstrates emerging disparities among affected HCW subgroups. This scoping review emphasizes the importance of generating high quality evidence and developing informed interventions for HCW mental health with a focus on LMICs.","subset":"pubmed_abstract"} +{"meta":{"pmid":15796243,"dup_signals":{"dup_doc_count":19,"dup_details":{"curated_sources":2,"unknown":17}}},"text":"Asynchronous, all-optical signal processing based on the self-frequency shift of a gigahertz Raman soliton.\nUltrafast asynchronous all-optical signal processing is experimentally demonstrated. It is based on the intensity-dependent, self-frequency shift of a gigahertz Raman soliton. We demonstrate error-free, asynchronous, all-optical, bit-by-bit, self-signal recognition and demultiplexing from contended optical packets without use of an optical buffer, control pulse, or bit-phase synchronization. Fourfold, contended, 9.95-Gbit\/s optical packets are transmitted through a conventional repeater span of 80 km and simultaneously demultiplexed to multiwavelength 9.95-Gbit\/s optical packets with 0.5-dB processing sensitivity. Furthermore, we successfully accomplish demultiplexing from overlapping signals in contended optical packets with better than 3-dB recognition sensitivity. We confirm the capability of realizing a 3x cascade operation from bit-error-rate measurements.","subset":"pubmed_abstract"} +{"meta":{"pmid":23794270,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-10":1,"2024-30":1,"unknown":8}}},"text":"Capturing and testing perceptual-cognitive expertise: a comparison of stationary and movement response methods.\nNumerous methods have been used to study expertise and performance. In the present article, we compare the cognitive thought processes of skilled soccer players when responding to film-based simulations of defensive situations involving two different experimental conditions. Participants either remained stationary in a seated position (n = 10) or were allowed to move (n = 10) in response to life-size film sequences of 11 versus 11 open-play soccer situations viewed from a player's perspective. Response accuracy and retrospective verbal reports of thinking were collected across the two task conditions. In the movement-based response group, participants generated a greater number of verbal report statements, including a higher proportion of evaluation, prediction, and action planning statements, than did participants in the stationary group. Findings suggest that the processing strategies employed during performance differ depending on the nature of the response required of participants. Implications for behavioral methods and experimental design are discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":10799897,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Arthropod- and host-specific Borrelia burgdorferi bbk32 expression and the inhibition of spirochete transmission.\nAntisera to BBK32 (a Borrelia burgdorferi fibronectin-binding protein) and BBK50, two Ags synthesized during infection, protect mice from experimental syringe-borne Lyme borreliosis. Therefore, B. burgdorferi bbk32 and bbk50 expression within Ixodes scapularis ticks and the murine host, and the effect of BBK32 and BBK50 antisera on spirochetes throughout the vector-host life cycle were investigated. bbk32 and bbk50 mRNA and protein were first detected within engorged ticks, demonstrating regulated expression within the vector. Then bbk32 expression increased in mice at the cutaneous site of inoculation. During disseminated murine infection, bbk32 and bbk50 were expressed in several murine tissues, and mRNA levels were greatest in the heart and spleen at 30 days. BBK32 antisera protected mice from tick-borne B. burgdorferi infection and spirochete numbers were reduced by 90% within nymphs that engorged on immunized mice. Moreover, 75% of these ticks did not retain spirochetes upon molting, and subsequent B. burgdorferi transmission by adult ticks was impaired. Larval acquisition of B. burgdorferi by I. scapularis was also inhibited by BBK32 antisera. These data demonstrate that bbk32 and bbk50 are expressed during tick engorgement and that BBK32 antisera can interfere with spirochete transmission at various stages of the vector-host life cycle. These studies provide insight into mechanisms of immunity to Lyme borreliosis and other vector-borne diseases.","subset":"pubmed_abstract"} +{"meta":{"pmid":30386564,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":7}}},"text":"Genetically determined fungal pathogen tolerance and soil variation influence ectomycorrhizal traits of loblolly pine.\nSelection on genetically correlated traits within species can create indirect effects on one trait by selection on another. The consequences of these trait correlations are of interest because they may influence how suites of traits within species evolve under differing selection pressures, both natural and artificial. By utilizing genetic families of loblolly pine either tolerant (t) or susceptible (s) to two different suites of pathogenic fungi responsible for causing either pine decline or fusiform rust disease, we investigated trait variation and trait correlations within loblolly pine (Pinus taeda L.) by determining how ectomycorrhizal (EM) colonization relates to pathogen susceptibility. We detected interactions between susceptibility to pathogenic fungi and soil inoculation source on loblolly pine compatibility with the EM fungi Thelephora, and on relative growth rate of loblolly pine. Additionally, we detected spatial variation in the loblolly pine-EM fungi interaction, and found that variation in colonization rates by some members of the EM community is not dictated by genetic variation in the host plant but rather soil inoculation source alone. The work presented here illustrates the potential for indirect selection on compatibility with symbiotic EM fungi as a result of selection for resistance to fungal pathogens. Additionally, we present evidence that the host plant does not have a single \"mycorrhizal trait\" governing interactions with all EM fungi, but rather that it can interact with different fungal taxa independently. Synthesis. An understanding of the genetic architecture of essential traits in focal species is crucial if we are to anticipate and manage the results of natural and artificial selection. As demonstrated here, an essential but often overlooked symbiosis (that between plants and mycorrhizal fungi) may be indirectly influenced by directed selection on the host plant.","subset":"pubmed_abstract"} +{"meta":{"pmid":18451909,"dup_signals":{"dup_doc_count":95,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2018-17":4,"2018-09":1,"2018-05":3,"2017-43":3,"2017-39":3,"2017-34":3,"2017-30":3,"2017-26":3,"2017-22":4,"2017-17":4,"2017-09":6,"2017-04":6,"2016-50":2,"2016-44":6,"2016-36":5,"2016-30":5,"2016-22":3,"2016-18":3,"2016-07":3,"2015-48":4,"2015-40":1,"2015-35":2,"2015-32":1,"2015-27":4,"2015-22":4,"2017-13":4,"2015-18":1}}},"text":"Scattering polarization by anisotropic biomolecules.\nThe full polarization properties of anisotropic biomolecule optical scattering are investigated theoretically. By using a simple ellipsoid model of a single biomolecule, the scattering fields and Mueller matrices are derived from fundamental electromagnetism theory. The energy of scattered photons is not necessarily equal to that of the incident laser beam. This theory can be generally applied to the experiments of fluorescence, Raman scattering, and second-harmonic generation. Fitting of a single tetramethylrhodamine-labeled lipid molecule's anisotropic imaging experiment is demonstrated. This theory has provided a fundamental simulation analysis tool of understanding and developing the optical polarimetric sensing science and technology of the anisotropic biomolecules and biomedium. The medium dielectric constant of the model ellipsoid provides a theoretic background for correlating the optical polarization properties of a biomolecule to its microscopic electronic structure.","subset":"pubmed_abstract"} +{"meta":{"pmid":23981510,"dup_signals":{"dup_doc_count":25,"dup_dump_count":17,"dup_details":{"curated_sources":2,"2023-40":2,"2015-48":1,"2015-40":1,"2015-35":1,"2015-32":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":3,"2014-41":1,"2014-35":2,"2014-23":2,"2014-15":2,"2023-50":1,"2024-18":1,"2024-30":1}}},"text":"Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study.\nThe profile of cognitive and behavioral variation observed in individuals with fragile X syndrome (FXS), the most common known cause of inherited intellectual impairment, suggests aberrant functioning of specific brain systems. Research investigating animal models of FXS, characterized by limited or lack of fragile X mental retardation protein, (FMRP), has linked brain dysfunction to deficits in the cholinergic and glutamatergic systems. Thus, we sought to examine in vivo levels of neurometabolites related to cholinergic and glutamatergic functioning in males and females with FXS. The study participants included 18 adolescents and young adults with FXS, and a comparison group of 18 individuals without FXS matched for age, sex and general intellectual functioning. Proton magnetic resonance spectroscopy (MRS) was used to assess neurometabolite levels in the caudate nucleus, a region known to be greatly enlarged and involved in abnormal brain circuitry in individuals with FXS. A general linear model framework was used to compare group differences in metabolite concentration. We observed a decrease in choline (P = 0.027) and in glutamate + glutamine (P = 0.032) in the caudate nucleus of individuals with FXS, relative to individuals in the comparison group. This study provides evidence of metabolite differences in the caudate nucleus, a brain region of potential importance to our understanding of the neural deficits underlying FXS. These metabolic differences may be related to aberrant receptor signaling seen in animal models. Furthermore, identification of the specific neurometabolites involved in FXS dysfunction could provide critical biomarkers for the design and efficacy tracking of disease-specific pharmacological treatments.","subset":"pubmed_abstract"} +{"meta":{"pmid":12423194,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Relationship between football playing ability and selected performance measures.\nThe relationships between football playing ability (FPA) and selected anthropometric and performance measures were determined among NCAA Division I-A football players (N = 40). Football playing ability (determined by the average of coaches' rankings) was significantly correlated with vertical jump (VJ) in all groups (offense, defense, and position groups of wide receiver-defensive back, offensive linemen-defensive linemen, and running back-tight end-linebacker). Eleven of 50 correlations (groups by variables), or 22%, were important for FPA. Five of the 11 relationships were related to VJ. Forward stepwise regression equations for each group explained over half of the criterion variable, FPA, as indicated by the R(2) values for each model. Vertical jump was the prime predictor variable in the equations for all groups. The findings of this study are discussed in relation to the specificity hypothesis. Strength and conditioning programs that facilitate the capacity for football players to develop forceful and rapid concentric action through plantar flexion of the ankle, as well as extension of the knee and hip, may be highly profitable.","subset":"pubmed_abstract"} +{"meta":{"pmid":28621350,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Photoinduced structural distortions and singlet-triplet intersystem crossing in Cu(i) MLCT excited states monitored by optically gated fluorescence spectroscopy.\nCopper(i) phenanthroline complexes represent viable earth-abundant alternatives to the ubiquitous Ru(ii) tris-bipyridine photosensitizers owing to their similar metal-to-ligand charge transfer (MLCT) properties. A well-established complication of Cu(i) phenanthroline complexes is that they can undergo significant photo-induced structural rearrangements, leading to excited states that are highly susceptible to exciplex formation and short-lived. In this work, a comprehensive analysis of the photo-induced structural distortions and singlet-triplet intersystem crossing dynamics of a series of four sterically encumbered Cu(i) phenanthroline chromophores has been conducted, namely, [Cu(dsbp)2]+ (dsbp = 2,9-di-sec-butyl-1,10-phenanthroline), [Cu(dsbtmp)2]+ (dsbtmp = 2,9-di-sec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline), [Cu(dipp)2]+ (dipp = 2,9-di-isopropyl-1,10-phenanthroline), and [Cu(diptmp)2]+ (diptmp = 2,9-di-isopropyl-3,4,7,8-tetramethyl-1,10-phenanthroline). Upconverted fluorescence decay kinetics were measured at wavelengths along the blue side of the photoluminescence spectrum. The experimental results displayed strong wavelength dependence of the singlet emission, with rapid sub-picosecond decay dominating at higher energies. At lower emission energies, increasing contribution of a longer decay component was revealed. This wavelength dependence is a signature of the excited state structural rearrangement of the phenanthroline ligands which concomitantly lower the excited state energy. The obtained time constants were in excellent agreement with those measured in the complementary ultrafast transient absorption experiments. The sub-picosecond component (prompt fluorescence) is associated with the photo-induced structural rearrangement that lowers the energy of the singlet excited state. The longer decay component represents the lifetime of the S1 excited state, and thus the time-scale of singlet-triplet intersystem crossing. Lastly, the observed dual emission was further characterized by constructing picosecond time-resolved emission spectra from the measured kinetic data. These qualitative luminescence spectra capture the resulting emission from both the S1 initial state and the S1 flattened state, providing further insight into the energy-lowering excited state distortion across the series.","subset":"pubmed_abstract"} +{"meta":{"pmid":23966295,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer.\nBasal-like breast cancer (BLBC) is an aggressive disease that lacks a clinically approved targeted therapy. Traditional chemotherapy is effective in BLBC, but it spares the cancer stem cell (CSC)-like population, which is likely to contribute to cancer recurrence after the initial treatment. Dual specificity phosphatase-4 (DUSP4) is a negative regulator of the mitogen-activated protein kinase (MAPK) pathway that is deficient in highly aggressive BLBCs treated with chemotherapy, leading to aberrant MAPK activation and resistance to taxane-induced apoptosis. Herein, we investigated how DUSP4 regulates the MAP-ERK kinase (MEK) and c-jun-NH2-kinase (JNK) pathways in modifying CSC-like behavior. DUSP4 loss increased mammosphere formation and the expression of the CSC-promoting cytokines interleukin (IL)-6 and IL-8. These effects were caused in part by loss of control of the MEK and JNK pathways and involved downstream activation of the ETS-1 and c-JUN transcription factors. Enforced expression of DUSP4 reduced the CD44(+)\/CD24(-) population in multiple BLBC cell lines in a MEK-dependent manner, limiting tumor formation of claudin-low SUM159PT cells in mice. Our findings support the evaluation of MEK and JNK pathway inhibitors as therapeutic agents in BLBC to eliminate the CSC population.","subset":"pubmed_abstract"} +{"meta":{"pmid":37565425,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":5,"2024-22":2,"2024-10":1,"2024-30":1,"unknown":5}}},"text":"Variation in care for patients presenting with hip fracture in six high-income countries: A cross-sectional cohort study.\nHip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries. We performed a retrospective serial cross-sectional cohort study of adults aged \u226566 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30-day readmission rates, and time-to-surgery. The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30-day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%-45%) and THA (0.2%-10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%-60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30-day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada). We observed substantial between-country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence-based surgical approaches.","subset":"pubmed_abstract"} +{"meta":{"pmid":36646051,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":6,"2024-22":1,"2024-10":1,"2024-30":1,"unknown":10}}},"text":"Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study.\nMicrovascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these co-morbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and\/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity. The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow pre-clinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.","subset":"pubmed_abstract"} +{"meta":{"pmid":26465198,"dup_signals":{"dup_doc_count":18,"dup_dump_count":13,"dup_details":{"curated_sources":4,"2023-50":2,"2023-14":1,"2022-40":1,"2022-33":1,"2022-05":1,"2021-39":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-29":1,"2024-22":1}}},"text":"Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner.\nEstrogens are well known for their enhancing effects on hippocampus-sensitive cognition. However, estrogens can also impair learning and memory, particularly the acquisition of striatum-sensitive tasks. These cognitive shifts appear to be mediated through local estrogen receptor (ER) activation in each neural structure, but little information is known regarding which specific ER subtypes drive the opposing effects on learning. Elucidating the mnemonic roles of discrete ER subtypes is essential for predicting how treatments with distinct ER pharmacology such as drugs, hormone therapies, and phytoestrogen supplements affect cognitive abilities in and thus the daily lives of the women who take them. The present study examined the effects of the ER\u03b1-selective compound propyl pyrazole triol and the ER\u03b2-selective compounds diarylpropionitrile and Br-ERb-041 on place and response learning in young adult female rats. Long-Evans rats were ovariectomized and maintained on phytoestrogen-free chow for 3 weeks before behavioral training, with treatments administered via subcutaneous injection 48 and 24 hours before testing. A dose-response paradigm was used, with each compound tested at 4 different doses in separate groups of rats. Propyl pyrazole triol, diarylpropionitrile, and Br-ERb-041 all enhanced place learning and impaired response learning, albeit with distinct dose-response patterns for each compound and task. These results are consistent with the detection of ER\u03b1 and ER\u03b2 in the hippocampus and striatum and suggest that learning is modulated via activation of either ER subtype.","subset":"pubmed_abstract"} +{"meta":{"pmid":2582238,"dup_signals":{"dup_doc_count":16,"dup_dump_count":10,"dup_details":{"curated_sources":4,"2022-05":1,"2021-49":1,"2021-31":1,"2021-17":2,"2020-50":1,"2020-34":1,"2020-29":1,"2020-16":2,"2023-06":1,"2024-10":1}}},"text":"Human cellular src gene: nucleotide sequence and derived amino acid sequence of the region coding for the carboxy-terminal two-thirds of pp60c-src.\nThe nucleotide sequence of the 3' two-thirds of a highly conserved, molecularly cloned human cellular src gene (c-src) has been determined. This region of the c-src gene encodes the tyrosine kinase domain of the cellular src protein (pp60c-src) and corresponds to exons 6 through 12 of the chicken c-src gene, as well as nucleotides 545 to 1542 of the Rous sarcoma virus src gene (v-src). The human c-src sequence is very strongly conserved with respect to both the chicken c-src and the Rous sarcoma virus v-src genes, with nearly 90% nucleotide homology observed in this region. Amino acid sequence conservation in this region is even greater; 98% of the amino acids are conserved between human and chicken c-src. Furthermore, the exon sizes and the locations of the exon-intron boundaries are identical in the human and chicken c-src genes. However, sequences within the introns have not been conserved, and the introns within the human c-src gene are significantly larger than the corresponding introns within the chicken c-src gene. The strong amino acid conservation between the carboxy-terminal two-thirds of pp60c-src of species as divergent as humans and chickens suggests that this portion of the pp60c-src protein specifies one or more functional domains that are of great importance to some aspect of normal cellular growth or differentiation.","subset":"pubmed_abstract"} +{"meta":{"pmid":28853610,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.\nBackground The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm3, p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.","subset":"pubmed_abstract"} +{"meta":{"pmid":24600397,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Autonomic dysfunction in muscular dystrophy: a theoretical framework for muscle reflex involvement.\nMuscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and\/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.","subset":"pubmed_abstract"} +{"meta":{"pmid":11237869,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Differential expression of chicken dimerization cofactor of hepatocyte nuclear factor-1 (DcoH) and its novel counterpart, DcoHalpha.\nWe have used differential display PCR to study altered gene expression in immortalized chicken embryo fibroblasts (CEFs) that have been established in our laboratory. This technique resulted in the cloning of a novel counterpart of the previously cloned chicken dimerization cofactor of hepatocyte nuclear factor (HNF)-1 (cDcoH), which was identified as cDcoHalpha. The steady-state mRNA levels of cDcoHalpha were up-regulated in all immortal CEFs tested compared with primary CEF cells. cDcoH and cDcoHalpha showed opposite patterns of mRNA expression due to differential regulation of transcription rates, but not mRNA half-lives, in primary and immortal CEFs. Expression of cDcoHalpha increased in the late G1 and early S phases of the cell cycle, while cDcoH mRNA increased in the late S and G2\/M phases. In contrast with consistent expression of both genes in primary quiescent cells, cDcoH mRNA, but not cDcoHalpha mRNA, was dramatically decreased in primary senescent cells. The highest levels of cDcoHalpha mRNA were found in the kidney, liver, heart and ovarian follicles, while the major tissues expressing cDcoH were hypothalamus, kidney and liver. cDcoH and cDcoHalpha probes did not cross-hybridize to human hepatocyte mRNA. When transfected into human HepG2 cells, both cDcoH and cDcoHalpha showed similar functional activity as measured by increased expression of a reporter gene, as well as alpha-fetoprotein and albumin genes that both contain HNF-1 binding elements in their promoters. Our results suggest that the novel chicken DcoHalpha might function as a transcriptional cofactor for HNF-1 in specific cellular-environmental states.","subset":"pubmed_abstract"} +{"meta":{"pmid":27047451,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":15}}},"text":"Biogeochemical and Microbial Variation across 5500 km of Antarctic Surface Sediment Implicates Organic Matter as a Driver of Benthic Community Structure.\nWestern Antarctica, one of the fastest warming locations on Earth, is a unique environment that is underexplored with regards to biodiversity. Although pelagic microbial communities in the Southern Ocean and coastal Antarctic waters have been well-studied, there are fewer investigations of benthic communities and most have a focused geographic range. We sampled surface sediment from 24 sites across a 5500 km region of Western Antarctica (covering the Ross Sea to the Weddell Sea) to examine relationships between microbial communities and sediment geochemistry. Sequencing of the 16S and 18S rRNA genes showed microbial communities in sediments from the Antarctic Peninsula (AP) and Western Antarctica (WA), including the Ross, Amundsen, and Bellingshausen Seas, could be distinguished by correlations with organic matter concentrations and stable isotope fractionation (total organic carbon; TOC, total nitrogen; TN, and \u03b4(13)C). Overall, samples from the AP were higher in nutrient content (TOC, TN, and NH4 (+)) and communities in these samples had higher relative abundances of operational taxonomic units (OTUs) classified as the diatom, Chaetoceros, a marine cercozoan, and four OTUs classified as Flammeovirgaceae or Flavobacteria. As these OTUs were strongly correlated with TOC, the data suggests the diatoms could be a source of organic matter and the Bacteroidetes and cercozoan are grazers that consume the organic matter. Additionally, samples from WA have lower nutrients and were dominated by Thaumarchaeota, which could be related to their known ability to thrive as lithotrophs. This study documents the largest analysis of benthic microbial communities to date in the Southern Ocean, representing almost half the continental shoreline of Antarctica, and documents trophic interactions and coupling of pelagic and benthic communities. Our results indicate potential modifications in carbon sequestration processes related to change in community composition, identifying a prospective mechanism that links climate change to carbon availability.","subset":"pubmed_abstract"} +{"meta":{"pmid":18616936,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":13}}},"text":"DNA methyltransferase loading, but not de novo methylation, is an oocyte-autonomous process stimulated by SCF signalling.\nEpigenetic reprogramming occurs during oocyte growth in mice, a stage where a number of important events are occurring, including transcription of maternal mRNAs for storage in the mature egg, global transcriptional silencing and the acquisition of meiotic competence. Oocyte growth occurs in conjunction with follicular development over a period of many days. The signals involved in initiating different stages in oocyte and follicular development and the concurrent epigenetic changes are poorly understood. Here we examine the role of stem cell factor (SCF or Kit ligand) on the early- to mid-stages of oocyte growth and on DNA methyltransferase expression and function using a one-step in vitro culture system. Our results show that SCF promotes early oocyte growth and development to the multilaminar follicle stage. Oocyte growth is sufficient to trigger transcription of Dnmt1 and Dnmt3L from dedicated oocyte promoters, and we show that eggs undergoing growth in the absence of follicle development in Foxo3 mutants show elevated levels of Dnmt1. The methyltransferase proteins undergo sequential relocalisation in the oocyte, with DNMT1 being exported from the nucleus at the bilaminar follicle stage, while DNMT3A is transported into the nucleus at the multilaminar stage, indicating an important role for trafficking in controlling imprinting. SCF is thought to signal partly through the phophostidylinositol 3 (PI3) kinase pathway: inhibiting this path was previously shown to prevent FOXO3 nuclear export and we could show here that it also prevented DNMT1 export. Some oocytes reached full size (70 microM) in this in vitro system, but no secondary follicles were formed, most likely due to failure of the thecal layer to form properly. De novo methylation of imprinted genes was seen in some oocyte cultures, with methylation levels being highest for Snrpn and Igf2r which are methylated early in vivo, while Peg1, which is methylated late, showed little or no methylation. SCF treatment did not increase the number of cultures showing methylation. We saw no evidence for de novo methylation of IAP repeats in our cultures. These results suggest that while methyltransferase loading is triggered by oocyte growth, in which SCF plays an important role, complete methylation probably requires progression to the secondary follicle stage and is unlikely to be affected by SCF.","subset":"pubmed_abstract"} +{"meta":{"pmid":34965508,"dup_signals":{"dup_doc_count":22,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-30":2,"2024-18":2,"unknown":16}}},"text":"Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.\nBreast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. Random samples of patients with BC (\u226540 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients (\"traced patients\"). Excess hazards of death by therapy use were modeled in a relative survival context. A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.","subset":"pubmed_abstract"} +{"meta":{"pmid":22526895,"dup_signals":{"dup_doc_count":17,"dup_dump_count":14,"dup_details":{"curated_sources":2,"2021-43":1,"2020-29":1,"2019-43":1,"2019-04":1,"2018-30":1,"2018-05":1,"2017-39":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2022-49":1,"2017-13":1,"2024-22":1}}},"text":"Impact of laminar flow velocity of different acids on enamel calcium loss.\nThe aim of the study was to evaluate the impact of flow velocity under laminar flow conditions of different acidic solutions on enamel erosion. A total of 240 bovine enamel specimens were prepared and allocated to 30 groups (n = 8 each). Samples of 18 groups were superfused in a flow chamber system with laminar flow behavior using 1 ml of citric acid or hydrochloric acid (HCl) of pH 2.0, 2.6 or 3.0. Flow rates in the sample chamber were adjusted to 10, 60 or 100 \u03bcl\/min. To simulate turbulent flow behavior, samples of six groups were immersed in 1 ml of the respective solution, which was vortexed (15 min, 600 rpm). For simulating non-agitated conditions, specimens of the remaining six groups were immersed in 1 ml of the respective solution without stirring. Calcium in the solutions, released from the enamel samples, was determined using Arsenazo III method. For acidic solutions of pH 2.6 and 3.0, erosive potential of citric acid was equivalent to that of HCl at a flow of 100 \u03bcl\/min. The same observation was made for the samples subjected to turbulent conditions at pH 3. At all other conditions, citric acid induced a significantly higher calcium loss than HCl. It is concluded that under slow laminar flow conditions, flow rate variations lead to higher erosive impact of citric acid compared to hydrochloric acid at pH 2.0, but not at pH \u2265 2.6 and increasing laminar flow or turbulent conditions. Erosive enamel dissolution under laminar flow conditions is a complex issue influenced by flow rate and acidic substrate.","subset":"pubmed_abstract"} +{"meta":{"pmid":34405142,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":11}}},"text":"Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: a multicentre observational cohort study.\nThe novel coronavirus SARS-CoV-2 causes the infectious disease COVID-19. Newly developed mRNA vaccines can prevent the spread of the virus. Headache is the most common neurological symptom in over 50% of those vaccinated. Detailed information about the clinical characteristics of this form of headache has not yet been described. The aim of the study is to examine in detail the clinical characteristics of headaches occurring after vaccination against COVID-19 with the BNT162b2 mRNA COVID-19 vaccine for the first time. In a multicentre observational cohort study, data on the clinical features and corresponding variables were recorded using a standardized online questionnaire. The questionnaire was circulated to 12 000 residential care homes of the elderly as well as tertiary university hospitals in Germany and the United Arab Emirates. The primary outcomes of this study are the clinical features of headache after vaccination. Comorbidities, treatment with medication and sociodemographic variables are also analysed. A total of 2349 participants reported headaches after vaccination with the BNT162b2 mRNA COVID-19 vaccine. Headaches occur an average of 18.0 \u00b1 27.0 h after vaccination and last an average duration of 14.2 \u00b1 21.3 h. Only 9.7% of those affected also report headaches resulting from previous vaccinations. In 66.6% of the participants, headache occurs as a single episode. A bilateral location is indicated by 73.1% of the participants. This is most often found on the forehead (38.0%) and temples (32.1%). A pressing pain character is indicated by 49.2% and 40.7% report a dull pain character. The pain intensity is most often moderate (46.2%), severe (32.1%) or very severe (8.2%). The most common accompanying symptoms are fatigue (38.8%), exhaustion (25.7%) and muscle pain (23.4%). Headaches after COVID-19 vaccination show an extensive complex of symptoms. The constellation of accompanying symptoms together with the temporal and spatial headache characteristics delimit a distinctive headache phenotype.","subset":"pubmed_abstract"} +{"meta":{"pmid":17550622,"dup_signals":{"dup_doc_count":12}},"text":"Targeting services to reduce social inequalities in utilisation: an analysis of breast cancer screening in New South Wales.\nMany jurisdictions have used public funding of health care to reduce or remove price at the point of delivery of services. Whilst this reduces an important barrier to accessing care, it does nothing to discriminate between groups considered to have greater or fewer needs. In this paper, we consider whether active targeted recruitment, in addition to offering a 'free' service, is associated with a reduction in social inequalities in self-reported utilization of the breast screening services in NSW, Australia. Using the 1997 and 1998 NSW Health Surveys we estimated probit models on the probability of having had a screening mammogram in the last two years for all women aged 40-79. The models examined the relative importance of socio-economic and geographic factors in predicting screening behaviour in three different needs groups - where needs were defined on the basis of a woman's age. We find that women in higher socio-economic groups are more likely to have been screened than those in lower groups for all age groups. However, the socio-economic effect is significantly less among women who were in the actively targeted age group. This indicates that recruitment and follow-up was associated with a modest reduction in social inequalities in utilisation although significant income differences remain.","subset":"pubmed_abstract"} +{"meta":{"pmid":16339180,"dup_signals":{"dup_doc_count":86,"dup_dump_count":50,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":4,"2023-23":4,"2023-14":3,"2023-06":1,"2022-49":2,"2022-40":1,"2022-27":3,"2022-21":1,"2022-05":3,"2021-43":1,"2021-39":5,"2021-31":3,"2021-25":1,"2021-21":1,"2021-17":1,"2021-10":3,"2021-04":1,"2020-50":1,"2020-45":1,"2020-40":3,"2020-24":1,"2019-18":1,"2019-09":2,"2018-51":1,"2018-47":1,"2018-43":1,"2018-39":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-22":1,"2018-17":1,"2018-13":2,"2017-51":2,"2017-43":2,"2017-34":2,"2017-30":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-22":2,"2024-18":2,"2024-10":2,"2017-13":1,"2024-30":1}}},"text":"Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels.\nATP-sensitive K+ (K(ATP)) channels are hetero-octamers of inwardly rectifying K+ channel (Kir6.2) and sulphonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). Heterozygous gain-of-function mutations in Kir6.2 cause neonatal diabetes, which may be accompanied by epilepsy and developmental delay. However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. We examined the effects of adenine nucleotides on K(ATP) channels containing wild-type or mutant (Q52R, R201H) Kir6.2 plus either SUR1 or SUR2A. In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1- and SUR2A-containing channels to similar extents, but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. Mg-nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. Both mutations also increased resting whole-cell K(ATP) currents through heterozygous SUR1-containing channels to a greater extent than for heterozygous SUR2A-containing channels. The greater ATP inhibition of mutant Kir6.2\/SUR2A than of Kir6.2\/SUR1 can explain why gain-of-function Kir6.2 mutations manifest effects in brain and beta-cells but not in the heart.","subset":"pubmed_abstract"} +{"meta":{"pmid":2550826,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":2,"2023-23":1,"2022-49":1,"2022-21":1,"2021-43":2,"2021-39":1,"2021-25":1,"2021-10":1,"2020-50":1,"2020-40":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2017-51":1,"2017-43":1,"2023-40":1,"2024-22":1}}},"text":"Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels.\nThe endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha 2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that alpha 2 cells generate Ca2+-dependent action potentials. The frequency of these action potentials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system, and co-localizes with insulin in pancreatic beta cells. We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes.","subset":"pubmed_abstract"} +{"meta":{"pmid":21498483,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":8}}},"text":"Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons.\nOsteonecrosis of the jaw (ONJ) in association with use of bisphosphonate (BP) has been described primarily in cancer patients receiving high-dose intravenous BP. The frequency of the condition in patients with osteoporosis appears to be low. We evaluated the frequency of BP-associated ONJ in Ontario in the cancer population and in those receiving BP for osteoporosis and metabolic bone disease. A survey developed by representatives of the Ontario Society of Oral and Maxillofacial Surgeons was mailed to Ontario oral and maxillofacial surgeons (OMFS) in December 2006, asking oral surgeons to provide information on cases of ONJ seen in the previous 3 calendar years (2004 to 2006). OMFS were subsequently contacted by telephone if they had not responded or if they had reported cases of ONJ. The frequency of ONJ in association with BP use was estimated from the number of patients with filled prescriptions for BP in Ontario between 2004 and 2006. The cumulative incidence of ONJ was calculated separately for patients using intravenous (IV) BP for cancer treatment and for patients using oral or IV BP for osteoporosis or other metabolic bone disease. Between 2004 and 2006, 32 ONJ cases were identified. Nineteen patients received IV BP for cancer treatment and 13 patients received oral or IV BP for osteoporosis or metabolic bone disease. Over a 3-year period the cumulative incidence of BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or other metabolic bone disease observations (1.04 per 100,000). The relative risk of low dose IV\/oral BP-associated ONJ was 0.002 (95% CI 0.001, 0.005) compared to high-dose IV BP. Other risk factors for ONJ were present in all cases in whom detailed assessment was available. The median duration of exposure to BP was 42 months (range 36 to 120 mo) and 42 months (range 11 to 79 mo) in osteoporosis patients and cancer patients, respectively. Over a 3-year period, the cumulative incidence for BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or metabolic bone disease observations (1.04 per 100,000). This study provides an approximate frequency of BP-associated ONJ in Canada. These data need to be quantified prospectively with accurate assessment of coexisting risk factors.","subset":"pubmed_abstract"} +{"meta":{"pmid":3611193,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"Crystalline tubes of myosin subfragment-2 showing the coiled-coil and molecular interaction geometry.\nWe have produced crystalline tubes of chicken breast myosin long subfragment-2 that show order to resolutions better than 2 nm. The tubes were formed from a thin sheet in which the myosin long subfragment-2 molecules were arranged on an approximately rectangular crystalline lattice with a = 14.1 +\/- 0.2 nm and b = 3.9 +\/- 0.1 nm in projection. Shadowing indicated that the tube wall was approximately 7 nm thick and that the sheets from which it was formed followed a right-handed helix. Superposition of the lattices from the top and bottom of the tube produced a moire pattern in negatively stained material, but images of single sheets were easily obtained by computer image processing. Although several molecules were superimposed perpendicular to the plane of the sheet, the modulation in density due to the coiled-coil envelope was clear, indicating that the coiled-coils in these molecules were in register (or staggered by an even number of quarter pitches). In projection the coiled-coil had an apparent pitch of 14.1 nm (the axial repeat of the unit cell), but the small number of molecules (probably four) superimposed perpendicular to the plane of the sheet meant that pitches within approximately 1 nm of this value could have shown a modulation. Therefore, a more precise determination of the coiled-coil pitch must await determination of the sheet's three-dimensional structure. The coiled-coils of adjacent molecules within the plane of the sheet were staggered by an odd number of quarter pitches. This arrangement was similar to that between paramyosin molecules in molluscan thick filaments and may have features in common with other coiled-coil protein assemblies, such as intermediate filaments. Each molecule in the crystal had two types of neighbor: one staggered by an odd number of quarter pitches and the other by an even number of quarter pitches, as has been proposed for the general packing of coiled-coils (Longley, W., 1975, J. Mol. Biol., 93:111-115). We propose a model for the detailed packing within the sheet whereby molecules are inclined slightly to the plane of the sheet so that its thickness is determined by the molecular length.","subset":"pubmed_abstract"} +{"meta":{"pmid":17628568,"dup_signals":{"dup_doc_count":16}},"text":"Articular cartilage mechanical and biochemical property relations before and after in vitro growth.\nThe aim of this study was to design in vitro growth protocols that can comprehensively quantify articular cartilage structure-function relations via measurement of mechanical and biochemical properties. Newborn bovine patellofemoral groove articular cartilage explants were tested sequentially in confined compression (CC), unconfined compression (UCC), and torsional shear before (D0, i.e. day zero) and after (D14, i.e. day 14) unstimulated in vitro growth. The contents of collagen (COL), collagen-specific pyridinoline (PYR) crosslinks, glycosaminoglycan, and DNA significantly decreased during in vitro growth; consequently, a wide range of biochemical properties existed for investigating structure-function relations when pooling the D0 and D14 groups. All D0 mechanical properties were independent of compression strain while only Poisson's ratios were dependent on direction (i.e. anisotropic). Select D0 and D14 group mechanical properties were correlated with biochemical measures; including (but not limited to) results that CC\/UCC moduli and UCC Poisson's ratios were correlated with COL and PYR. COL network weakening during in vitro growth due to reduced COL and PYR was accompanied by reduced CC\/UCC moduli and increased UCC Poisson's ratios.","subset":"pubmed_abstract"} +{"meta":{"pmid":28891762,"dup_signals":{"dup_doc_count":29,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2022-49":1,"2022-33":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":2,"2021-17":1,"2021-10":1,"2021-04":2,"2020-40":2,"2020-29":1,"2020-16":2,"2019-47":1,"2019-39":1,"2019-26":1,"2019-13":1,"2018-13":1,"2018-05":1,"2023-40":1,"2024-30":1}}},"text":"Reading and Phonological Awareness in Africa.\nLiteracy levels in Africa are low, and school instruction outcomes are not promising. Africa also has a disproportionate number of unschooled children. Phonological awareness (PA), especially phoneme awareness, is critically associated with literacy, but there is little evidence about whether PA is gained through literacy, schooling, or both, because most children studied are in education and can read at least letters. Our previous study of PA and reading in children in and out of school in Tanzania found that PA was associated with reading ability, not schooling or age, and many unschooled children learned to read. We retested 85 children from the baseline study, on measures of PA and literacy, approximately 2 years later. We found that more unschooled children had now learned to read but PA had generally not improved for these children. Unschooled children were still poorer at PA than schooled children. At 2 years, schooling now independently predicted PA and literacy. PA also predicted literacy and vice versa. Explicit phoneme awareness was again poor, even in accurate readers. More unschooled children have now learned to read, possibly because local literacy is in their first language; however, schooling improves reading and PA.","subset":"pubmed_abstract"} +{"meta":{"pmid":6471194,"dup_signals":{"dup_doc_count":11}},"text":"Acquired renal cystic disease in the end stage kidney: urological implications.\nA unique form of acquired renal cystic disease occurs commonly in the end stage kidneys of patients with chronic renal failure. Recent experience with 3 cases of acquired renal cystic disease has made us aware that the condition has significant urological implications. The pathogenesis of this disease is unknown but may be related to tubular obstruction, ischemia or the accumulation of toxic products. The diagnosis of acquired renal cystic disease is established by either ultrasound or computerized tomography, both of which demonstrate bilateral multiple small cysts scattered throughout the cortex and medulla of the contracted end stage kidney. Acquired renal cystic disease usually is asymptomatic but may be associated with either hemorrhage or neoplasia. Autopsy studies have revealed renal tumors in up to 45 per cent of the patients with acquired renal cystic disease. These tumors usually are small but our case 3 was a renal cell carcinoma that measured 4 cm. in diameter. Also, there have been other recent reports of large tumors and deaths of metastatic renal carcinoma in patients with acquired renal cystic disease. Patients with chronic renal failure should undergo periodic examination of the native kidneys by either ultrasound or computerized tomography. It may be difficult to distinguish benign from malignant lesions radiologically, and nephrectomy may be indicated when the diagnosis is uncertain.","subset":"pubmed_abstract"} +{"meta":{"pmid":22137250,"dup_signals":{"dup_doc_count":15,"dup_dump_count":13,"dup_details":{"curated_sources":2,"2018-22":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-26":1,"2017-22":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-47":1,"2017-13":1}}},"text":"Identification and characterization of Lactobacillus florum strains isolated from South African grape and wine samples.\nA total of 213 strains of lactic acid bacteria were examined in this study. Among these, 30 strains previously isolated from South African grape and wine samples remained unidentified. The identification of these isolates was performed by BLAST and phylogenetic analyses of 16S rDNA gene sequences, which indicated that the isolates belonged to Lactobacillus florum. In this work, we also designed a discriminative species-specific primer FLOR targeting the 16S rDNA gene of Lb. florum. The validity and specificity of this primer was confirmed. Of particular interest in this study was to further evaluate the identified strains for the presence of genes encoding enzymes of oenological relevance. Reference strains included three flower-associated Lb. florum (F9-1(T), F9-2 and F17) and two Lactobacillus lindneri (AWRI B530 and DSM 20691) strains. Lb. lindneri strains were incorporated as being the closest relatives of Lb. florum. PCR detection results revealed that all Lb. florum strains and Lb. lindneri AWRI B530 (grape isolate) possessed the majority of the tested genes relative to DSM 20691 (beer isolate); these enzyme-encoding genes included malolactic enzyme, peptidases (PepC, PepI, PepN), citrate lyase (\u03b1- and \u03b2-subunits), phenolic acid decarboxylase and arginine deiminase pathway enzymes (arginine deiminase and ornithine transcarbamylase). Sequence verification of PCR-generated fragments was performed by sequencing. The sequence data were used to construct the phylogenetic trees, which indicated that our Lb. florum isolates cluster with other Lb. florum strains of flower origin but rather distinct from other LAB species, with Lb. lindneri being the next closest species.","subset":"pubmed_abstract"} +{"meta":{"pmid":32859264,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":10}}},"text":"Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies.\nWhether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2\/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO2\/FiO2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml\/cmH2O [32-52] vs. 36 ml\/cmH2O [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2\/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2\/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.","subset":"pubmed_abstract"} +{"meta":{"pmid":18007707,"dup_signals":{"dup_doc_count":32,"dup_dump_count":15,"dup_details":{"curated_sources":4,"2017-39":2,"2016-44":2,"2016-40":1,"2016-36":3,"2016-30":2,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":2,"2015-40":2,"2015-35":2,"2015-32":2,"2015-27":3,"2015-22":2,"2015-18":2}}},"text":"Real-time, high velocity-resolution color Doppler optical coherence tomography.\nColor Doppler optical coherence tomography (CDOCT) is a noninvasive optical imaging technique for micrometer-scale physiological flow mapping simultaneously with morphological optical coherence tomography imaging. We have developed a novel CDOCT signal-processing strategy capable of imaging physiological flow rates at 8 frames\/s. Our new strategy features hardware-implemented digital autocorrelation across subsequent scans, permitting us to measure 300-Hz-8-kHz Doppler shifts upon signals of 0.6-MHz bandwidth. The performance of the CDOCT system was demonstrated in a flow phantom and in vivo in Xenopus laevis.","subset":"pubmed_abstract"} +{"meta":{"pmid":18766263,"dup_signals":{"dup_doc_count":19,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2024-30":1,"unknown":10}}},"text":"PFA-100 monitoring of von Willebrand factor (VWF) responses to desmopressin (DDAVP) and factor VIII\/VWF concentrate substitution in von Willebrand disease type 1 and 2.\nDose-response relationship was studied between PFA-100 closure times (PFA CTs) and factor (F)VIII-von Willebrand factor (VWF) parameters in patients with von Willebrand disease (VWD) type 1 and type 2 before and after treatment with DDAVP (n=84) or FVIII\/VWF concentrate (n=38). DDAVP treatment of patients with VWD type 1 normalised the PFA CTs by increasing VWF levels to normal. Of the 14 patients with VWD type 2, PFA CTs did not normalize in eight. Haemate-P substitution in patients with VWD type 1 induced a less favourable response as compared to DDAVP, because PFA CTs did not correct in all patients. Of 12 patients with VWD type 2 treated with Haemate-P, six showed a correction of PFA CTs (<250 sec), which correlated with the normalisation of the VWF CB\/Ag ratio. In-vitro studies were performed by using whole blood of patients with VWD and adding various amounts of FVIII\/VWF concentrate. Addition of Haemate-P induced an increase of the VWF CB\/Ag ratio from 0.30 to 0.70 in blood of patients with VWD type 2 with correction of the PFA CTs. Immunate did not result in an increase of VWF CB\/Ag ratio in blood of VWD type 2 patients, and the PFA CTs remained prolonged. We conclude that PFA-100 might be an adequate instrument not only for diagnosis but also for monitoring of DDAVP responses and FVIII\/VWF substitution of patients with VWD type 1 and 2, but this is dependent upon the type of VWD and the concentrate used.","subset":"pubmed_abstract"} +{"meta":{"pmid":30656350,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":10}}},"text":"The Effect of Inhomogeneous Trabecular Stiffness Relationship Selection on Finite Element Outcomes for Shoulder Arthroplasty.\nAn important feature of humeral orthopedic finite element (FE) models is the trabecular stiffness relationship. These relationships depend on the anatomic site from which they are derived; but have not been developed for the humerus. As a consequence, humeral FE modeling relies on relationships for other anatomic sites. The variation in humeral FE outcomes due to the trabecular stiffness relationship is assessed. Stemless arthroplasty FE models were constructed from CT scans of eight humeri. Models were loaded corresponding to 45 deg and 75 deg abduction. Each bone was modeled five times with the only variable being the trabecular stiffness relationship: four derived from different anatomic-sites and one pooled across sites. The FE outcome measures assessed were implant-bone contact percentage, von Mises of the change in stress, and bone response potential. The variance attributed to the selection of the trabecular stiffness relationship was quantified as the standard deviation existing between models of different trabecular stiffness. Overall, variability due to changing the trabecular stiffness relationship was low for all humeral FE outcome measures assessed. The variability was highest within the stress and bone formation potential outcome measures of the trabecular region. Variability only exceeded 10% in the trabecular stress change within two of the eight slices evaluated. In conclusion, the low variations attributable to the selection of a trabecular stiffness relationship based on anatomic-site suggest that FE models constructed for shoulder arthroplasty can utilize an inhomogeneous site-pooled trabecular relationship without inducing marked variability in the assessed outcome measures.","subset":"pubmed_abstract"} +{"meta":{"pmid":15830738,"dup_signals":{"dup_doc_count":46,"dup_dump_count":34,"dup_details":{"curated_sources":4,"2018-43":1,"2018-22":1,"2018-13":1,"2017-39":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2016-40":1,"2016-36":1,"2016-30":1,"2016-22":1,"2016-18":1,"2016-07":1,"2015-48":1,"2015-35":1,"2015-32":1,"2015-22":1,"2015-14":1,"2014-52":1,"2014-49":1,"2014-42":4,"2014-41":2,"2014-35":2,"2014-23":2,"2014-15":2,"2019-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2024-26":1}}},"text":"Patterns of alcohol consumption in a Northern Irish sample.\nThis paper examines the drinking habits of a Northern Irish sample during a six-month period in 1998. In addition the study examines the influence of contextual variables on the quantity and frequency of alcohol consumption. Questionnaires were administered to 600 participants; the response rate was 39.8% (239). An unexpected low abstinence rate was observed that, however, may be due to response bias. The results revealed high frequency (29.7% drink on four or more days a week) and high quantity of alcohol consumption (mean units per week 43.21, SD 40.33). Beer drinkers consumed the largest quantity of alcohol and also had the highest frequency of alcohol consumption. It was observed that 45.8% of all drinking events took place in a public bar and the popularity of the public bar for alcohol consumption was not influenced by age or gender. The present investigation revealed that almost half (45%) of individuals consume more than one type of beverage at one sitting, and there is a trend of consuming alcohol in more than one place during a single drinking session. These results indicate a distinctive drinking pattern within Northern Ireland and have implications for studies investigating the effects of alcohol on the social drinker.","subset":"pubmed_abstract"} +{"meta":{"pmid":34168419,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Massive parallelization boosts big Bayesian multidimensional scaling.\nBig Bayes is the computationally intensive co-application of big data and large, expressive Bayesian models for the analysis of complex phenomena in scientific inference and statistical learning. Standing as an example, Bayesian multidimensional scaling (MDS) can help scientists learn viral trajectories through space-time, but its computational burden prevents its wider use. Crucial MDS model calculations scale quadratically in the number of observations. We partially mitigate this limitation through massive parallelization using multi-core central processing units, instruction-level vectorization and graphics processing units (GPUs). Fitting the MDS model using Hamiltonian Monte Carlo, GPUs can deliver more than 100-fold speedups over serial calculations and thus extend Bayesian MDS to a big data setting. To illustrate, we employ Bayesian MDS to infer the rate at which different seasonal influenza virus subtypes use worldwide air traffic to spread around the globe. We examine 5392 viral sequences and their associated 14 million pairwise distances arising from the number of commercial airline seats per year between viral sampling locations. To adjust for shared evolutionary history of the viruses, we implement a phylogenetic extension to the MDS model and learn that subtype H3N2 spreads most effectively, consistent with its epidemic success relative to other seasonal influenza subtypes. Finally, we provide MassiveMDS, an open-source, stand-alone C++ library and rudimentary R package, and discuss program design and high-level implementation with an emphasis on important aspects of computing architecture that become relevant at scale.","subset":"pubmed_abstract"} +{"meta":{"pmid":19907537,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2015-18":1,"2024-26":1,"unknown":11}}},"text":"Acousto-optic control of speckle contrast in multimode fibers with a cylindrical piezoelectric transducer oscillating in the radial direction.\nWe report efficient acousto-optic control of speckle contrast at the output of multimode fibers (MMFs) using a cylindrical piezoelectric transducer (PZT) vibrating in the radial direction. With appropriate packaging of an MMF around the PZT, periodic stretching and subsequent intensity modulation were achieved over the wound fiber to result in time-averaged smoothing of the output within a short time. It was experimentally confirmed that light passed through the vibrating PZT-fiber assembly maintains the virtually partial coherence irrespective of the guide length and power splitting. Real-time vibration-off\/on movies were presented, and their single-frame excerpts were analyzed.","subset":"pubmed_abstract"} +{"meta":{"pmid":26097884,"dup_signals":{"dup_doc_count":52,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2023-40":3,"2023-23":2,"2023-06":2,"2022-40":1,"2022-27":3,"2022-21":1,"2022-05":2,"2021-43":2,"2021-39":3,"2021-31":3,"2021-21":2,"2021-17":1,"2021-10":2,"2021-04":1,"2020-50":2,"2020-40":4,"2018-43":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2023-50":1,"2024-26":4,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Methylation changes in the TFAP2E promoter region are associated with BRAF mutation and poorer overall & disease free survival in colorectal cancer.\nBRAF mutant colorectal cancer carries a poor prognosis which is thought to be related to poor response to conventional chemotherapy. BRAF mutation is associated with the serrated tumour phenotype. We hypothesised that one of the mechanisms by which BRAF mutant colorectal cancer demonstrate poor outcomes with chemotherapy is abnormal gene methylation. The Cancer Genome Atlas (TCGA) methylation data was analysed using a linear regression model with BRAF mutation as an independent variable. Expression datasets were also obtained to correlate functional changes. Top differentially methylated probes were taken forward for validation by methylation pyrosequencing. These probes were analysed on a cohort of patients enriched for BRAF mutations taken from the VICTOR and QUASAR2 studies. In an analysis of 91 tumours (9 BRAF mutant, 82 wild type), the Illumina probe cg11835197 was the probe identified as top differentially methylated (p = 2.56\u00d710-7, Bayes Factor (BF) =6.54). This probe covered a region -413bp from the promoter region of TFAP2E. We found a complex pattern of CpG specific methylation of this region which was associated with both overall (p=0.044) and disease free (p=0.046) survival. BRAF mutant tumours may attain part of their chemoresistance from abnormal TFAP2E methylation, which has not previously been described.","subset":"pubmed_abstract"} +{"meta":{"pmid":33236757,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2024-10":1,"unknown":12}}},"text":"How to manage CML patients with comorbidities.\nPatients with chronic myeloid leukemia (CML) often have comorbidities, at an incidence that might be higher than in the general population. Because of the favorable outcome of most patients with CML treated with tyrosine kinase inhibitors (TKIs), a greater number of comorbidities might be the most significant adverse feature for long-term survival. The presence of comorbidities may also affect the risk of developing adverse events with TKIs. This effect is perhaps best exemplified by the risk of developing arterio-occlusive events, which is greatest for patients who have other risk factors for such events, with the risk increasing with higher numbers of comorbidities. The coexistence of comorbidities in patients with CML not only may affect TKI selection but also demands close monitoring of the overall health condition of the patient to optimize safety and provide the opportunity for an optimal outcome to such patients. With optimal, holistic management of leukemia and all other conditions afflicting them, patients with CML and comorbidities may aim for a near-normal life expectancy, just as the more select patients enrolled in clinical trials now enjoy.","subset":"pubmed_abstract"} +{"meta":{"pmid":22731935,"dup_signals":{"dup_doc_count":27,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2022-27":1,"2022-05":1,"2021-49":1,"2021-43":1,"2021-39":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":1,"2020-40":1,"2020-29":1,"2020-16":2,"2020-10":2,"2020-05":1,"2019-51":1,"2019-43":1,"2019-39":1,"2019-35":1,"2019-26":1,"2023-50":1,"2024-22":1}}},"text":"Multidisciplinary guidelines for the management of tracheostomy and laryngectomy airway emergencies.\nAdult tracheostomy and laryngectomy airway emergencies are uncommon, but do lead to significant morbidity and mortality. The National Tracheostomy Safety Project incorporates key stakeholder groups with multi-disciplinary expertise in airway management. , the Intensive Care Society, the Royal College of Anaesthetists, ENT UK, the British Association of Oral and Maxillofacial Surgeons, the College of Emergency Medicine, the Resuscitation Council (UK) the Royal College of Nursing, the Royal College of Speech and Language Therapists, the Association of Chartered Physiotherapists in Respiratory Care and the National Patient Safety Agency. Resources and emergency algorithms were developed by consensus, taking into account existing guidelines, evidence and experiences. The stakeholder groups reviewed draft emergency algorithms and feedback was also received from open peer review. The final algorithms describe a universal approach to managing such emergencies and are designed to be followed by first responders. The project aims to improve the management of tracheostomy and laryngectomy critical incidents.","subset":"pubmed_abstract"} +{"meta":{"pmid":29139529,"dup_signals":{"dup_doc_count":14,"dup_dump_count":10,"dup_details":{"curated_sources":3,"2021-31":1,"2021-25":1,"2019-43":1,"2019-13":1,"2019-04":1,"2018-39":1,"2018-26":1,"2018-09":1,"2017-47":2,"2021-39":1}}},"text":"Lab-on-capillary: a rapid, simple and quantitative genetic analysis platform integrating nucleic acid extraction, amplification and detection.\nIn this work, we describe for the first time a genetic diagnosis platform employing a polydiallyldimethylammonium chloride (PDDA)-modified capillary and a liquid-based thermalization system for rapid, simple and quantitative DNA analysis with minimal user interaction. Positively charged PDDA is modified on the inner surface of the silicon dioxide capillary by using an electrostatic self-assembly approach that allows the negatively charged DNA to be separated from the lysate in less than 20 seconds. The capillary loaded with the PCR mix is incorporated in the thermalization system, which can achieve on-site real-time PCR. This system is based on the circulation of pre-heated liquids in the chamber, allowing for high-speed thermalization of the capillary and fast amplification. Multiple targets can be simultaneously analysed with multiplex spatial melting. Starting with live Escherichia coli (E. coli) cells in milk, as a realistic sample, the current method can achieve DNA extraction, amplification, and detection within 40 min.","subset":"pubmed_abstract"} +{"meta":{"pmid":18968746,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Arsenic round the world: a review.\nThis review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research studies are needed for improving arsenic risk assessment at low exposure levels urgently among all the arsenic research groups.","subset":"pubmed_abstract"} +{"meta":{"pmid":34249742,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":3,"2024-10":1,"2024-26":1,"unknown":7}}},"text":"Irradiation-Modulated Murine Brain Microenvironment Enhances GL261-Tumor Growth and Inhibits Anti-PD-L1 Immunotherapy.\nClinical evidence suggests radiation induces changes in the brain microenvironment that affect subsequent response to treatment. This study investigates the effect of previous radiation, delivered six weeks prior to orthotopic tumor implantation, on subsequent tumor growth and therapeutic response to anti-PD-L1 therapy in an intracranial mouse model, termed the Radiation Induced Immunosuppressive Microenvironment (RI2M) model. C57Bl\/6 mice received focal (hemispheric) single-fraction, 30-Gy radiation using the Leksell GammaKnife\u00ae Perfexion\u2122, a dose that does not produce frank\/gross radiation necrosis. Non-irradiated GL261 glioblastoma tumor cells were implanted six weeks later into the irradiated hemisphere. Lesion volume was measured longitudinally by in vivo MRI. In a separate experiment, tumors were implanted into either previously irradiated (30 Gy) or non-irradiated mouse brain, mice were treated with anti-PD-L1 antibody, and Kaplan-Meier survival curves were constructed. Mouse brains were assessed by conventional hematoxylin and eosin (H&E) staining, IBA-1 staining, which detects activated microglia and macrophages, and fluorescence-activated cell sorting (FACS) analysis. Tumors in previously irradiated brain display aggressive, invasive growth, characterized by viable tumor and large regions of hemorrhage and necrosis. Mice challenged intracranially with GL261 six weeks after prior intracranial irradiation are unresponsive to anti-PD-L1 therapy. K-M curves demonstrate a statistically significant difference in survival for tumor-bearing mice treated with anti-PD-L1 antibody between RI2M vs. non-irradiated mice. The most prominent immunologic change in the post-irradiated brain parenchyma is an increased frequency of activated microglia. The RI2M model focuses on the persisting (weeks-to-months) impact of radiation applied to normal, control-state brain on the growth characteristics and immunotherapy response of subsequently implanted tumor. GL261 tumors growing in the RI2M grew markedly more aggressively, with tumor cells admixed with regions of hemorrhage and necrosis, and showed a dramatic loss of response to anti-PD-L1 therapy compared to tumors in non-irradiated brain. IHC and FACS analyses demonstrate increased frequency of activated microglia, which correlates with loss of sensitivity to checkpoint immunotherapy. Given that standard-of-care for primary brain tumor following resection includes concurrent radiation and chemotherapy, these striking observations strongly motivate detailed assessment of the late effects of the RI2M on tumor growth and therapeutic efficacy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23286227,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2013-20":1,"unknown":9}}},"text":"Comparative analysis of homology models of the AH receptor ligand binding domain: verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor.\nThe aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness.","subset":"pubmed_abstract"} +{"meta":{"pmid":29509811,"dup_signals":{"dup_doc_count":19,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":1,"2024-10":1,"unknown":12}}},"text":"Access to primary care for socio-economically disadvantaged older people in rural areas: A qualitative study.\nWe aim to explore the barriers to accessing primary care for socio-economically disadvantaged older people in rural areas. Using a community recruitment strategy, fifteen people over 65 years, living in a rural area, and receiving financial support were recruited for semi-structured interviews. Four focus groups were held with rural health professionals. Interviews and focus groups were audio-recorded and transcribed. Thematic analysis was used to identify barriers to primary care access. Older people's experience can be understood within the context of a patient perceived set of unwritten rules or social contract-an individual is careful not to bother the doctor in return for additional goodwill when they become unwell. However, most found it difficult to access primary care due to engaged telephone lines, availability of appointments, interactions with receptionists; breaching their perceived social contract. This left some feeling unwelcome, worthless or marginalised, especially those with high expectations of the social contract or limited resources, skills and\/or desire to adapt to service changes. Health professionals' described how rising demands and expectations coupled with service constraints had necessitated service development, such as fewer home visits, more telephone consultations, triaging calls and modifying the appointment system. Multiple barriers to accessing primary care exist for this group. As primary care is re-organised to reduce costs, commissioners and practitioners must not lose sight of the perceived social contract and models of care that form the basis of how many older people interact with the service.","subset":"pubmed_abstract"} +{"meta":{"pmid":1525012,"dup_signals":{"dup_doc_count":12,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2017-13":1,"unknown":3}}},"text":"Eggshell zona radiata-proteins from cod (Gadus morhua): extra-ovarian origin and induction by estradiol-17 beta.\nUsing Atlantic cod (Gadus morhua) as a model organism, the aim of this report was to delineate whether teleostean eggshell zona radiata proteins have their origin, i.e., site of synthesis, in gonadal or somatic tissues. Estradiol-17 beta was administered intraperitoneally to one-year-old cod (Gadus morhua) with either undeveloped gonads or with differentiated gonads. By immunoblotting procedures estradiol-dependent protein induction was investigated using specific rabbit antisera directed against cod eggshell proteins and brown trout vitellogenin. No immunological cross-reactions were observed between the two antisera, and eggshell proteins and vitellogenin were detected in blood plasma and somatic tissues only in estradiol-treated cod. Three plasma-components were immunoreactive to antiserum directed against eggshell proteins, and these proteins possessed molecular weights of 78, 54 and 47 kDa, identical to the molecular weights of the cod eggshell alpha, beta and gamma zona radiata-proteins. These three immunoreactive plasma-components were observed after administration of estradiol-17 beta to both sexes, also in males having reached spermiation, and in juveniles of either sex without developed gonads. The data are interpreted to signify that cod eggshell zona radiata-proteins originate in an extra-ovarian tissue and are transported in the blood for deposition in the ovaries. We propose that oogenesis involves estradiol-17 beta regulation of both eggshell zona radiata-proteins and vitellogenin synthesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":21544174,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-26":1,"unknown":8}}},"text":"TTX, cations and spider venom modify avian muscle tone in vitro.\nAgents that reduce skeletal muscle tone may have a number of useful clinical applications, e.g., for muscle spasticity and other muscle disorders. Recently, we reported that the venoms of two species of Australian theraphosid (Araneae, Theraphosidae) spiders (Coremiocnemis tropix and Selenotholus foelschei) reduced the baseline tension of chick biventer cervicis nerve-muscle preparation. The purpose of this study was to determine the underlying physiology mediating the change in muscle tension, which was addressed by conducting isometric tension experiments. We found that MgCl(2) (20mM), CaCl(2) (20mM), tetrodotoxin (1\u03bcM) or C. tropix venom (2\u03bcl\/ml) produced a similar decrease in baseline tension, whereas d-tubocurarine (100\u03bcM), gadolinium (1mM), verapamil (10mM), an increase in osmotic pressure by the addition of glucose (40mM), or the presence\/absence of electrical stimulation did not produce a significant change in baseline tension. We suggest that mechanosensitive or muscle TTX-sensitive sodium channels are activated during muscle stretch. This may have implications for the treatment of stretch induced muscle damage.","subset":"pubmed_abstract"} +{"meta":{"pmid":16386394,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-26":1,"unknown":9}}},"text":"Sub-lethal concentrations of waterborne copper are toxic to lateral line neuromasts in zebrafish (Danio rerio).\nIn teleosts, the lateral line system is composed of neuromasts containing hair cells that are analogous to those present in the inner ear of all vertebrates. In the zebrafish embryo and early larva, this system is composed of the anterior lateral line (ALL), which covers the head, and the posterior lateral line (PLL), present in the trunk and tail. The mechanosensory hair cells found in neuromasts can be labeled in vivo using fluorescent dyes such as 4-di-2-Asp (DiAsp) or FM1-43. We have studied the effects of water-borne copper exposure on the function of the lateral line system in zebrafish larvae. Our results show that transient incubation of post-hatching larvae for 2h with non-lethal concentrations of copper (1-50 microM CuSO4) induces cellular damage localized to neuromasts, apoptosis, and loss of hair cell markers. This effect is specific to copper, as other metals did not show these effects. Since hair cells in fish can regenerate, we followed the reappearance of viable hair cells in neuromasts after copper removal. In the PLL, we determined that there is a threshold concentration of copper above which regeneration does not occur, whereas, at lower concentrations, the length of time it takes for viable hair cells to reappear is dependent on the amount of copper used during the treatment. The ALL behaves differently though, as regeneration can occur even after treatments with concentrations of copper an order of magnitude higher than the one that irreversibly affects the PLL. Regeneration of hair cells is dependent on cell division within the neuromasts as damage that precludes proliferation prevents reappearance of this cell type.","subset":"pubmed_abstract"} +{"meta":{"pmid":15836790,"dup_signals":{"dup_doc_count":11}},"text":"Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-kappaB p50-deficient mice.\nMarginal zone (MZ) B cells play important roles in the early phases of humoral immune responses. In addition to possessing an inherent capacity to rapidly differentiate into antibody secreting cells, MZ B cells also help to regulate the fate of both T-independent and T-dependent blood-borne antigens in the spleen. For T-dependent antigens, MZ B cells bind IgM-antigen complexes in a complement-dependent manner. Once MZ B cells bind IgM-containing immune complexes (IgM-IC), they transport them into B cell follicles for deposition onto follicular dendritic cells (FDCs), an important component of secreted IgM's ability to enhance adaptive immune responses. To further define the requirement for MZ B cells in IgM-IC deposition, mice deficient in the NF-kappaB protein p50, which have been reported to lack MZ B cells, were analyzed for their ability to trap IgM-IC onto FDCs. Mice (2 months of age) deficient in p50 (p50-\/-) had small numbers of MZ B cells, as determined by cell surface phenotype and localization in the splenic MZ. These cells bound high levels of IgM-IC both in vivo and in vitro. Subsequent to the binding of IgM-IC by the MZ B cells in p50-\/- mice, small amounts of IgM-IC were found localized on FDCs, suggesting that the MZ B cells retained their ability to transport these complexes into splenic follicles. Strikingly, MZ B cells accumulated with age in p50-\/- mice. By 6 months of age, p50-\/- mice contained normal numbers of these cells as defined by CD21\/CD23 profile and high level expression of CD1d, CD9, and IgM, and by their positioning around the marginal sinus. However, FDCs from these older p50-\/- mice exhibited a reduced capacity to trap IgM-IC and retain complement components. These results demonstrate that while the p50 component of the NF-kappaB transcription complex plays an important role in the early development of MZ B cells, MZ B cells can develop and accumulate in mice lacking this protein. These results highlight the interface between genetic deficiencies and age, and suggest that different transcription factors may play distinct roles in the development and maintenance of cell populations at different ages.","subset":"pubmed_abstract"} +{"meta":{"pmid":18182647,"dup_signals":{"dup_doc_count":16,"dup_dump_count":12,"dup_details":{"curated_sources":4,"2020-34":1,"2020-24":1,"2020-05":1,"2019-47":1,"2019-39":1,"2019-30":1,"2019-22":1,"2019-13":1,"2019-04":1,"2018-47":1,"2023-14":1,"2024-30":1}}},"text":"Melatonin for insomnia in children with autism spectrum disorders.\nWe describe our experience in using melatonin to treat insomnia, a common sleep concern, in children with autism spectrum disorders. One hundred seven children (2-18 years of age) with a confirmed diagnosis of autism spectrum disorders who received melatonin were identified by reviewing the electronic medical records of a single pediatrician. All parents were counseled on sleep hygiene techniques. Clinical response to melatonin, based on parental report, was categorized as (1) sleep no longer a concern, (2) improved sleep but continued parental concerns, (3) sleep continues to be a major concern, and (4) worsened sleep. The melatonin dose varied from 0.75 to 6 mg. After initiation of melatonin, parents of 27 children (25%) no longer reported sleep concerns at follow-up visits. Parents of 64 children (60%) reported improved sleep, although continued to have concerns regarding sleep. Parents of 14 children (13%) continued to report sleep problems as a major concern, with only 1 child having worse sleep after starting melatonin (1%), and 1 child having undetermined response (1%). Only 3 children had mild side-effects after starting melatonin, which included morning sleepiness and increased enuresis. There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures. The majority of children were taking psychotropic medications. Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with autism spectrum disorders. Controlled trials to determine efficacy appear warranted.","subset":"pubmed_abstract"} +{"meta":{"pmid":30140426,"dup_signals":{"dup_doc_count":15,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-18":1,"2024-30":1,"unknown":12}}},"text":"Dysregulation of the calcium handling protein, CCDC47, is associated with diabetic cardiomyopathy.\nDiabetes mellitus is associated with an increased risk in diabetic cardiomyopathy (DCM) that is distinctly not attributed to co-morbidities with other vasculature diseases. To date, while dysregulation of calcium handling is a key hallmark in cardiomyopathy, studies have been inconsistent in the types of alterations involved. In this study human cardiomyocytes were exposed to an environmental nutritional perturbation of high glucose, fatty acids, and l-carnitine to model DCM and iTRAQ-coupled LC-MS\/MS proteomic analysis was used to capture proteins affected by the perturbation. The proteins captured were then compared to proteins currently annotated in the cardiovascular disease (CVD) gene ontology (GO) database to identify proteins not previously described as being related to CVD. Subsequently, GO analysis for calcium regulating proteins and endoplasmic\/sarcoplasmic reticulum (ER\/SR) associated proteins was carried out. Here, we identified CCDC47 (calumin) as a unique calcium regulating protein altered in our in vitro nutritional perturbation model. The cellular and functional role of CCDC47 was then assessed in rat cardiomyocytes. In rat H9C2 myocytes, overexpression of CCDC47 resulted in increase in ionomycin-induced calcium release and reuptake. Of interest, in a diet-induced obese (DIO) rat model of DCM, CCDC47 mRNA expression was increased in the atrium and ventricle of the heart, but CCDC47 protein expression was significantly increased only in the atrium of DIO rats compared to lean control rats. Notably, no changes in ANP, BNP, or \u03b2-MHC were observed between DIO rats and lean control rats. Together, our in vitro and in vivo studies demonstrate that CCDC47 is a unique calcium regulating protein that is associated with early onset hypertrophic cardiomyopathy.","subset":"pubmed_abstract"} +{"meta":{"pmid":17300239,"dup_signals":{"dup_doc_count":17,"dup_dump_count":6,"dup_details":{"curated_sources":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":1,"2015-18":1,"unknown":10}}},"text":"Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial.\nMoisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.","subset":"pubmed_abstract"} +{"meta":{"pmid":22385844,"dup_signals":{"dup_doc_count":36,"dup_dump_count":33,"dup_details":{"curated_sources":3,"2023-14":1,"2022-49":1,"2022-33":1,"2022-21":1,"2021-49":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-10":1,"2020-50":1,"2020-40":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-10":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-09":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2017-30":1,"2017-22":1,"2023-40":1,"2024-10":1,"2017-13":1,"2024-26":1}}},"text":"Analysis of molecular movement reveals latticelike obstructions to diffusion in heart muscle cells.\nIntracellular diffusion in muscle cells is known to be restricted. Although characteristics and localization of these restrictions is yet to be elucidated, it has been established that ischemia-reperfusion injury reduces the overall diffusion restriction. Here we apply an extended version of raster image correlation spectroscopy to determine directional anisotropy and coefficients of diffusion in rat cardiomyocytes. Our experimental results indicate that diffusion of a smaller molecule (1127 MW fluorescently labeled ATTO633-ATP) is restricted more than that of a larger one (10,000 MW Alexa647-dextran), when comparing diffusion in cardiomyocytes to that in solution. We attempt to provide a resolution to this counterintuitive result by applying a quantitative stochastic model of diffusion. Modeling results suggest the presence of periodic intracellular barriers situated \u223c1 \u03bcm apart having very low permeabilities and a small effect of molecular crowding in volumes between the barriers. Such intracellular structuring could restrict diffusion of molecules of energy metabolism, reactive oxygen species, and apoptotic signals, enacting a significant role in normally functioning cardiomyocytes as well as in pathological conditions of the heart.","subset":"pubmed_abstract"} +{"meta":{"pmid":33303861,"dup_signals":{"dup_doc_count":13,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-22":1,"2024-10":2,"2024-26":1,"unknown":8}}},"text":"Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts.\nFOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise \"clicks\", which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.","subset":"pubmed_abstract"} +{"meta":{"pmid":28824393,"dup_signals":{"dup_doc_count":21,"dup_details":{"curated_sources":2,"unknown":19}}},"text":"Guidelines for Assessment of Gait and Reference Values for Spatiotemporal Gait Parameters in Older Adults: The Biomathics and Canadian Gait Consortiums Initiative.\nBackground: Gait disorders, a highly prevalent condition in older adults, are associated with several adverse health consequences. Gait analysis allows qualitative and quantitative assessments of gait that improves the understanding of mechanisms of gait disorders and the choice of interventions. This manuscript aims (1) to give consensus guidance for clinical and spatiotemporal gait analysis based on the recorded footfalls in older adults aged 65 years and over, and (2) to provide reference values for spatiotemporal gait parameters based on the recorded footfalls in healthy older adults free of cognitive impairment and multi-morbidities. Methods: International experts working in a network of two different consortiums (i.e., Biomathics and Canadian Gait Consortium) participated in this initiative. First, they identified items of standardized information following the usual procedure of formulation of consensus findings. Second, they merged databases including spatiotemporal gait assessments with GAITRite\u00ae system and clinical information from the \"Gait, cOgnitiOn & Decline\" (GOOD) initiative and the Generation 100 (Gen 100) study. Only healthy-free of cognitive impairment and multi-morbidities (i.e., \u2264 3 therapeutics taken daily)-participants aged 65 and older were selected. Age, sex, body mass index, mean values, and coefficients of variation (CoV) of gait parameters were used for the analyses. Results: Standardized systematic assessment of three categories of items, which were demographics and clinical information, and gait characteristics (clinical and spatiotemporal gait analysis based on the recorded footfalls), were selected for the proposed guidelines. Two complementary sets of items were distinguished: a minimal data set and a full data set. In addition, a total of 954 participants (mean age 72.8 \u00b1 4.8 years, 45.8% women) were recruited to establish the reference values. Performance of spatiotemporal gait parameters based on the recorded footfalls declined with increasing age (mean values and CoV) and demonstrated sex differences (mean values). Conclusions: Based on an international multicenter collaboration, we propose consensus guidelines for gait assessment and spatiotemporal gait analysis based on the recorded footfalls, and reference values for healthy older adults.","subset":"pubmed_abstract"} +{"meta":{"pmid":7901864,"dup_signals":{"dup_doc_count":40,"dup_dump_count":28,"dup_details":{"curated_sources":4,"2023-40":1,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-21":2,"2021-49":3,"2021-43":1,"2021-31":2,"2021-21":1,"2021-17":1,"2021-10":1,"2021-04":1,"2020-45":2,"2019-26":1,"2019-04":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-13":1,"2018-05":1,"2017-51":1,"2017-43":2,"2017-34":2,"2023-50":1,"2024-26":1,"2024-10":2,"2024-30":1}}},"text":"The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers.\nApomorphine, a non-selective dopamine agonist, has been used as a pharmacological probe for investigating central dopaminergic neurotransmission in psychiatric illness. In this study repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of apomorphine (5 or 10 micrograms\/kg), or placebo. The difference in rCBF, before and after drug (apomorphine versus placebo), was used to identify brain areas affected by apomorphine. Compared to placebo, both doses of apomorphine increased blood flow in the anterior cingulate cortex. Apomorphine 10 micrograms\/kg also increased prefrontal rCBF (right > left). No decreases in rCBF were noted following either dose of apomorphine. Apomorphine-induced increases of anterior cingulate blood flow might serve as an in vivo index of central dopamine function. Such an approach would complement established neuroendocrine challenge paradigms for investigating central dopamine neurotransmission in psychiatric illness.","subset":"pubmed_abstract"} +{"meta":{"pmid":30458333,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":11}}},"text":"Cognitive functions in young adults with generalized anxiety disorder.\nAnxiety and worry are central symptoms of Generalized Anxiety Disorder (GAD) that have been theorized to negatively impact cognitive functions. However, most of the research has focused on threat-related or emotionally-charged stimuli, and a surprisingly small number of investigations examined 'cold' cognitive functions using classic neuropsychological tests. Such investigations are particularly important given that some theoretical models suggest compensatory mechanisms associated with anxiety that in certain circumstances may result in intact performance. The aim of the present study is to assess the neuropsychological profile associated with GAD, using a comprehensive neuropsychological battery. A sample of 23 college students meeting criteria for DSM-5 GAD and 20 control participants completed a psychometrically valid comprehensive computerized neuropsychological battery and clinical questionnaires. The GAD sample presented with significantly elevated symptomatic rates of anxiety, worry, depression and stress. However, no significant differences were found on any neuropsychological outcome measures or domain indexes. Effect sizes were small, some of which favored the GAD sample. Despite substantial psychopathological burden, GAD exhibited intact cognitive functioning. These results support the Cognitive Control Theory of Anxiety, suggesting that elevated primary anxiety may not impact 'cold' cognitive functions in the absence of threat or substantial cognitive load. Given that this is one of the only studies employing a comprehensive neuropsychological battery in GAD, more research is needed in this population to replicate these results and to examine the impact of anxiety on cognitive functions at varying degrees of cognitive load in this population.","subset":"pubmed_abstract"} +{"meta":{"pmid":29140146,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Awareness and Attitude Toward Use of Dietary Supplements and the Perceived Outcomes Among Saudi Adult Male Members of Fitness Centers in Saudi Arabia.\nDietary supplements are believed to enhance athletic performance and\/or prevent\/reverse pathological states. Despite the increasing use of dietary supplements in Saudi Arabia, systematic studies in this field are lacking. This study aims to assess the relation between demographic and social characteristics and dietary supplement use among adult males in Saudi Arabia. Demographic and dietary supplements data from fitness club participants were collected through a questionnaire, and the Pearson chi-square test was used to determine associations. A total of 448 apparently healthy adult males above 20 years of age, who were registered at fitness centers located in Saudi Arabia, participated in the study. The majority (275 [62%]) of the study participants were younger (20-30 years), of normal weight (189 [43%]), without health problems (332 [79%]), and obtained an undergraduate degree or higher (336 [77%]). The majority (58%) took supplements under the supervision of a professional and the rest depended on Internet (22%), friends (12%), or books (4%) for choosing supplement types. The main motives of the participants for visiting the fitness center were: weight loss (N = 149 [35%]), keeping fit (N = 101 [24%]), and muscle building (N = 151 [35%]). One hundred and fifty-five participants (44%) were taking supplements on a daily basis with 34 (10%) having taken it for a prolonged duration (>1 year). The most commonly used supplements were proteins (29%) and multivitamins (21%). Supplement use was not associated with the participants' family income or level of education but was positively associated with younger age (<31 years), \u03c72(2, N = 443) = 4.96, p = .03.","subset":"pubmed_abstract"} +{"meta":{"pmid":29071316,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Off-center motion of a trapped elastic capsule in a microfluidic channel with a narrow constriction.\nOwing to their significance in capsule-related engineering and biomedical applications, a number of studies have considered the dynamics of elastic capsules flowing in constricted microchannels. However, these studies have focused on capsules moving along the channel centerline. In the present study, we numerically investigate the transient motion of an elastic capsule in a microfluidic channel with a rectangular constriction, which is initially trapped at the constriction inlet while off the channel centerline (i.e., on the channel bottom-wall). Under the push of the surrounding flow, the capsule can squeeze into the constriction, but only if the capsule deformability or the constriction size is sufficiently large. We find that the critical capillary number leading to the penetration of the capsule into the constriction is larger for off-centerline capsules compared to centered capsules. The centered capsule is stationary at the steady state when it remains stuck at the constriction; in contrast, the off-centerline capsule is not stationary but exhibits a tank-treading motion, i.e., its overall shape maintains a nonspherical shape with a protrusion into the constriction while its membrane exhibits a continuous rotation. Further, we examine the dependence of the capsule motion type, capsule deformation degree and membrane tension distribution on the capillary number (measuring the effects of flow strength and membrane mechanics) and constriction geometries (including the constriction height and width). Finally, we discuss the mechanism governing the capsule motion by analyzing the hydrodynamic forces acting on the capsule. The shear force acting on the capsule top owing to the fluid flow in the gap between the capsule top and the channel top-wall is the main source inducing the membrane tank-treading rotation.","subset":"pubmed_abstract"} +{"meta":{"pmid":22362732,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":2,"2024-30":2,"2024-22":2,"2014-10":1,"2013-20":1,"unknown":10}}},"text":"Effective stiffening of DNA due to nematic ordering causes DNA molecules packed in phage capsids to preferentially form torus knots.\nObservation that DNA molecules in bacteriophage capsids preferentially form torus type of knots provided a sensitive gauge to evaluate various models of DNA arrangement in phage heads. Only models resulting in a preponderance of torus knots could be considered as close to reality. Recent studies revealed that experimentally observed enrichment of torus knots can be qualitatively reproduced in numerical simulations that include a potential inducing nematic arrangement of tightly packed DNA molecules within phage capsids. Here, we investigate what aspects of the nematic arrangement are crucial for inducing formation of torus knots. Our results indicate that the effective stiffening of DNA by the nematic arrangement not only promotes knotting in general but is also the decisive factor in promoting formation of DNA torus knots in phage capsids.","subset":"pubmed_abstract"} +{"meta":{"pmid":18182393,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":12}}},"text":"JunD protects the liver from ischemia\/reperfusion injury by dampening AP-1 transcriptional activation.\nThe AP-1 transcription factor modulates a wide range of cellular processes, including cellular proliferation, programmed cell death, and survival. JunD is a major component of the AP-1 complex following liver ischemia\/reperfusion (I\/R) injury; however, its precise function in this setting remains unclear. We investigated the functional significance of JunD in regulating AP-1 transcription following partial lobar I\/R injury to the liver, as well as the downstream consequences for hepatocellular remodeling. Our findings demonstrate that JunD plays a protective role, reducing I\/R injury to the liver by suppressing acute transcriptional activation of AP-1. In the absence of JunD, c-Jun phosphorylation and AP-1 activation in response to I\/R injury were elevated, and this correlated with increased caspase activation, injury, and alterations in hepatocyte proliferation. The expression of dominant negative JNK1 inhibited c-Jun phosphorylation, AP-1 activation, and hepatic injury following I\/R in JunD-\/- mice but, paradoxically, led to an enhancement of AP-1 activation and liver injury in JunD+\/- littermates. Enhanced JunD\/JNK1-dependent liver injury correlated with the acute induction of diphenylene iodonium-sensitive NADPH-dependent superoxide production by the liver following I\/R. In this context, dominant negative JNK1 expression elevated both Nox2 and Nox4 mRNA levels in the liver in a JunD-dependent manner. These findings suggest that JunD counterbalances JNK1 activation and the downstream redox-dependent hepatic injury that results from I\/R, and may do so by regulating NADPH oxidases.","subset":"pubmed_abstract"} +{"meta":{"pmid":19725024,"dup_signals":{"dup_doc_count":14}},"text":"Adaptive group sequential design for phase II clinical trials: a Bayesian decision theoretic approach.\nBayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade-off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations.We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study.Our method is illustrated in the context of a single-arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.","subset":"pubmed_abstract"} +{"meta":{"pmid":12700216,"dup_signals":{"dup_doc_count":15,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-10":1,"2013-48":1,"2024-26":1,"unknown":10}}},"text":"Retest reliability of surveillance questions on health related quality of life.\nHealth related quality of life (HRQoL) is an important surveillance measure for monitoring the health of populations, as proposed in the American public health plan, Healthy People 2010. The authors investigated the retest reliability of four HRQoL questions from the US Behavioral Risk Factor Surveillance System (BRFSS). Randomly sampled BRFSS respondents from the state of Missouri were re-contacted for a retest of the HRQoL questions. Reliability was estimated by kappa statistics for categorical questions and intraclass correlation coefficients for continuous questions. Missouri, United States. 868 respondents were re-interviewed by telephone about two weeks after the initial interview (mean 13.5 days). Participants represented the adult, non-institutionalised population of Missouri: 59.1% women; mean age 49.5 years; 93.2% white race. Retest reliability was excellent (0.75 or higher) for Self-Reported Health and Healthy Days measures, and moderate (0.58 to 0.71) for other measures. Reliability was lower for older adults. Other demographic subgroups (for example, gender) showed no regular pattern of differing reliability and there was very little change in reliability by the time interval between the first and second interview. Retest reliability of the HRQoL Core is moderate to excellent. Scaling options will require future attention, as will research into appropriate metrics for what constitutes important population group differences and change in HRQoL.","subset":"pubmed_abstract"} +{"meta":{"pmid":16989901,"dup_signals":{"dup_doc_count":14,"dup_dump_count":12,"dup_details":{"curated_sources":1,"2023-14":1,"2023-06":1,"2022-49":1,"2022-33":2,"2022-21":1,"2021-49":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-22":1,"2023-40":1}}},"text":"Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy.\nTo evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes. Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial. Six hundred eighty-five patients randomized at 70 clinical sites. Ophthalmologic examination was performed at screening and at each 3-month visit. Retinopathy status was assessed every 6 months with Early Treatment Diabetic Retinopathy Study (ETDRS) standard 7-field 30 degrees color stereoscopic fundus photography. Levels of diabetic retinopathy and diabetic macular edema were determined by 2 independent graders masked to site and treatment assignment, with additional independent adjudication as required. Eligible patients had a best-corrected visual acuity (VA) score of > or =45 letters, retinopathy level > or = 47A and < or = 53E, and no prior panretinal photocoagulation in at least one eye. Effect of oral ruboxistaurin (32 mg\/day) on reduction of sustained moderate visual loss (> or =15-letter decrease in ETDRS VA score maintained > or = 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy. Sustained moderate visual loss occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin-treated patients after 12 months. Baseline-to-end point visual improvement of > or =15 letters was more frequent (4.9% vs. 2.4%) and > or =15-letter worsening was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to placebo (P = 0.005). When clinically significant macular edema was >100 microm from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 microm (68% vs. 50%, P = 0.003). Initial laser treatment for macular edema was 26% less frequent in eyes of ruboxistaurin-treated patients (P = 0.008). Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with nonproliferative retinopathy.","subset":"pubmed_abstract"} +{"meta":{"pmid":12662225,"dup_signals":{"dup_doc_count":11}},"text":"Management of gallstone pancreatitis in Auckland: progress and compliance.\nRecent advances in the management of acute gallstone pancreatitis include the introduction of laparoscopic cholecystectomy,defining the role of endoscopic retrograde cholangiopancreatography(ERCP) and early cholecystectomy to prevent recurrent pancreatitis. The aim of the present study was to review the current management of gallstone pancreatitis in Auckland Hospital, compare findings with a similar study published a decade ago and to determine the extent to which the management is compliant with recently published consensus guidelines. A retrospective review of consecutive patients admitted with acute pancreatitis during a 39-month study period was undertaken. Data were recorded regarding demographics, diagnosis, predicted and actual severity of gallstone pancreatitis (index and recurrent attacks), the role of ERCP and computed tomography scanning, the timing of cholecystectomy (open and laparoscopic), intraoperative cholangiography, duration of hospital stay, complications and mortality. : There were 216 patients admitted with acute pancreatitis,106 of whom had proven gallstones. An ERCP was performed in 62(59%) patients with gallstone pancreatitis but not more commonly in patients with severe pancreatitis, and common bile duct stones were identified in 26% of these patients. Of the 70 (66%)patients who had a cholecystectomy, 56 (80%) had it within 3 weeks of admission. Although the proportion of patients with gallstone pancreatitis who had a cholecystectomy is similar to the earlier study, there has been a significant increase in the proportion of patients having a cholecystectomy during the index admission (chi2 = 3.83; P = 0.05). This has resulted in a reduction in recurrent pancreatitis (P < 0.001). Although the overall mortality from gallstone pancreatitis has not significantly decreased, it has for patients with predicted severe gallstone pancreatitis (P = 0.02). : There has been reasonable compliance with published guidelines and some progress in the management of gallstone pancreatitis,particularly in relation to performing timely laparoscopic cholecystectomy with a reduction in the incidence of recurrent pancreatitis. Concerns remain regarding the overuse of diagnostic ERCP in patients with mild pancreatitis.","subset":"pubmed_abstract"} +{"meta":{"pmid":35154171,"dup_signals":{"dup_doc_count":11,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2024-10":1,"2024-26":1,"unknown":6}}},"text":"Agro-Morphological Characterization of Lentil Germplasm of Indian National Genebank and Development of a Core Set for Efficient Utilization in Lentil Improvement Programs.\nLentil (Lens culinaris Medik.) is one of the major cool-season pulse crops worldwide. Its increasing demand as a staple pulse has led to the unlocking of diverse germplasm collections conserved in the genebanks to develop its superior varieties. The Indian National Genebank, housed at the Indian Council of Agricultural Research (ICAR)-National Bureau of Plant Genetic Resources, New Delhi, India, currently has 2,324 accessions comprising 1,796 indigenous and 528 exotic collections. This study was conducted to unveil the potential of lentil germplasm by assessing its agro-morphological characteristics and diversity, identifying trait-specific germplasm, and developing a core set. The complete germplasm set was characterized for two years, i.e., 2017-2018 and 2018-2019, and data were recorded on 26 agro-morphological traits. High phenotypic variability was observed for nine quantitative and 17 qualitative traits. A core set comprising 170 accessions (137 Indian and 33 exotic) was derived based on the characterization data as well as geographical origin using a heuristic method and PowerCore software. This core set was found to be sufficiently diverse and representative of the entire collection based on the comparison made using Shannon-Weaver diversity indices and \u03c72 test. These results were further validated by summary statistics. The core set displayed high genetic diversity as evident from a higher coefficient of variance in comparison to the entire set for individual traits and overall Shannon-Weaver diversity indices (entire: 1.054; core: 1.361). In addition, the total variation explained by the first three principal components was higher in the core set (70.69%) than in the entire collection (68.03%). Further, the conservation of pairwise correlation values among descriptors in the entire and core set reflected the maintenance of the structure of the whole set. Based on the results, this core set is believed to represent the entire collection, completely. Therefore, it constitutes a potential set of germplasm that can be used in the genetic enhancement of lentils.","subset":"pubmed_abstract"} +{"meta":{"pmid":26119296,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Modulation of Hsp60 in response to coral brown band disease.\nBrown band disease (BrB), a virulent coral disease characterized by a dense concentration of ciliates ingesting coral tissue, is responsible for ongoing coral losses on Indo-Pacific reefs. Although several efforts have been made to identify the microbial communities associated with BrB and study the disease ecology, less attention has been given to the effect of ciliate presence on coral physiology. Levels of the mitochondrial heat shock protein 60-kDa (Hsp60, a biomarker indicative of cellular stress) were analyzed in apparently healthy coral polyps located at different distances along the advancing front of infection in Acropora muricata colonies affected by BrB in a Maldivian reef. Different Hsp60 levels were found in different parts of the same colony. Starting from a basal protein level in the healthy control colonies, a down-regulation of Hsp60 expression was detected near the ciliate band, indicating that the Hsp60 defense activity was probably already compromised due to the rapid progression rate of the BrB ciliate on the diseased branches and\/or to the etiology of the disease. Moving away from the band, the Hsp60 levels gradually returned to a state comparable to that found in the control, showing that cellular damage was confined to areas near the infection. In conclusion, we propose the analysis of Hsp60 modulation as a useful tool for examining physiological variations that are not detected at the morphological level in corals subjected to epizootic diseases, while providing new insights into the immune response of corals.","subset":"pubmed_abstract"} +{"meta":{"pmid":17582661,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-18":1,"unknown":9}}},"text":"Acute variations in homocysteine levels are related to creatine changes induced by physical activity.\nAlthough many studies have focused on the effects of the physical activity on plasma homocysteine (Hcy) levels, the data gathered up to now are contradictory. In fact, it is true that some researches highlighted an exercise-induced fall in Hcy concentrations, but there are many reports proving that the physical exercise does not contribute to depress plasma Hcy levels and\/or that in some instances it would even produce an increase. As a result, the question about the nature of the relationship between Hcy and physical activity remains unanswered. In this study, we have investigated whether the modification in Hcy level after a moderate physical activity was explainable in the light of the common connection of physical activity and Hcy to creatine (Cn). In 16 young volunteers aged from 21 to 37, divided into sedentary (n=6) and athletes (n=10) sub-groups, before and after an incremental cycle ergometer stress test, performed every 30 days for 4 months, we measured the plasma levels of guanidino acetic acid (GAA), ornithine (Orn), glycine (Gly), arginine (Arg), methionine (Met) as well as the plasma levels of Cn and of total and reduced form of the homocysteine (tHcy, rHcy). By difference in the total proteins (tProt) amount between the pre- and post-exercise phases also the dehydration degree of the subjects was measured. After exercise rHcy decreased, tHcy was unchanged while Cn increased. Gly, Arg and Met at the end of exercise remained unaffected whereas, interestingly, GAA decreased in both sub-groups while Orn was significant diminished in athletes and, although not significantly, the same trend was observable in the sedentaries group. These findings support an interesting hypothesis on the key role of the creatine haemoconcentration as an important modality by which physical exercise would affect plasma Hcy levels.","subset":"pubmed_abstract"} +{"meta":{"pmid":22649097,"dup_signals":{"dup_doc_count":75,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-14":1,"2022-05":1,"2021-10":1,"2021-04":2,"2020-50":2,"2020-45":2,"2020-40":3,"2020-34":1,"2020-24":1,"2020-05":2,"2019-18":2,"2019-13":3,"2019-09":1,"2019-04":1,"2018-47":5,"2018-43":2,"2018-39":1,"2018-30":2,"2018-26":1,"2018-22":2,"2018-09":2,"2018-05":2,"2017-43":2,"2017-39":2,"2017-34":1,"2017-30":1,"2017-26":2,"2017-22":2,"2017-17":2,"2017-09":1,"2017-04":1,"2016-50":3,"2016-44":4,"2016-40":3,"2016-36":2,"2016-30":1,"2015-48":1,"2023-50":1,"2017-13":3,"2024-26":1}}},"text":"Sequence-specific recognition of a PxLPxI\/L motif by an ankyrin repeat tumbler lock.\nAnkyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI\/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI\/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI\/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI\/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.","subset":"pubmed_abstract"} +{"meta":{"pmid":18199254,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":9}}},"text":"Effects of lamb sucking on the bacterial flora of teat duct and mammary gland of ewes.\nWe aimed (i) to determine differences in bacterial flora of teat duct and mammary gland of ewes before and after suckling, (ii) to evaluate factors potentially affecting those. We collected samples of teat duct material and mammary secretion from 11 ewes immediately before and after sucking by lambs, as well as 120 min later. We processed samples bacteriologically and compared changes in infection by the Sign Test. We isolated bacteria from 3.5% duct and 1.5% secretion samples before suckling. Respective figures post-suckling were 10.6% and 2.0%, and 120 min later 6.8% and 1.5%. We recorded differences in infection of duct samples before and after suckling in 40 cases; bacteria were isolated before suckling from six samples, whereas after it from 34 (p < 0.001). Also, we recorded differences in samples collected after suckling and 120 min later in 12 cases; bacteria were isolated immediately post-suckling from eight samples, whereas 120 min later from four (p = 0.375). No significant changes were seen for secretion. We found neither difference between ewes with single or twin lambs, nor among stages of lactation. Mostly, we isolated staphylococci: 70% of isolates before suckling, 80% of isolates after it, 91% of isolates 120 min later. After suckling we also isolated two Mannheimia haemolytica strains. Suckling predisposes to entrance of bacteria into the teat; however, increased teat infections did not result in mammary infections. Isolation of M. haemolytica post-suckling indicates that lambs act as source of infection for this pathogen.","subset":"pubmed_abstract"} +{"meta":{"pmid":25046130,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Molecular iron(III) phosphonates: synthesis, structure, magnetism, and M\u00f6ssbauer studies.\nThe reaction of Fe(ClO4)2\u00b76H2O with t-BuPO3H2 or Cl3CPO3H2 in the presence of an ancillary pyrazole phenolate as a coligand, H2phpzH [H2phpzH = 3(5)-(2-hydroxyphenyl)pyrazole], afforded tetra- and pentanuclear Fe(III) phosphonate complexes [Fe4(t-BuPO3)4(HphpzH)4]\u00b75CH3CN\u00b75CH2Cl2 (1) and [HNEt3]2[Fe5(\u03bc3-O)(\u03bc-OH)2 (Cl3CPO3)3(HphpzH)5(\u03bc-phpzH]\u00b73CH3CN\u00b72H2O (2). Single-crystal X-ray structural analysis reveals that 1 possesses a cubic double-4-ring (D4R) core similar to what is found in zeolites. The molecular structure of 2 reveals it to be pentanuclear. It crystallizes in the chiral P1 space group. Magnetic studies on 1 and 2 have also been carried out, which reveal that the bridging phosphonate ligands mediate weak antiferromagnetic interactions between the Fe(III) ions. Magnetization dynamics of 1 and 2 have been corroborated by a M\u00f6ssbauer spectroscopy analysis.","subset":"pubmed_abstract"} +{"meta":{"pmid":9463643,"dup_signals":{"dup_doc_count":14,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2020-05":2,"2019-51":1,"2019-18":1,"2019-09":1,"2018-22":1,"2017-51":1,"2016-44":1,"2015-48":1,"2020-16":1}}},"text":"Problem-based medical education: development of a theoretical foundation and a science-based professional attitude.\nProblem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Link\u00f6ping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Link\u00f6ping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evidence as to whether our present evaluation is correct.","subset":"pubmed_abstract"} +{"meta":{"pmid":12686719,"dup_signals":{"dup_doc_count":12,"dup_dump_count":6,"dup_details":{"curated_sources":2,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2013-20":2,"2015-18":1,"unknown":3}}},"text":"Gene Therapy for Pediatric Cancer: State of the Art and Future Perspectives.\nWhile modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. \"Corrective\" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional drugs and\/or radiation, thereby increasing the therapeutic index. Finally, it may be possible to attack the tumor indirectly by using genes that modify the behavior of the immune system, either by making the tumor more immunogenic, or by rendering host effector cells more efficient. Several gene therapy applications have already been reported for pediatric cancer patients in preliminary Phase 1 studies. Although no major clinical success has yet been achieved, improvements in gene delivery technologies and a better understanding of mechanisms of tumor progression and immune escape have opened new perspectives for the cure of pediatric cancer by combining gene therapy with standard therapeutic available treatments.","subset":"pubmed_abstract"} +{"meta":{"pmid":29524850,"dup_signals":{"dup_doc_count":29,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2021-31":2,"2020-40":2,"2020-29":3,"2020-24":1,"2020-16":1,"2020-10":1,"2020-05":1,"2019-51":2,"2019-43":2,"2019-35":2,"2019-26":2,"2019-18":2,"2019-13":2,"2019-04":1,"2018-43":1,"2018-34":1,"2018-22":1,"2021-43":1}}},"text":"Visible light-induced insulin aggregation on surfaces via photoexcitation of bound thioflavin T.\nInsulin is known to form amyloid aggregates when agitated in a hydrophobic container. Amyloid aggregation is routinely measured by the fluorescence of the conformational dye thioflavin T, which, when incorporated into amyloid fibers, fluoresces at 480 nm. The kinetics of amyloid aggregation in general is characterized by an initial lag-phase, during which aggregative nuclei form on the hydrophobic surface. These nuclei then lead to the formation of fibrils presenting a rapid growth during the elongation phase. Here we describe a novel mechanism of insulin amyloid aggregation which is surprisingly devoid of a lag-time for nucleation. The excitation of thioflavin T by visible light at 440 nm induces the aggregation of thioflavin T-positive insulin fibrils on hydrophobic surfaces in the presence of strong agitation and at physiological pH. This process is material surface-induced and depends on the fact that surface-adsorbed insulin can bind thioflavin T. Light-induced insulin aggregation kinetics is thioflavin T-mediated and is based on an energy transfer from visible light to the protein via thioflavin T. It relies on a constant supply of thioflavin T and insulin from the solution to the aggregate. The growth rate increases with the irradiance and with the concentration of thioflavin T. The supply of insulin seems to be the limiting factor of aggregate growth. This light-induced aggregation process allows the formation of local surface-bound aggregation patterns.","subset":"pubmed_abstract"} +{"meta":{"pmid":24594295,"dup_signals":{"dup_doc_count":91,"dup_dump_count":48,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":4,"2023-23":2,"2023-14":2,"2023-06":4,"2022-49":4,"2022-33":2,"2022-27":3,"2022-21":1,"2022-05":3,"2021-49":1,"2021-43":1,"2021-39":4,"2021-31":3,"2021-25":1,"2021-21":2,"2021-17":5,"2021-10":3,"2021-04":1,"2020-50":2,"2020-45":1,"2020-40":3,"2020-29":1,"2020-05":1,"2019-47":1,"2019-43":1,"2019-39":1,"2019-26":1,"2019-22":1,"2019-09":1,"2019-04":1,"2018-43":2,"2018-34":2,"2018-26":2,"2018-17":2,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2024-26":1,"2024-18":3,"2024-10":1,"2017-13":1,"2024-30":1}}},"text":"Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI.\nIdentification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques. Atherosclerotic plaques were collected from 20 consecutive patients (n=10 from symptomatic patients, n=10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory immunohistochemistry. Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation (r=.64, p<.001). The asymptomatic plaque population exhibited heterogeneity in terms of inflammation. The dual-targeted SPIO-induced MR signal not only tracked closely with endothelial activation (i.e. endothelial expression of VCAM-1 and E-selectin), but also reflected the macrophage burden within plaque lesions, offering a potential imaging tool for quantitative MRI of inflammatory activity in atherosclerosis. These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future.","subset":"pubmed_abstract"} +{"meta":{"pmid":17923888,"dup_signals":{"dup_doc_count":22,"dup_dump_count":7,"dup_details":{"curated_sources":2,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":2,"2013-20":2,"2017-13":1,"unknown":11}}},"text":"[Alcohol consumption in pregnancy: performance of the Brazilian version of the questionnaire T-ACE].\nTo assess the performance characteristics of the Brazilian version of the Tolerance, Annoyed, Cut down and Eye-opener (T-ACE) questionnaire to screen alcohol consumption during pregnancy. Observational, cross-sectional study in a sequential sample of 450 women in the third trimester of pregnancy, attended in a maternity ward in a city of Southeastern Brazil, in 2001. The following instruments were used: a questionnaire to gather sociodemographic data, the T-ACE, a questionnaire to verify history of alcohol consumption throughout gestation, and a clinical interview to identify the harmful use of and dependence on alcohol, according to ICD-10 diagnostic criteria. Concordance tests among different interviewers as well as test-\/re-test reliability tests were performed. A total of 100 women (22.1%) were identified as positive by the T-ACE. The kappa indexes for concordance and reliability were 0.95, with 97% of concordant responses. When compared to the ICD-10 criteria and to the pattern of consumption, the T-ACE, with a cut-off point of two or higher, presented sensitivity and specificity coefficients of 100% and 85%, and of 97.9% and 86.6%, respectively. The Brazilian version of the T-ACE seemed to appropriately meet the performance criteria that qualify it as a basic instrument for the screening of alcohol consumption during pregnancy. Its use in the routine and practice of obstetric services is recommended in view of the tendency for increased alcohol consumption among women, the difficulties to identify alcohol abuse by pregnant women, and the risk of developmental problems in children.","subset":"pubmed_abstract"} +{"meta":{"pmid":25864797,"dup_signals":{"dup_doc_count":35,"dup_dump_count":28,"dup_details":{"curated_sources":2,"2023-23":1,"2023-14":1,"2022-49":1,"2022-40":1,"2022-33":1,"2022-21":1,"2022-05":1,"2021-43":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":2,"2021-10":2,"2020-50":2,"2020-24":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-39":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-47":1,"2017-39":1,"2023-50":1,"2024-30":2,"2024-26":2,"2024-22":1}}},"text":"When trends intersect: The challenge of protecting freshwater ecosystems under multiple land use and hydrological intensification scenarios.\nIntensification of the use of natural resources is a world-wide trend driven by the increasing demand for water, food, fibre, minerals and energy. These demands are the result of a rising world population, increasing wealth and greater global focus on economic growth. Land use intensification, together with climate change, is also driving intensification of the global hydrological cycle. Both processes will have major socio-economic and ecological implications for global water availability. In this paper we focus on the implications of land use intensification for the conservation and management of freshwater ecosystems using Australia as an example. We consider this in the light of intensification of the hydrologic cycle due to climate change, and associated hydrological scenarios that include the occurrence of more intense hydrological events (extreme storms, larger floods and longer droughts). We highlight the importance of managing water quality, the value of providing environmental flows within a watershed framework and the critical role that innovative science and adaptive management must play in developing proactive and robust responses to intensification. We also suggest research priorities to support improved systemic governance, including adaptation planning and management to maximise freshwater biodiversity outcomes while supporting the socio-economic objectives driving land use intensification. Further research priorities include: i) determining the relative contributions of surface water and groundwater in supporting freshwater ecosystems; ii) identifying and protecting freshwater biodiversity hotspots and refugia; iii) improving our capacity to model hydro-ecological relationships and predict ecological outcomes from land use intensification and climate change; iv) developing an understanding of long term ecosystem behaviour; and v) exploring systemic approaches to enhancing governance systems, including planning and management systems affecting freshwater outcomes. A major policy challenge will be the integration of land and water management, which increasingly are being considered within different policy frameworks.","subset":"pubmed_abstract"} +{"meta":{"pmid":22355442,"dup_signals":{"dup_doc_count":27,"dup_dump_count":21,"dup_details":{"curated_sources":4,"2023-23":1,"2021-21":1,"2020-50":2,"2020-16":1,"2020-10":1,"2019-51":1,"2019-22":1,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2018-05":1,"2017-47":2,"2017-39":1,"2017-22":1,"2017-17":1,"2017-04":1,"2016-50":1,"2023-40":1}}},"text":"A Kenyan perspective on the use of animals in science education and scientific research in Africa and prospects for improvement.\nAnimal experimentation is common in Africa, a region that accords little priority on animal protection in comparison to economic and social development. The current study aimed at investigating the prevalence of animal experimentation in Kenya, and to review shortfalls in policy, legislation, implementation and enforcement that result in inadequate animal care in Kenya and other African nations. Data was collected using questionnaires, administered at 39 highly ranked academic and research institutions aiming to identify those that used animals, their sources of animals, and application of the three Rs. Perceived challenges to the use of non-animal alternatives and common methods of euthanasia were also queried. Data was analyzed using Epidata, SPSS 16.0 and Microsoft Excel. Thirty-eight (97.4%) of thirty-nine institutions reported using animals for education and\/or research. Thirty (76.9%) institutions reported using analgesics or anesthetics on a regular basis. Thirteen (33.3%) institutions regularly used statistical methods to minimize the use of animals. Overall, sixteen (41.0%) institutions explored the use of alternatives to animals such as cell cultures and computer simulation techniques, with one (2.6%) academic institution having completely replaced animals with computer modeling, manikins and visual illustrations. The commonest form of euthanasia employed was chloroform administration, reportedly in fourteen (29.8%) of 47 total methods (some institutions used more than one method). Twenty-eight (71.8%) institutions had no designated ethics committee to review or monitor protocols using animals. Animals are commonly used in academic and research institutions in Kenya. The relative lack of ethical guidance and oversight regarding the use of animals in research and education presents significant concerns.","subset":"pubmed_abstract"} +{"meta":{"pmid":23031463,"dup_signals":{"dup_doc_count":35,"dup_dump_count":27,"dup_details":{"curated_sources":4,"2022-40":1,"2022-27":2,"2022-05":2,"2021-49":3,"2021-43":1,"2021-39":1,"2021-31":1,"2021-21":1,"2021-10":1,"2021-04":1,"2020-50":1,"2020-40":1,"2020-29":1,"2019-22":1,"2019-18":1,"2019-13":1,"2018-47":1,"2018-30":1,"2018-13":1,"2017-43":1,"2017-22":1,"2017-09":1,"2017-04":1,"2023-50":1,"2024-22":1,"2024-10":1,"2024-30":1}}},"text":"Merging and characterising phenotypic data on conventional and rare traits from dairy cattle experimental resources in three countries.\nThis study set out to demonstrate the feasibility of merging data from different experimental resource dairy populations for joint genetic analyses. Data from four experimental herds located in three different countries (Scotland, Ireland and the Netherlands) were used for this purpose. Animals were first lactation Holstein cows that participated in ongoing or previously completed selection and feeding experiments. Data included a total of 60 058 weekly records from 1630 cows across the four herds; number of cows per herd ranged from 90 to 563. Weekly records were extracted from the individual herd databases and included seven traits: milk, fat and protein yield, milk somatic cell count, liveweight, dry matter intake and energy intake. Missing records were predicted with the use of random regression models, so that at the end there were 44 weekly records, corresponding to the typical 305-day lactation, for each cow. A total of 23 different lactation traits were derived from these records: total milk, fat and protein yield, average fat and protein percentage, average fat-to-protein ratio, total dry matter and energy intake and average dry matter intake-to-milk yield ratio in lactation weeks 1 to 44 and 1 to 15; average milk somatic cell count in lactation weeks 1 to 15 and 16 to 44; average liveweight in lactation weeks 1 to 44; and average energy balance in lactation weeks 1 to 44 and 1 to 15. Data were subsequently merged across the four herds into a single dataset, which was analysed with mixed linear models. Genetic variance and heritability estimates were greater (P < 0.05) than zero for all traits except for average milk somatic cell count in weeks 16 to 44. Proportion of total phenotypic variance due to genotype-by-environment (sire-by-herd) interaction was not different (P > 0.05) from zero. When estimable, the genetic correlation between herds ranged from 0.85 to 0.99. Results suggested that merging experimental herd data into a single dataset is both feasible and sensible, despite potential differences in management and recording of the animals in the four herds. Merging experimental data will increase power of detection in a genetic analysis and augment the potential reference population in genome-wide association studies, especially of difficult-to-record traits.","subset":"pubmed_abstract"} +{"meta":{"pmid":8266787,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Provoked flux motion of cochlear blood flow measured with laser Doppler flowmetry in guinea pig.\nAlthough progress has been made in the study of cochlear blood flow (CBF) regulation since laser Doppler flowmetry (LDF) was introduced, cochlear vasomotion has not been investigated. Therefore, the primary objective of this study was to determine if oscillatory fluctuations of CBF could be provoked. Guinea pigs were anesthetized with diazepam (5 mg\/kg) and fentanyl (0.32 mg\/kg). Blood pressure (BP) was recorded from a carotid artery cannula. The cochlea and pons cerebellum were ventrally exposed; the bilateral CBF and brain blood flow (BBF) or skin blood flow (SBF) were monitored by LDF. After administration of phentolamine (0.25-0.75 mg\/kg, i.v.), ipsilateral CBF in 7 of 16 animals showed a 2-5 min episode of oscillation. During artificial hyperventilation, continuous oscillation of CBF was recorded (the flux motion frequency was 3.5 +\/- 0.5 cycles per min and its amplitude 25.8 +\/- 5.6% from baseline). The time-dependent flux change (the waveform) was the same throughout a single cochlea but different between cochleae of the same animal. Compared to BBF, CBF vasomotion frequency was lower, and amplitude larger. SBF exhibited no such motion. Flux motion could be eliminated by inhalation of pure oxygen or 5% CO2 in oxygen or by the smooth muscle relaxants, papaverine and hydralazine. Phentolamine-induced vasomotion may be due to a hypotensive perfusion pressure, and hyperventilation-enhanced vasomotion may be caused by changing blood gas concentrations and by hormonal or neuronal activity. Oxygen and CO2 inhalation slightly increased BP and this change in perfusion pressure was probably associated with weakened vasomotion.(ABSTRACT TRUNCATED AT 250 WORDS)","subset":"pubmed_abstract"} +{"meta":{"pmid":24774504,"dup_signals":{"dup_doc_count":14,"dup_details":{"curated_sources":2,"unknown":12}}},"text":"anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab.\nThe complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.","subset":"pubmed_abstract"} +{"meta":{"pmid":24949225,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-10":1,"2024-18":1,"unknown":7}}},"text":"What influences the awareness of physician quality information? Implications for Medicare.\nExamine the factors that are associated with awareness of physician quality information (PQI) among older people with one or more chronic illnesses and the implications for Medicare. Random digit-dial survey of adults with one or more chronic illnesses. Structural equation modeling to examine factors related to awareness of PQI. Awareness of PQI is low (13 percent), but comparable to findings in general population surveys. Age, race, education, and self-reported health status are associated with PQI awareness. Trust in the Internet as a source of health care information and not trusting one's physician as a source of information both are associated with a greater likelihood of being aware of PQI. Patients with high levels of activation have greater trust in physicians as information sources, but this is not associated with awareness, nor is degree of satisfaction with their care experience. Awareness of PQI among older persons with chronic illnesses is relatively low across all socio-economic and demographic subgroups. Changes in population characteristics over time are unlikely to improve awareness in this population, nor are changes in patient activation or satisfaction with care. Medicare would need a broad-based effort if it wishes to raise PQI awareness among Medicare beneficiaries in the near term. Before undertaking resource-intensive efforts to increase awareness, Medicare may want to consider what level of awareness actually is needed to accomplish the overall objective for PQI transparency, which is raising the quality of care received by beneficiaries. It may be that relatively low levels of awareness are sufficient.","subset":"pubmed_abstract"} +{"meta":{"pmid":11387440,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Stimulation of RNA polymerase II elongation by hepatitis delta antigen.\nTranscription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.","subset":"pubmed_abstract"} +{"meta":{"pmid":9060685,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Role of CCR5 in infection of primary macrophages and lymphocytes by macrophage-tropic strains of human immunodeficiency virus: resistance to patient-derived and prototype isolates resulting from the delta ccr5 mutation.\nThe alpha-chemokine receptor fusin (CXCR-4) and beta-chemokine receptor CCR5 serve as entry cofactors for T-cell (T)-tropic and macrophage (M)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively, when expressed with CD4 in otherwise nonpermissive cells. Some M-tropic and dual-tropic strains can also utilize other beta-chemokine receptors, such as CCR2b and CCR3. A mutation of CCR5 (delta ccr5) was recently found to be common in certain populations and appears to confer protection against HIV-1 in vivo. Here, we show that this mutation results in a protein that is expressed intracellularly but not on the cell surface. Primary CD4 T cells from delta ccr5 homozygous individuals were highly resistant to infection with prototype M-tropic HIV-1 strains, including an isolate (YU-2) that uses CCR5 and CCR3, but were permissive for both a T-tropic strain (3B) and a dual-tropic variant (89.6) that uses CXCR-4, CCR5, CCR3, or CCR2b. These cells were also resistant to M-tropic patient isolates but were readily infected by T-tropic patient isolates. Primary macrophages from delta ccr5 homozygous individuals were also resistant to infection with M-tropic strains, including YU-2, but the dual-tropic strain 89.6 was able to replicate in them even though macrophages are highly resistant to CXCR-4-dependent T-tropic isolates. These data show that CCR5 is the essential cofactor for infection of both primary macrophages and T lymphocytes by most M-tropic strains of HIV-1. They also suggest that CCR3 does not function for HIV-1 entry in primary lymphocytes or macrophages, but that a molecule(s) other than CCR5 can support entry into macrophages by certain virus isolates. These studies further define the cellular basis for the resistance to HIV-1 infection of individuals lacking functional CCR5.","subset":"pubmed_abstract"} +{"meta":{"pmid":28076460,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":11}}},"text":"The accuracy of fine-needle aspiration cytology for diagnosis of parotid gland masses: a clinicopathological study of 114 patients.\nFine-needle aspiration cytology is a valuable method for preoperative assessment of head and neck tumors. However, its accuracy in detection of salivary gland masses is controversial compared with other methods. The aim of this work was to evaluate the effectiveness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. Over a 10-year period, 126 parotid gland masses were resected. Retrospective chart reviews of 114 patients were performed. The results of FNAC and final histological diagnosis were compared and the accuracy of FNAC was determined. Final histological evaluation revealed 11 malignant tumors and 103 benign lesions. Pleomorphic adenoma was the most common neoplasm (63%), followed by Warthin's tumor (17.5%). The sensitivity of FNAC in detecting malignant tumors was 73% and the specificity was 97%. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 97%. The overall accuracy of FNAC in detecting parotid masses was 95%. False-negative diagnosis was found in mucoepidermoid carcinoma, acinic cell carcinoma, and epithelial-myoepithelial carcinoma whereas there was false-positive diagnosis in cases of pleomorphic adenoma and normal parotid gland tissue. FNAC is a reliable minimally invasive diagnostic method with a high sensitivity in diagnosis of lesions in parotid glands. The sensitivity of detection of malignant tumors in parotid glands was low due to the biopsy technique used, and depended on tumor location. Postoperative complications decreased after superficial parotidectomy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23384159,"dup_signals":{"dup_doc_count":18,"dup_details":{"curated_sources":2,"unknown":16}}},"text":"Wolbachia association with the tsetse fly, Glossina fuscipes fuscipes, reveals high levels of genetic diversity and complex evolutionary dynamics.\nWolbachia pipientis, a diverse group of \u03b1-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI)). This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA) haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep). Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina fuscipes fuscipes, but it is not limited to a single host haplotype, suggesting that CI did not impact its population structure. However, host population genetic differentiation could have been generated if multiple Wolbachia strains interacted in some populations. Here, we investigated Wolbachia genetic variation in G. f. fuscipes populations of known host genetic composition in Uganda. We tested for the presence of multiple Wolbachia strains using Multi-Locus Sequence Typing (MLST) and for an association between geographic region and host mtDNA haplotype using Wolbachia DNA sequence from a variable locus, groEL (heat shock protein 60). MLST demonstrated that some G. f. fuscipes carry Wolbachia strains from two lineages. GroEL revealed high levels of sequence diversity within and between individuals (Haplotype diversity = 0.945). We found Wolbachia associated with 26 host mtDNA haplotypes, an unprecedented result. We observed a geographical association of one Wolbachia lineage with southern host mtDNA haplotypes, but it was non-significant (p = 0.16). Though most Wolbachia-infected host haplotypes were those found in the contact region between host mtDNA groups, this association was non-significant (p = 0.17). High Wolbachia sequence diversity and the association of Wolbachia with multiple host haplotypes suggest that different Wolbachia strains infected G. f. fuscipes multiple times independently. We suggest that these observations reflect a transient phase in Wolbachia evolution that is influenced by the long gestation and low reproductive output of tsetse. Although G. f. fuscipes is superinfected with Wolbachia, our data does not support that bidirectional CI has influenced host genetic diversity in Uganda.","subset":"pubmed_abstract"} +{"meta":{"pmid":8916191,"dup_signals":{"dup_doc_count":11}},"text":"Lack of interaction between devazepide and 8-OH-DPAT-induced hyperphagia in the rat.\nRecently, a number of studies have provided evidence suggesting that CCK and 5-HT interact in the control of food intake. However, the majority of these studies have relied on the administration of exogenous CCK to investigate potential interactions. The aim of the present study was to focus on the potential role of endogenous CCK in 5-HT-CCK interactions. Our prediction was that the CCKA antagonist, devazepide, alone would potentiate the hyperphagic effect of the 5-HT1A agonist, 8-OH-DPAT, in free-feeding rats. The results showed that devazepide, at a dose that had no intrinsic effect (1.0 mg\/kg), did not enhance the hyperphagic effect of 8-OH-DPAT (100 and 300 micrograms\/kg). This suggests that when serotonergic inhibitory activity is reduced by 5-HT1A-receptor stimulation, there is no compensatory increase of endogenous CCK activity to excite 5-HT neurons and thereby inhibit food intake.","subset":"pubmed_abstract"} +{"meta":{"pmid":10606304,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Fingerstick Helicobacter pylori antibody test: better than laboratory serological testing?\nAntibody testing is the recommended method to screen for Helicobacter pylori (H. pylori) infection. Whole-blood fingerstick antibody tests are simple, in-office tests providing rapid results, but the accuracy of first-generation tests was lower than other diagnostic tests. We assessed a new whole-blood antibody test, using endoscopic biopsy tests as a \"gold standard,\" and compared it with a laboratory quantitative serological test. Two hundred-one patients not previously treated for H. pylori who were undergoing endoscopy had gastric biopsies for rapid urease test and histological examination; whole-blood antibody tests and quantitative serological tests were also performed. Two separate gold standards for H. pylori infection were employed: either rapid urease test or histological exam positive; and both rapid urease test and histological exam positive. Sensitivities for whole-blood test versus quantitative serology with gold standard 1 (either biopsy test positive) were 86% versus 92% (95% confidence interval [CI] of difference, -2-14%; p = 0.19) and specificities were 88% versus 77% (95% CI of difference, 0.4-22%; p = 0.052). Sensitivities with gold standard 2 (both biopsy tests positive) were 90% versus 94% (95% CI of difference, -4-12%; p = 0.41) and specificities were 79% versus 67% (95% CI of difference, 1-24%; p = 0.048). New generation in-office, whole-blood antibody tests that can achieve a sensitivity and specificity similar to or better than those of widely used quantitative laboratory serological tests may be used as the initial screening tests of choice for H. pylori.","subset":"pubmed_abstract"} +{"meta":{"pmid":12373000,"dup_signals":{"dup_doc_count":14}},"text":"A functional study on CysLT(1) receptors in human eosinophils.\nThe cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors: CysLT(1) receptor and CysLT(2) receptor. This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT(1). Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity >99%). They were subjected to reverse transcription-PCR analysis and flow-cytometric analysis for CysLT(1). Binding assays were performed with [(3)H]LTD(4). Purified eosinophils loaded with Fura-2 acetoxymethyl ester were stimulated with CysLTs, and Ca(2+) influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD(4) at 10(-6) M for 60 min followed by incubation for 4 h at 37 degrees C in the presence or absence of IL-5 and eosinophil-derived neurotoxin (EDN) release was evaluated. The expression of the mRNA and protein of CysLT(1) on eosinophils and [(3)H]LTD(4)-specific binding to eosinophils were observed. Neither Th1 cytokine (IFN-gamma) nor Th2 cytokines (IL-4 or IL-5) affected CysLT(1) expression in eosinophils. CysLTs induced an increase in intracellular free Ca(2+) in eosinophils via CysLT(1), as suggested by the efficient inhibition by a CysLT(1) antagonist, pranlukast, in addition to the rank order of potency being LTD(4), LTC(4) and LTE(4). LTD(4) stimulated eosinophils to migrate at 10(-6) M via CysLT(1). LTE(4) also induced significant eosinophil migration at 10(-6) M. LTD(4) enhanced EDN release induced by IL-5 via CysLT(1). CysLTs induce migration and enhance degranulation in eosinophils via CysLT(1). Accordingly, interaction of CysLTs and CysLT(1) on eosinophils has the potential to play a prominent role in the pathophysiology of asthma.","subset":"pubmed_abstract"} +{"meta":{"pmid":26349315,"dup_signals":{"dup_doc_count":80,"dup_dump_count":53,"dup_details":{"curated_sources":4,"2022-40":3,"2022-21":2,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":1,"2021-31":1,"2021-25":1,"2021-21":1,"2021-17":3,"2021-10":1,"2021-04":4,"2020-50":1,"2020-45":1,"2020-40":1,"2020-34":1,"2020-29":1,"2020-24":3,"2020-16":1,"2020-10":1,"2020-05":2,"2019-51":1,"2019-47":1,"2019-43":2,"2019-39":2,"2019-35":1,"2019-30":1,"2019-26":2,"2019-22":1,"2019-18":1,"2019-13":1,"2019-09":1,"2019-04":1,"2018-51":2,"2018-43":1,"2018-34":1,"2018-30":1,"2018-26":1,"2018-17":2,"2018-13":1,"2018-09":1,"2018-05":1,"2017-51":2,"2017-47":1,"2017-43":2,"2017-39":1,"2017-34":2,"2017-30":1,"2017-26":3,"2017-22":1,"2017-17":1,"2017-09":1,"2017-13":1}}},"text":"Antileishmanial efficacy of Boerhaavia diffusa L. and Ocimum sanctum L. against experimental visceral leishmaniasis.\nThe chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Down regulation of immune system further aggravates the problems. To combat this situation we evaluated the leishmanicidal efficacy of Boerhaavia diffusa and Ocimum sanctum through oral route in L. donovani infection in BALB\/c mice. Results have demonstrated maximum clearance of the parasites from infected animals treated with combination of B. diffusa and O. sanctum (@ 100 and 400 mg\/kg body wt., respectively 5 days) as depicted through Leishman Donovan Units in liver. Up-regulation of cell-mediated immunity was also observed in animals of this group as heightened delayed type hypersensitivity responses and increased IgG2a levels were observed. Moreover, increased levels of SGOT, SGPT, serum urea, blood urea nitrogen and serum creatinine were brought down to normal levels. Since VL is associated immunosuppression, the above treatment is a good option as it helps in the up-regulation of Th1 responses and reduction in parasite load in L. donovani infected mice. These findings suggest a new option for antileishmanial chemotherapy at lower cost and nil toxicity.","subset":"pubmed_abstract"} +{"meta":{"pmid":20943646,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Gastrointestinal neuroendocrine tumors.\nGastrointestinal neuroendocrine tumors (GI-NETs) are a genetically diverse group of malignancies that sometimes produce peptides causing characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (non-functioning); both types frequently synthesize more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources the incidence and prevalence of GI-NETs is increasing. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require medical management with the aim of relieving symptoms and suppressing tumor growth and spread. Somatostatin analogues can improve the symptoms of carcinoid syndrome and stabilize tumor growth (PROMID study) in many patients. An antiproliferative effect can also be achieved with the m-TOR inhibitor everolimus, alone or in combination with octreotide LAR. The vascular endothelial growth factor inhibitor sunitinib has demonstrated antitumor effects in pancreatic NETs. Pasireotide, the multi-receptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome. Peptide receptor radiotherapy with yttrium 90-DOTATOC or lutetium 177-DOTATE are also new interesting treatment options for NETs.","subset":"pubmed_abstract"} +{"meta":{"pmid":8855281,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.\nThe aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously identified in rat [Jung, J.S., Bhat, R.V., Preston, G.M., Guggino, W.B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a lambda EMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.","subset":"pubmed_abstract"} +{"meta":{"pmid":29676176,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Effect of MeCP2 on TGF- \u03b21-induced Extracellular Matrix Production in Nasal Polyp-derived Fibroblasts.\nPurpose Methyl-CpG-binding protein 2 (MeCP2), known as a transcriptional regulator, has been suggested to play an important role in myofibroblast differentiation in the lung. The purpose of this study was to investigate the role of MeCP2 in transforming growth factor (TGF)- \u03b21-induced myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs). Methods To identify the expression of MeCP2 in nasal polyp tissues, immunohistochemistry staining and Western blot were performed. TGF- \u03b21-induced NPDFs were treated with 5-azacytidine, a DNA methylation inhibitor, and the expression levels of \u03b1-SMA and fibronectin were determined by semiquantitative reverse transcription polymerase chain reaction, immunofluorescent staining, and Western blotting. The total soluble collagen was analyzed by the Sircol collagen assay. MeCP2 silenced by MeCP2-specific small interference ( si) RNA was verified by Western blot. Results The expression levels of MeCP2 increased in nasal polyp tissues compared to normal inferior turbinate tissues. 5-Azacytidine significantly inhibited the expression of \u03b1-SMA and fibronectin mRNA in a dose-dependent manner. In addition, 5-azacytidine suppressed collagen production and the expression of MeCP2 in the same manner. The expression levels of a-SMA and collagen production were significantly blocked by MeCP2 silencing in TGF- \u03b21-induced NPDFs. Conclusions Our data suggest that MeCP2 plays an essential role in TGF- \u03b21-induced myofibroblast differentiation and ECM production in NPDFs.","subset":"pubmed_abstract"} +{"meta":{"pmid":30842454,"dup_signals":{"dup_doc_count":52,"dup_dump_count":25,"dup_details":{"curated_sources":4,"2023-40":1,"2023-23":5,"2023-14":2,"2023-06":2,"2022-49":2,"2022-40":1,"2022-33":1,"2022-27":5,"2022-21":2,"2022-05":1,"2021-49":2,"2021-43":2,"2021-39":3,"2021-31":3,"2021-21":1,"2021-17":1,"2021-10":2,"2021-04":1,"2020-50":1,"2020-45":2,"2020-40":1,"2020-34":2,"2023-50":1,"2024-26":2,"2024-10":2}}},"text":"Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos.\nVEGFA signaling controls physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VEGFA have been uncovered, vegfa transcriptional regulation in vivo remains unclear. Here, we show that the ETS transcription factor, Etv6, positively regulates vegfa expression during Xenopus blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits expression of the repressor foxo3, to prevent Foxo3 from binding to and repressing the vegfa promoter. Etv6 also directly activates expression of the activator klf4; reflecting a genome-wide paucity in ETS-binding motifs in Etv6 genomic targets, Klf4 then recruits Etv6 to the vegfa promoter to activate its expression. These two mechanisms (double negative gate and feed-forward loop) are classic features of gene regulatory networks specifying cell fates. Thus, Etv6's dual function, as a transcriptional repressor and activator, controls a major signaling pathway involved in endothelial and blood development in vivo.","subset":"pubmed_abstract"} +{"meta":{"pmid":3355415,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"The quantitative effect of 0.5% ketorolac tromethamine solution and 0.1% dexamethasone sodium phosphate solution on postsurgical blood-aqueous barrier.\nAnterior chamber fluorophotometry was performed after the oral administration of fluorescein sodium in patients undergoing extracapsular cataract extraction and posterior chamber intraocular lens insertion before and after surgery. The administration of 0.5% ketorolac tromethamine solution (ketorolac solution) eye drops before and after surgery decreased the breakdown of the blood-aqueous barrier as compared with 0.1% dexamethasone sodium phosphate solution (dexamethasone solution) eye drops at each period, as measured by fluorophotometry. A single injection below Tenon's capsule of a short-acting corticosteroid had been given to each patient at the end of each surgical procedure. Slit-lamp observations of postoperative ocular inflammation were not different between treatment groups. Both ketorolac and dexamethasone solutions were well tolerated by patients. Ketorolac solution was more effective than dexamethasone solution in facilitating reestablishment of the blood-aqueous barrier after surgery, as measured by fluorophotometry, and was equal to dexamethasone solution as observed by slit-lamp observations. This study suggests that ketorolac ophthalmic solution may be effective and safe as a nonsteroidal anti-inflammatory agent for topical use after cataract surgery and intraocular lens implantation in place of topically administered corticosteroids.","subset":"pubmed_abstract"} +{"meta":{"pmid":26928056,"dup_signals":{"dup_doc_count":24,"dup_dump_count":18,"dup_details":{"curated_sources":4,"2022-33":2,"2021-17":1,"2021-04":1,"2020-16":1,"2019-43":1,"2019-35":2,"2019-13":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-26":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2017-34":1,"2017-26":1}}},"text":"Reverse engineering the face space: Discovering the critical features for face identification.\nHow do we identify people? What are the critical facial features that define an identity and determine whether two faces belong to the same person or different people? To answer these questions, we applied the face space framework, according to which faces are represented as points in a multidimensional feature space, such that face space distances are correlated with perceptual similarities between faces. In particular, we developed a novel method that allowed us to reveal the critical dimensions (i.e., critical features) of the face space. To that end, we constructed a concrete face space, which included 20 facial features of natural face images, and asked human observers to evaluate feature values (e.g., how thick are the lips). Next, we systematically and quantitatively changed facial features, and measured the perceptual effects of these manipulations. We found that critical features were those for which participants have high perceptual sensitivity (PS) for detecting differences across identities (e.g., which of two faces has thicker lips). Furthermore, these high PS features vary minimally across different views of the same identity, suggesting high PS features support face recognition across different images of the same face. The methods described here set an infrastructure for discovering the critical features of other face categories not studied here (e.g., Asians, familiar) as well as other aspects of face processing, such as attractiveness or trait inferences.","subset":"pubmed_abstract"} +{"meta":{"pmid":9387776,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"[Effects of subtotal nephrectomy and high salt intake on atrial natriuretic peptide in the brains of rats].\nIn order to explore the role of brain atrial natriuretic peptide (ANP) in regulating water and electrolytes, the changes of the ANP content of various brain areas in the status of high salt intake and in 3\/4 nephrectomy rats. In control group, a wide distribution of ANP was observed in different areas of the brain. The amount of daily water intake and urine were larger, and urine sodium concentration was lower in the 3\/4 nephrectomy group than those in the control group (P < 0.05). In the ten nuclei we have studied, ANP content was not significantly different from that of the control (P > 0.05). In the high salt group, water intake, urine volume and urine sodium concentration were significantly higher than those in the control. In this group, brain ANP increased in the periventricular nuclues (PVN) and arcute nucleus (Arc) (P < 0.05). The results indicate that ANP in anteroventral region of the third ventricle (AV3V) might play important role in the regulation of water and electolytes.","subset":"pubmed_abstract"} +{"meta":{"pmid":23667446,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.\nTriple negative breast cancers (TNBC) are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.","subset":"pubmed_abstract"} +{"meta":{"pmid":6129633,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":12}}},"text":"Functional implications of cross-orientation inhibition of cortical visual cells. I. Neurophysiological evidence.\nSimple and complex cells of striate cortex of anaesthetized and paralysed cats were stimulated with two superimposed one-dimensional grating stimuli of different orientations to investigate inhibitory effects of non-optimally oriented stimuli. We confirmed that a stimulus of orientation orthogonal to a cell's long axis significantly reduces the cell's discharge rate. Further experiments revealed the following. (i) The inhibition was typically stronger for simple than for complex cells. (ii) It is very broadly tuned for orientation, all orientations outside the cell's tuning band having a comparable inhibitory effect. (iii) Similarly, it is broadly tuned for spatial frequency. These last two results suggest that the inhibition arises not from a single cell but from a pool of cells. (iv) The pattern of the discharge of the inhibition in response to stimulation by phase-reversed sinusoidal gratings is consistent with the notion that the inhibition arises from complex cells. A second series of recordings of stimulation by visual noise patterns demonstrated how 'cross-orientation inhibition' prevents simple cells from responding to two-dimensional visual noise while allowing them to respond to comparable one-dimensional noise patterns. We suggest that this mechanism may serve to render simple cells selectively sensitive to one-dimensional stimuli, such as the contours or borders of visual objects.","subset":"pubmed_abstract"} +{"meta":{"pmid":22133063,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Evaluation of long-term patient satisfaction and experience with the Baha\u00ae bone conduction implant.\nEvaluate long-term patient satisfaction with bone-anchored hearing aids (the Baha\u00ae, now referred to by Cochlear as a 'bone conduction implant') in our hospital clinic spanning the eighteen-year period from the inception of our Baha program. The researchers further wished to analyse the various factors leading to patient satisfaction\/dissatisfaction with their Baha. We developed a new questionnaire to obtain a comprehensive impression of individual patient practices, general satisfaction, and experiences with their Baha in respect to time spent using Baha, sound quality, annoyance from noise disturbance, ease of communication, cosmetic appearance, and satisfaction with the Baha amongst patient relatives, an aspect not previously investigated. The study design was retrospective and executed as a postal questionnaire. The questionnaire was developed by the authors of this paper. Patients operated on for a Baha at our hospital from 1989 to 2007. The response rate was 92.4%. Eighty-six percent were satisfied or very satisfied with their Baha. Ninety-one percent of respondents could communicate using their Baha in a one-on-one conversational setting. A primary factor leading to dissatisfaction, experienced by 70% of responding patients, was annoyance from wind noise. Baha was found to yield good overall patient satisfaction over the long-term, and it was possible to identify specific factors attributing to satisfaction\/dissatisfaction.","subset":"pubmed_abstract"} +{"meta":{"pmid":23412694,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":13}}},"text":"Multiple brain metastases - current management and perspectives for treatment with electrochemotherapy.\nDue to the advanced oncological treatments of cancer, an overall increase in cancer incidence, and better diagnostic tools, the incidence of brain metastases is on the rise. This review addresses the current treatment options for patients with multiple brain metastases, presenting electrochemotherapy (ECT) as one of the new experimental treatments for this group of patients. Neurosurgery, stereotactic surgery, and whole-brain radiotherapy are the evidence-based treatments that can be applied for patients with multiple brain metastases. Treatment with chemotherapy and molecularly targeted agents may also be warranted. Several experimental treatments are emerging, one of which is ECT, an effective cancer treatment comprising electric pulses given by electrodes in the tumor tissue, causing electroporation of the cell membrane, and thereby augmenting uptake and the cytotoxicity of the chemotherapeutic drug bleomycin by 300 times. Preclinical data are promising and the first patient has been treated in an ongoing clinical trial for patients with brain metastases. Perspectives for ECT in the brain include treatment of primary and secondary brain tumors as well as soft tissue metastases elsewhere.","subset":"pubmed_abstract"} +{"meta":{"pmid":24196534,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":9}}},"text":"Molecular interactions of serotonin (5-HT) and endothelin-1 in vascular smooth muscle cells: in vitro and ex vivo analyses.\nElevated levels of serotonin (5-HT) and endothelin-1 (ET-1) may be involved in cardiovascular complications of diabetes mellitus. Data suggest supraphysiological concentrations of 5-HT (10(-6) M) potentiate the ability of ET-1 to stimulate DNA synthesis and vascular smooth muscle cell (VSMC) proliferation in vitro via activation of mitogen-activated protein kinase (p42\/44 MAPK) and Janus kinase 2 (JAK2) pathways. Additionally, 5-HT enhances agonist-induced contractions via p42\/44 MAPK and an unknown tyrosine kinase. However, the exact mechanisms of the 5-HT\/ET-1 interactions and whether these effects occur at physiological levels (10(-9) M) are unknown. Therefore, we hypothesized that interactions between 5-HT and ET-1 at physiological concentrations in VSMC enhanced activation of both p42\/44 MAPK and JAK2 pathways contributing to vascular growth and contractile responses. With the use of rat VSMC and Western blot analysis, our data suggest no effect of acute (30 min) preincubation with 5-HT (10(-9) M) and\/or ET-1 (10(-9) M) on the activation of either pathway in normal or high glucose conditions. To determine if there was altered vascular reactivity in intact vessels we tested the effects of 5-HT and ET-1 interaction using myographs to measure isometric contractions of rat thoracic aortic rings. 5-HT (10(-9) M) and ET-1 (10(-12) M) stimulate enhanced contractile responses to each other that were inhibited by JAK2 and p42\/44 MAPK antagonists. Our findings demonstrate that both 5-HT and ET-1 at physiological concentrations could interact with each other and activate p42\/44 MAPK and JAK2 signaling pathways to cause an increase in smooth muscle contraction that could lead to altered vascular function.","subset":"pubmed_abstract"} +{"meta":{"pmid":16971897,"dup_signals":{"dup_doc_count":75,"dup_dump_count":40,"dup_details":{"curated_sources":2,"2023-50":2,"2023-40":1,"2023-23":3,"2023-14":3,"2023-06":3,"2022-49":2,"2022-27":3,"2022-21":3,"2021-49":1,"2021-43":2,"2021-31":3,"2021-21":3,"2021-17":1,"2021-10":2,"2021-04":2,"2020-50":2,"2020-45":1,"2020-40":2,"2019-13":1,"2019-04":1,"2018-51":1,"2018-43":2,"2018-34":1,"2018-30":1,"2018-26":2,"2018-17":1,"2018-13":2,"2018-09":1,"2017-51":2,"2017-43":2,"2017-34":2,"2017-30":1,"2017-22":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2024-26":2,"2024-10":6,"2017-13":1}}},"text":"Molecular mechanisms of muscular dystrophies: old and new players.\nThe study of the muscle cell in the muscular dystrophies (MDs) has shown that mutant proteins result in perturbations of many cellular components. MDs have been associated with mutations in structural proteins, signalling molecules and enzymes as well as mutations that result in aberrant processing of mRNA or alterations in post-translational modifications of proteins. These findings have not only revealed important insights for cell biologists, but have also provided unexpected and exciting new approaches for therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":24038614,"dup_signals":{"dup_doc_count":22,"dup_dump_count":11,"dup_details":{"curated_sources":2,"2023-50":4,"2023-40":1,"2023-23":3,"2023-14":2,"2022-49":1,"2022-27":3,"2022-21":1,"2022-05":1,"2021-49":2,"2024-18":1,"2024-26":1}}},"text":"The representation of oral fat texture in the human somatosensory cortex.\nHow fat is sensed in the mouth and represented in the brain is important in relation to the pleasantness of food, appetite control, and the design of foods that reproduce the mouthfeel of fat yet have low energy content. We show that the human somatosensory cortex (SSC) is involved in oral fat processing via functional coupling to the orbitofrontal cortex (OFC), where the pleasantness of fat texture is represented. Using functional MRI, we found that activity in SSC was more strongly correlated with the OFC during the consumption of a high fat food with a pleasant (vanilla) flavor compared to a low fat food with the same flavor. This effect was not found in control analyses using high fat foods with a less pleasant flavor or pleasant-flavored low fat foods. SSC activity correlated with subjective ratings of fattiness, but not of texture pleasantness or flavor pleasantness, indicating a representation that is not involved in hedonic processing per se. Across subjects, the magnitude of OFC-SSC coupling explained inter-individual variation in texture pleasantness evaluations. These findings extend known SSC functions to a specific role in the processing of pleasant-flavored oral fat, and identify a neural mechanism potentially important in appetite, overeating, and obesity.","subset":"pubmed_abstract"} +{"meta":{"pmid":14595069,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Human milk, breastfeeding, and transmission of human immunodeficiency virus type 1 in the United States. American Academy of Pediatrics Committee on Pediatric AIDS.\nTransmission of human immunodeficiency virus type 1 (HIV-1) through breastfeeding has been conclusively demonstrated. The risk of such transmission has been quantified, the timing has been clarified, and certain risk factors for breastfeeding transmission have been identified. In areas where infant formula is accessible, affordable, safe, and sustainable, avoidance of breastfeeding has represented one of the main components of mother-to-child HIV-1 transmission prevention efforts for many years. In areas where affordable and safe alternatives to breastfeeding may not be available, interventions to prevent breastfeeding transmission are being investigated. Complete avoidance of breastfeeding by HIV-1-infected women has been recommended by the American Academy of Pediatrics and the Centers for Disease Control and Prevention and remains the only means by which prevention of breastfeeding transmission of HIV-1 can be absolutely ensured. This technical report summarizes the information available regarding breastfeeding transmission of HIV-1.","subset":"pubmed_abstract"} +{"meta":{"pmid":19398878,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-22":1,"2024-26":1,"unknown":8}}},"text":"Renal cell carcinoma: biological features and rationale for molecular-targeted therapy.\nCancer cells are characterized by indefinite proliferation, invasiveness and metastases. These characteristics are usually related to one another. Namely, cancer cells that proliferate rapidly tend to invade and metastasize. Renal cell carcinoma (RCC) typically does not proliferate rapidly nor does it invade the surrounding tissues, but it does metastasize. RCC has several peculiar characteristics that are not observed in other cancers: a relatively late recurrence, a high frequency of paraneoplastic syndrome, hypervascularity and the spontaneous regression of metastatic lesions after the excision of the primary tumor. These clinical observations suggest that cytokines or growth factors are important contributors to microenvironments favoring the growth of cancer cells. Thus, the blockade of cell-to-cell communication might have some therapeutic potential. Accordingly, a popular strategy for molecular-targeted therapy for RCC targets the vasculization of RCC induced by vascular endothelial growth factor (VEGF). This review highlights the biological features of RCC that are relevant to molecular-targeted therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23729312,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"Shear force at failure and stiffness of all-inside meniscal repair devices.\nThe purpose of this study was to determine the failure load and stiffness of various meniscal repair devices. A total of 61 fresh-frozen porcine menisci (medial and lateral) were used for the study. A 30-mm vertical, full-thickness tear was created and repaired using one of three all-inside fixation devices and one inside-out repair in the vertical mattress pattern. We used the MaxBraid (Biomet, Warsaw, IN) inside-out suture as a control. The other devices tested were the Meniscal Cinch (Arthrex, Naples, FL), Ultra FasT-Fix (Smith & Nephew, Andover, MA), and the MaxFire MarXmen (Biomet, Warsaw, IN). In addition, two devices, MaxFire MarXmen and Ultra FasT-Fix, were tested using a horizontal mattress configuration. Using the vertical mattress pattern, the Meniscal Cinch had the highest average load to failure. The Meniscal Cinch was significantly less stiff than the other three devices (p < 0.04). For the MarXmen and Ultra FasT-Fix, no differences were noted for load to failure between horizontal and vertical mattress patterns. The mode of failure was significantly different when comparing the two different surgical techniques for the MaxFire MarXmen (p = 0.005). The MaxFire MarXmen device produced a significantly stiffer (p < 0.001) construct when following the manufacturer's instructions (5.8 N\/mm) than with the technique used for the other all-inside devices (2.5 N\/mm) The Meniscal Cinch had the highest load-to-failure value but the lowest stiffness of the group in the vertical mattress configuration. There was little difference in biomechanical properties between vertical and horizontal repair. Importantly, there was a significant difference in stiffness and failure mode for the MaxFire MarXmen when the manufacturer guidelines were not specifically followed.","subset":"pubmed_abstract"} +{"meta":{"pmid":35131690,"dup_signals":{"dup_doc_count":14,"dup_dump_count":3,"dup_details":{"curated_sources":1,"2024-26":3,"2024-22":1,"2024-18":1,"unknown":8}}},"text":"Youth drinking in decline: What are the implications for public health, public policy and public debate?\nYouth drinking has declined across most high-income countries in the last 20 years. Although researchers and commentators have explored the nature and drivers of decline, they have paid less attention to its implications. This matters because of the potential impact on contemporary and future public health, as well as on alcohol policy-making. This commentary therefore considers how youth drinking trends may develop in future, what this would mean for public health, and what it might mean for alcohol policy and debate. We argue that the decline in youth drinking is well-established and unlikely to reverse, despite smaller declines and stabilising trends in recent years. Young people also appear to be carrying their lighter drinking into adulthood in at least some countries. This suggests we should expect large short- and long-term public health benefits. The latter may however be obscured in population-level data by increased harm arising from earlier, heavier drinking generations moving through the highest risk points in the life course. The likely impact of the decline in youth drinking on public and policy debate is less clear. We explore the possibilities using two model scenarios, the reinforcement and withdrawal models. In the reinforcement model, a 'virtuous' circle of falling alcohol consumption, increasing public support for alcohol control policies and apparent policy successes facilitates progressive strengthening of policy, akin to that seen in the tobacco experience. In the withdrawal model, policy-makers turn their attention to other problems, public health advocates struggle to justify proposed interventions and existing policies erode over time as industry actors reassert and strengthen their partnerships with government around alcohol policy. We argue that disconnects between the tobacco experience and the reinforcement model make the withdrawal model a more plausible scenario. We conclude by suggesting some tentative ways forward for public health actors working in this space.","subset":"pubmed_abstract"} +{"meta":{"pmid":30563812,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Developing, Implementing, and Evaluating a Multimedia Patient Decision Aid Program to Reform the Informed Consent Process of a Peripherally Inserted Central Venous Catheter Procedure: Protocol for Quality Improvement.\nInformed consent has considerable clinical, ethical, and legal implications for patient safety and liability. Little information is available about the use of multimedia patient decision aids (PtDA) in the consent process for therapeutic invasive procedures such as the peripherally inserted central venous catheter (PICC). In addition, none of the available studies have designed their multimedia PtDAs based on the Agency for Healthcare Research and Quality's (AHRQ) comprehensive guide for informed consent. This paper describes a patient-centered, systematic, multidisciplinary approach to develop, implement, and alpha test a multimedia PtDA to reform the informed consent process of a PICC for patients in 10 acute and intensive care units. The development, implementation, and evaluation processes of the PtDA followed the phases in the Multimedia Production Framework: preproduction, production, and postproduction. Within this framework, we applied the criteria for judging the quality of PtDAs, the AHRQ's Health Literacy Universal Precautions Toolkit, and the AHRQ's Patient Education Materials Assessment Tool Guide. The methodology was guided by the Interprofessional Shared Decision-Making Model and the AHRQ's Making Informed Consent an Informed Choice guide. In the preproduction phase, we (1) reviewed the current consent form; (2) observed 18 consent processes; (3) surveyed the vascular access team (N=6 nurses) about their perception of the current process; (4) surveyed 30 patients for knowledge recall and retention, overall satisfaction, and attitude toward using a multimedia PtDA; and (5) wrote and reviewed the script for the multimedia program. The production phase focused on filming the PtDA in English and Spanish languages. The postproduction phase included integrating the multimedia programs into the care processes, developing a modified workflow for the consent process, and alpha testing of the English and Spanish PtDAs by (1) a group of 5 patients for clarity and understandability of the information; (2) nurses using the AHRQ's Patient Education Materials Assessment Tool Audio and Video; and (3) by the multidisciplinary change team. Based on the alpha testing, patients indicated that the content was easy to follow and read; nurses provided positive feedback, and their comments were mainly related to the changes in the workflow in the consent process of the PICC after using the PtDA; and the multidisciplinary change team suggested edits related to changing a few scenes. The final multimedia program consisted of 7 min and 37 s demonstrating detailed information about the PICC. A systematic development of PtDAs for nonurgent invasive procedures may eliminate many limitations of the conventional consent process by ensuring comprehensive, standardized, and easy-to-comprehend information and providing sufficient time for the patients to reflect on the information. To be effective, PtDAs should follow a systematic, patient-centered, evidence-based, and rigorous approach in the development, implementation, and evaluation processes. RR1-10.2196\/10709.","subset":"pubmed_abstract"} +{"meta":{"pmid":24922532,"dup_signals":{"dup_doc_count":14,"dup_dump_count":7,"dup_details":{"curated_sources":4,"2018-47":1,"2018-39":2,"2018-30":1,"2018-17":1,"2018-05":2,"2017-43":2,"2019-09":1}}},"text":"Ubiquitin Specific Protease 26 (USP26) expression analysis in human testicular and extragonadal tissues indicates diverse action of USP26 in cell differentiation and tumorigenesis.\nUbiquitin specific protease 26 (USP26), a deubiquitinating enzyme, is highly expressed early during murine spermatogenesis, in round spermatids, and at the blood-testis barrier. USP26 has also been recognized as a regulator of androgen receptor (AR) hormone-induced action involved in spermatogenesis and steroid production in in vitro studies. Prior mutation screening of USP26 demonstrated an association with human male infertility and low testosterone production, but protein localization and expression in the human testis has not been characterized previously. USP26 expression analysis of mRNA and protein was completed using murine and human testis tissue and human tissue arrays. USP26 and AR mRNA levels in human testis were quantitated using multiplex qRT-PCR. Immunofluorescence colocalization studies were performed with formalin-fixed\/paraffin-embedded and frozen tissues using primary and secondary antibodies to detect USP26 and AR protein expression. Human microarray dot blots were used to identify protein expression in extra-gonadal tissues. For the first time, expression of USP26 and colocalization of USP26 with androgen receptor in human testis has been confirmed predominantly in Leydig cell nuclei, with less in Leydig cell cytoplasm, spermatogonia, primary spermatocytes, round spermatids, and Sertoli cells. USP26 likely affects regulatory proteins of early spermatogenesis, including androgen receptor with additional activity in round spermatids. This X-linked gene is not testis-specific, with USP26 mRNA and protein expression identified in multiple other human organ tissues (benign and malignant) including androgen-dependent tissues such as breast (myoepithelial cells and secretory luminal cells) and thyroid tissue (follicular cells). USP26\/AR expression and interaction in spermatogenesis and androgen-dependent cancer warrants additional study and may prove useful in diagnosis and management of male infertility.","subset":"pubmed_abstract"} +{"meta":{"pmid":2462794,"dup_signals":{"dup_doc_count":18,"dup_dump_count":15,"dup_details":{"curated_sources":3,"2020-16":1,"2020-05":1,"2019-43":1,"2019-35":1,"2019-22":1,"2019-13":1,"2018-51":1,"2018-43":1,"2018-34":1,"2018-26":1,"2018-17":1,"2018-05":1,"2017-47":1,"2017-39":1,"2020-40":1}}},"text":"Isoenzymic characterization of seven strains of Toxoplasma gondii by isoelectrofocusing in polyacrylamide gels.\nToxoplasma gondii strains are usually defined by biological parameters such as pathogenicity in mice. A characterization of toxoplasma strains by biochemical techniques has not been reported. In this study, extracts of tachyzoites of 7 toxoplasma strains were compared on the basis of their isoenzyme patterns for 39 enzymes by means of isoelectrofocusing in polyacrylamide gels. Eighteen enzymes gave clear and reproducible bands. Of these, 14 had identical electrophoretic patterns for all strains. Two different isoenzyme types were found for the enzymes aspartate aminotransferase, glutathione reductase, glucose phosphate isomerase, and amylase. This allowed the description of 3 isoenzyme pattern groups among the 7 toxoplasma strains. The possible relationship between biological behavior and isoenzyme pattern groups is discussed.","subset":"pubmed_abstract"} +{"meta":{"pmid":27488190,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-18":1,"unknown":11}}},"text":"Force and twist dependence of RepC nicking activity on torsionally-constrained DNA molecules.\nMany bacterial plasmids replicate by an asymmetric rolling-circle mechanism that requires sequence-specific recognition for initiation, nicking of one of the template DNA strands and unwinding of the duplex prior to subsequent leading strand DNA synthesis. Nicking is performed by a replication-initiation protein (Rep) that directly binds to the plasmid double-stranded origin and remains covalently bound to its substrate 5'-end via a phosphotyrosine linkage. It has been proposed that the inverted DNA sequences at the nick site form a cruciform structure that facilitates DNA cleavage. However, the role of Rep proteins in the formation of this cruciform and the implication for its nicking and religation functions is unclear. Here, we have used magnetic tweezers to directly measure the DNA nicking and religation activities of RepC, the replication initiator protein of plasmid pT181, in plasmid sized and torsionally-constrained linear DNA molecules. Nicking by RepC occurred only in negatively supercoiled DNA and was force- and twist-dependent. Comparison with a type IB topoisomerase in similar experiments highlighted a relatively inefficient religation activity of RepC. Based on the structural modeling of RepC and on our experimental evidence, we propose a model where RepC nicking activity is passive and dependent upon the supercoiling degree of the DNA substrate.","subset":"pubmed_abstract"} +{"meta":{"pmid":25872420,"dup_signals":{"dup_doc_count":11}},"text":"A molecular imprinted SPR biosensor for sensitive determination of citrinin in red yeast rice.\nA novel and sensitive molecular imprinted surface plasmon resonance (SPR) biosensor was developed for selective determination of citrinin (CIT) in red yeast rice. Firstly, the gold surface of SPR chip was modified with allyl mercaptane. Then, CIT-imprinted poly(2-hydroxyethyl methacrylate-methacryloylamidoglutamic acid) (p(HEMA-MAGA)) film was generated on the gold surface modified with allyl mercaptane. The unmodified and imprinted surfaces were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM) and contact angle measurements. The linearity range and the detection limit were obtained as 0.005-1.0 ng\/mL and 0.0017 ng\/mL, respectively. The SPR biosensor was applied to determination of CIT in red yeast rice sample.","subset":"pubmed_abstract"} +{"meta":{"pmid":27800100,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Acceptance of provider-initiated testing and counseling for HIV infection by caregivers in a tertiary health institution in Abuja, Nigeria: a cross sectional study.\nLess than 10% of HIV positive children are enrolled into antiretroviral treatment program in the country. Provider-initiated testing and counseling was introduced to increasing uptake of HIV testing. The aim of this study is to determine the acceptability and factors undermining the acceptance of this laudable initiative by parents\/caregivers of children attending paediatric out patient clinical services in our health institution. A cross sectional study of children aged 18 months to 18 years and their parents\/caregivers attending paediatric outpatient clinic of the hospital was undertaken for the above objectives. There were statistically more female parents\/caregivers (82.5%, p=0.00), more male patients (52.9 %, p= 0.02), and 11.9% adolescents in this study. While 91.7% of parents\/caregivers admitted not having knowledge of provider-initiated testing and counseling, 95.6% knew what HIV was. Acceptance of the program was high (98.7%), majority (89.7%) wanting to know the HIV status of their children\/wards. Non-acceptance was small (1.2%), there main reason being prior knowledge of their HIV status. Prevalence of HIV among tested children was 1.7%. There was a strong relationship between having willingness to test for HIV and many of the study variables with religion of the parents\/caregivers having the strongest relationship [OR: 13.94, (CI 1.82, 55.34)], and tribe having list association, [OR: 3.60, (CI 1.85, 17.14)]. There was general wiliness to accept HIV test for children by their parents\/caregiver in this study, and HIV prevalence in children is on a downward trend; its sustenance to be continued and adolescent clinics need to be created.","subset":"pubmed_abstract"} +{"meta":{"pmid":11374203,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":3,"unknown":12}}},"text":"Recognising the style of spatially exaggerated tennis serves.\nA technique for the construction of exaggerated human movements was developed and its effectiveness tested for the case of categorising tennis serves as flat, slice, or topspin. The technique involves treating movements as points in a high-dimensional space and uses average movements as the basis for constructing exaggerated movements. Exaggerated movements of a particular style are defined as those points in the space of movements which lie on a line originating at the style average and in the direction defined by the difference between the style average and the grand average. In order to visualise the movements, computer animation techniques were employed to transform the three-dimensional coordinates of the movement into the motion of a solid-body figure. These solid-body models were used in perceptual experiments to assess the effectiveness of the exaggeration technique. After an initial training session on the exemplars from the original library, subjects viewed the synthetic tennis-serve motions and in two separate sessions either made three-alternative, categorisation judgments after viewing a single serve or rated dissimilarity after viewing a pair of serves. Results from both accuracy in the categorisation task and structure of a multidimensional scaling solution of the matrix of dissimilarities indicated that, as distance from the grand average increased, the service motion became more distinct and more accurately identified.","subset":"pubmed_abstract"} +{"meta":{"pmid":22023221,"dup_signals":{"dup_doc_count":30,"dup_dump_count":24,"dup_details":{"curated_sources":4,"2023-50":2,"2023-23":1,"2023-14":1,"2023-06":1,"2022-40":1,"2022-05":1,"2021-39":1,"2020-29":1,"2020-16":1,"2020-05":1,"2019-51":1,"2019-43":1,"2019-35":1,"2019-26":1,"2019-18":1,"2019-04":1,"2018-47":1,"2018-39":1,"2018-30":1,"2018-22":1,"2018-13":1,"2017-51":1,"2017-43":1,"2024-22":2}}},"text":"Population growth dynamics of carbon nanotubes.\nUnderstanding the population growth behavior of filamentary nanostructures, such as carbon nanotubes (CNTs), is hampered by the lack of characterization techniques capable of probing statistical variations with high spatial resolution. We present a comprehensive methodology for studying the population growth dynamics of vertically aligned CNT forests, utilizing high-resolution spatial mapping of synchrotron X-ray scattering and attenuation, along with real-time height kinetics. We map the CNT alignment and dimensions within CNT forests, revealing broadening and focusing of size distributions during different stages of the process. Then, we calculate the number density and mass density of the CNT population versus time, which are true measures of the reaction kinetics. We find that the mass-based kinetics of a CNT population is accurately represented by the S-shaped Gompertz model of population growth, although the forest height and CNT length kinetics are essentially linear. Competition between catalyst activation and deactivation govern the rapid initial acceleration and slow decay of the CNT number density. The maximum CNT density (i.e., the overall catalyst activity) is limited by gas-phase reactions and catalyst-surface interactions, which collectively exhibit autocatalytic behavior. Thus, we propose a comprehensive picture of CNT population growth which combines both chemical and mechanical cooperation. Our findings are relevant to both bulk and substrate-based CNT synthesis methods and provide general insights into the self-assembly and collective growth of filamentary nanostructures.","subset":"pubmed_abstract"} +{"meta":{"pmid":21865995,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Volunteers in plastic surgery guidelines for providing surgical care for children in the less developed world: part II. Ethical considerations.\nMany international volunteer groups provide free reconstructive plastic surgery for the poor and underserved in developing countries. An essential issue in providing this care is that it meets consistent guidelines for both quality and safety-a topic that has been addressed previously. An equally important consideration is how to provide that care in an ethical manner. No literature presently addresses the various issues involved in making those decisions. With these ethical considerations in mind, the Volunteers in Plastic Surgery Committee of the American Society of Plastic Surgeons\/Plastic Surgery Foundation undertook a project to create a comprehensive set of guidelines for volunteer groups planning to provide this type of reconstructive plastic surgery in developing countries. The committee worked in conjunction with the Society for Pediatric Anesthesia on this project. The Board of the American Society of Plastic Surgeons\/Plastic Surgery Foundation has approved the ethical guidelines created for the delivery of care in developing countries. The guidelines address the variety of ethical decisions that may be faced by a team working in an underdeveloped country. These guidelines make it possible for a humanitarian effort to anticipate the types of ethical decisions that are often encountered and be prepared to deal with them appropriately. Any group seeking to undertake an international mission trip in plastic surgery should be able to go to one source to find a detailed discussion of the perceived needs in providing ethical humanitarian care. This document was created to satisfy that need and is a companion to our original guidelines addressing safety and quality.","subset":"pubmed_abstract"} +{"meta":{"pmid":32790792,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":11}}},"text":"Caffeine increases motor output entropy and performance in 4 km cycling time trial.\nCaffeine improves cycling time trial performance through enhanced motor output and muscle recruitment. However, it is unknown if caffeine further increases power output entropy. To investigate the effects of caffeine effects on cycling time trial performance and motor output entropy (MOEn), nine cyclists (VO2MAX of 55 \u00b1 6.1 mL.kg.-1min-1) performed a 4 km cycling time trial (TT4km) after caffeine and placebo ingestion in a counterbalanced order. Power output data were sampled at a 2 Hz frequency, thereafter entropy was estimated on a sliding-window fashion to generate a power output time series. A number of mixed models compared performance and motor output entropy between caffeine and placebo every 25% of the total TT4km distance. Caffeine ingestion improved power output by 8% (p = 0.003) and increased MOEn by 7% (p = 0.018). Cyclists adopted a U-shaped pacing strategy after caffeine ingestion. MOEn mirrored power output responses as an inverted U-shape MOEn during the time trial. Accordingly, a strong inverse correlation was observed between MOEn and power output responses over the last 25% of the TT4km (p < 0.001), regardless of the ingestion, likely reflecting the end spurt during this period (p = 0.016). Caffeine ingestion improved TT4km performance and motor output responses likely due to a greater power output entropy.","subset":"pubmed_abstract"} +{"meta":{"pmid":23755234,"dup_signals":{"dup_doc_count":29,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":1,"unknown":25}}},"text":"Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid Fatty Acid composition in a muscle type specific manner in sheep.\nWe previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1\u03b1 (PGC1\u03b1) mRNA in BF, but increased PGC1\u03b1 expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6\/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1\u00bd years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep.","subset":"pubmed_abstract"} +{"meta":{"pmid":8389276,"dup_signals":{"dup_doc_count":28,"dup_dump_count":22,"dup_details":{"curated_sources":4,"2022-27":1,"2021-39":1,"2021-25":1,"2020-50":1,"2020-40":1,"2020-34":1,"2020-10":1,"2020-05":1,"2019-43":1,"2019-26":1,"2019-22":1,"2019-09":2,"2018-51":1,"2018-43":1,"2018-30":1,"2018-13":1,"2018-05":1,"2017-47":1,"2022-49":1,"2024-18":2,"2013-20":1,"2024-22":1}}},"text":"Demonstration of the anti-viral activity of garlic extract against human cytomegalovirus in vitro.\nThe in vitro anti-viral activity of garlic extract (GE) on human cytomegalovirus (HCMV) was evaluated by tissue culture, plaque reduction and early antigen assay. A dose dependent inhibitory effect of GE was evident when GE was applied simultaneously with HCMV. But the effect was stronger when the monolayers were pretreated with GE. In addition, the anti-viral effect of GE persisted long in infected cells after its being removed from the culture medium. The strongest anti-viral effect of GE was demonstrated when it was applied continuously. It is therefore recommended that clinical use of GE against HCMV infection should be persistent and the prophylactic use of GE is preferable in immunocompromised patients.","subset":"pubmed_abstract"} +{"meta":{"pmid":23414116,"dup_signals":{"dup_doc_count":13,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":10}}},"text":"'We are despised in the hospitals': sex workers' experiences of accessing health care in four African countries.\nSex workers in east and southern Africa are exposed to multiple occupational health and safety risks. Detailed understanding of barriers to accessing care would optimise design of improved services for this population. In this study, trained sex workers conducted 55 in-depth interviews and 12 focus group discussions with 106 female, 26 male and 4 transgender sex workers across 6 urban sites in Kenya, Zimbabwe, Uganda and South Africa. Data were analysed thematically, following an interpretive framework. Participants cited numerous unmet health needs, including diagnosis and treatment for sexually transmitted infections and insufficient access to condoms and lubricant. Denial of treatment for injuries following physical assault or rape and general hostility from public-sector providers was common. Resources permitting, many sex workers attended private services, citing higher quality and respect for dignity and confidentiality. Sex workers in southern Africa accessed specialised sex worker clinics, reporting mostly positive experiences. Across sites, participants called for additional targeted services, but also sensitisation and training of public-sector providers. Criminalisation of sex workers and associated stigmatisation, particularly of transgender and male sex workers, hinder HIV-prevention efforts and render access to mainstream healthcare precarious. Alongside law reform, sex worker-led peer outreach work should be strengthened and calls by sex workers for additional targeted services heeded.","subset":"pubmed_abstract"} +{"meta":{"pmid":8640970,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Relation of hormone-replacement therapy to measures of plasma fibrinolytic activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators.\nThe mechanisms by which replacement hormones may reduce the risk of coronary heart disease are not fully understood. Of specific interest is a potential effect of replacement hormones on plasma fibrinolytic activity, a putative determinant of thrombotic events. We investigated the relation of current use of replacement hormones to three measures of plasma fibrinolytic activity: tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and D-dimer. The sample was composed of 288 women, free of clinical cardiovascular disease, who were selected for a case-control study of atherosclerosis: 142 women with ultrasonographic evidence of carotid intimal-medial thickening (cases) and 146 control subjects. Twenty percent (59 women) reported current use of replacement hormones. TPA antigen and PAI-1 antigen were highly correlated with each other (r = .67), whereas D-dimer correlated only weakly with TPA or PAI-1. Compared with nonusers, current users of replacement hormones had lower mean levels of TPA and PAI-1 antigens, suggesting enhanced fibrinolytic potential. In the entire sample, the multivariate-adjusted geometric mean values of TPA antigen were 6.3 and 7.3 ng\/mL among current users and nonusers, respectively (P = .01); the corresponding values for PAI-1 antigen were 6.1 and 7.5 ng\/mL (P = .13). These results were generally consistent for both atherosclerosis cases and their control subjects. D-dimer levels were lower in current hormone users than in nonusers, but the difference was not statistically significant (P > .15) in any of the analyses. The use of replacement hormones appears to be associated with enhancement of endogenous fibrinolytic potential. Enhanced plasma fibrinolytic activity among hormone users may explain, in part, the inverse association between hormone replacement therapy and coronary heart disease.","subset":"pubmed_abstract"} +{"meta":{"pmid":33090867,"dup_signals":{"dup_doc_count":19,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-30":1,"unknown":16}}},"text":"Mock jurors' evaluation of firearm examiner testimony.\nFirearms experts traditionally have testified that a weapon leaves \"unique\" toolmarks, so bullets or cartridge casings can be visually examined and conclusively matched to a particular firearm. Recently, due to scientific critiques, Department of Justice policy, and judges' rulings, firearms experts have tempered their conclusions. In two experiments, we tested whether this ostensibly more cautious language has its intended effect on jurors (Experiment 1), and whether cross-examination impacts jurors' perception of firearm testimony (Experiment 2). Four hypotheses were tested. First, jurors will accord significant weight to firearm testimony that declares a \"match\" compared to testimony that does not (Experiments 1 and 2). Second, variations to \"match\" language will not affect guilty verdicts (Experiment 1). Third, only the most cautious language (\"cannot exclude the gun\") would lower guilty verdicts (Experiment 1). Fourth, cross-examination will reduce guilty verdicts depending on specific language used (Experiment 2). In two preregistered, high-powered experiments with 200 mock jurors per cell, participants recruited from Qualtrics Panels were presented with a criminal case containing firearms evidence, which varied the wording of the examiner's conclusion and whether cross-examination was present. These variations include conclusion language used by practitioners, language advised by government organizations, and language required by judges in several cases. Participants gave a verdict, rated the evidence and expert in all conditions. Guilty verdicts significantly increased when a match was declared compared to when a match was not declared. Variation in conclusion language did not affect guilty verdicts nor did it affect jurors' estimates of the likelihood the defendant's gun fired the bullet recovered at the crime scene. In contrast, however, a more cautious conclusion that an examiner \"cannot exclude the defendant's gun\" did significantly reduce guilty verdicts and likelihood estimates alike. The presence of cross-examination did not affect these findings. Apart from the most limited language (\"cannot exclude the defendant's gun\"), judicial intervention to limit firearms conclusion language is not likely to produce its intended effect. Moreover, cross-examination does not appear to affect perceptions or individual juror verdicts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).","subset":"pubmed_abstract"} +{"meta":{"pmid":33298934,"dup_signals":{"dup_doc_count":19,"dup_dump_count":2,"dup_details":{"curated_sources":1,"2024-22":1,"2024-26":1,"unknown":16}}},"text":"Effects of the agility boot camp with cognitive challenge (ABC-C) exercise program for Parkinson's disease.\nFew exercise interventions practice both gait and balance tasks with cognitive tasks to improve functional mobility in people with PD. We aimed to investigate whether the Agility Boot Camp with Cognitive Challenge (ABC-C), that simultaneously targets both mobility and cognitive function, improves dynamic balance and dual-task gait in individuals with Parkinson's disease (PD). We used a cross-over, single-blind, randomized controlled trial to determine efficacy of the exercise intervention. Eighty-six people with idiopathic PD were randomized into either an exercise (ABC-C)-first or an active, placebo, education-first intervention and then crossed over to the other intervention. Both interventions were carried out in small groups led by a certified exercise trainer (90-min sessions, 3 times a week, for 6 weeks). Outcome measures were assessed Off levodopa at baseline and after the first and second interventions. A linear mixed-effects model tested the treatment effects on the Mini-BESTest for balance, dual-task cost on gait speed, SCOPA-COG, the UPDRS Parts II and III and the PDQ-39. Although no significant treatment effects were observed for the Mini-BESTest, SCOPA-COG or MDS-UPDRS Part III, the ABC-C intervention significantly improved the following outcomes: anticipatory postural adjustment sub-score of the Mini-BESTest (p = 0.004), dual-task cost on gait speed (p = 0.001), MDS-UPDRS Part II score (p = 0.01), PIGD sub-score of MDS-UPDRS Part III (p = 0.02), and the activities of daily living domain of the PDQ-39 (p = 0.003). Participants with more severe motor impairment or more severe cognitive dysfunction improved their total Mini-BESTest scores after exercise. The ABC-C exercise intervention can improve specific balance deficits, cognitive-gait interference, and perceived functional independence and quality of life, especially in participants with more severe PD, but a longer period of intervention may be required to improve global cognitive and motor function.","subset":"pubmed_abstract"} +{"meta":{"pmid":29774807,"dup_signals":{"dup_doc_count":11,"dup_details":{"curated_sources":2,"unknown":9}}},"text":"Robotic Pyelolithotomy, Extended Pyelolithotomy, Nephrolithotomy, and Anatrophic Nephrolithotomy.\nWe are a reporting on the indications, techniques, and limitations of robotic surgery in the management of renal stones disease. Robotic surgery is a good tool to manage large kidney and ureteral stones, particularly in patients with anatomic anomalies. We describe three techniques in managing staghorn kidney stones: robotic anatrophic nephrolithotomy, robotic pyelolithotomy, and robotic nephrolithotomy. Robotic pyelolithotomy (RP) is ideal for patients with large renal pelvis and partial staghorn stone with a wide extra-renal pelvis. Robotic nephrolithotomy (RN) is ideal for stones inside a calyceal diverticulum or a partial staghorn eroding into the renal parenchyma. Renal vascular control could be avoided in most of those surgeries. Robotic anatrophic nephrolithotomy (RAN) is the most complex procedure and is reserved for patients with complete staghorn stones when percutaneous approach was not successful or not feasible. Control of renal vasculature is required for RAN. For robotic kidney surgeries, patients are positioned in a lateral decubitus position. Four or five ports are placed based on the stone location and surgeon's preference. We prefer the trans-peritoneal approach as it gives us the optimal exposure. For RP and RN, hilar control is usually not required. The renal pelvis\/ renal parenchyma is incised, and the stones are carefully removed. If needed intra-operative flexible nephoscopy can be used to remove residual stones fragments. The collecting system is closed using an absorbable suture. DJ stent if needed is placed in an antegrade fashion. For RAN, the kidney is fully mobilized, and hilar control is required to avoid excessive bleeding. The kidney is incised along Brodel's line and the stones are extracted. The kidney parenchyma is then closed using 1 or 2 layers. We achieved an almost 100% stone free rate with RP and RN. RAN remains a challenging procedure with a success rate around 70%. Robotic surgery is a viable option to manage large renal and ureteral stones particularly in situations where endoscopic approach is not successful or feasible.","subset":"pubmed_abstract"} +{"meta":{"pmid":9238858,"dup_signals":{"dup_doc_count":16,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":13}}},"text":"The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland.\nA remarkably constant feature of vertebrate physiology is a daily rhythm of melatonin in the circulation, which serves as the hormonal signal of the daily light\/dark cycle: melatonin levels are always elevated at night. The biochemical basis of this hormonal rhythm is one of the enzymes involved in melatonin synthesis in the pineal gland-the melatonin rhythm-generating enzyme-serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, E.C. 22.214.171.124). In all vertebrates, enzyme activity is high at night. This reflects the influences of internal circadian clocks and of light. The dynamics of this enzyme are remarkable. The magnitude of the nocturnal increase in enzyme activity ranges from 7- to 150-fold on a species-to-species basis among vertebrates. In all cases the nocturnal levels of AA-NAT activity decrease very rapidly following exposure to light. A major advance in the study of the molecular basis of these changes was the cloning of cDNA encoding the enzyme. This has resulted in rapid progress in our understanding of the biology and structure of AA-NAT and how it is regulated. Several constant features of this enzyme have become apparent, including structural features, tissue distribution, and a close association of enzyme activity and protein. However, some remarkable differences among species in the molecular mechanisms involved in regulating the enzyme have been discovered. In sheep, AA-NAT mRNA levels show relatively little change over a 24-hour period and changes in AA-NAT activity are primarily regulated at the protein level. In the rat, AA-NAT is also regulated at a protein level; however, in addition, AA-NAT mRNA levels exhibit a 150-fold rhythm, which reflects cyclic AMP-dependent regulation of expression of the AA-NAT gene. In the chicken, cyclic AMP acts primarily at the protein level and a rhythm in AA-NAT mRNA is driven by a noncyclic AMP-dependent mechanism linked to the clock within the pineal gland. Finally, in the trout, AA-NAT mRNA levels show little change and activity is regulated by light acting directly on the pineal gland. The variety of mechanisms that have evolved among vertebrates to achieve the same goal-a rhythm in melatonin-underlines the important role melatonin plays as the hormonal signal of environmental lighting in vertebrates.","subset":"pubmed_abstract"} +{"meta":{"pmid":3662636,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"HLA class II antigens (DR, DQ loci) and peripheral arthritis in ankylosing spondylitis.\nFifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.","subset":"pubmed_abstract"} +{"meta":{"pmid":10761922,"dup_signals":{"dup_doc_count":14,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2015-18":1,"unknown":12}}},"text":"Yeast Sm-like proteins function in mRNA decapping and decay.\nOne of the main mechanisms of messenger RNA degradation in eukaryotes occurs by deadenylation-dependent decapping which leads to 5'-to-3' decay. A family of Sm-like (Lsm) proteins has been identified, members of which contain the 'Sm' sequence motif, form a complex with U6 small nuclear RNA and are required for pre-mRNA splicing. Here we show that mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead to inhibition of mRNA decapping. In addition, the Lsm1-Lsm7 proteins co-immunoprecipitate with the mRNA decapping enzyme (Dcp1), a decapping activator (Pat1\/Mrt1) and with mRNA. This indicates that the Lsm proteins may promote decapping by interactions with the mRNA and the decapping machinery. In addition, the Lsm complex that functions in mRNA decay appears to be distinct from the U6-associated Lsm complex, indicating that Lsm proteins form specific complexes that affect different aspects of mRNA metabolism.","subset":"pubmed_abstract"} +{"meta":{"pmid":28255546,"dup_signals":{"dup_doc_count":87,"dup_dump_count":33,"dup_details":{"curated_sources":3,"2023-40":9,"2023-23":3,"2023-14":3,"2023-06":5,"2022-49":1,"2022-40":3,"2022-27":3,"2022-21":3,"2022-05":2,"2021-49":3,"2021-43":2,"2021-39":4,"2021-31":5,"2021-21":1,"2021-17":4,"2021-10":2,"2021-04":6,"2020-50":2,"2020-45":2,"2020-40":3,"2020-34":1,"2019-04":1,"2018-43":1,"2018-30":1,"2018-17":1,"2018-05":1,"2017-43":1,"2023-50":1,"2024-30":2,"2024-26":3,"2024-22":1,"2024-18":2,"2024-10":2}}},"text":"Aggressive restenosis after percutaneous intervention in two coronary loci in a patient with human immunodeficiency virus infection.\nA 54-year-old black African woman, 22 years human immunodeficiency virus (HIV)-positive, presented with an acute coronary syndrome. She was taking two nucleoside reverse transcriptase inhibitors and two protease inhibitors. Viral load and CD4 count were stable. Angiography revealed a right coronary artery lesion, which was treated with everolimus eluting stent. She also underwent balloon angioplasty to the first diagonal. She re-presented on three different occasions and technically successful coronary intervention was performed. The patient has reported satisfactory compliance with dual anti platelet therapy throughout. She was successfully treated with surgical revascularisation. The patient did not experience any clinical recurrence on follow up. This case demonstrates exceptionally aggressive multifocal and recurrent instent restenosis in a patient treated for HIV infection, raising the possibility of an association with HIV infection or potentially components of retro viral therapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":7448125,"dup_signals":{"dup_doc_count":46,"dup_dump_count":24,"dup_details":{"curated_sources":3,"2023-50":4,"2023-40":2,"2023-23":3,"2023-14":3,"2022-49":2,"2022-33":2,"2022-27":3,"2022-05":2,"2021-39":2,"2021-25":2,"2021-17":2,"2021-04":2,"2020-40":2,"2019-13":1,"2018-51":1,"2018-39":1,"2018-30":1,"2018-17":1,"2018-09":1,"2017-51":1,"2017-43":1,"2024-26":2,"2024-22":1,"2024-10":1}}},"text":"The genetic basis of Hb Q-H disease.\nA Chinese family has been studied in which two siblings have haemoglobin Q-H disease. Using a combination of haematological and haemoglobin analysis, globin chain synthesis, analysis of alpha\/beta globin messenger RNA ratios and restriction endonuclease mapping, it has been shown that each of these siblings has received one chromosome on which both alpha chain genes have been deleted and another on which there is only a single alpha chain locus which carries the alpha Q mutation. Their genotype is thus --\/-alpha Q. Despite the fact that the haemoglobin Q mutation in this family is carried on a chromosome with a single alpha chain locus, heterozygous carriers for the variant have only 25% or less haemoglobin Q. Our observations indicate that the molecular basis for haemoglobin Q-alpha thalassaemia is similar to that for the common form of haemoglobin H disease in Orientals. Furthermore, they provide clear evidence that the level of an alpha chain variant in heterozygous carriers is not a reliable reflection of the number of alpha globin genes.","subset":"pubmed_abstract"} +{"meta":{"pmid":28334866,"dup_signals":{"dup_doc_count":22,"dup_dump_count":5,"dup_details":{"curated_sources":2,"2024-30":3,"2024-26":4,"2024-22":4,"2024-18":2,"2024-10":2,"unknown":5}}},"text":"C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia.\nA non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS\/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS\/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells. The C9orf72 hexanucleotide repeat expansion led to haploinsufficiency resulting in severely defective intracellular and extracellular vesicle trafficking and a dysfunctional trans-Golgi network phenotype in patient-derived fibroblasts and induced pluripotent stem cell-derived motor neurons. Genetic ablation of RAB7L1or C9orf72 in SH-SY5Y cells recapitulated the findings in C9ALS\/FTD fibroblasts and induced pluripotent stem cell neurons. When C9ORF72 was overexpressed or antisense oligonucleotides were targeted to the C9orf72 hexanucleotide repeat expansion to upregulate normal variant 1 transcript levels, the defective vesicle trafficking and dysfunctional trans-Golgi network phenotypes were reversed, suggesting that both loss- and gain-of-function mechanisms play a role in disease pathogenesis. In conclusion, we have identified a novel mechanism for C9ALS\/FTD pathogenesis highlighting the molecular regulation of intracellular and extracellular vesicle trafficking as an important pathway in C9ALS\/FTD pathogenesis.","subset":"pubmed_abstract"} +{"meta":{"pmid":24075400,"dup_signals":{"dup_doc_count":21}},"text":"The complexity of nurses' attitudes and practice of sedation at the end of life: a systematic literature review.\nSedation is administered to some palliative care patients at the end of their life. Nurses play an important role in this practice. To systematically review the evidence on nurses' attitudes and practice of end-of-life sedation. We searched eight electronic databases, four key palliative care journals, and reference lists for empirical studies published in English, between 1990 and 2012, on nurses and their attitudes toward and practice of sedation until a patient's death. A total of 10 studies met the inclusion criteria. Data were generated from 7515 nurses in four main settings (specialized palliative care unit, home, nursing home, and acute hospital) from seven countries (Belgium, Canada, Japan, The Netherlands, Norway, U.K., and U.S.). On average, the quality of the evidence was good; hence, we analyzed all selected studies. Based on the findings from a previous review, we categorized the emerging themes into: 1) important factors leading to the patient receiving palliative sedation (PS), 2) nurses' attitudes toward PS, and 3) nurses' experience of PS at the end of a patient's life. In general, nurses had a positive but cautious attitude toward the practice of PS. Most saw it as a last resort treatment for relieving suffering and refractory symptoms, and its practice was often influenced by their level of education, expertise, and the roles they played per setting. Most nurses administered sedation until death only within the given circumstances because of the anticipatory benefits in controlling refractory symptoms and suffering. Some of them experienced burdens during PS delivery; these could be supported by operational guidelines and task-related training.","subset":"pubmed_abstract"} +{"meta":{"pmid":34311468,"dup_signals":{"dup_doc_count":11,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-18":1,"2024-26":1,"unknown":7}}},"text":"Genomic Evidence for Speciation with Gene Flow in Broadcast Spawning Marine Invertebrates.\nHow early stages of speciation in free-spawning marine invertebrates proceed is poorly understood. The Western Pacific abalones, Haliotis discus, H. madaka, and H. gigantea, occur in sympatry with shared breeding season and are capable of producing viable F1 hybrids in spite of being ecologically differentiated. Population genomic analyses revealed that although the three species are genetically distinct, there is evidence for historical and ongoing gene flow among these species. Evidence from demographic modeling suggests that reproductive isolation among the three species started to build in allopatry and has proceeded with gene flow, possibly driven by ecological selection. We identified 27 differentiation islands between the closely related H. discus and H. madaka characterized by high FST and dA, but not high dXY values, as well as high genetic diversity in one H. madaka population. These genomic signatures suggest differentiation driven by recent ecological divergent selection in presence of gene flow outside of the genomic islands of differentiation. The differentiation islands showed low polymorphism in H. gigantea, and both high FST, dXY, and dA values between H. discus and H. gigantea, as well as between H. madaka and H. gigantea. Collectively, the Western Pacific abalones appear to occupy the early stages speciation continuum, and the differentiation islands associated with ecological divergence among the abalones do not appear to have acted as barrier loci to gene flow in the younger divergences but appear to do so in older divergences.","subset":"pubmed_abstract"} +{"meta":{"pmid":22669896,"dup_signals":{"dup_doc_count":17,"dup_dump_count":15,"dup_details":{"curated_sources":2,"2018-43":1,"2018-34":1,"2018-22":1,"2018-09":1,"2017-47":1,"2017-39":1,"2017-34":1,"2017-26":1,"2017-17":1,"2017-09":1,"2017-04":1,"2016-50":1,"2016-44":1,"2019-04":1,"2017-13":1}}},"text":"Phytoestrogen genistein up-regulates endothelial nitric oxide synthase expression via activation of cAMP response element-binding protein in human aortic endothelial cells.\nWe previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis. However, chemical inhibition of protein kinase A (PKA) or adenoviral transfer of the specific endogenous PKA inhibitor gene completely abolished PKA activity and genistein-stimulated eNOS expression and NO production. Accordingly, genistein induced PKA activity and subsequent phosphorylation of cAMP response element (CRE)-binding protein (CREB) at Ser133. Suppression of CREB by small interfering RNA transfection abolished genistein-enhanced eNOS expression and NO production. Consistently, deletion of the CRE site within human eNOS promoter eliminated genistein-stimulated eNOS promoter activity. These findings provide the first evidence to our knowledge that genistein may play a beneficial role in vascular function through targeting the PKA\/CREB\/eNOS\/NO signaling pathway.","subset":"pubmed_abstract"} +{"meta":{"pmid":17687049,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-22":1,"unknown":9}}},"text":"Dendritic HCN2 channels constrain glutamate-driven excitability in reticular thalamic neurons.\nHyperpolarization activated cyclic nucleotide (HCN) gated channels conduct a current, I(h); how I(h) influences excitability and spike firing depends primarily on channel distribution in subcellular compartments. For example, dendritic expression of HCN1 normalizes somatic voltage responses and spike output in hippocampal and cortical neurons. We reported previously that HCN2 is predominantly expressed in dendritic spines in reticular thalamic nucleus (RTN) neurons, but the functional impact of such nonsomatic HCN2 expression remains unknown. We examined the role of HCN2 expression in regulating RTN excitability and GABAergic output from RTN to thalamocortical relay neurons using wild-type and HCN2 knock-out mice. Pharmacological blockade of I(h) significantly increased spike firing in RTN neurons and large spontaneous IPSC frequency in relay neurons; conversely, pharmacological enhancement of HCN channel function decreased spontaneous IPSC frequency. HCN2 deletion abolished I(h) in RTN neurons and significantly decreased sensitivity to 8-bromo-cAMP and lamotrigine. Recapitulating the effects of I(h) block, HCN2 deletion increased both temporal summation of EPSPs in RTN neurons as well as GABAergic output to postsynaptic relay neurons. The enhanced excitability of RTN neurons after I(h) block required activation of ionotropic glutamate receptors; consistent with this was the colocalization of HCN2 and glutamate receptor 4 subunit immunoreactivities in dendritic spines of RTN neurons. The results indicate that, in mouse RTN neurons, HCN2 is the primary functional isoform underlying I(h) and expression of HCN2 constrains excitatory synaptic integration.","subset":"pubmed_abstract"} +{"meta":{"pmid":32556973,"dup_signals":{"dup_doc_count":18,"dup_dump_count":4,"dup_details":{"curated_sources":1,"2024-30":2,"2024-22":1,"2024-18":1,"2024-10":1,"unknown":12}}},"text":"Acoustic Speech Analytics Are Predictive of Cerebellar Dysfunction in Multiple Sclerosis.\nSpeech production relies on motor control and cognitive processing and is linked to cerebellar function. In diseases where the cerebellum is impaired, such as multiple sclerosis (MS), speech abnormalities are common and can be detected by instrumental assessments. However, the potential of speech assessments to be used to monitor cerebellar impairment in MS remains unexplored. The aim of this study is to build an objectively measured speech score that reflects cerebellar function, pathology and quality of life in MS. Eighty-five people with MS and 21 controls participated in the study. Speech was independently assessed through objective acoustic analysis and blind expert listener ratings. Cerebellar function and overall disease disability were measured through validated clinical scores; cerebellar pathology was assessed via magnetic resonance imaging, and validated questionnaires informed quality of life. Selected speech variables were entered in a regression model to predict cerebellar function. The resulting model was condensed into one composite speech score and tested for prediction of abnormal 9-hole peg test (9HPT), and for correlations with the remaining cerebellar scores, imaging measurements and self-assessed quality of life. Slow rate of syllable repetition and increased free speech pause percentage were the strongest predictors of cerebellar impairment, complemented by phonatory instability. Those variables formed the acoustic composite score that accounted for 54% of variation in cerebellar function, correlated with cerebellar white matter volume (r = 0.3, p = 0.017), quality of life (r = 0.5, p < 0.001) and predicted an abnormal 9HPT with 85% accuracy. An objective multi-feature speech metric was highly representative of motor cerebellar impairment in MS.","subset":"pubmed_abstract"} +{"meta":{"pmid":28627960,"dup_signals":{"dup_doc_count":12,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2024-10":1,"unknown":9}}},"text":"Lack of functional normalisation of tumour vessels following anti-angiogenic therapy in glioblastoma.\nNeo-angiogenesis represents an important factor for the delivery of oxygen and nutrients to a growing tumour, and is considered to be one of the main pathodiagnostic features of glioblastomas (GBM). Anti-angiogenic therapy by vascular endothelial growth factor (VEGF) blocking agents has been shown to lead to morphological vascular normalisation resulting in a reduction of contrast enhancement as seen by magnetic resonance imaging (MRI). Yet the functional consequences of this normalisation and its potential for improved delivery of cytotoxic agents to the tumour are not known. The presented study aimed at determining the early physiologic changes following bevacizumab treatment. A time series of perfusion MRI and hypoxia positron emission tomography (PET) scans were acquired during the first week of treatment, in two human GBM xenograft models treated with either high or low doses of bevacizumab. We show that vascular morphology was normalised over the time period investigated, but vascular function was not improved, resulting in poor tumoural blood flow and increased hypoxia.","subset":"pubmed_abstract"} +{"meta":{"pmid":21847618,"dup_signals":{"dup_doc_count":18,"dup_dump_count":1,"dup_details":{"curated_sources":1,"2024-10":1,"unknown":16}}},"text":"Percent lipid is associated with body size but not task in the bumble bee Bombus impatiens.\nIn some group-living organisms, labor is divided among individuals. This allocation to particular tasks is frequently stable and predicted by individual physiology. Social insects are excellent model organisms in which to investigate the interplay between physiology and individual behavior, as division of labor is an important feature within colonies, and individual physiology varies among the highly related individuals of the colony. Previous studies have investigated what factors are important in determining how likely an individual is, compared to nestmates, to perform certain tasks. One such task is foraging. Corpulence (i.e., percent lipid) has been shown to determine foraging propensity in honey bees and ants, with leaner individuals being more likely to be foragers. Is this a general trend across all social insects? Here we report data analyzing the individual physiology, specifically the percent lipid, of worker bumble bees (Bombus impatiens) from whom we also analyze behavioral task data. Bumble bees are also unusual among the social bees in that workers may vary widely in size. Surprisingly we find that, unlike other social insects, percent lipid is not associated with task propensity. Rather, body size closely predicts individual relative lipid stores, with smaller worker bees being allometrically fatter than larger worker bees.","subset":"pubmed_abstract"} +{"meta":{"pmid":29522202,"dup_signals":{"dup_doc_count":15,"dup_details":{"curated_sources":2,"unknown":13}}},"text":"Natural History of Established and De Novo Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis.\nThe course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. Three hundred seventy-three patients were identified (mean age, 47.5 \u00b1 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56\/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093\/ibd\/izx096_video1izx096.video15746673864001.","subset":"pubmed_abstract"} +{"meta":{"pmid":28831481,"dup_signals":{"dup_doc_count":13,"dup_details":{"curated_sources":2,"unknown":11}}},"text":"A new strategy for inducing dipole moments in charge-transfer complexes: introduction of asymmetry into axially ligated iron phthalocyanines.\nIntroduction of asymmetry into charge-transfer complexes composed of axially ligated iron phthalocyanines was achieved. In the obtained crystals of TPP[FeIII(Pc)(CN)Cl]2, TPP[FeIII(Pc)(CN)Br]2, and TPP[FeIII(Pc)BrCl]2 (TPP = tetraphenylphosphonium and Pc = phthalocyanine), the axial positions of the iron atoms were occupied by 50\/50 ratios of the ligands CN\/Cl, CN\/Br, and Br\/Cl, respectively. The crystal structures of the obtained CT complexes were isostructural to those composed of the symmetric analogues of the type [FeIII(Pc)L2] (L = CN, Cl or Br); the [FeIII(Pc)LL'] units formed regular one-dimensional chains along the c-axis following the symmetry of the P42\/n space group. Despite forming similar regular chains to the symmetric systems, the electrical resistivities and activation energies were enhanced in the obtained CT complexes compared to those in symmetric systems, indicating that the charge-ordered states were stabilised by the introduction of asymmetry. More specifically, the dielectric relaxation behaviour of the inhomogeneous disordered TPP[FeIII(Pc)(CN)Cl]2 probably suggests that a dipole moment was induced in this material.","subset":"pubmed_abstract"} +{"meta":{"pmid":30629970,"dup_signals":{"dup_doc_count":21,"dup_dump_count":18,"dup_details":{"curated_sources":1,"2021-39":1,"2021-31":1,"2021-25":1,"2021-17":1,"2021-04":1,"2020-45":1,"2020-29":1,"2020-24":1,"2020-16":1,"2020-05":1,"2019-51":2,"2019-43":1,"2019-35":1,"2019-26":1,"2019-22":1,"2019-18":1,"2019-09":2,"2021-43":1}}},"text":"The use of Genomic Allergen Rapid Detection (GARD) assays to predict the respiratory and skin sensitising potential of e-liquids.\nElectronic cigarettes (e-cigarettes) are an increasingly popular alternative to combustible tobacco cigarettes among smokers worldwide. A growing body of research indicates that flavours play a critical role in attracting and retaining smokers into the e-cigarette category, directly contributing to declining smoking rates and tobacco harm reduction. The responsible selection and inclusion levels of flavourings in e-liquids must be guided by toxicological principles. Some flavour ingredients, whether natural extracts or synthetic, are known allergens. In this study, we used the Genomic Allergen Rapid Detection (GARD) testing strategy to predict and compare the respiratory and skin sensitising potential of three experimental and two commercial e-liquids. These novel, myeloid cell-based assays use changes in the transcriptional profiles of genomic biomarkers that are collectively relevant for respiratory and skin sensitisation. Our initial results indicate that the GARD assays were able to differentiate and broadly classify e-liquids based on their sensitisation potential, which are defined mixtures. Further studies need to be conducted to assess whether and how these assays could be used for the screening and toxicological assessment of e-liquids to support product development and commercialisation.","subset":"pubmed_abstract"} +{"meta":{"pmid":17742806,"dup_signals":{"dup_doc_count":11,"dup_dump_count":1,"dup_details":{"curated_sources":2,"2017-13":1,"unknown":8}}},"text":"The threat of soil erosion to long-term crop production.\nNational increases in row crops at the expense of hay and pasture crops, particularly on steeper slopes, have made the control of erosion a difficult prospect. Management practices that fit the various field conditions are needed to accomplish effective erosion control. These measures should be selected on the basis of soil characteristics, landscape type, and the amount of ongoing erosion. The maintenance of a cropland base adequate to our needs must be a primary national goal.","subset":"pubmed_abstract"} +{"meta":{"pmid":14576434,"dup_signals":{"dup_doc_count":15,"dup_dump_count":1,"dup_details":{"curated_sources":3,"2017-13":4,"unknown":8}}},"text":"Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.\nRisks of breast and ovarian cancer were determined for Ashkenazi Jewish women with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2. We selected 1008 index cases, regardless of family history of cancer, and carried out molecular analysis across entire families. The lifetime risk of breast cancer among female mutation carriers was 82%, similar to risks in families with many cases. Risks appear to be increasing with time: Breast cancer risk by age 50 among mutation carriers born before 1940 was 24%, but among those born after 1940 it was 67%. Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2 mutation carriers. Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset.","subset":"pubmed_abstract"} +{"meta":{"pmid":8915425,"dup_signals":{"dup_doc_count":12,"dup_dump_count":2,"dup_details":{"curated_sources":2,"2024-26":6,"2024-22":4}}},"text":"Estimation of arcuate artery resistive index as a diagnostic tool for aminoglycoside-induced acute renal failure in dogs.\nTo determine the potential clinical usefulness of duplex Doppler estimation of arcuate artery resistive index (a measure of intrarenal blood flow impedance) for diagnosis of aminoglycoside-induced nephrotoxicosis. 30 adult, female, mixed-breed dogs, allotted to 3 groups of 10 dogs each as: toxic dosage of gentamicin, therapeutic dosage of gentamicin, and saline solution sham equivalent in volume to that of the toxic dosage of gentamicin. After baseline screening to establish normalcy (serum biochemical analysis, endogenous creatinine clearance determination, urinalysis, urine protein-to-creatinine ratio, urine culture, gray-scale sonography, and percutaneous ultrasound-guided renal biopsy), results of arcuate artery resistive index determination were compared with serum creatinine and urine specific gravity values on a Monday-Wednesday-Friday data collection schedule for 10 days. Endogenous creatinine clearance determination, ultrasound-guided renal biopsy, and urine culture were repeated at the end of data collection in all 3 groups. Significant differences in resistive index measurements were not observed, despite clinicopathologic and renal biopsy results compatible with severe acute tubular necrosis in dogs of the toxic dosage group. Duplex Doppler sonography of arcuate artery blood flow impedance, expressed as the resistive index, appears to have poor clinical usefulness as a diagnostic tool in this disorder. Normal arcuate artery resistive index values obtained in dogs for which aminoglycoside-induced nephrotoxicosis is suspected do not exclude the disorder. If abnormal arcuate artery resistive index values are obtained for such dogs, further evaluation for nephropathies other than aminoglycoside-induced nephrotoxicosis may be considered.","subset":"pubmed_abstract"} +{"meta":{"pmid":11300485,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Tracking the common ancestry of antigenically distinct cancer variants.\nIn the months and years after first diagnosis, cancers often show an increase in their malignancy such as faster growth, resistance to chemo- and\/or hormonal therapy, and loss of antigens targeted by immunotherapy. Our objective was to develop a model in which one can track the changes occurring as a result of in vivo immune selection, such as the loss of antigen, the emergence of previously hidden antigens, or the acquisition of new tumor-specific antigens. In this study, we used the primary UV-induced murine tumor 8101, which consists predominantly of regressor tumor cells that express the immunodominant mutant p68 antigen, but this tumor also contains progressor variants that have lost this antigen. To search for tumor-specific antigens on the immune escape progressors, we raised CD8+ T cells specific for these variants. We found that one of the escape variants expressed a previously unrecognized, unique tumor-specific antigen. However, this unique antigen was not readily detectable on any of the other 8101 lines we tested. To prove that these antigenically distinct cancer variants had indeed been derived from the same tumor and neither represented new tumors nor contaminations by other cell lines, we used unique tumor-specific p53 mutations as a lineage-specific marker to demonstrate that these antigenically distinct progressor variants were derived from the 8101 tumor. Because p53 mutations occur very early during UV carcinogenesis and vary from tumor to tumor, they provide convenient reliable markers for tracking the origin of cancers arising after immune selection or immunotherapy.","subset":"pubmed_abstract"} +{"meta":{"pmid":27775737,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"Hydrogen-bonded networks of [Fe(bpp)2]2+ spin crossover complexes and dicarboxylate anions: structural and photomagnetic properties.\nThe paper reports the syntheses, crystal structures, thermal and (photo)magnetic properties of spin crossover salts of formula [Fe(bpp)2](C6H8O4)\u00b74H2O (1\u00b74H2O), [Fe(bpp)2](C8H4O4)\u00b72CH3OH\u00b7H2O (2\u00b72MeOH\u00b7H2O) and [Fe(bpp)2](C8H4O4)\u00b75H2O (2\u00b75H2O) (bpp = 2,6-bis(pyrazol-3yl)pyridine; C6H8O4 = adipate dianion; C8H4O4 = terephthalate dianion). The salts exhibit an intricate network of hydrogen bonds between low-spin iron(ii) complexes and carboxylate dianions, with solvent molecules sitting in the voids. Desolvation is accompanied by a low-spin (LS) to high-spin (HS) transformation in the materials. The dehydrated phase 2 undergoes a two-step transition with a second step showing thermal hysteresis (T1\/2\u2191 = 139 K and T1\/2\u2193 = 118 K). 2 displays a quantitative LS to HS photomagnetic conversion, with a T(LIESST) value of 63 K.","subset":"pubmed_abstract"} +{"meta":{"pmid":7510627,"dup_signals":{"dup_doc_count":12,"dup_dump_count":8,"dup_details":{"curated_sources":1,"2024-10":1,"2017-13":1,"2015-18":1,"2015-11":1,"2015-06":1,"2014-10":1,"2013-48":1,"2024-22":1,"unknown":3}}},"text":"Methodological considerations in measurement of the P300 component of the auditory oddball ERP in schizophrenia.\nTwenty-three schizophrenic patients and 26 age-matched control subjects were studied using the P300 recorded during the auditory oddball task, with counting. Our aim was to assess the most suitable method of measurement and analysis of P300 amplitude and latency for use in clinical studies of schizophrenia. The effect of high-pass filtering, peak definition method and recording electrode site were all investigated. We have developed a technique, based on a least-mean-squares approximation to data, which seems particularly well suited to dealing with multi-peak P300 complexes. We have also investigated the spectral composition of the P300 and have found some evidence to support a proposed 2-frequency model of the P300 complex.","subset":"pubmed_abstract"} +{"meta":{"pmid":29326635,"dup_signals":{"dup_doc_count":15,"dup_dump_count":9,"dup_details":{"curated_sources":4,"2021-31":1,"2021-17":1,"2021-04":1,"2020-45":2,"2020-40":1,"2020-10":2,"2019-26":1,"2019-18":1,"2021-43":1}}},"text":"Beyond Disease: Happiness, Goals, and Meanings among Persons with Multiple Sclerosis and Their Caregivers.\nThe experience of persons with multiple sclerosis (MS) and their caregivers is usually investigated in terms of emotional distress and health-related quality of life, while well-being indicators remain largely underexplored. In addition, findings are often interpreted from the clinical perspective, neglecting socio-cultural aspects that may crucially contribute to individuals' functioning. At the methodological level, most studies rely on scaled instruments, not allowing participants to freely express their needs and resources. Based on the bio-psycho-social perspective endorsed by the International Classification of Functioning, well-being indicators were investigated among 62 persons with MS (PwMS), their 62 caregivers and two control groups, matched by age and gender. Participants completed the Positive Affect Negative Affect Schedule (PANAS), the Satisfaction with Life Scale (SWLS), and the Eudaimonic and Hedonic Happiness Investigation instrument (EHHI). EHHI provides information on participants' happiness, goals and meanings through scaled and open-ended questions, contextualized within major life domains. No relevant differences emerged among PwMS and caregivers, compared with the respective control groups, as concerns life domains associated with happiness, goals and meaning. Participants across groups prominently mentioned family, highlighting its intrinsic value and its relevance as a sharing context; health did not represent a major theme for PwMS; community, society and religion\/spirituality issues were substantially neglected by all participants. PwMS and caregivers reported lower levels of positive affect than their control groups, while no substantial differences emerged for negative affect, happiness and meaningfulness levels in life and across most domains. Results suggest that the experience of MS is associated with well-being in relevant life domains, such as family and close relationships. Although PwMS and caregivers identified a lower number of goals and meaning-related opportunities compared to control groups, they showed a positive adjustment to disease through the development of personal and family resources. These assets are often undervalued by health professionals and social institutions, while they could be fruitfully exploited through the active involvement of PwMS and their families as expert and exemplary informants in initiatives aimed at promoting the well-being of individuals and communities.","subset":"pubmed_abstract"} +{"meta":{"pmid":19673758,"dup_signals":{"dup_doc_count":16,"dup_dump_count":3,"dup_details":{"curated_sources":2,"2024-18":1,"2013-20":1,"2024-30":1,"unknown":11}}},"text":"Strong-meter and weak-meter rhythm identification in spina bifida meningomyelocele and volumetric parcellation of rhythm-relevant cerebellar regions.\nChildren with spina bifida meningomyelocele (SBM) are impaired relative to controls in terms of discriminating strong-meter and weak-meter rhythms, so congenital cerebellar dysmorphologies that affect rhythmic movements also disrupt rhythm perception. Cerebellar parcellations in children with SBM showed an abnormal configuration of volume fractions in cerebellar regions important for rhythm function: a smaller inferior-posterior lobe, and larger anterior and superior-posterior lobes.","subset":"pubmed_abstract"} +{"meta":{"pmid":31300541,"dup_signals":{"dup_doc_count":12,"dup_details":{"curated_sources":2,"unknown":10}}},"text":"AP-1 Signaling by Fra-1 Directly Regulates HMGA1 Oncogene Transcription in Triple-Negative Breast Cancers.\nThe architectural chromatin protein HMGA1 and the transcription factor Fra-1 are both overexpressed in aggressive triple-negative breast cancers (TNBC), where they both favor epithelial-to-mesenchymal transition, invasion, and metastasis. We therefore explored the possibility that Fra-1 might be involved in enhanced transcription of the HMGA1 gene in TNBCs by exploiting cancer transcriptome datasets and resorting to functional studies combining RNA interference, mRNA and transcriptional run-on assays, chromatin immunoprecipitation, and chromosome conformation capture approaches in TNBC model cell lines. Our bioinformatic analysis indicated that Fra-1 and HMGA1 expressions positively correlate in primary samples of patients with TNBC. Our functional studies showed that Fra-1 regulates HMGA1 mRNA expression at the transcriptional level via binding to enhancer elements located in the last two introns of the gene. Although Fra-1 binding is required for p300\/CBP recruitment at the enhancer domain, this recruitment did not appear essential for Fra-1-stimulated HMGA1 gene expression. Strikingly, Fra-1 binding is required for efficient recruitment of RNA Polymerase II at the HMGA1 promoter. This is permitted owing to chromatin interactions bringing about the intragenic Fra-1-binding enhancers and the gene promoter region. Fra-1 is, however, not instrumental for chromatin loop formation at the HMGA1 locus but rather exerts its transcriptional activity by exploiting chromatin interactions preexisting to its binding. IMPLICATIONS: We demonstrate that Fra-1 bound to an intragenic enhancer region is required for RNA Pol II recruitement at the HMGA1 promoter. Thereby, we provide novel insights into the mechanisms whereby Fra-1 exerts its prooncogenic transcriptional actions in the TNBC pathologic context.","subset":"pubmed_abstract"} diff --git a/data/pubmed_abstract/11-100/10_108.jsonl b/data/pubmed_abstract/11-100/10_108.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..63b01de8d54e5f5f637166e1beb83ae73ca5b999 --- /dev/null +++ b/data/pubmed_abstract/11-100/10_108.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:863338566e74658cf3a58bdaf4b4ca0f5052c90449a4229ccbe23af5230bd38d +size 18782539 diff --git a/data/pubmed_abstract/11-100/11_108.jsonl b/data/pubmed_abstract/11-100/11_108.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..d30aae626d01d2eda4b6f8ab16eaf0cc5dd56ffc --- /dev/null +++ b/data/pubmed_abstract/11-100/11_108.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid 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